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NINTEDANIB CAP,ORAL
NEW
NINTEDANIB ESYLATE, OFEV
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NINTEDANIB ESYLATE, OFEV |
2026-04-09 |
Exclusion Criteria- Current smoker
- Child Pugh B or C hepatic impairment
- For IPF diagnosis: currently on pirfenidone (ESBRIET)
- Documented ongoing nonadherence to prior medications or medical treatment
- Pregnant or has not received contraceptive counseling regarding potential risk vs. benefit of taking nintedanib if pregnancy occurs
Inclusion Criteria by Diagnosis- Idiopathic Pulmonary Fibrosis (IPF)
- Treatment initiated and followed by VA/VA Community Care Pulmonologist experienced in diagnosis and management of interstitial lung disease
- Diagnosis confirmed preferably through multidisciplinary evaluation (e.g., pulmonologist, radiologist, pathologist)
- Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)
- Treatment initiated and followed by VA/VA Community Care Pulmonologist or Rheumatologist experienced in diagnosis and management of SSc-ILD
- Diagnosis confirmed preferably through multidisciplinary discussion (e.g., pulmonologist, rheumatologist, radiologist, pathologist)
- Demonstrates disease progression: absolute decline in FVC% predicted >10% from baseline OR DLCO levels >15% from baseline while on mycophenolate or cyclophosphamide, OR patient is unable to take mycophenolate or cyclophosphamide
- Chronic Fibrosing Interstitial Lung Disease – Progressive Phenotype (CFILD)
- Treatment initiated and followed by VA/VA Community Care Pulmonologist experienced in diagnosis and management of CFILD
- Diagnosis confirmed preferably through multidisciplinary discussion (e.g., pulmonologist, rheumatologist, radiologist, pathologist)
- Meets criteria for disease progression within a 24-month period: worsening symptoms with relative decline >10% in FVC; OR worsening symptoms with relative decline >15% in DLCO; OR worsening symptoms with radiological appearance accompanied by >5–<10% relative decrease in FVC
Dose Modifications for Liver Chemistry Abnormalities- AST or ALT >3 but ≤5x upper limit of normal (ULN), without symptoms or hyperbilirubinemia after starting therapy: Discontinue confounding medications, exclude other causes, monitor closely; reduce to 100mg twice daily or place on temporary hold; repeat liver chemistry tests as clinically indicated; resume at 100mg twice daily or full dosage when normalized
- Permanently discontinue nintedanib if AST or ALT >3 but ≤5x ULN accompanied by symptoms or hyperbilirubinemia, OR if AST/ALT >5x ULN regardless of symptoms or hyperbilirubinemia
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SEMAGLUTIDE INJ,SOLN
NEW
WEGOVY HD
|
WEGOVY HD |
2026-04-02 |
Indication & Primary Use- Primarily indicated for patients requiring weight management.
- Semaglutide (OZEMPIC) should not be used for weight management alone.
Formulary Status & Preference- Available non-formulary with criteria for use in weight management.
- No preference for semaglutide (WEGOVY) over liraglutide (SAXENDA).
- Conversion from liraglutide (SAXENDA) is not necessary for patients who are doing well and losing weight.
Conversion Criteria: Liraglutide (SAXENDA) to Semaglutide (WEGOVY)- Suggested conversion doses are off-label; selection of a more conservative dose may be considered only if clinically appropriate on a case-by-case basis.
- Conversion dose and/or titration may need adjustment based on tolerability and glucose control in patients with T2DM.
- For patients currently on 3.0 mg daily liraglutide: Initiate 0.5 mg subcutaneous once weekly for 4 weeks, then 1.0 mg subcutaneous once weekly for 4 weeks, then 1.7 mg subcutaneous once weekly for 4 weeks, followed by 2.4 mg subcutaneous once weekly for maintenance.
Conversion Criteria: Semaglutide (OZEMPIC) to Semaglutide (WEGOVY)- For patients currently receiving semaglutide (OZEMPIC) 1.0 mg subcutaneous once weekly for T2DM: Initiate 1.0 mg subcutaneous once weekly for a total of 4 weeks (combining OZEMPIC and/or WEGOVY), then 1.7 mg subcutaneous once weekly for 4 weeks, followed by 2.4 mg subcutaneous once weekly for maintenance.
- For patients receiving semaglutide (OZEMPIC) 2.0 mg subcutaneous once weekly: Consider conversion to 2.4 mg subcutaneous once weekly only if the patient has received the 2.0 mg dose for at least 4 weeks.
- When switching from semaglutide (OZEMPIC) once weekly to semaglutide (WEGOVY) once weekly, administer the first dose of semaglutide (WEGOVY) 7 days after discontinuing semaglutide (OZEMPIC).
Titration & Administration Requirements- All other patients being started on semaglutide (WEGOVY) should be titrated according to the recommended schedule available in the prescribing information.
- Patient education must be provided.
Exclusion Criteria- Known pregnancy
- Lactating
- Type 1 diabetes (exception: may be considered under careful supervision if followed by a diabetes/weight management specialist)
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History of pancreatitis (exception: does not apply when the cause is known and no longer presents a risk)
- Known PDR, severe NPDR, clinically significant ME, or DME unless risks/benefits discussed with patient, documented in EHR with monitoring plans/follow-up with an eye specialist informed at initiation
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention (CLI) targeting diet, physical activity, and behavioral changes
- BMI ≥ 30 kg/m² with at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, metabolic dysfunction-associated steatotic liver disease)
- Indicated to reduce a secondary cardiovascular event in patients with previous myocardial infarction, previous stroke, or symptomatic peripheral arterial disease (defined as intermittent claudication with ankle–brachial index <0.85, peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease) who have overweight or obesity
Additional Inclusion Criteria- For females who can become pregnant: Pregnancy must be excluded prior to receiving semaglutide (WEGOVY); contraceptive counseling on potential risks vs. benefits if pregnancy occurs is required
Exclusion Criteria- Child-Pugh score ≥ 7 (bilirubin adjustable for Gilbert syndrome; score adjusted for patients taking anticoagulants)
- Decompensated liver cirrhosis manifested by complications (noncardiac ascites, variceal hemorrhage, hepatic encephalopathy, spontaneous bacterial peritonitis)
- Most recent assessment showing: FibroScan LSM > 18 kPa or VCTE consistent with cirrhosis; MRE > 5.0 kPa; FIB-4 > 2.67 (unless LSM < 18 kPa); liver biopsy indicating cirrhosis (METAVIR stage F4)
- Hepatocellular carcinoma currently not actively managed by hepatology or multidisciplinary team
- Uncontrolled liver disease associated with condition other than metabolic dysfunction (e.g., biliary obstruction, viral hepatitis, autoimmune hepatitis, hereditary liver disease, drug-induced liver disease)
- Heavy alcohol ingestion > 3 consecutive months within the previous 1 year (≥4 drinks/day for men, ≥3 drinks/day for women; defined by specific volumes/ABV)
- Personal or first-degree family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History or presence of pancreatitis (except when cause is known and no longer presents a risk)
- Type 1 diabetes (unless followed by a diabetes specialist for careful supervision)
- Known PDR, severe NPDR, clinically significant ME, or DME (unless risks/benefits discussed, documented in EHR with monitoring plans, and eye specialist informed at initiation)
- Known pregnancy
- Lactating
Inclusion Criteria- Initiated by a VA/VA Community Care gastroenterologist/hepatologist or locally designated expert
- Documented plan for addressing and monitoring appropriate lifestyle interventions
- Documented plan to change medications that cause or exacerbate steatohepatitis to alternative agents as applicable and clinically appropriate
Diagnostic & Fibrosis Parameters- Overweight/obese patients: Documented MASH with moderate to advanced fibrosis (stage F2 or F3) diagnosed within past 6 months on noninvasive tests OR past 36 months on liver biopsy
- Lean patients with suspected MASH: Documented MASH with moderate to advanced fibrosis (stage F2 or F3) diagnosed on liver biopsy within past 36 months (exclude non-MASH diagnoses)
- Noninvasive test thresholds for MASH F2–F3: ELF score 9.2–10.5; LSM 8.0–18.0 kPa; MRE 3.1–4.4 kPa
- Weight loss targets: Slow rate (5% within 6 months, cumulative ≥10% within 18 months); ≥5% improves hepatic steatosis, ≥7% improves liver inflammation/resolves MASH, ≥10% improves/stabilizes hepatic fibrosis; lean MASLD may improve histology with 3%–5% weight loss
- FIB-4 should be used with caution in patients >65 years due to lower reliability
Specialist Initiation & Monitoring Requirements- Patients on semaglutide for MASH only must be initiated by a VA/VA Community Care gastroenterologist/hepatologist OR a locally designated expert in MASH management
- Diabetic eye exam results required on file within past 12 months (or 24 months if no evidence of retinopathy); planned follow-up with eye provider for history of diabetic retinopathy; ophthalmology consult obtained for any concerns related to use
Pregnancy & Lactation Counseling- Females who can become pregnant: Pregnancy must be excluded prior to receiving semaglutide; patient counseled on contraceptives and risks/benefits if pregnancy occurs
- Females breastfeeding/providing breastmilk: Counseling provided on potential risks vs benefits of treatment
Other- Other justification field available for clinical documentation
Indication & Patient Population- Treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3) in adults
- Applicable to overweight or obese patients and lean patients with biopsy-confirmed MASH with stage 2 or 3 liver fibrosis
Dosing & Administration- Initial Dosage: 0.25 mg SC once weekly for 4 weeks
- Escalation (once weekly SC): 0.5 mg on Weeks 5–8, 1 mg on Weeks 9–12, and 1.7 mg on Weeks 13–16
- Maintenance: 2.4 mg from Week 17 onward; if not tolerated, decrease to 1.7 mg once weekly; consider reescalation to 2.4 mg
Pretreatment Requirements- Check baseline glucose in patients with type 2 diabetes (T2D) due to hypoglycemia risk
- Consider dosage reduction of concomitant insulin or insulin secretagogues (e.g., sulfonylureas) prior to initiation
Monitoring & Safety Considerations- Monitor glucose in patients with T2D
- Monitor renal function in patients with adverse reactions (e.g., vomiting, diarrhea) that could lead to volume depletion
- Monitor for diabetic retinopathy complications in patients with history of diabetic retinopathy
- Monitor for increased heart rate
- Monitor for depression or suicidal thoughts
Contraindications & Warnings- Contraindicated in personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Contraindicated in pregnancy; may cause fetal harm. Discontinue at least 2 months before a planned pregnancy
- Lactation: Likely present in human milk; weigh risks vs benefits
- Warnings include: Thyroid C-cell tumors, acute pancreatitis, acute gallbladder disease, hypoglycemia (with insulin/secretagogue), acute kidney injury, severe gastrointestinal adverse reactions, hypersensitivity reactions, diabetic retinopathy complications (in T2D), increased heart rate, suicidal behavior and ideation, pulmonary aspiration during general anesthesia or deep sedation
Lifestyle & Adjunctive Therapy Requirements- Must be used in patients with a documented plan on addressing and monitoring appropriate lifestyle interventions
- Should be combined with a reduced calorie diet and increased physical activity
- Comprehensive lifestyle intervention (CLI) should aim for 5–10% weight loss after six months; treatment should continue until long-term weight loss goals are achieved or modified if short/intermediate-term goals are not met
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TAPENTADOL TAB,SA (EXTENDED RELEASE)
NEW
NUCYNTA ER, TAPENTADOL ER
|
NUCYNTA ER, TAPENTADOL ER |
2026-03-19 |
Transitioning Veteran/Continuity of Care- Veteran is transitioning care from Department of Defense to VHA and has determined to continue tapentadol SA.
Exclusion Criteria- Intended use for mild pain, acute pain, or postoperative pain (exception: may be appropriate if patient already receiving prior to surgery or postoperative pain expected moderate/severe persisting extended period).
- Intended use as an as-needed (prn) analgesic.
- Significant respiratory depression, conditions predisposing to significant respiratory depression (acute/severe bronchial asthma), or known/suspected gastrointestinal obstruction including paralytic ileus.
- Severe renal or severe hepatic impairment.
- Hypersensitivity to tapentadol or other SA tablet contents.
- Unable to swallow whole tablets/requires tablets to be crushed before administration.
- Receiving a monoamine oxidase inhibitor (MAOI) or has taken an MAOI within the last 14 days.
- Intent to consume or likelihood of consuming alcoholic beverages or products containing alcohol during therapy.
Inclusion Criteria- Indication: Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options (non-opioid and immediate-release opioid) are inadequate.
- AND documented contraindication, history of intolerable medication-related adverse effects (to IR or SA forms), or inadequate analgesia despite appropriate upwards titration of dosage in separate trials of morphine SA and oxycodone SA.
Dosage and Administration- Available strengths: 50, 100, 150, 200, and 250 mg.
- Tablets must be swallowed whole; not crushed, chewed, or dissolved.
- May be administered with or without food.
- Opioid-naïve/non-tolerant patients: Initiate at 50 mg every 12 hours.
- Titration: Dose increases of 50 mg no more than twice daily every 3 days.
- Maximum daily dose: 500 mg/day. Do not convert from >200 MME morphine equivalent daily dose.
- Steady state plasma concentrations achieved after third dose (24 hours after first twice-daily administration).
- Elderly patients: Recommended doses same as younger patients with normal function; consider starting at lower range due to possibility of reduced clearance.
- Renal impairment: No dosage adjustment for mild/moderate. Not recommended for severe renal impairment (CrCl < 30 ml/min).
- Hepatic impairment: No adjustment for mild (Child-Pugh Score 5 to 6). Moderate (7 to 9): Initiate 50 mg daily, max 100 mg once daily. Not recommended for severe (10 to 15).
- Conversion from fentanyl TDS: Initiate 18 hours after patch removal. Conservative initial dose: 50 mg every 12 hours per 25 mcg fentanyl TDS; titrate per pain relief and tolerability.
- Conversion from methadone: Consult clinician with expertise in methadone dosing.
- Breakthrough pain: Rescue doses of tapentadol IR or other short-acting analgesic (alone or with acetaminophen, aspirin, NSAIDs) as needed or ~1 hour before anticipated incident pain.
- Co-therapy: Consider long-duration opioid + nonopioid analgesic (acetaminophen/NSAID) for opioid-sparing effects or additive analgesia.
Safety and Monitoring Considerations- No consistent safety/tolerability advantage over morphine SA. Serious adverse reactions include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, shock. Non-serious events (constipation, nausea, somnolence) typically seen on initiation and decrease over time.
- Risk of addiction, abuse, misuse, overdose, and death.
- Co-ingestion with alcohol increases plasma levels and fatal overdose risk; avoid all alcohol-containing products.
- Concomitant CNS depressants (other opioids, sedative hypnotics, tranquilizers, general anesthetics, phenothiazines) increase risk of respiratory depression, profound sedation, coma, death; reduce dose of one/both if combined.
- Monitor blood pressure during initiation/titration due to hypotensive potential.
- Life-threatening respiratory depression more likely in elderly, cachectic/debilitated patients, or those with significant respiratory disease.
- Avoid in impaired consciousness/coma, head injury, or increased intracranial pressure (respiratory depressant effects may be magnified).
- Serotonin syndrome risk with serotonergic drugs (SSRIs, SNRIs, TCAs, triptans, mirtazapine, trazodone, tramadol, MAOIs).
- Seizure disorders may be aggravated/induced; use with caution in patients with history of seizures.
- Pregnancy Category C: Use only if benefit justifies risk to fetus. Not recommended during/immediately prior to labor (prolongs labor, neonatal respiratory depression/dependence/withdrawal).
- Insufficient information on breast milk excretion; monitor infants for excess sedation/respiratory depression and withdrawal symptoms.
- Crushing/chewing/dissolving causes uncontrolled delivery leading to overdose/death.
Provider Guidance and Risk Mitigation- Implement risk mitigation strategies per VA/DOD Clinical Practice Guideline on Opioid Therapy for Chronic Pain (2017).
- Strategies include: Informed consent conversation covering risks/benefits/alternatives, ongoing random urine drug testing (with confirmatory testing), checking state PDMPs, monitoring for overdose potential/suicidality, providing overdose education, prescribing naloxone rescue with education.
- Initiation/Continuation: VA/DOD guideline recommends against initiating long-term opioid therapy for chronic pain. For existing patients, continue risk mitigation, assess for OUD, consider tapering if risks exceed benefits.
- Tapering: Screen/treat complicating conditions first (mental health disorders like PTSD/anxiety/depression, OUD/SUD, medical complications, sleep apnea). Typical taper: 5-20% dose reduction every 4 weeks.
- OUD Management: Aberrant behaviors may emerge during taper/discontinuation or as tolerance develops. DSM-5 criteria include craving, tolerance, withdrawal, using larger amounts/longer period, spending time obtaining/using/recovering, continued use despite problems. Suspected OUD requires addiction-focused medical management in PACT, referral to Interdisciplinary Pain Management Team with Addiction Medicine/MAT expertise, or Primary Care Mental Health/specialty care. Offer treatment in comfortable setting if declined.
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TAZEMETOSTAT TAB
NEW
|
|
2026-03-19 |
Exclusion Criteria- Positive Hepatitis B surface antigen with abnormal LFTs (Tbili >1.5x Upper Limit of Normal and/or Alk phos, ALT and AST > 3x Upper Limit of Normal or > 5x Upper Limit of Normal if liver metastasis)
- Positive Hepatitis C Virus RNA with abnormal LFTs (Tbili > 1.5x Upper Limit of Normal and/or Alk phos, ALT and AST > 3x Upper Limit of Normal or > 5x Upper Limit of Normal if liver metastasis)
- Unmanageable drug or food interaction
- Unable to take oral medications due to malabsorption syndrome or other gastrointestinal syndrome
- Inclusion Criteria (One must be met)
- Metastatic or locally advanced epithelioid sarcoma, not eligible for complete resection
- Relapsed or refractory follicular lymphoma, with an EZH2 mutation and received at least 2 prior systemic therapies
- Relapsed or refractory follicular lymphoma, who have exhausted all treatment options
- Additional Inclusion Criteria (General & Performance) (All must be met)
- Care for the oncologic condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance status 0-2
- Additional Inclusion Criteria (Reproductive & Contraception) (All must be met)
- For patients who can become pregnant: Pregnancy must be excluded prior to receiving tazemetostat
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 6 months after stopping treatment
- For patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for at least 3 months after stopping treatment
- Advise patients not to breastfeed during treatment and for 7 months following the last dose
Indications- • Metastatic or locally advanced epithelioid sarcoma, not eligible for complete resection
- • Relapsed or refractory follicular lymphoma (FL), with an EZH2 mutation
- • Relapsed or refractory FL without a mutation, but only when no alternative treatment options exist
Patient Selection & Clinical Context- • Epithelioid sarcoma: Considered a reasonable option to avoid known cumulative toxicities of chemotherapy; chemotherapy may be considered due to slightly improved response rates.
- • Follicular lymphoma: May be considered if an EZH2 mutation is detected after 2 prior therapies. In the relapsed setting with no other reasonable therapeutic alternatives, may be considered regardless of EZH2-mutation status.
Dosing & Administration- • 200 mg oral tablets
- • 800 mg PO twice daily
Safety Monitoring & Precautions for Use- • Monitor patients long-term for development of secondary malignancies (T-cell lymphoblastic lymphoma, MDS, AML)
- • Advise use of effective non-hormonal contraception due to embryo-fetal toxicity and potential reduction in efficacy of hormonal contraceptives
- • Avoid concomitant administration with strong and moderate CYP3A inhibitors or inducers; reduce dose if interaction cannot be avoided
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IBREXAFUNGERP TAB
|
|
2026-03-06 |
Exclusion Criteria- Concomitant administration of CYP3A inducing drugs
- Pregnancy or lactation
Inclusion Criteria (Vulvovaginal Candidiasis)- Signs and symptoms consistent with vulvovaginal candidiasis (VVC) which has not responded to trials of both a topical azole preparation AND fluconazole (unless contraindicated or not tolerated)
- At least 3 episodes of recurrent symptomatic VVC in 12 months and has failed at least 6 months of maintenance fluconazole (unless contraindicated or not tolerated, or isolate is documented to be fluconazole-resistant)
Additional Inclusion Criteria (Pregnancy & Contraception)- For patients who can become pregnant: Pregnancy MUST be excluded prior to receiving ibrexafungerp
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 days after stopping treatment
Other Justification- Any other indication (e.g., off-label for invasive candidiasis, invasive aspergillosis) should be restricted to Infectious Diseases or other facility authorized provider
Supplemental Information & Dosing- CDC STI guidelines recommend vaginal culture or PCR be obtained from women with complicated VVC to confirm clinical diagnosis and identify non–albicans Candida
- Culture and susceptibility testing should be considered for patients who remain symptomatic due to increasing C. albicans azole resistance and frequent azole resistance in non–albicans Candida
- Normal dose for treatment of VVC: 300mg twice daily for 1 day; decrease to 150mg twice daily for 1 day in those on strong CYP3A inhibitors
- Normal dose for prevention of recurrent VVC: 300mg administered 12 hours apart for 1 day monthly for 6 months
Indication- Treatment of vulvovaginal candidiasis (VVC) in adult and post-menarchal pediatric females.
Dosage & Administration- 300 mg administered as two 150 mg tablets by mouth twice daily for one day.
Contraindications- Pregnancy (may cause fetal harm based on animal studies).
- Hypersensitivity to ibrexafungerp.
Warnings & Precautions- Risk of fetal toxicity: Associated with fetal malformations in pregnant rabbits during organogenesis.
- Lactation: No data available regarding presence in human or animal milk, effects on breast-fed infants, or effects on milk production.
- Verify pregnancy status in females of reproductive potential prior to initiating treatment.
- Effective contraception must be used during treatment and for 4 days after completion.
Adverse Reactions- Common: Diarrhea, nausea, abdominal pain, dizziness, vomiting.
- Serious adverse reactions: None reported during clinical trials.
- Other adverse reactions (<2% of patients): Dysmenorrhea, flatulence, back pain, elevated transaminases, vaginal bleeding, rash/hypersensitivity reactions.
Drug-Drug Interactions- CYP3A4 Substrate: Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) may significantly increase serum concentration; recommend dose reduction to 150 mg approximately 12 hours apart for one day.
- CYP3A4 Inducers: Strong/moderate CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort, long-acting barbiturates, bosentan, efavirenz, etravirine) likely to significantly reduce serum concentration; avoid concomitant administration.
- CYP3A4, P-gp, and OATP1B3 Inhibitor: Effect on pharmacokinetics of substrates not considered clinically significant due to short treatment duration.
Special Populations- Pregnancy: Contraindicated due to potential fetal harm.
- Lactation: Insufficient data regarding presence in milk or effects on infants/milk production.
- Females of Reproductive Potential: Verify pregnancy status prior to starting treatment.
- Geriatric Use (≥65 years): Insufficient trial numbers to determine response differences; no clinically meaningful pharmacokinetic differences observed compared to younger patients.
Formulary & Place in Therapy- Indicated for acute, moderate-severe VVC in non-pregnant adult females with azole-resistant organisms or contraindications to topical/oral azole antifungals.
- Represents the only approved non-azole treatment regimen for VVC.
- Clinical failure should be investigated fully; if azole resistance is suspected, culture and susceptibility testing are recommended.
- Diarrhea and other gastrointestinal side effects are common and dose-dependent.
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LANADELUMAB-FLYO INJ,SOLN
|
|
2026-03-05 |
Exclusion Criteria- Angioedema or abdominal pain not associated with C1 inhibitor deficiency
Inclusion Criteria (ALL must be met)- Restricted to VA / VA Community Care allergy/immunology or dermatology provider; or for use in Emergency Medicine/Urgent Care
- Diagnosis of Hereditary Angioedema due to C1 inhibitor deficiency (HAE-C1INH) as established by laboratory testing
Additional Inclusion Criteria (ONE must be met)- Long-term prophylaxis for HAE-C1INH attacks after consideration of either an attenuated androgen or antifibrinolytic
Clinical Context & Decision-Making Requirements- Prior consideration of an attenuated androgen or antifibrinolytic must be discussed with the patient using shared decision-making, including efficacy, routes of administration, and side effects of each therapy
- Baseline attack rate criteria may include at least 2 attacks per month or baseline attack rate in clinical trials
- Need for long-term prophylaxis should be determined using shared decision-making
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NIROGACESTAT TAB
|
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2026-03-02 |
Exclusion Criteria- Severe renal impairment (e.g., eGFR < 40 ml/min/1.73m2)
- Severe hepatic impairment (e.g., Child-Pugh Class C)
- Unmanageable drug-drug interactions (e.g., concomitant CYP3A inhibitors/inducers, proton pump inhibitors, etc.)
- Active or uncontrolled infection
- Known pregnancy
- Lactation
Inclusion Criteria- Diagnosis of progressive desmoid tumor
- Progressive disease or unmanageable toxicity from prior treatment with a tyrosine kinase inhibitor (e.g., sorafenib or pazopanib), unless contraindicated
- Care is provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Additional Inclusion Criteria- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits, the use of effective contraception and avoid breastfeeding during therapy and for 1 week after stopping treatment.
Indication & Patient Population- Adult patients with progressing desmoid tumors who require systemic treatment
- Patients with desmoid tumors not amenable to surgery
- Patients who have not received previous treatment or have refractory/recurrent disease after >1 line of therapy (defined as >20% progression according to RECIST within 12 months before screening)
Dosing & Administration- 150 mg orally twice daily
- Administered in continuous 28-day cycles
- Continue until disease progression or unacceptable toxicity
Monitoring & Safety Considerations- Monitor for diarrhea, ovarian toxicity, hepatotoxicity, electrolyte abnormalities, and embryo-fetal toxicity
- Ovarian toxicity: Female reproductive function and fertility may be impaired; reversible upon discontinuation
- Hepatotoxicity: AST increased in 30% of patients; ALT increased in 33%
- Assess patient-reported outcomes including pain intensity, physical function, role function, and quality of life
Contraindications & Warnings- No boxed warnings or contraindications stated
- Avoid strong or moderate CYP3A4 inducers and inhibitors
- Avoid PPIs and H2 antagonists
Guideline & Pathway Criteria- FDA-approved therapy for progressive desmoid tumors
- NCCN: Preferred category 1 along with sorafenib
- VA STS pathway: Systemic therapy indicated for desmoid tumors with anatomic location showing morbid progression
- Selection between nirogacestat and alternative TKIs (e.g., sorafenib) should be directed by patient symptoms, comorbidities, and toxicity profile
Clinical Context & Use Considerations- Desmoid tumors are rare, slow-growing, locally invasive mesenchymal tumors with no potential to metastasize; 20-30% may spontaneously regress
- Management depends on tumor location, symptoms, and progression; may involve surveillance, surgery, radiation, local ablation, cytotoxic chemotherapy, or TKI therapy
- If rapid response is needed or oral absorption is compromised, cytotoxic chemotherapy may be preferred
- Nirogacestat evidence demonstrates benefit in pain reduction, physical functioning, and quality of life compared to placebo
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POMALIDOMIDE CAP,ORAL
POMALYST
|
POMALYST |
2026-02-26 |
Exclusion Criteria- Absolute neutrophil count (ANC) < 500/mm3
- Hemoglobin < 8 g/dL; Must transfuse to hemoglobin above 8 gm/dL prior to therapy initiation
- Platelet count < 50,000/mm3
- Eastern Cooperative Oncology Group performance status > 2
- Patient has not been screened for Hepatitis B Virus
- Active or uncontrolled infection
- Known pregnancy
- Lactating
Inclusion Criteria- Relapsed or refractory multiple myeloma, following at least 2 lines of therapy that included lenalidomide and a proteasome inhibitor
- Diagnosis of Kaposi sarcoma
Additional Inclusion Criteria- Care is provided by a VA or VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Venous thromboembolism (VTE) risk scoring (i.e. SAVED, IMPEDE) performed for consideration of VTE prophylaxis
REMS & Pregnancy Safety Requirements- Patients who can become pregnant and patients with partners who can become pregnant must comply with pregnancy testing and contraception requirements for pomalidomide under the POMALYST REMS program
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ZANUBRUTINIB CAP,ORAL
|
|
2026-02-19 |
Exclusion Criteria- Patient has not been screened for Hepatitis B Virus (HBV)
- Unmanageable drug-drug or drug-food interaction identified
- History of stroke or intracranial hemorrhage in prior 6 months
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (NYHA Class 3 or 4), or myocardial infarction in prior 6 months
- Current or history of Central Nervous System (CNS) lymphoma
- Active or uncontrolled infection
- Known pregnancy
- Lactating
Indications- Relapsed or refractory mantle cell lymphoma and progressive disease or intolerance to at least one prior therapy
- Relapsed or refractory marginal zone lymphoma and received at least one anti-CD20-based regimen
- Waldenstrom macroglobulinemia
- Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) if acalabrutinib is not clinically appropriate for patient
- Relapsed or refractory follicular lymphoma, in combination with obinutuzumab, after two or more lines of therapy
Additional Clinical Requirements- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0-2
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for 1 week after the last dose
- Advise patients not to breastfeed/provide breastmilk during treatment and for at least 2 weeks after the last dose
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TAPENTADOL TAB
NUCYNTA, TAPENTADOL HCL
|
NUCYNTA, TAPENTADOL HCL |
2026-02-12 |
Transitioning Care Exception- Veteran is transitioning care from the Department of Defense to VHA, and a VA prescriber has determined continuation of tapentadol IR tablets is safe and clinically appropriate (remainder of criteria not applicable)
Inclusion Criteria- Intended use for treatment of moderate to severe acute pain where opioid use is appropriate
- Patient has documented intolerance, contraindication, or lack of sufficient analgesic response to at least 4 other formulary short-acting immediate-release opioids (tramadol, codeine, codeine/acetaminophen, hydrocodone/acetaminophen, oxycodone/acetaminophen, oxycodone, hydromorphone, morphine)
- OR Patient is approved for tapentadol SA tabs and tapentadol IR is required for breakthrough pain
Exclusion Criteria- Intended use is for treatment of mild pain
- Patient is opioid naïve and initial single dosage is > 100 mg
- Significant respiratory depression, conditions predisposing to significant respiratory depression (acute or severe bronchial asthma), or known/suspected gastrointestinal obstruction including paralytic ileus
- Severe renal or hepatic impairment
- Receiving a monoamine oxidase inhibitor (MAOI) or has taken an MAOI within 14 days
- Hypersensitivity to tapentadol
Dosage and Administration- Available strengths: 50, 75, and 100 mg
- First day of dosing: Second dose may be administered as soon as one hour after first dose if adequate pain relief not attained; subsequent dosing is 50, 75, or 100 mg up to every 4 to 6 hours, adjusted for adequate analgesia with acceptable tolerability
- Daily doses > 700 mg on day 1 and > 600 mg on subsequent days are not recommended
- Consider starting elderly patients at the lower range of recommended dosages
- No FDA-approved dosing instructions exist for conversion from another opioid; use provided conversion factors to estimate dose, but reduce calculated MME to 50–67% to avoid accidental overdose due to incomplete cross-tolerance and individual variability
Safety and Warnings- Does not offer consistent advantages over morphine IR regarding safety or tolerability
- Serious adverse reactions: potentially life-threatening respiratory depression, profound sedation, hypotension
- Non-serious adverse events: nausea, vomiting, constipation, dry mouth, fatigue, dizziness, somnolence, pruritus
- Concomitant use with other CNS depressants (other opioids, alcohol, sedative hypnotics, tranquilizers, general anesthetics, phenothiazines, skeletal muscle relaxants) increases risk of respiratory depression, profound sedation, coma, death, and hypotension
- VA/DOD guideline recommends against concurrent use of opioids and benzodiazepines; consider tapering one or both when risks exceed benefits and obtain specialty consultation if combined therapy is contemplated
- Avoid in patients with impaired consciousness or coma, head injury, or increased intracranial pressure (respiratory depressant effects may be magnified)
- Potentially life-threatening serotonin syndrome may occur when combined with serotonergic drugs (SSRIs, SNRIs, TCAs, triptans, mirtazapine, trazodone, tramadol, MAOIs)
- Seizure disorders may be aggravated or induced; use with caution in patients with history of seizures
- Abuse potential via crushing, chewing, snorting, or injecting poses significant risk of overdose and death; consider provision of naloxone rescue kit as risk mitigation
Special Populations- Pregnancy: Category C; use only if potential benefit to mother justifies potential risk to fetus
- Labor/Delivery: Not recommended during or immediately prior to labor (can prolong labor and cause neonatal respiratory depression, physical dependence, and withdrawal syndrome)
- Lactation: Insufficient information on excretion in breast milk; monitor infants for excess sedation, respiratory depression, and withdrawal symptoms when therapy is stopped
Risk Mitigation and Opioid Management- Implement risk mitigation strategies per VA/DOD Clinical Practice Guideline on Management of Opioid Therapy (2017): informed consent conversation, ongoing random urine drug testing, checking state PDMPs, monitoring for overdose potential and suicidality, providing overdose education, prescribing naloxone rescue kit with accompanying education
- Do not initiate long-term opioid therapy for chronic pain; for patients already on long-term therapy, continue risk mitigation, assess for OUD, and consider tapering when risks exceed benefits
- Opioid Tapering: Screen and treat complicating conditions before initiating taper (mental health disorders like PTSD/anxiety/depression, OUD/SUD, medical complications, sleep disorders including sleep apnea); typical taper involves dose reductions of 5% to 20% every 4 weeks
- OUD Management: Monitor for aberrant behaviors; if OUD suspected, provide addiction-focused medical management in PACT or refer to Interdisciplinary Pain Management Team with Addiction Medicine expertise/MAT, or Primary Care Mental Health/specialty care
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LASMIDITAN TAB,ORAL
REYVOW
|
REYVOW |
2026-01-15 |
Exclusion Criteria- Concurrent therapy with a P-glycoprotein substrates sensitive to minor changes in plasma concentration (e.g., digoxin)
- Concurrent therapy with ubrogepant or rimegepant
- Concurrent therapy with a triptan agent once lasmiditan is initiated
- Pregnancy
- Patient unable to comply with not engaging in activities requiring mental alertness (e.g. driving) for at least 8 hours after taking lasmiditan
Inclusion Criteria- Treatment initiated by a VA/VA Community Care neurologist or locally designated headache expert
- Diagnosis of migraine, with or without aura, per the International Classification of Headache Disorders (ICHD-3)
- Moderate to severe migraine intensity
- Contraindication, intolerance, or lack of response to trial of two different triptans
Triptan Contraindications & Interactions- Vascular contraindications: ischemic coronary artery disease, previous stroke or transient ischemic attack, peripheral vascular disease, ischemic bowel disease, or uncontrolled hypertension
- Drug interaction-related contraindications: concurrent use of a MAO inhibitor
Indication- Acute treatment of migraine with or without aura in adults.
Patient Population & Clinical Context- Adults with a history of 3–8 migraine attacks and less than 15 headache days per month.
- Patients with cardiovascular risk factors or disease for whom triptan use is contraindicated.
- Triptan-experienced population, including patients who did not demonstrate an acceptable response to triptans.
Dosing & Administration- Doses of 50 mg, 100 mg, and 200 mg demonstrated efficacy for pain freedom at 2 hours.
- Administer as the first treatment for each new migraine attack within 4 hours of pain onset.
- Do not repeat a dose until more than 48 hours after treatment of an attack.
Safety Monitoring & Precautions- Monitor closely for CNS depression, dizziness, balance disorders, somnolence, fatigue, sedation, and paresthesia (occurring >2% greater than placebo).
- Monitor closely for cardiovascular effects, including potential decrease in heart rate and/or increase in blood pressure, particularly in patients who may not tolerate these changes.
- Monitor closely for signs of serotonin syndrome (mental status changes, autonomic instability, neuromuscular changes, GI symptoms, seizures) when used alone or with other serotonergic agents; discontinue immediately if signs/symptoms arise.
- Patients must be able to abstain from activities requiring mental alertness for at least 8 hours after administration due to driving impairment risks.
Contraindications & Restrictions- Not recommended in patients with severe hepatic impairment.
- Should not be taken with alcohol or other sedating medications.
- Classified as a controlled substance monitored by the DEA; associated with euphoria and hallucinations.
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SARILUMAB INJ,SOLN
|
|
2026-01-15 |
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for infection has been initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Congenital or acquired immunodeficiency
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 unless associated with Duffy-null Associated Neutrophil Count
- Baseline platelet count <150,000/mm3
- Baseline ALT and/or AST > 1.5x the upper limit of normal (ULN)
Inclusion Criteria- Diagnosis of moderate to severe rheumatoid arthritis
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response
Additional Inclusion Criteria & Clinical Precautions- If HBsAg-negative but anti-HBc-positive and consult is indicated: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- Females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
- Females who are lactating/providing breastmilk: Counseling provided on potential risks and benefits of treatment
- Antiviral prophylaxis for hepatitis B virus should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed or initiated by end of first year, preferably when dosage is low, disease is stable, or immune response is robust
- May be used with methotrexate, other nonbiologic DMARDs, mycophenolate, hydroxychloroquine, or glucocorticoids; concomitant use of potent immunosuppressives should generally be avoided
- Routine rescreening for hepatitis B or C is not required for prescription renewals; retesting in high-risk patients should be considered
Exclusion Criteria- Uncontrolled, active, severe infection (including undrained abscess)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis
- Untreated HIV infection
- Concomitant live or live-attenuated vaccines, or administration of such vaccines less than 2 weeks prior to initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 (unless associated with Duffy-null Associated Neutrophil Count)
- Baseline platelet count < 150,000/mm3
- Baseline alanine transaminase (ALT) and/or aspartate transaminase (AST) > 1.5x the upper limit of normal (ULN)
Inclusion Criteria- Diagnosis of polymyalgia rheumatica (PMR)
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening
- Initiated concurrently with or after glucocorticoid therapy (unless glucocorticoids are medically inadvisable)
Additional Inclusion Criteria- For HBsAg-negative, anti-HBc-positive patients where consult is indicated: E-consult with GI/liver or infectious diseases expert for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- Patients capable of pregnancy: Counseling provided on treatment risks vs benefits and requirement for effective contraception during therapy
- Lactating patients/providing breastmilk: Counseling provided on potential risks and benefits of treatment
Monitoring & Safety Considerations- Antiviral prophylaxis for hepatitis B should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed or initiated by the end of the first year, preferably when dosage is low or disease is stable
- Routine rescreening for hepatitis B or C is not required for prescription renewals; retesting in high-risk patients should be considered
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TEPLIZUMAB-MZWV INJ,SOLN
TZIELD
|
TZIELD |
2026-01-15 |
Exclusion Criteria- Type 1 or type 2 diabetes
- Lymphocyte count less than 1,000 lymphocytes/mcL
- Hemoglobin less than 10 g/dL
- Platelet count less than 150,000 platelets/mcL
- Absolute neutrophil count less than 1,500 neutrophils/mcL
- Elevated ALT or AST greater than 2 times the upper limit of normal (ULN) or bilirubin greater than 1.5 times ULN
- Laboratory or clinical evidence of acute infection with Epstein-Barr virus or cytomegalovirus
- Active serious infection or chronic active infection other than localized skin infections
- Requires inactivated or mRNA vaccinations within the 2 weeks prior to teplizumab treatment, during treatment, or 6 weeks after completion of treatment
- Requires live-attenuated vaccinations within the 8 weeks prior to teplizumab treatment, during treatment, or up to 52 weeks after treatment
- Note: Safety of immunization with live-attenuated vaccines has not been studied; teplizumab may interfere with immune response and decrease vaccine efficacy. Administer all age-appropriate vaccinations prior to starting treatment. Administer live-attenuated vaccines at least 8 weeks prior. Administer inactivated or mRNA vaccines at least 2 weeks prior.
Inclusion Criteria- Provider is a VA or VA Community Care endocrinologist
- Has relative with type 1 diabetes (age ≤45 years if parent, sibling, or offspring; age ≤20 years if second or third degree relative)
- At least two positive pancreatic islet cell autoantibodies (Anti-GAD65, insulin autoantibody, anti-IA-2, islet cell autoantibody, anti-ZnT8)
- Dysglycemia without overt hyperglycemia on TWO occasions during an oral glucose tolerance test (OGTT)
- Dysglycemia defined as: fasting glucose level of 110 to 125 mg/dL, OR a 2-hour postprandial plasma glucose level of 140 mg/dL and less than 200 mg/dL, OR a postprandial glucose level at 30, 60, or 90 minutes ≥200 mg/dL
Pregnancy and Reproductive Considerations- Pregnancy must be excluded prior to receiving teplizumab
- Do not use during pregnancy and at least 30 days (6-half-lives) prior to planned pregnancy
- Counseling provided on potential risks vs benefits of treatment
- Use of effective contraception during therapy
Indication & Patient Population- Indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adults and pediatric patients aged 8 years and older with Stage 2 T1D
- Adults up to age 45 years
- Must have a relative with T1D
- Must have ≥2 pancreatic islet cell autoantibodies
- Must demonstrate dysglycemia on oral glucose tolerance test (OGTT)
Pre-Treatment Screening & Laboratory Requirements- Obtain complete blood count and liver enzyme tests prior to initiating therapy
- Lymphocyte count must be ≥1,000 lymphocytes/mcL
- Hemoglobin must be ≥10 g/dL
- Platelet count must be ≥150,000 platelets/mcL
- Absolute neutrophil count must be ≥1,500 neutrophils/mcL
- ALT or AST must not exceed 2 times the upper limit of normal (ULN)
- Bilirubin must not exceed 1.5 times ULN
- No laboratory or clinical evidence of acute infection with Epstein-Barr virus (EBV) or cytomegalovirus (CMV)
- Females of reproductive potential require a pregnancy test prior to treatment
Administration & Dosing Criteria- Administer by intravenous infusion over a minimum of 30 minutes once daily for 14 days
- Dosing schedule: Day 1: 65 mcg/m2; Day 2: 125 mcg/m2; Day 3: 250 mcg/m2; Day 4: 500 mcg/m2; Days 5-14: 1,030 mcg/m2
- Premedicate prior to infusion for the first 5 days with a nonsteroidal anti-inflammatory drug or acetaminophen, an antihistamine, and/or an antiemetic
Monitoring & Management During Therapy- Monitor liver enzymes; discontinue if ALT or AST develops >5 times ULN
- Monitor white blood cell counts during treatment; discontinue if prolonged severe lymphopenia (<500 cells/µL lasting 1 week or longer) develops
- Treat cytokine release syndrome (CRS) symptoms with antipyretics, antihistamines, and/or antiemetics
- If severe CRS develops, temporarily pause dosing for 1-2 days (administer remaining doses on consecutive days to complete the 14-day course) or discontinue treatment
- Discontinue treatment if serious infections develop
Exclusions & Contraindications- Not recommended in patients with active serious infection or chronic active infection other than localized skin infections
- Discontinue for severe hypersensitivity reactions
- Only one course of therapy is approved; effect of repeated courses is unknown
Special Populations & Precautions- Pregnancy: Do not receive during pregnancy and at least 30 days before a planned pregnancy
- Breastfeeding: Pump and discard breast milk during treatment and for 20 days after receiving treatment
- Vaccinations: Administer all age-appropriate vaccinations prior to starting; live-attenuated vaccines at least 8 weeks prior; inactivated or mRNA vaccines at least 2 weeks prior
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TAFAMIDIS CAP,ORAL
VYNDAQEL
|
VYNDAQEL |
2026-01-05 |
Indication- Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Provider Requirements- Provider is a VA or VA Community Care cardiologist or locally designated ATTR-CM provider
Diagnostic & Laboratory Criteria- Diagnosis of wild type or hereditary TTR genotype ATTR-CM based on 1) endomyocardial biopsy OR 2) echo/MRI suggestive of amyloidosis confirmed with radionuclide imaging (e.g., technetium-pyrophosphate [Tc99-PYP] scintigraphy)
- Assessment of monoclonal protein screen for and exclusion of light chain (AL) amyloidosis
Clinical Presentation- History of symptomatic heart failure (at least one hospitalization for heart failure OR clinical evidence of heart failure manifested by signs and symptoms of volume overload or elevated intracardiac pressures)
Counseling & Documentation- Discussion with patient/caregiver/family member regarding realistic treatment expectations and discontinuation should be documented
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment
Exclusion Criteria- Heart failure without definitive evidence of transthyretin-mediated amyloidosis (ATTR) (e.g., heart failure secondary to ischemic heart disease)
- Patient receiving concomitant therapy for ATTR amyloidosis (e.g., patisiran, eplontersen, inotersen, vutrisiran, acoramidis)
- End stage heart disease and anticipated survival < 1 year
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ESCITALOPRAM TAB,ORAL
ESCITALOPRAM OXALATE, LEXAPRO
|
ESCITALOPRAM OXALATE, LEXAPRO |
2026-01-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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PERAMPANEL SUSP,ORAL
FYCOMPA
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FYCOMPA |
2025-12-31 |
Exclusion Criteria- Preexisting aggression, hostility, irritability, anger, homicidal ideation and threats that is uncontrolled/untreated
- Severe hepatic impairment (Child Pugh Class C)
- CrCL 10-30 ml/min or on hemodialysis
Inclusion Criteria- Medication management by a VA Neurologist or VA purchased Neurology care
- Inadequate response, intolerable side effects, or contraindication to two formulary antiepileptic medications for partial seizures (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, divalproex sodium, topiramate, zonisamide) or primarily generalized seizures (lamotrigine, levetiracetam, topiramate, valproate, zonisamide)
Special Populations & Pregnancy- Category C for women of childbearing potential
- Adverse events observed in animal reproduction studies
- Limited information on use in pregnancy; if inadvertent exposure occurs, close monitoring of the mother and fetus/newborn is recommended
Dosage & Administration- Without enzyme-inducing AEDs: Starting dose 2 mg once daily at bedtime. Titrate by increments of 2 mg once daily no more frequently than weekly intervals based on clinical response and tolerability. Recommended maintenance: Partial-Onset Seizures 8 to 12 mg once daily; Primary Generalized Tonic-Clonic Seizures 8 mg once daily.
- With enzyme-inducing AEDs (phenytoin, carbamazepine, oxcarbazepine): Starting dose 4 mg once daily at bedtime. Titrate by increments of 2 mg once daily no more frequently than weekly intervals. Maintenance dose not established; highest studied dose is 12 mg once daily.
Monitoring & Safety Considerations- Black box warning for serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger and homicidal ideation and threats (occurs regardless of prior psychiatric history or concomitant medications)
- Increased risk of suicidal thoughts or behavior; monitor for emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
- Avoid strong CYP3A4 inducers (rifampin, St. John's wort)
- Effectiveness of hormonal contraceptives containing levonorgestrel may decrease with 12 mg once daily dose
- Concomitant enzyme-inducing antiepileptics may compromise perampanel efficacy
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CLADRIBINE TAB,ORAL
MAVENCLAD
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MAVENCLAD |
2025-12-11 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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LENACAPAVIR INJ,SOLN
SUNLENCA, YEZTUGO
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SUNLENCA, YEZTUGO |
2025-12-02 |
Indications & Patient Population- HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant (MDR) HIV-1 infection failing current antiretroviral treatment (ART) regimen due to resistance, intolerance, or safety considerations
- Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition
Dosing & Administration Requirements- Administered as extended-release injectable suspension for subcutaneous (SQ) administration
- Maintenance dose: 927 mg (3 mL = 2 vials) SQ injection every 26 weeks (±2 weeks) from the date of the last SQ injection
- Requires oral initiation dosing prior to maintenance injections (Option #1 for HIV treatment/PrEP or Option #2 for HIV treatment only)
- Dosing series must be restarted with initiation dosing if more than 28 weeks have elapsed since the last injection
Safety, Monitoring & Contraindications- Boxed warning: Risk of drug resistance with use of LEN for PrEP in undiagnosed HIV-1 infection
- Must test for HIV-1 infection prior to initiating LEN and with each subsequent injection using a test approved or cleared by the FDA; do not initiate unless negative infection status is confirmed
- Contraindicated with concomitant administration of strong CYP3A inducers (risk of loss of therapeutic effect and development of resistance)
- Not recommended with moderate CYP3A inducers, P-gp inhibitors, UGT1A1 inhibitors, or strong CYP3A4 inhibitors (including cobicistat and ritonavir) due to risk of increased LEN serum concentration
- LEN is a moderate CYP3A inhibitor; may increase exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last SQ dose
- Immune reconstitution syndrome possible during initial phase for HIV treatment
- If discontinued, initiate an alternative fully suppressive ART or PrEP regimen within 28 weeks after the last LEN dose; subtherapeutic serum concentrations may extend beyond 12 months after stopping LEN for PrEP
Adherence & Place in Therapy Considerations- For HIV treatment: Reserve for patients unable to formulate a viable suppressive regimen with two fully active agents due to predicted resistance (genotypic or phenotypic), drug intolerance, DDIs, or dual-mixed/CXCR4-tropism (for maraviroc)
- Requires patient understanding and commitment to receive LEN SQ injection every 26 weeks (±2 weeks) administered by a healthcare provider
- For PrEP: Reserved for individuals with contraindications, intolerance, or inability to adhere to oral TDF/FTC; daily oral TDF/FTC remains the preferred first-line PrEP agent
Storage & Handling- Oral tablets must be dispensed only in original blister pack and stored at 20–25 °C
- SQ injection dosing kit (2 single-dose vials) must be stored at 20–25 °C in the original carton to protect from light until preparation
- Injection should be administered as soon as possible once solutions are drawn into syringes
Indications & Target Populations- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.
Exclusion Criteria- Significant noncompliance with follow-up appointments unless barriers to compliance have been significantly addressed by provider
- Drug interactions that preclude administration of lenacapavir (moderate or strong CYP3A or P-gp inducers; combined P-gp, UGT1A1 and strong 3A4 inhibitors)
Inclusion Criteria (All Required)- Lenacapavir prescribed by, or in collaboration with, a provider with experience or training in the administration of PrEP (designated facility providers)
- Substantial risk of HIV acquisition (sex without condoms, multiple sexual partners, recent or frequent sexually transmitted infections, sexual relationship with HIV infected partner, injection drug use with equipment sharing)
- Documentation that patient agrees to required HIV testing and dosing schedule
Additional Inclusion Criteria (One Required)- Intolerance or contraindication to Truvada (TDF/FTC)
- CrCl of 15-59 mL/min or multiple risk factors for significant renal dysfunction
- Patient specific factors impacting adherence to daily oral PrEP (e.g., cognitive difficulties, gastrointestinal dysfunction, unstable housing, stigma, or fear of discovery)
Testing Requirements- Confirmed negative HIV-1 Ag/Ab lab based test within 7 days of each administration
- HIV RNA test recommended prior to initiation; results should not delay initiation; if unavailable, obtain repeat HIV-1 Ag/Ab test within 1 month of initiation
Administration & Dosing- Subcutaneous administration into the abdomen (preferred) or thigh (alternative) only
- Day 1: 927mg by subcutaneous injection (2 x 1.5mL injections) AND 600mg orally (2 x 300mg tablets)
- Day 2: 600mg orally (2 x 300mg tablets), self-administered at home
- Every 6 months (26 weeks +/- 2 weeks): 927mg by subcutaneous injection (2 x 1.5mL injections)
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CARBIDOPA/ LEVODOPA CAP,SA
CARBIDOPA-LEVODOPA ER, RYTARY
|
CARBIDOPA-LEVODOPA ER, RYTARY |
2025-10-30 |
Exclusion Criteria- Currently taking a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine) or have recently (within 14 days) taken a nonselective MAO inhibitor
Inclusion Criteria- Patient is under the care of a VA or VA Community Care neurologist or locally designated expert
- Clinical diagnosis of Parkinson’s disease (PD), post-encephalitic parkinsonism, or parkinsonism that may follow intoxication by carbon monoxide or manganese
- Motor fluctuations (“wearing off”) that require dosing of dopaminergic medications at intervals of every 4 hours or less
- Combination of carbidopa/levodopa controlled-release (CR) and immediate-release (IR) tablet formulations throughout the day have not adequately resolved OFF periods
- Contraindication, intolerance, or inadequate therapeutic response to at least one agent from two of the following classes: dopamine agonist, catechol-O methyl transferase [COMT] inhibitor, monoamine oxidase type B [MAO B] inhibitor
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GLECAPREVIR/ PIBRENTASVIR PELLET
MAVYRET
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MAVYRET |
2025-10-22 |
Exclusion Criteria- Limited life expectancy
- Documented ongoing nonadherence to prescribed medications or medical treatment
- Concurrent use of drugs not recommended with GLE/PIB (e.g., rifampin, atazanavir, darunavir, efavirenz, etravirine or ritonavir)
- Severe hepatic impairment (Child-Pugh B/C or history of hepatic decompensation)
- Prior hepatitis C virus (HCV) treatment failure of both an NS3/4A protease inhibitor AND an NS5A inhibitor
- Hepatitis B surface antigen (HBsAg) positive and not on antiviral treatment with entecavir or tenofovir
- Contraindication to ribavirin (RBV) IF RBV is indicated (includes history of significant cardiac disease, significant anemia, pregnancy, and men whose female partner is pregnant or plans to become pregnant)
Inclusion Criteria- Care is provided by or in consultation with a VA/VA Community Care Hepatitis C Specialist
- Treatment regimen and duration consistent with HCV genotype (GT) and patient characteristics according to VA HCV Treatment considerations
- HCV GT 1-6 or ungenotyped but detectable HCV RNA
- Completed hepatitis B screening: at minimum HBsAg, HBV core antibody (anti-HBc) and HBV surface antibody (anti-HBs)
- Adherence counseling performed including laboratory follow-up and documented understanding by patient
- Additional Inclusion Criteria (One of the following must be true)
- GT 1-6 or ungenotyped but detectable HCV RNA with or without compensated cirrhosis and are treatment naïve
- GT 1-6 with or without compensated cirrhosis with prior treatment experience with pegylated interferon, ribavirin +/- sofosbuvir (SOF)
- GT 1 with or without compensated cirrhosis and prior NS3/4A experience (but SOF and NS5A naïve)
- GT 1 with or without compensated cirrhosis and prior NS5A inhibitor experience but NS3/4A naïve
- With SOF and RBV for GT 1-6 with or without compensated cirrhosis and treatment experienced with sofosbuvir / velpatasvir / voxilaprevir or SOF plus GLE/PIB
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REMIBRUTINIB TAB,ORAL
RHAPSIDO
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RHAPSIDO |
2025-10-09 |
Indication & Patient Selection- Indicated for treatment of chronic spontaneous urticaria (CSU) in adult patients who remain symptomatic despite use of H1 AH treatment.
- Patients must have CSU diagnosed > 6 months that remained symptomatic despite H1 AH use.
- Symptomatic disease on H1 AH requires itch and hives for at least 6 consecutive weeks prior to screening, with UAS7 > 16, ISS7 > 6, and HSS7 > 6 during the 7 days prior to randomization.
Dosing & Administration- Dosage: 25 mg by mouth twice daily.
- Available as 25 mg tablet.
Safety Monitoring & Precautions- Monitor for signs and symptoms of bleeding; discontinue remibrutinib if bleeding occurs.
- Temporarily interrupt therapy 3–7 days before and after surgery, depending on surgery type and bleeding risk.
- Avoid use of live or live-attenuated vaccines due to lack of data on effect.
Contraindications & Drug Interactions- No boxed warnings or contraindications listed.
- Avoid concomitant use with strong or moderate CYP3A4 inhibitors or inducers; remibrutinib is a CYP3A4 substrate.
- Remibrutinib is a P-gp inhibitor; closer monitoring recommended for P-gp substrates where minimal concentration changes may cause serious ADEs (e.g., digoxin).
- Concomitant use with antithrombotic drugs may increase bleeding risk; risks and benefits should be considered. Lack of data on anticoagulant concomitant use due to patient exclusion in trials.
Place in Therapy & Treatment Algorithm- Considered an alternative to omalizumab or dupilumab for patients remaining symptomatic despite maximized H1 AH (up to 4 times the approved daily dose).
- Omalizumab is the preferred second-line agent after inadequate response to H1 AH up to 4x dose.
- Maximum doses of H1 AH should be continued in combination with second-line therapies.
- Low-dose cyclosporine may be considered as a third-line agent for more refractory symptoms/disease.
- Therapy can be stepped down by reducing doses or extending dosing intervals when the urticaria control test (UCT) score equals 16.
Special Populations- Hepatic impairment: Avoid use in patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C); exposure is increased in any degree of liver impairment.
- Renal impairment: No clinically significant effect on pharmacokinetics in mild, moderate, or severe renal impairment.
- Pregnancy: Data lacking to evaluate risk of major birth defects, miscarriage, or other adverse maternal/fetal outcomes; pregnancy exposure registry available.
- Lactation: No data; consider developmental/health benefits of breastfeeding alongside mother’s clinical need and potential ADEs on the breastfed child.
Exclusion Criteria- Concurrent use of live or live attenuated vaccines (within the past 4 weeks)
Inclusion Criteria- Provider must be a VA or VA Community Care allergy specialist, dermatologist, or designated expert in the management of allergic conditions
- Diagnosis of severe chronic spontaneous urticaria (e.g., UAS7 >28 and/or UCT <12)
- Unacceptable symptoms despite a therapeutic trial of 1 non-sedating H antihistamine titrated up to 4 times the usual daily dose
- Inadequate response to a 3-month trial of omalizumab 300 mg every 4 weeks (minimum of 3 doses), unable to tolerate, or not a candidate for omalizumab
- Inadequate response to a 6-month trial of dupilumab 300 mg every 2 weeks (minimum of 12 doses), unable to tolerate, or not a candidate for dupilumab
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy; pregnancy register enrollment recommended if pregnancy occurs
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APREMILAST MISCELLANEOUS
OTEZLA XR
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OTEZLA XR |
2025-10-02 |
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy of apremilast
- Untreated or unstable depression or suicidality, unless a mental health consultant concurs with apremilast treatment
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Adult (18 years of age or older) with recurrence of 2 or more oral ulcers associated with Behçet's disease
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy
- Untreated or unstable depression or suicidality, unless a mental health consultant concurs with apremilast treatment
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Nonsevere or predominantly oligoarticular peripheral inflammatory disease and a definite or provisional diagnosis of active psoriatic arthritis (note: ineffective for joint erosions and axial disease)
- Conventional synthetic immunomodulator (methotrexate, leflunomide or sulfasalazine) is medically inadvisable, not tolerated, or not adequate after 12 weeks
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Clinical Adjudication & Supplemental Considerations- Conventional synthetic immunomodulator: Adequate trial requires NO or partial treatment benefit after 12 weeks at doses of 15–25 mg/wk (or lower if limited by toxicity); for inadequate responders, consider switching to subcutaneous methotrexate. For other immunomodulators, require NO or partial treatment benefit after 12 weeks at recommended doses (or lower if limited by toxicity).
- TNFI therapy: Prior trial is not required but should be recommended if medically advisable. For TNFI inadequate/nonresponders, consider switching to a second TNFI, another biologic, or tofacitinib rather than apremilast monotherapy.
- TNFI may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent infections, serious infections, etc.
- Aversity to injections or barriers to in-clinic administration (e.g., travel) should be adjudicated case by case as a reason why a TNFI is medically inadvisable.
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy of apremilast.
- Untreated or unstable depression or suicidality unless mental health consultation concurs with apremilast treatment.
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care dermatologist or locally-designated expert.
- Diagnosis of plaque psoriasis.
- Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate.
Additional Inclusion Criteria (One must be met)- Documented mild to moderate disease AND tried and had an inadequate response to ≥ 3 classes of topical therapies (≥ 1 month per class) or intolerance unless medically inadvisable (prior trials not required).
- Documented moderate to severe disease, impaired function or quality of life, or involvement of special areas AND 1 conventional immunomodulator and 2 classes of targeted immunomodulators are medically inadvisable (prior trials not required).
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
Indication- Treatment of adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy
- FDA-approved for mild to moderate plaque psoriasis (expanded indication December 2021)
Patient Eligibility & Diagnosis- Documented diagnosis of plaque psoriasis for ≥ 6 months
- Patients must be cared for by a VA or VA Community Care dermatologist
Prior Therapy Requirements- Inadequate response to 2 or more topical therapies (e.g., corticosteroids in different potencies, vitamin D analogs such as calcipotriene or calcitriol, calcineurin inhibitors such as tacrolimus or pimecrolimus for sensitive areas, or retinoids such as tazarotene)
- Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate
Dosing & Administration- Initiated with a 5-day upward dosage titration to a maintenance dose of 30 mg orally twice daily starting on Day 6
- Slowly up-titrate dosage
Safety & Monitoring Considerations- No routine lab monitoring required
- Decrease dose for renal impairment
- Monitor for GI AEs/diarrhea (risk of dehydration in elderly)
- Avoid strong CYP3A4 inducers
Place in Therapy Considerations- Used as monotherapy
- Appropriate for patients who prefer to avoid frequent injections and lab monitoring and are willing to accept delayed onset and lower chance of skin clearance
- Alternative systemic therapies (methotrexate, cyclosporine, retinoids, targeted biologic agents including TNF inhibitors, IL-12/23 inhibitors, IL-17A inhibitors, IL-17A receptor inhibitor, and IL-23 inhibitors) may be considered for mild to moderate psoriasis recalcitrant to therapies approved for mild–moderate plaque psoriasis including apremilast
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APREMILAST TAB,SA,24HR (EXTENDED RELEASE)
OTEZLA XR
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OTEZLA XR |
2025-10-02 |
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy of apremilast
- Untreated or unstable depression or suicidality, unless a mental health consultant concurs with apremilast treatment
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Adult (18 years of age or older) with recurrence of 2 or more oral ulcers associated with Behçet's disease
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy of apremilast.
- Untreated or unstable depression or suicidality unless mental health consultation concurs with apremilast treatment.
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care dermatologist or locally-designated expert.
- Diagnosis of plaque psoriasis.
- Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate.
Additional Inclusion Criteria (One must be met)- Documented mild to moderate disease AND tried and had an inadequate response to ≥ 3 classes of topical therapies (≥ 1 month per class) or intolerance unless medically inadvisable (prior trials not required).
- Documented moderate to severe disease, impaired function or quality of life, or involvement of special areas AND 1 conventional immunomodulator and 2 classes of targeted immunomodulators are medically inadvisable (prior trials not required).
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy
- Untreated or unstable depression or suicidality, unless a mental health consultant concurs with apremilast treatment
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Nonsevere or predominantly oligoarticular peripheral inflammatory disease and a definite or provisional diagnosis of active psoriatic arthritis (note: ineffective for joint erosions and axial disease)
- Conventional synthetic immunomodulator (methotrexate, leflunomide or sulfasalazine) is medically inadvisable, not tolerated, or not adequate after 12 weeks
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Clinical Adjudication & Supplemental Considerations- Conventional synthetic immunomodulator: Adequate trial requires NO or partial treatment benefit after 12 weeks at doses of 15–25 mg/wk (or lower if limited by toxicity); for inadequate responders, consider switching to subcutaneous methotrexate. For other immunomodulators, require NO or partial treatment benefit after 12 weeks at recommended doses (or lower if limited by toxicity).
- TNFI therapy: Prior trial is not required but should be recommended if medically advisable. For TNFI inadequate/nonresponders, consider switching to a second TNFI, another biologic, or tofacitinib rather than apremilast monotherapy.
- TNFI may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent infections, serious infections, etc.
- Aversity to injections or barriers to in-clinic administration (e.g., travel) should be adjudicated case by case as a reason why a TNFI is medically inadvisable.
Indication- Treatment of adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy
- FDA-approved for mild to moderate plaque psoriasis (expanded indication December 2021)
Patient Eligibility & Diagnosis- Documented diagnosis of plaque psoriasis for ≥ 6 months
- Patients must be cared for by a VA or VA Community Care dermatologist
Prior Therapy Requirements- Inadequate response to 2 or more topical therapies (e.g., corticosteroids in different potencies, vitamin D analogs such as calcipotriene or calcitriol, calcineurin inhibitors such as tacrolimus or pimecrolimus for sensitive areas, or retinoids such as tazarotene)
- Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate
Dosing & Administration- Initiated with a 5-day upward dosage titration to a maintenance dose of 30 mg orally twice daily starting on Day 6
- Slowly up-titrate dosage
Safety & Monitoring Considerations- No routine lab monitoring required
- Decrease dose for renal impairment
- Monitor for GI AEs/diarrhea (risk of dehydration in elderly)
- Avoid strong CYP3A4 inducers
Place in Therapy Considerations- Used as monotherapy
- Appropriate for patients who prefer to avoid frequent injections and lab monitoring and are willing to accept delayed onset and lower chance of skin clearance
- Alternative systemic therapies (methotrexate, cyclosporine, retinoids, targeted biologic agents including TNF inhibitors, IL-12/23 inhibitors, IL-17A inhibitors, IL-17A receptor inhibitor, and IL-23 inhibitors) may be considered for mild to moderate psoriasis recalcitrant to therapies approved for mild–moderate plaque psoriasis including apremilast
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AVATROMBOPAG CAP,SPRINKLE
DOPTELET SPRINKLE
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DOPTELET SPRINKLE |
2025-10-02 |
Indication & Clinical Purpose- Thrombocytopenia due to chronic liver disease (CLD)
- Small-molecule thrombopoietin receptor agonist (TPORA) used to prophylactically and temporarily increase platelet counts prior to invasive procedures
- Aims to decrease prophylactic platelet transfusion and the need for rescue therapy for bleeding
Exclusion Criteria- Thrombocytopenia due to a cause other than CLD (e.g., Immune Thrombocytopenia)
- Past or present arterial or venous thrombotic or thromboembolic event(s) or prothrombotic condition(s), including portal, splenic, mesenteric, or systemic thrombosis
- Uncontrolled generalized infection
- Exposure to eltrombopag or romiplostim in the previous 90 days, or lusutrombopag within the previous 35 days
- Planned invasive procedure where routine preprocedural platelet transfusion is not recommended (bone marrow aspiration/biopsy, traction removal of tunneled central venous catheter, paracentesis)
- Attempting to normalize platelet counts
Inclusion Criteria- Care provided by a VA/VA Community Care hepatologist or locally designated expert in CLD
- Pretreatment platelet count less than 50 x 10^9/L (severe thrombocytopenia) within the 2 weeks prior to initiation
- CLD (Child-Pugh class C is conditionally not recommended due to limited data and exclusion from clinical trials; no clinically meaningful pharmacokinetic effects observed)
- Scheduled to undergo an elective invasive procedure within the next 27 days
- Use of platelet transfusions is medically inadvisable (e.g., risk of transfusion reaction, volume overload, platelet refractoriness, acute lung injury) or patient declines blood products
- In the previous 6 months: Absence of portal vein thrombosis on computed tomography (CT) or magnetic resonance imaging (MRI) OR presence of hepatopetal portal vein blood flow on doppler ultrasonography
Exclusion Criteria- Stem cell disorder (i.e., myelodysplastic syndrome)
- Patient has not received prior therapy with steroids to increase platelet counts
- Thrombocytopenia secondary to bone marrow suppressive anti-cancer therapy, antibiotics, or other drugs
- Thromboembolic events within the past year (unless evaluated by a hematology provider and deemed an appropriate candidate)
- Pregnancy and/or breastfeeding
Inclusion Criteria- Diagnosis of chronic Immune Thrombocytopenia (ITP)
- Platelet count < 30,000 mm³ and/or persistent bleeding resistant/refractory to glucocorticoids
- Relapse after second-line therapies (unless contraindicated or patient is not a candidate): Splenectomy, Rituximab
Counseling & Management Requirements- For patients who can become pregnant: Counseling provided on potential risks vs. benefits of taking drug if patient were to become pregnancy
- Advise patients not to breastfeed during treatment and for 2 weeks following
Exclusion Criteria- Anticipated antiviral treatment includes a direct-acting antiviral (DAA) for chronic HCV
- Currently receiving peginterferon and ribavirin with or without DAA for chronic HCV
- Any contraindications to peginterferon and ribavirin apply
- Active malignancy or stem cell disorder
- Prior history of arterial or venous thrombosis plus ≥2 risk factors (hereditary thrombophilic disorders, estrogen hormone replacement therapy, systemic contraception therapy containing estrogen, smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer)
- Serious cardiac, cerebrovascular, or pulmonary disease
- Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin
- Known hypersensitivity, intolerance, or allergy to peginterferon and ribavirin, eltrombopag tablets, or ingredients
- Evidence of decompensated liver disease (Child-Pugh score ≥7 and/or clinical manifestations)
- Patient infected with HIV
Inclusion Criteria- Under care of and/or in collaboration with an experienced VA HCV practitioner
- Provider has discussed risks/benefits with patient; shared decision made for use
- Diagnosis of chronic HCV infection
- Baseline platelet count <75,000/μL
- Appropriate candidates for peginterferon and ribavirin combination antiviral therapy
- Treatment with peginterferon and ribavirin (dual therapy) anticipated after reaching target platelet goal
- Abdominal imaging negative for portal vein thrombosis within past 3 months
Dosing & Administration- Initiate prior to peginterferon and ribavirin therapy to obtain target platelet count
- Initial dose: 25 mg once daily on empty stomach (1 hour before or 2 hours after meal)
- Adjust by 25 mg increments every 2 weeks to achieve target platelet count (≥90,000/μL for peginterferon alfa-2a; ≥100,000/μL for peginterferon alfa-2b)
- Use lowest dose to achieve/maintain necessary platelet count
- Maintain same pre-treatment dose when starting antiviral therapy; modify during therapy to maintain counts between 50,000-150,000/μL
- Dose reduction NOT needed solely based on East Asian ethnicity
- Maximum dose: 100 mg/day
- If platelets <50,000/μL after ≥2 weeks: increase by 25 mg; wait 2 weeks to assess
- If platelets ≥150,000-200,000/μL: decrease by 25 mg; wait 2 weeks
- If platelets >200,000/μL: stop eltrombopag; monitor twice weekly; reinitiate at dose reduced by 25 mg (or 12.5 mg if previously on 25 mg) when count <100,000/μL
Monitoring Requirements- Prior to initiation: CBC with differential (including platelet), ocular exam for cataracts, Liver Function Panel (Total/Direct bilirubin, AST, ALT, albumin, total protein)
- During therapy: CBC weekly until stable then monthly; Serum liver tests (ALT, AST, bilirubin) every 2 weeks during adjustment then monthly; fractionate bilirubin if elevated; repeat tests within 3-5 days if abnormal; monitor weekly until resolved/stabilized/baseline; regular ocular exams for cataracts
- Upon discontinuation: CBCs weekly for at least four weeks
Safety & Risk Considerations- Box warnings for hepatotoxicity and risk of hepatic decompensation (ascites, hepatic encephalopathy, variceal hemorrhage, spontaneous bacterial peritonitis, hepatocellular carcinoma, death)
- Patients with albumin <3.5g/dL or MELD scores ≥10 at baseline have greatest risk of hepatic decompensation
- High thromboembolism risk: may increase risk; consider risk vs benefit
- Cataracts developed/worsened in 8% of treated patients
Discontinuation Guidelines- Discontinue when antiviral therapy is discontinued
- Discontinue for hepatotoxicity if ALT increases to ≥3X ULN (normal liver) or ≥3X baseline (pre-treatment elevations) and is progressive, persistent ≥4 weeks, accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury/hepatic decompensation
- Non-response: Consider discontinuing after 9 weeks at maximum dose (100 mg/day) if platelet count not increased sufficiently to initiate antiviral therapy
Specific Populations & Interactions- HIV: No safety/efficacy data; limited drug-drug interaction studies
- Renal insufficiency (CrCl<50ml/min): Not studied; use with caution
- Hepatic insufficiency: Clearance reduced in moderate-severe impairment; initial dose 25 mg daily; monitor serum liver tests; AUC ~2-fold higher; half-life prolonged 2-fold
- Pregnancy: Category C; discuss risks/benefits; consider enrollment in Promacta Pregnancy Registry
- Interactions: Substrate of CYP1A2/CYP2C8; inhibitor of OATP1B1/UGTs; chelates polyvalent cations. Separate administration from iron, calcium, aluminum, magnesium, selenium, zinc-containing meds/supplements/food by at least 4 hours.
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NATALIZUMAB-SZTN INJ,SOLN
TYRUKO
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TYRUKO |
2025-10-02 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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APIXABAN TAB,SUSP,ORAL
ELIQUIS
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ELIQUIS |
2025-10-01 |
Indications- Atrial fibrillation/flutter (AF)
- Acute venous thromboembolism (VTE), or prevention of recurrent VTE
- Primary prophylaxis of VTE in patients undergoing hip or knee replacement surgery
- Other indication for anticoagulation (local adjudication required)
Exclusions- Mechanical heart valve
- Moderate to severe rheumatic mitral valve stenosis (for AF/flutter only)
- Antiphospholipid syndrome (APS)
- Known significant liver disease (e.g., acute clinical hepatitis, cirrhosis [Child-Pugh C], or hepatic disease associated with coagulopathy)
- Pregnancy
- Breastfeeding
Pre-Treatment Assessment & Monitoring- Assessment of renal function (CrCl) and hemoglobin, hematocrit, and platelets
- Consider liver function testing in patients with a history of or risk for hepatic insufficiency
- Provider must assess DOAC choice, dose, and duration considering patient’s age, renal function, liver function, concurrent medications, and indication
- Identify and address modifiable risk factors for bleeding (e.g., NSAIDs, antiplatelet therapy)
- Document the treatment plan including duration in the patient’s chart
Dosing & Administration Requirements- For acute VTE: Administer 10 mg twice daily for 7 days as oral loading dose BEFORE starting maintenance doses
- Review drug dosing errors and drug-drug interactions, especially with new starts
Special Populations & Clinical Considerations- Bioprosthetic heart valve placement in the past 3 months: Appropriate based on shared decision-making process between provider and patient
- Severe renal impairment (CrCl <25-30 ml/min) or hemodialysis: Individual evaluation of risks and benefits recommended; net clinical benefit unclear
- Apixaban may be the preferred DOAC when CrCl is less than 30 ml/min
- For patients who can become pregnant: Counsel on potential risks vs benefits of treatment and use of effective contraception during therapy
FDA Approved Adult Indications- Non-valvular atrial fibrillation
- Treatment of DVT and PE (after 5-10 days of parenteral anticoagulant)
- Reduction in the risk of recurrent DVT and PE following initial therapy
- Post-surgical VTE prophylaxis following hip replacement surgery
- Post-surgical VTE prophylaxis following knee replacement surgery
Oversight & Initiation- Chronic DOAC therapy requires initial assessment, education, and follow-up by locally designated staff (e.g., anticoagulation management program or other designees).
- Facilities should utilize decision support tools and/or anticoagulation staff for upfront review to verify appropriate candidate selection, agent choice, and dosing upon initiation.
- Short-term treatment (e.g., post-surgical VTE prophylaxis) or very low dose regimens should follow education/monitoring protocols similar to alternative agents in that setting.
Laboratory Monitoring- Baseline: Serum creatinine (SCr) to estimate creatinine clearance (CrCl); CrCl estimated using Cockcroft-Gault equation with actual body weight for apixaban trials. Hemoglobin, hematocrit, and platelets required. Liver function tests may be considered for patients with history/risk of hepatic insufficiency. PT/aPTT may be obtained for emergency reference. Baseline values drawn within 1-3 months are acceptable per provider clinical judgment based on age/health status/comorbidities.
- Follow-up: SCr monitored at least annually (more frequently if CrCl < 60 ml/min, concomitant illness worsening renal function, or age ≥ 75 years). Hemoglobin, hematocrit, and platelets monitored at least annually or as clinically dictated. Liver function testing considered for underlying liver disease or clinical indication.
Patient Education- Initial and periodic education must cover: capsule/tablet identification, proper storage, therapy indication, risks/benefits, anticipated duration, daily dose/dosing changes (e.g., loading doses), administration considerations, drug interactions, monitoring requirements, adherence importance, management of missed/extra doses, signs/symptoms of bleeding/thromboembolic events, avoidance of major bleeding risk medications (e.g., NSAIDs, antiplatelets) unless instructed, non-bleeding adverse events, fall risks/mitigation, medication supply acquisition, pre-procedure provider notification for peri-procedural management, anticoagulation provider contact information, and gender-specific considerations for women of childbearing age (menstrual difficulties, pregnancy, contraception).
Adherence Monitoring- Monitor adherence, refill history, and medication tolerance, especially at therapy initiation.
- Utilize population management tools, telephone follow-up, face-to-face visits, secure messaging, or combinations based on site resources.
Follow-up Care- Initial: Within 2-4 weeks of initiation (or sooner if clinically indicated) to assess tolerance, bleeding, thromboembolic events, other adverse events (e.g., GI intolerance), adherence, correct dosing (e.g., transition from high-intensity initiation dosing for acute VTE), duplicate therapy, and reinforce education.
- Periodic/Long-term: Reassess adherence, screen for drug interactions, monitor labs as needed. Time points, methods, and responsible staff determined locally per VHA Directive 1108.16(1).
Quality Assurance- Incorporate DOACs into ongoing quality assurance plans per VHA Directive 1108.16(1).
- Report adverse events per local protocols and P&T Committee; enter into VA ADERS.
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
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APIXABAN CAP,SPRINKLE
ELIQUIS SPRINKLE
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ELIQUIS SPRINKLE |
2025-09-30 |
Indications- Atrial fibrillation/flutter (AF)
- Acute venous thromboembolism (VTE), or prevention of recurrent VTE
- Primary prophylaxis of VTE in patients undergoing hip or knee replacement surgery
- Other indication for anticoagulation (local adjudication required)
Exclusions- Mechanical heart valve
- Moderate to severe rheumatic mitral valve stenosis (for AF/flutter only)
- Antiphospholipid syndrome (APS)
- Known significant liver disease (e.g., acute clinical hepatitis, cirrhosis [Child-Pugh C], or hepatic disease associated with coagulopathy)
- Pregnancy
- Breastfeeding
Pre-Treatment Assessment & Monitoring- Assessment of renal function (CrCl) and hemoglobin, hematocrit, and platelets
- Consider liver function testing in patients with a history of or risk for hepatic insufficiency
- Provider must assess DOAC choice, dose, and duration considering patient’s age, renal function, liver function, concurrent medications, and indication
- Identify and address modifiable risk factors for bleeding (e.g., NSAIDs, antiplatelet therapy)
- Document the treatment plan including duration in the patient’s chart
Dosing & Administration Requirements- For acute VTE: Administer 10 mg twice daily for 7 days as oral loading dose BEFORE starting maintenance doses
- Review drug dosing errors and drug-drug interactions, especially with new starts
Special Populations & Clinical Considerations- Bioprosthetic heart valve placement in the past 3 months: Appropriate based on shared decision-making process between provider and patient
- Severe renal impairment (CrCl <25-30 ml/min) or hemodialysis: Individual evaluation of risks and benefits recommended; net clinical benefit unclear
- Apixaban may be the preferred DOAC when CrCl is less than 30 ml/min
- For patients who can become pregnant: Counsel on potential risks vs benefits of treatment and use of effective contraception during therapy
FDA Approved Adult Indications- Non-valvular atrial fibrillation
- Treatment of DVT and PE (after 5-10 days of parenteral anticoagulant)
- Reduction in the risk of recurrent DVT and PE following initial therapy
- Post-surgical VTE prophylaxis following hip replacement surgery
- Post-surgical VTE prophylaxis following knee replacement surgery
Oversight & Initiation- Chronic DOAC therapy requires initial assessment, education, and follow-up by locally designated staff (e.g., anticoagulation management program or other designees).
- Facilities should utilize decision support tools and/or anticoagulation staff for upfront review to verify appropriate candidate selection, agent choice, and dosing upon initiation.
- Short-term treatment (e.g., post-surgical VTE prophylaxis) or very low dose regimens should follow education/monitoring protocols similar to alternative agents in that setting.
Laboratory Monitoring- Baseline: Serum creatinine (SCr) to estimate creatinine clearance (CrCl); CrCl estimated using Cockcroft-Gault equation with actual body weight for apixaban trials. Hemoglobin, hematocrit, and platelets required. Liver function tests may be considered for patients with history/risk of hepatic insufficiency. PT/aPTT may be obtained for emergency reference. Baseline values drawn within 1-3 months are acceptable per provider clinical judgment based on age/health status/comorbidities.
- Follow-up: SCr monitored at least annually (more frequently if CrCl < 60 ml/min, concomitant illness worsening renal function, or age ≥ 75 years). Hemoglobin, hematocrit, and platelets monitored at least annually or as clinically dictated. Liver function testing considered for underlying liver disease or clinical indication.
Patient Education- Initial and periodic education must cover: capsule/tablet identification, proper storage, therapy indication, risks/benefits, anticipated duration, daily dose/dosing changes (e.g., loading doses), administration considerations, drug interactions, monitoring requirements, adherence importance, management of missed/extra doses, signs/symptoms of bleeding/thromboembolic events, avoidance of major bleeding risk medications (e.g., NSAIDs, antiplatelets) unless instructed, non-bleeding adverse events, fall risks/mitigation, medication supply acquisition, pre-procedure provider notification for peri-procedural management, anticoagulation provider contact information, and gender-specific considerations for women of childbearing age (menstrual difficulties, pregnancy, contraception).
Adherence Monitoring- Monitor adherence, refill history, and medication tolerance, especially at therapy initiation.
- Utilize population management tools, telephone follow-up, face-to-face visits, secure messaging, or combinations based on site resources.
Follow-up Care- Initial: Within 2-4 weeks of initiation (or sooner if clinically indicated) to assess tolerance, bleeding, thromboembolic events, other adverse events (e.g., GI intolerance), adherence, correct dosing (e.g., transition from high-intensity initiation dosing for acute VTE), duplicate therapy, and reinforce education.
- Periodic/Long-term: Reassess adherence, screen for drug interactions, monitor labs as needed. Time points, methods, and responsible staff determined locally per VHA Directive 1108.16(1).
Quality Assurance- Incorporate DOACs into ongoing quality assurance plans per VHA Directive 1108.16(1).
- Report adverse events per local protocols and P&T Committee; enter into VA ADERS.
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
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MAGNESIUM SULFATE/ POTASSIUM SULFATE/ SODIUM SULFATE SOLN,ORAL
SOD SULF-POTASS SULF-MAG SULF, SUPREP
|
SOD SULF-POTASS SULF-MAG SULF, SUPREP |
2025-09-30 |
Inclusion Criteria- Failure unrelated to compliance or other causes, contraindication or intolerance to formulary PEG-3350 bowel prep regimens.
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ZANUBRUTINIB TAB,ORAL
BRUKINSA
|
BRUKINSA |
2025-08-28 |
Exclusion Criteria- Patient has not been screened for Hepatitis B Virus (HBV)
- Unmanageable drug-drug or drug-food interaction identified
- History of stroke or intracranial hemorrhage in prior 6 months
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (NYHA Class 3 or 4), or myocardial infarction in prior 6 months
- Current or history of Central Nervous System (CNS) lymphoma
- Active or uncontrolled infection
- Known pregnancy
- Lactating
Indications- Relapsed or refractory mantle cell lymphoma and progressive disease or intolerance to at least one prior therapy
- Relapsed or refractory marginal zone lymphoma and received at least one anti-CD20-based regimen
- Waldenstrom macroglobulinemia
- Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) if acalabrutinib is not clinically appropriate for patient
- Relapsed or refractory follicular lymphoma, in combination with obinutuzumab, after two or more lines of therapy
Additional Clinical Requirements- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0-2
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for 1 week after the last dose
- Advise patients not to breastfeed/provide breastmilk during treatment and for at least 2 weeks after the last dose
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BRENSOCATIB TAB
BRINSUPRI
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BRINSUPRI |
2025-08-21 |
Indication- Treatment of non-cystic fibrosis bronchiectasis (NCFB) in adults.
Patient Population & Eligibility- Adults with a diagnosis of NCFB (clinical symptoms for at least 3 months, including chronic cough and purulent sputum production) confirmed by CT scan.
- History of >2 exacerbations in the prior year.
- Indicated for patients despite use of chronic macrolide therapy or who are unable to use macrolides or inhaled antipseudomonal antibiotics.
- Not recommended for patients with a primary diagnosis of COPD or asthma until more evidence is available.
- Subgroup analyses indicate no benefit for patients with postbronchodilator FEV1 <50%, Bronchiectasis Severity Index (BSI) >9, and/or an asthma diagnosis.
Dosing & Administration- 10 mg or 25 mg tablets administered once daily.
Safety Monitoring & Precautions- Monitor for dermatologic adverse events, including new rash, dry skin, and hyperkeratosis; refer to a Dermatologist if a new rash or skin condition develops.
- Monitor for increased risk of gingival and periodontal effects; advise patients to maintain routine dental hygiene and attend regular dental checkups.
- Monitor liver function tests (AST/ALT elevation noted, resolving upon discontinuation).
- Monitor for severe infections (pneumonia and severe infection rates reported).
- Effectiveness and safety of live attenuated vaccines are unknown when administered during treatment.
Contraindications & Warnings- No boxed warnings or contraindications listed.
- Primary diagnosis of COPD or asthma excludes patients from trial eligibility and use should be avoided until more evidence is available.
Exclusion Criteria- Exacerbation/worsening symptoms are primarily due to asthma and/or COPD
- Actively smoking
- Diagnosis of cystic fibrosis
- Known or suspected immunodeficiency disorder (history of invasive opportunistic infections)
Monitoring- Gingival and periodontal adverse events have been reported
- Patients should be advised to perform routine daily dental hygiene
- Regular dental checkups are recommended
- Core Inclusion Criteria (All must be met)
- Provider is a VA or VA Community Care pulmonologist or designated expert
- Chronic cough and/or mucopurulent sputum production for at least 3 months within the past year
- Diagnosis of non-cystic fibrosis bronchiectasis (NCFB) confirmed by CT scan (completed within the past 2 years with no case of pneumonia reported within 12 months of the CT scan)
- > 2 pulmonary exacerbations requiring antibiotics or > 1 severe exacerbation requiring hospitalization in past 12 months
- Continues to have exacerbations despite receiving long-term antibiotic therapy (e.g., > 3 months of macrolide or inhaled antipseudomonal antibiotic) with adherence confirmed by review of refill history, OR unable to take long-term antibiotics
- Receiving guideline-directed therapies for NCFB including treatment of underlying causes, airway clearance techniques, mucoactive agents, inhalers, pulmonary rehabilitation, etc., as clinically indicated
- Additional Inclusion Criteria (Select if applicable)
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
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ACECLIDINE SOLN,OPH
VIZZ
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VIZZ |
2025-08-14 |
Patient Population & Clinical Characteristics- Adults aged 45-75 years of either sex
- Refractive range from -4.00 to +1.00 D sphere
- Astigmatism up to 2.00 D
- Spherical equivalent no more myopic than -4.00 D
Administration & Dosing- Ophthalmic solution: aceclidine 1.44% in a single-dose vial
- Instill 1 drop in each eye, wait 2 minutes and instill a second drop in each eye once daily from the same single-dose vial
- Contact lenses should be removed prior to aceclidine administration
Warnings & Precautions- Blurred vision
- Risk of retinal tear/detachment
- Iritis
- Hypersensitivity
- Potential for eye injury and contamination
Exclusion Criteria- Female of childbearing potential who is currently pregnant, nursing, or planning a pregnancy
- Known contraindications or sensitivity to the use of any study medications or their components
- Active ocular infection, positive history of an ocular herpetic infection, preauricular lymphadenopathy, or ongoing active ocular inflammation
- Moderate or severe dry eye
- Clinically significant abnormal lens findings
→ Full criteria details
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FERRIC MALTOL CAP,ORAL
ACCRUFER
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ACCRUFER |
2025-08-12 |
Indication- Treatment of iron deficiency in adults
Patient Population & Clinical Context- Adults with iron deficiency anemia (IDA)
- Specifically studied in patients with inflammatory bowel disease (IBD) and chronic kidney disease (CKD) not on dialysis
- Studied in patients intolerant or refractory to treatment with oral iron therapy
Dosing & Administration- 30 mg capsules
- Recommended dose: 30 mg twice daily, taken one hour before or two hours after a meal
- Capsules should not be opened for chewed
- Separate administration from other oral medications by at least 4 hours if concomitant use may decrease bioavailability of iron or the other medication
Contraindications- Hypersensitivity to ferric maltol (reactions may include shock, clinically significant hypotension, loss of consciousness, and/or collapse)
- Hemochromatosis and other iron overload syndromes
- Receiving repeated blood transfusions
Warnings & Precautions- Increased risk of IBD flare: Avoid use in patients with active IBD flare due to potential risk for increased gastrointestinal inflammation
- Iron overload: Excess iron storage and possibly iatrogenic hemosiderosis can occur with excessive therapy; assess iron parameters prior to treatment and monitor while on therapy; do not administer to patients with iron overload or those receiving IV iron
- Risk of overdose in children due to accidental ingestion: Keep product out of reach of children; contact a doctor or poison control center immediately in case of accidental overdose
Place in Therapy & Formulary Criteria- Requires a prescription (non-formulary status)
- Oral iron therapies available on the VA National Formulary should be used first for management of IDA where oral iron is indicated
- Use may be determined on a case-by-case basis depending on patient-specific considerations including efficacy or tolerability to current available options, convenience, and cost
- IV iron may be considered where oral iron therapy is ineffective or not tolerated, in selected patients with impaired absorption or ongoing blood loss, or in patients with IDA and CKD on dialysis
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DELGOCITINIB CREAM,TOP
ANZUPGO
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ANZUPGO |
2025-08-07 |
Indication & Patient Population- Adults with moderate to severe chronic hand eczema (CHE)
- CHE defined as hand eczema persisting for >3 months or returning ≥2 times within the previous 12 months
- Patients who have had an inadequate response to topical corticosteroids, or for whom topical corticosteroids are not advisable
Dosing & Administration- Apply a thin layer twice daily to affected areas only on the hands and wrists
- Maximum dosage: Do not use more than 30 grams per 2 weeks or 60 grams per month
- Dosage form: Cream 2% (20 mg/g)
Pretreatment Requirements- Complete any necessary guideline-recommended immunizations, including herpes zoster vaccinations
- Consider viral hepatitis screening prior to initiation
- Consider lipid panel assessment prior to initiation
Monitoring & Safety Warnings- Monitor for infections
- Monitor for viral hepatitis reactivation
- Monitor for nonmelanoma skin cancer (NMSC)
- Monitor for increases in total cholesterol, low-density lipoprotein, cholesterol, and triglycerides
- Assess for serious infections, immunizations status, and potential risks related to JAK inhibition (mortality, major adverse cardiovascular events, thrombosis, malignancies excluding NMSC)
Contraindications & Precautions- Not recommended for use in patients with active hepatitis B or hepatitis C
- Insufficient human data for pregnancy; animal studies showed post-implantation loss but no embryofetal toxicity in rabbits, and decreased fetal weight/skeletal variations in rats
- Advise breastfeeding women to avoid direct contact with the nipple and surrounding area immediately after applying to hands/wrists
Therapeutic Positioning & Sequencing- Positioned after use of moderate-to-high-potency topical corticosteroids, tacrolimus ointment 0.1%, and tapinarof cream 1% (if CHE is the atopic subtype)
Exclusion Criteria- Uncontrolled active infection (may be started/restarted once treatment for the infection is initiated)
- Active hepatitis B or hepatitis C
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation of therapy
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care dermatologist or locally-designated expert
- Documented diagnosis of moderate or severe chronic hand eczema (persisted for more than 3 months or returned twice or more in the previous 12 months)
- Offered all age-appropriate vaccinations prior to initiating therapy, including for herpes zoster
- High or super-high potency topical corticosteroid therapy is medically inadvisable, not tolerated, or not adequate (after ≥ 4 weeks)
- Topical tacrolimus ointment 0.1% therapy is medically inadvisable, not tolerated, or not adequate (after ≥ 4 weeks)
Additional Inclusion Criteria- For atopic subtype chronic hand eczema: Topical tapinarof cream 1% therapy is medically inadvisable, not tolerated, or not adequate (after ≥ 4 weeks)
- Females who are pregnant or planning to become pregnant: Counseling provided on potential risks vs benefits of treatment
- Females who are lactating/providing breastmilk to an infant or planning to do so: Counseling provided on the risks and benefits of treatment
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FIDAXOMICIN TAB
DIFICID
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DIFICID |
2025-07-24 |
Exclusion Criteria- Prescribed for the treatment of systemic infections
- History of hypersensitivity reaction to fidaxomicin or another macrolide antibiotic
- Asymptomatic Clostridioides difficile colonization
- Fulminant Clostridioides difficile infection (CDI) (e.g., life-threatening CDI or toxic megacolon) or ileus
Inclusion Criteria- Clinical symptom onset (e.g., 3 or more unformed stools in 24 hours after discontinuation of laxatives) AND laboratory confirmation of CDI
- PLUS at least one of the following:
- Initial episode of CDI who is at increased risk of CDI recurrence (age ≥65 years old, concomitant antibiotic use during CDI treatment, and/or immunosuppression)
- Recurrent episode of CDI
Dosage and Administration- Standard regimen: 200 mg orally twice daily for 10 days with or without food
- Extended-pulse regimen: 200 mg orally twice daily for 5 days, then 200 mg orally every other day for 20 days with or without food
Supplemental Clinical Information & Management Guidelines- Recurrence is typically defined as a repeated symptomatic, laboratory-confirmed case of CDI within 12 weeks after a prior episode
- Patients at high risk of CDI recurrence include age ≥65 years old, concomitant antibiotic use during CDI treatment, and immunosuppression
- Vancomycin 125 mg PO QID x 10 days is an acceptable alternative treatment regimen for a first episode of CDI
- A repeat standard course of vancomycin or a tapered and pulse vancomycin regimen are acceptable alternative options for the first recurrent episode of CDI (vancomycin taper/pulsed regimen is also acceptable for subsequent recurrences)
- Infectious Diseases and/or Gastroenterology consults should be considered for patients with multiple CDI recurrences or fulminant CDI
- Discontinue therapy with the inciting antimicrobial as soon as possible, as this may influence the risk of CDI recurrence
Indications & Clinical Use- • Treatment of initial and recurrent non-fulminant Clostridioides difficile infection (CDI)
- • First-line treatment option for initial, recurrent, non-severe, and severe, non-fulminant CDI episodes
- • Appropriate choice for first recurrence in patients initially treated with vancomycin who experience recurrence
Dosing & Regimens- • Standard regimen: 200 mg by mouth twice daily (BID) for 10 days
- • Extended-pulse regimen: 200 mg BID for 5 days followed by one tablet every other day (QOD) on days 7–25
Contraindications & Exclusions- • History of hypersensitivity reaction to fidaxomicin or another macrolide antibiotic
- • Systemic infections
- • Asymptomatic C. difficile colonization
- • Fulminant CDI or patients with ileus
Guideline Recommendations & Formulary Criteria- • Preferred first-line agent per IDSA/SHEA guidelines, particularly for patients at high risk of recurrence
- • Recommended as an alternative to vancomycin after an initial course of vancomycin or metronidazole for first recurrence
- • Standard or extended-pulse regimen recommended for second or subsequent recurrences (per IDSA/SHEA; ACG guidelines do not specifically recommend fidaxomicin for subsequent recurrences)
- • Updated VA Criteria For Use aligns with 2021 guidelines to broaden the role of fidaxomicin as a treatment option for CDI and address prior underutilization in the VA system
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RIVAROXABAN GRNL,RCNST-ORAL
XARELTO
|
XARELTO |
2025-07-17 |
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
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OLEZARSEN INJ,SOLN
TRYNGOLZA
|
TRYNGOLZA |
2025-07-16 |
Exclusion Criteria- Serious hypersensitivity reaction to olezarsen
- Severe hypertriglyceridemia due to multifactorial chylomicronemia syndrome (MCS) or other causes, including secondary causes
Inclusion Criteria- Provider is a VA or VA Community Care Cardiologist, Endocrinologist, or designated lipid expert with experience in managing familial lipid disorders
- Genetically confirmed diagnosis of familial chylomicronemia syndrome (FCS)
- Commitment to adhering to a fat restricted diet of <20 grams/day
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
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ACOLTREMON SOLN,OPH
TRYPTYR
|
TRYPTYR |
2025-07-03 |
Indication- Treatment of the signs and symptoms of dry eye disease
Dosage Form & Administration- Ophthalmic solution: 0.003% acoltremon in a single-dose vial
- Dosed twice daily
Warnings & Precautions- Potential for eye injury and contamination
- Should not be administered while wearing contact lenses
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BOSENTAN TAB,SUSP,ORAL
TRACLEER
|
TRACLEER |
2025-06-26 |
Exclusion Criteria- Known pregnancy
- Baseline hepatic transaminase elevations >3 times the upper limit of normal
- Moderate or severe liver impairment (e.g., Child-Pugh Class B or C)
Inclusion Criteria- Care provided by a VA/VA Community Care provider experienced in the management of pulmonary arterial hypertension (PAH) (certified and enrolled in the bosentan REMS Program)
- World Health Organization (WHO) Group 1 PAH
- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis: mean pulmonary artery pressure >25 mmHg, pulmonary artery wedge pressure ≤15 mm Hg, and pulmonary vascular resistance >3 Wood Units
- Baseline hepatic transaminase testing and commitment to monthly testing
- Intolerance, inadequate response, or unable to use ambrisentan (ambrisentan is the preferred endothelin receptor antagonist when clinically appropriate)
Reproductive Safety & Counseling- Females who can become pregnant: Pregnancy must be excluded prior to receiving bosentan; counseling on potential risk vs benefit and effective contraception use prior to, during, and one month after stopping treatment is required
- Males of reproductive potential: Counseling provided on the potential risk of bosentan to adversely affect spermatogenesis and impair fertility
Hemodynamic & Clinical Context Considerations- Hemodynamic definition applies to the majority of PAH patients and is recommended by the 7th World Symposium for Pulmonary Hypertension for consideration of PAH-specific drug therapy including endothelin receptor antagonists
- Decisions for hemodynamic parameters outside specified thresholds should be made by PAH specialists in the context of the individual patient's entire presentation
- mPAP and PVR thresholds have been expanded to include mPAP >20 mmHg and PVR >2 Wood Units, though most PAH therapies were studied in populations meeting the older definition
- Consensus is lacking on whether PAH treatment should be considered in patients with mildly elevated pressures per the 7th World Symposium
- PAWP ≤15 mm Hg is traditionally used to rule out pulmonary hypertension due to left-heart disease, where PAH-specific therapies have not been shown to benefit and may result in harm
- REVEAL U.S. registry data suggests PAH may exist in patients with PAWP 16-18 mmHg; survival did not significantly differ from those with PAWP ≤15 mm Hg at diagnosis
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SOFPIRONIUM GEL,TOP
SOFDRA
|
SOFDRA |
2025-06-17 |
Indication- Treatment of primary axillary hyperhidrosis in adults
Dosing & Administration- Apply a single pump actuation to each armpit once daily at bedtime
- Topical gel 12.45% (w/w) supplied in a 50-mL bottle with metered dose pump and applicator
Patient Population Considerations- Geriatric Use: Insufficient data; dosage should usually start at the low end
- Renal Impairment: Not studied
- Hepatic Impairment: Not studied
Contraindications & Warnings/Precautions- Contraindicated in medical conditions that can be exacerbated by anticholinergic effects (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjögren’s syndrome)
- Warnings include urinary retention, control of body temperature, and operating machinery or an automobile
- Top adverse events (≥ 2%): Dry mouth, blurred vision, mydriasis, urinary retention; Local skin reactions: Pain, erythema, dermatitis, pruritus, irritation, exfoliation
Drug Interactions- Concomitant anticholinergics
- Strong inhibitors of CYP2D6 (avoid)
Pregnancy & Lactation- Pregnancy: Insufficient human data; no significant embryofetal developmental adverse effects in animals; no specific recommendations about use in pregnancy
- Lactation: Insufficient human data; detected in animal milk; likely to be present in human milk; consider risks vs benefits
VA Place in Therapy / Criteria-for-Use- Second-line (2L) treatment for primary axillary hyperhidrosis
- Indicated for patients with an inadequate response or intolerance to an aluminum chloride hexahydrate antiperspirant
- Indicated for patients for whom a prescription antiperspirant is medically inadvisable
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PERAMPANEL TAB
FYCOMPA
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FYCOMPA |
2025-06-12 |
Exclusion Criteria- Preexisting aggression, hostility, irritability, anger, homicidal ideation and threats that is uncontrolled/untreated
- Severe hepatic impairment (Child Pugh Class C)
- CrCL 10-30 ml/min or on hemodialysis
Inclusion Criteria- Medication management by a VA Neurologist or VA purchased Neurology care
- Inadequate response, intolerable side effects, or contraindication to two formulary antiepileptic medications for partial seizures (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, divalproex sodium, topiramate, zonisamide) or primarily generalized seizures (lamotrigine, levetiracetam, topiramate, valproate, zonisamide)
Special Populations & Pregnancy- Category C for women of childbearing potential
- Adverse events observed in animal reproduction studies
- Limited information on use in pregnancy; if inadvertent exposure occurs, close monitoring of the mother and fetus/newborn is recommended
Dosage & Administration- Without enzyme-inducing AEDs: Starting dose 2 mg once daily at bedtime. Titrate by increments of 2 mg once daily no more frequently than weekly intervals based on clinical response and tolerability. Recommended maintenance: Partial-Onset Seizures 8 to 12 mg once daily; Primary Generalized Tonic-Clonic Seizures 8 mg once daily.
- With enzyme-inducing AEDs (phenytoin, carbamazepine, oxcarbazepine): Starting dose 4 mg once daily at bedtime. Titrate by increments of 2 mg once daily no more frequently than weekly intervals. Maintenance dose not established; highest studied dose is 12 mg once daily.
Monitoring & Safety Considerations- Black box warning for serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger and homicidal ideation and threats (occurs regardless of prior psychiatric history or concomitant medications)
- Increased risk of suicidal thoughts or behavior; monitor for emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
- Avoid strong CYP3A4 inducers (rifampin, St. John's wort)
- Effectiveness of hormonal contraceptives containing levonorgestrel may decrease with 12 mg once daily dose
- Concomitant enzyme-inducing antiepileptics may compromise perampanel efficacy
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AVIBACTAM/ AZTREONAM INJ,LYPHL
EMBLAVEO
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EMBLAVEO |
2025-06-05 |
Indication- In combination with metronidazole (MTZ) for adults who have limited or no alternative options for the treatment of complicated intra-abdominal infections (cIAI) caused by susceptible gram-negative bacteria
- Approval based on limited clinical safety and efficacy data
Dosing & Administration- IV injection vial containing 1.5 g aztreonam and 0.5 g avibactam (total dose 2g)
- For CrCl > 50 mL/min: 2g IV every 6 hours, infused over 3 hours, following a loading dose of 2.67g
- Dose adjustments required for kidney dysfunction
Patient Selection & Clinical Context- Likely limited to select patients with infections caused by difficult-to-treat gram-negative bacteria
- Generally managed by experts in Infectious Diseases and Antimicrobial Stewardship to ensure appropriate use
- Infections due to Enterobacterales producing metallo-beta-lactamases (MBLs) are uncommon in the US; typically seen in patients with extensive prior antibiotic exposure or international travel
- Less than 20% of carbapenem-resistant Enterobacterales (CRE) in the US produce MBL
- Can be used in patients with severe IgE-mediated cephalosporin allergy (other than ceftazidime)
Safety & Monitoring- Most common adverse reactions: hepatic adverse reactions, anemia, diarrhea, hypokalemia, and pyrexia
- ALT elevations > 5x the upper limit of normal occurred in 3.8% of patients
- Discontinuation due to elevated hepatic enzymes occurred in only 4 patients across development trials
- No unexpected adverse events noted
Preparation & Handling Requirements- Must be administered over 3 hours every 6 hours
- Complicated preparation and possible drug wastage
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TREPROSTINIL CAP,INHL
YUTREPIA
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YUTREPIA |
2025-06-05 |
Provider & Care Setting Requirements- Care provided by a VA or VA Community Care provider experienced in the management of PAH
Diagnostic & Hemodynamic Criteria- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis
- Mean pulmonary artery pressure greater than 20 mmHg
- Pulmonary capillary wedge pressure 15 mmHg or less
- Pulmonary vascular resistance greater than 2 Wood units
Classification & Clinical Status- World Health Organization (WHO) Group 1 PAH
- Unacceptable or deteriorating clinical status on PAH-directed therapy with, or not a candidate for, an endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5i)
- Efficacy established in patients with NYHA Functional Class III symptoms
Formulation & Dosing Preferences- Nebulized solution preferred if patient requires more than one cartridge or capsule per dose using the DPI (e.g., >64 mcg of TYVASO or >106 mcg of YUTREPIA)
- Dry powder inhalers (DPIs) reserved for patients with documented inability to use the nebulized product
Adjudication & Documentation- Individual cases that are exceptions to inclusion/exclusion criteria should be adjudicated at the local facility level per P&T committee and pharmacy services policy/procedures
- Product information should be consulted for detailed prescribing information
Provider & Care Setting Requirements- Care must be provided by a VA or VA Community Care provider experienced in the management of pulmonary hypertension (PH).
Diagnosis & Indication Criteria- Definitive, confirmed diagnosis of interstitial lung disease (ILD) (e.g., diffuse parenchymal lung disease on chest CT).
- Examples of ILD include idiopathic interstitial pneumonia, combined pulmonary fibrosis and emphysema, connective tissue disease, and chronic hypersensitivity pneumonitis.
- Definitive, confirmed diagnosis of WHO Group 3 PH associated with ILD.
Hemodynamic Criteria (via Right-Heart Catheterization)- Mean pulmonary artery pressure of at least 25 mmHg.
- Pulmonary capillary wedge pressure of 15 mmHg or less.
- Pulmonary vascular resistance greater than 3 Wood units.
Formulation & Dosing Preferences- Nebulized solution is preferred for patients requiring more than one cartridge per dose using the dry powder inhaler (DPI) (e.g., >64 mcg of TYVASO or >106 mcg of YUTREPIA).
- DPI should be reserved for patients with a documented inability to use the nebulized product.
Adjudication & Clinical Management- All inclusion criteria must be met.
- Individual cases that are exceptions to exclusion/inclusion criteria or require formulation preference adjustments should be adjudicated at the local facility level per P&T Committee and Pharmacy Services policies/procedures.
Indications- Pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability
- Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability
Patient Population & Eligibility- WHO Group 1 PAH patients who are either prostacyclin naïve and on ≤2 nonprostacyclin oral PAH agents, or transitioning from stable doses of nebulized treprostinil
- Patients with PH-ILD (not specifically evaluated in clinical trials but considered for use)
- May be useful for patients who are unable to use DPIs that require strong inhalation due to low inspiratory effort requirement
Dosing Requirements- Treatment naïve: Initiate at 26.5 mcg four times daily
- Target maintenance dose: 79.5 to 106 mcg four times daily
- Transitioning from treprostinil nebulized inhalation solution (TYVASO): Dose determined by current TYVASO breaths per dose (≤5 breaths = 26.5 mcg; 6–8 breaths = 53 mcg; 9–11 breaths = 79.5 mcg; 12–14 breaths = 106 mcg; 15–17 breaths = 132.5 mcg requiring 2 capsules; ≥18 breaths = 159 mcg requiring 2+ capsules)
- Doses exceeding 106 mcg require two capsules and double the cost
Safety & Monitoring Considerations- Monitor for common adverse events: cough, headache, throat irritation, dizziness
- Discontinuation due to adverse events observed at 12% in clinical trials
- Assess risk of symptomatic hypotension (vasodilator effect)
- Assess risk of bleeding (platelet aggregation inhibitor)
- Monitor for bronchospasm, with increased risk in patients with asthma, COPD, or other bronchial hyperreactivity
- Adjust/monitor for CYP2C8 inhibitor co-administration (increased exposure) and CYP2C8 inducer co-administration (decreased exposure)
Formulary & Use Context- Considered an alternative to treprostinil inhaled nebulized solution (TYVASO) or TYVASO DPI for PAH and PH-ILD
- Approved based on demonstration of safety and tolerability rather than efficacy
- Requires administration via a specialized capsule-based inhaler; device discarded every 7 days
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TELISOTUZUMAB VEDOTIN-TLLV INJ,LYPHL
EMRELIS
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EMRELIS |
2025-05-29 |
Indication & Patient Selection- Previously treated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)
- High c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining]
- Currently approved under accelerated approval
Dosing & Administration- 1.9 mg/kg intravenously every 2 weeks
- Continue until disease progression or unacceptable toxicity
- Available as 20 mg or 100 mg telisotuzumab vedotin as lyophilized powder in a single-dose vial
Monitoring & Precautions- Monitor for vision changes, dry eye, and other ocular symptoms; hold or consider discontinuation according to severity
- Ensure adequate venous access or administer via central line to reduce discomfort associated with infusion
- Assess ECOG performance status (0-1) and prior systemic therapy lines (1-2 lines, including 1 line of cytotoxic chemotherapy)
Warnings & Contraindications- No boxed warnings or contraindications listed
- Embryo-fetal toxicity: Can cause fetal harm in a pregnant woman; advise effective contraception
- Peripheral neuropathy: Occurred in 51% of patients (11% grade 3); led to discontinuation in 13%
- ILD/pneumonitis: Occurred in 10% of patients (3% grade 3, 0.6% grade 4); led to discontinuation in 7%
- Infusion-related reactions: Occurred in 3% of patients (1.2% grade 3, 0.6% grade 4); led to discontinuation in 0.6%
Adverse Events & Management- Pre-medications recommended for patients who experience an infusion-related reaction (administered 30-60 minutes prior to subsequent infusions): Diphenhydramine 25-50mg PO/IV, Famotidine 20mg PO/IV, Acetaminophen 650-1,000mg PO/IV, Methylprednisolone 125mg IV (or equivalents)
- Adverse events occurring in ≥20% of patients: decreased albumin, increased glucose, peripheral neuropathy, decreased calcium, increased ALT, decreased lymphocytes, increased GGT, decreased hemoglobin, increased AST, decreased phosphorous/sodium, increased alkaline phosphatase, fatigue, peripheral edema, decreased appetite
- Fatal events (5%): ILD/pneumonitis, pneumonia, sudden death, noninfectious endocarditis, myocardial infarction
Exclusion Criteria- Radiation therapy to the lungs within 6 months
- History of interstitial lung disease (ILD) or pneumonitis requiring steroids, or prior ILD or pneumonitis within 3 months
- Unresolved grade ≥2 adverse events
- Major surgery within 3 weeks
VA-Specific Considerations- c-Met protein expression is not currently routinely evaluated in VHA
- Risk vs. benefit analysis should be considered due to notable incidence of fatal adverse events and pending phase III data (TeliMET NSCLC-01)
- Currently not listed in VA Oncology Clinical Pathways; c-Met overexpression not mentioned in pathways
Exclusion Criteria- Absolute neutrophil count (ANC) <1,000/mm3 (unless Duffy null phenotype), platelets <100,000/mm3
- CrCl <30 mL/minute
- Moderate or severe hepatic impairment: total bilirubin >1.5 times ULN and any AST or with liver metastases: total bilirubin >1.5 times ULN, or AST or ALT >5 times ULN
- Symptomatic or unstable brain metastases
- History of interstitial lung disease (ILD) or pneumonitis requiring steroids, or prior ILD or pneumonitis within 3 months
- Evidence of pulmonary fibrosis
- Grade ≥2 or history of Grade ≥3 peripheral neuropathy
- Known pregnancy
- Lactating
Inclusion Criteria- Locally-advanced or metastatic non-squamous EGFR-wildtype non-small cell lung cancer (NSCLC)
- High c-Met protein overexpression (≥50% of tumor cells with strong 3+ staining)
- Progression on prior systemic cytotoxic chemotherapy and immunotherapy
Care Setting & Performance Status- Care provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Goals of care and role of Palliative Care consult discussed and documented
Reproductive Health & Counseling Requirements- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 2 months after stopping treatment for women and 4 months after for men.
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ELTROMBOPAG POWDER,ORAL
ELTROMBOPAG OLAMINE, PROMACTA
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ELTROMBOPAG OLAMINE, PROMACTA |
2025-05-22 |
Exclusion Criteria- Stem cell disorder (i.e., myelodysplastic syndrome)
- Patient has not received prior therapy, with steroids, to increase platelet counts
- Thrombocytopenia is secondary to bone marrow suppressive anti-cancer therapy, antibiotics or other drugs
- Thromboembolic events within the past year, unless evaluated by a hematology provider and deemed to be an appropriate candidate
- Pregnancy and/or lactating
Inclusion Criteria- Diagnosis of chronic immune thrombocytopenia (ITP)
- Platelet count less than 30,000 mm3 and/or persistent bleeding resistant / refractory to glucocorticoids
- Patient has relapse after the following second-line therapies (unless contraindicated or patient is not a candidate): Splenectomy and rituximab
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
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ELTROMBOPAG TAB
ELTROMBOPAG OLAMINE, PROMACTA
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ELTROMBOPAG OLAMINE, PROMACTA |
2025-05-22 |
Exclusion Criteria- Anticipated antiviral treatment includes a direct-acting antiviral (DAA) for chronic HCV
- Currently receiving peginterferon and ribavirin with or without DAA for chronic HCV
- Any contraindications to peginterferon and ribavirin apply
- Active malignancy or stem cell disorder
- Prior history of arterial or venous thrombosis plus ≥2 risk factors (hereditary thrombophilic disorders, estrogen hormone replacement therapy, systemic contraception therapy containing estrogen, smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer)
- Serious cardiac, cerebrovascular, or pulmonary disease
- Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin
- Known hypersensitivity, intolerance, or allergy to peginterferon and ribavirin, eltrombopag tablets, or ingredients
- Evidence of decompensated liver disease (Child-Pugh score ≥7 and/or clinical manifestations)
- Patient infected with HIV
Inclusion Criteria- Under care of and/or in collaboration with an experienced VA HCV practitioner
- Provider has discussed risks/benefits with patient; shared decision made for use
- Diagnosis of chronic HCV infection
- Baseline platelet count <75,000/μL
- Appropriate candidates for peginterferon and ribavirin combination antiviral therapy
- Treatment with peginterferon and ribavirin (dual therapy) anticipated after reaching target platelet goal
- Abdominal imaging negative for portal vein thrombosis within past 3 months
Dosing & Administration- Initiate prior to peginterferon and ribavirin therapy to obtain target platelet count
- Initial dose: 25 mg once daily on empty stomach (1 hour before or 2 hours after meal)
- Adjust by 25 mg increments every 2 weeks to achieve target platelet count (≥90,000/μL for peginterferon alfa-2a; ≥100,000/μL for peginterferon alfa-2b)
- Use lowest dose to achieve/maintain necessary platelet count
- Maintain same pre-treatment dose when starting antiviral therapy; modify during therapy to maintain counts between 50,000-150,000/μL
- Dose reduction NOT needed solely based on East Asian ethnicity
- Maximum dose: 100 mg/day
- If platelets <50,000/μL after ≥2 weeks: increase by 25 mg; wait 2 weeks to assess
- If platelets ≥150,000-200,000/μL: decrease by 25 mg; wait 2 weeks
- If platelets >200,000/μL: stop eltrombopag; monitor twice weekly; reinitiate at dose reduced by 25 mg (or 12.5 mg if previously on 25 mg) when count <100,000/μL
Monitoring Requirements- Prior to initiation: CBC with differential (including platelet), ocular exam for cataracts, Liver Function Panel (Total/Direct bilirubin, AST, ALT, albumin, total protein)
- During therapy: CBC weekly until stable then monthly; Serum liver tests (ALT, AST, bilirubin) every 2 weeks during adjustment then monthly; fractionate bilirubin if elevated; repeat tests within 3-5 days if abnormal; monitor weekly until resolved/stabilized/baseline; regular ocular exams for cataracts
- Upon discontinuation: CBCs weekly for at least four weeks
Safety & Risk Considerations- Box warnings for hepatotoxicity and risk of hepatic decompensation (ascites, hepatic encephalopathy, variceal hemorrhage, spontaneous bacterial peritonitis, hepatocellular carcinoma, death)
- Patients with albumin <3.5g/dL or MELD scores ≥10 at baseline have greatest risk of hepatic decompensation
- High thromboembolism risk: may increase risk; consider risk vs benefit
- Cataracts developed/worsened in 8% of treated patients
Discontinuation Guidelines- Discontinue when antiviral therapy is discontinued
- Discontinue for hepatotoxicity if ALT increases to ≥3X ULN (normal liver) or ≥3X baseline (pre-treatment elevations) and is progressive, persistent ≥4 weeks, accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury/hepatic decompensation
- Non-response: Consider discontinuing after 9 weeks at maximum dose (100 mg/day) if platelet count not increased sufficiently to initiate antiviral therapy
Specific Populations & Interactions- HIV: No safety/efficacy data; limited drug-drug interaction studies
- Renal insufficiency (CrCl<50ml/min): Not studied; use with caution
- Hepatic insufficiency: Clearance reduced in moderate-severe impairment; initial dose 25 mg daily; monitor serum liver tests; AUC ~2-fold higher; half-life prolonged 2-fold
- Pregnancy: Category C; discuss risks/benefits; consider enrollment in Promacta Pregnancy Registry
- Interactions: Substrate of CYP1A2/CYP2C8; inhibitor of OATP1B1/UGTs; chelates polyvalent cations. Separate administration from iron, calcium, aluminum, magnesium, selenium, zinc-containing meds/supplements/food by at least 4 hours.
Exclusion Criteria- Stem cell disorder (i.e., myelodysplastic syndrome)
- Patient has not received prior therapy, with steroids, to increase platelet counts
- Thrombocytopenia is secondary to bone marrow suppressive anti-cancer therapy, antibiotics or other drugs
- Thromboembolic events within the past year, unless evaluated by a hematology provider and deemed to be an appropriate candidate
- Pregnancy and/or lactating
Inclusion Criteria- Diagnosis of chronic immune thrombocytopenia (ITP)
- Platelet count less than 30,000 mm3 and/or persistent bleeding resistant / refractory to glucocorticoids
- Patient has relapse after the following second-line therapies (unless contraindicated or patient is not a candidate): Splenectomy and rituximab
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
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PHENTERMINE/ TOPIRAMATE CAP,SA
PHENTERMINE-TOPIRAMATE ER, QSYMIA
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PHENTERMINE-TOPIRAMATE ER, QSYMIA |
2025-05-15 |
Exclusion Criteria- Pregnancy
- Lactating
- Glaucoma
- Hyperthyroidism
- Patient has history of suicidal attempts or active suicidal ideation (unless mental health consultation supports benefit of phentermine/topiramate in patient with history of suicide attempts or recent suicidal ideation)
Inclusion Criteria- Verifiable participation in a comprehensive lifestyle intervention that targets all three aspects of weight management: diet, physical activity, behavioral changes
- BMI is greater than or equal to 30 kg/m2 OR BMI is greater than or equal to 27 kg/m2 with at least one weight-related comorbidity (examples include hypertension, type 2 diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, metabolic dysfunction-associated steatotic liver disease)
- If taking topiramate for another condition (e.g., seizure disorder, migraines), the dose of topiramate is adjusted, as indicated, so the cumulative dose does not exceed 400 mg/day
Additional Inclusion Criteria (Select if applicable)- For patients who can become pregnant: Pregnancy has been excluded prior to receiving phentermine/topiramate; monthly pregnancy tests are recommended
- For patients who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy
Indications & Eligibility- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance
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NIPOCALIMAB-AAHU INJ,SOLN
IMAAVY
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IMAAVY |
2025-05-08 |
Indication & Patient Population- Generalized myasthenia gravis (gMG) in adult and pediatric patients 12 years of age and older
- Must be anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive
- Not supported for antibody-negative patients
- LRP4+ gMG is not included in the FDA-approved indication due to insufficient patient numbers in clinical trials
Dosing & Administration Requirements- Initial dose: Single 30 mg/kg IV infusion administered over at least 30 minutes
- Maintenance dose: 15 mg/kg IV infusion administered over at least 15 minutes every 2 weeks, starting 2 weeks after the initial dose
- Must be diluted with 0.9% sodium chloride
- Must use a 0.2 micron in-line or add-on filter
Contraindications- History of serious hypersensitivity reaction to nipocalimab or its excipients
Warnings, Precautions & Monitoring- Infections: Increased risk; delay administration in patients with an active infection
- Hypersensitivity reactions (anaphylaxis, angioedema, rash, urticaria, eczema): Discontinue infusion if a reaction occurs
- Infusion-related reactions (headache, rash, nausea, chills): Discontinue for severe reactions; mild to moderate reactions may be considered for rechallenge with close observation, slower infusion rate, and premedication
- Monitor patients for 30 minutes after each infusion for infusion-related or hypersensitivity reactions
- Live or live-attenuated vaccines are not recommended during treatment
Drug Interactions & Exclusions- Should not be combined with other IgG-affecting agents for chronic management (e.g., IVIg, rozanolixizumab, efgartigimod)
- May reduce the effectiveness of immunoglobulin products and monoclonal antibodies (regardless of indication)
Clinical Context & Use Considerations- May be considered a steroid-sparing treatment option in AChR+ or MuSK+ gMG patients when traditional oral immunosuppressants (azathioprine, mycophenolate, steroids) are ineffective
- Offers fast-onset steroid-sparing control of gMG symptoms as a neonatal Fc receptor antagonist with pre-defined scheduled dosing
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CEFTOBIPROLE INJ,PWDR
ZEVTERA
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ZEVTERA |
2025-05-01 |
Indications & Patient Population- FDA approved for patients aged 18 years and over
- Staphylococcus aureus bloodstream infection (SAB), including right-sided infective endocarditis caused by MSSA and MRSA
- Acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of MSSA, MRSA, Streptococcus pyogenes, and Klebsiella pneumoniae
- Community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of MSSA, MRSA, S. pneumoniae, H. flu, H. parainfluenzae, E. coli, and K. pneumoniae
Dosing & Administration Criteria- Dose: 667 mg IV (CFB medocaril 667 mg is equivalent to CFB 500 mg)
- SAB: Q6h on days 1 to 8, then Q8H from day 9
- ABSSSI and CABP: Q8H
- Infusion time: 2 hours
- Renal dose adjustments required for CrCl <50 ml/min and >150 ml/min
- Reconstitution: Lyophilized powder requires reconstitution with sterile water for injection or 5% dextrose injection; shake vigorously until dissolution (up to 10 minutes) then dilute in 250 mL bag of 0.9% sodium chloride (NS) or 5% dextrose in water (D5W)
- Storage: Reconstituted infusion stored at room temperature for 6 hours (D5W) or 4 hours (NS), or refrigerated for 94 hours (D5W) or 24 hours (NS)
- Must not be mixed or co-administered with calcium-containing solutions
Efficacy & Clinical Evidence Context- Demonstrated non-inferiority to comparators in Phase 3 randomized, double-blinded trials for SAB, ABSSSI, and CABP per FDA definitions
- SAB: Non-inferior to daptomycin +/- aztreonam; superiority not achieved; overall treatment success 69.8% vs 68.7%; microbiologic eradication 82% vs 77%
- ABSSSI: Non-inferior to vancomycin +/- aztreonam for early clinical response and clinical cure at test of cure (TOC); superior to vancomycin group in clinically evaluable population for primary endpoint
- CABP: Non-inferior to ceftriaxone +/- linezolid for clinical cure rate and microbiological eradication rate at TOC
- Not approved for ventilator-associated bacterial pneumonia (VABP) due to increased mortality observed in trials
Safety, Contraindications & Monitoring- Contraindicated in patients with known hypersensitivity to components of CFB or other members of the cephalosporin class
- Boxed warnings: None
- Warnings/Precautions: Increased mortality with unapproved use in VABP; neurotoxicity including seizures and encephalopathy possible across cephalosporin generations
- Discontinue CFB if seizures or other adverse CNS reactions occur
- Common adverse reactions: Anemia, nausea, hypokalemia, vomiting, hepatic enzyme and bilirubin increased, diarrhea, blood creatinine increased, hypertension, leukopenia, pyrexia
- Serious adverse events/deaths/discontinuation: Increased mortality in VABP patients, serious hypersensitivity and skin reactions, seizures and other CNS reactions, C. difficile associated diarrhea
- Thrombosis: Increased frequency observed in CFB arm vs daptomycin arm (5.2% vs 2%) in ERADICATE trial; overall less likely given confounding factors; monitored via post-market surveillance
Place in Therapy & Formulary Guidance- Limited role for pneumonia (CAP/HAP) and SSTI due to numerous potential treatment options
- SAB: Treatment options limited, particularly for MRSA bacteremia; vancomycin requires therapeutic drug monitoring and can cause renal insufficiency; daptomycin commonly used; ceftaroline used commonly despite lack of RCTs/FDA indication for this use; linezolid has limited data for complicated bacteremia and long-term myelosuppression risk
- CFB supports better understanding of optimal dosing due to RCT data compared to ceftaroline
- Disadvantages include frequency of dosing (especially for SAB) and limited stability, which may limit use as a second-line agent for SAB
- Use should involve local ID experts and Antimicrobial Stewardship Champions to ensure appropriate use given complexities of drug, dosing, and spectrum
- ABSSSI: Single treatment option combining MRSA and gram-negative coverage may be useful in certain clinical settings
- CABP: Important limitation is coverage of ESBL & Acinetobacter and dosing schedule (667mg IV Q8H); monotherapy may simplify initial empirical treatment relative to combination therapies
- MSSA SAB/RIE: Treatment includes cefazolin, nafcillin, oxacillin, and DAP; vancomycin can be used in patients with beta-lactam allergy or those who cannot receive other drugs
Pregnancy & Lactation Considerations- Pregnancy: No clinical data available; not associated with adverse developmental effects in rats or rabbits at doses clinically equivalent to MHRD
- Lactation: Detected in rat milk; no data on presence in human milk, effects on breastfed infant, or effects on milk production; no concerns for serious adverse reactions in breastfed infant; risk/benefit discussion recommended
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USTEKINUMAB INJ,SOLN
STELARA
|
STELARA |
2025-04-24 |
Exclusion Criteria- Untreated latent or active tuberculosis infection
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once controlled)
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- History or development of reversible posterior leukoencephalopathy syndrome (RPLS)
- Known or suspected noninfectious pneumonia (e.g., interstitial pneumonia, eosinophilic pneumonia, cryptogenic pneumonia)
- Administration of Bacillus Calmette-Guerin (BCG) vaccine including therapeutic intravesical BCG within 1 year prior to starting or for 1 year after discontinuation
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (use with caution)
Core Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally-designated expert
- Current or prior moderate to severe Crohn’s disease (CD) confirmed by endoscopy or imaging
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- Vedolizumab or upadacitinib was tried (unless medically inadvisable) and not tolerated or not adequate, or lost response
- Risankizumab-rzaa was tried (unless medically inadvisable) and not tolerated or not adequate, or lost response
Additional Inclusion Criteria (Mechanistic/Sequencing)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar and adalimumab are preferred TNFIs in CD)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI therapy in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to infliximab/biosimilar and another TNFI for CD despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
Additional Inclusion Criteria (Patient-Specific/Consultation)- If HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive: Consultation with a GI/liver or infectious diseases expert for advice on antiviral prophylaxis vs. preemptive monitoring for HBV reactivation
- For women who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
Sequencing & Monitoring Guidance- 1L: Infliximab or adalimumab
- 2L/3L: Vedolizumab, upadacitinib, or risankizumab-rzaa (one drug should be risankizumab-rzaa)
- 4L: Mirikizumab-mrkz or ustekinumab
- Routine retesting for TB and hepatitis C screening is not required for prescription renewals; retesting in high-risk patients should be considered
Infection Screening & Management- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once controlled)
- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Exclusion: HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients can be treated)
- Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs])
- Inclusion: Current or past completion of hepatitis C screening (may initiate while waiting for results)
Malignancy & Vaccination History- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Exclusion: Administration of Bacillus Calmette-Guerin (BCG) vaccine including therapeutic intravesical BCG within 1 year prior to starting ustekinumab
Disease Diagnosis & Clinical Status- Inclusion: Diagnosis of chronic (at least 6 months) moderate to severe plaque psoriasis
- Exclusion: History or development of reversible posterior leukoencephalopathy syndrome (RPLS)
- Exclusion: Known or suspected noninfectious pneumonia (e.g., interstitial pneumonia, eosinophilic pneumonia, cryptogenic pneumonia)
Prior Therapy Requirements- Inclusion: Methotrexate monotherapy is medically inadvisable, not tolerated or not adequate
- Inclusion: Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate (i.e., NO treatment benefit after 12 treatments or inadequate partial response after 24 treatments)
- Inclusion: ONE tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
- Inclusion: ONE IL-17Ai (ixekizumab preferred over secukinumab) is medically inadvisable, not tolerated, or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
Provider Oversight- Inclusion: Prescribed and monitored by a VA/VA Community Care dermatologist or locally-designated expert
Exclusion Criteria- Untreated latent or active tuberculosis infection
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis
- Untreated HIV infection
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- History or development of reversible posterior leukoencephalopathy syndrome (RPLS)
- Known or suspected noninfectious pneumonia (e.g., interstitial pneumonia, eosinophilic pneumonia, cryptogenic pneumonia)
- Administration of Bacillus Calmette-Guerin (BCG) vaccine including therapeutic intravesical BCG within 1 year prior to starting or 1 year after therapy
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally-designated expert
- Inflammatory articular disease (joint, spine, and/or entheseal) with a definite or provisional diagnosis of psoriatic arthritis
- Completed tuberculosis test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Current or past completion of hepatitis C screening
- ONE TNFI therapy is medically inadvisable, not tolerated, or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
- ONE IL-17AI (ixekizumab preferred) is medically inadvisable (e.g., severe or recurrent Candida infections), not tolerated, or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
Clinical Precautions & Management Considerations- Ustekinumab may be started/restarted once infections are controlled; initiation is permitted after starting antiviral prophylaxis for HBV
- Treated, well-controlled, asymptomatic HIV-positive patients are eligible for treatment
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Consultation with a hepatologist or infectious diseases expert is recommended to advise on initiating prophylactic antiviral therapy versus deferred prophylactic therapy with preemptive monitoring
- Anti-HBs titers ≥10 IU/L are generally considered protective and may identify patients requiring initial/booster vaccination or those with occult HBV from past infection
- TNFI may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in a first-degree relative, lupus, recurrent infections, or serious infections
- IL-17AI may be medically inadvisable due to inflammatory bowel disease (IBD), severe or recurrent Candida infections, or suicide ideation/behavior (specific to brodalumab)
Exclusion Criteria- Untreated latent or active tuberculosis infection
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once controlled)
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- History or development of reversible posterior leukoencephalopathy syndrome (RPLS)
- Known or suspected noninfectious pneumonia (e.g., interstitial pneumonia, eosinophilic pneumonia, cryptogenic pneumonia)
- Administration of Bacillus Calmette-Guerin (BCG) vaccine including therapeutic intravesical BCG within 1 year prior to starting or 1 year after therapy
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (use with caution)
Inclusion Criteria (General Prerequisites)- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally-designated expert
- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
Additional Inclusion Criteria (Prior Therapy & Failure Types)- One of vedolizumab, tofacitinib, upadacitinib, etrasimod, or ozanimod was tried (unless medically inadvisable) and not tolerated or not adequate, or lost response
- Risankizumab-rzaa was tried (unless medically inadvisable) and not tolerated or not adequate, or lost response
- ONE of the following must be selected:
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar is the preferred TNFI in UC)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI therapy in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
Special Populations & Consultations- If HBsAg-negative but anti-HBc-positive: GI/liver or infectious diseases expert consulted for advice on whether to start antiviral prophylaxis or preemptively monitor for HBV reactivation
- For women who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception
Monitoring, Sequencing, & Clinical Notes- Routine retesting for TB, HBV, and HCV is not required for prescription renewals; retesting in high-risk patients should be considered
- Antiviral prophylaxis for HBV requires agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated before initiation when possible; recombinant zoster vaccine should be completed/initiated by end of first year, preferably at low dosage/stable disease
- Sequencing: 1L = Infliximab or adalimumab; 2L/3L = Vedolizumab, tofacitinib, upadacitinib, etrasimod, ozanimod, or risankizumab-rzaa (one drug must be risankizumab-rzaa); 4L = Mirikizumab-mrkz, guselkumab, or ustekinumab
- Infliximab/biosimilar is the preferred TNFI in UC; adalimumab is less preferred than vedolizumab and tofacitinib in TNFI-exposed UC patients
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ATRASENTAN TAB
VANRAFIA
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VANRAFIA |
2025-04-17 |
Indication & Patient Population- • Adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression
- • Generally requires a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g
- • Persistent proteinuria (≥1 g/day) despite being on a maximally tolerated dose of a RAS inhibitor and failure of other agents
- • Biopsy-proven IgA nephropathy with an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m²
- • Excludes patients with secondary IgA nephropathy or a history of heart failure
Dosing & Administration- • 0.75 mg taken orally once daily, with or without food
- • Administered as add-on therapy to maximally tolerated renin-angiotensin system (RAS) inhibition (ACE inhibitor or ARB)
- • Patients must be on a stable, maximum tolerated dose of an ACE inhibitor or ARB for at least 12 weeks prior to screening/initiation
Contraindications & Safety Requirements- • Pregnancy is contraindicated; pregnancy must be excluded before starting treatment
- • Effective contraception required before, during, and for two weeks after treatment
- • Hypersensitivity to atrasentan or any component of the product
- • Monitor liver enzymes before and during treatment as clinically indicated due to hepatotoxicity risk
- • Monitor for fluid retention; consider diuretic use and interrupt atrasentan if clinically significant fluid retention occurs
- • Counsel men about potential adverse effects on spermatogenesis/fertility
Formulary & Use Restrictions- • Indicated specifically for reduction of proteinuria in primary IgAN at risk of rapid progression (UPCR ≥ 1.5 g/g)
- • Considered as an adjunct prior to or as an alternative to immunosuppression in select high-risk cases
- • Not established whether atrasentan slows kidney function decline; continued approval contingent upon verification of clinical benefit in a confirmatory trial
- • Avoid concomitant use with strong or moderate CYP3A inducers or OATP1B1/1B3 inhibitors due to altered exposure and efficacy/safety risks
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TICAGRELOR TAB,ORAL
BRILINTA
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BRILINTA |
2025-04-17 |
Exclusion Criteria- Active pathological bleeding
- Clinically important anemia or thrombocytopenia
- History of intracranial hemorrhage (ICH)
- Severe hepatic impairment
- Increased risk for symptomatic bradycardia events (e.g., sick sinus syndrome, 2nd or 3rd degree atrioventricular block, bradycardia-related syncope not protected by a pacemaker)
- Concomitant simvastatin or lovastatin in doses greater than 40 mg daily
- Concomitant use of strong CYP3A4 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole)
- Concomitant use of strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, and phenobarbital)
- Concomitant oral anticoagulant therapy (clopidogrel is preferred P2Y12 inhibitor for use in combination with an oral anticoagulant)
- Anticipated urgent coronary artery bypass graft (CABG) surgery (i.e., within 5 days)
- Receiving concomitant aspirin at a dose of greater than 100 mg daily
Inclusion Criteria- Acute Coronary Syndromes (ACS) & PCI
- ST-elevation myocardial infarction acute coronary syndrome (STEMI-ACS) undergoing percutaneous coronary intervention (PCI) or receiving no reperfusion
- Non-ST elevation acute coronary syndrome (NSTE-ACS) with at least 2 of the following: ST-segment changes on electrocardiogram indicating ischemia, positive cardiac biomarkers, and/or other high risk feature
- Definite or probable acute stent thrombosis in patients compliant with aspirin and clopidogrel
- Extended Dual Antiplatelet Therapy (DAPT)
- Extended duration dual antiplatelet therapy (DAPT=aspirin plus P2Y12 inhibitor) beyond 12 months following an ACS event as per Cardiology re-evaluation; reduce dose to 60 mg twice daily
- Antiplatelet Resistance or Allergy
- Reduced clopidogrel response (e.g., any documented CYP2C19 intermediate or poor metabolizer phenotypes or high on-treatment platelet reactivity by P2Y12 reaction units [PRU] testing) and continued indication for P2Y12 inhibitor therapy
- Undergoing PCI with or without ACS in patients with clopidogrel or true aspirin allergy
- Stable CAD with Type 2 Diabetes
- Confirmed CAD and type 2 diabetes without prior MI, at particularly high ischemic risk AND low bleed risk given neutral net clinical benefit – restricted to Cardiology
- Cerebrovascular Disease (Stroke/TIA)
- Non-cardioembolic acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack when no other recommended antiplatelet agents are appropriate for use – restricted to Neurology
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FINASTERIDE/ TADALAFIL CAP,ORAL
ENTADFI
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ENTADFI |
2025-04-10 |
Clinical Category: Monotherapy & Combination Therapy Restrictions- A PDE5I should not be used routinely for the management of LUTS-BPH as monotherapy.
- A PDE5I should not be used in combination with alpha blockers for BPH/LUTS, as it offers no symptom improvement advantage over either agent alone per American Urological Association (AUA) guidelines.
Clinical Category: Formulary PDE5I Initiation & Substitution Criteria- Consider when more established pharmacotherapies are not an option or have not demonstrated benefit.
- Initiate a formulary alpha blocker first using shared decision making and patient-specific factors. If ED is present, may consider adding a formulary PDE5I (with quantity limits) to an alpha blocker.
- Consider substituting or adding a formulary PDE5I if unable to tolerate or lack of response to an adequate trial (12 weeks) of a formulary alpha blocker titrated to maximum therapeutic dose.
- If adding a PDE5I, the patient must be on a stable dose of the alpha-blocker prior to initiation; the PDE5I should then be started at the lowest recommended dose.
Clinical Category: Clinical Scenarios for Formulary PDE5I Monotherapy Consideration- In place of an alpha blocker in the interim if cataract surgery is planned or likely (due to risk of intraoperative floppy iris syndrome).
- When an alpha blocker is contraindicated or not tolerated and an antimuscarinic is not appropriate due to post-void residual >250 mL, contraindication, ineffective trial, or substantial contribution to existing anticholinergic burden.
- (Note: The document explicitly states that only sildenafil, tadalafil, and vardenafil have been studied for BPH/LUTS; avanafil-specific criteria are not provided in the text.)
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TERAZOSIN SOLN,ORAL
TEZRULY
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TEZRULY |
2025-04-10 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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REVAKINAGENE TARORETCEL-LWEY IMPLANT
ENCELTO
|
ENCELTO |
2025-04-03 |
Indication & Patient Population- Treatment of adults with idiopathic macular telangiectasia type 2 (MacTel)
- Specifically indicated for non-neovascular MacTel
Administration & Dosing Requirements- Single-dose implant containing 200,000 to 440,000 allogeneic retinal pigment epithelial cells expressing recombinant human ciliary neurotropic factor (rhCNTF)
- Requires intravitreal surgical placement
Inclusion Criteria- Positive diagnosis of MacTel with evidence of fluorescein leakage typical of MacTel
- At least one additional feature: hyperpigmentation outside a 500-micron radius from fovea center, retinal opacification, crystalline deposits, right-angle vessels, or inner/outer lamellar cavities
- Inner Segment-Outer Segment Junction Line (IS/OS) Photoreceptor (PR) break in study eye(s) with en face ellipsoid zone (EZ) area between 0.16 mm² and 2.00 mm² measured by SD-OCT
- Best corrected visual acuity (BCVA) of 54-letter score or better (20/80 or better) on ETDRS chart at screening
- Steady fixation in foveal or parafoveal area with sufficiently clear media for good quality photographs
- Age greater than 21 years and less than 80 years at screening
- Ability to provide written informed consent
- Women of childbearing potential must agree to use highly effective contraception (Germany and France only)
Exclusion Criteria- Medically unable to comply with study procedures or follow-up visits
- Received intravitreal steroid therapy for non-neovascular MacTel within the last 3 months
- Ever received intravitreal anti-VEGF therapy in the study eye OR received intravitreal anti-VEGF in the fellow eye within the past 3 months at randomization
- Evidence of ocular disease other than MacTel that may confound diagnosis, procedures, or outcome (e.g., glaucoma, severe nonproliferative or proliferative diabetic retinopathy, uveitis)
- Chronic requirement (≥4 weeks at a time) for ocular medications and/or diagnosed disease that may be vision-threatening or affect primary outcome (artificial tears permitted)
- Evidence of intraretinal neovascularization or subretinal neovascularization (SRNV), hemorrhage, hard exudate, subretinal fluid, or intraretinal fluid in either eye
- Evidence of central serous chorio-retinopathy in either eye
- Evidence of pathologic myopia in either eye
- Significant corneal or media opacities in either eye
- History of vitrectomy, penetrating keratoplasty, trabeculectomy, or trabeculoplasty
- Lens opacities: cortical opacity > standard 3, posterior subcapsular opacity > standard 2, or nuclear opacity > standard 3 (AREDS grading)
- Undergone lens removal in the previous 3 months or YAG laser within 4 weeks
- Participated in any other clinical trial of an intervention within the last 6 months
- Currently on chemotherapy
- Pregnant or breastfeeding
- History of malignancy that would compromise 24-month study survival
- History of ocular herpes virus in either eye
- Physical or mental condition increasing risk of participation or interfering with procedures/assessments
- Evidence of intraretinal hyperreflectivity by OCT
Contraindications- Active or suspected ocular or periocular infections
- Known hypersensitivity to Endothelial Serum Free Media (Endo-SFM)
Warnings & Precautions- Severe vision loss
- Infectious endophthalmitis
- Retinal tear and detachment
- Vitreous hemorrhage
- Implant extrusion
- Cataract formation
- Suture related complications
- Delayed dark adaption
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TERIPARATIDE INJ,SOLN
BONSITY, FORTEO
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BONSITY, FORTEO |
2025-04-03 |
Exclusion Criteria- History of hypersensitivity reaction or contraindication to teriparatide (including Paget’s disease, hyper or hypocalcemia, hypercalciuria, bone cancer, bone metastases, radiation treatment to the skeleton, and hyperparathyroidism)
- Pregnancy or lactating
- Inclusion Criteria (All must be met)
- Diagnosis of osteoporosis or at risk for glucocorticoid-induced osteoporosis
- Prescriber is a VA/Community Care endocrinologist, rheumatologist, nephrologist, geriatrician, or locally designated expert
- Total daily dietary and supplemental calcium intake is 1000 to 1200 mg/day
- 25-hydroxyvitamin D concentration >30 ng/ml or >20 ng/mL with appropriate intake (e.g., cholecalciferol >800 international units per day)
- Additional Inclusion Criteria (One of the following must be met)
- Osteoporotic fracture and a T-score at the hip or spine < -2.5
- Very high fracture probability by Fracture Risk Assessment Tool (FRAX) (e.g., major osteoporosis fracture >30%, hip fracture >4.5%)
- T-score < -3.0
- More than 2 osteoporotic fractures
- Continued loss of bone mineral density or sustained osteoporotic fracture despite treatment with an approved osteoporosis therapy (e.g., bisphosphonate or denosumab)
Post-Treatment Requirement- Following a 2-year course, initiate antiresorptive therapy to maintain bone density gains
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ANSUVIMAB-ZYKL INJ,LYPHL
EBANGA (NATIONAL STOCKPILE)
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EBANGA (NATIONAL STOCKPILE) |
2025-03-20 |
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RIVAROXABAN TAB
XARELTO
|
XARELTO |
2025-03-13 |
Indications- Atrial fibrillation/flutter (AF)
- Acute venous thromboembolism (VTE), or prevention of recurrent VTE
- Primary prophylaxis of VTE in patients undergoing hip or knee replacement surgery
- Other indication for anticoagulation (local adjudication required)
Exclusions- Mechanical heart valve
- Moderate to severe rheumatic mitral valve stenosis (for AF/flutter only)
- Antiphospholipid syndrome (APS)
- Known significant liver disease (e.g., acute clinical hepatitis, cirrhosis [Child-Pugh C], or hepatic disease associated with coagulopathy)
- Pregnancy
- Breastfeeding
Pre-Treatment Assessment & Monitoring- Assessment of renal function (CrCl) and hemoglobin, hematocrit, and platelets
- Consider liver function testing in patients with a history of or risk for hepatic insufficiency
- Provider must assess DOAC choice, dose, and duration considering patient’s age, renal function, liver function, concurrent medications, and indication
- Identify and address modifiable risk factors for bleeding (e.g., NSAIDs, antiplatelet therapy)
- Document the treatment plan including duration in the patient’s chart
Dosing & Administration Requirements- For acute VTE: Administer 10 mg twice daily for 7 days as oral loading dose BEFORE starting maintenance doses
- Review drug dosing errors and drug-drug interactions, especially with new starts
Special Populations & Clinical Considerations- Bioprosthetic heart valve placement in the past 3 months: Appropriate based on shared decision-making process between provider and patient
- Severe renal impairment (CrCl <25-30 ml/min) or hemodialysis: Individual evaluation of risks and benefits recommended; net clinical benefit unclear
- Apixaban may be the preferred DOAC when CrCl is less than 30 ml/min
- For patients who can become pregnant: Counsel on potential risks vs benefits of treatment and use of effective contraception during therapy
Clinical Indication & Context- Low-dose (2.5 mg twice daily) rivaroxaban plus aspirin only for chronic, stable coronary artery disease (CAD)
Exclusion Criteria- Indication for non-aspirin antiplatelet therapy including dual antiplatelet therapy (e.g., aspirin plus clopidogrel, ticagrelor, or prasugrel)
- Indication for therapeutic dose of an oral anticoagulant (e.g., atrial fibrillation, venous thromboembolism treatment, etc.)
- Recent stroke (within past 30 days) or any history of hemorrhagic stroke
- Heart failure (ejection fraction [EF] less than 40% or NYHA class III or IV symptoms)
- Estimated glomerular filtration rate (eGFR) less than 15 ml/min
- Known hepatic disease associated with coagulopathy
- Concurrent use of combined P-glycoprotein and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin)
- Concurrent use of combined P-glycoprotein and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir and ritonavir combinations, cobicistat)
- Pregnancy
- Breastfeeding
- High risk of bleeding per clinician discretion
Inclusion Criteria- Prescribed low dose aspirin (75 to 100 mg) once daily as indicated for use with rivaroxaban LOW-DOSE (2.5 mg twice daily)
- One of the following must be met:
- Documented myocardial infarction in the past 20 years
- Multivessel coronary disease with symptoms or history of angina (stable or unstable)
- Multivessel percutaneous coronary intervention
- Multivessel coronary artery bypass graft (CABG) surgery
- One of the following must be met:
- Age 65 years or older
- Less than 65 years old with documented atherosclerosis or revascularization in two vascular beds (coronary vascular bed plus one additional vascular bed, e.g., aorta, brain, gastrointestinal tract, limbs, kidneys)
- Less than 65 years old with two or more risk factors: current smoker (within the last year), diabetes, renal impairment (estimated glomerular filtration rate [GFR] less than 60 mL/min), or atherosclerotic ischemic stroke at least one month ago
- Exclusion Criteria (Patient should NOT receive low-dose rivaroxaban if any of the following are met)
- Indication for therapeutic dose of an oral anticoagulant (e.g., atrial fibrillation, venous thromboembolism treatment, etc.)
- Indication for non-aspirin antiplatelet therapy including dual antiplatelet therapy (e.g., aspirin plus clopidogrel, ticagrelor, or prasugrel)
- Recent stroke (within the past 30 days) or any history of hemorrhagic stroke
- Estimated glomerular filtration rate (eGFR) less than 15 ml/min
- Known hepatic disease associated with coagulopathy
- Concurrent use of combined P-glycoprotein and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin)
- Concurrent use of combined P-glycoprotein and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir and ritonavir combinations, cobicistat)
- Pregnancy
- Breastfeeding
- High risk of bleeding per clinician discretion
Primary Inclusion Criteria- Prescribed low dose aspirin (75 to 100 mg) once daily as indicated for use with rivaroxaban LOW-DOSE (2.5 mg twice daily)
- Additional Inclusion Criteria (Patient must fulfill at least one of the following)
- Current or prior revascularization procedure for the treatment of PAD
- History of limb or foot amputation due to PAD
- Symptomatic PAD, including history of intermittent claudication or critical limb threatening ischemia with objective clinical confirmation (i.e., ankle-brachial index ratio measures, peripheral angiography)
Indication & Administration Parameters- Use is restricted to low-dose rivaroxaban (2.5 mg twice daily) combined with aspirin ONLY in the setting of PAD
- Concomitant clopidogrel may be used for a finite period of time (e.g., 30 days and up to 6 months) following a lower-extremity revascularization procedure
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
FDA Approved Adult Indications- Non-valvular atrial fibrillation
- Treatment of DVT and PE (after 5-10 days of parenteral anticoagulant)
- Reduction in the risk of recurrent DVT and PE following initial therapy
- Post-surgical VTE prophylaxis following hip replacement surgery
- Post-surgical VTE prophylaxis following knee replacement surgery
Oversight & Initiation- Chronic DOAC therapy requires initial assessment, education, and follow-up by locally designated staff (e.g., anticoagulation management program or other designees).
- Facilities should utilize decision support tools and/or anticoagulation staff for upfront review to verify appropriate candidate selection, agent choice, and dosing upon initiation.
- Short-term treatment (e.g., post-surgical VTE prophylaxis) or very low dose regimens should follow education/monitoring protocols similar to alternative agents in that setting.
Laboratory Monitoring- Baseline: Serum creatinine (SCr) to estimate creatinine clearance (CrCl); CrCl estimated using Cockcroft-Gault equation with actual body weight for apixaban trials. Hemoglobin, hematocrit, and platelets required. Liver function tests may be considered for patients with history/risk of hepatic insufficiency. PT/aPTT may be obtained for emergency reference. Baseline values drawn within 1-3 months are acceptable per provider clinical judgment based on age/health status/comorbidities.
- Follow-up: SCr monitored at least annually (more frequently if CrCl < 60 ml/min, concomitant illness worsening renal function, or age ≥ 75 years). Hemoglobin, hematocrit, and platelets monitored at least annually or as clinically dictated. Liver function testing considered for underlying liver disease or clinical indication.
Patient Education- Initial and periodic education must cover: capsule/tablet identification, proper storage, therapy indication, risks/benefits, anticipated duration, daily dose/dosing changes (e.g., loading doses), administration considerations, drug interactions, monitoring requirements, adherence importance, management of missed/extra doses, signs/symptoms of bleeding/thromboembolic events, avoidance of major bleeding risk medications (e.g., NSAIDs, antiplatelets) unless instructed, non-bleeding adverse events, fall risks/mitigation, medication supply acquisition, pre-procedure provider notification for peri-procedural management, anticoagulation provider contact information, and gender-specific considerations for women of childbearing age (menstrual difficulties, pregnancy, contraception).
Adherence Monitoring- Monitor adherence, refill history, and medication tolerance, especially at therapy initiation.
- Utilize population management tools, telephone follow-up, face-to-face visits, secure messaging, or combinations based on site resources.
Follow-up Care- Initial: Within 2-4 weeks of initiation (or sooner if clinically indicated) to assess tolerance, bleeding, thromboembolic events, other adverse events (e.g., GI intolerance), adherence, correct dosing (e.g., transition from high-intensity initiation dosing for acute VTE), duplicate therapy, and reinforce education.
- Periodic/Long-term: Reassess adherence, screen for drug interactions, monitor labs as needed. Time points, methods, and responsible staff determined locally per VHA Directive 1108.16(1).
Quality Assurance- Incorporate DOACs into ongoing quality assurance plans per VHA Directive 1108.16(1).
- Report adverse events per local protocols and P&T Committee; enter into VA ADERS.
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SUZETRIGINE TAB,ORAL
JOURNAVX
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JOURNAVX |
2025-02-13 |
Exclusion Criteria- Use for >5 days for any episode of care (treatment not to exceed 14 days may be considered case-by-case)
- Severe Renal Impairment (eGFR <15 mL/min – CKD-EPI body surface area adjusted)
- Severe Liver Disease (Child-Pugh class C, kinetics unknown)
- Unmanageable drug-drug interactions (e.g., CYP 3A4 strong inhibitor or inducer)
- Patients with pre-operative, long-term pain management already utilizing daily use of pain medications (e.g., NSAIDs or opioids)
- Patients with a history (or current) arrhythmia or abnormal findings on EKG
- Known pregnancy
Inclusion Criteria- Patients undergoing surgical procedure expected to result in moderate-to-severe pain
- Patients unable to use or with insufficient response to systemic NSAIDs or acetaminophen as part of Enhanced Recovery After Surgery (ERAS) protocol
- Patient unable to use opioids or use of opioids, including buprenorphine, is inadvisable
Pregnancy & Reproductive Considerations- For females who can become pregnant: Pregnancy must be excluded prior to receiving suzetrigine
- For females who can become pregnant on contraceptives containing progestins other than levonorgestrel and norethindrone: Counseling provided on potential risks vs benefits of treatment and the use of alternative contraception during therapy
Dosing & Management Adjustments- Moderate hepatic illness (Child-Pugh B) or taking moderate CYP3A4 inhibitors: After 4 doses (start of day 3), reduce dose frequency to once every 24 hours; avoid use in patients on strong or moderate CYP3A4 inducers
Clinical Context & Justifications- Pre-operative/long-term pain management: Efficacy unknown for patients already on pre-surgical pain therapy that can be continued or titrated; use can be considered case-by-case
- Opioid minimization: When use of opioids is appropriate, such use should not be avoided purely for the sake of opioid minimization; with appropriate monitoring and risk mitigation, opioids can be a component of a multi-modal pain management strategy even in high-risk patients
- Combination with opioids: Not studied in combination with opioids, but may be considered case-by-case when post-operative opioids will be used and opioid minimization is particularly important (e.g., abdominal surgery)
Indication- Treatment of moderate to severe acute pain in adults
Dosage & Administration- Tablet for oral use
- Loading dose: 100 mg on empty stomach
- Maintenance dose: 50 mg every 12 hours, initiated 12 hours after loading dose start
Contraindications & Warnings- Concomitant use with strong CYP3A4 inhibitors is contraindicated
- Patients using contraceptives containing progestins other than levonorgestrel and norethindrone require additional nonhormonal contraception (e.g., condoms) or alternative contraceptives during suzetrigine therapy and for 28 days after the last dose
Clinical Evidence & VHA Population Considerations- Currently indicated only as a treatment for acute pain
- Demonstrates modest reduction in pain with a small effect size that is numerically better than placebo; clinical significance of this difference is uncertain (e.g., similar request for rescue medication)
- Did not perform better than low-dose opioid therapy (e.g., 20 MEDD)
- Not studied in context of usual post-operative pain protocols
- Studied primarily in middle-aged females; generalizability to how a VHA Veteran population would respond to treatment is unclear
- No evidence demonstrates it performs better than treatment options commonly used postoperatively and already on formulary (e.g., NSAIDs, intravenous APAP, opioids, local and regional blocks)
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NIVOLUMAB/ HYALURONIDASE-NVHY INJ,SOLN
OPDIVO QVANTIG
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OPDIVO QVANTIG |
2025-01-13 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression requiring a corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Known pregnancy
- Breastfeeding
Inclusion Criteria (One must be fulfilled)- Indication is FDA-approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria (All must be fulfilled)- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (If applicable)- For females who can become pregnant: Pregnancy must be excluded prior to receiving either nivolumab product
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 5 months after stopping treatment
Product-Specific Administration Guidelines- Nivolumab IV has approval in classical Hodgkin Lymphoma; nivolumab/hyaluronidase SUBQ does not replace nivolumab IV in this setting
- Nivolumab/hyaluronidase-nvhy should not replace nivolumab when given in combination with ipilimumab
Indications- Solid tumors including: Renal cell carcinoma (RCC), melanoma, non-small cell lung cancer (NSCLC), Squamous Cell Carcinoma (SCC) of the head & neck, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma (ESCC), gastroesophageal junction (GEJ) cancer, gastric cancer, and esophageal adenocarcinoma
Dosage & Administration- Dosing varies by malignancy; may be given in combination with other agents except ipilimumab
- Every 2-week dosing: 600 mg/10,000 units
- Every 3-week dosing: 900 mg/15,000 units
- Every 4-week dosing: 1200 mg/20,000 units
- Administered via subcutaneous injection over 3-5 minutes in the abdomen or thigh by a healthcare professional
- Dose volume varies from 5-10 mL; dose to be drawn up into a syringe
Contraindications & Warnings- None listed for contraindications or boxed warnings
- Severe and fatal immune-mediated adverse reactions
- Complications of allogeneic hematopoietic stem cell transplant
- Embryo-fetal toxicity
- Should not be administered intravenously
Combination Restrictions- Not approved for use in combination with ipilimumab
- Should not be used in combination with a thalidomide analogue and dexamethasone for multiple myeloma outside of the clinical trial setting
VHA Formulary & Clinical Considerations- Demonstrated noninferiority to intravenous nivolumab based on pharmacokinetic endpoints (time-averaged exposure over 28 days and minimum steady-state exposure) and overall response rate relative risk in advanced/metastatic clear cell RCC
- May replace intravenous nivolumab when given as monotherapy
- Not approved for use in Hodgkin Lymphoma; should not replace intravenous nivolumab in this setting
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PRUCALOPRIDE TAB,ORAL
MOTEGRITY
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MOTEGRITY |
2025-01-09 |
Exclusion Criteria- Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the GI tract (e.g., Crohn’s disease, ulcerative colitis, toxic megacolon / megarectum)
- Untreated or unstable depression or suicidality
- End-stage renal disease requiring dialysis
- Age less than 18 years
- Presence of severe or frequent diarrhea
Inclusion Criteria- Men or women 18 years or older with chronic idiopathic constipation (CIC)
- Intolerance or inadequate response to a 1-month trial of at least one bulk forming laxative (e.g., psyllium, oxidized cellulose, calcium polycarbophil) with fluids, unless there is a contraindication or risk factor(s) for serious adverse event(s)
- Intolerance or inadequate response to a 1-month trial of either PEG-3350 powder for oral solution (17 g twice daily) or other osmotic laxative, unless there is a contraindication or risk factor(s) for serious adverse event(s)
- Intolerance or inadequate response to a 1-month trial of lubiprostone (24 mcg twice daily), unless there is a contraindication or risk factor(s) for serious adverse event(s)
Clinical Recommendations & Definitions- Chronic idiopathic constipation (CIC) excludes drug-induced chronic constipation and chronic constipation due to neurogenic and non-neurogenic disorders.
- GI consultation is highly recommended to diagnose and evaluate CIC.
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ZENOCUTUZUMAB-ZBCO INJ,SOLN
BIZENGRI
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BIZENGRI |
2025-01-02 |
Exclusion Criteria- Interstitial Lung Disease or pneumonitis
- Clinically significant cardiac disease defined as: Baseline Left Ventricular Ejection Fraction < 50%, Uncontrolled hypertension or arrhythmia, Congestive Heart Failure (New York Heart Association Class 3 or 4)
- Platelets <75 X 109/L or Hemoglobin <9 grams/dL
- Absolute Neutrophil Count <1.5 x 109/L unless Duffy-null phenotype
- Total bilirubin > 1.5 X Upper Limit of Normal unless due to Gilbert’s syndrome
- Creatine Clearance < 30ml/min
- Pregnancy
- Lactation
Required Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Oncologic Indication Requirements- NRG1 gene fusion positive (RNA based sequencing preferred) Non-Small Cell Lung Cancer with progression on or after prior systemic therapy including platinum-based chemotherapy and/or targeted therapy if clinically indicated
- NRG1 gene fusion positive (RNA based sequencing preferred) advanced, unresectable, or metastatic pancreatic adenocarcinoma with progression on or after prior systemic therapy including fluoropyrimidine- and/or gemcitine-based chemotherapy
Reproductive Health & Counseling Requirements- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 2 months after stopping treatment
Indication & Patient Population- Adults with advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion
- Adults with advanced, unresectable, or metastatic pancreatic adenocarcinoma harboring a NRG1 gene fusion
- Disease progression on or after prior systemic therapy
Dosing & Administration- 750 mg IV every 2 weeks until disease progression or unacceptable toxicity
- First dose requires premedication with a corticosteroid such as dexamethasone 10 mg, an H1 antihistamine equivalent to dexchlorpheniramine 5 mg, and acetaminophen 1000 mg
- Corticosteroid may not be indication in subsequent cycles; may be used as necessary for future doses
Safety & Monitoring Requirements- Monitor for at least 1 hour following first infusion due to risk of infusion-related reactions/hypersensitivity/anaphylaxis
- Evaluate baseline LVEF and monitor at regular intervals during treatment as clinically indicated
- Assess for interstitial lung disease/pneumonitis
- Contraindications: None
Formulary & Clinical Pathway Status- Both FDA approvals are under accelerated approval based on overall response rate (ORR)
- Not yet placed on VA clinical pathways for NSCLC or pancreatic adenocarcinoma
- Second or third-line treatment option for NRG1 gene fusion positive NSCLC who have progressed on/after systemic therapy platinum-based chemotherapy and/or targeted therapy if clinically indicated
- Second- or third-line treatment option for NRG1 gene fusion positive pancreatic adenocarcinoma with progression on/after systemic therapy including fluoropyrimidine- and/or gemcitabine-based chemotherapy
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ACORAMIDIS TAB
ATTRUBY
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ATTRUBY |
2024-12-05 |
Exclusion Criteria- Heart failure without definitive evidence of transthyretin-mediated amyloidosis (ATTR) (e.g., heart failure secondary to ischemic heart disease)
- Patient receiving concomitant therapy for ATTR (e.g., patisiran, inotersen, eplontersen, tafamidis, vutrisiran)
- End stage heart disease and anticipated survival < 1 year
Inclusion Criteria- Provider is a VA or VA Community Care cardiologist or locally designated ATTR-CM provider
- Diagnosis of wild type or hereditary TTR genotype ATTR-CM based on endomyocardial biopsy OR echo/MRI suggestive of amyloidosis confirmed with radionuclide imaging (e.g., technetium pyrophosphate [Tc99-PYP] scintigraphy)
- Assessment of monoclonal protein screen for and exclusion of light chain (AL) amyloidosis
- History of symptomatic heart failure (at least one hospitalization for heart failure OR clinical evidence of heart failure manifested by signs and symptoms of volume overload or elevated intracardiac pressures)
- Discussion with patient/caregiver/family member regarding realistic treatment expectations and discontinuation should be documented
Additional Inclusion Criteria- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment
Indication- Treatment of cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) to reduce CV death and CV-related hospitalization.
Patient Selection & Diagnostic Criteria- Adults with a diagnosis of ATTR-CM and clinical heart failure.
- ATTR-CM diagnosis based on endomyocardial biopsy with confirmatory typing or positive results (Perugini grade ≥2) on technetium-99m scintigraphy combined with biochemical exclusion of light chain (AL) amyloidosis.
- Clinical heart failure determined by ≥1 prior heart failure hospitalization, signs and symptoms of volume overload, or heart failure requiring diuretic treatment.
- Key clinical parameters: 6MWD ≥150m, NT-proBNP ≥300 pg/mL, LV wall thickness ≥12 mm.
Dosing & Administration- 712 mg (2 x 356 mg tablets) orally twice daily, with or without food.
- Tablets must be swallowed whole.
Monitoring & Safety Parameters- Monitor for increases in serum creatinine and decreases in estimated glomerular filtration rate (eGFR), generally occurring within 4 weeks of initiation.
- Renal function changes are reversible upon discontinuation.
Contraindications, Warnings & Drug Interactions- No boxed warnings, contraindications, or other warnings stated.
- Avoid use with UGT inducers and strong CYP3A inducers.
- More frequent monitoring may be needed when co-administered with sensitive substrates of CYP2C9.
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TESTOSTERONE PREFILLED SYRINGE
AZMIRO
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AZMIRO |
2024-11-21 |
Exclusion Criteria- Active prostate cancer
- Active breast cancer
- Uncontrolled or untreated erythrocytosis (e.g., Hematocrit >48%)
- Severe, untreated Obstructive Sleep Apnea (OSA)
- Unevaluated Prostate Specific Antigen (PSA) level greater than 4 ng/mL or PSA greater than 3 ng/mL in individuals with risk factors for prostate cancer
- Severe lower urinary tract symptoms (International Prostate Symptom Score [IPSS] >19)
- Inadequately controlled congestive heart failure
- Acute Coronary syndrome (ACS), stroke (CVA), or revascularization procedure in the last 4 months
- Thrombophilia or history of unprovoked venous thromboembolism
- Severe liver disease or renal failure
- Desire for future fertility
- Active, unaddressed anabolic steroid misuse
Inclusion Criteria- Hypogonadism diagnosed by at least one clinical sign or symptom consistent with androgen deficiency
- HIV infected men with low testosterone levels and weight loss
- Receiving high doses of glucocorticoids who have low testosterone levels (daily dose greater than 5mg of prednisone or equivalent for at least 6 months)
- Status post bilateral orchiectomy or unilateral orchiectomy (with documented atrophy of second testicle)
- Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism and signs/symptoms of hypogonadism
Additional Pre-Initiation Requirements- Document that other potential treatable causes of symptoms of low testosterone levels and their suspected etiologies have been addressed
- Two, unequivocally low baseline, fasting, total testosterone levels (determined based on local laboratory assay and patient specific factors), at least one week apart, between 8am - 10am
- Prior to initiation, potential risks and benefits discussed and documented in the medical record
- Baseline Hemoglobin and Hematocrit, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and prolactin levels assessed
- Discussion regarding prostate cancer screening and monitoring occurred; if shared decision-making results in screening, PSA is measured
Clinical & Laboratory Considerations- For patients with Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism, a single baseline testosterone level is sufficient
- Free testosterone assessment recommended if concern for Sex Hormone Binding Globulin (SHBG) alterations exists (e.g., elderly, obesity, diabetes, liver or HIV disease, medications such as anticonvulsants/anabolic steroids/progestins, thyroid disease); acceptable measurement methods include equilibrium dialysis or calculation using total testosterone, SHBG, and albumin levels
- For patients on long-standing TRT (>1 year) without documentation, the requirement for two low baseline serum total testosterone levels may be waived case-by-case
- Risk factors for prostate cancer include African-American background, first-degree relative with prostate cancer, and exposure to Agent Orange
Indications for Evaluation- • Men presenting with specific symptoms: erectile dysfunction, low libido, decreased frequency of morning erections, new unexplained gynecomastia, decreased body hair, eunuchoid features on exam, small testes, loss of male hair and gynecomastia
- • Men with findings associated with hypogonadism: infertility, unexplained anemia, fractures
- • Men with a history of conditions likely to cause hypogonadism: traumatic brain injury, orchiectomy, pituitary dysfunction, testicular trauma, chronic opioid use
Laboratory & Biochemical Assessment Criteria- • Serum total and/or free testosterone must be unequivocally and consistently low
- • Measurements must be obtained in the early morning (6–10 am), fasting state, and confirmed on at least two separate occasions
- • Total testosterone levels <150 ng/dL require evaluation for secondary/central hypogonadism
- • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must be measured to distinguish primary from secondary hypogonadism
- • Abnormal immunoassay results must be confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS)
- • Free testosterone should be measured when conditions affecting sex hormone-binding globulin (SHBG) are present: obesity, diabetes mellitus, glucocorticoid use, nephrotic syndrome, thyroid disease, acromegaly, androgen/estrogen use, liver disease
- • Harmonized lower limit of normal for total testosterone is 264 ng/dL for CDC-certified assays with normal SHBG
Contraindications to Testosterone Replacement Therapy (TRT)- • Active prostate or breast cancer
- • Uncontrolled/untreated erythrocytosis (initial hematocrit >48% or 54% on TRT)
- • Severe, untreated obstructive sleep apnea
- • Elevated prostate-specific antigen (PSA) (>4 ng/mL)
- • Severe lower urinary tract symptoms
- • Inadequately controlled congestive heart failure
- • Acute coronary syndrome, stroke, or revascularization procedure within 4 months
- • Thrombophilia or history of unprovoked venous thromboembolism
- • Severe liver disease or renal failure
- • Active, unaddressed anabolic steroid misuse
- • Desire for future fertility
Initiation, Monitoring, & Dosing Parameters- • Discontinue TRT if symptoms do not significantly and consistently improve after 6–12 months despite testosterone levels within the reference range
- • Monitor testosterone (including free/bioavailable), hemoglobin, hematocrit, and PSA at 3–6 months after initiation, again at 12 months
- • Dose adjustments indicated if testosterone falls outside laboratory limits or total testosterone exceeds 900 ng/dL
- • Discontinue testosterone if hematocrit exceeds 54%
- • Blood draw timing: midway between injections for injectable formulations; 2–8 hours after application for gel once steady-state is achieved (typically after ≥1 week)
- • PSA monitoring: baseline, repeated at 12 months, then annually (or sooner if clinically indicated)
Specialist Referral Criteria- • Endocrinology: Total testosterone <150 ng/dL with inappropriately normal or decreased LH/FSH; new/established contraindications to TRT; gynecomastia due to hypogonadism
- • Urology (for males receiving TRT): PSA rising >1.4 ng/mL from baseline or >4 ng/mL at any time; lack of improvement or intolerance of PDE-5 inhibitors
Alternative Therapies & Specific Clinical Scenarios- • Human chorionic gonadotropin (HCG) reserved for hypogonadotropic hypogonadism in men seeking to maintain fertility (restricted to endocrinology and infertility specialists)
- • Clomiphene may be considered on a case-by-case basis in males with hypogonadotropic hypogonadism desiring fertility prior to HCG use
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AVANAFIL TAB,ORAL
STENDRA
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STENDRA |
2024-10-31 |
Formulary Status- Avanafil is non-formulary.
- Sildenafil and tadalafil are available on the VA National Formulary (PA-F).
Prescribing & Clinical Evaluation Requirements- Prescriptions for erectile dysfunction must be written by a VA prescriber following an appropriate clinical evaluation.
- Prescribing clinician is responsible for ensuring no contraindications exist for the prescribed PDE5 inhibitor.
- Patient must understand treatment choices, associated risks, and benefits.
Quantity & Dispensing Limits- Limited to 6 doses per month for management of erectile dysfunction.
- Quantities less than 6 doses per month dispensed only at request of patient or prescriber.
- Greater quantities may be approved on a case-by-case basis (e.g., couples trying to conceive, veterans with inconsistent response).
- Quantity limit does not apply for management of pulmonary hypertension.
Adverse Event Reporting- All adverse events must be reported in the VA Adverse Drug Event Reporting System (VA ADERS/VA MedSafe).
Lost Prescription Management- Lost prescriptions will not be replaced during the intended time period; authorized refills become available at the next scheduled refill date.
Clinical Category: Monotherapy & Combination Therapy Restrictions- A PDE5I should not be used routinely for the management of LUTS-BPH as monotherapy.
- A PDE5I should not be used in combination with alpha blockers for BPH/LUTS, as it offers no symptom improvement advantage over either agent alone per American Urological Association (AUA) guidelines.
Clinical Category: Formulary PDE5I Initiation & Substitution Criteria- Consider when more established pharmacotherapies are not an option or have not demonstrated benefit.
- Initiate a formulary alpha blocker first using shared decision making and patient-specific factors. If ED is present, may consider adding a formulary PDE5I (with quantity limits) to an alpha blocker.
- Consider substituting or adding a formulary PDE5I if unable to tolerate or lack of response to an adequate trial (12 weeks) of a formulary alpha blocker titrated to maximum therapeutic dose.
- If adding a PDE5I, the patient must be on a stable dose of the alpha-blocker prior to initiation; the PDE5I should then be started at the lowest recommended dose.
Clinical Category: Clinical Scenarios for Formulary PDE5I Monotherapy Consideration- In place of an alpha blocker in the interim if cataract surgery is planned or likely (due to risk of intraoperative floppy iris syndrome).
- When an alpha blocker is contraindicated or not tolerated and an antimuscarinic is not appropriate due to post-void residual >250 mL, contraindication, ineffective trial, or substantial contribution to existing anticholinergic burden.
- (Note: The document explicitly states that only sildenafil, tadalafil, and vardenafil have been studied for BPH/LUTS; avanafil-specific criteria are not provided in the text.)
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ZOLBETUXIMAB-CLZB INJ,LYPHL
VYLOY
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VYLOY |
2024-10-31 |
Exclusion Criteria- PD-L1 by Combined Positive Score (CPS) > 5 (unless patient is not a candidate for an immune checkpoint inhibitor)
- Prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies
- Absolute Neutrophil Count < 1500/mm3
- Platelets < 100,000/mm3
- Total bilirubin > 1.5x Upper Limit of Normal (or > 3x Upper Limit of Normal with liver metastases)
- Estimated Creatinine Clearance < 30ml/min
- Lactation
Inclusion Criteria- Locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma
- HER2-negative tumor
- CLDN18.2 positive tumor (≥75% of tumor cells showing moderate-to-strong staining)
- Treatment plan includes zolbetuximab with a fluoropyrimidine- and platinum-based regimen (i.e. mFOLFOX6 or CAPOX) as first-line therapy
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (if applicable)- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment; treatment should be given if the benefit outweighs the potential risk
- For females who are lactating: breastfeeding/providing breastmilk to an infant is not recommended during therapy and for 8 months after stopping treatment.
Indication & Patient Selection- First-line treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) negative gastric or gastroesophageal junction adenocarcinoma
- Tumors must be CLDN18.2 positive, as determined by an FDA-approved test
- Administered in combination with fluoropyrimidine and platinum-containing chemotherapy (mFOLFOX6 or CAPOX)
Dosing & Administration- Initial dose: 800 mg/m2 IV
- Subsequent doses: 600 mg/m2 IV every 3 weeks or 400 mg/m2 IV every 2 weeks
- Continue therapy until disease progression or unacceptable toxicity
- Supplied as 100 mg lyophilized powder in a single-dose vial
Monitoring & Safety Management- Monitor patients during the infusion and for 2 hours afterwards (or longer as needed) for hypersensitivity and infusion-related reactions
- Pretreat patients with antiemetics prior to each infusion due to the highly emetogenic chemotherapy regimen
- Manage nausea and vomiting with antiemetics, fluid replacement, infusion interruptions, and infusion rate adjustments
Clinical Pathway & Guideline Recommendations- NCCN Guidelines: Listed as a preferred first-line category 1 regimen for HER2-negative, CLDN18.2 positive locally advanced, unresectable, or metastatic gastric or GEJ cancer in combination with chemotherapy
- VA Oncology Clinical Pathway (Esophageal Cancer V1.2025): Recommended first-line for stage IVB adenocarcinoma (HER2 negative, MSS) in patients who are candidates for cytotoxic chemotherapy, test positive for CLDN18.2, and are not candidates for immunotherapy or have PD-L1 CPS <5%
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FOSCARBIDOPA/ FOSLEVODOPA INJ,SOLN
VYALEV
|
VYALEV |
2024-10-24 |
Exclusion Criteria- Currently taking or taken within 14 days a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine)
- Patient has not demonstrated a response to prior levodopa use
Inclusion Criteria- Diagnosis of Idiopathic Parkinson’s disease
- Patient is under the care of a VA or VA Community Care neurologist
- Motor fluctuations (“wearing off”) that require dosing of dopaminergic medications at intervals every 4 hours or less
- Either combination of carbidopa/levodopa controlled-release (CR) and immediate-release (IR) tablet formulations or carbidopa/levodopa extended-release (ER) capsules throughout the day have not adequately resolved OFF periods
- Contraindication, intolerance, or inadequate therapeutic response to at least one agent from two of the following classes: dopamine agonist, catechol-O methyl transferase [COMT] inhibitor, monoamine oxidase type B [MAO B] inhibitor
- Discussion with the patient/caregiver/family regarding realistic efficacy expectations, device management, and potential device-related complications should be documented in the patient’s medical record.
Indication & Patient Population- Treatment of motor fluctuations in adults with advanced Parkinson’s disease
- Considered when oral medications can no longer manage motor fluctuations and dyskinesias
Dosing & Administration Requirements- 24-hour/day continuous subcutaneous infusion
- Infusion rate calculated based on the patient’s current levodopa dose
- Requires use of VYAFUSER pump (Phillips-Medisize portable infusion pump)
- Dosage form: 120mg foscarbidopa and 2,400mg foslevodopa per 10mL vial
Contraindications- Concurrent or recent (within 2 weeks) administration of a nonselective monoamine oxidase inhibitor (MAOI)
Warnings & Precautions- Somnolence and falling asleep during activities of daily living
- Hallucinations/psychosis
- Development or worsening of impulse control/compulsive behavior
- Infusion site reactions/infections (e.g., redness, nodules)
- Withdrawal-emergent hyperpyrexia and confusion
- Dyskinesia
- Ischemic cardiovascular events
- Glaucoma
Clinical Considerations & Monitoring- Non-motor symptoms of advanced PD (e.g., severe dementia, chronic hallucinations, or psychosis) may impact therapy selection
- Requires specialized monitoring due to acceptable risk profile with device-assisted therapies
- Mitigation strategies for infusion site reactions include topical or subQ steroids, oral NSAIDs, and topical cooling
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TROSPIUM/ XANOMELINE CAP,ORAL
COBENFY, COBENFY STARTER PACK
|
COBENFY, COBENFY STARTER PACK |
2024-10-10 |
Indication- • Treatment of schizophrenia
Patient Selection & Clinical Criteria- • Adults aged 18–65 years with a diagnosis of schizophrenia
- • Recent worsening of psychosis warranting hospital admission
- • Positive and Negative Syndrome Scale (PANSS) score of 80 or higher
- • Clinical Global Impression-Severity (CGI-S) score of 4 or higher
Dosing & Administration- • Capsules available in strengths: 50mg/20mg, 100mg/20mg, 125mg/30mg
- • Days 1–2: 50 mg xanomeline and 20 mg trospium twice daily
- • Days 3–7: 100 mg xanomeline and 20 mg trospium twice daily
- • Beginning on day 8: Flexible dosing with optional increase to 125 mg xanomeline and 30 mg trospium twice daily or return to 100 mg/20 mg based on tolerability
Contraindications- • Urinary retention
- • Moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment
- • Gastric retention
- • History or hypersensitivity to KarXT or trospium
- • Untreated narrow-angle glaucoma
Warnings & Precautions- • Risk of urinary retention
- • Not recommended in patients with mild hepatic impairment (Child-Pugh Class A)
- • Risk of use in patients with biliary disease
- • Decreased gastrointestinal motility
- • Risk of angioedema
- • Risk of use in patients with narrow-angle glaucoma
- • Increases in heart rate
- • Anticholinergic adverse reaction in patients with renal impairment (not recommended for use in moderate and severe renal impairment, eGFR <60ml/min)
- • Central nervous system effects
Required Pre-prescribing Assessments- • Assess liver enzymes and bilirubin prior to initiation
- • Assess heart rate at baseline
Formulary & Clinical Considerations- • Formulary status: NF/TBD
- • Considerations include GI side effects and hypertension/increased heart rate
- • Note that efficacy trials were limited to 5 weeks; long-term efficacy and safety beyond controlled inpatient settings are not fully characterized
Exclusion Criteria- Moderate or severe renal impairment (eGFR < 60 ml/min)
- Mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe (Child-Pugh Class C) hepatic impairment
- Untreated narrow-angle glaucoma
- Active biliary disease (e.g., symptomatic gallstones)
- Uncontrolled hypertension
- Concomitant condition with risk of urinary retention (e.g., neurogenic bladder, benign prostatic hyperplasia, bladder outlet obstruction, diabetic cystopathy)
- Concomitant condition with risk of bowel obstruction (e.g., gastric retention, inflammatory bowel disease, intestinal atony, neurogenic bowel)
Inclusion Criteria- Diagnosis of schizophrenia
- Prescriber is a VA/VA Community Care psychiatrist
- Insufficient response or intolerance to trials of three of the following antipsychotics categories: partial dopamine agonism (e.g., aripiprazole), low dopamine affinity (e.g., olanzapine) and moderate to high dopamine affinity (e.g., risperidone)
- Inadequate response, intolerance, or patient determined not to be a candidate for clozapine
Monitoring & Prerequisites- Liver enzymes, bilirubin, and heart rate should be assessed prior to initiation and as clinically indicated during treatment
- Adherent to, and achieved a target dose consistent with the effective doses specified in the FDA label for at least 6 weeks
- If intolerance is due to metabolic effects, efforts to mitigate these effects have been attempted with an adequate trial of at least 2 of the following: MOVE program participation, Metformin, Topiramate
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ATEZOLIZUMAB/ HYALURONIDASE-TQJS INJ,SOLN
TECENTRIQ HYBREZA
|
TECENTRIQ HYBREZA |
2024-09-26 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Lactating
Inclusion Criteria- Indications & Administration
- Indication is FDA approved
- Off-label use supported by high-level published data
- If administering with chemotherapy and/or bevacizumab, administer prior to chemotherapy and/or bevacizumab if given on the same day
- Care Coordination & Documentation
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Performance Status
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception
- Female patients of child-bearing potential and male patients with female partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment. Use effective contraception during therapy and for 5 months after the last dose.
- Product Substitution/Transition
- Do not substitute atezolizumab/hyaluronidase SubQ for atezolizumab IV on a mg per mg basis. Patients may transition products at the next dose.
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LEBRIKIZUMAB-LBKZ INJ,SOLN
EBGLYSS PEN, EBGLYSS SYRINGE
|
EBGLYSS PEN, EBGLYSS SYRINGE |
2024-09-26 |
Exclusion Criteria- Use of live (attenuated) vaccines immediately prior to or during treatment
- Concurrent use with therapeutic biologics unless potential risk-benefits favor use
- Untreated parasitic (helminth) infection
Inclusion Criteria (New Starts)- Diagnosis of chronic atopic dermatitis made or confirmed by a VA/VA Community Care dermatologist
- Prescribed by a VA/VA Community Care dermatologist, allergist, or immunologist, or other locally designated expert in the management of atopic dermatitis in consultation with a VA/VA Community Care dermatologist, allergist, or immunologist
- Offered all age-appropriate vaccinations prior to initiating therapy
- Assessment of moderate to severe atopic dermatitis in the last 2 weeks as determined by either a gestalt assessment of “moderate” or “severe” OR Eczema Area and Severity Index (EASI) ≥ 16
- Refractory to ≥ 2 classes of topical therapies for atopic dermatitis (e.g., corticosteroids, calcineurin inhibitors, PDE4 inhibitors, JAK inhibitors) for ≥ 4 weeks total unless the therapy is medically inadvisable or not tolerated
Additional Inclusion Criteria- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
- For females who are pregnant or plan to become pregnant: Counseling provided on potential risks vs benefits of treatment
- For females who are lactating/providing breastmilk to an infant or planning to do so: Counseling provided on the potential risks vs benefits of treatment
Sequencing & Clinical Management Notes- Consider tralokinumab-ldrm prior to lebrikizumab-lbkz if patient weighs <100 kg
- First-line therapy options include dupilumab, tralokinumab-ldrm, lebrikizumab-lbkz, or nemolizumab-ilto; second-line includes abrocitinib or upadacitinib
- Consider offering methotrexate, azathioprine, or mycophenolate mofetil in the context of shared decision-making (prior trials not required), conditional on risk-benefit certainty, onset speed, follow-up feasibility, comorbidities, and patient values/preferences
- Unless contraindicated, recombinant zoster vaccine should be completed or at least initiated by the end of the first year of treatment
Indication- Treatment of adults with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
- Can be used with or without topical corticosteroids (TCS).
Dosing & Administration- Induction: 500 mg subcutaneous (SC) at Weeks 0 and 2, then 250 mg SC every 2 weeks until Week 16 or later when adequate clinical response is achieved.
- Maintenance: 250 mg SC every 4 weeks.
Pretreatment Requirements- Complete all age-appropriate vaccinations according to current guidelines.
- Avoid use of live vaccines immediately before and during treatment.
- Treat any pre-existing parasitic (helminth) infections.
- No screening recommended for infection, tuberculosis, or hepatitis B virus.
Monitoring & Safety- Monitor for adverse reactions including conjunctivitis and keratitis, injection site reactions, and herpes zoster.
- No laboratory test monitoring recommendations.
- Contraindicated in patients with hypersensitivity.
- Warnings include hypersensitivity, conjunctivitis and keratitis, parasitic (helminth) infections, and avoidance of live vaccines during treatment.
VA Formulary Place in Therapy- May be used for patients with moderate-to-severe AD who are refractory to ≥ 2 classes of topical therapies for ≥ 4 weeks total unless medically inadvisable or not tolerated.
- May be considered as an alternative to dupilumab and tralokinumab-ldrm based on a favorable efficacy-safety-cost profile.
- Biologics are recommended when there is refractoriness, intolerance, or inability to use mid- to high-potency topical therapies.
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ETHINYL ESTRADIOL/ NORETHINDRONE TAB,ORAL DISINTEGRATING
FEMLYV
|
FEMLYV |
2024-09-19 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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PALOPEGTERIPARATIDE INJ,SOLN
YORVIPATH
|
YORVIPATH |
2024-09-12 |
Indication- Hypoparathyroidism in adults
Patient Population & Clinical Scenarios- Adults with hypo-PTH Dx for at least 26 weeks and on stable doses of ≥0.5 mcg calcitriol and >800 mg/d calcium
- Patients refractory to standard care with therapeutic doses of calcium and calcitriol
- Specific clinical scenarios where patients may benefit:
- Hyperphosphatemia
- Corrected calcium below target levels or symptomatic hypocalcemia
- Hypercalcuria or nephrolithiasis despite thiazide use
- Malabsorption syndromes
- Declining eGFR
- ED visit or hospitalization for hypocalcemia or requiring IV calcium in any setting
Dosing & Administration- Initial dose: 18 mcg subcutaneously once daily
- Dose adjustments: In 3 mcg increments based on serum calcium levels, supplemental calcitriol, and supplemental calcium doses
- Maximum dose: 30 mcg/day
Monitoring Requirements- Periodically measure serum calcium and monitor for signs/symptoms of hypercalcemia and hypocalcemia
- Monitor for signs/symptoms of orthostatic hypotension
- Measure serum calcium and digoxin levels frequently if concomitant use may predispose to digoxin toxicity with hypercalcemia
- Measure serum calcium more frequently when used with other drugs known to affect serum calcium levels
Contraindications & Precautions- Severe hypersensitivity to palopegteriparatide or any of its excipients
- Not recommended in patients at increased risk of osteosarcoma
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TISLELIZUMAB-JSGR INJ,SOLN
TEVIMBRA
|
TEVIMBRA |
2024-08-29 |
Indications & Patient Population- First-line treatment, in combination with a platinum-containing regimen, for unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (> 1)
- Subsequent therapy as a single agent for unresectable or metastatic ESCC if no prior immune checkpoint inhibitor has been used
- First-line treatment, in combination with platinum- and fluoropyrimidine-based chemotherapy, for unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (> 1)
- Population includes patients with unresectable, recurrent, or metastatic ESCC; untreated, unresectable, or metastatic HER2-negative gastric/GEJ adenocarcinoma
- Exclusions: Active or uncontrolled CNS disease, active autoimmune disease, medical condition requiring systemic corticosteroids or immune suppressants, fistula or esophageal obstruction (ESCC), prior ICI therapy (for subsequent ESCC therapy)
Dosing & Administration- 150 mg IV every 2 weeks, 200 mg IV every 3 weeks, 300 mg IV every 4 weeks, or 400 mg IV every 6 weeks
- Dosage form: Injection, 100 mg/10 mL (10 mg/mL) solution in a single dose vial
Safety & Monitoring Requirements- Monitor for severe and fatal immune-mediated adverse reactions
- Monitor for infusion-related reactions (occur in 5% of patients; > grade 3 in 0.2%)
- Manage infusion-related reactions by slowing and/or interrupting the infusion rate
- Assess risk for complications of allogeneic hematopoietic stem cell transplantation (GVHD, hepatic veno-occlusive disease)
- Assess embryo-fetal toxicity; can cause fetal harm when administered to a pregnant woman
VA Formulary & Clinical Pathway Criteria- VA Oncology Clinical Pathways for Esophageal Cancer (v7.2025) and Gastric Cancer (v4.2025) do not include tislelizumab
- Preferred 1L regimens per NCCN/UpToDate direct to nivolumab or pembrolizumab-containing regimens based on PD-L1 CPS thresholds (> 1, > 5, > 10) and histology (adenocarcinoma vs. squamous cell carcinoma)
- FDA ODAC meta-analysis indicates survival benefit for ICI addition in advanced ESCC only with CPS > 1, not CPS < 1
- Assessment indicates tislelizumab does not appear to provide additional benefit over the current ICI landscape for ESCC or gastric/GEJ adenocarcinoma
Exclusion Criteria- Autoimmune disease
- Immunosuppression requiring a corticosteroid equivalent to > 10 mg per day of prednisone
- Primary Immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Known pregnancy
- Lactating
Inclusion Criteria- Indication is FDA-approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Reproductive & Pregnancy Considerations- For females who can become pregnant: Pregnancy must be excluded prior to receiving tislelizumab
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for 4 months after stopping treatment
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CARBIDOPA/ LEVODOPA CAP,SA
CREXONT
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CREXONT |
2024-08-22 |
Exclusion Criteria- Currently taking a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine) or have recently (within 14 days) taken a nonselective MAO inhibitor
Inclusion Criteria- Patient is under the care of a VA or VA Community Care neurologist or locally designated expert
- Clinical diagnosis of Parkinson’s disease (PD), post-encephalitic parkinsonism, or parkinsonism that may follow intoxication by carbon monoxide or manganese
- Motor fluctuations (“wearing off”) that require dosing of dopaminergic medications at intervals of every 4 hours or less
- Combination of carbidopa/levodopa controlled-release (CR) and immediate-release (IR) tablet formulations throughout the day have not adequately resolved OFF periods
- Contraindication, intolerance, or inadequate therapeutic response to at least one agent from two of the following classes: dopamine agonist, catechol-O methyl transferase [COMT] inhibitor, monoamine oxidase type B [MAO B] inhibitor
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NEMOLIZUMAB-ILTO INJ,LYPHL
NEMLUVIO
|
NEMLUVIO |
2024-08-22 |
Exclusion Criteria- Use of live vaccines during therapy
Core Inclusion Criteria- Documented clinical diagnosis of prurigo nodularis for ≥ 6 months with ≥ 20 prurigo nodularis lesions on the body bilaterally
- Documented patient-reported, moderate-to-very severe itching related to prurigo nodularis within the past 4 weeks
- Prescribed and monitored by a VA / VA Community Care dermatologist or a locally designated expert in consultation with a VA / VA Community Care dermatologist
- Inadequate response or intolerance to one of the following topical therapies (unless medically inadvisable): higher potency (Group 1–3) topical corticosteroid (≥ 2 weeks), pimecrolimus (≥ 12 weeks), or calcipotriene (≥ 8 weeks)
- An oral antihistamine, doxepin, or amitriptyline is medically inadvisable, not tolerated, or not adequate (after ≥ 2 weeks)
- Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate
- Completed all age-appropriate vaccinations as per current immunization guidelines (preferably ≥ 2 weeks before initiating therapy)
Additional Inclusion Criteria (Select If Applicable)- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
- For patients who are lactating / providing breastmilk to an infant or planning to do so: Counseling provided on the potential risks vs benefits of treatment.
Phototherapy Parameters & Definitions- Considered inadequate if NO treatment benefit after 12 treatments or inadequate partial response after 24 treatments.
- Medically inadvisable reasons include (and are not limited to) CONFIRMED (preferably by a written biopsy report) history of skin cancer, melanoma, or strong likelihood of developing them (e.g., Fitzpatrick skin type I or II = pale skin, easily sunburns).
Indication & Patient Population- Treatment of adults with prurigo nodularis (PN)
- Documented clinical diagnosis of PN
- ≥ 20 bilateral PN nodules
Dosing Requirements- Body Weight < 90 kg: 60 mg (two 30-mg injections) SC then 30 mg every 4 weeks
- Body Weight ≥ 90 kg: 60 mg (two 30-mg injections) SC then 60 mg every 4 weeks
Prior Therapy Criteria- Inadequate response (after ≥ 2 weeks per therapy) or intolerance to either:
- Two topical therapies (e.g., corticosteroids, calcipotriene, or calcineurin inhibitor) OR
- One topical therapy and an intralesional corticosteroid
- Unless these therapies are medically inadvisable
Safety & Contraindications- Known hypersensitivity to drug or excipients
- Avoid use of live vaccines during treatment
Treatment Monitoring & Trial Duration- Onset of Treatment: Week 4 based on PP-NRS–4 and IGA-0/1 responder rates
- Duration of an Adequate Therapeutic Trial: Peak responder rate was not reached by Week 16 based on PP-NRS–4 and IGA-0/1
Diagnosis & Provider Requirements- Diagnosis of chronic atopic dermatitis made or confirmed by a VA/VA Community Care dermatologist.
- Prescribed by a VA/VA Community Care dermatologist, allergist, immunologist, or other locally designated expert in the management of atopic dermatitis in consultation with a VA/VA Community Care dermatologist, allergist, or immunologist.
Disease Severity & Treatment History- Assessment of moderate to severe atopic dermatitis in the last 2 weeks as determined by either a gestalt assessment of “moderate” or “severe” OR Eczema Area and Severity Index (EASI) ≥16.
- Refractory to ≥2 classes of topical therapies for atopic dermatitis (e.g., corticosteroids, calcineurin inhibitors, PDE4 inhibitors, JAK inhibitors) for ≥ 4 weeks total.
Concomitant Therapy & Monotherapy Considerations- Used concomitantly with topical corticosteroids and/or topical calcineurin inhibitors initially until disease has sufficiently improved, then topical therapies may be discontinued.
- If topical therapies are medically inadvisable, there is a lack of evidence to support use of nemolizumab monotherapy.
Special Populations & Counseling Requirements- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
- For females who are pregnant or plan to become pregnant: Counseling provided on potential risks vs benefits of treatment.
- For females who are lactating / providing breastmilk to an infant or plan to do so: Counseling provided on the potential risks vs benefits of treatment.
Exclusion Criteria- Use of live (attenuated) vaccines during treatment with nemolizumab-ilto.
- Concurrent use with therapeutic biologics unless potential risk-benefits favor use.
Dosing & Sequencing Guidelines- Initial dose: 60 mg then 30 mg every 4 weeks.
- Maintenance dose (after 16 weeks for patients who achieve clear or almost clear skin): 30 mg SC every 8 weeks.
- First-line therapy options include dupilumab, tralokinumab-ldrm, lebrikizumab-lbkz, or nemolizumab-ilto.
- Second-line therapy options include abrocitinib or upadacitinib.
- Methotrexate, azathioprine, and mycophenolate mofetil may be considered with shared decision-making based on lower certainty of risk-benefits, slow onset, feasibility of adhering to follow-ups for laboratory monitoring, comorbidities, and patient values/preferences.
Indication & Patient Population- Adults and pediatric patients ≥ 12 years of age with moderate-to-severe atopic dermatitis
- Disease not adequately controlled with topical prescription therapies
- Used in combination with topical corticosteroids and/or calcineurin inhibitors
- Associated pruritus (PP-NRS ≥ 4; Pruritus VAS score ≥ 50)
Dosage & Administration- Initial therapy: 60 mg (two 30-mg injections) SC, followed by 30 mg SC every 4 weeks
- Maintenance therapy: For patients who achieve clear or almost clear skin after Week 16, recommended dose is 30 mg SC every 8 weeks
- Discontinue use of topical therapies after disease has sufficiently improved
Pretreatment Requirements & Screening- Complete all age-appropriate vaccinations per current immunization guidelines prior to initiating treatment
- No recommendations for infection, tuberculosis, or hepatitis B virus screening
Monitoring & Safety Considerations- Monitor for hypersensitivity reactions
- For patients taking CYP450 substrates (particularly narrow therapeutic index), monitor for effect or drug concentration and modify dosage of the substrate after initiating or discontinuing nemolizumab-ilto
- Higher body weight (>87 kg vs <62 kg) reduces systemic drug exposure, which may impact Investigator Global Assessment of skin lesion response but not pruritus improvement
Contraindications & Warnings- Contraindicated in patients with known hypersensitivity
- Warning for hypersensitivity reactions
- Avoid use of live vaccines during treatment
Special Populations & Organ Function- Pregnancy: Insufficient data; may be transferred from mother to fetus. Consider delaying live virus immunizations in exposed infants by a minimum of 3 months post-birth based on drug half-life.
- Lactation: Insufficient data; weigh potential risks vs benefits.
- Geriatric (≥65 years): Insufficient number of patients included in clinical trials to determine differential response.
- Hepatic/Renal Impairment: Mild to moderate impairment shows no clinically significant pharmacokinetic differences. Severe impairment effects are unknown.
VHA Place in Therapy / Utilization Criteria- Appropriate for patients with moderate-to-severe AD who have an inadequate response to topical prescription therapy (corticosteroids with or without calcineurin inhibitors)
- May be considered for patients experiencing inadequate response or intolerance to anti-IL-4/-13 or anti-IL-13 agents due to novel anti-IL-31 mechanism
- Lacks ocular adverse effects (e.g., conjunctivitis, keratoconjunctivitis) and risk of helminth infections associated with other targeted systemic monoclonal antibodies
- Offers a better safety profile than JAK inhibitors regarding risks of mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis
- Dosing convenience may be favorable due to every 4 or 8 weeks interval compared to every 2 weeks regimens for some alternatives; initial dosing schedule may be simpler than lebrikizumab-lbkz
- Maintenance therapy at 30 mg every 8 weeks represents the lowest cost option among targeted systemic therapies (excluding tralokinumab-ldrm 300 mg every 4 weeks for patients <100 kg); every 4 weeks maintenance has the highest drug cost
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SELADELPAR CAP,ORAL
LIVDELZI
|
LIVDELZI |
2024-08-22 |
Exclusion Criteria- Decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation event, including hepatorenal syndrome, MELD ≥ 12, hepatocellular carcinoma, hepatic encephalopathy, international normalized ratio (INR) > 1.3, platelet count < 150 x 103/microL
- Compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)
- Complete biliary obstruction
- Severely advanced primary biliary cholangitis (PBC) defined as total bilirubin greater than upper limit of normal (ULN) and albumin less than the lower limit of normal
- Alanine aminotransferase (ALT and/or aspartate aminotransferase (AST) > 3 times ULN
- Other chronic liver conditions, such as primary sclerosing cholangitis, autoimmune hepatitis, metabolic dysfunction-associated steatohepatitis (MASH), and alpha-1 antitrypsin deficiency
- Concomitant OAT3 inhibitors or strong CYP2C9 inhibitors
Inclusion Criteria- Prescribed and monitored by a VA or VA Community Care hepatologist or locally designated expert in PBC
- Documented diagnosis of PBC without cirrhosis or PBC with compensated cirrhosis and no evidence of portal hypertension
- Tried ursodiol monotherapy (unless medically inadvisable) and had intolerance or inadequate response after 12 months (stable dose for at least 3 months at 13–15 mg/kg/day)
- Tried elafibranor (unless medically inadvisable) and had intolerance or inadequate response after 13 weeks
Additional Inclusion Criteria- For patients who are pregnant or plan to become pregnant: Counseling provided on potential risks vs benefits of treatment
- For patients who are lactating / providing breastmilk to an infant or plan to do so: Counseling provided on potential risks vs benefits of treatment
Indication- Treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
- Accelerated approval based on reduction of alkaline phosphatase (ALP); improvement in survival or prevention of liver decompensation events has not been demonstrated. Continued approval contingent upon verification and description of clinical benefit in confirmatory trials.
Dosage & Administration- 10 mg orally once daily with or without food.
- Available as 10-mg capsules.
Pretreatment Evaluations & Monitoring- Pretreatment: Clinical and laboratory liver assessments (ALT, AST, total bilirubin, alkaline phosphatase).
- Monitoring during therapy: Clinical and laboratory liver assessments as per routine patient care.
Avoid in Patients With / Contraindications- Complete biliary obstruction.
- Concomitant OAT3 inhibitors (e.g., probenecid, rifampicin).
- Concomitant strong CYP2C9 inhibitors (e.g., fluconazole, fluoxetine, ticlopidine).
- Decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).
Warnings, Precautions & Discontinuation Criteria- Consider discontinuing therapy for: Worsening of liver tests; Progression to moderate or severe (Child-Pugh B or C) hepatic impairment.
- Interrupt therapy for: Worsening of liver tests or development of clinical hepatitis (e.g., jaundice, right upper quadrant pain, eosinophilia); Suspected biliary obstruction.
- Other warnings/precautions include bone fractures and liver test abnormalities (observed at higher than recommended doses [50 mg and 200 mg daily]).
Special Populations- Pregnancy: Insufficient human data; animal studies showed reduction of fetal growth and pre-weaning survival without malformations or adverse embryofetal survival. No clinical recommendations provided.
- Lactation: Insufficient human data; weigh benefits vs risks.
- Geriatric (≥65 years): No overall differences in safety or effectiveness compared to younger adults; no dosage adjustment necessary.
- Renal Impairment: No dosage adjustment for mild, moderate, or severe renal impairment; not studied in patients with end-stage renal disease on dialysis.
- Hepatic Impairment: Mild (Child-Pugh A) requires no dosage adjustment; moderate or severe (Child-Pugh B or C) requires consideration of discontinuing therapy.
Place in Therapy / CFU Context- Second-line therapy after UDCA.
- An adequate trial of UDCA is defined as ≥ 1 year at 13–15 mg/kg/d, with ≥ 3 months at a stable dosage.
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VORASIDENIB TAB
VORANIGO
|
VORANIGO |
2024-08-15 |
Exclusion Criteria- High-risk features (uncontrolled seizures, neurocognitive deficits, contrast-enhancing lesion)
- Unmanageable drug interactions
- Pregnancy
- Lactating
Inclusion Criteria- Grade 2 astrocytoma or oligodendroglioma (MRI residual non-enhancing disease) with an IDH1 or IDH2 mutation following surgery (biopsy, sub-total resection, or gross total resection)
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Reproductive Safety & Contraception Requirements- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 3 months after stopping treatment
Indication & Tumor Characteristics- Grade 2 astrocytoma or oligodendroglioma
- Susceptible IDH1 or IDH2 mutation (centrally confirmed)
- Following surgery (biopsy, sub-total resection, or total/gross-total resection)
Patient Selection & Performance Status- Karnofsky PS ≥80
- Measurable (non-enhancing) disease / minimal residual non-enhancing disease on MRI
Prior Treatment & Disease State- Residual or recurrent disease
- At least 1 prior surgery
- No use of corticosteroids for glioma
Exclusion Criteria- Uncontrolled seizures
- Brain-stem involvement
- Clinically relevant functional neurocognitive deficits
- Baseline QTc ≥450 msec
- Pregnancy
- Lactation
- Concomitant CYP3A4 or CYP2C9 substrates with narrow therapeutic index
Monitoring & Safety Requirements- Hepatoxicity (monitor q 2weeks for first 2 months, then monthly)
- EF toxicity (non-hormonal contraception due to drug interaction)
VA Clinical Pathway Integration- Grade 2 IDH-mutant astrocytoma or oligodendroglioma without high-risk features (age >40 with residual tumor, neurologic symptoms, contrast-enhancing tumor, atypical neuroimaging)
- Specifically for patients with residual non-enhancing disease on MRI or without a gross total resection
- Replaces current surveillance as the imminent standard of care per VA Clinical Pathway
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SELPERCATINIB TAB
RETEVMO
|
RETEVMO |
2024-08-08 |
Exclusion Criteria- Symptomatic CNS metastases
- GFR < 30 mL/min
- Uncontrolled hypertension
- Baseline QTc >470 msec
- Strong or Moderate CYP3A4 inducers
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Locally Advanced or Metastatic non-small cell lung cancer with a RET gene fusion
- Advanced or Metastatic Medullary Thyroid Cancer (MTC) with a RET mutation requiring systemic therapy
- Advanced or Metastatic Thyroid Cancer with a RET gene fusion requiring systemic therapy who are radioactive iodine-refractory (if radioactive iodine is appropriate)
- Advanced or Metastatic solid tumors with a RET gene fusion that progressed on or following prior therapy or who have no satisfactory alternative treatment options
Additional Inclusion Criteria- Care is provided by a VA/VA purchased care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Pregnancy Counseling Requirement- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
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VADADUSTAT TAB
VAFSEO
|
VAFSEO |
2024-07-25 |
Exclusion Criteria- Uncontrolled Hypertension
- History of myocardial infarction, cerebrovascular event or acute coronary syndrome in prior 3 months
- Cirrhosis or active, acute liver disease
- Unmanageable drug-drug interaction
- Patient risk of gastrointestinal erosion (i.e. history of GI bleed, peptic ulcer disease, current tobacco and alcohol use) outweighs potential benefit of vadadustat
Inclusion Criteria- Anemia related to chronic kidney disease receiving dialysis chronically (>3 months)
- Insufficient response to or unable to use ESA’s
- Care provided by a VHA dialysis provider (for contracted care/Community Care patients, medication is supplied by the contracted care provider as part of a bundled payment)
Additional Inclusion Criteria (Females Who Can Become Pregnant)- Pregnancy must be excluded prior to receiving vadadustat
- Counseling on potential risks vs benefits of treatment has been provided
- Use of effective contraception during therapy is required
Indication & Patient Population- Anemia in Chronic Kidney Disease (CKD) in patients receiving dialysis for at least 3 months
- Dialysis-dependent CKD (DD-CKD)
Treatment Prerequisites & Restrictions- ESAs should remain the standard for treatment of anemia due to CKD
- Use restricted to patients with anemia due to CKD receiving maintenance dialysis AND who have failed to respond to treatment with a formulary ESA
- Not indicated as a substitute for transfusion in patients requiring immediate correction of anemia
- Not recommended for anemia due to CKD in patients not on dialysis
Dosing & Monitoring Targets- Initial dose 300mg once daily, with dose adjusted in 150mg increments (increases occurring no sooner than at 4-week intervals)
- Recommended doses range 150mg to 600mg/day
- Dose adjusted to reduce need for RBC transfusions while maintaining Hgb 10-11g/dL
- Use lowest dose sufficient to reduce the need for RBC transfusions
Safety Warnings & Contraindications- Contraindicated in uncontrolled hypertension and known hypersensitivity to vadadustat or its components
- Boxed warning: Increased risk of thrombotic vascular events including MACE; targeting a Hgb level > 11g/dL is expected to further increase risk of death and thrombotic events
- No trial has identified a Hgb target level, dose of vadadustat, or dosing strategy that does not increase these risks
- May cause a worsening of hypertension
- Increased risk of hepatotoxicity (use not recommended in patients with active liver disease)
- Increased risk of venous or arterial thrombus including thrombus of vascular access
- Seizures, gastrointestinal erosions, and malignancies have all been reported
Risk-Benefit Considerations- Has not been shown to improve quality of life, fatigue, or patient well-being
- FDA review notes risks of hepatotoxicity and gastrointestinal erosions that are not risks of ESAs
- Expected to fill a niche role for patients who are non-responsive or unable to utilize ESAs
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DONANEMAB-AZBT INJ,SOLN
KISUNLA
|
KISUNLA |
2024-07-18 |
Demographic & Age Requirements- Exclusion: Age less than 60 years
Cognitive & Clinical Diagnosis- Inclusion: Patient meets criteria for mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD)
- Exclusion: Any medical, neurological, or mental health condition that may be a major contributing or primary cause of cognitive impairment
Neuroimaging & MRI Findings- Exclusion: Contraindication to or unable to complete brain MRI
- Exclusion: Evidence of other clinically significant lesions on brain MRI that indicate another cause of dementia
- Exclusion: Evidence on screening MRI that would exclude treatment (including more than 4 microhemorrhages; a single macro hemorrhage greater than 10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of acute/subacute cerebral contusion, acute/subacute stroke, aneurysms, vascular malformations, or infective lesions; severe small vessel, or white matter disease; space occupying lesions; or intra-axial brain tumors)
- Inclusion: Patient has had a brain MRI scan within the last 6 months
Laboratory & Biomarker Requirements- Exclusion: ApoE e4 homozygote
- Exclusion: Thyroid stimulating hormone above normal range (TSH > 5 mU/L if < 65 years old; TSH > 7.5 mU/L if > 65 years old)
- Exclusion: Low serum vitamin B12 levels
- Exclusion: Untreated human immunodeficiency virus (HIV)
- Inclusion: Amyloid PET imaging, cerebrospinal fluid (CSF) analysis consistent with AD (e.g., Beta-amyloid(1-42) (Abeta42) < 1030 pg/ml), or a clearly positive blood biomarker (e.g., FDA-cleared Lumipulse G pTau 217/B-Amyloid 42 Plasma Ratio >0.00738)
Psychiatric, Safety & Substance Use- Exclusion: Transient ischemic attack, stroke, or seizures within the past year
- Exclusion: Answer “yes” to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation item 4 or 5, or any suicidal behavior assessment within the past 6 months
- Exclusion: Hospitalized or treated for suicidal behavior in the past 5 years
- Exclusion: Current substance use disorder or positive urine drug screen
Medical Comorbidities & Bleeding Risk- Exclusion: Any immunological disease which is not controlled, or which requires treatment with biologic drugs
- Exclusion: Untreated bleeding disorder, platelet count <50,000 x 109/L, or international normalized ratio [INR] >1.5
- Exclusion: Malignant neoplasm under active therapy (unless approved by oncologist)
Medication Restrictions- Exclusion: Receiving medication(s) with anti-platelet or anti-coagulant properties (e.g., apixaban, clopidogrel, NSAIDs, t-PA), except aspirin
Provider & System Requirements- Inclusion: Prescriber is a VA (not VA Community care) board certified neurologist, geriatric psychiatrist, or geriatrician who specializes in treating dementia
- Inclusion: Patient has a signed informed consent on file; if genotype testing is not performed, the patient and provider accept the risk
- Inclusion: Mini-Mental State Examination (MMSE) score > 21 or Saint Louis University Mental Status (SLUMS) score or Montreal Cognitive Assessment (MoCA) score of > 16, or Functional Assessment Staging Test (FAST) Stage score of 2-4
- Inclusion: Neuroradiology is available to review serial MRI scans, either at site, or through National Teleradiology
- Inclusion: A process is in place before starting therapy to ensure the provider and pharmacy are notified to hold the infusion until the ordering physician can assess the patient and decide whether to continue treatment
Indication- Treatment of mild cognitive impairment (MCI) or mild dementia secondary to Alzheimer’s disease.
Patient Selection & Eligibility- Age 60 to 85 years.
- Gradual and progressive change in memory function reported by participant or informant for > 6 months.
- Mini–Mental State Examination (MMSE) score of 20 to 28.
- Amyloid pathology (>37 Centiloids).
- Presence of tau pathology (low/medium or high on PET scan).
- Adequate literacy, vision, and hearing for neuropsychological testing.
- Stable concomitant symptomatic AD medications and other cognition-impacting medications for at least approximately 30 days prior to initiation.
Dosing & Administration- Intravenous (IV) infusion over 30 minutes every 4 weeks.
- First three doses: 700 mg.
- Subsequent doses: 1400 mg every 4 weeks.
- Dose reduction to 700 mg if amyloid plaque level is 11 to <25 Centiloids.
- Switch to placebo if amyloid plaque level is <11 Centiloids on any single scan or 11 to <25 Centiloids on two consecutive scans.
Monitoring & Imaging Requirements- Recent brain magnetic resonance imaging (MRI) required prior to initiating treatment.
- Periodic MRI monitoring required prior to the 2nd, 3rd, 4th, and 7th infusions.
- Amyloid PET scans performed at 24 and 52 weeks to assess amyloid plaque levels for dose adjustment or discontinuation.
Safety & Precautions- Enhanced clinical vigilance for Amyloid-Related Imaging Abnormalities (ARIA) during the first 24 weeks of treatment.
- Increased risk of ARIA in apolipoprotein E e4 homozygotes compared to heterozygotes and noncarriers.
- Increased risk of ARIA-E and ARIA-H in patients with pretreatment microhemorrhages and/or superficial siderosis.
- Clinical evaluation including MRI if symptoms suggestive of ARIA occur.
- Infusion-related reactions: Reduce infusion rate or discontinue; consider pre-medication with antihistamines, acetaminophen, and/or corticosteroids at subsequent dosing.
Contraindications & Exclusions- Significant neurological disease other than AD affecting cognition or study completion (e.g., other dementias, serious brain infection, Parkinson’s disease, multiple concussions, epilepsy/recurrent seizures except febrile childhood seizures).
- Current serious or unstable illnesses across cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic systems.
- History of cancer within the last 5 years (except non-metastatic basal/squamous cell carcinoma of skin, in situ cervical cancer, nonprogressive prostate cancer, or low-risk cancers).
- Psychiatric diagnosis likely to confound drug effect interpretation or cognitive assessment, or history of schizophrenia/chronic psychosis.
- Actively suicidal status.
- History of alcohol or drug use disorder within 2 years prior to screening (except tobacco use disorder).
- Clinically significant multiple/severe drug allergies, significant atopy, or severe posttreatment hypersensitivity reactions.
- Clinically important abnormality in physical/neurological exam, vital signs, ECG, or labs detrimental to participant.
- Contraindications for MRI or PET.
- MRI evidence of ARIA-E, >4 cerebral microhemorrhages, >1 area superficial siderosis, macro hemorrhage, or severe white matter disease.
- Elevated liver enzymes: ALT ≥2.5x ULN, AST ≥2.5x ULN, total bilirubin ≥1.5x ULN, or alkaline phosphatase ≥2x ULN.
- Prior passive anti-amyloid immunotherapy within <5 half-lives prior to initiation.
- Active immunization against Aβ in any other study.
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IVABRADINE TAB
CORLANOR, IVABRADINE HCL
|
CORLANOR, IVABRADINE HCL |
2024-07-18 |
Exclusion Criteria- Acute decompensated heart failure
- Recent myocardial infarction (within the past 2 months)
- Cardiac resynchronization therapy started (within past 6 months)
- Atrial fibrillation or atrial flutter
- Congenital heart disease as etiology of heart failure
- Primary severe valvular heart disease as etiology of heart failure
- Clinically significant hypotension
- Sick sinus syndrome, sinoatrial block or 2nd or 3rd degree atrioventricular block (unless a functioning demand pacemaker is present)
- Pacemaker with atrial or ventricular pacing greater than 40% of the time, or with stimulation threshold at the atrial or ventricular level at least 60 beats per minute
- Family history or congenital long QT syndrome or treated with selected QT-prolonging agents
- Concomitant Class I antiarrhythmic agents
- Concomitant diltiazem or verapamil
- Concomitant strong or moderate CYP3A4 inhibitors, or CYP3A4 inducers
- Severe hepatic impairment (Child-Pugh C)
Inclusion Criteria- Provider Requirement: Initial prescription must be provided by a VA/VA Community Care cardiologist or other locally designated provider.
- Indication 1: Stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction (≤35%), on guideline-directed medical therapy including a beta-blocker at maximum tolerated dose (or unable to use), in normal sinus rhythm, with resting heart rate at least 70 bpm.
- Indication 2: Symptomatic inappropriate sinus tachycardia with persistent symptoms despite treatment with a beta-blocker, or unable to use a beta-blocker.
- Heart Rate Measurement Standard: Resting heart rate must be measured by 12-lead electrocardiogram after at least 5 minutes rest on 2 consecutive visits.
Additional Inclusion Criteria- Females of Childbearing Potential: For patients who can become pregnant, counseling must be provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
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AVACINCAPTAD INJ,SOLN
IZERVAY
|
IZERVAY |
2024-07-15 |
Exclusion Criteria- Geographic atrophy that is secondary to a condition other than age-related macular degeneration (AMD)
- Ocular or periocular infections
- Active intraocular inflammation
Inclusion Criteria- Provider is a VA or VA Community Care ophthalmologist
- Diagnosis of geographic atrophy secondary to AMD
Monitoring & Management- Monitor for signs of neovascular AMD due to increased rates associated with use
- If anti-VEGF therapy is required, administer separately from avacincaptad administration
Indication & Patient Population- • Indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
- • Patients must be aged ≥ 50 years with best-corrected visual acuity (BCVA) 20/25 to 20/320.
- • Requires a diagnosis of GA secondary to AMD that is nonfoveal centered, and in part within 1500µm from the foveal center.
- • Total GA lesion area must be ≥ 2.5 and ≤ 17.5 mm2 (1 to 7 disc areas); if multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA).
Dosing & Administration- • Recommended dose is 2 mg (0.1 mL of 20 mg/mL solution) administered by intravitreal injection to each affected eye.
- • Dosing frequency is once monthly (approximately 28 ± 7 days).
- • Treatment duration is limited to up to 12 months due to submitted data limitations.
Contraindications- • Ocular or periocular infection.
- • Active intraocular inflammation.
Monitoring & Safety Considerations- • Patients should be monitored for signs of neovascular AMD (wet AMD) or choroidal neovascularization (CNV)/macular neovascularization (MNV).
- • Perfusion of the optic nerve head must be monitored following injection and managed as needed.
- • Transient increases in intraocular pressure (IOP) may occur post-injection and should be managed as needed.
Use Restrictions & Place in Therapy- • In the absence of contraindications, use should be restricted to the treatment of GA secondary to AMD.
- • Patients with evidence of CNV or MNV in either eye were excluded from clinical trials, indicating this population is not established for use.
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ENSIFENTRINE SUSP,INHL
OHTUVAYRE
|
OHTUVAYRE |
2024-07-11 |
Disease Diagnosis & Severity- Diagnosis of asthma (Exclusion)
- Treatment of acute bronchospasm or an acute exacerbation of chronic obstructive pulmonary disease (COPD) (Exclusion)
- Moderate to severe COPD (e.g., post-bronchodilator FEV1 30-70% predicted and FEV1/FVC <0.7, confirmed by pulmonary function testing) (Inclusion)
- Inadequate symptom control (e.g., dyspnea score of at least 2 on Medical Research Council dyspnea scale) (Inclusion)
Prior Therapy & Exacerbation History- Receiving maintenance bronchodilator therapy with a long-acting beta-agonist (LABA) AND a long-acting anticholinergic (LAMA) AND an inhaled corticosteroid (unless inhaled corticosteroid is contraindicated) for at least 3 months (Inclusion)
- Had at least 2 moderate COPD exacerbations (requiring systemic steroids and/or antibiotics) or at least 1 severe COPD exacerbation (requiring hospitalization) in the previous 12 months (Inclusion)
- Patient is unable to tolerate or had an inadequate response to roflumilast and/or azithromycin after therapeutic trial (e.g., continued exacerbations after at least 6 months) or is clinically not appropriate for either agent (e.g., risks outweigh benefits) (Inclusion)
Psychiatric Considerations- History of depression (e.g., major depressive disorder [MDD]), suicidal thoughts or behaviors, unless determined in consultation with a mental health specialist or primary care provider that ensifentrine can be used (Exclusion/Caution)
- Other psychiatric adverse events including insomnia and anxiety; use with caution in patients with these or other mental health disorders (e.g., psychotic disorder, bipolar disorder, PTSD), especially if not fully controlled (Exclusion/Caution)
- Potential for psychiatric events with ensifentrine such as mood changes, depression, anxiety and suicidal thoughts and/or behaviors have been discussed with the patient and documented in medical record (Inclusion)
Hepatic Function- Moderate to severe hepatic impairment as exposure to ensifentrine may increase up to 2.3-fold (Exclusion/Caution)
Smoking Status- Patient is non-smoking or, if not, he/she is enrolled in a quit smoking program or on medications to assist with smoking cessation; current smokers may be considered if unable or refuse to quit (Additional Guidance/Inclusion)
Reproductive Potential- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy (Additional Inclusion Criteria)
Provider & Administrative Requirements- Provider is a VA or VA Community Care pulmonologist or designated expert (Inclusion)
- Adherent to COPD medications as evidenced by a review of prescription refill history (Inclusion)
- Patient has demonstrated correct inhaler technique (documented in medical record) (Inclusion)
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HEPARIN/ TAUROLIDINE INJ,SOLN
DEFENCATH
|
DEFENCATH |
2024-07-11 |
Indication- Reduce the incidence of catheter-related bloodstream infections (CRBSIs) in adult patients receiving chronic hemodialysis (HD) via a central venous catheter (CVC)
- Approved under the Limited Population Pathway for Antimicrobial/Antifungal Drugs (LPAD)
Dosage & Administration- Instilled into the catheter lumen after each dialysis session
- Removed/aspirated from the catheter prior to subsequent hemodialysis sessions
- Not intended for systemic administration
- Should not be used as a catheter lock flush product
Patient Population- Adult patients receiving intermittent HD (>= 2 per week) via a permanent tunneled cuffed silicone or polyurethane CVC
- Excludes patients who have received antibiotics, thrombolytics, or are immunosuppressed
- Requires life expectancy > 6 months
Contraindications & Warnings- Known heparin induced thrombocytopenia (HIT)
- Known hypersensitivity to taurolidine, heparin, the citrate component of the drug, or pork products
- Discontinue if HIT occurs and institute supportive care
Formulations- 3mL CLS in a single-use vial containing 40.5mg/3000 Units of taurolidine and heparin, respectively
- Under Review: 5mL CLS in a single-use vial containing 67.5mg and 5000 Units of taurolidine and heparin, respectively
VHA Use Considerations- Demonstrated fewer CRBSIs than heparin alone but has not been compared head-to-head versus a 4% citrate solution (which is routinely used and has inherent antimicrobial properties)
- Taurolidine containing CLS have been studied off-label in other populations (e.g., Oncology, GI TPN requiring patients), but VHA requests to date have been infrequent; potential for off-label use is difficult to predict
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ROZANOLIXIZUMAB-NOLI INJ,SOLN
RYSTIGGO
|
RYSTIGGO |
2024-07-11 |
Exclusion Criteria- Concomitant therapy with other monoclonal antibody or neonatal Fc receptor antagonist (e.g., efgartigimod)
- Thymectomy within 3 months
- Intravenous immunoglobulin (IVIG) or plasma exchange within 1 month
- Untreated hepatitis B, hepatitis C, or HIV with low CD4 count
- Active, untreated infection
Core Inclusion Criteria- Care provided by a VA/VA Community Care neurologist
- Acetylcholine receptor (AChR) antibody positive generalized myasthenia gravis or muscle-specific tyrosine kinase (MuSK) antibody positive myasthenia gravis
- Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV
- Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) total score ≥ 5
Additional Inclusion Criteria (Therapy-Specific)- Bridge therapy: Inadequate symptom control, contraindication, or intolerance to high dose steroid burst, plasma exchange or IVIG
- AChR+ chronic therapy: Inadequate symptom control to maximally tolerated pyridostigmine and at least two immunosuppressive agents separately trialed for at least 6 months each (e.g., azathioprine, cyclosporine, mycophenolate)
- MuSK+ chronic therapy: Inadequate symptom control to rituximab trialed for at least 6 months
- AChR+ or MuSK+ chronic therapy: History of intolerance or contraindication preventing trial of above immunosuppressive agents
Indication & Patient Population- Generalized myasthenia gravis (gMG) who are positive for acetylcholine receptor antibody (AChR+) or muscle-specific tyrosine kinase antibody (MuSK+)
- Not supported for other antibody types of MG including LRP4+ and seronegative disease
Dosing & Administration- Single dose vial for injection 280mg/2mL administered via subcutaneous (SC) infusion
- Administered weekly for 6 weeks per treatment cycle
- Repeat cycles as needed no more than 63 days from start of previous cycle
Safety & Monitoring Requirements- Monitor patients for 15 minutes after administration for possible development of hypersensitivity reactions (including angioedema and rash)
- Avoid in active infection, which may mean delaying or holding treatment until infection resolves
- Live or live-attenuated vaccines are not recommended during treatment
Contraindications & Treatment Restrictions- Should not be used with other IgG-affecting agents for chronic management including intravenous immunoglobulin (IVIg) or efgartigimod
Therapeutic Positioning- Short-term bridge therapy to initiation or switch of chronic immunosuppressant therapy in patients with gMG who are AChR+ or MuSK+
- Steroid-sparing chronic treatment option when other traditional oral immunosuppressants (azathioprine, mycophenolate) and/or steroids are ineffective
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LIRAGLUTIDE INJ,SOLN
SAXENDA, VICTOZA 2-PAK, VICTOZA 3-PAK
|
SAXENDA, VICTOZA 2-PAK, VICTOZA 3-PAK |
2024-07-04 |
Indications & Eligibility- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance
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EDARAVONE INJ,SOLN
RADICAVA
|
RADICAVA |
2024-06-20 |
Exclusion Criteria- Notably decreased respiratory function and dyspnea (total score of 3 or less points on ALSFRS-R items for dyspnea, orthopnea, or respiratory insufficiency)
- Bilevel positive airway pressure (BiPAP) dependent (use 24 hours per day)
- Other medical illness that will limit evaluation of motor function and efficacy (e.g., Parkinson’s disease, schizophrenia, significant dementia, other major medical morbidity)
- Other possible causes for current symptoms as applicable not ruled out (e.g., cervical spondylosis or multifocal motor neuropathy)
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist or locally designated ALS expert
- Diagnosis of ALS made or confirmed by a VA/VA Community Care neurologist or locally designated ALS expert
- Documentation of an itemized ALSFRS-R score in the electronic medical record
- Preserved function in either upper limbs (e.g., self-feed, self-dressing, typing) or lower limbs (e.g., walking)
- Discussion with patient/caregiver/family regarding realistic treatment expectations and discontinuation of therapy documented in the patient’s medical record
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ELAFIBRANOR TAB
IQIRVO
|
IQIRVO |
2024-06-20 |
Indication & Patient Selection- Treatment of primary biliary cholangitis (PBC) in combination with ursodiol (UDCA) in adults with an inadequate response to UDCA
- Monotherapy in patients unable to tolerate UDCA
- Accelerated approval based on reduction of alkaline phosphatase (ALP); improvement in survival or prevention of liver decompensation events has not been demonstrated
Dosage & Administration- 80 mg orally once daily with or without food
- Available as 80 mg tablets
Pretreatment Evaluations- Evaluate for muscle pain or myopathy
- Verify that patients of reproductive potential are not pregnant
- Obtain baseline liver tests (ALT, AST, TB, ALP)
Monitoring Requirements- Monitor liver tests (ALT, AST, TB, ALP)
- Monitor bone health
- Monitor for decompensation in patients with cirrhosis
Contraindications & Restrictions on Use- Use not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy)
- Avoid use in decompensated liver disease
Dose Modifications & Discontinuation Criteria- Renal impairment (mild, moderate, or severe): No dosage modification recommended
- Mild hepatic impairment: No dosage modification required
- Moderate or severe hepatic impairment (Child-Pugh B or C) or progression to the same: Consider discontinuing therapy
- Worsening liver tests after restarting elafibranor in patients with drug-induced liver injury (DILI): Consider discontinuing therapy
Interrupt Therapy Criteria- New onset or worsening of muscle injury, muscle pain, myopathy, or rhabdomyolysis
- Worsening liver tests or evidence of clinical hepatitis in patients with DILI
- Hypersensitivity reactions
- Suspected biliary obstruction
Place in Therapy & Clinical Context- Recommended as add-on therapy to UDCA in patients with PBC without decompensated cirrhosis who have an inadequate response to UDCA
- Monotherapy reserved for patients with intolerance to UDCA
- An adequate trial of UDCA is defined as at least 1 year at a dosage of 13–15 mg/kg/d, with ≥ 3 months at a stable dosage
- No dosage adjustment necessary for patients ≥65 years; closer monitoring of adverse effects recommended for patients >75 years
- Efficacy not significantly impacted by body weight (43–120 kg) or BMI (14.5–54 kg/m²)
Indication & Diagnosis- Documented diagnosis of primary biliary cholangitis (PBC) without cirrhosis or PBC with compensated cirrhosis and no evidence of portal hypertension
Exclusion Criteria- Decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation event, including hepatorenal syndrome, MELD ≥ 12, hepatocellular carcinoma, hepatic encephalopathy, international normalized ratio (INR) > 1.3, platelet count < 150
- Compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)
- Complete biliary obstruction
- Severely advanced primary biliary cholangitis (PBC) defined as total bilirubin greater than upper limit of normal (ULN) and albumin less than the lower limit of normal
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5 times the ULN
- Creatine phosphokinase (CPK) > 2 times the ULN
- Other chronic liver conditions, such as primary sclerosing cholangitis, autoimmune hepatitis, metabolic dysfunction-associated steatohepatitis (MASH), and alpha-1 antitrypsin deficiency
- Myopathy or rhabdomyolysis
- Pregnancy
- Lactating
Inclusion Criteria- Tried ursodiol monotherapy (unless medically inadvisable) and had intolerance or inadequate response after 12 months (stable dose for at least 3 months at 13 to 15 mg/kg/day)
Specialist Oversight & Monitoring- Prescribed and monitored by a VA or VA Community Care hepatologist or locally designated expert in primary biliary cholangitis (PBC)
Reproductive Health & Contraception- Pregnancy has been excluded prior to receiving elafibranor
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment; counseling provided on the use of effective non-hormonal contraception or addition of a barrier method to hormonal contraceptives during therapy and for 3 weeks after the last dose
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IMETELSTAT INJ,LYPHL
RYTELO
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RYTELO |
2024-06-20 |
Exclusion Criteria- Concurrent use of erythropoiesis stimulating agents (ESAs)
- Platelet count less than 75 x 109/L
- Absolute neutrophil count less than 1.5 x 109/L unless with Duffy Null phenotype
- Severe hepatic impairment defined as total bilirubin > 3x upper limit of normal (ULN) unless with Gilbert syndrome
- Severe renal impairment defined as serum creatinine < 30 ml/min
- Deletion 5q (del[5q]) karyotype
- Myelodysplastic syndromes / myeloproliferative neoplasm overlap syndrome
- Known pregnancy
- Lactation
Inclusion Criteria- Confirmed diagnosis of low- to intermediate-1 risk myelodysplastic syndrome (MDS)
- Transfusion-dependent, requiring regular red blood cell (RBC) transfusions of ≥4 RBC units over 8 weeks
- Documentation of inadequate response, loss of response, intolerance or contraindication to an 8-week course of an erythropoiesis stimulating agent (ESA)
- Documentation of inadequate response, loss of response, intolerance or contraindication to a 9-week course of luspatercept-aamt at maximal tolerated doses (i.e. 1.75 mg/kg subcutaneously every 3 weeks)
Additional Inclusion Criteria- For females who can become pregnant: Pregnancy should be excluded prior to receiving imetelstat
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
- For lactating females: Advise against breastfeeding during treatment and for 1 week after the last dose
Indication & Patient Population- Adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS)
- Transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks
- Patients who have not responded to, lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs)
Dosing & Administration- 7.1 mg/kg IV over 2 hours every 4 weeks
- Continue until progressive disease or unacceptable toxicity
Line of Therapy & Treatment Sequence- Not a first-line (1L) treatment
- May serve as second-line (2L) or third-line (3L) therapy
- Recommended for patients who have not previously used imetelstat
Clinical Subgroups & Biomarkers- Low or intermediate-1 risk disease per International Prognostic Scoring System (IPSS)
- Endogenous erythropoietin concentration >500 mU/mL
- Non-del(5q) MDS
- Applicable regardless of ring sideroblasts (RS) status or high transfusion burden
Safety & Clinical Considerations- High rates of grade 3–4 neutropenia and thrombocytopenia observed; associated with higher need for cytopenia treatments and higher rates of infections and hemorrhagic events
- Embryofetal toxicity warning present
- Not recommended for myelofibrosis (current use is off-label; awaiting phase III trial results)
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RSV VACCINE INJ,SUSP
MRESVIA
|
MRESVIA |
2024-06-13 |
Indication & Target Population- Prevention of lower respiratory tract disease caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older.
- ACIP recommends administration for adults ≥ 75 years of age or those aged 60–74 years with one or more risk factors for severe RSV.
Patient Selection Criteria & Risk Factors- Risk factors for severe RSV include:
- Chronic lung disease (asthma, COPD, interstitial lung disease)
- Chronic cardiovascular disease (e.g., CHF or coronary artery disease, excluding isolated hypertension)
- Moderate/severe immunocompromise
- Diabetes mellitus with end organ damage (e.g., neuropathy, retinopathy, or requiring insulin or SGLT2 inhibitor)
- Neurologic or neuromuscular condition impairing airway clearance or causing respiratory muscle weakness (e.g., poststroke aphasia, amyotrophic lateral sclerosis)
- Advanced chronic kidney disease or liver disease (e.g., cirrhosis)
- Hematologic disorders (e.g., sickle cell disease or thalassemia)
- Severe obesity (BMI ≥ 40 kg/m2)
- Residence in a nursing home or other long-term care facility
- Frailty
- Advanced age
- Other underlying conditions determined by a healthcare provider to increase severe RSV risk
- Clinical trial exclusions included clinically unstable comorbidities, immunocompromise, and history of myocarditis or pericarditis within 2 months prior to screening.
- Efficacy in patients with multiple comorbidities, immunocompromised states, or frailty remains unknown/unclear.
Contraindications & Precautions- Contraindicated in patients with a history of severe allergic reaction to any component of MRESVIA.
- Requires prevention and management of allergic reactions and syncope following administration.
- Immunocompromised individuals may have a diminished immune response.
Dosing & Administration- Single intramuscular dose.
- Supplied as a single-dose prefilled syringe containing frozen suspension; must be thawed prior to administration.
Co-administration Guidelines- Co-administration with other adult vaccines during the same visit is acceptable (including seasonal influenza, COVID-19, pneumococcal, Td/Tdap, and recombinant zoster).
- Clinical data for co-administration is currently only available for influenza vaccines; co-administration may increase local or systemic reactogenicity.
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UPADACITINIB SOLN,ORAL
RINVOQ LQ
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RINVOQ LQ |
2024-06-13 |
Indication & Diagnosis- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA/VA Community Care gastroenterologist or UC expert
Exclusion Criteria- Uncontrolled, active, severe infection (including C. difficile and undrained abscess) [may start/restart once infection treatment initiated]
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis [may initiate after starting antiviral prophylaxis]
- Untreated HIV infection [treated, well-controlled, asymptomatic HIV-positive patients may be treated]
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or cervical cancer (unless treating gastroenterologist and oncologist agree risk-benefits favor use)
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL [may start/restart once values normalize]
- End stage renal disease (eGFR < 15 mL/min/1.73 m2)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant live or live-attenuated vaccines, or administration of inactivated/live/live-attenuated vaccines < 2 weeks before initiation
- Concomitant JAK inhibitors, biologic immunomodulators, or potent immunosuppressants (e.g., azathioprine, cyclosporine)
- Concomitant strong CYP3A4 inducers
- Pregnancy (during therapy and for 4 weeks after last dose)
- Breastfeeding/providing breastmilk to an infant (during therapy and for 6 days after last dose)
Inclusion Criteria (All Must Be Met)- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, anti-HBs)
- Current or past completion of hepatitis C screening [may initiate while waiting for results]
Additional Inclusion Criteria (One Must Be Met)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar is preferred TNFI in UC)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in presence of adequate TNFI levels (mechanistic failure)
- Loss of response to a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
Additional Inclusion Criteria (Select if Appropriate)- If HBsAg-negative but anti-HBc-positive: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis vs. preemptive monitoring for HBV reactivation
- For women who can become pregnant: Pregnancy status verified; counseling provided on risks vs benefits and use of effective contraception during therapy and for 4 weeks after discontinuation
Dosing & Sequencing Requirements- Prescribe at FDA-recommended dose for UC, adjusting for severe renal impairment (eGFR 15 to <30 mL/min/1.73 m2), mild/moderate hepatic impairment (Child-Pugh A or B), and strong CYP3A4 inhibitors
- Sequencing: 1L Infliximab (preferred) or adalimumab; 2L/3L includes upadacitinib (one drug must be risankizumab-rzaa as 2L or 3L); 4L Mirikizumab-mrkz, guselkumab, or ustekinumab
- Routine retesting for TB, HBV, HCV not required for prescription renewals; retest in high-risk patients
Infections & Screening Requirements- Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Must complete tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Must complete hepatitis B screening (at minimum, HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs])
- Must have current or past completion of hepatitis C screening
Malignancy & Cardiovascular/Thrombotic Risk- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Laboratory & Organ Function Parameters- Lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once resolved)
- Severe hepatic impairment (Child-Pugh class C)
Concomitant Medications, Vaccines & Reproductive Health- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics or potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), except overlaps during treatment transition
- Concomitant therapy with strong CYP3A4 inducers (e.g., rifampin)
- Pregnancy
- Breastfeeding
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Provider Oversight & Diagnostic Requirements- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Has inflammatory articular disease (joint, spine, and/or entheseal) and a definite or provisional diagnosis of active psoriatic arthritis
Prior Biologic Therapy & Adjudication Considerations- ONE tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, or not adequate after 3 months
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- TNFI may be medically inadvisable for reasons including heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent/serious infections, or aversity to injections/barriers to in-clinic administration (adjudicated case-by-case)
- IL-17A inhibitor (ixekizumab preferred) may be medically inadvisable due to inflammatory bowel disease (IBD), as they can worsen IBD
- Ustekinumab may be medically inadvisable for axial psoriatic arthritis, as it is ineffective for ankylosing spondylitis
Indication & Disease Severity- Diagnosis of chronic atopic dermatitis
- Within 2 weeks of starting upadacitinib therapy, determination of severity by Gestalt Assessment (GA) of “moderate” or “severe” OR Eczema Area and Severity Index (EASI) ≥ 16 (scale 0–72)
- When practical, SCORing Atopic Dermatitis (SCORAD) index and Patient Oriented Eczema Measure (POEM) may be considered
Exclusion Criteria & Contraindications- Uncontrolled active infection (may start/restart once treatment for the infection is initiated)
- Untreated latent or active tuberculosis
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis; agents with high genetic barrier to resistance such as entecavir or tenofovir should be used)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients can be treated)
- Congenital or acquired immunodeficiency
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless dermatologist and oncologist agree risk-benefits favor use)
- Thrombosis or major adverse cardiovascular events in which potential harms are expected to outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once values normalize)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, or potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus) [except overlaps during treatment transition; co-use with antirheumatic doses of conventional immunomodulators such as methotrexate or leflunomide is acceptable]
- Pregnancy
- Breastfeeding
- Administration of inactivated, live, or live-attenuated vaccines within 2 weeks before initiation
Infectious Disease Screening & Monitoring- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Routine retesting not required for prescription renewals; consider in high-risk patients
Prior Therapy Requirements- Dupilumab OR tralokinumab-ldrm therapy is medically inadvisable, not tolerated, not adequate, or lost response (NO response after 12 weeks or inadequate response after 16 weeks)
- If dupilumab or tralokinumab-ldrm is contraindicated, therapies required prior to those biologic agents must still be tried
Vaccination Requirements- Offered all age-appropriate vaccinations prior to initiating therapy
- When possible, vaccinations should be updated before initiation
- Unless contraindicated, recombinant zoster (SHINGRIX equivalent) vaccine should be completed or at least initiated by the end of the first year of treatment, preferably when dosage is low, disease is stable, or at other times when a robust immune response can be expected
Special Populations & Counseling- For females who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits
- If HBsAg-negative but anti-HBc-positive and consult deemed indicated: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
Provider Oversight- Prescribed and monitored by a VA/VA Community Care dermatologist OR an immunologist, allergist, or locally designated expert in the management of atopic dermatitis in consultation with a VA/VA Community Care dermatologist
Indication & Patient Population- • Adults with refractory, moderate to severe atopic dermatitis
- • Patients who are candidates for systemic therapy
Treatment History & Place in Therapy- • Indicated when other systemic drug products, including biologics, have provided an inadequate response or when use of those therapies is medically inadvisable
- • May be used following inadequate response or intolerance to other systemic therapies, including but not limited to phototherapy, short-term induction therapy with cyclosporine or a systemic corticosteroid (if indicated), two conventional maintenance therapies, and dupilumab
- • Place in therapy is equivalent to abrocitinib
Limitations of Use- • Not recommended for co-administration with other JAK inhibitors (JAKIs)
- • Not recommended for co-administration with biologic immunomodulators
- • Not recommended for co-administration with other immunosuppressants
Dosing & Administration- • Adults < 65 years: Initiate at 15 mg once daily; if response is inadequate, increase to 30 mg once daily; discontinue if response to 30 mg is inadequate; use the lowest effective dose to maintain response
- • Adults ≥ 65 years: 15 mg once daily
- • Severe renal impairment (CrCL < 30 mL/min): 15 mg once daily
- • Mild or moderate renal impairment (CrCL > 30 mL/min): No dosage adjustment is needed
Pre-treatment Requirements- • Refer to the prescribing information for important pre-treatment assessments
Indication & Patient Population- • Adults with active psoriatic arthritis (PsA)
- • Patients who have had an inadequate response or intolerance to one or more TNFIs
- • Patients who refuse TNFI therapy due to safety concerns
Treatment History & Sequencing- • Placed after TNFIs in the treatment sequence
- • May be used despite therapy with one TNFI
- • May be preferred over ustekinumab, IL-23 inhibitors, apremilast, and abatacept for patients requiring treatment for axial PsA or ankylosing spondylitis
- • May be less preferable than tofacitinib and other agents (except abatacept) for patients with psoriatic nail involvement
- • Tofacitinib may be preferred over upadacitinib when a JAKI is indicated due to cost considerations
Dosing & Administration- • 15 mg once daily (only dose approved for PsA; escalation to 30 mg is only approved for atopic dermatitis)
- • No dosage adjustment required for renal impairment in PsA
- • May be used as monotherapy
Treatment Duration & Response Assessment- • A 12-week trial may be adequate; if nonresponse occurs by 12 weeks, an alternative treatment may be considered. For partial responders at 12 weeks, therapy may continue up to 24 weeks to improve response.
Limitations & Safety Considerations- • Not recommended in combination with other JAKIs, biologic DMARDs, or potent immunosuppressants (e.g., azathioprine, cyclosporine)
- • Not recommended in severe (Child-Pugh class C) liver disease
- • Carries Boxed Warnings for mortality, malignancy, major adverse cardiovascular events, and thrombosis regardless of indication
Pre-treatment Requirements- • Refer to the prescribing information for important pre-treatment assessments
Infection & Screening- Uncontrolled active infection, including undrained abscess; upadacitinib may be started/restarted once the infection treatment has been initiated
- Untreated latent or active tuberculosis infection
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis; upadacitinib may be initiated after starting antiviral prophylaxis
- Untreated HIV infection; treated, well-controlled, asymptomatic HIV-positive patients can be treated with upadacitinib
- Current or past completion of hepatitis C screening; upadacitinib may be initiated while waiting for test results
- If HBsAg-negative but anti-HBc-positive and patient’s practitioner deems consult is indicated, a GI/liver or infectious diseases expert has been (e-)consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
Malignancy & Cardiovascular Risk- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or cervical cancer, unless it is documented that the treating rheumatologist and oncologist agree that risk-benefits favor using the drug
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh the anticipated benefits
Laboratory Values & Organ Function- Lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3 , or hemoglobin < 8 g/dL; upadacitinib may be started/restarted once values normalize
- Severe hepatic impairment (Child-Pugh class C)
Gastrointestinal Risk- At increased risk of gastrointestinal perforation (e.g., history of diverticulitis, concomitant glucocorticoids) where potential harms of therapy are expected to outweigh the anticipated benefits
Concomitant Medications & Vaccinations- Concomitant JAK inhibitors, biologic immunomodulators (e.g., tocilizumab, abatacept), or potent immunosuppressants such as azathioprine and cyclosporine
- Concomitant methotrexate at antirheumatic doses (≤25 mg/WEEK) is allowable but may increase risks of immunosuppression and infection
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation of upadacitinib; when possible, vaccinations should be updated before the patient initiates upadacitinib, with recombinant zoster (SHINGRIX) vaccine completed or at least initiated by the end of the first year of treatment
- Concomitant strong CYP3A4 inDUCers
Pregnancy & Lactation- Pregnancy (during therapy and for 4 weeks after the last dose of upadacitinib)
- Breastfeeding/providing breastmilk to an infant (during therapy and for 6 days after the last dose)
- For females who can become pregnant: pregnancy status verified; counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 weeks after discontinuation of therapy
Dietary Restrictions- Ingestion of food or drink containing grapefruit during therapy
Diagnosis & Clinical Monitoring- Definite or provisional diagnosis of active giant cell arteritis
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Initiated concurrently or after glucocorticoid therapy unless glucocorticoids are medically inadvisable
Screening & Renewal Procedures- Routine rescreening for hepatitis B or hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for the infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are permitted)
- Congenital or acquired immunodeficiency
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless treating rheumatologist and oncologist agree risk-benefits favor use)
- At increased risk of thrombosis where potential harms are expected to outweigh anticipated benefits
- Lymphopenia, neutropenia, or anemia (may start/restart once resolved; defined as lymphocyte count <500 cells/mm3, absolute neutrophil count <1000 cells/mm3, hemoglobin <8 g/dL)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, or potent immunosuppressants (except during treatment transition overlaps)
- Concomitant therapy with strong CYP3A4 inducers (e.g., rifampin)
- Pregnancy
- Breastfeeding
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Moderate to severe active rheumatoid arthritis
- Prescribed at the FDA-recommended dose for rheumatoid arthritis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response
Additional Inclusion/Justification Criteria- If HBsAg-negative but anti-HBc-positive and consult is deemed indicated: Consultation with a GI/liver or infectious diseases expert for advice on starting antiviral prophylaxis or preemptively monitoring for HBV reactivation
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 5 months after stopping treatment
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits of treatment
Indication & Patient Selection- • Treatment of adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs)
- • Limitation of Use: Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs, or potent immunosuppressants such as azathioprine and cyclosporine
Pretreatment Tests & Evaluations- • Tuberculosis (TB) screening
- • Viral hepatitis screening (hepatitis B, hepatitis C)
- • Complete blood count (noting neutrophils, lymphocytes, hemoglobin)
- • Liver panel
- • Pregnancy status
- • Update immunizations, including for varicella zoster or herpes zoster prophylaxis per immunization guidelines
Dosing & Administration- • Induction: 45 mg once daily for 8 weeks (extended-release tablets)
- • Maintenance: 15 mg once daily; a dose of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease
- • Discontinue upadacitinib if an adequate response is not achieved with 30 mg
- • Use the lowest effective dosage needed to maintain response
Monitoring During Therapy- • Lipid panel (total cholesterol, LDL, HDL) approximately 12 weeks after initiation of therapy, then per lipid guidelines
- • Complete blood count per routine management
- • Latent TB testing and TB activation monitoring
- • Liver panel per routine management
- • Viral hepatitis reactivation monitoring per guidelines
Efficacy & Response Criteria- • Clinical remission defined as Adapted Mayo score ≤ 2, with stool frequency score (SFS) ≤ 1 and not greater than baseline, rectal bleeding score (RBS) = 0, and endoscopic subscore ≤ 1 without friability
- • Onset of treatment benefit: Earliest significant treatment difference occurred at Week 2; post hoc analysis demonstrated significant differences as early as Day 1 based on SFS ≤ 1/0, RBS = 0, and a 2-item patient-reported outcome (SFS ≤ 1 and RBS = 0)
- • Duration of an adequate therapeutic trial: Approximately 16 weeks (based on extended induction substudy where 58.4% of Week 8 nonresponders achieved clinical response at Week 16); no FDA-approved extended induction dosage regimen is available
Safety Considerations & Warnings- • Boxed warnings, contraindications, and other warnings/precautions are consistent with other approved indications for upadacitinib
- • Common adverse events (≥5%): Induction therapy (upper respiratory tract infection, acne, increased blood creatine phosphokinase, neutropenia); Maintenance therapy (upper respiratory tract infection, increased blood creatine phosphokinase, neutropenia, elevated liver enzymes, rash)
- • Specific safety risks noted: Venous thromboembolism, herpes zoster infection, hepatic disorder (mostly transaminase elevations), neutropenia, and CPK elevation
- • Avoid pregnancy during upadacitinib therapy and for 4 weeks after the end of therapy
Place in Therapy Context- • Alternative to tofacitinib for patients with moderate to severely active UC who have an inadequate response to vedolizumab (if TNFIs are medically inadvisable) or nonresponse, inadequate response, loss of response, or intolerance to TNFIs
- • Network meta-analyses indicate upadacitinib may be significantly more effective than tofacitinib in inducing clinical remission, with similar efficacy for maintenance of clinical remission and glucocorticoid-free remission
- • Associated with the lowest probability of discontinuations due to adverse events relative to infliximab, vedolizumab, and adalimumab, but a higher risk of adverse events than all other drugs except adalimumab 80/40 mg
Indications & Patient Population- • Treatment of adults with active ankylosing spondylitis (AS) who have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs).
- • Treatment of adults with active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have had an inadequate response or intolerance to TNFIs.
- • Limitations of Use: Not recommended for use in combination with other JAKIs, biologic immunomodulators, or potent immunosuppressants such as azathioprine and cyclosporine.
Dosage & Administration- • 15 mg once daily.
- • Form: Extended-release tablets.
Dose Modifications & Interruptions- • Renal impairment: No dosage adjustment recommended for mild, moderate, or severe renal impairment in patients treated for AS or nr-axSpA.
- • Hepatic impairment: Use is not recommended in severe hepatic impairment. No dosage adjustment needed for mild or moderate hepatic impairment (Child-Pugh A or B) in patients treated for AS or nr-axSpA.
- • Strong CYP3A4 inducers: Use is not recommended.
- • Strong CYP3A4 inhibitors: No dosage modification recommendation for AS or nr-axSpA.
- • Infections: Interrupt treatment; may restart when infection is controlled.
- • Hematologic parameters: Interrupt treatment if absolute neutrophil count < 1000 cells/mm3, absolute lymphocyte count < 500 cells/mm3, or hemoglobin < 8 g/dL; may restart once values return to above these thresholds.
- • Hepatic transaminases: Interrupt treatment for elevated hepatic transaminases or suspected drug-induced liver injury until diagnosis is excluded.
Safety Monitoring & Precautions- • Pretreatment tests and evaluations are similar to those for previously approved indications.
- • Boxed warnings, contraindications, and other warnings/precautions are the same as for other approved indications.
- • Common adverse events (≥1%): Upper respiratory tract infections, acne, herpes simplex, headache, blood creatine phosphokinase increased, cough, hypersensitivity, folliculitis, nausea, abdominal pain, pyrexia, increased weight, herpes zoster, influenza, fatigue, neutropenia, myalgia, and influenza-like illness.
Place in Therapy / Clinical Context- • May be used for active AS/r-axSpA or active nr-axSpA with objective signs of inflammation who have an inadequate response or intolerance to TNFIs or for whom TNFIs are medically inadvisable.
- • For active nr-axSpA candidates for JAKI therapy, upadacitinib may be preferred over tofacitinib due to lack of evidence supporting tofacitinib's off-label use for nr-axSpA.
- • JAKIs may be used as alternatives to IL-17AIs when TNFI therapy is inadequate, not tolerated, or medically inadvisable.
- • Evidence does not support use of targeted biologic or synthetic immunomodulators for treatment of patients without inflammatory disease; objective signs of inflammation (e.g., elevated high-sensitivity CRP and/or sacroiliitis on MRI) are required.
Infectious Disease- Active, serious systemic or localized infection (including undrained abscess)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are permitted)
Malignancy & Hematology- Malignancy in the previous 5 years (except successfully treated nonmelanoma skin cancer or cervical cancer, unless rheumatologist and oncologist agree risk-benefit favors use)
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL
Hepatic Function- Severe hepatic impairment (Child-Pugh class C)
Cardiovascular & Thrombotic Risk- Increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Concomitant Medications & Vaccines- Concomitant JAK inhibitors, biologic immunomodulators, or potent immunosuppressants (azathioprine, cyclosporine), except during treatment transitions
- Concomitant strong CYP3A4 inducers (e.g., rifampin)
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Diagnosis & Provider Requirements- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Definite or provisional diagnosis of active axial spondyloarthritis (ankylosing spondylitis/radiographic axial spondyloarthritis or nonradiographic axial spondyloarthritis) made by a VA/VA Community Care rheumatologist
Prior Therapy Requirements- One tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated, or not adequate after 3 months
Laboratory & Screening Requirements- Completed tuberculosis test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening
Additional Inclusion Criteria- If HBsAg-negative but anti-HBc-positive and consult indicated: GI/liver or ID expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- For patients who can become pregnant: Pregnancy status verified; counseling provided on potential risks vs benefits of treatment and use of effective contraception
Clinical Context & Monitoring Notes- Use with extreme caution in patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
- Upadacitinib may be used with methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine
- Vaccinations should be updated before initiation; recombinant zoster vaccine should be completed or initiated by end of first year, preferably when dosage is low, disease is stable, or immune response can be expected
- Applies only to new starts; stable patients should not be switched for nonmedical reasons
Indication & Patient Population- Adults with moderately to severely active Crohn’s disease
- Patients who have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs)
- Limited to second-line use
Dosage & Administration Criteria- Induction: 45 mg once daily for 12 weeks
- Maintenance: 15 mg once daily; a dosage of 30 mg once daily may be considered for refractory, severe, or extensive disease
- Discontinue upadacitinib if an adequate response is not achieved with 30 mg daily
- Use the lowest effective dosage needed to maintain response
- Formulation: Extended-release tablets (15 mg, 30 mg, 45 mg)
Limitations & Contraindications- Not recommended for use in combination with other JAKIs
- Not recommended for use in combination with biologic therapies for Crohn’s disease
- Not recommended for use in combination with potent immunosuppressants such as azathioprine and cyclosporine
Laboratory Monitoring Requirements- Lipid panel (total cholesterol, LDL, HDL) about 12 weeks after initiation of therapy, then per lipid guidelines
- Complete blood count as per routine management
- Latent TB testing and TB activation screening
- Liver panel as per routine management
- Viral hepatitis reactivation screening per guidelines
Efficacy & Clinical Response Criteria- Clinical remission: CDAI < 150; stool frequency ≤ 2.8 daily and average daily abdominal pain score ≤ 1.0 with neither worse than baseline (PRO-2)
- Endoscopic response: >50% decrease from baseline in SES-CD, or ≥2-point reduction from baseline if baseline SES-CD is 4
- Clinical response: ≥30% decrease in stool frequency and/or abdominal pain, or ≥100-point decrease from baseline in CDAI
- Onset of clinical response (CDAI-100) observed at Week 2
Safety Considerations- Monitor for gastrointestinal perforations
- Safety profile is consistent with other approved indications
Place in Therapy & Selection Criteria- Appropriate for induction and maintenance therapy of moderate to severe, active luminal CD
- May be less preferred than risankizumab-rzaa and ustekinumab in patients with co-existing plaque psoriasis
- Preferred over vedolizumab in patients with extraintestinal involvement
Exclusion Criteria- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once infection treatment initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or cervical cancer unless treating gastroenterologist and oncologist agree risk-benefits favor use
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once values normalize)
- End stage renal disease (eGFR < 15 mL/min/1.73 m2)
- Severe hepatic impairment (Child-Pugh C)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Concomitant JAK inhibitors, biologic immunomodulators, or potent immunosuppressants such as azathioprine and cyclosporine
- Concomitant strong CYP3A4 inducers
- Pregnancy (during therapy and for 4 weeks after the last dose)
- Breastfeeding / providing breastmilk to an infant (during therapy and for 6 days after the last dose)
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally designated Crohn’s disease expert
- Current or prior moderate to severe Crohn’s disease (CD) confirmed by endoscopy or imaging
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
Additional Inclusion Criteria (One Required)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar and adalimumab/biosimilar are preferred TNFIs in CD)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of TNFI in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to infliximab/biosimilar and another TNFI for CD despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
Adjudication & Supplemental Considerations- HBsAg-negative but anti-HBc-positive: GI/liver or infectious diseases expert must be consulted for advice on starting antiviral prophylaxis vs preemptive monitoring for HBV reactivation
- Women who can become pregnant: Pregnancy status must be verified; counseling provided on risks vs benefits and use of effective contraception during therapy and for 4 weeks after discontinuation
- Routine retesting for TB, Hepatitis B, and Hepatitis C screening is not required for prescription renewals (retesting in high-risk patients should be considered)
- Drug Sequencing: First-line = Infliximab or adalimumab; Second/Third-line = Vedolizumab, upadacitinib, or risankizumab-rzaa (one drug must be risankizumab-rzaa as 2L or 3L); Fourth-line = Mirikizumab-mrkz or ustekinumab
- Dosing: Prescribe at FDA-recommended dose for ulcerative colitis, adjusting for severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m2), mild to moderate hepatic impairment (Child-Pugh A or B), and strong CYP3A4 inhibitors
- Vaccinations: Update before initiation when possible; recombinant zoster vaccine should be completed/initiated by end of first year, preferably at low dose/stable disease/robust immune response expected
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FUTIBATINIB TAB
LYTGOBI
|
LYTGOBI |
2024-05-30 |
Exclusion Criteria- Unmanageable CYP3A inhibitor/inducer interaction identified
- Clinically significant corneal or retinal disorder identified by ophthalmologic examination
- Serum phosphate greater than upper limit of normal
- Untreated, clinically unstable brain and/or central nervous system metastases
- Pregnancy
- Breastfeeding
Inclusion Criteria- Care provided by a VA or VA Community Care provider of Hematology/Oncology services
- Diagnosis of advanced/metastatic or surgically unresectable cholangiocarcinoma
- Documented disease progression after at least one platinum-based chemotherapy regimen
- Confirmed tumor expression of Fibroblast Growth Factor Receptor 2(FGFR2) fusion or select rearrangement by FDA-approved next generation sequencing
- Baseline ophthalmology exam, including optical coherence tomography (OCT) has been performed
- Goals of care and role of palliative care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 or 1
Additional Criteria- For women of childbearing potential: Pregnancy should be excluded prior to receiving futibatinib and the patient provided contraceptive counseling on potential risks vs. benefits of taking futibatinib if patient were to become pregnant.
- Advise women not to breastfeed during treatment with futibatinib and for 1 week after the last dose.
Indication & Patient Population- Adults with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma (iCCA)
- Must harbor FGFR2 gene fusions or other rearrangements identified prospectively by DNA testing
- Must have disease progression after ≥1 prior regimen including gemcitabine plus platinum-based chemotherapy
- Must have radiographically measurable disease per RECIST v 1.1
Dosing & Administration- Starting dose: 20mg/day (5 tablets) once daily until disease progression or unacceptable toxicity occurs
- Administered in 21-day cycles with no days off
- Treatment interruptions and/or dose reduction indicated for any grade 3 or grade 4 laboratory related events
- No dose adjustments recommended for renal or hepatic failure
Monitoring & Precautions- Monitor serum phosphate and adjust dose based on severity (hyperphosphatemia median onset day 5)
- Initiation of phosphate lowering therapy is likely
- Perform comprehensive ophthalmologic examination including optical coherence tomography (OCT) prior to initiation, every 2 months for first 6 months, every 3 months thereafter, and urgently at any time for visual symptoms
- Advise patients of reproductive potential regarding fetal risk and require use of effective contraception
Contraindications & Warnings- No boxed warnings or contraindications listed
- Hyperphosphatemia occurred in 85% of patients; adverse effects leading to treatment discontinuation were uncommon (2%)
- Risk of retinal pigment epithelial detachment (RPED)
- Can cause fetal harm
Drug Interactions- Avoid dual P-gp and strong CYP3A inhibitors (e.g., itraconazole) due to increased futibatinib exposure and adverse effects
- Avoid dual P-gp and strong CYP3A inducers (e.g., rifampin) due to decreased futibatinib exposure and reduced efficacy
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TARLATAMAB-DLLE INJ,LYPHL
IMDELLTRA
|
IMDELLTRA |
2024-05-30 |
Indication- Extensive-stage small cell lung cancer (ES-SCLC) in adult patients with disease progression on or after platinum-based chemotherapy (granted accelerated approval).
Patient Selection & Performance Status- Adults with histologically or cytologically confirmed SCLC.
- Recurrent or relapsed disease following at least one platinum-based treatment and at least one other line of therapy.
- Good performance status (ECOG PS 0-1).
- Symptomatic brain metastases are an exclusion criterion; asymptomatic brain metastases are acceptable.
Dosing & Administration Requirements- Administered intravenously over one hour at a constant flow rate using an infusion pump.
- Cycle 1 step-up dosing: Day 1 (1 mg), Day 8 (10 mg), Day 15 (10 mg). Cycles 2 and onward: Day 1 and Day 15 (10 mg each). Each cycle is 28 days.
- Only qualified healthcare professionals with appropriate medical support capable of managing severe reactions (CRS, ICANS) should administer the drug.
- Patients must be well hydrated prior to administration.
Pre- and Post-Medication Criteria- Cycle 1: Dexamethasone 8 mg IV (or equivalent) administered within one hour prior to tarlatamab on Days 1 and 8.
- Cycle 1: Normal saline 1 liter IV over 4-5 hours administered immediately after completion of tarlatamab on Days 1, 8, and 15.
Monitoring & Safety Requirements- Monitor for 22 to 24 hours from the start of infusion on Cycle 1 Day 1.
- Patients should remain within one hour of an appropriate healthcare setting accompanied by a caregiver for 48 hours following the first infusion.
- Extended monitoring is required if Grade ≥2 cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or neurological toxicity occurs during prior treatments.
- Monitor complete blood counts at baseline, prior to each dose, and as clinically indicated; withhold or permanently discontinue based on severity of cytopenias.
- Monitor for infections at baseline, during treatment, and as clinically indicated; withhold or permanently discontinue based on severity.
- Monitor liver enzymes and bilirubin at baseline, prior to each dose, and as clinically indicated; withhold or permanently discontinue based on severity of hepatotoxicity.
- Monitor for hypersensitivity reactions during treatment; withhold or permanently discontinue based on severity.
- Patients must avoid driving and operating heavy machinery until neurological symptoms resolve.
Special Populations & Contraindications- Pregnancy: Females of reproductive potential must undergo pregnancy testing prior to treatment initiation. Effective contraception is required during treatment and for two months after the last dose due to potential fetal harm.
- Lactation: Breastfeeding is contraindicated during treatment and for two months after the last dose.
- Pediatric use: Safety and efficacy have not been established.
- Contraindications: None stated.
Clinical Pathway & Place in Therapy Criteria- Recommended following failure of first-line chemotherapy and an initial subsequent line of therapy.
- Per VA Clinical Pathways: Indicated for patients with good performance status (ECOG PS 0-1) who have failed retreatment with a platinum-based doublet (if chemo-sensitive) and lurbinectedin.
- Per NCCN guidelines: Not a preferred agent in chemo-sensitive disease; listed as another recommended regimen after re-treatment with a first-line platinum-based doublet. In chemo-resistant disease, listed as a preferred regimen alongside lurbinectedin and topoisomerase inhibitors.
- Initial treatment with lurbinectedin or topotecan is reasonable before administering tarlatamab due to cost and safety profile considerations.
Exclusion Criteria- Facility is not equipped to monitor and manage Cytokine Release Syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), if necessary
- Patient is unable to be monitored during and for 22-24 hours after step-up doses on Cycle 1 Day 1 and Day 8 at an appropriate healthcare setting
- Patient is unable to stay within 1 hour of an appropriate healthcare facility for 48 hours after Cycle 1 Day 1 and Day 8 infusions
- Untreated or symptomatic brain metastases and leptomeningeal disease
- Prior recurrent grade 2 or higher pneumonitis or severe immunotherapy-related adverse events leading to discontinuation
- Evidence of interstitial lung disease or active, non-infectious pneumonitis
- Pregnancy
- Lactation
Inclusion Criteria- Extensive stage small cell lung cancer with disease progression after first-line platinum-based chemotherapy
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnancy: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 2 months after stopping treatment
- For patients with treated brain metastases: definitive therapy must have been completed at least 2 weeks prior to treatment with no evidence of radiographic central nervous system progression afterwards
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VALBENAZINE CAP,SPRINKLE
INGREZZA SPRINKLE
|
INGREZZA SPRINKLE |
2024-05-09 |
Exclusion Criteria- Patient is actively suicidal or has untreated/inadequately treated depression
- Congenital long QT interval, or QTc >450 ms (men) / >470 ms (women)
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB/RBBB), or cardiac device (candidates may be considered with cardiology evaluation)
- Concurrent use of a monoamine oxidase inhibitor (MAOI)
- Current or recent reserpine use within the past 20 days
- Concurrent use of another VMAT2 inhibitor
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnant or lactating
- Concurrent use of a strong CYP3A4 inducer
Inclusion Criteria- Diagnosis of tardive dyskinesia secondary to a dopaminergic blocking agent (e.g., antipsychotic or metoclopramide)
- TD interferes with functional status (self-care, ambulation), quality of life, or causes social stigma/isolation/embarrassment
- Prescriber has documented specific movement(s) (facial, oral, extremity, trunk) in medical record along with impact on function, quality of life, or socialization
- Recent Abnormal Involuntary Movement Scale (AIMS) score recorded in medical record
- ECG performed to confirm QTc <450 ms (men) / <470 ms (women)
- If initial prescriber is a resident/fellow/trainee, attending psychiatrist or neurologist must verify diagnosis and need for valbenazine
Exclusion Criteria- Active suicidality or untreated/inadequately treated depression
- Congenital long QT interval or QTc >450 ms (men) / >470 ms (women)
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB/RBBB), or presence of a cardiac device (requires cardiology evaluation for consideration)
- Concurrent use of monoamine oxidase inhibitors (MAOIs)
- Current or recent reserpine use within the past 20 days
- Concurrent use of another VMAT2 inhibitor
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnancy or lactation
- Concurrent use of strong CYP3A4 inducers
Inclusion Criteria- Documented diagnosis of Huntington disease in the medical record
- Disabling or painful chorea that interferes with functional status (self-care, ambulation), quality of life, or causes social stigma/isolation/embarrassment
- Documentation of specific movement(s) (facial, oral, extremity, trunk) and their impact on function, quality of life, or socialization
- Verification by an attending psychiatrist or neurologist if the initial prescriber is a resident, fellow, or other trainee
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APROCITENTAN TAB
TRYVIO
|
TRYVIO |
2024-05-03 |
Exclusion Criteria- Resistant or pseudoresistant hypertension due to nonadherence, suboptimal antihypertensive therapy, or secondary causes including primary aldosteronism
- Recent cerebrovascular or cardiovascular event (e.g., transient ischemic attack, stroke, myocardial infarction in the past 6 months)
- Clinically significant unstable cardiac disease (e.g., uncontrolled symptomatic arrhythmias, current decompensated heart failure, baseline class III or IV heart failure, or class II heart failure with relevant mitral valve insufficiency or aortic stenosis)
- Severe renal impairment with eGFR less than 15 ml/min or on dialysis
- ALT (alanine transferase) or AST (aspartate transferase) elevations of greater than 3 times the upper limit of normal, or moderate to severe hepatic impairment (Child-Pugh class B and C)
- Baseline severe anemia (e.g., hemoglobin less than 10 g/dL)
- Treatment with another endothelin receptor antagonist (ERA)
- Known pregnancy
- Lactating
Inclusion Criteria- Provider is a VA or VA Community Care cardiology or nephrology specialist or other locally designated provider
- Resistant hypertension defined as inadequate control of blood pressure with documented adherence and the use of maximally tolerated doses of triple therapy and spironolactone (if appropriate)
- Medication profile reviewed to eliminate or minimize the concurrent use of drugs that elevate blood pressure (e.g., NSAIDs)
- Lifestyle modifications on how to reduce blood pressure have been discussed with patient and documented (e.g., diet, alcohol consumption, exercise)
- Baseline evaluation of labs including serum transaminases, bilirubin, hemoglobin, and NT-proBNP (or BNP)
Additional Inclusion Criteria- For females who can become pregnant: Pregnancy must be excluded prior to receiving aprocitentan
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for one month after stopping treatment
- For males of reproductive potential: Counseling provided on the potential risk of aprocitentan to adversely affect spermatogenesis and impair fertility
Clinical Definitions & Clarifications- Secondary causes of resistant hypertension workup should include plasma renin activity and serum aldosterone to calculate aldosterone/renin ratio
- Triple therapy must include a diuretic (thiazide-type), calcium channel blocker, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (beta-blocker may also be used for patients with another compelling indication)
- Spironolactone (or eplerenone if spironolactone is not tolerated) should be considered as a fourth line agent in patients when appropriate (e.g., in patients without contraindications, prior intolerance, severe renal impairment, high potassium)
- Aprocitentan is associated with risk of fluid retention, edema, and worsening of heart failure, especially in patients with cardiovascular risk factors
- Patients with renal artery stenosis may be predisposed to fluid retention/pulmonary edema; alternate therapies should be considered in these patients
Indication & Clinical Context- Indicated for treatment of hypertension in combination with other antihypertensive agents when blood pressure is inadequately controlled on other agents
- Indicated as add-on treatment for resistant hypertension (defined as blood pressure above goal on maximally tolerated doses of triple therapy: a diuretic, calcium channel blocker, and ACE inhibitor or angiotensin II receptor blocker)
Dosage & Administration- 12.5 mg oral tablet dosed orally once daily; only the 12.5 mg dose is FDA approved
Patient Selection & Exclusion Criteria- Appropriate for patients with uncontrolled hypertension despite treatment with three or more antihypertensive agents from different drug classes and SBP ≥140 mmHg
- Not recommended in patients with eGFR <15 ml/min/1.73 m2 or on dialysis
- Not recommended in patients with moderate to severe hepatic impairment (Child-Pugh class B and C)
- Not recommended in patients with NYHA stage III or IV heart failure, unstable cardiac function, or NTproBNP ≥500 pg/mL
Contraindications & Warnings- Contraindicated in pregnancy due to risk of embryo-fetal toxicity and fetal death
- Contraindicated in hypersensitivity
- Associated with hepatotoxicity; discontinue if symptoms suggestive of hepatotoxicity occur or if transaminases are elevated with bilirubin >2 times ULN
- Associated with fluid retention/edema; monitor for worsening heart failure
- Associated with decreased hemoglobin and anemia
Monitoring Requirements- Obtain baseline serum aminotransferase levels and total bilirubin prior to initiation; monitor periodically during treatment
- Do not initiate if AST or ALT >3 times ULN
- Obtain baseline hemoglobin prior to initiation; monitor periodically during treatment
- Monitor for signs and symptoms of fluid retention, weight gain, and worsening heart failure
- Females who can become pregnant must have monthly negative pregnancy tests during treatment and one month after discontinuation
Pre-Initiation & Management Prerequisites- Requires a multidisciplinary approach to hypertension management prior to initiation
- Requires ambulatory blood pressure monitoring and confirmation of medication adherence before adding a fourth agent
- Pharmacologic and lifestyle factors exacerbating blood pressure (e.g., NSAIDs, alcohol consumption, obstructive sleep apnea, obesity, physical inactivity) must be addressed
- Secondary and pseudoresistant hypertension should be considered; evaluation of medication adherence and reinforcement of nonpharmacologic interventions are required before adding a fourth agent
- Professional guidelines recommend considering spironolactone as a fourth-line agent when appropriate (or eplerenone if spironolactone is not tolerated)
REMS Requirements- Only available through the TRYVIO REMS program due to embryo-fetal toxicity risk
- Requires prescriber enrollment, training, and certification, and pharmacy certification
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ESTRADIOL GEL,TRANSDERMAL
ESTROGEL
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ESTROGEL |
2024-05-03 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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MIRABEGRON TAB,SA
MIRABEGRON ER, MYRBETRIQ
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MIRABEGRON ER, MYRBETRIQ |
2024-05-03 |
Exclusion Criteria- Urinary incontinence due to stress or stress-predominant incontinence
- Severe hepatic impairment (Child-Pugh Class C)
- End-stage renal disease (CrCl/eGFR < 15 ml/min or receiving hemodialysis)
- Systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 110 mmHg
Inclusion Criteria- History of overactive bladder (OAB), either urge or mixed type
- At least one of the following must be fulfilled:
- Documented history of mental status changes with anticholinergic medication
- 12-week trials with 2 formulary anticholinergic/antimuscarinic OAB drugs OR one formulary and one nonformulary anticholinergic/antimuscarinic OAB drug resulting in treatment failure or intolerable adverse effects
- Diagnosis of Alzheimer’s disease or other dementia, cognitive impairment, gastric retention, xerostomia, uncontrolled narrow-angle glaucoma, or other condition for which an anticholinergic drug is contraindicated or could be harmful
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NOGAPENDEKIN ALFA INBAKIC-PMLN INJ,SOLN
ANKTIVA
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ANKTIVA |
2024-05-03 |
Exclusion Criteria- Current or previous evidence of muscle-invasive or metastatic bladder cancer
- Pregnancy
- Lactating
Inclusion Criteria (All must be met)- Formulary agents for BCG-unresponsive disease have been used previously unless there is a contraindication or they are not medically advisable
- In combination with Bacillus Calmette-Guerin (BCG) for BCG-unresponsive non-muscle invasive bladder cancer
- Carcinoma in situ (CIS) with or without papillary tumors (Ta or T1 high-grade tumors)
Additional Clinical Requirements- Care is provided by a VA/VA Community Care oncology or urology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
Definition/Justification- BCG-unresponsive: Received 2 courses of BCG within 12 months (5 of 6 induction instillations and at least 2 of 3 maintenance doses OR at least 2 of 6 instillations of a second induction when maintenance not given)
Indication & Patient Population- BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors
- Used specifically under use with BCG
- Trial population included patients with CIS ± Ta/T1 disease and Ta/T1 disease with complete resection
- Median age 71 years; 74-87% male; median prior BCG doses of 12
Dosage & Administration- Dosage form: Solution for intravesical use
- Induction: 400mcg intravesically with BCG weekly for 6 weeks (may require 2nd induction)
- Maintenance: 400mcg intravescially with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19
- If complete response at week 25 or later, may continue maintenance with BCG weekly for 3 weeks months 25, 31, and 37
Safety & Monitoring Requirements- Boxed warnings: None
- Contraindications: None
- Other warnings: Risk of lethal metastatic disease by delaying cystectomy
- Top 5 adverse events: Dysuria, hematuria, urinary frequency, urination urgency, urinary track infection
- Drug interactions: None
Clinical Context & Utilization Considerations- Indicated for use with BCG in patients with BCG-unresponsive NMIBC
- Demonstrates clinical responses with less toxicity than systemic treatments and can be administered in the outpatient setting
- Ongoing BCG shortage may interfere with use as a therapeutic choice
- Alternative options include cystectomy, intravesical chemotherapy, pembrolizumab, nadofaragene firadenovec, or sequential gemcitabine and docetaxel
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DANICOPAN TAB
VOYDEYA
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VOYDEYA |
2024-04-11 |
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Inclusion Criteria- Prescribed by a REMS registered VA or VA Community Care hematologist, oncologist, immunologist or genetic specialist
- Laboratory-confirmed diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH), as evidenced by detectable GPI-deficient hematopoietic clones (Type III PNH red blood cells (RBC)) via Flow Cytometry
- Evidence of clinically significant hemolysis (e.g., Hemoglobin <10g/dL) despite 6 months of stable therapy with anti-C5 inhibitor (e.g., ravulizumab or eculizumab)
- Complete or update vaccination for encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis at least 2 weeks prior to the first dose of therapy according to current Advisory Committee on Immunization Practices (ACIP)
Indication & Patient Population- Add-on therapy to ravulizumab or eculizumab for treatment of extravascular hemolysis in adults with Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Adults with confirmed PNH and clinically significant extravascular hemolysis (e.g., Hgb <9.5) despite stable anti-C5 treatment
Dosage & Administration- 150mg to 200mg three times daily
- Available as 50mg and 100mg oral tablets
Contraindications- Hypersensitivity to danicopan
- Unresolved serious infection caused by encapsulated bacteria (Strep. Pneumoniae, Neisseria meningitidis, or H. influenzae type B)
Warnings & Monitoring- Risk of serious infections caused by encapsulated bacteria; complete or update vaccination at least 2 weeks prior to first dose unless risks of delaying therapy outweigh infection risk
- Not recommended in severe hepatic impairment (Child-Pugh class C)
- Insufficient data regarding risk of birth defects in pregnancy
- Cessation of breastfeeding recommended during treatment and for 3 days after final dose
- Hepatic enzyme elevations reported; baseline screening and monitoring recommended
- Monitor for hemolysis after cessation of therapy
Drug Interactions- BCRP inhibitor: May increase plasma concentrations of BCRP substrates
- P-glycoprotein inhibitor: May increase plasma concentrations of P-gp substrates
- Rosuvastatin: Exposure significantly increased; dose should not exceed 10mg/day when used concomitantly
Adverse Reactions- Headache (11%), vomiting (7%), pyrexia (7%), ALT increase (5%), hypertension (5%)
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SOTATERCEPT-CSRK INJ,LYPHL
WINREVAIR, WINREVAIR (2 PACK)
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WINREVAIR, WINREVAIR (2 PACK) |
2024-04-11 |
Exclusion Criteria- Platelet count less than 50,000/mm3
- Uncontrolled or untreated erythrocytosis
- Uncontrolled systemic hypertension
- Active serious bleeding
- Pregnancy
- Lactating
Inclusion Criteria- Care provided by a VA/VA Community Care provider experienced in the management of Pulmonary Arterial Hypertension (PAH)
- World Health Organization (WHO) Group 1 PAH (idiopathic, heritable, drug-induced, connective tissue disease induced, or after shunt correction)
- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis: mean pulmonary artery pressure greater than 20 mmHg, pulmonary capillary wedge pressure 15 mmHg or less, and pulmonary vascular resistance greater than 5 Wood units
- WHO functional class II or III
- On stable doses of background PAH therapy for at least 90 days
- Risk factors for bleeding have been considered and addressed, including evaluating the continued need for use of drugs that increase bleeding risk (e.g., anticoagulants, NSAIDs, antiplatelets)
Additional Inclusion Criteria- All patients of reproductive potential: Counseling provided on potential risk of fertility impairment
- Patients who can become pregnant: Pregnancy should be excluded prior to receiving sotatercept. Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 4 months after stopping treatment
Indication & Patient Population- Indicated for treatment of adults with pulmonary arterial hypertension (PAH) WHO Group 1 to increase exercise capacity, improve WHO functional class, and reduce risk of clinical worsening events.
- Applicable PAH subtypes: idiopathic, heritable, drug-induced, connective tissue disease-associated, or after shunt correction.
- Patients must be symptomatic (WHO functional class II or III) and on stable doses of PAH background therapy for at least 90 days.
Exclusion Criteria- Other Group 1 subtypes: PAH associated with HIV, portal-pulmonary disease, schistosomiasis, or veno-occlusive disease.
- Platelet count <50,000/mm3.
- Hepatic aminotransferase levels >3 times the upper limit of normal.
Dosing & Administration- Available as lyophilized powder for injection in single-use vials (45 mg and 60 mg).
- Starting dose: 0.3 mg/kg by subcutaneous (SC) injection once every 3 weeks.
- Target dose: 0.7 mg/kg SC once every 3 weeks.
- Store in refrigerator until ready for use.
- Administered as a weight-based subcutaneous injection; requires laboratory monitoring of platelets and hemoglobin.
Monitoring & Dose Modifications- Check hemoglobin and platelet counts prior to each dose for the first 5 doses (or longer if values are unstable).
- Delay treatment for at least 3 weeks if any of the following occur:
- Hemoglobin increased >2.0 g/dL from previous dose and is above ULN
- Hemoglobin increased >4.0 g/dL from baseline
- Hemoglobin increased >2.0 g/dL above ULN
- Platelet count decreased to <50,000/mm3
Safety & Warnings- No boxed warnings or contraindications stated.
- Erythrocytosis: Increased hemoglobin >2g/dL above ULN occurred in 15% of patients; severe erythrocytosis may increase risk of thromboembolic events or hyperviscosity syndrome.
- Thrombocytopenia: Platelet counts <50,000/mm3 seen in 3% of patients (all receiving epoprostenol).
- Serious bleeding: Increased bleed risk observed; serious bleeding more likely with prostacyclin therapy, antithrombotics, or low platelet count. Excess bleeding primarily epistaxis and gingival bleeding.
- Adverse reactions occurring in >10% of patients: Headache, epistaxis, rash, telangiectasia, diarrhea, dizziness, erythema.
Reproductive Considerations- Embryo-fetal toxicity: May cause fetal harm; advise use of effective contraception during treatment and for at least 4 months after stopping.
- Impaired fertility: May impair fertility in females and males.
Geriatric Use- No difference in efficacy between patients <65 years and ≥65 years.
- More bleeding events observed in older vs younger subgroups.
- Insufficient numbers of patients aged 75 years and older to evaluate efficacy and safety.
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PEMIVIBART INJ,SOLN
PEMGARDA (EUA)
|
PEMGARDA (EUA) |
2024-04-04 |
Indication & Patient Eligibility- Pre-exposure prophylaxis (PrEP) of COVID-19 in adults and pediatric individuals (12 years of age and older weighing at least 40 kg)
- Must not be currently infected with SARS-CoV-2
- Must not have had a known recent exposure to an individual infected with SARS-CoV-2
- Must have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications/treatments and may not mount an adequate immune response to COVID-19 vaccination, including:
- Active treatment for solid tumor and hematologic malignancy
- Hematologic malignancies associated with poor responses to COVID-19 vaccines regardless of current treatment status (e.g., chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma, acute leukemia)
- Receipt of solid organ transplant or an islet transplant and taking immunosuppressive therapy
- Receipt of chimeric antigen receptor (CAR)-T-cell or hematopoietic stem cell transplant (withing 2 years of transplant or taking current immunosuppressive therapy)
- Moderate to severe primary immunodeficiency (e.g., common variable immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome)
- Advanced or untreated HIV (those with CD4+ cell < 200/mm3, history of AIDS-defining illness without immune reconstitution or clinical manifestations of symptomatic HIV)
- Active treatment with high-dose corticosteroids (i.e., ≥ 20mg/day prednisone or equivalent for ≥ 2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, and biologic agents that are immunosuppressive or immunomodulatory (e.g., B-cell depleting agents)
Contraindications & Limitations of Use- Contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis to any component
- NOT authorized for treatment of COVID-19
- NOT authorized for post-exposure prophylaxis of COVID-19 in individuals exposed to someone infected with SARS-CoV-2
- NOT a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended
- Should not be used for at least two weeks after COVID-19 vaccination
- Authorized only when the combined national frequency of variants with substantially reduced susceptibility to PEM is ≤ 90%
Dosing & Administration Requirements- Single intravenous (IV) infusion of 4500 mg
- Repeat doses every 3 months
- Infused over a minimum of 60 minutes
- No adjustment recommended for hepatic or renal dysfunction, in geriatrics, or in pregnant or lactating persons
- Must be prepared and administered by a qualified healthcare worker using aseptic technique
- Must use an inline 0.2-micron filter
- Entire contents of the bag must be administered; line flushed with 0.9% sodium chloride after completion
Monitoring & Safety Requirements- Must be administered in a setting where healthcare providers have immediate access to medications to treat anaphylaxis and the ability to activate the emergency medical system
- Clinically monitor individuals during the 60-minute infusion and for at least 2 hours after completion
- Immediately discontinue administration and initiate appropriate supportive care if signs/symptoms of a severe allergic reaction occur; permanently discontinue PEM in those with anaphylaxis
- For mild infusion-related reactions, consider slowing or stopping the infusion, administer appropriate medications/supportive care, and monitor for 2 hours after discontinuation or completion
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RESMETIROM TAB
REZDIFFRA
|
REZDIFFRA |
2024-03-28 |
Indication- Treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (stages F2 to F3) in conjunction with diet and exercise.
- Approved under accelerated approval based on improvement of NASH and fibrosis; continued approval contingent upon verification of clinical benefit in confirmatory trials.
Patient Selection & Diagnosis- Requires diagnosis of MASH/NASH with F2–F3 fibrosis and NAS ≥ 4 based on liver biopsy.
- Patients must participate in a comprehensive lifestyle intervention (CLI).
Dosage & Administration- < 100 kg: 80 mg orally once daily.
- ≥ 100 kg: 100 mg orally once daily.
- With moderate CYP2C8 inhibitors (e.g., clopidogrel): < 100 kg → 60 mg orally once daily; ≥ 100 kg → 80 mg orally once daily.
Monitoring & Safety- Monitor for hepatotoxicity during treatment.
- Monitor for gallbladder-related adverse reactions.
- Common adverse events (≥5%): diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, dizziness.
- Median time to onset of diarrhea: 6–17 days; median duration: 20 days.
- Gallbladder-related adverse reactions occurred in < 1 per 100 patient-years across all treatment groups.
Contraindications & Limitations- Avoid use in patients with decompensated cirrhosis.
- Avoid use in moderate to severe (Child-Pugh Class B or C) hepatic impairment.
- Not indicated for MASH with cirrhosis; no evidence supports off-label use for MASH cirrhosis.
Drug Interactions- Avoid strong CYP2C8 inhibitors (e.g., gemfibrozil).
- Avoid OATP1B1 and OATP1B3 inhibitors (e.g., cyclosporine).
- Reduce statin doses as recommended for atorvastatin, pravastatin, rosuvastatin, simvastatin.
- Monitor for substrate adverse effects with CYP2C8 substrates.
Treatment Duration & Response- Patients should participate for at least 6 months.
- Discontinue resmetirom if liver function worsens.
- Onset of significant treatment benefit: No data before Week 52 for NASH resolution or fibrosis improvement; 36 weeks for change from baseline in ALT.
Exclusion Criteria- Child-Pugh score ≥ 7
- Decompensated liver cirrhosis (e.g., noncardiac ascites, variceal hemorrhage, hepatic encephalopathy, spontaneous bacterial peritonitis)
- Recent assessment indicating cirrhosis: FibroScan > 18 kPa / VCTE consistent with cirrhosis, MRE > 5.0 kPa, FIB-4 > 2.67 (unless LSM < 18 kPa), or liver biopsy indicating METAVIR stage F4
- Hepatocellular carcinoma not actively managed by hepatology or a multidisciplinary team
- Uncontrolled liver disease from non-metabolic dysfunction causes (e.g., biliary obstruction, viral hepatitis, autoimmune hepatitis, hereditary or drug-induced liver disease)
- Heavy alcohol ingestion for > 3 consecutive months within the past year (≥4 drinks/day for men, ≥3 drinks/day for women)
- Untreated hyperthyroidism or hypothyroidism
- Concomitant use of strong CYP2C8 inhibitors (e.g., gemfibrozil)
- Concomitant use of systemic OATP inhibitors (e.g., cyclosporine)
Core Inclusion Criteria- Documented noncirrhotic MASH with METAVIR F2–F3 fibrosis and NAS ≥ 4 on liver biopsy within the past 36 months
- Prescribed by a VA/VA Community Care gastroenterologist/hepatologist or locally designated expert in MASH management
- Documented plan for lifestyle interventions (nutrition, exercise, weight loss)
- Documented plan to modify or replace medications that cause or exacerbate steatohepatitis with clinically appropriate alternatives
Additional/Conditional Inclusion Criteria- Overweight/obese patients: Must demonstrate medical inadvisability, intolerance, or inadequate response to a GLP-1RA with evidence for noncirrhotic MASH with moderate to advanced liver fibrosis
- Patients who can become pregnant: Counseling on potential risks vs benefits of treatment
- Females breastfeeding/providing breastmilk: Counseling on potential risks vs benefits of treatment
Warnings & Clinical Management Considerations- Withhold therapy during acute gallbladder events or acute cholecystitis until resolved due to risk of cholelithiasis and cholecystitis
- Monitor for increased plasma concentrations of certain statins; limit rosuvastatin and simvastatin to 20 mg/day, and pravastatin and atorvastatin to 40 mg/day
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MENINGOCOCCAL POLYSACCHARIDE CONJUGATE INJ,LYPHL
PENBRAYA, PENMENVY MEN A-B-C-W-Y
|
PENBRAYA, PENMENVY MEN A-B-C-W-Y |
2024-03-21 |
Indication & Population- Active immunization to prevent invasive disease caused by Neisseria meningitidis serogroups A, B, C, W, and Y
- Individuals 10 through 25 years of age
Administration & Dosing- Injectable suspension for intramuscular use
- Single dose after reconstitution of the Lyophilized MenACWY Component with the MenB Component (approximately 0.5 mL)
- Administered according to a 0, 6-month schedule
Contraindications- Severe allergic reaction (e.g., anaphylaxis) to any other diphtheria toxoid-containing vaccine
Warnings & Precautions- Management of allergic reactions
- Syncope
- Limitation of vaccine effectiveness
- Altered immunocompetence
- Guillian-Barre syndrome
Clinical Guidance & Place in Therapy- May be used when both MenACWY and MenB are indicated at the same visit
- Healthy persons aged 16–23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine
- Persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia)
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BUDESONIDE SUSP,ORAL
EOHILIA
|
EOHILIA |
2024-02-22 |
Exclusion Criteria- CYP3A4 inhibitors including grapefruit juice or other unmanageable drug interactions
- Severe (Child-Pugh C) hepatic impairment
Inclusion Criteria- Diagnosis of eosinophilic esophagitis (EoE) including histologic evidence of eosinophilic inflammation (≥ 15 eosinophils / high power field) made or confirmed by a VA / VA Community Care gastroenterologist
- Prescribed by a VA / VA Community Care gastroenterologist OR an immunologist, allergist, or other designated expert in the management of EoE in consultation with a VA / VA Community Care gastroenterologist
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment.
Indication & Population- Adult and pediatric patients 11 years of age and older with eosinophilic esophagitis (EoE)
- Limited to a 12-week treatment duration; safety and efficacy for longer than 12 weeks have not been established
Dosage & Administration- 2 mg orally twice daily for 12 weeks
- Administered as an oral suspension (2 mg/10 mL single-dose stick packs)
- Do not take with or mix with food or liquid
- Wait at least 30 minutes after administration before eating, drinking, or rinsing the mouth with water
- When rinsing the mouth, spit out water without swallowing
Contraindications- Hypersensitivity to budesonide
Warnings & Precautions- Hypercorticism and adrenal axis suppression
- Immunosuppression and increased risk of infection
- Erosive esophagitis
- Reduction in growth velocity (pediatric patients)
- Symptoms of steroid withdrawal in patients transferred from other systemic glucocorticoids
- Other glucocorticoid effects
- Kaposi’s sarcoma
Adverse Reactions- Respiratory tract infection, gastrointestinal mucosal candidiasis, headache, gastroenteritis, throat irritation (≥3% incidence)
Special Populations & Organ Impairment- Severe hepatic impairment (Child-Pugh Class C): Use is not recommended
- Moderate hepatic impairment (Child-Pugh Class B): Monitor for hypercorticism
- Pregnancy: May cause fetal harm
- Lactation: Insufficient studies in humans; weigh risks vs benefits
Formulary/VA Clinical Context- Preferred over oral viscous budesonide (OVB) due to a standardized formulation and reduced time, effort, and cost burdens for patients self-preparing swallowed topical glucocorticoids (STGs) or obtaining them from compounding pharmacies
- May be considered as an alternative to swallowed aerosolized fluticasone (SAF) for 12-week treatment of EoE
- Evidence supports large histologic effects and moderate full (histologic and symptomatic) response in patients with EoE
- No active-controlled trials directly comparing BOS to patient-mixed STGs or SAF to inform relative efficacy, safety, mucosal contact time, and place in therapy
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ELTROMBOPAG TAB
ALVAIZ
|
ALVAIZ |
2024-02-22 |
Exclusion Criteria- Stem cell disorder (i.e., myelodysplastic syndrome)
- Patient has not received prior therapy, with steroids, to increase platelet counts
- Thrombocytopenia is secondary to bone marrow suppressive anti-cancer therapy, antibiotics or other drugs
- Thromboembolic events within the past year, unless evaluated by a hematology provider and deemed to be an appropriate candidate
- Pregnancy and/or lactating
Inclusion Criteria- Diagnosis of chronic immune thrombocytopenia (ITP)
- Platelet count less than 30,000 mm3 and/or persistent bleeding resistant / refractory to glucocorticoids
- Patient has relapse after the following second-line therapies (unless contraindicated or patient is not a candidate): Splenectomy and rituximab
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Exclusion Criteria- Anticipated antiviral treatment includes a direct-acting antiviral (DAA) for chronic HCV
- Currently receiving peginterferon and ribavirin with or without DAA for chronic HCV
- Any contraindications to peginterferon and ribavirin apply
- Active malignancy or stem cell disorder
- Prior history of arterial or venous thrombosis plus ≥2 risk factors (hereditary thrombophilic disorders, estrogen hormone replacement therapy, systemic contraception therapy containing estrogen, smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer)
- Serious cardiac, cerebrovascular, or pulmonary disease
- Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin
- Known hypersensitivity, intolerance, or allergy to peginterferon and ribavirin, eltrombopag tablets, or ingredients
- Evidence of decompensated liver disease (Child-Pugh score ≥7 and/or clinical manifestations)
- Patient infected with HIV
Inclusion Criteria- Under care of and/or in collaboration with an experienced VA HCV practitioner
- Provider has discussed risks/benefits with patient; shared decision made for use
- Diagnosis of chronic HCV infection
- Baseline platelet count <75,000/μL
- Appropriate candidates for peginterferon and ribavirin combination antiviral therapy
- Treatment with peginterferon and ribavirin (dual therapy) anticipated after reaching target platelet goal
- Abdominal imaging negative for portal vein thrombosis within past 3 months
Dosing & Administration- Initiate prior to peginterferon and ribavirin therapy to obtain target platelet count
- Initial dose: 25 mg once daily on empty stomach (1 hour before or 2 hours after meal)
- Adjust by 25 mg increments every 2 weeks to achieve target platelet count (≥90,000/μL for peginterferon alfa-2a; ≥100,000/μL for peginterferon alfa-2b)
- Use lowest dose to achieve/maintain necessary platelet count
- Maintain same pre-treatment dose when starting antiviral therapy; modify during therapy to maintain counts between 50,000-150,000/μL
- Dose reduction NOT needed solely based on East Asian ethnicity
- Maximum dose: 100 mg/day
- If platelets <50,000/μL after ≥2 weeks: increase by 25 mg; wait 2 weeks to assess
- If platelets ≥150,000-200,000/μL: decrease by 25 mg; wait 2 weeks
- If platelets >200,000/μL: stop eltrombopag; monitor twice weekly; reinitiate at dose reduced by 25 mg (or 12.5 mg if previously on 25 mg) when count <100,000/μL
Monitoring Requirements- Prior to initiation: CBC with differential (including platelet), ocular exam for cataracts, Liver Function Panel (Total/Direct bilirubin, AST, ALT, albumin, total protein)
- During therapy: CBC weekly until stable then monthly; Serum liver tests (ALT, AST, bilirubin) every 2 weeks during adjustment then monthly; fractionate bilirubin if elevated; repeat tests within 3-5 days if abnormal; monitor weekly until resolved/stabilized/baseline; regular ocular exams for cataracts
- Upon discontinuation: CBCs weekly for at least four weeks
Safety & Risk Considerations- Box warnings for hepatotoxicity and risk of hepatic decompensation (ascites, hepatic encephalopathy, variceal hemorrhage, spontaneous bacterial peritonitis, hepatocellular carcinoma, death)
- Patients with albumin <3.5g/dL or MELD scores ≥10 at baseline have greatest risk of hepatic decompensation
- High thromboembolism risk: may increase risk; consider risk vs benefit
- Cataracts developed/worsened in 8% of treated patients
Discontinuation Guidelines- Discontinue when antiviral therapy is discontinued
- Discontinue for hepatotoxicity if ALT increases to ≥3X ULN (normal liver) or ≥3X baseline (pre-treatment elevations) and is progressive, persistent ≥4 weeks, accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury/hepatic decompensation
- Non-response: Consider discontinuing after 9 weeks at maximum dose (100 mg/day) if platelet count not increased sufficiently to initiate antiviral therapy
Specific Populations & Interactions- HIV: No safety/efficacy data; limited drug-drug interaction studies
- Renal insufficiency (CrCl<50ml/min): Not studied; use with caution
- Hepatic insufficiency: Clearance reduced in moderate-severe impairment; initial dose 25 mg daily; monitor serum liver tests; AUC ~2-fold higher; half-life prolonged 2-fold
- Pregnancy: Category C; discuss risks/benefits; consider enrollment in Promacta Pregnancy Registry
- Interactions: Substrate of CYP1A2/CYP2C8; inhibitor of OATP1B1/UGTs; chelates polyvalent cations. Separate administration from iron, calcium, aluminum, magnesium, selenium, zinc-containing meds/supplements/food by at least 4 hours.
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INFLIXIMAB-DYYB INJ,SOLN
ZYMFENTRA, ZYMFENTRA PEN
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ZYMFENTRA, ZYMFENTRA PEN |
2024-02-08 |
Indications & Treatment Phase- Maintenance treatment of adults with moderately to severely active Crohn’s disease following treatment with an infliximab product administered intravenously.
- Maintenance treatment of adults with moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously.
- Treatment phase is restricted to maintenance only; lacks indication for fistulizing CD.
Patient Population & Clinical Status- Adults who experience a clinical response or improvement in moderate to severe, active CD or moderate to severe, active UC at Week 10 or thereafter following IV induction doses of infliximab/biosimilar at Weeks 0, 2, and 6.
- Patients who are clinically stable and receiving IV infliximab/biosimilar to maintain clinical remission.
- Patients unable to adhere with IV maintenance infusion schedules.
Switching & Administration Criteria- For patients responding to maintenance therapy with an IV infliximab product, administer the first SC dose in place of the next scheduled IV infusion, then every 2 weeks thereafter.
- Dosage regimen for Week 10 and on: 120 mg subcutaneously once every 2 weeks.
Safety & Contraindication Considerations- Not contraindicated in moderate or severe heart failure (unlike INFLECTRA at doses > 5 mg/kg).
- Warning to avoid use in patients with congestive heart failure; monitor closely and discontinue therapy if symptoms of CHF develop.
Indication & Disease Severity- Moderate to severe active Crohn’s disease (CD) or moderate to severe active ulcerative colitis (UC)
Prescriber & Monitoring Requirements- Prescribed and monitored by a VA / VA Community Care gastroenterologist/hepatologist or locally designated expert in inflammatory bowel disease
Baseline Diagnostic Criteria- Disease confirmed by endoscopy or imaging at baseline
Clinical Response & Maintenance Requirements (One of the following must be met)- Achieved clinical response after Week 10 following three intravenous (IV) induction doses of infliximab/biosimilar at Weeks 0, 2 and 6
- Clinically stable and receiving IV infliximab/biosimilar to maintain clinical remission
Alternative Administration Justification- Unable to accommodate or comply with maintenance therapy intravenous infusion schedule (e.g., difficult intravenous access, travel limitations, work requirements, lack of sick leave)
Clinical Response Definitions- UC clinical response: Decrease from baseline of ≥ 2 points and at least 30% on the modified Mayo score (range 0–9), including subscores for stool frequency, rectal bleeding, and endoscopic findings
- CD clinical response: Decrease from baseline in the Crohn’s Disease Activity Index (CDAI) of ≥ 100 points
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IPTACOPAN CAP,ORAL
FABHALTA
|
FABHALTA |
2024-01-11 |
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Inclusion Criteria- Prescribed by a REMS registered VA or VA Community Care hematologist, oncologist, immunologist or genetic specialist
- Laboratory-confirmed diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH), as evidenced by detectable GPI-deficient hematopoietic clones (Type III PNH red blood cells (RBC)) via Flow Cytometry
- Evidence of clinically significant hemolysis (e.g., Hemoglobin <10g/dL) despite 6 months of stable therapy with anti-C5 inhibitor (e.g., ravulizumab or eculizumab)
- Complete or update vaccination for encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis at least 2 weeks prior to the first dose of therapy according to current Advisory Committee on Immunization Practices (ACIP)
Indication & Population- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Adult patients with confirmed PNH and hemoglobin <10g/dL
Dosage & Administration- 200mg oral capsules administered twice daily
Contraindications- Hypersensitivity to iptacopan
- Unresolved serious infection caused by encapsulated bacteria (Streptococcus pneumoniae, Neisseria meningitidis, or H. influenzae type B)
Warnings & Precautions- Risk of serious infections caused by encapsulated bacteria
- Use not recommended in severe renal impairment (eGFR<30mL/min) or severe hepatic impairment (Child-Pugh class C)
- Insufficient data to make recommendation regarding risk of birth defects in pregnancy
- Breastfeeding cessation recommended during treatment and for 5 days after final dose
Drug Interactions- Strong CYP2C8 inducers (e.g., rifampin) or inhibitors (e.g., gemfibrozil) can significantly decrease or increase iptacopan exposure
Monitoring & Pre-treatment Requirements- Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose, unless risks of delaying therapy outweigh risk of developing a serious infection
- Monitor for hemolysis after cessation of therapy
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ZILUCOPLAN INJ,SOLN
ZILBRYSQ
|
ZILBRYSQ |
2024-01-11 |
Indication & Patient Population- Generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor antibody positive (AChR+)
- No evidence to support use in MuSK+, LRP4+, or seronegative disease
Dosage & Administration- Once daily subcutaneous (SubQ) injection
- Weight-based dosing: <56 kg = 16.6 mg; ≥56 kg to <77 kg = 23 mg; ≥77 kg = 32.4 mg
- Can be self-administered
Safety, Monitoring & REMS Requirements- REMS program required to reduce risk of meningococcal infections
- Meningococcal vaccination must be completed at least 2 weeks prior to administering the first dose
- Monitor for early signs of meningococcal infection; evaluate immediately if infection is suspected
- Contraindicated in patients with unresolved Neisseria meningitidis infection
- Increased susceptibility to infections, particularly encapsulated bacteria; vaccination for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae recommended
- Obtain lipase and amylase levels at baseline; discontinue if pancreatitis is suspected until ruled out
Clinical Use Considerations & Limitations- Effective as a steroid-sparing treatment option for AChR+ gMG
- May be considered as add-on therapy when traditional oral immunosuppressants (azathioprine, mycophenolate, steroids) with or without acetylcholinesterase inhibitor (pyridostigmine) are ineffective
- Not studied as chronic immunotherapy in combination with plasma exchange, intravenous immunoglobulin (IVIg), rituximab, neonatal Fc receptor antagonists, or other complement inhibitors
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Thymectomy within 12 months
- Concomitant therapy with neonatal Fc receptor antagonists (e.g., efgartigimod), rituximab, or other complement inhibitors (e.g., eculizumab, ravulizumab)
- Chronic therapy with intravenous immunoglobulin or plasma exchange (may be used for exacerbations)
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist
- Diagnosis of acetylcholine receptor (AChR) antibody positive generalized myasthenia gravis (gMG)
- Not a candidate for thymectomy
- Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV
- Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) total score ≥ 6
- Vaccination against pneumococcal disease and Neisseria meningitidis with both Meningococcal conjugate vaccine (MenACWY) and Meningococcal serogroup B vaccine
Additional Inclusion Criteria- One of the following must be met:
- Inadequate symptom control to maximally tolerated pyridostigmine and at least two immunosuppressive agents separately trialed for at least 6 months each (e.g., azathioprine, cyclosporine, mycophenolate)
- History of intolerance or contraindication preventing trial of immunosuppressive agents (e.g., azathioprine, cyclosporine, mycophenolate)
- Lack of symptom control despite 4 or more courses of plasma exchange, high-dose steroid bursts and/or intravenous immune globulin within a 12-month period
Vaccination & Emergency Management- In emergent cases where waiting to initiate zilucoplan at least two weeks after completion of vaccination is not possible, patients should begin the vaccination series at the time of initial zilucoplan dosing and be provided with appropriate prophylaxis.
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ALFUZOSIN TAB,SA
ALFUZOSIN HCL ER, UROXATRAL
|
ALFUZOSIN HCL ER, UROXATRAL |
2024-01-01 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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ROFLUMILAST FOAM,TOP
ZORYVE
|
ZORYVE |
2023-12-28 |
Exclusion Criteria- Moderate to severe liver impairment (Child-Pugh B or C)
Inclusion Criteria- Moderate to severe seborrheic dermatitis
- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated expert
- Tried and had intolerance or inadequate response to a combination of topical antifungal (including shampoo) plus topical corticosteroid for ≥ 4 consecutive weeks unless medically inadvisable
- Tried and had intolerance or inadequate response to a combination of topical antifungal (including shampoo) plus topical calcineurin inhibitor (e.g., tacrolimus ointment or pimecrolimus cream) for ≥ 4 consecutive weeks unless medically inadvisable
Additional Inclusion Criteria (Special Populations)- Pregnancy/Planning pregnancy: Counseling provided on potential risks vs benefits of treatment; patient informed that it is not known whether use will harm the unborn baby. Avoid use during labor and delivery.
- Breastfeeding/Planning breastfeeding: Counseling provided on how to minimize potential drug exposure to the breastfed infant via breast milk per prescribing information. Advise patients not to apply directly to the nipple or areola, and if applied to the chest, to avoid direct contact with the infant’s skin.
Indication & Patient Population- Treatment of seborrheic dermatitis (SD) in adults
- Moderate to severe SD (predominantly moderate disease severity)
- Patients with an inadequate response, intolerance, or medical inadvisability to combination topical antifungal plus TCS and combination topical antifungal plus topical calcineurin inhibitor
Place in Therapy & Step Requirements- 2nd-line alternative for SD of the face in patients requiring frequent use of TCSs
- May be added to topical antifungal therapy
- Alternative to a TCI for maintenance therapy
- First nonsteroidal, non-antifungal product approved for the treatment of SD
Dosage & Administration Parameters- Applied once daily to affected areas on skin and/or scalp when not wet
- Topical foam 0.3% in 60-gram pressurized cans
- Maximum body surface area (BSA) of 20%
Safety & Contraindications- Contraindicated in moderate to severe liver impairment (Child-Pugh B or C)
- Flammable formulation requiring appropriate handling precautions
- PDE4-related adverse events (psychiatric and gastrointestinal) occurred at significantly lower rates than vehicle
- Local adverse events occurred at similar rates to vehicle
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TRAVOPROST IMPLANT
IDOSE TR
|
IDOSE TR |
2023-12-28 |
Exclusion Criteria- Ocular or periocular infection
- Corneal endothelial dystrophy
- Prior corneal transplant
- Prior treatment with travoprost implant in affected eye
- Active intraocular inflammation
Inclusion Criteria- Provider is a VA/VA Community Care ophthalmologist
- Diagnosis of open-angle glaucoma or ocular hypertension
- Unable to use at least one topical agent from each drug class, OR is using a topical agent and requires additional intraocular pressure lowering but unable to use at least one topical agent from remaining drug classes
- Among the agents tried, at least two were preservative-free or contained a non-benzalkonium chloride preservative
- Laser trabeculoplasty is contraindicated or has not had adequate response to prior laser treatment
Device & Procedural Requirements- Implant is Magnetic Resonance Imaging (MRI) Conditional
- Patients must be informed that the implant is MR Conditional per their Patient ID card
- Patients requiring MRI must inform their healthcare provider of the implanted device
- Product labeling conditions for safe scanning must be followed to prevent patient injury
Indication- Reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension
Patient Selection Criteria- Inclusions
- ≥18 years old
- Diagnosis of open-angle glaucoma (OAG) or ocular hypertension (OHT)
- Currently on 0-2 topical glaucoma medications
- Mean diurnal IOP and individual IOP 21-36 mmHg at baseline visit
- Central corneal thickness (CCT) 440-620µm
- Open iridocorneal angle (Shaffer grade ≥3) with normal anatomy
- Best-corrected visual acuity (BCVA) ≥20/80 Snellen
- Exclusions
- Cup/Disc ratio > 0.8
- Visual field mean deviation of -12dB or worse
- Active ocular inflammation
- Prior argon laser trabeculoplasty or incisional glaucoma surgery
Contraindications- Ocular or periocular infection
- Corneal endothelial dystrophy
- Prior corneal transplant
- Hypersensitivity to travoprost or components
Warnings & Precautions- Use with caution in patients with narrow iridocorneal angles (Shaffer grade < 3) or other angle abnormalities that could impair proper placement of iDose TR at the planned implantation site
- Use with caution in aphakic patients, pseudophakic patients with a torn posterior lens capsule, or known risk factors for macular edema
- Active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated
- Device dislocation; if implant becomes dislocated, it should be surgically removed
- Increased pigmentation of the iris can occur and is likely to be permanent
- MRI Conditional status: Patients must inform healthcare provider that they have an iDose TR implanted in the eye if requiring MRI
- Intraocular inflammation
- Endophthalmitis
- Macular edema
Administration & Dosing- Administered intracamerally through a small, clear corneal incision and anchored into the sclera at the iridocorneal angle
- Inserted directly through the trabecular meshwork of the anterior chamber angle into the sclera
- Requires implantation in an operating room
- Do not readminister to an eye that received a prior travoprost implant
Clinical Guidance & Place in Therapy- Limited to patients who are unable to use topical agents, including preservative-free or non-benzalkonium chloride agents
- Appropriate when laser trabeculoplasty is contraindicated or has not had adequate response to prior laser treatment
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RISPERIDONE INJ,SUSP,SA
RISPERDAL CONSTA, RISPERIDONE ER, RYKINDO
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RISPERDAL CONSTA, RISPERIDONE ER, RYKINDO |
2023-12-21 |
Transitioning Veteran- Veteran is transitioning care from the Department of Defense to VHA
- VA prescriber has determined continuing the medication is safe and clinically appropriate after assessing and consulting with the Veteran
- (Note: If met, remainder of criteria for use is not applicable)
- Exclusion Criteria (If any are met, patient should NOT receive a long-acting injectable antipsychotic)
- Patient has never taken the long-acting injectable antipsychotic ordered in any formulation (e.g., oral)
- Patient has a hypersensitivity to the antipsychotic ordered (consider risperidone and paliperidone cross-sensitive)
- Inclusion Criteria (Patient must meet ALL of the following)
- Diagnosis of schizophrenia or schizoaffective disorder, or bipolar disorder
- Prescriber is a VA Mental Health Provider
- Patient has taken and tolerated the antipsychotic ordered prior to receiving it as a LAI for an adequate length of time (consider risperidone and paliperidone cross-tolerant)
- Patient will be transitioned from oral medication to the long-acting injectable per guidelines/manufacturer recommendations
- Inclusion Criteria (Patient must meet ONE of the following)
- Patient has relapsed or been hospitalized for the intended indication or complications of the intended indication because of nonadherence when treated with oral antipsychotics
- Patient’s care environment is such that a LAI is a more reliable route of administration (e.g., homeless, lack of medication supervision, or the medication cannot be stored safely)
Indications- Schizophrenia in adults
- Maintenance monotherapy treatment of bipolar I disorder in adults
Administration & Preparation- Route: Intramuscular (IM) injection into deltoid or gluteal muscle
- Refrigeration: Not required
- Reconstitution/Shaking Requirements:
- Aripiprazole Maintena: Room temperature; shake 20 seconds (pre-filled syringe) or 30 seconds (vial)
- Aripiprazole Aristada: Tap 10x + shake 30 seconds (syringe)
- Aripiprazole Asimtufii: Tap 10x + shake 10 seconds (syringe)
Dosing & Scheduling- Aripiprazole Maintena: Monthly dosing; conversions include 15mg oral to 300mg IM monthly, and 20mg oral to 400mg IM monthly
- Aripiprazole Aristada: Monthly, q6 weeks, or q2 months dosing; conversions include 10mg oral to 441mg IM monthly, 15mg oral to 662mg IM monthly/882mg q6wks/1064mg q2months IM, and 20mg oral to 882mg IM monthly
- Aripiprazole Asimtufii: Q2 months dosing; conversion includes 400mg IM qmonth to 960mg q2months
Oral Overlap Requirements- Maintena and Asimtufii: Require 14-day oral overlap
- Aristada: Requires 21-day oral overlap unless administered with Initio (675mg) plus a 30 mg oral dose, which eliminates the need for oral overlap
Formulary & Logistical Considerations- Formulary status: PA-F with CFU for all three dosage forms
- Medication selection should be based on patient-specific characteristics, patient preferences, and medication side effect profiles per the 2023 VA/DoD CPG for Schizophrenia
- Aristada represents 41% market share among aripiprazole LAIs, has a high PADR approval rate, and is the least expensive LAI among the aripiprazole products
- To avoid oral overlap, Aristada should be administered with Initio for maximum benefit and may be administered monthly or q2months (1064mg only)
- Reported adverse drug events (ADEs) are low, pharmacologically expected, and similar across all aripiprazole LAI dosage forms
- Logistical considerations include route of administration, oral overlap requirements, staff education for administration (duration product must be shaken, injection speed, injection location), refrigeration requirements, and cost
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ZURANOLONE CAP,ORAL
ZURZUVAE
|
ZURZUVAE |
2023-12-08 |
Exclusion Criteria- Patient is receiving a CYP3A4 inducer
- Active or untreated substance use disorder (SUD)
Inclusion Criteria- Diagnosis of postpartum unipolar depression without psychosis
- Patient is 12 months or less postpartum
- Rapid response needed due to suicidality or homicidality
- The prescriber is a VA/VA Community Care Mental Health Provider
- Patient has been counseled about lack of data in human pregnancy and has made an informed decision about whether to use contraception during the 14-day treatment course and for 1 week following the completion of therapy
- Patient agrees not to drive or engage in other potentially hazardous activities until at least 12 hours after administration for the duration of the 14-day treatment course
Administration & Counseling Requirements- Take with fat-containing food (e.g., 400 to 1,000 calories, 25-50% fat) for optimal absorption
- Patient counseling required regarding passage into breast milk; shared decision-making needed to balance clinical need against developmental and health benefits of breastfeeding (consider continuation, pumping and discarding milk through 1 week past treatment completion, or cessation)
Indication & Patient Population- • Treatment of postpartum depression (PPD) in adults
- • PPD defined as a perinatal major depressive episode with onset during pregnancy or within 4 weeks of delivery
- • Severe depression indicated by baseline 17-item Hamilton Rating Scale for Depression (HAM-D 17) score >26
Dosing & Administration- • Oral capsules available in 20 mg, 25 mg, and 30 mg strengths
- • Administered once daily in the evening with fat-containing food for a 14-day treatment course
- • Food effect: Low-fat meal (400-500 calories, 25% fat) increases Cmax 3.5-fold and AUC ~1.8-fold; high-fat meal (800-1000 calories, 50% fat) increases Cmax 4.3-fold and AUC ~2-fold compared to fasted conditions
Concomitant Medications & Interactions- • Concomitant use of existing oral antidepressants permitted if patient maintained a stable dose for at least 30 days prior to baseline
- • Avoid concomitant use with CYP3A4 inducers
- • Avoid concomitant use with other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) due to increased risk of psychomotor impairment, somnolence, cognitive impairment, and respiratory depression
Safety & Precautions- • Boxed warning for impaired ability to drive or engage in other potentially hazardous activities due to CNS depressant effects
- • Patients must be advised not to drive or engage in hazardous activities until at least 12 hours after administration for the duration of the 14-day treatment course; patients may be unable to self-assess driving competence or impairment degree
- • Increased risk of falls may impact ability to care for an infant or other children
- • May cause fetal harm; advise pregnant women of potential risk to exposed infants
- • Advise females of reproductive potential to use effective contraception during treatment and for one week after the final dose
- • Present in low levels in human milk; limited data on effects on breastfed infants or milk production
- • Dose-dependent abuse potential comparable to alprazolam
Place in Therapy & Clinical Considerations- • Use is strictly limited to a 14-day treatment course
- • Evidence suggests benefit primarily in individuals with severe PPD
- • Determination of step/place in therapy is difficult as studies compared zuranolone only to placebo, not treatment as usual
- • Use must be weighed against other effective treatment options (e.g., interpersonal psychotherapy, cognitive-behavioral therapy, antidepressant medications) and safety considerations
- • Maintenance management of PPD will likely require usual care (oral antidepressant and/or evidence-based psychotherapy)
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TORIPALIMAB-TPZI INJ,SOLN
LOQTORZI
|
LOQTORZI |
2023-12-07 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression requiring a corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy
- Lactating
Inclusion Criteria- Indication is FDA-approved
- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Reproductive Health & Contraception Requirements- Female patients of child-bearing potential: Counseling provided on contraception and risks vs. benefits of treatment; use effective contraception during therapy and for 4 months after the last dose
- Male patients with female partners of child-bearing potential: Counseling provided on contraception and risks vs. benefits of treatment; use effective contraception during therapy and for 4 months after the last dose
Indications- First-line treatment in combination with cisplatin and gemcitabine for metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC)
- Single agent for recurrent unresectable or metastatic NPC with progressive disease on or after platinum-containing chemotherapy
Dosing & Administration- In combination with cisplatin and gemcitabine: 240 mg IV every 3 weeks
- As a single agent: 3 mg/kg IV every 2 weeks
- Dosage form: Injection 240 mg/6 mL [40 mg/mL] solution as a single-dose vial
Patient Eligibility / Inclusion Criteria- Metastatic or recurrent, locally advanced NPC
- First-line setting: No prior systemic therapy for recurrent or metastatic disease; if recurrent disease, last treatment (radiotherapy or chemotherapy) > 6 months from last treatment
- Subsequent-line setting: Refractory to standard chemotherapy including >2 lines of systemic chemo; first line must have included a platinum-based regimen; neoadjuvant, adjuvant, or concurrent chemoradiotherapy counts as a line of therapy only if progressive disease occurs; intolerance to chemotherapy is not considered a line of therapy
- ECOG Performance Status 0-1
Exclusion Criteria- Autoimmune conditions (other than stable hypothyroidism or Type I diabetes mellitus within 6 months after end of treatment)
- Requirement for systemic immunosuppression
- Active CNS metastases
Clinical Guidelines & VA Pathway Alignment- VA Head & Neck Oncology Pathway: Recommended as first-line therapy in patients with recurrent or metastatic NPC who are candidates for immunotherapy and cisplatin
- NCCN Guidelines v4.2024 (Preferred 1L): Cisplatin/gemcitabine; cisplatin/gemcitabine + toripalimab; cisplatin/gemcitabine + other PD-1 inhibitor
- NCCN Guidelines v4.2024 (Preferred Subsequent Line): Toripalimab for disease progression on or after platinum-containing therapy
Safety & Monitoring Considerations- No boxed warnings or contraindications listed
- Monitor for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity
- Prednisone-equivalent >10 mg/day may diminish immune checkpoint inhibitor effect
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CAPIVASERTIB TAB
TRUQAP
|
TRUQAP |
2023-11-30 |
Indication & Patient Population- Adult patients (pre-, peri-, post-menopausal women or men) with hormone receptor (HR)-positive, HER2-negative, locally advanced (inoperable) or metastatic breast cancer
- Patients must have one or more PIK3CA/AKT1/PTEN-alterations (activating mutations in PIK3CA and AKT1; inactivating alterations in PTEN)
- Disease status: Progressive disease on aromatase inhibitors (AI) with or without a CDK4/6 inhibitor in the metastatic setting, or within 12 months of neoadjuvant or adjuvant AI
Dosing & Administration- 400 mg orally twice daily, with or without food
- Schedule: 4 days on followed by 3 days off per 28-day treatment cycle
- Administered in combination with fulvestrant (500 mg intramuscular injection on cycle 1 days 1 and 15, then day 1 of each subsequent 28-day cycle)
Contraindications- Severe hypersensitivity to capivasertib or any of its components
Monitoring & Management Requirements- Hyperglycemia: Test fasting blood glucose (FBG) and HbA1C; optimize glucose levels; monitor per prescribing information. Type I diabetes/IDDM patients are excluded.
- Diarrhea: Monitor for signs and symptoms; initiate anti-diarrheal medication at first indication; manage with dose reductions as needed.
- Cutaneous adverse reactions: Monitor for signs and symptoms; consider dermatology consultation; corticosteroids (topical or systemic) may be required.
- Embryo-fetal toxicity precautions apply.
- Regularly scheduled monitoring and patient/caregiver education are required, particularly for patients with concomitant diabetes or GI conditions.
VA/NCCN Pathway Alignment- VA Breast Cancer – Stage IV ER+ or PR+/HER2- pathway directs use in patients who have progressed on prior endocrine therapy and have a molecular alteration identified in AKT-PTEN
- NCCN Invasive Breast Cancer Guidelines V4.2025 (Category 1) list capivasertib plus fulvestrant as preferred second or subsequent-line therapy for recurrent, unresectable, or metastatic ER+/PR+/HER2- patients with PIK3CA, AKT2, or PTEN alterations who have progressive disease after >1 prior line of endocrine therapy
Exclusion Criteria- Uncontrolled hyperglycemia
- Chronic, uncontrolled diarrhea
- Severe renal impairment (CrCl 15-29 ml/min)
- Severe hepatic impairment (bilirubin > 3x upper limit of normal and any AST)
- Unmanageable drug-drug or drug-food interaction
- Pregnancy
- Lactating
Inclusion Criteria- Locally advanced, unresectable or metastatic breast cancer
- Hormone receptor (HR)-positive, HER2-negative disease
- Activating PIK3CA or AKT1 mutations or PTEN gene alteration as detected by an approved test
- Progressive disease on or after an endocrine-based regimen
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0 – 1
- Goals of care and role of Palliative Care consult have been discussed and documented
Reproductive Health & Counseling Requirements- Pregnancy must be excluded prior to receiving capivasertib for females who can become pregnant
- Counseling on potential risks vs benefits of treatment provided for females who can become pregnant and males with partners who can become pregnant
- Use of effective contraception required during therapy and for 4 months after the last dose for the aforementioned populations
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BIMEKIZUMAB-BKZX INJ,SOLN
BIMZELX, BIMZELX AUTOINJECTOR
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BIMZELX, BIMZELX AUTOINJECTOR |
2023-11-23 |
Indication & Patient Population- Treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
Treatment Line & Sequence Requirements- Proposed as a 5th–6th-line systemic therapy for moderate to severe PPsO.
- Indicated after methotrexate, phototherapy (if available and feasible), a TNF inhibitor (TNFI), and less-costly IL-17A inhibitors (IL-17Ais) and IL-23 inhibitors (IL-23is).
Pretreatment Evaluations & Monitoring- Evaluate for tuberculosis infection.
- Assess liver enzymes, alkaline phosphatase, and bilirubin.
- Update all age-appropriate vaccinations as per current guidelines prior to initiation.
Dosing & Administration Criteria- 320 mg subcutaneously at Weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter.
- For patients weighing ≥ 120 kg, consider 320 mg every 4 weeks after Week 16.
Clinical Considerations & Place in Therapy- May be preferred over ustekinumab 90 mg due to greater efficacy and lower cost; however, it is higher in cost than ustekinumab 45 mg.
- For severe PPsO (defined as affecting >10% body surface area, impairing work or biopsychosocial function, affecting hands/feet/nails/scalp/face/genital area, or causing intractable pruritus/pain/bleeding), an IL-17A antagonist (preferably ixekizumab) rather than a TNFI can be considered on a case-by-case basis.
- An IL-17A/F antagonist (e.g., bimekizumab-bkzx) or IL-23 antagonist (e.g., risankizumab) may be considered for severe PPsO as an alternative to a TNFI (e.g., infliximab/biosimilar) if an IL-17A antagonist is medically inadvisable.
Safety & Precautions Influencing Use- Boxed warnings: None.
- Contraindications: None.
- Other warnings affecting clinical decision-making: Suicidal ideation and behavior, infections, tuberculosis, liver biochemical abnormalities, inflammatory bowel disease, immunizations.
Exclusion Criteria- History of severe or untreated depression, suicidal ideation/behavior, or risk factors for suicide (e.g., depression, bipolar disorder) – relative contraindication when potential risks outweigh benefits
- Uncontrolled active infection, including undrained abscess and fungal infection; therapy may be started/restarted only once the infection is controlled
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive status without antiviral prophylaxis; initiation permitted only after starting prophylaxis
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are eligible)
- Concomitant live or live-attenuated vaccines, or administration of any inactivated/live/attenuated vaccines less than 4 weeks prior to initiation
- Concomitant treatment with natalizumab or other drugs with contraindicated drug interactions (e.g., Bacillus Calmette-Guerin [BCG] vaccine) unless risk-benefits favor use
- Acute liver disease or cirrhosis
- Diagnosis of inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
Inclusion Criteria- Definite or provisional diagnosis of active ankylosing spondylitis or radiographic axial spondyloarthritis
- Prescription and monitoring by a VA/VA Community Care rheumatologist or locally-designated expert
- All age-appropriate vaccinations offered prior to initiating therapy
- Completed tuberculosis (TB) testing using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and anti-HBs)
- Current or past completion of hepatitis C screening; initiation permitted while awaiting test results
- Documented pre-treatment liver enzymes, alkaline phosphatase, and bilirubin levels
- Tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated, or inadequate (defined as no or partial response after 3 months) or loss of initial response
- Intolerance or inadequate response (no or partial response after 3 months) to both ixekizumab and secukinumab
Additional/Conditional Inclusion Criteria- HBsAg-negative but anti-HBc-positive patients: Consultation with a GI/liver or infectious diseases expert required to advise on antiviral prophylaxis versus preemptive monitoring for HBV reactivation
- Patients of childbearing potential: Counseling provided regarding treatment risks vs. benefits and requirement for effective contraception during therapy
- Pregnant patients or those planning pregnancy: Counseling provided regarding treatment risks vs. benefits
- Lactating patients or those planning to breastfeed: Counseling provided regarding treatment risks vs. benefits
Treatment Sequencing & Initiation Requirements- Ixekizumab is the preferred interleukin-17A inhibitor for new starts
- First-line therapy: TNFi
- Second-line after TNFi failure: IL-17Ai (ixekizumab preferred before secukinumab, which is preferred before bimekizumab-bkzx) or Janus kinase inhibitor (tofacitinib or upadacitinib)
- Criteria apply only to new starts; stable patients on bimekizumab-bkzx should not be switched to a criteria-required prior drug for nonmedical reasons
Exclusion Criteria- History of depression or suicidal ideation/behavior/risk factors for suicide (relative contraindication when risks outweigh benefits)
- Uncontrolled active infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated/live/live-attenuated vaccines less than 2 weeks before initiation
- Acute liver disease or cirrhosis
- Active inflammatory bowel disease
Inclusion Criteria- Moderate to severe hidradenitis suppurativa (HS)
- Prescribed and monitored by a VA/VA Community Care dermatologist or locally-designated expert
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and anti-HBs)
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- Documented results of pre-treatment liver enzymes, alkaline phosphatase, and bilirubin
- Adalimumab/biosimilar (preferred) or infliximab/biosimilar (alternative) is medically inadvisable, not tolerated, or not adequate (NO/partial response after 3 months) or lost initial response
- Had intolerance or inadequate response (NO/partial response after 3 months) to secukinumab
Additional Inclusion Criteria- If HBsAg-negative but anti-HBc-positive: Consultation with gastroenterologist/hepatologist or infectious diseases expert for advice on antiviral prophylaxis vs. preemptive monitoring for HBV reactivation
- Patients of childbearing potential: Counseling provided on risks vs benefits and use of effective contraception during therapy
- Pregnant or plan to become pregnant: Counseling provided on risks vs benefits
- Lactating/providing breastmilk/planning to do so: Counseling provided on risks vs benefits
Clinical Monitoring & Management- Antiviral prophylaxis for HBV should use agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed/initiated by end of first year, preferably when dosage is low, disease is stable, or immune response can be expected
- Non-live and live vaccines should be administered 2 or more weeks before initiating interleukin immunosuppressives
Exclusion Criteria- History of severe or untreated depression, suicidal ideation/behavior, or risk factors for suicide (relative contraindication when risks outweigh benefits)
- Uncontrolled active infection (including undrained abscess and fungal infection); therapy may be started/restarted once controlled
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis; initiation permitted after starting prophylaxis
- Untreated HIV infection (treated, well-controlled, asymptomatic patients are eligible)
- Concomitant live or live-attenuated vaccines, or administration of inactivated/live/attenuated vaccines within 4 weeks prior to initiation
- Concomitant treatment with natalizumab or other drugs with contraindicated interactions (unless risk-benefit favors use)
- Acute liver disease or cirrhosis
- Diagnosis of inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
Inclusion Criteria- Definite or provisional diagnosis of active nonradiographic axial spondyloarthritis made by a VA/VA Community Care rheumatologist
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total anti-HBc, and anti-HBs)
- Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Documented pre-treatment liver enzymes, alkaline phosphatase, and bilirubin
- Tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated, or inadequate (no/partial response after 3 months) or loss of initial response
- Intolerance or inadequate response (no/partial response after 3 months) to ixekizumab and secukinumab
- Ixekizumab is the preferred interleukin-17A inhibitor for new starts
Additional Inclusion Criteria / Special Populations- Patients of childbearing potential: Counseling on treatment risks vs benefits and use of effective contraception during therapy
- Pregnant patients or those planning pregnancy: Counseling on treatment risks vs benefits
- Lactating patients or those planning to breastfeed: Counseling on treatment risks vs benefits
- HBsAg-negative but anti-HBc-positive patients (if practitioner deems consult indicated): GI/liver or ID expert e-consult for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
Diagnosis & Clinical Presentation- Inflammatory articular disease (joint, spine, and/or entheseal) with a definite or provisional diagnosis of psoriatic arthritis
Screening & Laboratory Requirements- Completed tuberculosis test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Documented pre-treatment liver enzymes, alkaline phosphatase, and bilirubin
Contraindications & Exclusions- Diagnosis of inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
- History of severe or untreated depression, suicidal ideation/behavior, or risk factors for suicide (relative contraindication when risks outweigh benefits)
- Uncontrolled active infection (including undrained abscess and fungal infection); therapy may be started/restarted once controlled
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis; initiation permitted after starting prophylaxis
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are eligible)
- Concomitant live or live-attenuated vaccines, or administration of such vaccines less than 4 weeks prior to initiation
- Concomitant treatment with natalizumab or other drugs with contraindicated interactions (e.g., BCG vaccine) unless risk-benefits favor use
- Acute liver disease or cirrhosis
Treatment History & Sequencing- Tumor necrosis factor inhibitor (TNFi) must be medically inadvisable, not tolerated, or inadequate (NO or partial response after 3 months) or lost initial response
- Must have intolerance or inadequate response (NO or partial response after 3 months) to ixekizumab and secukinumab
- Ixekizumab is the preferred interleukin-17A inhibitor for new starts
- First-line therapy: TNFi (adalimumab/biosimilar, certolizumab, etanercept, or infliximab/biosimilar)
- First-line exception: IL-17Ai (ixekizumab preferred) may be used first-line instead of a TNFi for severe concomitant psoriasis
- Second-line after TNFi: IL-17Ai (ixekizumab preferred before secukinumab, which is preferred before bimekizumab-bkzx) or JAKi (tofacitinib or upadacitinib); apremilast if no joint erosions or axial disease
- Third-line after TNFi and IL-17Ai: IL-23i (guselkumab or risankizumab-rzaa) or IL-12/23i (ustekinumab)
Counseling & Patient Management- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally-designated expert
- Offered all age-appropriate vaccinations prior to initiating therapy
- Patients of childbearing potential: Counseling on risks vs benefits and use of effective contraception during therapy
- Pregnant patients or those planning pregnancy: Counseling on risks vs benefits
- Lactating patients/providing breastmilk or planning to do so: Counseling on risks vs benefits
- HBsAg-negative but anti-HBc-positive patients: GI/liver or infectious diseases expert consultation required for advice on antiviral prophylaxis vs preemptive monitoring
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FRUQUINTINIB CAP,ORAL
FRUZAQLA
|
FRUZAQLA |
2023-11-23 |
Indication & Patient Population- Metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, and anti-VEGF therapy/RAS wild-type anti-EGFR therapy if medically appropriate.
- Patients who have exhausted all standard treatment options including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, an anti-EGFR therapy (if RAS wild-type), and progressive disease or intolerance to trifluridine-tipiracil (with or without bevacizumab).
- Heavily pretreated patients who have exhausted all other viable lines of therapy including fluoropyrimidine, oxaliplatin, irinotecan, anti-EGFR inhibitor, anti-VEGF, trifluridine/tipiracil or regorafenib-based therapy.
Dosing Regimen- 5mg PO daily for days 1-21 of a 28-day cycle until progression of disease or intolerable toxicity.
- Available as oral capsules: 5mg & 1mg.
Trial Inclusion Criteria- Age 18-75 years
- Histologically and/or cytologically confirmed metastatic colorectal cancer
- Progression on/intolerant of at least two prior lines of standard therapy (including fluoropyrimidine, oxaliplatin, irinotecan, anti-EGFR, anti-VEGF therapies) or progressive disease or intolerance to trifluridine/tipiracil and/or regorafenib therapy
- Body weight ≥ 40kg
- ECOG Performance status ≤ 1
- Life expectancy > 12-weeks
Trial Exclusion Criteria- Prior use of VEGF inhibitor (excluding bevacizumab)
- Baseline cytopenias, liver dysfunction, renal dysfunction, proteinuria, uncontrolled hypertension, uncontrolled infection, or significant electrolyte abnormality
- CNS metastases
- Persistent grade >1 toxicity from prior treatment (excluding neuropathy grade ≤2)
- History severe bleed or thromboembolic events within 6-months
Safety Monitoring & Management Requirements- Hypertension: Adjust anti-hypertensive therapy as appropriate; hold/discontinue if control cannot be achieved.
- Hemorrhagic Events: Permanently discontinue if serious hemorrhage occurs.
- Infections: Hold for grade 3-4 infections and resume after resolution.
- Gastrointestinal Perforations: Permanently discontinue if occurs.
- Hepatotoxicity: Hold and adjust depending on severity and persistence.
- Proteinuria: Hold and adjust depending on severity and persistence.
- Palmar-Plantar Erythrodysesthesia (PPE): Hold and adjust depending on severity and persistence.
- Posterior Reversible Encephalopathy Syndrome (PRES): Permanently discontinue if develops.
- Impaired Wound Healing: Do not give within 2 weeks of a major surgery.
- Arterial Thromboembolic Events: Exercise caution in patients with recent thromboembolic events.
- Allergic Reactions to FD&C Yellow No. 5 & No. 6: Note sensitivity more frequently seen in those with aspirin allergy (dyes only present in 1mg capsule).
- Embryo-Fetal Toxicity: Avoid during pregnancy and take precautions to avoid conception while on treatment.
- Drug Interactions: Avoid concomitant use with strong or moderate CYP3A inducers as they may decrease efficacy.
VHA Pathway & Clinical Guidelines Context- Designated as a 3rd line therapy for advanced/metastatic colorectal cancer for patients who would not qualify for anti-EGFR therapy.
- Replaced regorafenib in the VHA pathway; follows trifluridine-tipiracil.
- NCCN Guidelines Category 2A recommendation for advanced/metastatic colorectal cancer that has progressed through fluoropyrimidine, oxaliplatin, irinotecan, EGFR targeting (if appropriate), and other biomarker directed therapy.
- Considered a more tolerable 3rd line agent for mCRC due to toxicity profile limitations of regorafenib.
Exclusion Criteria- Unmanageable drug-drug interaction
- Severe renal impairment (creatinine clearance < 30 mL/min)
- Baseline proteinuria (Protein of ≥2g on urinalysis/24 hours or 24-hour urine protein of ≥ 1.0g)
- Moderate or severe hepatic impairment (total bilirubin > 1.5 times the Upper Limit of Normal, unless with Gilbert syndrome)
- Uncontrolled hypertension
- Major surgery within 2 weeks or until adequate wound healing has been achieved
- Pregnancy
- Lactating
Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (Metastatic Colorectal Cancer)- Diagnosis of metastatic colorectal cancer
- Received prior treatment with or is not a candidate to receive a fluoropyrimidine-based regimen
- Received prior treatment with or is not a candidate to receive an oxaliplatin-based regimen
- Received prior treatment with or is not a candidate to receive an irinotecan-based regimen
- If KRAS wild type, received an anti-EGFR agent (i.e. cetuximab or panitumumab)
- Received prior treatment with or is not a candidate to receive trifluridine-tipiracil with or without bevacizumab
Additional Inclusion Criteria (Reproductive Health & Contraception)- Patients of child-bearing potential and patients with partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment
- Use effective contraception during therapy and for 2 weeks after the last dose
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VONOPRAZAN TAB
VOQUEZNA
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VOQUEZNA |
2023-11-16 |
Exclusion Criteria- Concomitant therapy with rilpivirine, atazanavir, nelfinavir, and other antiretrovirals dependent on gastric pH for absorption
- Concomitant therapy with other drugs dependent on gastric pH for absorption that should be avoided with acid inhibiting drugs
- Concomitant use with St. John’s Wort, rifampin, efavirenz or other strong or moderate CYP3A4 inducers
- Concomitant proton pump inhibitor (PPI) therapy
- Inability to swallow tablets whole
- Lactation; patients should not breastfeed/provide breastmilk during treatment
Inclusion Criteria- Endoscopy-confirmed erosive esophagitis (all grades) despite treatment with ≥ 8 weeks of properly timed / administered double-dose or twice daily formulary PPI
- Prescribed and monitored by a VA / VA Community Care gastroenterologist or locally designated expert in erosive esophagitis
Additional Inclusion Criteria- Endoscopy-confirmed erosive esophagitis (all grades) despite treatment with ≥ 8 weeks of properly timed / administered double-dose or twice daily esomeprazole or rabeprazole (PPIs less affected by CYP2C19 polymorphisms)
- Unmanageable intolerance to PPI therapy
Special Populations & Counseling- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
Indications- • Healing of all grades of erosive esophagitis (EE) and relief of heartburn associated with EE in adults
- • Maintenance of healing of all grades of EE and relief of heartburn associated with EE in adults
Dosage & Administration- • Healing Phase: 20 mg once daily for 8 weeks
- • Maintenance Phase: 10 mg once daily for up to 6 months
- • Renal Impairment (Healing): ≥30 mL/min: 20 mg once daily; <30 mL/min: 10 mg once daily. Maintenance phase follows normal renal function dosing.
- • Hepatic Impairment (Healing): Child-Pugh Class A: 20 mg once daily; Classes B and C: 10 mg once daily. Maintenance phase follows normal hepatic function dosing.
Patient Selection & Place in Therapy- • Alternative treatment for healing and maintenance of healing in patients with EE confirmed by endoscopy and, if indicated, pH monitoring
- • Indicated for patients who are PPI-refractory or for whom PPIs are not tolerated
- • PPI refractoriness is defined as an inadequate endoscopic response or intolerance to ≥8-week trials of properly timed/administered double-dose or twice daily formulary PPI and properly timed/administered double-dose or twice daily esomeprazole or rabeprazole (PPIs less affected by CYP2C19 polymorphisms)
Contraindications- • Hypersensitivity
- • Rilpivirine-containing products
Warnings & Precautions- • Presence of gastric malignancy (despite symptomatic response to treatment)
- • Acute tubulointerstitial nephritis
- • Clostridioides difficile-associated diarrhea (CDAD)
- • Bone fracture
- • Severe cutaneous adverse reactions
- • Vitamin B12 / cobalamin deficiency
- • Hypomagnesemia and mineral metabolism
- • Interactions with diagnostic investigations for neuroendocrine tumors
- • Fundic gland polyps (particularly with therapy beyond 1 year); use the shortest duration of therapy clinically required
Exclusion Criteria- Concomitant therapy with rilpivirine, atazanavir, nelfinavir, and other antiretrovirals dependent on gastric pH for absorption
- Concomitant therapy with other drugs dependent on gastric pH for absorption that should be avoided with acid inhibiting drugs
- Concomitant use with St. John’s Wort, rifampin, efavirenz or other strong or moderate CYP3A4 inducers
- Concomitant proton pump inhibitor (PPI) therapy
- Inability to swallow tablets whole
- Lactation; patients should not provide breastmilk to infants during treatment
- Core Inclusion Criteria (All must be met)
- Acid reflux symptoms that started ≥ 6 months ago, are currently occurring (in the past 2 weeks), are bothersome to the patient, and frequent (occurring on ≥ 4 of 7 consecutive days) or nocturnal
- Acid reflux symptoms are related to gastroesophageal reflux disease (GERD)
- Prescribed and monitored by a VA / VA Community Care gastroenterologist or locally designated expert
- Confirmed abnormal esophageal acid exposure on 96-hour Bravo pH monitoring or 24-hour impedance pH monitoring OFF any acid suppression (i.e., symptoms not due to non-acid reflux)
- Failure of twice-daily PPI documented by acid reflux on 24-hour impedance pH monitoring ON twice-daily PPI therapy
- No esophageal erosions on endoscopy
- No spastic esophageal motility disease on esophageal manometry
- Patient has persistent, bothersome symptoms related to GERD despite ≥ 8 weeks of properly timed/administered double-dose or twice daily formulary PPI (omeprazole or pantoprazole per VA National Formulary)
- Additional Inclusion Criteria (One of the following must be selected)
- Patient has persistent, bothersome symptoms related to GERD despite ≥ 8 weeks of properly timed/administered double-dose or twice daily esomeprazole or rabeprazole (PPIs less affected by CYP2C19 polymorphisms)
- Unmanageable intolerance to PPI therapy
- Reproductive Safety & Counseling (Select if appropriate)
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
→ Full criteria details
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MIRIKIZUMAB-MRKZ INJ,SOLN
OMVOH, OMVOH PEN
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OMVOH, OMVOH PEN |
2023-11-09 |
Diagnosis & Indication- Moderate to severe, active ulcerative colitis (UC) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA / VA Community Care gastroenterologist / hepatologist or locally designated expert in UC
- Exclusion Criteria (Patient will NOT meet criteria if ANY are present)
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once infection treatment is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless potential benefits outweigh risks based on shared decision-making
- Mandatory Inclusion Criteria (ALL must be met)
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- Obtained liver panel including bilirubin
- Additional Inclusion Criteria: Biologic/Small Molecule Failure (ONE of the following must be met)
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable and vedolizumab is medically inadvisable, not tolerated, or not adequate
- Primary nonresponse, inadequate partial response, or loss of response to TNFI therapy in the presence of adequate TNFI levels
- Loss of response (with active disease confirmed by endoscopy or imaging) to infliximab / biosimilar despite TDM-based optimized dosing to address pharmacokinetic failure
- Loss of response (with active disease confirmed by endoscopy or imaging) to one TNFI in the presence of adequate TNFI levels
- Additional Inclusion Criteria: Prior Therapy Failure (ALL must be met)
- Tofacitinib or upadacitinib is medically inadvisable, not tolerated or not adequate
- Etrasimod or ozanimod is medically inadvisable, not tolerated or not adequate
- Risankizumab-rzaa is medically inadvisable, not tolerated or not adequate
- Additional Inclusion Criteria: Special Populations & Safety (Select if appropriate)
- If HBsAg-negative but anti-HBc-positive: A GI / liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
- For females who can become pregnant and patients with female partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
Monitoring & Supplemental Considerations- Routine retesting for TB, Hepatitis B, and Hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated before initiation when possible; recombinant zoster vaccine should be completed/initiated by the end of the first year, preferably when dosage is low, disease is stable, or a robust immune response is expected
- Medically inadvisable criteria for prior therapies include:
- Tofacitinib/upadacitinib: ≥1 cardiovascular risk factor; presence/history of thrombosis (PE, DVT, arterial); severe hepatic impairment; concurrent use with myelosuppressive agents; history of GI perforation; history of chronic/interstitial lung disease
- Etrasimod/ozanimod: recent MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III/IV HF; Mobitz type II second- or third-degree AV block, sick sinus syndrome, sinoatrial block (except functioning pacemakers); infections, bradyarrhythmia, AV conduction delays, liver disease, macular edema, uncontrolled hypertension; severe untreated sleep apnea (ozanimod); concomitant MAOI (ozanimod)
- Ustekinumab: history of noninfectious pneumonia (interstitial, eosinophilic, cryptogenic organizing)
- TNFIs: heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent/serious infections
- Vedolizumab: liver disease and history of progressive multifocal leukoencephalopathy (PML)
- For HBsAg-negative but anti-HBc-positive patients, anti-HBs titers do not guarantee protection against HBV reactivation; management depends on the patient’s risk of HBV reactivation
Indication & Patient Population- Treatment of moderately to severely active ulcerative colitis (UC) in adults
- Patients with an inadequate response, intolerance, or medical inadvisability to conventional, biologic, or tofacitinib therapy
Pre-treatment Evaluations & Immunizations- Evaluate for tuberculosis (TB) before initiating therapy
- Obtain baseline liver enzymes and bilirubin levels
- Administer all age-appropriate vaccinations according to current immunization guidelines
Dosage Regimen- Induction Therapy: 300 mg by IV infusion at Weeks 0, 4, and 8
- Maintenance Therapy: 200 mg by SC injection (two consecutive injections of 100-mg each) at Week 12, then every 4 weeks thereafter
- No dosage modifications required due to patient factors (increases in body mass index or increases in clearance with increased body weight)
Contraindications & Safety Considerations- Contraindicated: History of serious hypersensitivity reaction to mirikizumab-mrkz or excipients
- Warnings/Precautions: Infections, TB, hepatotoxicity
- Immunization precautions: Avoid live vaccines; no data on response to live or non-live vaccines
Place in Therapy & Formulary Criteria- FDA-approved in 2023 with no prerequisite therapy required
- VA CFU Place in Therapy: TBD
- Projected VA Place in Therapy: Alternative mechanism of action for moderate to severe, active UC; place relative to other biologic and targeted synthetic immunomodulators is uncertain
Exclusion Criteria- Uncontrolled, active, severe infection (including evidence of C. difficile and undrained abscess) [may start/restart once infection is controlled]
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis [may initiate after starting antiviral prophylaxis]
- Untreated HIV infection [treated, well-controlled, asymptomatic HIV-positive patients may be treated]
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless potential benefits outweigh risks based on shared decision-making
Core Inclusion Criteria- Current or prior moderate to severe Crohn’s disease (CD) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA / VA Community Care gastroenterologist or locally designated expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening [may initiate while waiting for test results]
- Obtained liver panel including bilirubin
- Vedolizumab or upadacitinib was tried (unless medically inadvisable) and not tolerated, not adequate, or lost response
- Risankizumab-rzaa was tried (unless medically inadvisable) and not tolerated, not adequate, or lost response
Therapy History & Sequencing Requirements- ONE of the following must be met:
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable [Infliximab/biosimilar and adalimumab are preferred TNFIs in CD]
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI therapy in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to infliximab/biosimilar and another TNFI for CD despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
- Required sequencing: First-line (1L) must be infliximab or adalimumab; Second/Third-line (2L/3L) must include vedolizumab, upadacitinib, or risankizumab-rzaa (with one drug being risankizumab-rzaa); Fourth-line (4L) is mirikizumab-mrkz or ustekinumab
Special Populations & Consultation Requirements- If HBsAg-negative but anti-HBc-positive: Consultation with a GI/liver or infectious diseases expert required for advice on antiviral prophylaxis vs. preemptive monitoring for HBV reactivation
- Females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception
Additional Clinical Considerations- Routine retesting for TB or hepatitis C is not required for prescription renewals; retesting should be considered for high-risk patients
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed or initiated by the end of the first year of treatment
- Criteria apply only to new starts; stable patients on maintenance therapy should not be switched for nonmedical reasons
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NADOFARAGENE FIRADENOVEC-VNCG INJ,SUSP
ADSTILADRIN
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ADSTILADRIN |
2023-10-11 |
Exclusion Criteria- Hypersensitivity to interferon alpha
- Current or previous evidence if muscle-invasive or metastatic bladder cancer
- Upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra
- Pregnancy in patients of reproductive potential
Inclusion Criteria- Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC)
- Carcinoma in situ (CIS) with or without papillary tumors (Ta or T1 high-grade tumors)
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care urology provider or in consultation with a VA urology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care have been discussed and documented
Contraception & Counseling Requirements- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 6 months after stopping treatment
BCG-Unresponsive Definition- Received 2 courses of BCG within 12 months (5 of 6 induction instillations and at least 2 of 3 maintenance doses OR at least 2 of 6 instillations of a second induction when maintenance not given)
Indication & Patient Population- • Treatment of patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-Muscle Invasive Bladder Cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.
- • Applicable to patients with CIS ± Ta/T1 disease.
Administration & Dosing Requirements- • Intravesical administration via bladder instillation.
- • Dosing interval: Every 3 months.
- • Adequate prior BCG therapy required: Administration of at least five of six doses of induction course plus either at least two of three doses of maintenance or at least two of six doses of a second induction course.
- • Pre-treatment with an anticholinergic agent is recommended prior to each instillation to minimize irritative symptoms.
Safety, Contraindications & Precautions- • Contraindicated in patients with prior hypersensitivity to interferon alpha or any component of the product.
- • No boxed warnings.
- • Monitor for increased glucose (Grade 3 or 4 occurred in 6% of study patients).
- • Advise patients regarding reproductive potential, risk to fetus, and breastfeeding.
- • Verify pregnancy status prior to use.
Storage & Handling Requirements- • Must be stored in a freezer at ≤-60°C.
- • May be stored for up to 3 months at -25°C to -15°C without exceeding carton expiration date.
- • Once removed from freezer, store for 24 hours at room temperature or refrigerated.
- • Protect vials from light.
Monitoring & Follow-up- • Mandatory bladder biopsy at 1 year.
- • Clinical response assessment includes complete response in CIS cohort and high-grade recurrence-free survival.
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VEDOLIZUMAB INJ,SOLN
ENTYVIO PEN
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ENTYVIO PEN |
2023-10-05 |
Inclusion Criteria- Had a clinical response after Week 6 following vedolizumab intravenous induction doses at Weeks 0 and 2
- OR is receiving intravenous doses of vedolizumab to maintain clinical remission
Clinical Response Definitions- Ulcerative Colitis: Reduction in total Mayo score of ≥ 3 points and ≥ 30% from baseline with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1.
- Crohn's Disease: ≥ 70-point decrease in Crohn's Disease Activity Index (CDAI) score from baseline.
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MOMELOTINIB TAB
OJJAARA
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OJJAARA |
2023-09-28 |
Exclusion Criteria- Uncontrolled active infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- Untreated HIV infection
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
- Unmanageable drug interaction
- Inability to swallow tablets whole
- Pregnancy unless expected benefits to the mother outweigh potential risks to the fetus
- Lactating
General Inclusion Criteria (All Required)- Prescribed and monitored by a VA / VA Community Care hematologist / oncologist
- Goals of care and role of Palliative Care consult have been discussed and documented
- Symptomatic intermediate or high-risk myelofibrosis (primary or secondary post-polycythemia vera or post-essential thrombocythemia)
- Currently no plan for allogeneic hematopoietic stem cell transplant
- Splenomegaly by palpation (≥ 5 cm below the costal margin) or imaging
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Completed hepatitis B screening (HBsAg, anti-HBc, and anti-HBs)
- Current or past completion of hepatitis C screening
Clinical Indication Pathways (One Required)- Myelofibrosis-associated anemia (hemoglobin < 10 g/dL) with symptomatic splenomegaly or constitutional symptoms, where primary reason for treatment is anemia
- Myelofibrosis-associated anemia (hemoglobin < 10 g/dL) without symptomatic splenomegaly or constitutional symptoms, following a prior trial of one non-Janus kinase inhibitor (non-JAKI) treatment
- Splenomegaly or symptoms with platelet count < 50 × 10^9/L as primary reason for treatment, following a prior trial of pacritinib unless medically inadvisable
- Splenomegaly or symptoms with platelet count ≥ 50 × 10^9/L, following a prior trial of ruxolitinib unless medically inadvisable (e.g., pre-existing severe anemia [hemoglobin < 8 g/dL] or thrombocytopenia with platelets < 50 × 10^9/L)
- Persistent grade 3 anemia (hemoglobin < 8.0 g/dL) despite ruxolitinib dosage reductions
Special Circumstances & Management Conditions- HBsAg-negative but anti-HBc-positive: Requires consultation with GI/liver or infectious diseases expert for antiviral prophylaxis vs preemptive monitoring for HBV reactivation
- Concomitant kinase inhibitor use: Must be discontinued per its prescribing information
- Uncontrolled acute or chronic liver disease: Treatment delayed until causes investigated and treated
- Severe liver impairment (Child-Pugh Class C): Initial dosage reduced to 150 mg once daily
- Concomitant BCRP substrate use: Dose decreased per prescribing information (e.g., rosuvastatin initially 5 mg once daily, max 10 mg daily)
- Patients who can become pregnant or have partners who can become pregnant: Counseling on risks vs benefits and use of effective contraception during therapy and for at least 1 week after last dose
- Patients who can lactate: Advised not to breastfeed during treatment and for at least 1 week after last dose
Laboratory, Screening, & Supportive Requirements- Obtained pretreatment complete blood count and hepatic panel
- Hemoglobin < 10 g/dL threshold applies only after coexisting causes of anemia (iron, folate, or vitamin B12 deficiency; bleeding; hemolysis) are ruled out and treated
- Antiviral prophylaxis for HBV must utilize agents with a high genetic barrier to resistance (entecavir or tenofovir)
- Non-JAKI treatments include: androgens, danazol, prednisone, thalidomide, lenalidomide, erythropoietin stimulating agents
Clinical Indication & Population- Treatment of intermediate or high-risk myelofibrosis (MF), including primary MF (PMF) or secondary MF (SMF; post polycythemia vera and post-essential thrombocythemia), in adults with anemia.
- VHA use is restricted to alloHCT-ineligible adults with INT- or high-risk primary or secondary MF.
Specific Clinical Scenarios & Prior Therapy Requirements- Anemia as primary treatment reason: MF-related anemia (Hg < 10 g/dL) with symptomatic splenomegaly or constitutional symptoms, where the primary reason for treatment is anemia.
- Anemia without splenomegaly/constitutional symptoms: Myelofibrosis-related anemia (hemoglobin < 10 g/dL) with neither symptomatic splenomegaly nor constitutional symptoms, requiring a prior trial of one non-Janus kinase inhibitor (non-JAKI) treatment for myelofibrosis-related anemia.
- Thrombocytopenia as primary treatment reason: Splenomegaly or symptoms where the primary reason for treatment is platelet count < 50 × 10^9/L, requiring a prior trial of pacritinib unless medically inadvisable.
- Post-Ruxolitinib use (Platelets ≥ 50 × 10^9/L): Splenomegaly or symptoms with platelet count ≥ 50 × 10^9/L, requiring a prior trial of ruxolitinib unless medically inadvisable (e.g., due to pre-existing severe anemia [hemoglobin < 8 g/dL] or thrombocytopenia with platelets < 50 × 10^9/L).
- Refractory Anemia: Persistent grade 3 anemia (hemoglobin < 8.0 g/dL) despite ruxolitinib dosage reductions.
Dosage & Administration Criteria- Standard regimen: 200 mg PO once daily with or without food.
- Severe hepatic impairment (Child-Pugh Class C): Reduce starting dose to 150 mg PO once daily.
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MOTIXAFORTIDE INJ,LYPHL
APHEXDA
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APHEXDA |
2023-09-28 |
Indication & Patient Population- Indicated for use in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.
Dosing & Administration- Dose: 1.25 mg/kg (actual wgt).
- Route: Slow subcutaneous injection.
- Timing: Administered 10–14 hours prior to initiation of the first apheresis.
- A second dose may be administered 10–14 hours prior to a third apheresis if needed.
Contraindications & Safety Monitoring- Contraindicated in patients with a history of hypersensitivity to motixafortide.
- Premedicate with H1-, H2-blocker and leukotriene inhibitor; administer in a staffed and equipped setting where immediate treatment can be provided for anaphylactic shock and hypersensitivity reactions.
- Premedication with acetaminophen is recommended to manage injection site reactions.
- Monitor WBC counts due to potential for leukocytosis.
- Advise patients of embryo-fetal toxicity risk; require use of effective contraception.
VHA-Specific Use Cases- Consider for patients with hypersensitivity or allergy to plerixafor.
- Consider for patients experiencing insufficient cell mobilization utilizing filgrastim and plerixafor.
- Should be available in HSCT settings in anticipation of inadequate PBSC collections.
Exclusion Criteria- Leukemia diagnosis
- Pregnancy
- Lactating
Inclusion Criteria- Care provided by a VA/VA Community Care hematology or oncology provider
- Plan for autologous transplantation for multiple myeloma
Additional Inclusion Criteria (One of the following must be met)- Allergy to plerixafor
- Prior mobilization attempt was insufficient following filgrastim and plerixafor
Reproductive Health & Pregnancy Management- For patients who can become pregnant: Pregnancy must be excluded prior to receiving motixafortide
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 8 days after stopping treatment
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LISDEXAMFETAMINE CAP,ORAL
LISDEXAMFETAMINE DIMESYLATE, VYVANSE
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LISDEXAMFETAMINE DIMESYLATE, VYVANSE |
2023-09-07 |
Continuity of Care Inclusion Criteria- Veteran is transitioning care from the Department of Defense to VHA
- Medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making
- Medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making
Non-Continuity of Care Exclusion Criteria- Use with or within 2 weeks of a monoamine oxidase inhibitor (MAOI)
Non-Continuity of Care Inclusion Criteria- Diagnosis of Binge Eating Disorder (BED), did not respond to, is unable to tolerate an adequate trial of, or has a contraindication to topiramate AND a formulary selective serotonin reuptake inhibitor (SSRI)
- Diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), did not respond to, is unable to tolerate an adequate trial of, or has a contraindication to methylphenidate AND a formulary amphetamine product
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ALBUTEROL/ BUDESONIDE INHL,ORAL
AIRSUPRA
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AIRSUPRA |
2023-08-31 |
Exclusion Criteria- Diagnosis of chronic obstructive pulmonary disease (COPD) alone
- Patients with asthma/COPD overlap should be adjudicated locally
Inclusion Criteria- Initial prescription is by or in consult with a VA/VA Community Care pulmonologist, allergist/immunologist, or designated expert
- Diagnosis of asthma
- Receiving medium- to high-dose inhaled corticosteroids (or maximally tolerated dose) AND at least 3 months of a long-acting beta-agonist and/or other controller medication such as tiotropium if appropriate
- One or more severe asthma exacerbations in the prior 12 months
- Inadequate symptom control (e.g., short-acting beta-agonist use more than 2 days per week, nighttime awakening due to asthma more than 1 time per week, limitation with normal activity, Asthma Control Test less than 19)
- Adherent to asthma medications as evidence by a review of prescription refill history during the last 12 months
- Patient has demonstrated correct inhaler technique (documented in chart)
Clinical Definitions & Considerations- Severe asthma exacerbation is defined as requiring systemic corticosteroids for at least 3 days, emergency room or urgent care visit during which systemic corticosteroids were used, or hospitalization due to asthma exacerbation
- In appropriate patients with asthma, consider a trial of maintenance and reliever therapy (SMART) with ICS-formoterol before attempting albuterol/budesonide; SMART should only be prescribed by providers with experience using this therapy
- Poor technique frequently is a cause of poor results in asthma
Indication & Patient Population- Indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma.
- Approved for use in patients 18 years of age and older.
Dosage & Administration- Dosage form: Pressurized metered dose inhalation aerosol delivering albuterol 90 mcg and budesonide 80 mcg per actuation (120 actuations per canister).
- Recommended dosage: 180 mcg/160 mcg administered as 2 actuations by oral inhalation as needed for asthma symptoms.
- Maximum frequency: Do not take more than 6 doses (12 inhalations) in a 24-hour period.
Clinical Context & Treatment Restrictions- Use should be reserved as an option for uncontrolled patients with asthma while receiving optimized therapy.
- Clinical trial population characteristics informing use: uncontrolled moderate-to-severe asthma; ≥1 severe asthma exacerbation in the previous 12 months; FEV1 40% to <90% of predicted normal; FEV1 reversibility of at least 12% to albuterol; ACQ-5 ≥1.5; medium-high dose ICS or low-high dose ICS/LABA for at least 3 months with or without other controller agents.
- Exclusions from clinical evaluation: COPD or other notable lung disease; use of systemic steroids within 3 months of screening; use of biologic drugs within 3 months or for a duration of 5 half-lives before screening.
Safety & Usage Precautions- If symptoms continue after using albuterol/budesonide, this may be a marker of destabilization of asthma and requires reevaluation of treatment.
- Excessive use may be fatal; do not exceed the maximum recommended dosage.
- Potential for misuse as maintenance therapy or in patients with COPD.
- Potential for error or confusion in patients familiar with using ICS or ICS/LABA for maintenance and albuterol as needed for symptoms.
Formulary & Therapeutic Position- National and international guidelines position the use of ICS/SABA (either fixed combination or separately one after the other) as a treatment option.
- Alternative formulary options include albuterol as needed, or albuterol combined with mometasone or ciclesonide used sequentially as needed (reserved for patients who clearly understand how to use).
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ELRANATAMAB-BCMM INJ,SOLN
ELREXFIO
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ELREXFIO |
2023-08-24 |
Indications- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
Exclusion Criteria- Known hypersensitivity to elranatamab or its excipients (e.g., polysorbate 80)
- Active viral, bacterial, or uncontrolled systemic fungal infection
- Known active central nervous system disease or signs of meningeal involvement
- Pregnancy
- Lactating
Inclusion Criteria- Relapsed or refractory multiple myeloma in a patient who has received at least four prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody
- Oncologic care provided by a VA or VA Community Care oncology provider certified with the ELREXFIO REMS Program
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- Hospitalization required due to risk of Cytokine Release Syndrome: 48 hours after step-up dose #1 and 24 hours after step-up dose #2
Additional Inclusion Criteria- For patients who can become pregnant or have partners who can become pregnant: counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for four months after stopping treatment
Indication & Patient Population- Adults with relapsed or refractory multiple myeloma
- Accelerated approval contingent upon clinical benefit verified in a confirmatory trial
Prior Therapy & Refractoriness Requirements- Received at least four prior lines of therapy (LOT)
- Prior regimens must include a proteasome inhibitor, an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody
- Refractory to at least one proteasome inhibitor, at least one IMiD, and at least one anti-CD38 monoclonal antibody
- May be used in patients with prior BCMA-directed therapy exposure (noted to have lower ORR in this population)
Dosing & Administration- Injectable for subcutaneous administration
- Step-up dosing: Day 1: 12 mg SQ; Day 4: 32 mg SQ; Day 8: 76 mg SQ (first full dose)
- Administer weekly through week 24 following step-up
- After 6 cycles, if partial response or better at 6 months and maintained for > 2 months, switch to dosing every 2 weeks until disease progression or unacceptable toxicity
Monitoring & Safety Requirements- Hospitalization recommended for the first two doses (step-up phase)
- REMS program required
- Monitor for cytokine release syndrome (CRS) and neurotoxicity including ICANS
- Manage risks of infections, neutropenia, hepatotoxicity, and embryo-fetal toxicity
Formulary & Place in Therapy- NCCN: Preferred bispecific antibody after > 4 LOT (category 2A)
- VA Multiple Myeloma pathway: Listed as preferred for RRMM s/p > 4 LOT
- Provides an option for patients with limited access to CAR T-cell therapy due to specialized centers or manufacturing issues
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NALMEFENE SOLN,NASAL
OPVEE
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OPVEE |
2023-08-24 |
Indications- Emergency treatment of known or suspected overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older.
Contraindications- Known hypersensitivity to nalmefene or excipients.
Warnings & Precautions- Risk of recurrent respiratory or central nervous system depression, especially in poly-drug overdose settings.
- Risk of limited efficacy with partial agonists or mixed agonists/antagonists (e.g., buprenorphine, pentazocine).
- Risk of severe, precipitated opioid withdrawal.
- Risk of overdose from attempts by an OPVEE-rescued patient to overcome the blockade.
Adverse Effects- Nasal discomfort, dizziness, fatigue, headache, nausea, hot flush, anxiety, and vomiting.
- Adverse effects are common and expected with abrupt reversal of opioid agonism.
Dosage, Administration & Patient Population- Single-use nasal administration device containing 2.7 mg nalmefene (3 mg nalmefene HCl) in 0.1 mL total volume; two dose units per package.
- Formulated with dodecylmaltoside (DDM), an absorption enhancer.
- Intended for bystander administration.
Clinical Limitations & Place in Therapy- Based on Phase I pharmacokinetic and pharmacodynamic studies only.
- Claims of higher potency than naloxone for reversing illicit fentanyl and fentanyl analogues are overstated without real-world experience.
- Post-marketing published study found no difference in recovery rates between nalmefene and naloxone in an emergency department setting for suspected opioid overdose.
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TALQUETAMAB-TGVS INJ,SOLN
TALVEY
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TALVEY |
2023-08-24 |
Indications- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
Exclusion Criteria- Known hypersensitivity to talquetamab or its excipients (e.g. polysorbate 20)
- Active viral, bacterial, or uncontrolled systemic fungal infection
- Known active central nervous system disease or signs of meningeal involvement
- Pregnancy
- Lactating
Indication & Treatment History- Relapsed or refractory multiple myeloma in a patient who has received at least four prior lines of therapy including a proteasome inhibitor, and immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Care Setting & Provider Requirements- Care for the oncologic condition provided by VA or VA Community Care oncology provider certified with the TALVEY REMS Program.
Performance Status & Supportive Care- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- Goals of care and role of Palliative Care consult have been discussed and documented
Safety Monitoring & Hospitalization- Due to risk of Cytokine Release Syndrome, patients should be hospitalized for 48 hours after all step-up doses in either the weekly or biweekly dosing schedules.
Reproductive Health & Counseling- For patients who can become pregnant and patients with partners who can become pregnant: counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for three months after stopping treatment.
Nutritional Management- For patients with poor nutritional intake or body mass index (BMI) < 18 (underweight): consult nutritionist/dietician.
Indication & Population- Adults with relapsed or refractory multiple myeloma
- ECOG PS 0-2
- Exclusions: CVA or seizure in prior 6 months, CNS or meningeal involvement, active or history of autoimmune disease (except vitiligo, resolved childhood atopic dermatitis, resolved Graves Disease)
Prior Therapy Requirements- Received at least four prior lines of therapy (LOT)
- Prior therapies must include a proteasome inhibitor, an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody
- Continued approval contingent upon clinical benefit verified in a confirmatory trial
Dosage & Administration- Injectable for subcutaneous administration
- Step-up dosing: D1: 0.01mg/kg SQ, D4: 0.06mg/kg SQ, D7: 0.4mg/kg (first full dose, then weekly)
- Alternate step-up schedule: D1: 0.01mg/kg SQ, D4: 0.06mg/kg SQ, D7: 0.4mg/kg SQ, D10: 0.8mg/kg SQ (first full dose, every 2 wks)
- SubQ dosing; hospitalization recommended x2
Monitoring & Safety Management- REMS program required
- Monitor for cytokine release syndrome (CRS) and neurotoxicity including ICANS
- Monitor for oral toxicity, weight loss, infection, cytopenia, skin toxicity, and hepatotoxicity
- Advise effective contraception during and 3 months post-dose due to embryo-fetal toxicity
VHA-Specific Considerations- First-in-class, off-the-shelf bispecific antibody directed against GPRC5D
- Provides an option for patients with limited access to CAR T-cell therapy due to specialized centers and/or manufacturing issues
- May be used as bridging therapy to CAR T-cell therapy due to quick time to response
- Caution use in patients with poor nutritional intake and/or BMI < 18; consult with nutrition services
Drug Interactions- May increase exposure of CYP substrates (Risk C: monitor)
- Avoid denosumab as immunosuppressive effect may be enhanced (Risk D: modify therapy)
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DURLOBACTAM/ SULBACTAM INJ,LYPHL
DURLOBACTAM (XACDURO), SULBACTAM (XACDURO), XACDURO
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DURLOBACTAM (XACDURO), SULBACTAM (XACDURO), XACDURO |
2023-08-17 |
Indication & Patient Population- • Indicated for patients 18 years of age and older
- • Indicated for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP)
- • Must be caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex
Dosing & Renal Adjustments- • Recommended dose: 1g sulbactam and 1g durlobactam administered intravenously every 6 hours over a 3-hour infusion
- • Dose adjustments required for estimated creatinine clearance (CrCl) < 45 mL/min or > 130 mL/min
- • CrCl > 130 mL/min: Decrease dosing interval to every 4 hours
- • CrCl 30–44 mL/min: Increase dosing interval to every 8 hours
- • CrCl 15–29 mL/min: Increase dosing interval to every 12 hours
- • CrCl < 15 mL/min: Administer every 12 hours for 3 doses, then switch to every 24 hours
Susceptibility & Microbiological Criteria- • Susceptibility testing must be used to guide treatment, particularly in strains resistant to sulbactam alone
- • Not active against Acinetobacter baumannii producing Ambler class B metallo-beta-lactamases or possessing PBP3 target site alterations
- • Approximately 3–6% of isolates may be nonsusceptible based on global surveys and clinical trial screening
Contraindications & Safety Monitoring- • Contraindicated in patients with known hypersensitivity to the components of sulbactam/durlobactam
- • Monitor for hypersensitivity reactions and C. difficile associated diarrhea
Place in Therapy & Usage Guidelines- • Likely most beneficial when the isolate is not susceptible to sulbactam AND no other active agent can be used in combination due to resistance or tolerability concerns, OR in patients failing ampicillin/sulbactam-based combination therapy
- • Infectious Diseases experts should be involved in prescribing decisions to prevent overuse and development of resistance
- • Limited safety database currently exists; hypersensitivity reactions were observed in clinical trials
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LOTILANER SOLN,OPH
XDEMVY
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XDEMVY |
2023-08-03 |
Indication- Treatment of Demodex blepharitis
Patient Population & Clinical Presentation- Patients with documented Demodex spp infection
- Patients with pathognomonic findings (collarettes)
- Patients with evidence of ocular rosacea (may benefit from earlier treatment to avoid topical steroids over a longer term)
- Patients unable to reliably use conservative measures (e.g., homeless patients)
Prerequisites & Prior Therapy Requirements- Use after other measures for blepharitis have been ineffective
- Observation of mites or evidence of persistent symptomatic blepharitis (scrub/debris in tear film, blocked meibomian glands, or eroded lid margins) that persists after failure of conservative measures
Prescriber Restrictions- Restricted to eye specialists (optometrists and ophthalmologists)
Dosing & Administration- One drop in each eye twice daily for 6 weeks
- Contact lenses should be removed prior to instillation and may be reinserted 15 minutes after administration
Safety & Contraindications- No boxed warnings or contraindications
- Risk of contamination: do not allow tip of container to contact eye, fingers, or other surfaces
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QUIZARTINIB TAB
VANFLYTA
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VANFLYTA |
2023-08-03 |
Indication & Population- Adults with newly diagnosed acute myeloid leukemia (AML) that is FLT3-ITD–positive as detected by an FDA-approved test
- Used in combination with standard cytarabine and anthracycline induction, cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy
- Not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (alloHCT) due to lack of demonstrated overall survival improvement
Dosing & Administration- Induction (7 + 3 regimen): 35.4 mg PO once daily on Days 8–21 of a 28-day cycle (Days 6–19 for 5 + 2 regimen)
- Consolidation: 35.4 mg PO once daily on Days 6–19 for up to 4 cycles
- Maintenance: 26.5 mg PO once daily on Days 1–14 of first cycle if QTcF ≤ 450 ms; increase to 53 mg once daily on Day 15 if QTcF ≤ 450 ms; maintain 26.5 mg once daily if QTcF > 500 ms during induction or consolidation
- Continue maintenance regimen without breaks between cycles for up to 36 cycles
- Available as 17.7 mg and 26.5 mg tablets
Contraindications- Severe hypokalemia (< 3 mmol/L)
- Severe hypomagnesemia (grade 3 < 0.4 mmol/L)
- Long QT syndrome (LQTS)
- History of ventricular arrhythmias or torsade de pointes
Monitoring & Safety Requirements- Monitor for and correct hypokalemia and hypomagnesemia
- Perform ECGs at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter
- Available exclusively through the VANFLYTA REMS restricted distribution program due to serious risks of QT prolongation, torsade de pointes, and cardiac arrest
Drug Interactions- Strong CYP3A inhibitors: Reduce quizartinib dosage
- Strong or moderate CYP3A inducers: Avoid co-use
- QT interval prolonging drugs: Monitor patients more frequently with ECG
Special Populations- Pregnancy: Can cause embryofetal harm; advise patients who can become pregnant of potential risk to a fetus
- Lactation: Avoid breastfeeding during treatment and for one month after the last dose
VA Formulary Criteria- Indicated for newly diagnosed FLT3-ITD–positive AML patients with an absolute contraindication to midostaurin, used in combination with standard chemotherapy for induction/consolidation and as maintenance monotherapy following consolidation without alloHCT
Diagnosis & Clinical Indication- Newly diagnosed acute myeloid leukemia (AML) positive for FLT3 internal tandem duplication (ITD) mutation
- Has an absolute contraindication or unmanageable intolerance to midostaurin
Treatment Regimen & Dosing Considerations- Use in combination with standard cytarabine and anthracycline induction and cytarabine consolidation regimens
- Use as maintenance monotherapy following consolidation chemotherapy
- When used concomitantly with strong CYP3A inhibitors: Dose of quizartinib is reduced as per prescribing information
Patient Selection & Performance Status- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Goals of care and role of Palliative Care consult have been discussed and documented
Safety, Monitoring & Exclusion Criteria- Uncorrected severe hypokalemia (< 3 mmol/L) or severe hypomagnesemia (< 0.4 mmol/L)
- History of ventricular arrhythmias or torsade de pointes
- Prolonged QTc interval (at baseline or during monitoring as recommended in prescribing information), including history of long QT syndrome
- Use for maintenance monotherapy following allogeneic hematopoietic stem cell transplantation
- Concomitant strong or moderate CYP3A inducers and unmanageable drug-drug interactions
- Inability to swallow the tablets whole
Special Populations & Counseling Requirements- Pregnant patients: Advised of the potential risk to a fetus
- Patients who can become pregnant: Pregnancy status verified within 7 days pre-treatment; counseled on potential risks vs benefits and use of effective contraception during treatment and for up to 7 months after the last dose
- Males with female partners who can become pregnant: Counseled on potential risks vs benefits and use of effective contraception during treatment and for up to 4 months after the last dose
- Lactating patients: Advised not to share breastmilk with infant during treatment and for 1 month after the last dose
Programmatic & Administrative Requirements- Provider and pharmacy must be certified in the VANFLYTA Risk Evaluation and Mitigation Strategy (REMS) restricted access program
- Prescribed and monitored by a VA or VA Community Care hematologist/oncologist
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ALPELISIB TAB,ORAL
PIQRAY
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PIQRAY |
2023-07-24 |
Indication & Patient Population- • Advanced or metastatic, HR+, HER2- PIK3CA-mutated breast cancer
- • Postmenopausal women and men who are HR+, HER2-, PIK3CA-mutation+
- • Patients who have progressed on AI-based therapy (with or without CDK4/6i)
- • Excluded populations: inflammatory br ca, DM type 1 or uncontrolled type 2, pneumonitis
Administration & Dosage- • Oral tablets to be taken with food
- • Administered in combination with fulvestrant 500mg IM injection
Monitoring & Precautions- • Close monitoring essential for potential cutaneous reactions, severe diarrhea/colitis, pneumonitis and hyperglycemia
- • Caution and close monitoring required in patients with diabetes
- • Severe diarrhea may result in dehydration, AKI
- • Monitor for adverse reactions > 20%: ↑glucose, ↑SCr, diarrhea, rash, ↑GGT, ↑ALT, ↑lipase, ↓lymphocytes, nausea, fatigue, ↓hgb, ↓appetite, stomatitis, vomiting, ↓calcium, ↓glucose, aPTT prolonged
Contraindications & Warnings- • Severe hypersensitivity to alpelisib or any component of the formulation
- • Warnings/Precautions include: Dermatologic, GI and pulmonary toxicity, hyperglycemia, hypersensitivity
- • No boxed warnings
Drug Interactions- • Avoid CYP3A4 inducers, BRCP inhibitors
- • Closely monitor with CYP2C9 substrates
Formulary & Restrictions- • PA-F for Alpelisib + fulvestrant and Fulvestrant alone
- • Restrict to H/O for Fulvestrant alone
Exclusion Criteria- Hypersensitivity to alpelisib or any of its components
Inclusion Criteria- Men or postmenopausal women with advanced or metastatic breast cancer
- Hormone receptor (HR)-positive, HER2-negative breast cancer
- Activating PIK3CA-mutation positive as detected by an approved test
- Progressive disease on or after an endocrine-based regimen
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0 – 1
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (Select if applicable)- For patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after end
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RSV VACCINE INJ,LYPHL
ABRYSVO, AREXVY, AREXVY ADJUVANT COMPONENT, AREXVY ANTIGEN COMPONENT
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ABRYSVO, AREXVY, AREXVY ADJUVANT COMPONENT, AREXVY ANTIGEN COMPONENT |
2023-07-20 |
Indication & Eligibility- Prevention of lower respiratory tract disease caused by respiratory syncytial virus in individuals 60 years of age and older
- Indicated for immunocompetent patients aged ≥60 years; patients with pre-existing chronic conditions may be included if medically stable
Dosing & Administration- Single intramuscular dose (0.5 mL) of lyophilized antigen with adjuvant suspension
- Revaccination at 12 months does not confer additional protection over a single dose
Contraindications & Warnings/Precautions- Contraindicated in patients with a history of severe allergic reaction to AREXVY or any component of the product
- Appropriate treatment must be available for management of possible anaphylactic reactions or syncope
- Immunocompromised persons may have a diminished response
Safety & Adverse Reactions- Solicited adverse events include injection site pain, fatigue, myalgia, headache, and arthralgia
- Severe reactogenicity events (Grade 3) occurred in 3.8% of vaccine recipients vs 0.9% of placebo
- Inflammatory neurologic events reported (1 case of Guillain-Barre syndrome, 2 cases of acute disseminated encephalomyelitis/transverse myelitis)
- Numeric imbalance in atrial fibrillation within 30 days postvaccination observed
- Trend towards higher reactogenicity when co-administered with high-dose or adjuvanted influenza vaccine
Clinical Guidance & Recommendations- FDA approved for ≥60 years of age as a single dose
- ACIP recommends adults ≥60 years may receive a single dose based on shared clinical decision making (SDCM) between patient and provider
- Co-administration with other adult vaccines during the same visit is acceptable, though data is limited to influenza vaccines; co-administration with other adjuvanted or reactogenic vaccines may increase local or systemic reactogenicity
- Efficacy in highest-risk populations (immunocompromised, frail, multiple comorbidities) and benefit on hospitalization or death remain unknown; more post-marketing surveillance data is needed
Risk Factors for Severe Disease & Benefit Considerations- Decision to vaccinate should consider individual risk for disease, characteristics/values/preferences, provider clinical discretion, and vaccine characteristics
- Those most likely to benefit include individuals with chronic medical conditions: chronic lung disease (asthma or COPD), cardiovascular disease (CHF or coronary artery disease), moderate/severe immunocompromise, diabetes mellitus, neurologic or neuromuscular condition, kidney or liver disease, hematologic disorders
- Additional risk factors include residence in a nursing home or other long-term care facility, frailty, advanced age, and other underlying conditions determined by a healthcare provider to increase severe RSV risk
Indication & Target Population- Prevention of lower respiratory tract disease caused by respiratory syncytial virus in individuals 60 years of age and older.
- ACIP recommends a single dose for adults ≥60 years based on shared clinical decision making.
Eligibility & Exclusions- Target population: Immunocompetent patients (healthy or with stable chronic conditions) aged ≥60 years.
- Trial exclusions: End stage renal disease, unstable cardiac disease, and conditions associated with risk of prolonged bleeding.
- Efficacy in highest risk populations (multiple comorbidities, immunocompromised, frail) is unknown as they were not included or underrepresented in clinical trials.
Contraindications & Warnings/Precautions- Contraindicated in patients with a history of severe allergic reaction to ABRYSVO or any component of the product.
- Requires prevention and management of allergic reactions and syncope following administration.
- Immunocompromised individuals may have a diminished immune response.
Dosing & Administration- Single intramuscular injection (0.5 mL) of lyophilized antigen reconstituted with Sterile Water Diluent.
Co-administration Guidelines- Co-administration with influenza vaccine is acceptable and met non-inferiority criteria, though titers were somewhat lower.
- Co-administration with other adult vaccines during the same visit is acceptable, but data is only available for flu vaccines; administering with other vaccines may increase local or systemic reactogenicity.
Clinical Decision-Making & Risk Assessment- Vaccination decision should be guided by shared clinical decision making between patient and provider.
- Consideration of individual risk for severe RSV disease, characteristics/values/preferences, provider clinical discretion, and vaccine characteristics.
- Factors increasing likelihood of benefit include: chronic lung disease (asthma or COPD), cardiovascular disease (CHF or coronary artery disease), moderate/severe immunocompromise, diabetes mellitus, neurologic or neuromuscular condition, kidney or liver disease, hematologic disorders, residence in a nursing home or long-term care facility, frailty, advanced age, and other underlying conditions determined by a healthcare provider to increase severe RSV risk.
- Post-marketing surveillance is recommended for potential immune-mediated diseases (e.g., Guillain-Barre syndrome) and atrial fibrillation.
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RITLECITINIB CAP,ORAL
LITFULO
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LITFULO |
2023-07-13 |
Indication & Patient Selection- Treatment of severe alopecia areata (AA) in adults and adolescents 12 years of age and older.
Contraindications & Limitations of Use- Known hypersensitivity to ritlecitinib or its excipients.
- Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants.
Pretreatment Evaluations & Immunizations- Tuberculosis screening; initiate preventive therapy for latent tuberculosis.
- Viral hepatitis screening (hepatitis B and C viruses).
- Lymphocyte and platelet counts; do not initiate treatment if absolute lymphocyte count is < 500/mm3 or platelet count is < 100,000/mm3.
- Liver function tests; do not recommend treatment in patients with severe (Child-Pugh C) hepatic impairment.
- Update immunizations according to current guidelines.
Dosing Regimen- 50 mg orally once daily with or without food.
Monitoring & Laboratory Evaluations- Lymphocyte and platelet counts 4 weeks after starting treatment, then per routine patient management.
Dosage Modifications & Management of Adverse Events- Platelet count < 50,000/mm3: Discontinue treatment.
- Lymphocyte count < 500/mm3: Interrupt therapy.
- Treatment interruptions for < 6 weeks are not expected to result in significant loss of regrown scalp hair.
Safety Warnings & Precautions- Boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.
- Avoid use of live vaccines during or shortly before treatment.
Indication & Diagnosis- Severe alopecia areata based on ≥ 50% scalp hair loss
- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated expert
- Prescribed at the FDA-recommended dose for severe alopecia areata
- Exclusion Criteria (Patient will NOT meet criteria if ANY of the following apply)
- Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless treating dermatologist and oncologist agree risk-benefits favor use)
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
- Platelets < 100,000/mcL or lymphocytes < 500 cells/mcL (may start/restart once values exceeded)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants (except overlaps during treatment transition)
- Concomitant therapy with strong CYP3A inducers (e.g., rifampin)
- Pregnancy
- Lactating
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Required Screening & Testing- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (at minimum: HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
Monitoring & Follow-up- Routine retesting for TB, hepatitis B, and hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
- Anti-HBs titers ≥ 10 IU/L are generally considered protective and may help identify need for initial or booster vaccination or occult HBV identification
- For HBsAg-negative but anti-HBc-positive patients, anti-HBs does not guarantee protection against HBV reactivation; management depends on patient’s risk of HBV reactivation
Special Populations & Counseling- If HBsAg-negative but anti-HBc-positive: GI/liver or infectious diseases expert must be consulted for advice on starting antiviral prophylaxis vs preemptive monitoring for HBV reactivation
- Patients who can become pregnant or have partners who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
- Lactating patients: Advised to avoid giving breastmilk during therapy and for at least 14 hours after the last dose
- Vaccinations should be updated before initiation when possible; recombinant zoster (SHINGRIX) vaccine should be completed or initiated by end of first year, preferably when dosage is low, disease is stable, or immune response can be expected
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REZAFUNGIN INJ,LYPHL
REZZAYO
|
REZZAYO |
2023-07-06 |
Indication & Patient Eligibility- FDA approved for patients ≥18 years of age with limited or no alternative options for treatment of candidemia and invasive candidiasis (IC).
- Designated as a limited use indication.
- Appropriate for patients requiring prolonged outpatient treatment who are unable to transition to oral azole stepdown therapy and face challenges with OPAT (e.g., inability to place PICC line).
Dosing & Administration- Administered once weekly via intravenous infusion.
- Regimen: 400 mg loading dose followed by 200 mg weekly thereafter.
- FDA limits the indication to a maximum of 4 doses; not studied beyond 4 weekly doses.
Clinical Limitations & Exclusions- Met only the 20% non-inferiority margin for 30-day all-cause mortality compared to caspofungin in the ReSTORE trial; did not meet the 10% margin required for unrestricted approval.
- Not studied for complicated infections including septic arthritis in a prosthetic joint, osteomyelitis, endocarditis or myocarditis, CNS infection or endophthalmitis, chronic disseminated candidiasis, or urinary tract candidiasis.
- Exhibits poor penetration into the CNS, eye, and urine.
Safety & Monitoring Requirements- Monitor for infusion-related reactions (e.g., flushing, sensation of warmth, urticaria, nausea, chest tightness); slow or pause infusion if reactions occur.
- Monitor patients who develop abnormal liver tests; evaluate risk/benefit of continuing therapy.
- Advise patients to use protection from sun exposure and other sources of UV radiation due to potential for phototoxicity/photosensitivity.
- No dose adjustment required for renal or hepatic insufficiency.
Preparation & Storage Parameters- Dilute in 250 mL of 0.9% Sodium Chloride Injection, 0.45% Sodium Chloride Injection, or 5% Dextrose injection (total infusion volume of 250 mL for either 400 mg or 200 mg doses).
- Store vials at controlled room temperature between 20°C and 25°C.
- Intravenous infusion solution is stable for 48 hours when stored between 5°C and 25°C.
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EFGARTIGIMOD/ HYALURONIDASE-QVFC INJ,SOLN
VYVGART HYTRULO
|
VYVGART HYTRULO |
2023-06-29 |
Indication- Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Exclusion Criteria- Sensory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
- Concomitant therapy with other monoclonal antibody therapy
- Immunoglobulin therapy or plasma exchange within 1 month
- Serum IgG level less than 600 mg/dL
- Active, untreated infection
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist or locally designated expert
- Diagnosis of typical CIDP or any CIDP variant except sensory CIDP
- Inflammatory neuropathy cause and treatment (INCAT) score of 2 or more
- Contraindication, intolerance, or inadequate symptom control after a minimum 3-month trial of each: corticosteroids and immunoglobulins
Additional Requirements- Plasma exchange may count as one of the two required trials.
Exclusion Criteria- Concomitant therapy with other monoclonal antibody or neonatal Fc receptor antagonist (e.g., rozanolixizumab)
- Thymectomy within 3 months
- Intravenous immunoglobulin (IVIG) or plasma exchange within 1 month
- Untreated hepatitis B, hepatitis C, or HIV with low CD4 count
- Serum IgG level less than 600 mg/dL
- Active, untreated infection
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist
- Anti-acetylcholine receptor (AChR) antibody positive
- Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV
- Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) total score ≥ 5
Additional Inclusion Criteria- One of the following must be met:
- Inadequate symptom control, contraindication, or intolerance to high dose steroid burst, plasma exchange or IVIG and patient requires rapid onset or bridge therapy
- Inadequate symptom control to maximally tolerated pyridostigmine and at least two immunosuppressive agents separately trialed for at least 6 months each (e.g., azathioprine, cyclosporine, mycophenolate, etc.)
- History of intolerance or contraindication preventing trial of immunosuppressive agents (e.g., azathioprine, cyclosporine, mycophenolate, etc.)
Indication- Chronic inflammatory demyelinating polyneuropathy (CIDP)
Dosage & Administration- 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase in a single-dose vial
- 1,008 mg/11,200 units once weekly via slow subcutaneous injection
- Must be administered by a healthcare professional
Contraindications- Hypersensitivity to efgartigimod, hyaluronidase, or other excipients included in the injection
Warnings & Precautions- Infections: Monitor for infections; most common was COVID-19, generally mild to moderate in severity
- Vaccinations: Avoid live or live-attenuated vaccinations while a patient is treated with efgartigimod
- Hypersensitivity and infusion-related reactions: Risk of severe anaphylaxis and hypotension leading to syncope; more common mild reactions include hypertension, chills, and pain
Monitoring Requirements- Patients should be monitored for 30 minutes after administration
- For mild to moderate infusion-related reactions, rechallenge can be considered with close observation, slower infusion rate, and pre-medication as applicable
Drug Interactions- May lower the effectiveness of other medications that bind to neonatal Fc receptor, including immunoglobulin products and monoclonal antibodies
Pregnancy & Lactation- Reduces circulating IgG levels, which may reduce maternal passive immunity to the fetus or infant
- May be transmitted from the mother to the developing fetus, potentially inhibiting the fetus’ own immunoglobulin production
Clinical Context/Notes- Utilized as maintenance therapy rather than induction therapy
- Subcutaneous formulation with hyaluronidase is specified; intravenous formulation has not been studied in CIDP
- Hyaluronidase alone does not have a clinical effect on CIDP
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GLOFITAMAB-GXBM INJ,SOLN
COLUMVI
|
COLUMVI |
2023-06-29 |
Indications- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
Exclusion Criteria- Facility is not equipped to monitor and manage Cytokine Release Syndrome (CRS), if necessary
- Patient unable to be hospitalized for step-up dose on Cycle 1, Day 8 and/or Day 15 followed by 24 hours of monitoring, if any grade of CRS is experienced on either day
- Absolute Neutrophil Count < 1500/µL, Platelet count < 75,000/µL (if no bone marrow involvement)
- Total bilirubin > 1.5 times the upper limit of normal (unless Gilbert’s syndrome or liver involvement)
- Alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase > 3 times the upper limit of normal (unless liver involvement)
- Creatinine clearance < 50 ml/min
- Active or uncontrolled infection
- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
Inclusion Criteria- Relapsed or refractory, diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) arising from follicular lymphoma (FL)
- Previously treated with > 2 prior lines of therapy (including 1 line with anti-CD20 monoclonal antibody)
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 month after stopping treatment.
Indication & Patient Population- Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) arising from follicular lymphoma (FL) after > 2 lines of therapy (LOT)
- Heavily pretreated population with median prior LOT of 3; includes patients with primary refractory disease, prior CAR T-cell therapy, and prior autologous hematopoietic stem cell transplantation (HSCT)
Performance Status & Laboratory Criteria- ECOG PS 0-1
- ANC > 1500 cells/mcL
- Platelets > 75,000 cells/mcL
- Transfusion-independent
- SCr < 1.5 x ULN (or CrCl > 50 ml/min)
- Transaminases < 3x ULN
Exclusion Criteria- Active or prior CNS lymphoma
- CNS disease
- Acute infection
- Recent infection requiring IV antibiotics
- Prior allogeneic HSCT
Dosing & Administration Requirements- Day 1: obinutuzumab 1000mg IV x1
- Day 8: Step up dose 1 glofitamab 2.5mg IV x1
- Day 15: Step up dose 2 glofitamab 10mg IV x1
- Cycles #2-12 (Day 1): glofitamab 30mg IV x1
- Repeat every 21 days for up to 12 cycles
Monitoring & Management Requirements- Monitor for neurologic toxicity, including ICANS; hold or discontinue based on severity
- Monitor signs and symptoms of serious infections; treat appropriately
- Monitor patients at risk for tumor flare
- Advise patients of embryo-fetal toxicity and potential fetal harm; require use of effective contraception
- Hospitalization recommended 24 hours after step up dose #1 and step up dose #2, if CRS occurs in cycle 1
- If CRS > Grade 2 occurs with infusion, hospitalize during and for 24 hours after completion of subsequent infusion
VA Clinical Pathway & Guideline Recommendations- Recommended per VA Oncology Clinical Pathway for multiply relapsed DLBCL if ASCT and CAR T-cell therapies are not an option and disease progression occurs following rituximab-bendamustine-polatuzumab
- Listed as a preferred regimen in NCCN guidelines for 3L and subsequent therapy for DLBCL
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PERFLUOROHEXYLOCTANE SOLN,OPH
MIEBO
|
MIEBO |
2023-06-29 |
Provider Requirements- Prescribing provider must be a VA/VA Community Care ophthalmologist or optometrist
Diagnosis- Dry eye disease associated with meibomian gland dysfunction
Prior Therapy Requirements- Documented lack of therapeutic response to at least two artificial tear agents from different categories OR documented corneal surface damage while frequently using artificial tear agents
- Lack of response to an adequate trial of ophthalmic cyclosporine unless unable to use (e.g., intolerance, etc.)
- Lack of response to an adequate trial of ophthalmic lifitegrast unless unable to use (e.g., intolerance, etc.)
Administration & Counseling Guidelines- Do not administer while wearing contact lenses; patients must remove contact lenses prior to and for at least 30 minutes after administration
- Wait 10–15 minutes between topical ophthalmic drops; instill aqueous drops first, followed by perfluorohexyloctane
Indication & Patient Population- Treatment of the signs and symptoms of dry eye disease
- Patients with dry eye disease due to meibomian gland dysfunction (MGD) who have not responded to or tolerated treatment with artificial tears, topical cyclosporine, and lifitegrast
Dosing & Administration- Administered as one drop in each eye four times daily
- Should not be administered while wearing contact lenses; remove contact lenses prior to and for at least 30 minutes after administration
- Wait 10-15 minutes between topical ophthalmic drops; instill aqueous drops first, followed by perfluorohexyloctane
Contraindications & Precautions- No boxed warnings
- No contraindications listed
- No other warnings/precautions listed
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SOTAGLIFLOZIN TAB,ORAL
INPEFA
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INPEFA |
2023-06-15 |
Indications- Reduce the risk of cardiovascular death, hospitalization for heart failure (HF), and urgent HF visit in adults with:
- HF or
- Type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and other CV risk factors
Dosing & Administration Criteria- Recommended starting dose is 200 mg once daily, administered not more than one hour before the first meal of the day
- After 2 weeks, the dose may be titrated to 400 mg once daily, as tolerated
- Withhold for at least three days prior to major surgery or procedures associated with prolonged fasting (if possible)
Pre-Initiation Assessment & Monitoring Requirements- Assess volume status and correct volume depletion if indicated before starting
- Assess renal function prior to initiation and as clinically indicated
- In patients with decompensated HF, dosing may begin only when the patient is hemodynamically stable
- Monitor for signs and symptoms of hypotension and renal function after starting therapy
- Evaluate patients for signs and symptoms of urinary tract infections during therapy and treat promptly if indicated
- Monitor and treat genital mycotic infections as appropriate
Contraindications- History of serious hypersensitivity reaction to sotagliflozin
Warnings & Precautions (Clinical Use Criteria)- Not indicated for glycemic control; not approved for T1DM due to significantly increased risk of diabetic ketoacidosis (DKA)
- Assess for ketoacidosis regardless of presenting blood glucose and discontinue if suspected; monitor patients for resolution before restarting
- Increased risk for volume depletion in patients with impaired renal function (eGFR < 60 ml/min/1.73 m2), elderly patients, or patients on loop diuretics
- May increase risk of hypoglycemia when combined with insulin or an insulin secretagogue; a lower dose of these agents may be required to minimize risk
- Assess for necrotizing fasciitis of the perineum (Fournier’s gangrene) if patients present with pain, tenderness, erythema, or swelling in the genital or perineal area along with fever or malaise; discontinue sotagliflozin and provide alternative HF therapy if suspected
Clinical Practice Guideline Recommendations- ACC/AHA/HFSA (2022): Recommended to reduce hospitalization for HF and CV mortality in symptomatic chronic HFrEF irrespective of T2DM; can be beneficial in HFmrEF and HFpEF; recommended for management of hyperglycemia and to reduce HF morbidity/mortality in patients with HF and T2DM
- ESC (2021): Recommended in patients with diabetes at high risk of CV disease or with CV disease to prevent HF hospitalizations; recommended in patients with T2DM at risk of CV events to reduce HF hospitalizations, major CV events, end-stage renal dysfunction, and CV death; recommended in patients with T2DM and HFrEF to reduce HF hospitalizations and CV death
- ADA (2023/2022): Recommended for adults with T2DM and established/high risk of atherosclerotic CV disease, HF, and/or CKD to reduce cardiorenal risk; recommended as part of glucose-lowering regimen independent of A1C; recommended for T2DM and diabetic kidney disease with eGFR ≥ 25 ml/min/1.73 m2 and urinary albumin ≥ 300 mg/g creatinine to reduce CKD progression and CV events
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ZAVEGEPANT SOLN,SPRAY,NASAL
ZAVZPRET
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ZAVZPRET |
2023-06-08 |
Exclusion Criteria- Patient has uncontrolled hypertension
- Patient has a history of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- Concurrent therapy with a triptan, ergot, or gepant once zavegepant is initiated
Inclusion Criteria- Treatment initiated by or in consultation with a VA/VA Community Care neurologist or locally designated headache expert
- Diagnosis of migraine, with or without aura, per the International Classification of Headache Disorders (ICHD-3)
- Moderate to severe migraine intensity
- Currently receiving preventive therapy for migraine if indicated
Additional Inclusion Criteria (One must be fulfilled)- Contraindication, intolerance, or lack of response to trial of two different oral gepants for acute migraine treatment at a clinically effective dose
- Patient requires a non-oral acute migraine therapy and has contraindication, intolerance, or lack of response to trial of at least two other non-oral acute migraine pharmacotherapies
Monitoring & Procedural Requirements- Discontinue zavegepant if signs or symptoms of Raynaud’s phenomenon develop
- Monitor patients with a history of Raynaud’s phenomenon for recurrence and worsening, and inform them of this possibility
- Locally designated headache expert must perform a comprehensive headache assessment including evaluation for medication overuse headache, other secondary headache types, adherence to prior headache therapies, and features requiring urgent/emergent evaluation; review headache history for triggers, effective preventive treatment, and nonpharmacologic interventions
- Scheduled blood pressure check required 2–4 weeks after initiation of therapy
Concomitant Therapy Considerations- Vascular contraindications to triptans and ergots include ischemic coronary artery disease, previous stroke or transient ischemic attack, peripheral vascular disease, or ischemic bowel disease; other contraindications may be drug interaction related (e.g., concurrent use of a MAO inhibitor)
- If using a combination of a calcitonin gene related peptide (CGRP)-targeted monoclonal antibody for preventative therapy and zavegepant for abortive therapy, patient must be evaluated and counseled on risks of concomitant therapy
- Safety evidence of concomitant CGRP acting agents is limited; patients may be prone to CGRP-related adverse events (vasodilation, GI motor-stimulation, prosecretory effects); consider alternative therapies for patients at high risk for ischemic events or severe constipation
Indication- • Acute treatment of migraine with or without aura
Dosing & Formulation- • Nasal spray: 10 mg/actuation
Contraindications & Warnings/Precautions- • History of hypersensitivity to zavegepant or any of its components
- • Hypersensitivity reactions including facial swelling and urticaria (occurred in less than 1% of patients in clinical trials)
Drug-Drug Interactions- • Avoid administration with inhibitors or inducers of the organic anion transporting polypeptide 1B3 (OATP1B3) or sodium taurocholate co-transporting polypeptide (NTCP) (e.g., rifampin, pretomanid, trofinetide, voclosporin)
- • Concurrent intranasal decongestant use may decrease absorption; if needed, administer intranasal decongestant at least 1 hour after zavegepant administration
Special Populations- • Hepatic Impairment: Avoid in severe (Child-Pugh Class C) impairment
- • Renal Impairment: Avoid in CrCl less than 30 mL/min
- • Pregnancy and Lactation: No data on developmental risk or presence in human milk; no adverse developmental effects observed in animal studies
Clinical Use Considerations- • May be used as an alternative for patients requiring a non-oral option (e.g., vomiting during migraine, severe nausea that swallowing pills aggravates)
- • May be used as an alternative for patients experiencing intolerance or therapeutic failure with other acute migraine intranasal spray medications (e.g., triptans, ergots) who require maintaining a non-oral route
- • No evidence to support off-label use in acute cluster headache treatment
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EPCORITAMAB-BYSP INJ,SOLN
EPKINLY
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EPKINLY |
2023-06-01 |
Indications- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
Exclusion Criteria- Facility is not equipped to monitor and manage Cytokine Release Syndrome (CRS), if necessary
- Absolute Neutrophil Count < 1000/µL
- Platelet count < 75,000/µL (if no bone marrow involvement)
- Total bilirubin > 1.5 times the upper limit of normal (unless Gilbert’s syndrome or liver involvement)
- Alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase > 3 times the upper limit of normal (unless liver involvement)
- Creatinine clearance < 45 ml/min
- Active or uncontrolled infection
- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
Inclusion Criteria- Relapsed or refractory, diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma
- Relapsed or refractory, follicular lymphoma (FL)
Additional Inclusion Criteria- Previously treated with > 2 prior lines of therapy (including 1 line with anti-CD20 monoclonal antibody)
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (Select if applicable)- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 months after stopping treatment
Monitoring & Administration Requirements- Patients with diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma should be hospitalized for step-up dose on Cycle 1, Day 15 (first 48 mg dose) followed by 24 hours of monitoring
Indications & Patient Population- Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma (HGBCL)
- Relapsed or refractory follicular lymphoma (FL) grade 1-3A
Prior Therapy Requirements- > 2 prior lines of therapy (LOT) for both DLBCL and FL indications
- For FL: must have received prior anti-CD20 monoclonal antibody, alkylator, or lenalidomide
Exclusion Criteria- CNS lymphoma
- Allogeneic hematopoietic stem cell transplant (allo HSCT) or solid organ transplant (SOT) [DLBCL cohort]
- Active infection
- Impaired T-cell immunity [DLBCL cohort]
- HIV infection, cardiovascular disease (CV disease), autoimmune disease [FL cohort]
Dosing & Administration Requirements- Requires step-up dosing regimen for both DLBCL and FL: Day 1 (0.16 mg SQ), Day 8 (0.8 mg SQ), Day 15 first full dose (48 mg SQ)
- Subsequent cycles follow a 28-day schedule with fixed 48 mg SQ dosing on specified days
- Therapy continues until progressive disease or toxicity
Safety Monitoring & Warnings- Boxed warnings for Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
- Additional warnings include infections, cytopenias, and embryo-fetal toxicity
- First full dose must be administered in a hospital setting with monitoring for CRS/ICANS
VA Formulary & Clinical Pathway Notes- Not included in VA Oncology Clinical Pathway for either DLBCL or FL indications
- Alternative options referenced to Appendix A (BiTE alternatives)
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FEZOLINETANT TAB
VEOZAH
|
VEOZAH |
2023-05-25 |
Inclusion Criteria- Moderate to severe vasomotor symptoms (VMS) associated with menopause
- Contraindication or intolerance to menopausal hormone therapy (MHT) or patient preference to avoid MHT
- Contraindication, intolerance, or insufficient response to one nonhormonal treatment for VMS
Exclusion Criteria- Known cirrhosis
- Severe renal impairment (estimated glomerular filtration rate [eGFR] less than 30 ml/min/1.73m2)
- Concomitant use of CYP1A2 inhibitors (e.g., cimetidine, mexiletine, fluvoxamine)
- Baseline AST, ALT, or total bilirubin ≥ 2 times the upper limit of normal
Laboratory Monitoring Requirements- Perform baseline liver function testing before initiating (ALT, AST, ALP, total and direct bilirubin)
- Perform follow-up liver function testing monthly for the first 3 months, then at 6 and 9 months after initiating
- Perform follow-up testing if any signs or symptoms of liver injury occur
- Consider periodic assessment of liver function during extended treatment
Discontinuation Criteria- Discontinue if transaminase elevations are greater than 5 times upper limit of normal
- Discontinue if transaminase elevations are greater than 3 times upper limit of normal and total bilirubin greater than 2 times upper limit of normal
Patient Counseling & Reassessment- Periodically reassess and discuss the need for continued treatment given the finite duration of VMS
- Advise patients on signs and symptoms of hepatotoxicity and when to seek medical attention
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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SEMAGLUTIDE INJ,SOLN
OZEMPIC
|
OZEMPIC |
2023-05-25 |
Indication & Patient Population- Type 2 diabetes
- Patients currently treated with semaglutide 1mg requiring additional glycemic control
- Trial population demographics: mean age 58 years, 59% men, 88% white, mean duration of diabetes 9.5 years, mean A1C 8.9%, mean fasting plasma glucose 194 mg/dL, mean weight 99.3 kg, 53% on sulfonylureas
Efficacy & Glycemic Control- Indicated as add-on to metformin +/- sulfonylureas
- Primary outcome: Change from baseline at week 40 in A1C (estimated treatment difference between 2mg and 1mg was 0.2%)
- A1C <7% achieved in 64% of patients on 2mg vs 56% on 1mg
- Fasting plasma glucose change: -59 mg/dL for 2mg vs -55 mg/dL for 1mg
- Blood pressure changes at week 40: -5.3 mmHg systolic and -0.8 mmHg diastolic for 2mg; -4.5 mmHg systolic and -0.4 mmHg diastolic for 1mg
Weight Management- Change in body weight at week 40: -6.4 kg for 2mg vs -5.6 kg for 1mg (estimated treatment difference -0.77 kg)
- Percentage of patients with weight loss: 7.2% for 2mg vs 6.2% for 1mg
Safety & Adverse Events- Gastrointestinal adverse events (nausea, vomiting, diarrhea) and hypoglycemia were comparable between doses
- No increase in other adverse events of interest with the 2mg dose compared to the 1mg dose: diabetic retinopathy complications, hepatobiliary issues, acute gallstone disease, pancreatitis, cardiovascular disease, allergic reactions
Intensification & Clinical Considerations- Verify adherence to current therapy
- Optimize current non-GLP1 agonist anti-glycemic medications as appropriate
- Consider addition of empagliflozin or insulin if appropriate
Formulary/Availability- Available on VANF; doses up to 1 mg are on National Contract (2mg dose is not on National Contract)
Indications & Inclusion Criteria- Diagnosis of Type 2 diabetes mellitus (T2DM)
- Must meet ONE of the following:
- Patient has established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD) and is not a good candidate for empagliflozin
- Patient whose glycemic goals are not met with empagliflozin plus maximally tolerated doses of metformin, unless unable to use
Exclusion Criteria- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility including gastroparesis (unless risks/benefits are discussed with the patient and documented in the Federal EHR with a plan to monitor and follow GI symptoms)
- History of pancreatitis (does not pertain to patients for whom the cause of pancreatitis is known and no longer presents a risk)
- Pregnancy
- Known PDR, severe NPDR, clinically significant ME, or DME (unless risks/benefits are discussed with the patient and documented in the Federal EHR with a plan to monitor and follow-up with an eye specialist who is informed upon initiation)
- Low body weight and/or presence of sarcopenia (unless risks/benefits are discussed with the patient and documented in the Federal EHR with a plan to closely monitor and follow changes in weight)
- Concomitant use of dipeptidyl peptidase 4 (DPP-4) inhibitors
Comorbidities & Special Populations- ASCVD defined as: history of acute coronary syndrome or myocardial infarction, stable or unstable angina, coronary heart disease with or without revascularization, other arterial revascularization, stroke, or atherosclerotic peripheral artery disease
- CKD defined as: eGFR <60 mL/min/1.73m2 OR Urinary Albumin-to-Creatinine Ratio >= 30mg/g
- Not FDA approved for glycemic control in Type 1 diabetes
- Breastfeeding: No data on presence in human milk; consider developmental and health benefits of breastfeeding along with mother’s clinical need and potential adverse effects on the breastfed infant
- Pancreatitis risk factors include hypertriglyceridemia (>1000 mg/dL), gallstones with intact gallbladder, and alcohol use disorder/excessive alcohol use
Monitoring & Management Requirements- Insulin is generally preferred during pregnancy; discontinue semaglutide at least 2 months before a planned pregnancy due to long washout period
- Metformin should be used prior to adding semaglutide in patients with or without known ASCVD/CKD whose glycemic goals are not met on empagliflozin, unless unable to use
- Insulin may be considered at any time prior to a GLP-1 agonist; preferred if patient is symptomatic, blood sugars >300 mg, A1C >10%, or desired A1C reduction is beyond what is achievable by a GLP-1 agonist
- Oral semaglutide (nonformulary) should be reserved for patients physically unable to use injectable therapy; consider other oral formulary agents first
- GLP-1 receptor agonists in combination with alpha glucosidase inhibitors or meglitinides are not recommended due to lack/insufficient data regarding combined use
- Ophthalmology consult should be obtained anytime there are concerns related to use in patients with diabetic retinopathy; provider should have results of diabetic eye examination completed within past 12 months on file before considering a GLP-1 agonist for these patients
- Individual cases that are exceptions to exclusion/inclusion criteria should be adjudicated at the local facility according to P&T Committee and Pharmacy Services policy/procedures
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RISPERIDONE INJ,SUSP,SA
UZEDY
|
UZEDY |
2023-05-18 |
Continuity of Care- Veteran is transitioning care from the Department of Defense to VHA
- Additional Inclusion Criteria (Select ONE):
- Medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making
- Medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making
Non-Continuity of Care Exclusion Criteria- Patient has never taken the long-acting injectable (LAI) antipsychotic ordered in any formulation (e.g., oral)
- Patient has a hypersensitivity to the antipsychotic ordered (consider risperidone and paliperidone cross-sensitive)
Non-Continuity of Care Inclusion Criteria- All of the following must be met:
- Diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder
- Initial prescriber is a VA Mental Health provider
- Patient has taken and tolerated the antipsychotic ordered prior to receiving it as a LAI for an adequate length of time (consider risperidone and paliperidone cross-tolerant)
- Patient will be transitioned from oral medication to the LAI per guideline/manufacturer recommendations
- One of the following must be met:
- Patient has relapsed or been hospitalized for the intended indication or complications of the intended indication because of nonadherence when treated with oral antipsychotics
- Patient’s care environment is such that a LAI is a more reliable route of administration (e.g., homeless, lack of medication supervision, or the medication cannot be stored safely)
Indication & Patient Population- Indicated for the treatment of schizophrenia in adults.
- Appropriate for patients with a schizophrenia diagnosis greater than one year and one or more relapse episodes in the last 24 months, or those who responded to an antipsychotic (other than clozapine) in the past year.
- Patients must be on stable oral risperidone doses between 2 mg/day and 5 mg/day; candidates with stable doses lower than 2 mg/day or higher than 5 mg/day are not appropriate.
Dosing & Administration Criteria- Administered as a subcutaneous extended-release injectable suspension.
- Dosing interval is either once monthly or every two months.
- Initiate therapy the day after the last dose of oral risperidone.
- Neither a loading dose nor supplemental oral risperidone doses are recommended when switching from oral to injectable therapy.
- Oral-to-injectable conversion: 2 mg/day oral = 50 mg SC q1m or 100 mg SC q2m; 3 mg/day = 75 mg/150 mg; 4 mg/day = 100 mg/200 mg; 5 mg/day = 125 mg/250 mg.
Safety, Warnings & Monitoring Requirements- Contraindicated in elderly patients with dementia-related psychosis due to increased mortality and cerebrovascular adverse reactions (including stroke).
- Monitor for neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes (hyperglycemia, diabetes mellitus, dyslipidemia, weight gain), hyperprolactinemia, orthostatic hypotension, syncope, falls, leukopenia/neutropenia/agranulocytosis, cognitive and motor impairment, seizures, dysphagia, priapism, and body temperature regulation issues.
- Pregnancy: Not studied in pregnancy; neonates exposed during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery.
- Lactation: Present in human breast milk (2.3–4.7% relative infant dose); monitor breastfed infants for sedation, failure to thrive, jitteriness, and EPS.
Formulation & Storage Specifications- Supplied as single-dose prefilled syringes (50, 75, 100, 125, 150, 200, and 250 mg) that do not require reconstitution.
- Requires refrigeration.
- Must be protected from light.
- Discard if the package is opened; must remain in an unopened package until administration.
- Staff education is required for proper storage and administration.
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FECAL MICROBIOTA-BRPK CAP,ORAL
VOWST
|
VOWST |
2023-05-11 |
Indication & Approved Population- • Prevention of recurrence of Clostridioides difficile infection (CDI) after completion of antibiotic treatment for recurrent CDI in individuals 18 years of age and older
- • Adults with recurrent CDI (rCDI), specifically those with 3 or more episodes within 12 months
Patient Selection & Clinical Guidance- • Adjunct therapy following a course of standard CDI antibiotic treatment
- • Consider for patients at high risk for rCDI who cannot use bezlotoxumab (e.g., active congestive heart failure or previously treated with bezlotoxumab)
- • Bezlotoxumab should generally be tried prior to fecal microbiota therapy unless not medically advisable or practicable
- • Ideally, specialists such as Infectious Diseases or Gastroenterology providers should be included in the decision for patient selection and safe use
- • Not approved for off-label indications; intent to use off-label requires discussion with local P&T and case adjudication
Exclusions & Safety Precautions- • Rigorous screening required due to risk of transmitting infectious agents from human fecal matter (e.g., shiga-toxin producing E.coli, extended-spectrum beta-lactamase producing E.coli, norovirus, SARS-CoV-2, monkeypox)
- • Potential presence of food allergens
- • Not appropriate for patients requiring continued or concomitant antibiotic therapy, as antibiotics may reduce effectiveness and were excluded from clinical trials
- • Patients with toxic megacolon, history of active inflammatory bowel disease within 3 months, or absolute neutrophil count < 500 cells/uL were excluded from trials; efficacy in these populations cannot be determined
Administration & Dosing Requirements- • Initiate 2-4 days after completion of CDI treatment
- • Dose: 4 capsules taken orally once daily for 3 consecutive days on an empty stomach prior to the first meal of the day
- • Pre-treatment requirement: 296 mL magnesium citrate the day before the first dose (or 250 mL polyethylene glycol if unable to take magnesium citrate)
- • Patients must be able to comply with administration procedures and laxative pretreatment
Special Populations- • Pregnancy: No data on use in pregnant individuals
- • Lactation: Unknown whether excreted in human milk
- • Geriatrics: Clinical trial data are not sufficient to determine if adults 65 years of age or greater respond differently than younger adults
Exclusion Criteria- History of severe allergic reactions to any component of VOWST
- Asymptomatic Clostridioides difficile colonization
- Absolute neutrophil count < 500 cells/mm3
- Likely to require antibiotic therapy for a condition other than Clostridioides difficile infection (CDI) OR planned surgery requiring perioperative antibiotics within 8 weeks after treatment
- Inability to use magnesium citrate or polyethylene glycol pretreatment or comply with administration on an empty stomach prior to the first meal of the day
Inclusion Criteria- At least 2nd episode of recurrent CDI (3rd episode overall) in the previous 12 months (defined as CDI recurring within 8 weeks of completion of standard CDI treatment)
- Successful treatment of current episode of CDI with standard of care CDI antibiotics (fidaxomicin or oral vancomycin)
- Administration occurs within 2-4 days after completion of standard of care CDI antibiotics (fidaxomicin or oral vancomycin)
- At least one episode of CDI was treated with fidaxomicin, unless not tolerated or contraindicated
Dosage and Administration- Pretreatment: 296 mL magnesium citrate on the day before and at least 8 hours prior to the FIRST dose (250 mL polyethylene glycol can be used as an alternative in patients with impaired kidney function)
- Fasting requirement: No food or drink, except a small amount of water, for at least 8 hours prior to the FIRST dose
- Dosing regimen: 4 capsules orally on an empty stomach prior to the first meal of the day once daily for 3 consecutive days
Indication and Limitations- Not FDA indicated or studied for an initial episode of CDI
- Should be avoided in patients with an absolute neutrophil count < 500 cells/mm3 (further data required before making a recommendation in this population)
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TOFERSEN INJ,SOLN
QALSODY
|
QALSODY |
2023-05-04 |
Exclusion Criteria- Notably decreased respiratory function and dyspnea (total score of 3 or less points on ALSFRS-R items for dyspnea, orthopnea, or respiratory insufficiency [sum of questions 10, 11 and 12 on the ALSFRS-R])
- Bilevel positive airway pressure (BiPAP) dependent (use 24 hours per day)
Inclusion Criteria- Care provided by a VA neurologist or locally designated ALS expert
- Diagnosis of superoxide dismutase 1 (SOD1) ALS made or confirmed by a VA neurologist or locally designated ALS expert
- Laboratory documentation of a pathogenic SOD1 mutation in the electronic medical record
- Documentation of an itemized ALSFRS-R score in the electronic medical record
Clinical/Study Parameters- Tofersen has only been studied in patients with forced vital capacity (FVC) of 50% or higher, or FVC of 45 – 50% if the FVC had not declined more than 5% in the last 6 months.
Indication- Adults with amyotrophic lateral sclerosis (ALS) who have a mutation in the SOD1 gene
- Indicated for SOD1 ALS only; no evidence of effectiveness in other familial types of ALS or sporadic ALS
Dosing & Administration- Intrathecal injection: 100 mg/15 mL solution in a single-dose vial
- Dosing regimen: 100 mg intrathecally every 14 days for 3 doses, then starting 28 days after the third dose, 100 mg intrathecally every 28 days
- Must be administered by a healthcare professional experienced in lumbar punctures
Safety & Monitoring- Myelitis and/or radiculitis: Symptomatic management with or without drug discontinuation may be required if symptoms occur
- Papilledema and elevated intracranial pressure (ICP): Requires treatment leading to symptom resolution; discontinuation is not required
- Aseptic meningitis: Monitor for serious cases; nonserious elevations of white blood cells in cerebrospinal fluid (CSF) have been reported
Special Populations- Pregnancy: No adequate data to assess risks for birth defects, miscarriage, or developmental/maternal effects
- Lactation: No data on presence in breast milk; weigh unknown infant developmental/health risks against maternal clinical need
Clinical & Therapeutic Requirements- Accelerated approval is based on reduction of serum neurofilament light chain (NfL) levels as a surrogate marker for slowed neurodegeneration
- Impact on specific functional domains and/or survival is unclear due to lack of established correlation between NfL changes and clinical change in ALS
- Continued FDA approval is contingent upon verification of clinical benefit in confirmatory trial(s)
- Patient/family/caregiver counseling regarding treatment administration implications (e.g., travel to clinic, tolerance of routine lumbar punctures) and realistic expectations for efficacy is imperative
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DEUTETRABENAZINE TAB,SA,24HR (EXTENDED RELEASE)
AUSTEDO XR, AUSTEDO XR TITRATION KT(WK1-4)
|
AUSTEDO XR, AUSTEDO XR TITRATION KT(WK1-4) |
2023-04-27 |
Exclusion Criteria- Actively suicidal or has untreated or inadequately treated depression
- Congenital long QT interval, or a QTc >450 ms for men or QTc >470 ms for women
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB or RBBB), or cardiac device (can be considered candidates with cardiology evaluation)
- Concurrent use of a monoamine oxidase inhibitor (MAOI) or within 14 days of discontinuing therapy with an MAOI
- Current or use of reserpine within the past 20 days
- Concurrent use of another VMAT2 inhibitor (i.e., tetrabenazine, valbenazine)
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnant or lactating
- Hepatic impairment
Inclusion Criteria: Treatment of Huntington Disease- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
- Diagnosis of Huntington disease documented in the medical record
- Chorea is disabling or painful and interferes with functional status (including self-care and ambulation), quality of life, or creates a social stigma sufficient to cause social isolation or embarrassment
- Prescriber has documented specific movement(s) (e.g., facial, oral, extremity, or trunk) in the medical record along with how the chorea is affecting function, quality of life, or socialization
Inclusion Criteria: Treatment of Dystonia- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
- No response or intolerant to alternative agents (local botulinum toxin injections, anticholinergics, or benzodiazepines)
Inclusion Criteria: Treatment of Tardive Dyskinesia- Diagnosis of tardive dyskinesia (TD) secondary to a dopaminergic blocking agent (e.g., antipsychotic or metoclopramide)
- TD interferes with functional status (including self-care and ambulation), quality of life, or creates a social stigma sufficient to cause social isolation or embarrassment
- Prescriber has documented specific movement(s) (e.g., facial, oral, extremity, or trunk) in the medical record along with how TD is affecting function, quality of life, or socialization
- Recent Abnormal Involuntary Movement Scale (AIMS) score is recorded in the medical record
- ECG performed to confirm a QTc <450 ms for men or QTc <470 ms for women
- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
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LOMITAPIDE CAP,ORAL
JUXTAPID
|
JUXTAPID |
2023-04-13 |
Exclusion Criteria- Pregnancy
- Lactating
- Concomitant use of moderate or strong inhibitors of CYP 3A4
- Moderate or severe liver disease (e.g., Child-Pugh Category B or C) or active liver disease, including unexplained persistent elevation of serum transaminases
Inclusion Criteria- Provider certification for prescribing due to increased risk of hepatotoxicity
- Diagnosis of homozygous familial hypercholesterolemia (HoFH)
- Patient education on and willingness/ability to follow a low-fat diet (<20% daily calories from fat)
- Insufficient reduction in LDL-C with PCSK9 inhibitor (e.g., alirocumab)
- Receipt of LDL-C apheresis, if patient is a candidate and therapy is accessible
- Confirmed negative pregnancy test, if applicable
Additional Inclusion Criteria- Pregnancy exclusion required prior to therapy for females who can become pregnant
- Counseling on treatment risks vs benefits and requirement for effective contraception during therapy for females who can become pregnant
Diagnostic & Safety Requirements- HoFH diagnosis must be confirmed via: 1) genetic testing (LDL receptor mutation: true homozygote or double heterozygote), OR 2) untreated LDL >500 mg/dL, OR 3) receiving maximal lipid-lowering therapy with confirmed adherence and LDL >300 mg/dL
- Diagnosis must include physical findings: tendon xanthomas at any age, arcus corneae in patients <45 years, or tuberous xanthomas/xanthelasma in patients <20 years
- Safety and efficacy not established for patients without HoFH; restricted to confirmed HoFH cases only
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RETIFANLIMAB-DLWR INJ,SOLN
ZYNYZ
|
ZYNYZ |
2023-04-06 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell transplant or solid organ transplant
- Pregnancy
- Lactating
Inclusion Criteria- Indication is FDA approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (Select if applicable)- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 months after stopping treatment
Indication & Approved Use- Metastatic or recurrent locally advanced Merkel cell carcinoma (accelerated approval)
- Rare, aggressive, cutaneous malignancy that predominantly affects older adults with light skin
Dosing & Administration- 500mg infusion over 30 minutes every 4 weeks
- Dosage form: 500g/20mL injection
Patient Population & Eligibility- Chemotherapy-naïve (or chemotherapy-refractory) advanced/metastatic Merkel cell carcinoma
- ECOG performance status 0-1
Formulary & Clinical Pathway Considerations- Optimal therapy for advanced disease is not well-defined; single-agent immunotherapy is generally preferred over chemotherapy
- Retifanlimab does not offer an advantage over pembrolizumab or avelumab in MCC
- Pembrolizumab and avelumab have durable responses with longer follow-up data than retifanlimab
NCCN & VA Oncology Clinical Pathway Recommendations- NCCN: Category 2B for Primary Locally Advanced Disease, Recurrent Disease, or Metastatic Disease
- VA Oncology Clinical Pathway: For metastatic disease and not a candidate for locoregional therapy, recommend Pembrolizumab
Alternative Treatment Options- Other recommended regimens (cat 2B): Avelumab, Pembrolizumab (Primary Locally Advanced/Recurrent); Pembrolizumab, Avelumab, Nivolumab, Retifanlimab (Disseminated/Metastatic)
- Alternative options: locoregional treatment (if a candidate) or nivolumab+ipilimumab or carboplatin+etoposide if previous PD-1 therapy
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TERIFLUNOMIDE TAB,ORAL
AUBAGIO
|
AUBAGIO |
2023-03-16 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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OMEPRAZOLE/ SODIUM BICARBONATE SUSP,ORAL
KONVOMEP
|
KONVOMEP |
2023-03-09 |
Pharmacology & Drug Interaction- Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
- Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.
Gastrointestinal Risk Management- PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
- For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.
Cardiovascular Risk Management- Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
- No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.
Prescribing Criteria- Deprescribe PPIs as much as possible per established de-prescribing guidelines.
- Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.
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PEGCETACOPLAN INJ,SOLN
EMPAVELI, SYFOVRE
|
EMPAVELI, SYFOVRE |
2023-03-02 |
Indication- Paroxysmal nocturnal hemoglobinuria (PNH)
Dosage & Administration- 1080 mg by subcutaneous infusion twice weekly
- Infusion duration: 30 minutes if using two infusion sides, or 60 minutes if using one infusion site
- Patient can self-administer
- Obtained via specialty pharmacy
REMS Requirements- Empaveli REMS program required for both prescribers and pharmacies
- Prescribers must enroll in the REMS program
- Providers must counsel patients on the risk of serious infection
- Providers must provide patients with REMS educational materials
- Patients must be vaccinated against encapsulated bacteria (Streptococcus pneumoniae, Neisseria meningitidis, Hemophilus influenzae) prior to initiation
- Vaccination should occur at least 2 weeks before the first dose
- Pharmacies must be REMS registered and submit daily data files to the REMS coordinator; use of the program’s specialty pharmacy is recommended due to administrative requirements
Contraindications & Warnings/Precautions- Hypersensitivity to pegcetacoplan or any component of the formulation
- Patients not currently vaccinated against encapsulated bacteria (unless risks of delaying treatment outweigh the risk of infection)
- Unresolved infection caused by encapsulated bacteria
- Boxed warning for serious infections caused by encapsulated bacteria; adhere to ACIP recommendations for vaccinations in people with complement deficiencies
- Live vaccines should not be administered
- Consider restarting pegcetacoplan treatment if signs of hemolysis occur after discontinuation
- Avoid breastfeeding during treatment and up to 40 days after the last dose
Place in Therapy/Clinical Guidance- Complement C3 inhibitor indicated for the treatment of PNH
- May be reasonable to consider in patients refractory to a complement C5 inhibitor, including those experiencing breakthrough hemolysis
- European Medical Association approved for patients who remain anemic after at least three months of complement C5 inhibitor therapy
Exclusion Criteria- Geographic atrophy that is secondary to a condition other than age-related macular degeneration
- Ocular or periocular infections
- Active intraocular inflammation
Inclusion Criteria- Provider is a VA or VA Community Care ophthalmologist
- Diagnosis of geographic atrophy secondary to age-related macular degeneration
Pregnancy & Reproductive Considerations- Pregnancy should be excluded prior to receiving pegcetacoplan
- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 40 days after stopping treatment
Monitoring & Management- Monitor for signs of neovascular AMD due to increased rates associated with clinical trial use
- If anti-VEGF is required, administer separately from pegcetacoplan administration
Indication- Treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)
- Specifically indicated for dry AMD (advanced late stage)
Dosage & Administration- Intravitreal injection of 15 mg (0.1 mL of 150 mg/mL solution) to each affected eye
- Dosing interval: Once every 25 to 60 days
Contraindications- Ocular or periocular infection
- Active intraocular inflammation
Warnings & Precautions- Neovascular AMD: Associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (CNV); monitor for signs. If anti-VEGF therapy is required, administer separately from pegcetacoplan.
- Retinal vasculitis: Post-marketing reports of occlusive and non-occlusive retinal vasculitis following injection; associated with intraocular inflammation. Discontinue use of 19-gauge filter needles; utilize kits containing 18-gauge needles.
- Endophthalmitis and retinal detachments
- Intraocular inflammation
- Increased intraocular pressure
Patient Population & Special Considerations- Women of childbearing potential: Use effective contraception during treatment and for 40 days after the last dose. Assess risks and benefits for women planning pregnancy.
- Patients with a history of choroidal neovascularization (CNV) in the fellow eye have a greater risk of developing exudative AMD.
Formulary Use Restrictions- Use should be restricted to the treatment of GA secondary to AMD when no contraindications are present.
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Inclusion Criteria- Prescribed by a REMS registered VA or VA Community Care hematologist, oncologist, immunologist or genetic specialist
- Laboratory-confirmed diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH), as evidenced by detectable GPI-deficient hematopoietic clones (Type III PNH red blood cells (RBC)) via Flow Cytometry
- Evidence of clinically significant hemolysis (e.g., Hemoglobin <10g/dL) despite 6 months of stable therapy with anti-C5 inhibitor (e.g., ravulizumab or eculizumab)
- Complete or update vaccination for encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis at least 2 weeks prior to the first dose of therapy according to current Advisory Committee on Immunization Practices (ACIP)
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SPARSENTAN TAB
FILSPARI
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FILSPARI |
2023-03-02 |
Indication- FDA approved to reduce proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g.
- Approved under accelerated approval based on reduction of proteinuria; it has not been established whether sparsentan slows kidney function decline. Continued approval is contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
Dosing & Administration- Available as 200 mg and 400 mg tablets.
- Administered once daily, swallowed whole with water prior to the morning or evening meal.
- Initial dosing is 200 mg orally once daily; after 14 days, increase to 400 mg once daily as tolerated.
REMS Requirements- Use is restricted to the FILSPARI Risk Evaluation and Mitigation Strategy (REMS) Program.
- Prescribers must be certified by enrolling and completing training.
- All patients must enroll prior to initiating treatment and comply with monitoring requirements.
- Pharmacies must be certified and dispense only to patients authorized to receive sparsentan.
Contraindications- Pregnancy.
- Concomitant use of angiotensin II receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren.
Monitoring & Safety Precautions- Hepatotoxicity: Measure transaminases and bilirubin before initiating treatment, monthly for the first 12 months, then every 3 months during treatment. Interrupt treatment if aminotransferase elevations exceed 3 times the upper limit of normal (ULN). Avoid initiation in patients with baseline aminotransferases >3x ULN due to increased risk and monitoring difficulty. Advise patients to immediately stop treatment and seek medical attention if symptoms of hepatotoxicity occur.
- Embryo-Fetal Toxicity: Require pregnancy testing before initiation, during treatment, and one month after discontinuation. Patients who can become pregnant must use effective contraception before, during, and for one month after treatment.
- Hypotension: Monitor patients at risk; consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status. Consider dose reduction or interruption if hypotension develops despite adjustments. Transient hypotensive response is not a contraindication to further dosing once blood pressure stabilizes.
- Acute Kidney Injury: Periodically monitor kidney function. Withhold or discontinue therapy in patients who develop a clinically significant decrease in kidney function. Particular risk exists for patients whose kidney function depends on the renin-angiotensin system (e.g., renal artery stenosis, CKD, severe congestive heart failure, volume depletion).
- Hyperkalemia: Periodically monitor serum potassium and treat appropriately. Increased risk in patients with advanced kidney disease or those taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes). Consider dose reduction or discontinuation if hyperkalemia develops.
- Fluid Retention: Evaluate clinically significant fluid retention to determine cause and potential need for diuretic adjustment; consider modifying sparsentan dose. Not evaluated in patients with heart failure.
Drug Interactions & Use Restrictions- RAS inhibitors, ERAs, aliskiren: Contraindicated due to increased risk of hypotension and hyperkalemia.
- Strong CYP3A inhibitors/inducers: Avoid concomitant use (increases or decreases sparsentan exposure, respectively).
- Moderate CYP3A inhibitors: Monitor for adverse reactions due to increased sparsentan exposure.
- Antacids/Acid-reducing agents: Avoid antacid use within 2 hours before or after sparsentan; avoid concomitant use of acid-reducing agents due to decreased sparsentan exposure.
- NSAIDs/COX-2 inhibitors: Monitor for signs of worsening renal function and increased risk of kidney injury.
- CYP2B6, 2C9, 2C19 substrates: Monitor for efficacy due to decreased substrate exposure.
- Sensitive P-gp and BCRP substrates: Avoid concomitant use due to increased substrate exposure.
- Agents increasing serum potassium: Monitor serum potassium frequently due to increased hyperkalemia risk.
Patient Selection/Clinical Context- Target population includes patients with biopsy-proven primary IgAN, proteinuria > 1 g/day at screening, eGFR > 30 mL/min/1.73 m2 at screening, on a stable dose of an ACEI and/or ARB at maximum tolerated dose for ≥12 weeks prior to screening, and SBP < 150 mmHg and DBP < 100 mmHg.
- Excludes patients with secondary IgAN or IgA vasculitis; cellular glomerular crescents > 25% on renal biopsy; other CKD causes; history of organ transplantation (except corneal); systemic immunosuppressants use > 2 weeks in the last 3 months; heart failure history/hospitalization/unexplained dyspnea/edema; significant cerebrovascular or coronary artery disease within 6 months; jaundice/hepatitis/liver disease or ALT/AST > 2x ULN; malignancy (except adequately treated BCC/SCC/cervical cancer in past 2 years); hematocrit < 27% or hemoglobin < 9 g/dL; potassium > 5.5 mEq/L; alcohol/illicit drug use disorder; serious side effect/allergy to ARB/ERA; or pregnancy/breastfeeding/planning pregnancy.
- Place in therapy follows optimized supportive care (lifestyle intervention, dietary sodium restriction, smoking cessation, weight control, exercise) and ACEI/ARB treatment for proteinuria > 0.5 g/d. Glucocorticoid therapy may be considered for patients remaining at high risk of progressive CKD despite maximal supportive care.
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DABIGATRAN PELLET
PRADAXA
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PRADAXA |
2023-02-23 |
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
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ELACESTRANT TAB
ORSERDU
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ORSERDU |
2023-02-09 |
Indication & Patient Population- • Treatment of ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer (MBC)
- • Indicated after progression on/after >1L endocrine therapy in men or postmenopausal women
- • Prior therapy must include 1L with a CDK4/6 inhibitor + AI or fulvestrant, OR progression on/within 12 months of adjuvant endocrine therapy
Clinical Monitoring & Management- • Evaluate hepatic function at baseline and throughout the course of treatment
- • Evaluate lipid profile at baseline and throughout the course of treatment
- • Assess for potential drug-drug interactions at baseline and throughout treatment
- • Take daily dose with food to minimize GI distress
Contraindications & Warnings/Precautions- • Contraindications: None
- • Boxed warnings: None
- • Warnings/Precautions: Dyslipidemia, Embryo-fetal toxicity
- • Avoid use in severe hepatic impairment (Child-Pugh C)
- • Dose-reduce in moderate hepatic impairment
Drug Interactions & Administration- • Avoid concomitant use with moderate-strong CYP3A4 inducers or inhibitors
- • Use caution with P-gp substrates and BCRP substrates due to increased concentration and adverse effects
- • Dosage form: Oral tablets (86 mg and 345 mg)
Exclusion Criteria- Hypersensitivity to elacestrant or any of its components
- Severe hepatic impairment (Child-Pugh C)
Inclusion Criteria- Men or postmenopausal women with advanced or metastatic breast cancer
- Hormone receptor (HR)-positive, HER2-negative breast cancer
- ESR1-mutation positive as detected by an approved test
- Progressive disease on or after an endocrine-based regimen that included a CDK4/6 inhibitor [including adjuvant regimens if progress within 12 months]
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0 – 1
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (Select if applicable)- For patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after treatment.
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PEXIDARTINIB CAP,ORAL
TURALIO
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TURALIO |
2023-02-09 |
Exclusion Criteria- Baseline ALT, AST, total bilirubin, or direct bilirubin > ULN (local laboratory reference values)
- Active liver or biliary tract disease, including increased alkaline phosphatase (ALP)
- Active or chronic hepatitis B viral infection
- Active or chronic hepatitis C viral infection
- Known active or chronic HIV infection
- Concomitant use of strong CYP3A inducers
- Concomitant use of proton pump inhibitors
- Concomitant use of hormonal contraceptives (CYP3A substrate), unless another highly effective nonhormonal contraception is used in combination
- Concomitant use of other CYP3A substrates when minimal decreases in drug concentration can result in serious therapeutic failures
- Unwilling or unable to comply with recommended laboratory monitoring
- Breastfeeding
Inclusion Criteria- Care provided by a VA/VA Community Care oncologist or locally designated expert
- Histologically confirmed, symptomatic, nonmetastatic TGCT, including pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCT-TS)
- TGCT is associated with severe morbidity or functional limitations
- TGCT is not amenable to improvement with surgery, or surgical resection is likely to be associated with potentially worse functional limitation or severe morbidity
- No improvement after 12 weeks of imatinib, disease progression despite imatinib, or imatinib is medically inadvisable (e.g., contraindication, unmanageable toxicity, etc.)
Dosing, Monitoring, and Program Requirements- Prescribed at the FDA-approved dose for TGCT, modified as recommended for moderate or strong CYP3A inhibitors and UGT inhibitors (if unavoidable), and for mild to severe renal impairment (CrCl 15–89 mL/min)
- Pregnancy excluded in the previous 14 days for women of childbearing potential and men who partner with women of childbearing potential
- Patient counseled on use of highly effective contraception and risks/benefits of treatment
- Prescriber must be certified; patient must be enrolled in the TURALIO REMS program
- Use without a prior trial of imatinib requires case-by-case request following a risk-benefit discussion between the patient and provider
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PIRTOBRUTINIB TAB
JAYPIRCA
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JAYPIRCA |
2023-02-09 |
Indications & Patient Population- Adult patients with relapsed or refractory mantle cell lymphoma (MCL)
- Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL)
Prior Therapy Requirements- MCL: At least two lines of systemic therapy, including a BTK inhibitor
- CLL/SLL: At least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor
Dosing & Administration- Recommended dosage: 200 mg once daily, with or without food
- Duration: Until disease progression or unacceptable toxicity
- Available tablet strengths: 50 mg, 100 mg
Renal Impairment- Dose reduction recommended for renal dysfunction
- Reduce dose by 50% for eGFR 15 to 29 ml/min/1.73m2 to a minimum dose of 50 mg daily
Safety & Monitoring Precautions- Infections: Monitor for signs and symptoms; consider prophylaxis for patients at increased risk, including opportunistic pathogens
- Hemorrhage: Monitor for signs of bleeding; consider risk versus benefit of concurrent antithrombotic agents
- Cytopenias: Monitor/manage neutropenia, thrombocytopenia, and anemia
- Cardiac Arrhythmias: Monitor for signs and symptoms; concurrent cardiac risk factors (e.g., hypertension or history of arrhythmias) may increase risk
- Second Primary Malignancy: Advise patients to wear sunscreen; monitor for development
- Hepatotoxicity: Evaluate liver function tests at baseline and throughout treatment; permanently discontinue for hepatotoxicity or hold if suspected
- Embryo-Fetal Toxicity: Recommend effective contraception during treatment and for one week after the last dose in females of reproductive potential
- Breastfeeding: Advise patients to avoid breastfeeding while taking pirtobrutinib and through 1 week after the last dose
- Older Adults: Higher rates of grade ≥3 adverse effects observed in patients aged ≥65 years
Exclusion Criteria- Patient has not been screened for Hepatitis B Virus (HBV)
- Unmanageable drug-drug or drug-food interaction identified
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (NYHA Class 3 or 4), or myocardial infarction in prior 6 months
- Current or history of central nervous system (CNS) lymphoma
- Active or uncontrolled infection
- Pregnancy
- Lactating
Inclusion Criteria (Indications & Prior Therapy)- Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor
- Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor
Additional Inclusion Criteria (Reproductive Health & Counseling)- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
- Advise patients not to breastfeed and/or provide breastmilk to an infant during treatment and for at least 1 weeks after the last dose
Additional Inclusion Criteria (Performance Status, Provider, & Care Planning)- Eastern Cooperative Oncology Group Performance Status 0-2
- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
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TRIAMCINOLONE INJ,SUSP
TRIESENCE, XIPERE
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TRIESENCE, XIPERE |
2023-02-06 |
Indication & Patient Population- • Treatment of macular edema associated with uveitis (UME) / non-infectious uveitis (anterior, intermediate, posterior, or panuveitis).
- • Patients with central subfield thickness (CST) of 300 µm or more measured by optical coherence tomography.
- • Patients who have had an inadequate response or clinically significant adverse events to periocular or intravitreal triamcinolone injection, or have contraindications to those therapies.
- • Steroid-responsive patients, particularly those unable to tolerate an additional increase in intraocular pressure (IOP).
Dosing & Administration- • Suprachoroidal injection via proprietary SCS Microinjector.
- • Dose: 4 mg of triamcinolone acetonide (0.1 mL) per administration.
- • Single-dose package intended for use in only one eye.
- • Administered at baseline and week 12.
- • Office-setting procedure requiring minimal training for the retinal specialist.
Contraindications & Exclusions- • Ocular or periocular infection.
- • Hypersensitivity to triamcinolone or its components.
- • Active ocular disease or infection in the study eye other than uveitis.
- • Uncontrolled glaucoma.
- • IOP greater than 22 mmHg.
- • Active ocular herpes simplex.
Safety & Monitoring Considerations- • Use of corticosteroids may produce cataracts, increased intraocular pressure, and glaucoma.
- • Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses.
- • Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex.
- • Corticosteroids should not be used in patients with active ocular herpes simplex.
Practice & Specialist Restrictions- • Use restricted to retina and uveitis specialists.
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TRIAMCINOLONE INJ,SUSP
TRIESENCE, XIPERE
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TRIESENCE, XIPERE |
2023-02-06 |
Indication & Patient Population- • Treatment of macular edema associated with uveitis (UME) / non-infectious uveitis (anterior, intermediate, posterior, or panuveitis).
- • Patients with central subfield thickness (CST) of 300 µm or more measured by optical coherence tomography.
- • Patients who have had an inadequate response or clinically significant adverse events to periocular or intravitreal triamcinolone injection, or have contraindications to those therapies.
- • Steroid-responsive patients, particularly those unable to tolerate an additional increase in intraocular pressure (IOP).
Dosing & Administration- • Suprachoroidal injection via proprietary SCS Microinjector.
- • Dose: 4 mg of triamcinolone acetonide (0.1 mL) per administration.
- • Single-dose package intended for use in only one eye.
- • Administered at baseline and week 12.
- • Office-setting procedure requiring minimal training for the retinal specialist.
Contraindications & Exclusions- • Ocular or periocular infection.
- • Hypersensitivity to triamcinolone or its components.
- • Active ocular disease or infection in the study eye other than uveitis.
- • Uncontrolled glaucoma.
- • IOP greater than 22 mmHg.
- • Active ocular herpes simplex.
Safety & Monitoring Considerations- • Use of corticosteroids may produce cataracts, increased intraocular pressure, and glaucoma.
- • Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses.
- • Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex.
- • Corticosteroids should not be used in patients with active ocular herpes simplex.
Practice & Specialist Restrictions- • Use restricted to retina and uveitis specialists.
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LECANEMAB-IRMB INJ,SOLN
LEQEMBI, LEQEMBI IQLIK
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LEQEMBI, LEQEMBI IQLIK |
2023-01-19 |
Exclusion Criteria- Age less than 60 years
- Medical, neurological, or mental health condition contributing to cognitive impairment
- Contraindication to or inability to complete brain MRI
- Transient ischemic attack, stroke, or seizures within the past year
- Evidence of other clinically significant lesions on brain MRI indicating another cause of dementia
- Screening MRI evidence excluding treatment (including >4 microhemorrhages, single macro hemorrhage >10 mm, superficial siderosis, vasogenic edema, acute/subacute cerebral contusion or stroke, aneurysms, vascular malformations, infective lesions, severe small vessel/white matter disease, space-occupying lesions, or intra-axial brain tumors)
- ApoE e4 homozygote
- Uncontrolled immunological disease or requirement for biologic drug treatment
- Untreated bleeding disorder, platelet count <50,000 x 109/L, or INR >1.5
- Thyroid stimulating hormone above normal range (TSH > 5 mU/L if < 65 years old; TSH > 7.5 mU/L if > 65 years old)
- Low serum vitamin B12 level
- Untreated human immunodeficiency virus (HIV)
- Malignant neoplasm under active therapy (unless approved by oncologist)
- Positive Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation item 4 or 5, or any suicidal behavior within the past 6 months
- Hospitalization or treatment for suicidal behavior in the past 5 years
- Current substance use disorder or positive urine drug screen
- Use of anti-platelet or anti-coagulant medications (e.g., apixaban, clopidogrel, NSAIDs, t-PA), except aspirin
Inclusion Criteria- Prescriber must be a VA board-certified neurologist, geriatric psychiatrist, or geriatrician specializing in dementia treatment
- Signed informed consent on file; if genotype testing is not performed, patient and provider accept the risk
- Meets criteria for mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD) dementia
- MRI scan completed within the last 6 months
- Amyloid PET imaging, cerebrospinal fluid (CSF) analysis consistent with AD (e.g., Beta-amyloid [1-42] < 1030 pg/ml), or clearly positive blood biomarker (e.g., FDA-cleared Lumipulse G pTau 217/B-Amyloid 42 Plasma Ratio >0.00738)
- Cognitive/functional assessment scores meeting thresholds: Mini-Mental State Examination (MMSE) score > 21, Saint Louis University Mental Status (SLUMS) score > 16, Montreal Cognitive Assessment (MoCA) score > 16, or Functional Assessment Staging Test (FAST) Stage 2-4
- Neuroradiology available to review serial MRI scans (at site or through National Teleradiology)
- Established process to hold infusion until ordering physician assesses patient and determines whether to continue treatment
Indication & Disease State- • Treatment of Alzheimer’s disease
- • Initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease
- • Confirmed presence of Aβ pathology
Patient Selection & Inclusion Criteria- • Diagnosis of MCI due to AD (CDR score 0.5) or mild AD (CDR score 0.5-1)
- • Memory impairment [Wechsler Memory Scale IV-Logical Memory (subscale) II] >1 standard deviation below age-adjusted mean
- • Positive biomarker for brain amyloid pathology (PET, CSF t-tau/Aβ)
- • Aged > 50 and < 90 years
- • MMSE score between 22 and 30
- • BMI > 17 and < 35
- • If using drugs to treat symptoms related to AD, doses must be stable for at least 12 weeks prior to baseline
Exclusion Criteria- • Any neurological condition (other than AD) that may contribute to cognitive impairment
- • Transient ischemic attack, stroke, or seizures within 1 year prior to screening
- • Psychiatric diagnosis or symptoms interfering with procedures (e.g., hallucinations, major depression, delusions)
- • Geriatric Depression Scale (GDS) score ≥ 8 at screening
- • Contraindications to MRI scanning (cardiac pacemaker/defibrillator, ferromagnetic metal implants)
- • Evidence of other clinically significant lesions on brain MRI indicating a dementia diagnosis other than AD
- • Significant pathological findings on brain MRI: >4 microhemorrhages; single macro hemorrhage >10 mm; superficial siderosis; vasogenic edema; cerebral contusion, encephalomalacia, aneurysms, vascular malformations, infective lesions; multiple lacunar infarcts/stroke involving a major vascular territory, severe small vessel/white matter disease; space-occupying lesions; brain tumors
- • Immunological disease not adequately controlled or requiring biologic drugs during treatment
- • Bleeding disorder not under adequate control (platelet count <50,000 or INR >1.5)
- • Thyroid stimulating hormone above normal range
- • Abnormally low serum vitamin B12 levels
- • HIV positive status
- • Malignant neoplasms within 3 years of screening
- • Suicidal ideation Type 4 or 5 on C-SSRS, suicidal behavior within 6 months before/at screening/baseline, or hospitalization/treatment for suicidal behavior in past 5 years
- • Drug or alcohol abuse/dependence within 2 years before screening or positive urine drug test at screening
Dosing & Administration- • Injection: 100 mg/ml
- • Intravenous (IV) infusion, 10 mg/kg, over an hour, every 2 weeks
Monitoring & Safety Management- • Requires a recent (within one year) brain MRI prior to initiating treatment
- • Periodic MRI monitoring required prior to the 5th, 7th, and 14th infusions
- • Enhanced clinical vigilance for amyloid-related imaging abnormalities (ARIA) during the first 14 weeks of treatment
- • Mild ARIA: Continue dosing if asymptomatic; suspend dosing if symptomatic
- • Moderate to severe ARIA: Temporarily suspend dosing until resolution
- • Severe ARIA-H: Permanently discontinue dosing
- • Infusion-related reactions: Reduce or discontinue infusion rate and administer appropriate therapy as clinically indicated; consider pre-medication with antihistamine, NSAIDs, or corticosteroids at subsequent dosing
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PIRFENIDONE CAP,ORAL
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2023-01-19 |
Indication & Diagnostic Requirements- Diagnosis of idiopathic pulmonary fibrosis (IPF)
- Must meet ATS/ERS/JRS/ALAT diagnostic requirements
- Confirmed through formal interdisciplinary discussion (Interstitial Lung Disease Consensus Committee or similar)
- Requires exclusion of other known causes of interstitial lung disease (e.g., environmental exposures, connective tissue disease, drug toxicity)
- Requires pattern of usual interstitial pneumonia on high-resolution computed tomography (HRCT) and/or specific combinations of HRCT and surgical lung biopsy patterns
Patient Selection & Exclusion Criteria- Patient should NOT receive pirfenidone if: IPF diagnosis unconfirmed; current smoker; severe hepatic impairment (Child Pugh Class C); end-stage renal disease requiring dialysis; currently receiving nintedanib; taking combination of moderate/strong CYP1A2 inhibitors with other CYP inhibitors that cannot be altered/discontinued; or documented ongoing nonadherence
- Treatment must be initiated and followed by a VA Pulmonologist experienced in ILD diagnosis and management
Dosage & Administration- Recommended dosage: 801 mg three times daily with food (total 2403 mg/day)
- Doses should be taken at the same time each day
- Titration schedule for initiation or resumption after ≥14-day lapse over 14 days: Days 1–7: one 267mg capsule three times daily; Days 8–14: two 267mg capsules three times daily; Day 15 onward: one 801mg tablet three times daily
- Dose modifications may be required for side effects, liver function abnormalities, or drug interactions
Monitoring & Laboratory Requirements- Pulmonary specialty follow-up including pulmonary function testing at least biannually to assess drug response
- Adherence monitoring required for maximal benefit
- Liver chemistries (AST, ALT, total bilirubin): obtain at baseline, monthly for 6 months, then every 3 months thereafter
- FVC and DLCO measurements: routine monitoring at 3–6 month intervals; more frequent testing if progressive dyspnea or rapidly progressive course present
- Advise patients to avoid/minimize sunlight/UV exposure and use SPF≥50 sunblock and occlusive clothing/hats due to photosensitivity/rash risk
Management of Adverse Reactions & Liver Abnormalities- AST/ALT >3 to ≤5x ULN without symptoms/hyperbilirubinemia: discontinue confounding medications, exclude other causes, monitor closely, repeat tests as indicated; maintain full dose if appropriate or reduce/interrupt until normal, then re-titrate
- AST/ALT >3 to ≤5x ULN with symptoms/hyperbilirubinemia: permanently discontinue and do not rechallenge
- AST/ALT >5x ULN: permanently discontinue and do not rechallenge
- Strong CYP1A2 inhibitors: Co-administration of pirfenidone with strong CYP1A1 inhibitors (ex: fluvoxamine, enoxacin) is not recommended; if unavoidable, reduce dose of pirfenidone to 267mg three times daily
- Moderate CYP1A2 inhibitors: Reduce dose of pirfenidone to 534mg three times daily in combination with high-dose moderate CYP1A2 inhibitor (ex: ciprofloxacin 750mg twice daily)
- Strong/moderate CYP1A2 inhibitors combined with other CYP inhibitors: Discontinue or avoid combinations due to unpredictable clearance effect
- Strong CYP1A2 inducers: Co-administration not recommended due to expected reduction in pirfenidone exposure and loss of efficacy
- Temporary dose reductions may be required to allow resolution of symptoms
Discontinuation Guidelines- Temporarily discontinue for mildly elevated liver function tests or moderate severity adverse reactions (rash, photosensitivity, gastrointestinal, or other)
- Permanently discontinue for: severe adverse drug reactions, liver function test abnormalities per monitoring criteria, significant nonadherence to therapy, or smoking
- Consider discontinuation for perceived treatment failure based on serial pulmonary function trends
Special Populations & Clinical Considerations- Pregnancy Category C; women of childbearing potential require contraceptive counseling; use during pregnancy only if maternal benefit outweighs fetal risk
- Unknown excretion in breast milk; decide to discontinue nursing or pirfenidone based on drug importance to mother
- Limited data for severe IPF (FVC < 50%); randomized controlled trials did not enroll patients with severe disease
- Lung transplant wait list: Inadequate data; case-specific assessment of risks and benefits recommended due to short median wait times and high mortality rates among listed patients
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UBLITUXIMAB-XIIY INJ,SOLN
BRIUMVI
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BRIUMVI |
2023-01-13 |
Indications- • Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (active SPMS).
Dosing & Administration- • Intravenous infusion via single-dose vial.
- • First infusion: 150 mg; second infusion: 450 mg administered two weeks after the first.
- • Maintenance dosing: 450 mg every 24 weeks, starting 24 weeks after the first infusion.
- • Initial infusion duration approximately 4 hours; subsequent infusions approximately 1 hour.
Efficacy Outcomes- • Significantly lower adjusted annualized relapse rate (ARR) compared to teriflunomide over 96 weeks.
- • Significant reduction in average number of contrast enhancing lesions and new or enlarged non-enhancing lesions.
- • No statistically significant difference in delay of disability progression or confirmed disability progression compared to teriflunomide.
Safety, Contraindications & Monitoring- • Contraindicated in patients with active hepatitis B infection or a history of life-threatening infusion reaction to ublituximab.
- • Infusion reactions (e.g., fever, chills, headache, flu-like symptoms, tachycardia, nausea, erythema, anaphylaxis) occurred in 48% of patients, primarily with the first infusion. Pre-medication with a steroid, antihistamine, and acetaminophen is recommended; careful observation with pausing or discontinuation based on severity is warranted.
- • Infections were the most common adverse reaction (56% incidence), with approximately 5% classified as serious. Monitor for bacterial, fungal, and viral infections.
- • Decreased immunoglobulins (IgG and IgM) observed; declines below the lower limit of normal are associated with higher infection rates. Monitor immunoglobulins during treatment as clinically indicated.
- • Vaccination requirements: Administer live vaccines at least 4 weeks prior to initiation; administer non-live vaccines at least 2 weeks prior. Do not administer live vaccines while on therapy. Non-live vaccines may be administered during treatment.
- • Fetal risk: Transient B-cell depletion and lymphocytopenia reported in infants of mothers exposed to anti-CD20 antibodies. Recommend pregnancy testing for individuals of childbearing potential prior to each infusion. Counsel to use effective contraception during treatment and for at least 6 months after the last infusion.
Patient Selection & Trial Eligibility Criteria- • Age 18–55 years with a relapsing form of MS.
- • Baseline Expanded Disability Status Scale (EDSS) score of 0 to 5.5.
- • Requirement for neurologic stability for 30 days prior to enrollment.
- • Excludes patients with ≥10 years disease duration and EDSS ≤2.
- • Requires washout periods for prior disease-modifying therapies (DMTs): anti-CD20 antibodies, alemtuzumab, natalizumab, teriflunomide, leflunomide, stem cell transplant; cladribine within 24 months; daclizumab, azathioprine, methotrexate, cyclophosphamide within 6 months; fingolimod, experimental S1P modulators, IVIg, plasmapheresis within 90 days; glatiramer, interferons, dimethyl fumarate, laquinimod, glucocorticoids within 30 days.
Place in Therapy & Clinical Considerations- • Classified as a high-efficacy disease-modifying therapy (DMT) for MS.
- • May be considered for patients with highly active MS or those who have experienced therapeutic inefficacy from other DMTs.
- • Comparative efficacy data show no statistically significant difference in ARR between ublituximab, ocrelizumab, ofatumumab, and off-label rituximab.
- • Has one of the shorter infusion times among IV infused anti-CD20 antibodies.
Exclusion Criteria- Diagnosis of primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis without activity (i.e., non-active SPMS)
- History of life-threatening infusion reaction to another anti-CD20 antibody (e.g., ocrelizumab, rituximab)
- Untreated active hepatitis B infection
- Untreated latent or active tuberculosis infection
- Concurrent use of another disease modifying therapy (DMT) to treat multiple sclerosis (MS) unless the previous agent will be discontinued when ublituximab is initiated
- Active infection or receiving chemotherapy
- Pregnancy
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist or locally designated MS expert (e.g., Spinal Cord Injury)
- Diagnosis of a relapsing form of multiple sclerosis established (relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome)
- Screening for hepatitis B virus (HBV) completed (HBsAg, HBsAb, and HBcAb); if HBsAb negative and HBcAb positive or HBsAg positive, consultation with a liver disease expert is required first
- Quantitative serum immunoglobulins tested; if low, neurologist documentation of risk/benefit assessment and/or immunology expert consultation prior to initiation
- Administration of all guideline-recommended eligible immunizations at least 4 weeks prior to treatment for live or live-attenuated vaccines, and whenever possible at least 2 weeks prior for inactivated vaccines
Additional Inclusion Criteria (One of the following must be met)- Current treatment with natalizumab combined with elevated risk factors for progressive multifocal leukoencephalopathy (PML) (anti-JC virus antibody positive, duration of therapy > 24 months, or prior immunosuppressant therapy)
- Ineffectiveness with at least one other MS DMT, defined as continued clinical relapses, central nervous system (CNS) lesion progression on MRI, or continued worsening of disability
- Highly active disease demonstrated by heavy burden of gadolinium enhancing and/or T2 lesions on MRI at onset of disease, high accumulation of CNS lesions on MRI, or rapid accrual of disability
Pregnancy & Reproductive Management- For patients who can become pregnant: Pregnancy must be excluded prior to receiving ublituximab
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and requirement for effective contraception during therapy and for 6 months after stopping treatment
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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LENACAPAVIR TAB
SUNLENCA, YEZTUGO
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SUNLENCA, YEZTUGO |
2023-01-05 |
Indications & Patient Population- HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant (MDR) HIV-1 infection failing current antiretroviral treatment (ART) regimen due to resistance, intolerance, or safety considerations
- Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition
Dosing & Administration Requirements- Administered as extended-release injectable suspension for subcutaneous (SQ) administration
- Maintenance dose: 927 mg (3 mL = 2 vials) SQ injection every 26 weeks (±2 weeks) from the date of the last SQ injection
- Requires oral initiation dosing prior to maintenance injections (Option #1 for HIV treatment/PrEP or Option #2 for HIV treatment only)
- Dosing series must be restarted with initiation dosing if more than 28 weeks have elapsed since the last injection
Safety, Monitoring & Contraindications- Boxed warning: Risk of drug resistance with use of LEN for PrEP in undiagnosed HIV-1 infection
- Must test for HIV-1 infection prior to initiating LEN and with each subsequent injection using a test approved or cleared by the FDA; do not initiate unless negative infection status is confirmed
- Contraindicated with concomitant administration of strong CYP3A inducers (risk of loss of therapeutic effect and development of resistance)
- Not recommended with moderate CYP3A inducers, P-gp inhibitors, UGT1A1 inhibitors, or strong CYP3A4 inhibitors (including cobicistat and ritonavir) due to risk of increased LEN serum concentration
- LEN is a moderate CYP3A inhibitor; may increase exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last SQ dose
- Immune reconstitution syndrome possible during initial phase for HIV treatment
- If discontinued, initiate an alternative fully suppressive ART or PrEP regimen within 28 weeks after the last LEN dose; subtherapeutic serum concentrations may extend beyond 12 months after stopping LEN for PrEP
Adherence & Place in Therapy Considerations- For HIV treatment: Reserve for patients unable to formulate a viable suppressive regimen with two fully active agents due to predicted resistance (genotypic or phenotypic), drug intolerance, DDIs, or dual-mixed/CXCR4-tropism (for maraviroc)
- Requires patient understanding and commitment to receive LEN SQ injection every 26 weeks (±2 weeks) administered by a healthcare provider
- For PrEP: Reserved for individuals with contraindications, intolerance, or inability to adhere to oral TDF/FTC; daily oral TDF/FTC remains the preferred first-line PrEP agent
Storage & Handling- Oral tablets must be dispensed only in original blister pack and stored at 20–25 °C
- SQ injection dosing kit (2 single-dose vials) must be stored at 20–25 °C in the original carton to protect from light until preparation
- Injection should be administered as soon as possible once solutions are drawn into syringes
Indications & Target Populations- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.
Exclusion Criteria- Significant noncompliance with follow-up appointments unless barriers to compliance have been significantly addressed by provider
- Drug interactions that preclude administration of lenacapavir (moderate or strong CYP3A or P-gp inducers; combined P-gp, UGT1A1 and strong 3A4 inhibitors)
Inclusion Criteria (All Required)- Lenacapavir prescribed by, or in collaboration with, a provider with experience or training in the administration of PrEP (designated facility providers)
- Substantial risk of HIV acquisition (sex without condoms, multiple sexual partners, recent or frequent sexually transmitted infections, sexual relationship with HIV infected partner, injection drug use with equipment sharing)
- Documentation that patient agrees to required HIV testing and dosing schedule
Additional Inclusion Criteria (One Required)- Intolerance or contraindication to Truvada (TDF/FTC)
- CrCl of 15-59 mL/min or multiple risk factors for significant renal dysfunction
- Patient specific factors impacting adherence to daily oral PrEP (e.g., cognitive difficulties, gastrointestinal dysfunction, unstable housing, stigma, or fear of discovery)
Testing Requirements- Confirmed negative HIV-1 Ag/Ab lab based test within 7 days of each administration
- HIV RNA test recommended prior to initiation; results should not delay initiation; if unavailable, obtain repeat HIV-1 Ag/Ab test within 1 month of initiation
Administration & Dosing- Subcutaneous administration into the abdomen (preferred) or thigh (alternative) only
- Day 1: 927mg by subcutaneous injection (2 x 1.5mL injections) AND 600mg orally (2 x 300mg tablets)
- Day 2: 600mg orally (2 x 300mg tablets), self-administered at home
- Every 6 months (26 weeks +/- 2 weeks): 927mg by subcutaneous injection (2 x 1.5mL injections)
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MOSUNETUZUMAB-AXGB INJ,SOLN
LUNSUMIO, LUNSUMIO VELO
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LUNSUMIO, LUNSUMIO VELO |
2023-01-05 |
Indications- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
Indication & Approval Status- Relapsed or refractory follicular lymphoma (FL) after 2 or more lines of therapy (LOT)
- Accelerated approval based on response rate; contingent upon verification and description in a confirmatory trial
Patient Population & Eligibility Criteria- Follicular lymphoma grade 1-3a
- ECOG PS 0-1
- s/p > 2 LOT (including anti-CD20 mab and alkylating agent)
- Patients with unfavorable characteristics: relapse after antiCD20 antibody, cytotoxic chemotherapy and lenalidomide or progression < 24 months from all prior treatments
- Not a candidate for cellular therapy
Dosing & Administration Requirements- C#1 Day 1 – 1mg IV over at least 4 hours; Day 8 – 2mg IV; Day 15 – 60mg IV
- C#2 Day 1 – 60mg IV over 2 hours if C#1 doses are tolerated
- C#3+ Day 1 – 30mg IV
- Time-limited dosing (8 or 17 cycles)
Safety & Monitoring Considerations- Boxed warning for CRS
- Monitor for neurologic toxicity, infections, cytopenias, tumor flare, and embryo-fetal toxicity
- CRS incidence: Gr 1-28%; Gr 2-15%; Gr 3-2%; Gr 4-0.5%; recurrent CRS 11%
Guideline & Pathway Recommendations- NCCN guidelines FL v3.2024: 3L and subsequent therapy; preferred regimen includes BiTE (mosunetuzumab)
- VA Oncology Clinical Pathway: Multiply relapsed FL in patients with unfavorable characteristics who are not candidates for cellular therapy
Exclusion Criteria- Facility is not equipped to monitor and manage Cytokine Release Syndrome (CRS)
- Absolute Neutrophil Count < 1000/µL, Platelet count < 75,000/µL (if no bone marrow involvement)
- Total bilirubin > 1.5 times the upper limit of normal (unless Gilbert’s syndrome or liver involvement)
- Alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase > 3 times the upper limit of normal (unless liver involvement)
- Creatinine clearance < 60 ml/min
- Active or uncontrolled infection
- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
Inclusion Criteria- Relapsed or refractory, follicular lymphoma (FL)
- Previously treated with > 2 prior lines of therapy (including 1 line with anti-CD20 monoclonal antibody)
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 3 months after stopping treatment.
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ADAGRASIB TAB
KRAZATI
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KRAZATI |
2022-12-22 |
Exclusion Criteria- Prior treatment with a KRAS G12C inhibitor
- Unmanageable drug interaction identified
- Baseline QTc >480 msec
- Baseline total bilirubin > 1.5 times the Upper Limit of Normal (ULN) [or > 3 times the ULN if associated with liver metastases or Gilbert’s disease] and AST/ALT > 3 times the ULN (or > 5 times the ULN if associated with liver metastases)
- Known pregnancy
- Lactating (during and for 1 week following last dose)
Inclusion Criteria- Diagnosis of KRAS G12C-mutated locally advanced (and ineligible for definitive therapy) or metastatic non-small cell lung cancer with at least 1 prior systemic therapy
- In combination with cetuximab for KRAS G12C-mutated locally advanced or metastatic colorectal cancer after receiving prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy
Additional Required Inclusion Criteria- Care for the oncologic condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
Additional Conditional Inclusion Criteria- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs. benefits and the use of effective contraception during therapy and for at least one week following the last dose
Indication & Patient Population- Adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)
- Patients who have received at least one prior systemic therapy
Diagnostic Testing & Patient Selection- Mutation status must be determined by an FDA-approved test
- Test tumor or plasma specimens for KRAS G12C mutation; if no mutation is detected in a plasma specimen, test tumor tissue
- Do not use in patients who have previously received another KRAS G12C inhibitor (e.g., sotorasib)
Dosing & Administration- Recommended dosage: 600 mg (3 x 200 mg tablets) orally twice daily
- Swallow tablets whole with or without food; take on an empty stomach until disease progression or unacceptable toxicity
- No clinically significant pharmacokinetic differences in patients with creatinine clearance 15-90 mL/min or mild to severe hepatic impairment
Monitoring & Laboratory Requirements- Monitor liver function laboratory tests prior to starting therapy (baseline total bilirubin ≤1.5 times ULN, or ≤3 times ULN if associated with liver metastases or Gilbert’s disease; AST and ALT ≤3 times ULN, or ≤5 times ULN if associated with liver metastases)
- Monitor EKG and electrolytes prior to starting therapy (exclude patients with baseline QTc >480 milliseconds or family history of long QT syndrome)
- Monitor for gastrointestinal toxicity, hepatotoxicity, interstitial lung disease/pneumonitis, and QTc interval prolongation
Contraindications & Drug Interactions- Avoid concomitant use with strong CYP3A4 inducers or inhibitors
- Avoid concomitant use with sensitive CYP3A4, CYP2C9, CYP2D6, or P-gp substrates due to risk of serious adverse reactions from minimal concentration changes
- Avoid concomitant use with drugs that prolong QT interval
- Avoid in patients with congenital long QT syndrome or concurrent QTc prolongation
Special Populations- Pregnancy: Adverse embryo-fetal events observed in animal reproduction studies; use with caution
- Breastfeeding: Not recommended during treatment and for 1 week after the last adagrasib dose due to potential for serious adverse reactions in the breastfed infant
Place in Therapy / Line of Treatment- Reserved for second-line and beyond settings following progression on or after first-line therapy (immunotherapy alone or with platinum-based chemotherapy)
- Indication is approved under accelerated approval based on objective response rate and duration of response; continued approval contingent upon verification of clinical benefit in confirmatory trial(s)
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DAXIBOTULINUMTOXINA-LANM INJ,LYPHL
DAXXIFY
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DAXXIFY |
2022-12-22 |
Exclusion Criteria- Hypersensitivity to botulinum toxins or any components in the formulation (e.g., human serum albumin, lactose, sucrose, disodium succinate)
- Co-administration with neuromuscular blockade
- Neurologic condition where botulinum toxins pose risk for additive neuromuscular compromise (e.g., myasthenia gravis, amyotrophic lateral sclerosis), unless risks/benefits have been discussed with the patient and documented in the medical record
- Use for cosmetic purposes
Inclusion Criteria (Indications)- Cervical dystonia or focal dystonia
- Blepharospasm or hemifacial spasm
- Severe focal hyperhidrosis with inadequate response or unmanageable intolerance to prescription topical therapy (e.g., aluminum chloride hexahydrate 20% topical solution)
- Upper or lower limb spasticity
- Overactive bladder or neurogenic bladder dysfunction with contraindication, intolerance, or inefficacy to behavioral therapy and at least one pharmacotherapy (e.g., antimuscarinic agent, beta-3 adrenergic agonist)
- Chronic migraine prevention with contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 2 of the following: beta blocker, topiramate, divalproex, and ACE inhibitor or ARB
- Pharyngoesophageal segment spasm (PES)
- Sialorrhea with contraindication, intolerance, or lack of therapeutic response to anticholinergics and/or speech therapy
- Chronic anal fissure refractory to conservative treatment including supportive measures (e.g., dietary fiber, sitz bath) and topical vasodilator (e.g., topical nitrates)
- Esophageal achalasia if patient is not a candidate for surgery
- Idiopathic (primary or genetic) or symptomatic (acquired) torsion dystonia
Dosage & Administration- 125 to 250 Units intramuscularly (IM) among affected muscles
- Administered no more frequently than every 3 months
- Available as sterile lyophilized powder in single-dose vials (50 Units or 100 Units)
Contraindications & Warnings- Known hypersensitivity to botulinum toxins or any other component in the formulation
- Infection at the injection site
- Boxed Warning: Distant spread of toxin may occur; symptoms can range from difficulty swallowing or breathing to death, with risk increased by certain underlying conditions
- Cardiovascular system adverse events (e.g., arrhythmia, myocardial infarction); use caution in patients with pre-existing cardiovascular disease
- Neuromuscular compromise: Increased risk of muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise in patients with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis)
Safety & Drug Interactions- Most common adverse events: Headache, dysphagia, injection site erythema or bruising, injection site pain, and muscular weakness
- Additive neuromuscular blocking effect may occur with concurrent use of aminoglycosides, anticholinergic drugs, muscle relaxants, or other agents interfering with neuromuscular transmission
Clinical Considerations & Place in Therapy- First-line option for the treatment of CD per American Academy of Neurology (AAN) 2016 practice guideline
- Insufficient evidence to support that any one botulinum toxin is more efficacious than another for CD
- No established unit-to-unit conversion from daxibotulinumtoxinA to other botulinum toxins
- Treatment effect may last longer than 12 weeks, though 20–36% of patients requested retreatment prior to the defined "loss of effect" point
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FECAL MICROBIOTA-JSLM SUSP,RTL
REBYOTA
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REBYOTA |
2022-12-22 |
Indication & Patient Population- • Prevention of recurrence of Clostridioides difficile infection (CDI) after completion of antibiotic treatment for recurrent CDI in individuals 18 years of age and older
- • Not indicated for the treatment of active CDI
- • Applicable to adults with recurrent CDI (rCDI), defined as beginning within 8 weeks after treatment for a primary episode
- • Patients must have completed at least 10 days of antibiotics for CDI with symptoms controlled (< 3 loose stools per day)
Dosing & Administration Timing- • Rectal enema, suspension: single 150 mL dose for rectal administration
- • Typically administered 24-72 hours after receipt of antibiotic treatment for CDI
- • Oral antibiotics should be avoided for up to 8 weeks after use
Contraindications & Safety Warnings- • Contraindicated in patients with severe allergic reactions (e.g., anaphylaxis) to any component of REB
- • Carries risk for transmitting infectious agents; requires rigorous screening and appropriate patient selection
- • Avoid use in patients with immune compromise, including those on corticosteroids (≥ 20mg/day prednisone or equivalent), absolute neutrophil count < 1000 cells/uL, or other conditions/therapies causing a compromised immune system
- • Appropriate treatment for acute allergic reactions must be available following administration due to potential anaphylactic reaction risk
- • May contain food allergens as it is manufactured from human fecal matter
Special Populations- • Pregnancy: Not absorbed systemically following rectal administration; maternal use not expected to result in fetal exposure
- • Lactation: Breastfeeding is not expected to result in exposure of the child to REB
- • Geriatrics: Clinical trial data are insufficient to determine if adults 65 years of age or greater respond differently than younger adults
Storage & Handling Requirements- • Store carton in ultracold freezer (−60°C to −90°C) upon receipt, or refrigerated at 2°C to 8°C for up to 5 days including thaw time; do not refreeze
- • Store administration set separately at 10°C to 34°C; do not store in the freezer
Clinical Context & Provider Oversight- • Intended as adjunct therapy following a course of standard CDI antibiotic therapy
- • Specialists (e.g., Infectious Diseases or Gastroenterology providers) should be included in the decision to use REB to ensure appropriate patient selection and safe use
- • Not approved for use in other gastrointestinal or non-GI conditions (e.g., IBD, IBS)
Exclusion Criteria- History of severe allergic reactions to any component of REBYOTA
- Asymptomatic Clostridioides difficile colonization
- Likely to require antibiotic therapy for a condition other than Clostridioides difficile infection (CDI) OR planned surgery requiring perioperative antibiotics within 8 weeks after treatment
- Severe immunosuppression (includes neutropenia, early post solid organ or peripheral blood stem cell transplant, or equivalent degree of immunosuppression from other diseases or medications)
Inclusion Criteria- At least 2nd episode of recurrent CDI (3rd episode overall) in the previous 12 months (defined as CDI recurring within 8 weeks of completion of standard CDI treatment)
- Successful treatment of current episode of CDI with standard of care CDI antibiotics (fidaxomicin or PO vancomycin)
- Administration within 1-3 days after completion of standard of care CDI antibiotics (fidaxomicin or PO vancomycin)
- At least one episode of CDI was treated with fidaxomicin, unless not tolerated or contraindicated
Dosage and Administration- Single dose of 150 mL rectally as an enema, 24-72 hours after the last dose of antibiotics for CDI
Supplemental Information- Not studied and not FDA indicated for an initial episode of CDI
- Should be avoided in immunocompromised patients; further data required before making a recommendation in this population
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FINGOLIMOD TAB,ORAL DISINTEGRATING
TASCENSO ODT
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TASCENSO ODT |
2022-12-22 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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OLUTASIDENIB CAP,ORAL
REZLIDHIA
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REZLIDHIA |
2022-12-15 |
Exclusion Criteria- Severe renal impairment (defined as CrCl < 30 ml/min)
- Severe hepatic impairment (defined as total bilirubin > 3x Upper limit of normal and any AST)
- Chronic or unresolved infection
- Unmanageable drug interaction
- Pregnancy
- Breastfeeding
Inclusion Criteria- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- ECOG performance status 0-2
- Presence of an isocitrate dehydrogenase-1 (IDH-1) mutation
- Diagnosis of relapsed or refractory acute myeloid leukemia
Reproductive Health & Counseling Requirements- Pregnancy must be excluded prior to receiving olutasidenib
- Patient must receive contraceptive counseling on potential risks vs. benefits of taking olutasidenib if pregnancy occurs during treatment
- Breastfeeding is contraindicated during treatment and for at least 2 weeks after the last dose
Indication & Patient Selection- Treatment of relapsed or refractory AML with susceptible IDH1 mutation
- Adults aged > 18 years
- ECOG PS 0-2
- QT-interval < 450 ms
- Presence of the IDH1 mutation from blood or marrow sample must be confirmed prior to therapy
- Excluded: patients with symptomatic CNS leukemia, uncontrolled infection or metabolic disorders, prior IDH inhibitor therapy
Dosing & Administration- 150 mg orally twice daily until disease progression, toxicity or HSCT
- Cycle = 28-days
Monitoring & Safety Requirements- Differentiation syndrome: If suspected, hold olutasidenib, initiate corticosteroids and hemodynamic monitoring until symptom resolution
- Hepatotoxicity: Monitor LFTs at baseline, at least once weekly x 2 months; every other week for 3rd month; once in 4th month, and every other month for remainder of therapy. May need to interrupt, hold or discontinue therapy.
- Adverse reactions > 20% include: ↑AST, ↑ALT, ↓potassium, ↓sodium, ↑alk phos, nausea, ↑SCr, fatigue, arthralgia, constipation, ↑lymphocytes, ↑T bili, leukocytosis, ↑uric acid, dyspnea, pyrexia, rash, ↑lipase, mucositis, diarrhea, transaminitis
Contraindications & Precautions- Contraindications: None
- Boxed warning: Differentiation syndrome (Noted in 16%, gr 3-4 in 8%)
- Warnings/Precautions: Hepatotoxicity (Noted in 23%, gr 3-4 in 13%)
Pregnancy & Lactation- Avoid in pregnancy; may cause fetal harm
- Avoid breastfeeding during therapy and for 2 weeks after last dose
Drug Interactions- Avoid strong or moderate CYP3A4 inducers
- Avoid sensitive CYP3A substrates; if unavoidable, monitor for loss of substrate effect
Place in Therapy/Additional Notes- Second FDA-approved IDH1 inhibitor for treatment of IDH1-mutated relapsed/refractory AML
- Not FDA-approved in combination with a hypomethylating agent (i.e., azacitidine, decitabine)
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MIRVETUXIMAB SORAVTANSINE-GYNX INJ,SOLN
ELAHERE
|
ELAHERE |
2022-11-25 |
Exclusion Criteria- Moderate to severe hepatic impairment defined total bilirubin > 1.5x Upper Limit of Normal (unless Gilbert syndrome with total bilirubin > 3x Upper Limit of Normal)
- Severe renal impairment (estimated CrCl 15-30 ml/min)
- Active or chronic corneal or ocular conditions requiring ongoing treatment
- Peripheral neuropathy > Grade 1
- Non-infectious interstitial lung disease, including pneumonitis
- Active or uncontrolled infection
- Unmanageable drug interaction identified
- Known pregnancy
- Lactating
Inclusion Criteria- Diagnosis of epithelial ovarian, fallopian tube or primary peritoneal cancer
- Received at least one prior systemic therapy
- Disease considered platinum-resistant
- Tumor is folate receptor-alpha (FRα) positive (> 75% viable tumor cells with mod (2+) or strong (3+) staining intensity)
- Use of mirvetuximab is as monotherapy or in combination with bevacizumab (or biosimilar)
- Care provided by a VA/VA Community Care gynecologic oncology or medical oncology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 – 1
- Baseline ophthalmology exam including visual acuity and slit lamp exam
Additional Inclusion Criteria- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 7 months after stopping treatment.
- For females who are lactating: Breastfeeding/providing breastmilk to an infant is not recommended during therapy and for 1 month after the last dose.
Indication & Patient Selection- FRα positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer in adults
- Patients who have received 1-3 prior systemic treatment regimens
- High FRα expression defined as > 75% viable tumor cells with moderate (2+) or strong (3+) staining intensity
- Patient selection must be based on an FDA-approved test
Dosing & Administration- Intravenous infusion of 6 mg/kg adjusted ideal body weight every 3 weeks until disease progression or unacceptable toxicity
- Supplied as a single-dose vial (100mg/20 mL) for dilution and intravenous infusion
Safety Monitoring & Precautions- Ocular toxicity: Premedicate with lubricating eye drops and topical steroid eye drops
- Pneumonitis: Hold therapy for Grade 2 pneumonitis until Grade 1 or lower; discontinue permanently for Grade 3 or 4
- Peripheral neuropathy: Withhold, reduce doses, or discontinue depending on severity
- Embryo-fetal toxicity: Advise patients of fetal risks; persons of reproductive potential must use effective contraception during treatment and for 7 months after the last dose
- Drug interactions: Monitor closely for adverse drug events with strong CYP3A4 inhibitors
Clinical Pathway & Guidelines- Preferred in platinum-refractory or platinum-resistant disease, but only in patients with FRα expression
- Category 2B recommendation in NCCN Ovarian Cancer Guidelines (useful in certain circumstances)
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OTESECONAZOLE CAP,ORAL
VIVJOA
|
VIVJOA |
2022-11-15 |
Exclusion Criteria- Pregnancy or lactation
- Person of child-bearing potential (defined as biological female who has no condition that constitutes permanent infertility (e.g. age greater than or equal to 47 years, tubal ligation, hysterectomy, salpingo-oophorectomy)
Inclusion Criteria- Acute signs and symptoms consistent with vulvovaginal candidiasis
- At least 3 symptomatic episodes of vulvovaginal candidiasis in 12 months
- Failure of at least 6 months of maintenance fluconazole (unless contraindicated, not tolerated or due to a fluconazole-resistant isolate expected to be susceptible to oteseconazole)
Dosing Options- Induction with fluconazole 150mg on days 1,4 and 7, followed by 150mg oteseconazole daily for 7 days, then weekly for 11 weeks
- Induction with oteseconazole 600mg on day 1, 450 mg on day 2, then 150mg weekly for 11 weeks (beginning day 14)
Indication & Patient Population- Indicated in females who are not of reproductive potential to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC)
- Defined as biological females who DO NOT have a reason for permanent infertility (e.g., age ≥ 47 years, tubal ligation, hysterectomy, salpingo-oophorectomy)
- Ideal population: post-menopausal women with RVVC (at least 3 symptomatic episodes in 12 months)
Dosing & Administration- Monotherapy: OTE 600 mg on day 1, 450 mg on day 2, then 150 mg weekly for 11 weeks starting day 14
- Sequential therapy with fluconazole: Fluconazole 150 mg as a single dose on days 1, 4, and 7 during induction; OTE 150 mg once daily days 14-20, then 150 mg once weekly for 11 weeks starting day 28
- Long half-life (~690 days) allows for weekly dosing after initial treatment
Contraindications & Warnings- Pregnancy or lactation
- Persons of reproductive potential (due to embryo-fetal toxicity/ocular abnormalities in animal studies and very long half-life)
- Previous hypersensitivity to OTE
- Embryo and fetal toxicity: Animal studies show ocular abnormalities including cataracts, opacities, exophthalmos/buphthalmos, optic nerve/retinal atrophy, lens degeneration, and hemorrhage
Special Populations & Dose Adjustments- Renal impairment: No dosage adjustment necessary for mild-moderate renal impairment (eGFR 30-89 mL/min); not recommended in severe renal impairment (eGFR <30 mL/min) or end-stage renal disease
- Hepatic impairment: No dosage adjustment necessary for mild hepatic impairment (Child-Pugh A); use not recommended for moderate-severe hepatic impairment (Child-Pugh B-C) due to insufficient safety information
- Geriatric: Very limited data in patients 65 years of age and older; unable to determine if they respond differently from younger patients
Place in Therapy & Clinical Guidance- Indicated for prevention of RVVC either as monotherapy or in conjunction with fluconazole in women with multiple symptomatic episodes (≥3 over a 12-month period)
- Ideal use is in post-menopausal women with RVVC for whom ibrexafungerp is not clinically appropriate or available
- Potential use likely to be low due to contraindication in women of childbearing potential, as RVVC is most common in young women
- Sustained remission may not always be successful; 50% of patients had a recurrent episode within 6 months of treatment completion
- May maintain activity against some fluconazole-resistant Candida spp., though elevated MICs suggest at least partial cross-resistance with other azoles. Clinical significance of higher MICs is unknown.
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TECLISTAMAB-CQYV INJ,SOLN
TECVAYLI
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TECVAYLI |
2022-11-03 |
Exclusion Criteria- Known hypersensitivity to teclistamab or its excipients
- Known active central nervous system involvement or signs of meningeal involvement
- Active viral, bacterial, or uncontrolled systemic fungal infection
- Pregnancy
- Breastfeeding
Inclusion Criteria- Relapsed or refractory multiple myeloma in a patient who has received at least four prior lines of therapy including a proteasome inhibitor, and immunomodulatory agent, and an anti-CD38 monoclonal antibody
- Care for the oncologic condition provided by VA or VA Community Care oncology provider certified with the Tecvayli REMS program
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- All step-up doses and first treatment dose must be administered in a hospital setting with observation for 48 hours following each dose due to the risk of cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS)
- Tocilizumab may be useful in patients not responding to dexamethasone for the management of CRS
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for five months after stopping treatment
- For patients who are breastfeeding: Counseling provided on avoiding breastfeeding while on treatment and for five months after stopping treatment
Indication & Patient Population- Relapsed or refractory multiple myeloma in patients who have received at least four prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Dosing & Administration- Subcutaneous administration only.
- Step-up dosing schedule: Day 1 (0.06 mg/kg), Day 4 (0.3 mg/kg), Day 7 (1.5 mg/kg). Doses may be administered 2 to 4 days after the prior dose, up to 7 days to allow for resolution of adverse reactions.
- Weekly dosing schedule: 1.5 mg/kg once weekly starting one week after the first treatment dose and doses thereafter.
- Pre-treatment medications required 1 to 3 hours prior to each step-up dose and the first treatment dose: corticosteroid (oral or IV dexamethasone 16 mg), H1 receptor antagonist (oral or IV diphenhydramine 50 mg or equivalent), and antipyretic (oral or IV acetaminophen 650-1000 mg or equivalent). Pre-treatment may also be required for subsequent doses in patients who repeat the step-up schedule due to delay or experience CRS.
Hospitalization & Monitoring Requirements- Patients must be hospitalized for 48 hours following administration of each step-up dose due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
- Monitor liver enzymes and bilirubin at baseline and during treatment due to hepatotoxicity risk.
- Monitor for signs and symptoms of infection; withhold treatment in patients with an active infection during the step-up dosing period.
- Monitor blood cell counts at baseline and during treatment; consider granulocyte colony stimulating factors (GCSF) for grade 4 neutropenia or grade 3 neutropenia accompanied by an infection.
Toxicity Management Criteria- CRS: Withhold teclistamab until CRS resolves. Administer pretreatment medications prior to next dose. Hospitalize patient for 48 hours following the next dose for Grade 2+ CRS. Permanently discontinue for Grade 3-4 CRS.
- ICANS: Withhold teclistamab until ICANS resolves. Administer dexamethasone 10 mg IV every 6 hours until resolution to grade 1 or less, then taper. Monitor neurologic symptoms and consider neurologist consultation. Hospitalize patient for 48 hours following the next dose for Grade 2+ ICANS. Permanently discontinue for Grade 3-4 ICANS.
REMS & Facility Requirements- Available only through the TECVAYLI REMS program.
- Prescribers must be certified and complete training; patients must be counseled on risks and provided a patient wallet card.
- Healthcare settings that dispense teclistamab must be certified with the program and verify ordering providers are certified.
- Treatment restricted to facilities capable of admitting patients for 48 hours to receive all step-up doses and first treatment dose, with staff trained in managing CRS and ICANS.
Special Populations & Contraindications- Contraindications: None explicitly stated.
- Embryo-fetal toxicity: Advise females of reproductive potential to use effective contraception during treatment and for five months after the last dose. Advise parents not to breastfeed during and for five months after the last dose.
Indications- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
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TREMELIMUMAB-ACTL INJ,SOLN
IMJUDO
|
IMJUDO |
2022-11-03 |
Indication & Patient Population- Unresectable hepatocellular carcinoma (uHCC)
- First-line (1L) setting
- Patients who are not candidates for atezolizumab and bevacizumab
- Candidates for immune checkpoint inhibitor (ICI) therapy but not candidates for bevacizumab
Dosing & Administration Criteria- Combination with durvalumab: Cycle 1, day 1 dosing followed by durvalumab monotherapy every 4 weeks
- Patients >30 kg: Tremelimumab 300 mg x 1 with durvalumab 1500 mg on Cycle 1, day 1
- Patients <30 kg: Tremelimumab 4 mg/kg x 1 with durvalumab 20 mg/kg on Cycle 1, day 1
Clinical Guidelines & Pathway Alignment- AASLD Clinical Practice Guideline 2023: Listed as a 1L option in non-VEGF candidates (i.e., bevacizumab)
- National VA Clinical Gastrointestinal Pathway 2023: Listed as a 1L option in HCC for ICI candidates who are not candidates for bevacizumab
- NCCN Guidelines Version 2.2023: Listed as a preferred 1L systemic therapy (category 1)
Safety Monitoring & Management Requirements- Monitor for early identification and management of immune-mediated adverse reactions impacting any organ or tissue (e.g., pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic reactions, pancreatitis)
- Evaluate appropriate labs; withhold or discontinue based on severity and type of reaction
- Interrupt, reduce rate, or permanently discontinue for infusion-related reactions based upon severity
- Avoid corticosteroids at therapy initiation as they may lessen therapeutic effect (though corticosteroids may be required to treat immune-mediated AEs)
Contraindications & Warnings- Embryo-fetal toxicity: Can cause fetal harm
- No boxed warnings or contraindications listed
Inclusion Criteria- Diagnosis of hepatocellular carcinoma
- No prior systemic therapy for Hepatocellular carcinoma (HCC), unless prior regimen discontinued premature due to intolerance
- Not a candidate to receive bevacizumab, therefore atezolizumab/bevacizumab regimen is not a 1L option
- Patient is able to receive durvalumab, in combination with tremelimumab
- Barcelona Clinic Liver Cancer stage B (not eligible for locoregional therapy) or stage C
- Child-Pugh score Class A
Additional Inclusion Criteria- Eastern Cooperative Oncology Group Performance Status 0 or 1
- Goals of care and role of Palliative Care Consult has been discussed and documented
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent greater than 10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic organ transplantation
- Untreated brain metastases
- Ascites requiring non-pharmacologic intervention in prior 6 weeks
- Hepatic encephalopathy in prior 12 months
- Uncontrolled systemic infection, including hepatitis B or C or known HIV
- Pregnancy
- Lactating
Additional Inclusion Criteria – Select if applicable- For patients who can become pregnant: Pregnancy must be excluded prior to receiving tremelimumab.
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for three months after stopping treatment.
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ROFLUMILAST TAB
DALIRESP
|
DALIRESP |
2022-10-27 |
Exclusion Criteria- Asthma without Chronic Obstructive Pulmonary Disease (COPD)
- Moderate-severe hepatic impairment (Child-Pugh B or C)
- Coadministration of strong CYP450 inducers
- Treatment of acute bronchospasm
- History of depression, anxiety, suicidal thoughts or behavior, unless determined with mental health specialist consultation that roflumilast can be used
- Pregnant or nursing status
- Co-administration of CYP3A4 or dual CYP3A4/CYP1A2 inhibitors or oral contraceptives containing gestodene and ethinyl estradiol (consider risk versus benefit)
- Patients with anxiety, insomnia, depression, or suicidal ideation/behavior (use cautiously, if at all)
- Patients with other mental health disorders (e.g., psychotic disorder, bipolar disorder, PTSD), especially if not fully controlled
Inclusion Criteria- Care provided by a VA/VA Community Care pulmonologist (or designated expert)
- COPD associated with chronic bronchitis (daily cough with production of sputum for 3 months, two years in a row)
- FEV1 less than or equal to 50% predicted
- At least 1 recorded COPD exacerbation requiring systemic steroids, unscheduled healthcare contact, or hospitalization in the previous year
- Maintenance bronchodilator therapy optimized (inhaled anticholinergics, long-acting beta-agonists)
- Inhaled corticosteroid therapy optimized unless use determined to be medically inappropriate
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TERLIPRESSIN INJ,PWDR
TERLIVAZ
|
TERLIVAZ |
2022-10-20 |
Indication- Improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function.
- Limitation of Use: Patients with a serum creatinine (SCr) > 5 mg/dL are unlikely to experience benefit.
Patient Selection & Baseline Assessments- Assess oxygen saturation (SpO2), Acute-on-Chronic Liver Failure (ACLF) Grade, and volume status prior to initiating therapy.
- Record the last available SCr value prior to initiating treatment.
- Preferred patient profile for benefit: Patients who do NOT have an ACLF Grade of 3, do NOT have an SCr ≥ 5 mg/dL, and are NOT listed for liver transplant with a MELD score ≥ 35.
Dosage & Administration Criteria- Initial Dose (Days 1–3): 0.85 mg every 6 hours by slow intravenous bolus injection (over 2 minutes).
- Day 4 Dose Adjustment: Assess SCr vs baseline.
- If SCr decreased by ≥ 30% from baseline: Continue 0.85 mg every 6 hours.
- If SCr decreased by < 30% from baseline: Increase to 1.7 mg every 6 hours.
- If SCr is at or above baseline value: Discontinue terlipressin.
- Duration: Continue until 24 hours after achieving a second consecutive SCr value of ≤ 1.5 mg/dL (at least 2 hours apart) or for a maximum of 14 days.
- Administration route: Can be administered through a peripheral or central line; a dedicated central line is not required.
Safety & Mitigation Criteria- Boxed Warning: Serious or fatal respiratory failure. Patients with ACLF Grade 3 (or volume overload) are at increased risk.
- Warning/Precaution: Benefit-risk profile may not be favorable in patients at high priority for liver transplant, such as those with MELD scores ≥ 35.
- Mitigation Strategy: Exclude patients meeting any of the following criteria: ACLF Grade 3, SCr ≥ 5 mg/dL, or listed for liver transplant with a MELD score ≥ 35.
Contraindications & Warnings- Contraindications: Hypoxia or worsening respiratory symptoms; ongoing coronary, peripheral, or mesenteric ischemia.
- Additional Warnings/Precautions: Terlipressin-related adverse reactions may make a patient ineligible for liver transplantation if patient is listed for liver transplant. Embryofetal toxicity and ischemic events are also noted.
Inclusion Criteria- Hospitalized inpatient status required
- Documented initial nonresponse to volume expansion (e.g., albumin)
- Documented diagnosis of hepatorenal syndrome with acute kidney injury made by a VA expert in GI/hepatology, nephrology, intensive care, or liver transplant surgery
Exclusion Criteria- Acute-on-chronic liver failure grade 3 (any 3 of: bilirubin > 12 mg/dL, SCr ≥ 3.5 or renal replacement, encephalopathy grade 3–4, INR ≥ 2.5, vasopressor for MAP < 70 mm Hg; or PaO2/FiO2 ratio ≤ 200, SpO2/FiO2 ratio ≤ 214 or intubated)
- SCr > 5 mg/dL
- Listed for liver transplant with MELD ≥ 35
- Hypoxia (e.g., SpO2 < 90%) or worsening respiratory symptoms (use permitted once oxygenation improves)
- Ongoing signs or symptoms of coronary, peripheral, or mesenteric ischemia
- History of severe cardiovascular conditions, cerebrovascular and ischemic disease
Diagnostic & Clinical Context Requirements- Diagnosis may be a potential or working diagnosis of HRS-AKI; clinical latitude is allowed
- Albumin volume challenge recommended for diagnostic workup to distinguish volume-responsive from volume-unresponsive acute renal failure/AKI
- Typical presentation includes ascites, hyponatremia, and low mean arterial pressure (MAP < 70)
- Use for uncertain diagnosis or as a "therapeutic trial" is not recommended
Administration & Dosing Parameters- Orders must be processed as urgent requests and dispensed within 3 hours
- Inpatient administration required; outpatient use adjudicated case-by-case (e.g., bridge to liver transplant)
- May be administered via peripheral line in non-ICU settings
- Concomitant albumin is NOT a requirement for use
- If concomitant albumin is used, doses preferably should not exceed 50 g/d
Monitoring & Discontinuation Guidelines- Hold albumin if evidence of volume overload, hypoxemia, or serum albumin levels >3.5 g/dL
- Terlipressin should be discontinued if no response by Day 4 (defined as SCr at or above baseline value)
- Maximum therapy duration is 14 days
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EFLAPEGRASTIM-XNST INJ,SOLN
ROLVEDON
|
ROLVEDON |
2022-10-13 |
Indications & Target Population- Decrease the incidence of infection (febrile neutropenia) in patients with non-myeloid malignancies receiving myelosuppressive cancer drugs.
- Not for mobilization for peripheral progenitor cells for stem cell transplantation.
- Clinical trial data supports use in early-stage breast cancer receiving adjuvant chemotherapy (docetaxel and cyclophosphamide).
Contraindications- Serious allergic reaction to human G-CSF.
Warnings & Precautions- Splenic rupture
- ARDS
- Serious allergic reactions
- Sickle Cell crisis
- Glomerulonephritis
- Leukocytosis
- Thrombocytopenia
- Capillary leak syndrome
- Stimulation of tumor growth
- MDS/AML in breast and lung cancer patients
Dosing & Administration- 13.2 ng/0.6mL pre-filled syringe for subcutaneous injection once each chemotherapy cycle.
Safety Profile- Adverse reactions ≥20%: fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, back pain.
- Safety during clinical trials was comparable to pegfilgrastim despite a lower G-CSF dose.
Formulary & Place in Therapy Considerations- No clear place in therapy for eflapegrastim instead of pegfilgrastim.
- Application withdrawn in 2019 due to manufacturing issues.
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BUPROPION/ DEXTROMETHORPHAN TAB,SA
AUVELITY
|
AUVELITY |
2022-10-06 |
Indication & Patient Population- Indicated for the treatment of major depressive disorder (MDD) in adults
- Clinical trial population included patients 18-65 years of age with a primary diagnosis of MDD, Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥25, and Clinician Global Impression-Severity (CGI-S) scale score ≥4
Contraindications- Seizure disorder
- Current or prior diagnosis of bulimia or anorexia nervosa
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
- Use with a monoamine oxidase inhibitor (MAOI) or within 14 days of stopping treatment with dextromethorphan and/or bupropion; do not use within 14 days of discontinuing an MAOI
- Known hypersensitivity to bupropion, dextromethorphan, or other components
Warnings & Precautions- Box warning for suicidal thoughts and behaviors in adolescents and young adults
- Seizure risk
- Increased blood pressure and hypertension; assess blood pressure prior to initiation and monitor periodically throughout therapy
- Activation of mania or hypomania; screen for personal or family history of bipolar disorder, mania, or hypomania prior to initiation
- Psychosis and other neuropsychiatric reactions
- Angle-closure glaucoma; avoid use in patients with untreated anatomically narrow angles
- Dizziness
- Serotonin syndrome
- Embryo-fetal toxicity; may cause fetal harm and is not recommended during pregnancy
Formulary Status & Clinical Guidance- Formulary status: Non-Formulary (NF) for MDD
- Not discussed in current MDD guidelines as the drug was unavailable when guidelines were developed
- Long-term published safety and efficacy data are lacking
- A trial in refractory depression (STRIDE-1) failed
- Potential abuse liability with long-term use in vulnerable patients requires further evaluation
- Represents an antidepressant combination with a unique mechanism of action for MDD management
Alternative Therapeutic Options- Bupropion, Citalopram, Duloxetine, Escitalopram, Mirtazapine, Sertraline, Venlafaxine, Vilazodone, and Vortioxetine are listed with respective indications (e.g., MDD, GAD, fibromyalgia, musculoskeletal pain, neuropathic pain with DM, OCD, PD, PTSD, PMDD, SAD) and formulary status (predominantly Formulary [F])
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FINGOLIMOD CAP,ORAL
GILENYA
|
GILENYA |
2022-10-06 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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TADALAFIL SUSP,ORAL
TADLIQ
|
TADLIQ |
2022-09-29 |
Clinical Category: Monotherapy & Combination Therapy Restrictions- A PDE5I should not be used routinely for the management of LUTS-BPH as monotherapy.
- A PDE5I should not be used in combination with alpha blockers for BPH/LUTS, as it offers no symptom improvement advantage over either agent alone per American Urological Association (AUA) guidelines.
Clinical Category: Formulary PDE5I Initiation & Substitution Criteria- Consider when more established pharmacotherapies are not an option or have not demonstrated benefit.
- Initiate a formulary alpha blocker first using shared decision making and patient-specific factors. If ED is present, may consider adding a formulary PDE5I (with quantity limits) to an alpha blocker.
- Consider substituting or adding a formulary PDE5I if unable to tolerate or lack of response to an adequate trial (12 weeks) of a formulary alpha blocker titrated to maximum therapeutic dose.
- If adding a PDE5I, the patient must be on a stable dose of the alpha-blocker prior to initiation; the PDE5I should then be started at the lowest recommended dose.
Clinical Category: Clinical Scenarios for Formulary PDE5I Monotherapy Consideration- In place of an alpha blocker in the interim if cataract surgery is planned or likely (due to risk of intraoperative floppy iris syndrome).
- When an alpha blocker is contraindicated or not tolerated and an antimuscarinic is not appropriate due to post-void residual >250 mL, contraindication, ineffective trial, or substantial contribution to existing anticholinergic burden.
- (Note: The document explicitly states that only sildenafil, tadalafil, and vardenafil have been studied for BPH/LUTS; avanafil-specific criteria are not provided in the text.)
Formulary Status- Avanafil is non-formulary.
- Sildenafil and tadalafil are available on the VA National Formulary (PA-F).
Prescribing & Clinical Evaluation Requirements- Prescriptions for erectile dysfunction must be written by a VA prescriber following an appropriate clinical evaluation.
- Prescribing clinician is responsible for ensuring no contraindications exist for the prescribed PDE5 inhibitor.
- Patient must understand treatment choices, associated risks, and benefits.
Quantity & Dispensing Limits- Limited to 6 doses per month for management of erectile dysfunction.
- Quantities less than 6 doses per month dispensed only at request of patient or prescriber.
- Greater quantities may be approved on a case-by-case basis (e.g., couples trying to conceive, veterans with inconsistent response).
- Quantity limit does not apply for management of pulmonary hypertension.
Adverse Event Reporting- All adverse events must be reported in the VA Adverse Drug Event Reporting System (VA ADERS/VA MedSafe).
Lost Prescription Management- Lost prescriptions will not be replaced during the intended time period; authorized refills become available at the next scheduled refill date.
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DEUCRAVACITINIB TAB
SOTYKTU
|
SOTYKTU |
2022-09-22 |
Indication & Patient Population- Treatment of moderate to severe plaque psoriasis (PsO) in adults who are candidates for systemic therapy or phototherapy.
- Not recommended for use in combination with other potent immunosuppressants.
Pretreatment Evaluation & Screening- Tuberculosis (TB) screening required; initiate TB treatment prior to deucravacitinib if positive. Do not initiate in patients with latent or active TB infection.
- Update immunizations.
- Consider hepatitis B or C screening; not recommended for patients with active hepatitis B or C.
- Consider baseline triglyceride levels.
- Obtain baseline liver enzymes; not recommended for severe hepatic impairment (Child-Pugh C).
- Consider baseline creatine phosphokinase (CPK) (US prescribing information does not recommend routine baseline CPK).
Monitoring During Therapy- Monitor triglyceride levels per clinical guidelines for hyperlipidemia.
- Monitor liver enzymes in patients with known or suspected liver disease per routine patient management.
- Consider checking CPK periodically or in patients with suspected/diagnosed myopathy; discontinue deucravacitinib if CPK becomes markedly elevated.
Dosing & Administration- Recommended dose: 6 mg orally once daily with or without food.
- Do not crush, cut, or chew tablets.
- Dosage form: Film-coated tablets, 6 mg in bottles of 30.
Special Populations & Dose Adjustments- Renal impairment: No dosage adjustments required.
- Hepatic impairment: No adjustments for mild (Child-Pugh A) or moderate (Child-Pugh B). Not recommended for severe (Child-Pugh C) hepatic impairment.
Safety, Contraindications & Precautions- Contraindication: Hypersensitivity.
- Warnings/Precautions: Infections, herpes viral reactivation, TB, malignancy including lymphomas, rhabdomyolysis and elevated CPK, triglyceride elevations, liver enzyme elevations, update immunizations (avoid live vaccines during treatment), potential JAK inhibitor-related adverse reactions.
- Lacks boxed warnings for serious infections, mortality, major adverse cardiovascular events (MACE), malignancy excluding nonmelanoma skin cancer, and thrombosis (insufficient evidence to determine if TYK2 inhibition increases these risks).
- No increased risk of serious/opportunistic infections, mortality, MACE, thrombosis, liver injury, or GI perforation reported.
- No hematologic adverse events; monitoring for cytopenias is not required.
Place in Therapy & Comparative Considerations- Not restricted to patients with disease not adequately controlled by other systemic drugs including biologics or when those therapies are inadvisable.
- Superior to apremilast for scalp psoriasis; numerically better for fingernail psoriasis.
- Requires monitoring of triglycerides, liver enzymes, and CPK (unlike apremilast, which requires no lab monitoring except potential age-related renal function checks).
- Offers oral administration convenience similar to other small molecules.
Exclusion Criteria- Uncontrolled active infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- Untreated active hepatitis C
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless treating dermatologist and oncologist agree risk-benefits favor use)
- Severe hepatic impairment (Child-Pugh C)
- Concomitant therapy with other potent immunosuppressants
- Concomitant live or live-attenuated vaccines or administration of non-live or live vaccines less than 2 weeks before initiation
Inclusion Criteria- Diagnosis of moderate to severe plaque psoriasis
- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated psoriasis expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed liver enzyme tests
- Methotrexate monotherapy is medically inadvisable, not tolerated, or inadequate (NO treatment benefit after 3 months, with at least 2 months at standard target dose of 15–25 mg ONCE WEEKLY PO/SC/IM, or inadequate response after 6 months)
- Phototherapy is medically inadvisable, unavailable, unfeasible, or inadequate (NO treatment benefit after 12 treatments or inadequate response after 24 treatments)
- Three targeted systemic antipsoriatic drugs (≥ 1 drug per class) are medically inadvisable, not tolerated, or not adequate: Inhibitors of TNF, IL-17 (ixekizumab preferred), IL-23 (e.g., risankizumab), IL-12/23 (ustekinumab), or PDE-4 (apremilast)
Additional Inclusion Criteria- If HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive: Consultation with a GI/liver or infectious diseases expert for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- For patients who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
Supplemental Clinical Considerations & Trial Requirements- TB Testing: Routine retesting not required for prescription renewals; consider retesting in high-risk patients (e.g., highly endemic areas)
- Methotrexate: Refer to contraindications/risks for serious adverse events; use lower than target doses if limited by toxicity
- Phototherapy Inadvisability: Includes confirmed history of skin cancer/melanoma or strong likelihood of developing them (e.g., Fitzpatrick skin type I or II)
- PDE-4 Inhibitor (Apremilast): NO treatment benefit after 4 months or inadequate response after 6 months; medically inadvisable if too low likelihood of lesion clearance for disease severity, patient averse to injections, or unacceptable risk of weight loss/depression/suicidality
- TNF Inhibitor: NO response after 12 weeks with ONE TNFI; inadequate response after 12-week trials of TWO TNFIs for total 24 weeks; or loss of initial response. Medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent/serious infections
- IL-17A Inhibitor: NO response after 12 weeks, inadequate/partial response after 24 weeks, or loss of initial response. Medically inadvisable due to inflammatory bowel disease and severe/recurrent Candida infections
- IL-23 Inhibitor: NO response after 16 weeks, inadequate/partial response after 34 weeks, or loss of initial response. Medically inadvisable due to liver cirrhosis in patients with comorbid Crohn’s disease
- IL-12/23 Inhibitor (Ustekinumab): NO response after 16 weeks, inadequate/partial response after 32 weeks, or loss of initial response. Medically inadvisable due to history of noninfectious pneumonia (e.g., interstitial, eosinophilic, cryptogenic organizing)
- Injection Aversity/Barriers: Aversity to injections or barriers to in-clinic administration adjudicated case-by-case as medically inadvisable
- HBV Reactivation Management: For anti-HBc-positive patients, presence of anti-HBs does not guarantee protection; evidence is insufficient to support using anti-HBs titers to decide on antiviral prophylaxis
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SPESOLIMAB-SBZO INJ,SOLN
SPEVIGO
|
SPEVIGO |
2022-09-15 |
Indication & Patient Population- Treatment of generalized pustular psoriasis (GPP) flares in adults.
- Supported for first-line use in patients with acute, non–life-threatening, moderate to severe GPP flare based on phase 2 trial evidence.
Disease Severity & Clinical Characteristics- Moderate to severe intensity GPP flare: GPP-PGA total score of ≥ 3 (Moderate), new or worsening pustules, GPP-PGA-P subscore of ≥ 2 (Mild), and ≥ 5% of body surface area (BSA) with erythema and pustules.
- Acute presentation characterized by rapid onset of erythematous, inflamed skin with generalized, extremely painful, small or coalesced, noninfectious, neutrophilic, pustular, nonacral skin lesions.
- Systemic manifestations may include fever, malaise, and fatigue; mucosal, eye (keratoconjunctivitis, uveitis, iritis), and arthritic manifestations may occur.
Pretreatment Tests & Evaluations- Tuberculosis (TB) screening required prior to initiation.
Dosage Regimen & Administration- Recommended dose: 900 mg IV infusion over 90 minutes as a single dose.
- A second single dose (900 mg IV infusion over 90 minutes) may be administered 1 week after the initial dose if flare symptoms persist.
- Dosage form: Injection of 450 mg/7.5 mL (60 mg/mL) solution in a single-dose vial.
Contraindications & Safety Precautions- Contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab or excipients, including drug reaction with eosinophilia and systemic symptoms (DRESS).
- Avoid live vaccines due to infection risk.
- Monitor for infections, TB reactivation, hypersensitivity, and infusion-related reactions.
Exclusion Criteria & Clinical Considerations- Not indicated for immediate life-threatening flares warranting intensive care treatment (e.g., cardiovascular/cytokine-driven shock, pulmonary distress syndrome, renal failure).
- Excluded in patients with severe, progressive, or uncontrolled hepatic disease (AST, ALT, or alkaline phosphatase > 3 times upper limit of normal [ULN] or total bilirubin > 2 times ULN).
- Avoid initiation within 2 weeks of dose escalation or initiation of cyclosporine, methotrexate, or retinoids.
- Avoid concurrent use of corticosteroids, methotrexate, cyclosporine, retinoids, IL-17A/RA inhibitors, IL-23 inhibitors, IL-12/23 inhibitor, TNF-alpha inhibitors, JAK inhibitors, PDE4 inhibitors, fumarates, photochemotherapy, natalizumab, alemtuzumab, rituximab, anakinra, topical psoriasis/skin medications, or granulocytes and monocytes adsorptive apheresis (GMA). (Note: Certolizumab may be used concurrently).
- Not recommended for use in women who are pregnant, nursing, or plan to become pregnant during treatment.
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IBRUTINIB SUSP,ORAL
IMBRUVICA
|
IMBRUVICA |
2022-09-08 |
Exclusion Criteria- Patient has not been screened for Hepatitis B Virus (HBV)
- Unmanageable drug-drug or drug-food interaction
- Active or uncontrolled infection
- History of stroke or intracranial hemorrhage in prior 6 months
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (NYHA Class 3 or 4) or myocardial infarction in prior 6 months
- Severe hepatic impairment (Child-Pugh C) or total bilirubin > 3x Upper Limit of Normal (unless non-hepatic origin or Gilbert syndrome)
- Known pregnancy
- Lactating
Inclusion Criteria- Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) if acalabrutinib is not clinically appropriate for patient
- Waldenstrom Macroglobulinemia
- Previously treated chronic Graft versus Host Disease (cGVHD) after Hematopoietic Stem Cell Transplant
Additional Inclusion Criteria- Care for the oncologic condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 - 2
Pregnancy and Lactation Counseling Requirements- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 month after stopping treatment
- Advise patients not to breastfeed/provide breastmilk during treatment and for 1 week after last dose
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INSULIN,GLARGINE,HUMAN (TOUJEO MAX) 300 UNIT/ ML
INSULIN GLARGINE MAX SOLOSTAR, TOUJEO MAX SOLOSTAR
|
INSULIN GLARGINE MAX SOLOSTAR, TOUJEO MAX SOLOSTAR |
2022-08-25 |
Exclusion Criteria- Hypersensitivity to insulin glargine or glargine biosimilar
Inclusion Criteria- Patient is insulin resistant (requires >1 unit/kg/day)
- Patient with recurrent episodes of hypoglycemia on insulin glargine 100 u/mL (e.g., > three Level 2 or one Level 3 hypoglycemic event within a one-month period) despite use of continuous glucose monitor (CGM) and adjustments made to current insulin regimen
Dosing & Device Considerations- TOUJEO MAX is preferred in patients with insulin resistance receiving high doses of insulin
- TOUJEO MAX delivers in 2-unit increments and can deliver up to 160 units in a single injection
Additional Clinical Requirements- Clinical need for concentrated, smaller volume insulin injections must be demonstrated
- Patients doing well on glargine 100 u/mL should not be switched to concentrated insulin solely for the purpose of achieving smaller volume injections
- Consider insulin sensitizing agents (metformin, empagliflozin, or semaglutide) unless contraindicated if not already receiving
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INSULIN,GLARGINE,HUMAN (TOUJEO) 300 UNIT/ ML
INSULIN GLARGINE SOLOSTAR, TOUJEO SOLOSTAR
|
INSULIN GLARGINE SOLOSTAR, TOUJEO SOLOSTAR |
2022-08-25 |
Exclusion Criteria- Hypersensitivity to insulin glargine or glargine biosimilar
Inclusion Criteria- Patient is insulin resistant (requires >1 unit/kg/day)
- Patient with recurrent episodes of hypoglycemia on insulin glargine 100 u/mL (e.g., > three Level 2 or one Level 3 hypoglycemic event within a one-month period) despite use of continuous glucose monitor (CGM) and adjustments made to current insulin regimen
Dosing & Device Considerations- TOUJEO MAX is preferred in patients with insulin resistance receiving high doses of insulin
- TOUJEO MAX delivers in 2-unit increments and can deliver up to 160 units in a single injection
Additional Clinical Requirements- Clinical need for concentrated, smaller volume insulin injections must be demonstrated
- Patients doing well on glargine 100 u/mL should not be switched to concentrated insulin solely for the purpose of achieving smaller volume injections
- Consider insulin sensitizing agents (metformin, empagliflozin, or semaglutide) unless contraindicated if not already receiving
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AMOXICILLIN/ CLARITHROMYCIN/ VONOPRAZAN MISCELLANEOUS
VOQUEZNA TRIPLE PAK
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VOQUEZNA TRIPLE PAK |
2022-08-22 |
Indication- Treatment of Helicobacter pylori (H. pylori) infection in adults.
Dosage & Administration- VOQUEZNA Triple Pak: Vonoprazan 20 mg, amoxicillin 1,000 mg, clarithromycin 500 mg. Take 12 hours apart (morning and evening), with or without food. Duration: 14 days.
- VOQUEZNA Dual Pak: Vonoprazan 20 mg twice daily plus amoxicillin 1,000 mg. Dosing schedule: Morning (1 vonoprazan tablet, 2 amoxicillin capsules), Mid-day (2 amoxicillin capsules), Evening (1 vonoprazan tablet, 2 amoxicillin capsules). Duration: 14 days.
- Dosing can be administered without regard to food.
Contraindications- Hypersensitivity to any component, including hypersensitivity to drugs in the same class.
- Contraindication to clarithromycin, including contraindicated concomitant medications or a history of cholestatic jaundice/hepatic dysfunction with prior clarithromycin.
- Concomitant use with rilpivirine-containing products.
Warnings & Precautions- Hypersensitivity reactions (serious and fatal reactions reported).
- Acute tubulointerstitial nephritis (reported with vonoprazan).
- Severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome/toxic epidermal necrolysis).
- Drug-induced enterocolitis syndrome (most commonly in pediatric patients, presenting as protracted vomiting 1–4 hours after drug injection).
- Clostridioides difficile-associated diarrhea.
- Rash with mononucleosis (due to amoxicillin component).
- Interaction with diagnostic investigations for neuroendocrine tumors (can cause false positive results secondary to drug-induced decreases in gastric acidity).
- Development of resistant bacteria.
- Clarithromycin-specific warnings: QT prolongation (avoid in known prolonged QT, ventricular arrhythmia, or other drugs/conditions known to prolong QT interval), hepatotoxicity, serious adverse events with CYP3A4-metabolized drugs, embryofetal toxicity (increased risk of miscarriage and fetal malformations), infertility (may impair fertility in males of reproductive potential based on animal studies), exacerbation of myasthenia gravis.
Special Populations- Pregnancy: No adequate and well-controlled studies. Animal studies show possible harm. Clarithromycin is associated with increased miscarriage and possible major congenital malformations. VOQUEZNA Triple Pak is NOT recommended in pregnancy unless no alternative therapy is appropriate.
- Renal impairment: No dose adjustment needed for estimated GFR ≥ 30 mL/min. Not recommended with GFR < 30 mL/min.
- Hepatic impairment: Standard doses for patients with Child-Pugh A hepatic impairment. Not recommended in Child-Pugh B or C.
Place in Therapy & Clinical Considerations- VOQUEZNA Dual Pak is a suggested first-line option for treatment-naïve patients based on demonstrated noninferiority to standard triple therapy, superiority in clarithromycin-resistant strains, and better tolerability compared to bismuth quadruple therapy.
- VOQUEZNA Triple Pak is suggested as a salvage regimen when clarithromycin susceptibility can be documented.
- Optimized bismuth quadruple therapy (BQT) for 14 days remains the only recommended first-line treatment option per updated ACG guidelines; Voquezna dual may be reserved for patients who cannot tolerate BQT.
- Rifabutin-based triple therapy is suggested as a first-line treatment but may be more beneficial as a second-line empiric regimen if BQT cannot be used.
- Other regimens (e.g., Voquezna triple, levofloxacin-based) require susceptibility testing.
- PPI-based triple therapy with clarithromycin or levofloxacin is no longer recommended in the absence of susceptibility testing due to high resistance rates.
- High-dose dual double-dose PPI plus amoxicillin is no longer recommended; vonoprazan dual therapy is preferred.
Exclusion Criteria- Pregnancy
- Need for concomitant rilpivirine administration
- Serious drug-drug interactions that cannot be managed (e.g., concomitant colchicine if renal or hepatic impairment, pimozide, lurasidone, lovastatin, simvastatin, strong CYP3A inducers)
- Known prolongation of QT interval or ongoing proarrhythmic condition (e.g. uncorrected hypokalemia or hypomagnesemia, significant bradycardia, concomitant Class IA or III antiarrhythmics)
Inclusion Criteria- Documented H.pylori by laboratory test or pathology
- Documented susceptibility to clarithromycin (If clarithromycin susceptibility cannot be documented by culture-based or molecular methods, exceptions to this criterion may be considered on a case-by-case basis with the guidance of a subject matter expert)
- At least one prior course of first-line regimen: bismuth quadruple or vonoprazan dual therapy unless not tolerated or contraindicated
- At least one course of salvage therapy with rifabutin triple therapy unless not tolerated or contraindicated
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AMOXICILLIN/ VONOPRAZAN MISCELLANEOUS
VOQUEZNA DUAL PAK
|
VOQUEZNA DUAL PAK |
2022-08-22 |
Exclusion Criteria- Need for concomitant rilpivirine administration
Inclusion Criteria- Documented H.pylori by laboratory test or pathology
- Treatment naïve patients with a contraindication or inability to use a course of bismuth quadruple therapy
Indication- Treatment of Helicobacter pylori (H. pylori) infection in adults.
Dosage & Administration- VOQUEZNA Triple Pak: Vonoprazan 20 mg, amoxicillin 1,000 mg, clarithromycin 500 mg. Take 12 hours apart (morning and evening), with or without food. Duration: 14 days.
- VOQUEZNA Dual Pak: Vonoprazan 20 mg twice daily plus amoxicillin 1,000 mg. Dosing schedule: Morning (1 vonoprazan tablet, 2 amoxicillin capsules), Mid-day (2 amoxicillin capsules), Evening (1 vonoprazan tablet, 2 amoxicillin capsules). Duration: 14 days.
- Dosing can be administered without regard to food.
Contraindications- Hypersensitivity to any component, including hypersensitivity to drugs in the same class.
- Contraindication to clarithromycin, including contraindicated concomitant medications or a history of cholestatic jaundice/hepatic dysfunction with prior clarithromycin.
- Concomitant use with rilpivirine-containing products.
Warnings & Precautions- Hypersensitivity reactions (serious and fatal reactions reported).
- Acute tubulointerstitial nephritis (reported with vonoprazan).
- Severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome/toxic epidermal necrolysis).
- Drug-induced enterocolitis syndrome (most commonly in pediatric patients, presenting as protracted vomiting 1–4 hours after drug injection).
- Clostridioides difficile-associated diarrhea.
- Rash with mononucleosis (due to amoxicillin component).
- Interaction with diagnostic investigations for neuroendocrine tumors (can cause false positive results secondary to drug-induced decreases in gastric acidity).
- Development of resistant bacteria.
- Clarithromycin-specific warnings: QT prolongation (avoid in known prolonged QT, ventricular arrhythmia, or other drugs/conditions known to prolong QT interval), hepatotoxicity, serious adverse events with CYP3A4-metabolized drugs, embryofetal toxicity (increased risk of miscarriage and fetal malformations), infertility (may impair fertility in males of reproductive potential based on animal studies), exacerbation of myasthenia gravis.
Special Populations- Pregnancy: No adequate and well-controlled studies. Animal studies show possible harm. Clarithromycin is associated with increased miscarriage and possible major congenital malformations. VOQUEZNA Triple Pak is NOT recommended in pregnancy unless no alternative therapy is appropriate.
- Renal impairment: No dose adjustment needed for estimated GFR ≥ 30 mL/min. Not recommended with GFR < 30 mL/min.
- Hepatic impairment: Standard doses for patients with Child-Pugh A hepatic impairment. Not recommended in Child-Pugh B or C.
Place in Therapy & Clinical Considerations- VOQUEZNA Dual Pak is a suggested first-line option for treatment-naïve patients based on demonstrated noninferiority to standard triple therapy, superiority in clarithromycin-resistant strains, and better tolerability compared to bismuth quadruple therapy.
- VOQUEZNA Triple Pak is suggested as a salvage regimen when clarithromycin susceptibility can be documented.
- Optimized bismuth quadruple therapy (BQT) for 14 days remains the only recommended first-line treatment option per updated ACG guidelines; Voquezna dual may be reserved for patients who cannot tolerate BQT.
- Rifabutin-based triple therapy is suggested as a first-line treatment but may be more beneficial as a second-line empiric regimen if BQT cannot be used.
- Other regimens (e.g., Voquezna triple, levofloxacin-based) require susceptibility testing.
- PPI-based triple therapy with clarithromycin or levofloxacin is no longer recommended in the absence of susceptibility testing due to high resistance rates.
- High-dose dual double-dose PPI plus amoxicillin is no longer recommended; vonoprazan dual therapy is preferred.
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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ACALABRUTINIB TAB
CALQUENCE
|
CALQUENCE |
2022-08-18 |
Exclusion Criteria- Patient has not been screened for Hepatitis B Virus (HBV)
- Unmanageable drug-drug interaction identified
- History of stroke or intracranial hemorrhage in prior 6 months
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (NYHA Class 3 or 4), or myocardial infarction in prior 6 months
- Active or uncontrolled infection
- Severe hepatic impairment (Child-Pugh C)
- Known pregnancy
- Lactating
Inclusion Criteria- Mantle Cell Lymphoma (MCL) and progressive disease or intolerance to at least one prior therapy
- Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
- Acalabrutinib is not effective in the setting of the BTKC481S mutation that confers resistance to ibrutinib
Additional Inclusion Criteria- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0-2
Additional Inclusion Criteria (Select if applicable)- For females who can become pregnant: Counseling on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for at least one week after the last dose
- Advise females not to breastfeed during treatment and for at least 2 weeks after the last dose
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ROFLUMILAST CREAM,TOP
ZORYVE
|
ZORYVE |
2022-08-11 |
Exclusion Criteria- Psoriasis other than the plaque variant
- Moderate to severe liver impairment (Child-Pugh B or C)
Required Inclusion Criteria (All must be met)- Diagnosis of plaque psoriasis (any severity)
- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated psoriasis expert
Additional Inclusion Criteria (One of the following must be met)- Tried and had intolerance or inadequate response to ≥ 2 classes of topical antipsoriatics unless medically inadvisable (≥ 1 month per class; e.g., corticosteroids, vitamin D analogs, calcineurin inhibitors, etc.; roflumilast required before tapinarof)
- Tried and had intolerance or inadequate response to 1 class of topical antipsoriatics and 1 systemic therapy (phototherapy, conventional immunomodulator, or targeted immunomodulator) unless medically inadvisable, not available, or not feasible
Pregnancy & Lactation Considerations- Pregnant patients or those planning pregnancy: Counseling provided on potential risks vs benefits; patient informed that it is not known whether use will harm the unborn baby. Avoid use during labor and delivery.
- Breastfeeding patients or those planning to breastfeed: Counseling provided on minimizing drug exposure via breast milk per prescribing information. Advise against applying directly to nipple/areola; if applied to chest, avoid direct contact with infant's skin.
Clinical Definitions & Clarifications- Prior trial of topical corticosteroids is not necessary and may be medically inadvisable for lesions in sensitive areas (face, intertriginous/skin-to-skin areas).
- Topical emollients and keratolytics do not count as topical antipsoriatics.
- Examples of topical antipsoriatic classes: Vitamin D analogs (calcipotriene, calcipotriol), Calcineurin inhibitors (tacrolimus, pimecrolimus), Retinoids (tazarotene), Coal tar, Aryl hydrocarbon receptor agonist (tapinarof).
- Phototherapy medically inadvisable reasons include confirmed history of skin cancer/melanoma or strong likelihood of developing them (e.g., Fitzpatrick skin type I or II).
- Phototherapy response criteria: NO treatment benefit after 12 treatments or inadequate partial response after 24 treatments.
- Systemic targeted immunomodulators include tumor necrosis factor inhibitors, interleukin-17A inhibitors (e.g., ixekizumab), interleukin-23 inhibitors (e.g., risankizumab-rzaa), interleukin-12/23 inhibitor (e.g., ustekinumab), and phosphodiesterase-4 inhibitors (e.g., apremilast).
- Conventional immunomodulator example: methotrexate.
Indication & Patient Population- • Topical treatment of plaque psoriasis, including intertriginous areas
- • Patients 12 years of age and older
Dosage & Administration- • Applied once daily to affected areas
- • Cream 0.3% (3 mg/g) in 60-g tubes
Prior Therapy Requirements (Place in Therapy)- • May be used for patients with plaque psoriasis who have an inadequate response or intolerance to:
- – ≥ 2 classes of topical antipsoriatics (e.g., topical corticosteroids, vitamin D analogs, calcineurin inhibitors, retinoids [tazarotene], or coal tar), unless the therapy is medically inadvisable; OR
- – 1 class of topical antipsoriatic and 1 class of systemic antipsoriatic (e.g., phototherapy, methotrexate, or biologic), unless medically inadvisable, not available, or not feasible
Safety Considerations & Contraindications- • Contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C)
- • Requires assessment of risk-benefits for potential drug interactions with CYP3A4 and CYP1A2 inhibitors, gestodene, and ethinyl estradiol
Clinical Limitations & Considerations- • Safety and efficacy of application to the scalp, palms, and soles are unknown (though treatment could be applied to affected palms and soles, these areas were not evaluated for efficacy)
- • Unknown safety and efficacy of concomitant use with other topical, systemic, or ultraviolet light therapies
- • Unknown topical corticosteroid sparing effects
- • Limited long-term safety data and real-world experience
Exclusion Criteria- Moderate to severe liver impairment (Child-Pugh B or C)
Inclusion Criteria- Moderate to severe seborrheic dermatitis
- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated expert
- Tried and had intolerance or inadequate response to a combination of topical antifungal (including shampoo) plus topical corticosteroid for ≥ 4 consecutive weeks unless medically inadvisable
- Tried and had intolerance or inadequate response to a combination of topical antifungal (including shampoo) plus topical calcineurin inhibitor (e.g., tacrolimus ointment or pimecrolimus cream) for ≥ 4 consecutive weeks unless medically inadvisable
Additional Inclusion Criteria (Special Populations)- Pregnancy/Planning pregnancy: Counseling provided on potential risks vs benefits of treatment; patient informed that it is not known whether use will harm the unborn baby. Avoid use during labor and delivery.
- Breastfeeding/Planning breastfeeding: Counseling provided on how to minimize potential drug exposure to the breastfed infant via breast milk per prescribing information. Advise patients not to apply directly to the nipple or areola, and if applied to the chest, to avoid direct contact with the infant’s skin.
Indication & Patient Population- Treatment of seborrheic dermatitis (SD) in adults
- Moderate to severe SD (predominantly moderate disease severity)
- Patients with an inadequate response, intolerance, or medical inadvisability to combination topical antifungal plus TCS and combination topical antifungal plus topical calcineurin inhibitor
Place in Therapy & Step Requirements- 2nd-line alternative for SD of the face in patients requiring frequent use of TCSs
- May be added to topical antifungal therapy
- Alternative to a TCI for maintenance therapy
- First nonsteroidal, non-antifungal product approved for the treatment of SD
Dosage & Administration Parameters- Applied once daily to affected areas on skin and/or scalp when not wet
- Topical foam 0.3% in 60-gram pressurized cans
- Maximum body surface area (BSA) of 20%
Safety & Contraindications- Contraindicated in moderate to severe liver impairment (Child-Pugh B or C)
- Flammable formulation requiring appropriate handling precautions
- PDE4-related adverse events (psychiatric and gastrointestinal) occurred at significantly lower rates than vehicle
- Local adverse events occurred at similar rates to vehicle
Exclusion Criteria- Moderate to severe liver impairment (Child-Pugh B or C) – relative contraindication
Core Inclusion Criteria- Diagnosis of mild to moderate atopic dermatitis
- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated expert
- Tried a topical corticosteroid and a topical calcineurin inhibitor (e.g., tacrolimus ointment 0.1% or 0.03% or pimecrolimus cream 1%) for ≥ 1 month per drug class, unless medically inadvisable, and had intolerance or an inadequate response
Additional Inclusion Criteria (Pregnancy & Lactation)- Pregnancy or planning to become pregnant: Counseling provided on potential risks vs benefits of treatment; patient informed that it is not known whether use will harm the unborn baby
- Lactating, providing breastmilk to an infant, or planning to do so: Counseling provided on how to minimize potential drug exposure to the breastfed infant via breast milk, as recommended in prescribing information
Administration & Counseling Requirements- Avoid use during labor and delivery
- Advise breastfeeding women not to apply roflumilast directly to the nipple or areola; if applied to the patient’s chest, avoid exposure via direct contact with the infant’s skin
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TECOVIRIMAT INJ,SOLN
TPOXX (NATIONAL STOCKPILE)
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TPOXX (NATIONAL STOCKPILE) |
2022-07-28 |
Indications & Patient Selection- JYNNEOS (Vaccine for Prevention)
- Indicated for pre- or post-exposure prophylaxis against monkeypox and smallpox in adults at high risk.
- Pre-exposure prophylaxis (PrEP): Recommended for laboratory workers handling orthopoxviruses; broader vaccination may be recommended when supply increases.
- Post-exposure prophylaxis (PEP): Indicated after high-risk exposure to monkeypox virus; ideally given within 4 days of exposure to prevent infection. Between 4–14 days post-exposure may be less effective. Beyond 14 days, benefits may outweigh risks in specific clinical situations (e.g., severely immunosuppressed patient with recent confirmed partner).
- Not expected to provide benefit if administered after onset of signs or symptoms of monkeypox.
- PEP++ (Enhanced PEP) criteria: Multiple sexual partners in the past 14 days in a jurisdiction with known monkeypox transmission.
- TPOXX / TECOVIRIMAT (Treatment)
- FDA approved for treatment of smallpox based on animal models; available under EA-IND protocol for non-variola orthopoxvirus infections including monkeypox during an outbreak.
- Consider for patients with severe disease: hemorrhagic disease, confluent lesions, sepsis, encephalitis, or conditions requiring hospitalization.
- Consider for persons at HIGH risk for severe disease: immunocompromised; pregnant/breastfeeding women; persons with complications (secondary skin infections, gastroenteritis with severe nausea/vomiting, diarrhea/dehydration, bronchopneumonia, concurrent disease/comorbidities); history or presence of atopic dermatitis or other exfoliative skin disorders.
- Consider for monkeypox virus aberrant infections: accidental implantation in eyes, mouth, genitals, or anus.
Dosing & Administration- JYNNEOS
- Standard (FDA-approved) regimen: 2 subcutaneous (SQ) doses of 0.5 mL each, 4 weeks apart, into fatty tissue over the triceps in the upper arm. Minimum interval is 28 days; may be given up to 4 days before or 7 days after. If delayed >7 days, administer ASAP without restarting series.
- Alternative (EUA) regimen: 0.1 mL administered intradermally (ID) on the volar surface of the forearm, second dose 28 days later. Preferred in VHA for most patients to maximize supply.
- Interchangeability: Adults who received standard SQ dosing may receive the second dose ID if no history of keloid development.
- TPOXX / TECOVIRIMAT
- Oral (Preferred): 600 mg every 12 hours for 14 days. Increase to 600 mg every 8 hours for patients weighing ≥120 kg. Must be given within 30 minutes of a full moderate or high fat meal.
- Intravenous (If unable to tolerate oral): Dilute with 0.9% sodium chloride or 5% dextrose. <120 kg: 20 mL (200 mg) + 40 mL diluent. ≥120 kg: 30 mL (300 mg) + 60 mL diluent. NOT diluted into prefilled infusion bags or given as IV bolus. Administer over 6 hours every 12 hours via syringe pump.
- Duration: 14 days. Modifications to dose, frequency, and duration may be necessary based on clinical condition, disease progression, therapeutic response, or clinical judgment (consult CDC EOC/FDA).
Contraindications- JYNNEOS: History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose.
- TPOXX / TECOVIRIMAT INJECTION: Severe renal impairment (CrCl < 30 mL/min). No contraindications to oral tecovirimat.
Precautions & Warnings- JYNNEOS
- History of severe allergic reaction (anaphylaxis) following gentamicin or ciprofloxacin (contains trace amounts).
- History of severe allergic reaction (anaphylaxis) to chicken or egg protein AND currently avoiding exposure to all chicken/egg products.
- Moderate to severe acute illness with or without fever (defer until improved).
- Immunocompromised patients may have a diminished immune response.
- Appropriate medical treatment must be available to manage possible anaphylactic reactions; weigh risk of severe reaction against disease risk.
- TPOXX / TECOVIRIMAT
- Use with caution in mild or moderate renal impairment (injection due to reduced clearance of hydroxypropyl-β-Cyclodextrin vehicle).
- Hypoglycemia when co-administered with repaglinide.
- Weak inducer of CYP3A and weak inhibitor of CYP2C8/CYP2C19; effects not clinically relevant for most substrates except increased repaglinide and decreased midazolam concentrations.
Storage, Handling & Monitoring- JYNNEOS
- Frozen: Thaw to room temperature before use. Use vials before date marked on carton. Once thawed, store refrigerated (36–46°F) for up to 8 weeks. Do not re-freeze.
- Room Temperature: Unpunctured vials up to 6 consecutive hours (46–77°F). Punctured vials must be stored refrigerated and discarded within 8 hours of first puncture.
- Monitoring: Observe after vaccination for immediate adverse reactions including syncope. Observation duration is 30 minutes for persons with history of anaphylaxis to gentamicin, ciprofloxacin, or chicken/egg protein (and avoiding exposure); 15 minutes for all others.
- TPOXX / TECOVIRIMAT
- Diluted IV solution: Store refrigerated up to 24 hours, or 4 hours at room temperature.
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RITUXIMAB-PVVR INJ,SOLN
RUXIENCE
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RUXIENCE |
2022-07-13 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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MONKEYPOX/ SMALLPOX INJ,SUSP
JYNNEOS, JYNNEOS (NATIONAL STOCKPILE)
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JYNNEOS, JYNNEOS (NATIONAL STOCKPILE) |
2022-07-11 |
Indications & Patient Selection- JYNNEOS (Vaccine for Prevention)
- Indicated for pre- or post-exposure prophylaxis against monkeypox and smallpox in adults at high risk.
- Pre-exposure prophylaxis (PrEP): Recommended for laboratory workers handling orthopoxviruses; broader vaccination may be recommended when supply increases.
- Post-exposure prophylaxis (PEP): Indicated after high-risk exposure to monkeypox virus; ideally given within 4 days of exposure to prevent infection. Between 4–14 days post-exposure may be less effective. Beyond 14 days, benefits may outweigh risks in specific clinical situations (e.g., severely immunosuppressed patient with recent confirmed partner).
- Not expected to provide benefit if administered after onset of signs or symptoms of monkeypox.
- PEP++ (Enhanced PEP) criteria: Multiple sexual partners in the past 14 days in a jurisdiction with known monkeypox transmission.
- TPOXX / TECOVIRIMAT (Treatment)
- FDA approved for treatment of smallpox based on animal models; available under EA-IND protocol for non-variola orthopoxvirus infections including monkeypox during an outbreak.
- Consider for patients with severe disease: hemorrhagic disease, confluent lesions, sepsis, encephalitis, or conditions requiring hospitalization.
- Consider for persons at HIGH risk for severe disease: immunocompromised; pregnant/breastfeeding women; persons with complications (secondary skin infections, gastroenteritis with severe nausea/vomiting, diarrhea/dehydration, bronchopneumonia, concurrent disease/comorbidities); history or presence of atopic dermatitis or other exfoliative skin disorders.
- Consider for monkeypox virus aberrant infections: accidental implantation in eyes, mouth, genitals, or anus.
Dosing & Administration- JYNNEOS
- Standard (FDA-approved) regimen: 2 subcutaneous (SQ) doses of 0.5 mL each, 4 weeks apart, into fatty tissue over the triceps in the upper arm. Minimum interval is 28 days; may be given up to 4 days before or 7 days after. If delayed >7 days, administer ASAP without restarting series.
- Alternative (EUA) regimen: 0.1 mL administered intradermally (ID) on the volar surface of the forearm, second dose 28 days later. Preferred in VHA for most patients to maximize supply.
- Interchangeability: Adults who received standard SQ dosing may receive the second dose ID if no history of keloid development.
- TPOXX / TECOVIRIMAT
- Oral (Preferred): 600 mg every 12 hours for 14 days. Increase to 600 mg every 8 hours for patients weighing ≥120 kg. Must be given within 30 minutes of a full moderate or high fat meal.
- Intravenous (If unable to tolerate oral): Dilute with 0.9% sodium chloride or 5% dextrose. <120 kg: 20 mL (200 mg) + 40 mL diluent. ≥120 kg: 30 mL (300 mg) + 60 mL diluent. NOT diluted into prefilled infusion bags or given as IV bolus. Administer over 6 hours every 12 hours via syringe pump.
- Duration: 14 days. Modifications to dose, frequency, and duration may be necessary based on clinical condition, disease progression, therapeutic response, or clinical judgment (consult CDC EOC/FDA).
Contraindications- JYNNEOS: History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose.
- TPOXX / TECOVIRIMAT INJECTION: Severe renal impairment (CrCl < 30 mL/min). No contraindications to oral tecovirimat.
Precautions & Warnings- JYNNEOS
- History of severe allergic reaction (anaphylaxis) following gentamicin or ciprofloxacin (contains trace amounts).
- History of severe allergic reaction (anaphylaxis) to chicken or egg protein AND currently avoiding exposure to all chicken/egg products.
- Moderate to severe acute illness with or without fever (defer until improved).
- Immunocompromised patients may have a diminished immune response.
- Appropriate medical treatment must be available to manage possible anaphylactic reactions; weigh risk of severe reaction against disease risk.
- TPOXX / TECOVIRIMAT
- Use with caution in mild or moderate renal impairment (injection due to reduced clearance of hydroxypropyl-β-Cyclodextrin vehicle).
- Hypoglycemia when co-administered with repaglinide.
- Weak inducer of CYP3A and weak inhibitor of CYP2C8/CYP2C19; effects not clinically relevant for most substrates except increased repaglinide and decreased midazolam concentrations.
Storage, Handling & Monitoring- JYNNEOS
- Frozen: Thaw to room temperature before use. Use vials before date marked on carton. Once thawed, store refrigerated (36–46°F) for up to 8 weeks. Do not re-freeze.
- Room Temperature: Unpunctured vials up to 6 consecutive hours (46–77°F). Punctured vials must be stored refrigerated and discarded within 8 hours of first puncture.
- Monitoring: Observe after vaccination for immediate adverse reactions including syncope. Observation duration is 30 minutes for persons with history of anaphylaxis to gentamicin, ciprofloxacin, or chicken/egg protein (and avoiding exposure); 15 minutes for all others.
- TPOXX / TECOVIRIMAT
- Diluted IV solution: Store refrigerated up to 24 hours, or 4 hours at room temperature.
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DABIGATRAN CAP,ORAL
DABIGATRAN ETEXILATE, PRADAXA
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DABIGATRAN ETEXILATE, PRADAXA |
2022-07-07 |
Indications- Atrial fibrillation/flutter (AF)
- Acute venous thromboembolism (VTE), or prevention of recurrent VTE
- Primary prophylaxis of VTE in patients undergoing hip or knee replacement surgery
- Other indication for anticoagulation (local adjudication required)
Exclusions- Mechanical heart valve
- Moderate to severe rheumatic mitral valve stenosis (for AF/flutter only)
- Antiphospholipid syndrome (APS)
- Known significant liver disease (e.g., acute clinical hepatitis, cirrhosis [Child-Pugh C], or hepatic disease associated with coagulopathy)
- Pregnancy
- Breastfeeding
Pre-Treatment Assessment & Monitoring- Assessment of renal function (CrCl) and hemoglobin, hematocrit, and platelets
- Consider liver function testing in patients with a history of or risk for hepatic insufficiency
- Provider must assess DOAC choice, dose, and duration considering patient’s age, renal function, liver function, concurrent medications, and indication
- Identify and address modifiable risk factors for bleeding (e.g., NSAIDs, antiplatelet therapy)
- Document the treatment plan including duration in the patient’s chart
Dosing & Administration Requirements- For acute VTE: Administer 10 mg twice daily for 7 days as oral loading dose BEFORE starting maintenance doses
- Review drug dosing errors and drug-drug interactions, especially with new starts
Special Populations & Clinical Considerations- Bioprosthetic heart valve placement in the past 3 months: Appropriate based on shared decision-making process between provider and patient
- Severe renal impairment (CrCl <25-30 ml/min) or hemodialysis: Individual evaluation of risks and benefits recommended; net clinical benefit unclear
- Apixaban may be the preferred DOAC when CrCl is less than 30 ml/min
- For patients who can become pregnant: Counsel on potential risks vs benefits of treatment and use of effective contraception during therapy
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
FDA Approved Adult Indications- Non-valvular atrial fibrillation
- Treatment of DVT and PE (after 5-10 days of parenteral anticoagulant)
- Reduction in the risk of recurrent DVT and PE following initial therapy
- Post-surgical VTE prophylaxis following hip replacement surgery
- Post-surgical VTE prophylaxis following knee replacement surgery
Oversight & Initiation- Chronic DOAC therapy requires initial assessment, education, and follow-up by locally designated staff (e.g., anticoagulation management program or other designees).
- Facilities should utilize decision support tools and/or anticoagulation staff for upfront review to verify appropriate candidate selection, agent choice, and dosing upon initiation.
- Short-term treatment (e.g., post-surgical VTE prophylaxis) or very low dose regimens should follow education/monitoring protocols similar to alternative agents in that setting.
Laboratory Monitoring- Baseline: Serum creatinine (SCr) to estimate creatinine clearance (CrCl); CrCl estimated using Cockcroft-Gault equation with actual body weight for apixaban trials. Hemoglobin, hematocrit, and platelets required. Liver function tests may be considered for patients with history/risk of hepatic insufficiency. PT/aPTT may be obtained for emergency reference. Baseline values drawn within 1-3 months are acceptable per provider clinical judgment based on age/health status/comorbidities.
- Follow-up: SCr monitored at least annually (more frequently if CrCl < 60 ml/min, concomitant illness worsening renal function, or age ≥ 75 years). Hemoglobin, hematocrit, and platelets monitored at least annually or as clinically dictated. Liver function testing considered for underlying liver disease or clinical indication.
Patient Education- Initial and periodic education must cover: capsule/tablet identification, proper storage, therapy indication, risks/benefits, anticipated duration, daily dose/dosing changes (e.g., loading doses), administration considerations, drug interactions, monitoring requirements, adherence importance, management of missed/extra doses, signs/symptoms of bleeding/thromboembolic events, avoidance of major bleeding risk medications (e.g., NSAIDs, antiplatelets) unless instructed, non-bleeding adverse events, fall risks/mitigation, medication supply acquisition, pre-procedure provider notification for peri-procedural management, anticoagulation provider contact information, and gender-specific considerations for women of childbearing age (menstrual difficulties, pregnancy, contraception).
Adherence Monitoring- Monitor adherence, refill history, and medication tolerance, especially at therapy initiation.
- Utilize population management tools, telephone follow-up, face-to-face visits, secure messaging, or combinations based on site resources.
Follow-up Care- Initial: Within 2-4 weeks of initiation (or sooner if clinically indicated) to assess tolerance, bleeding, thromboembolic events, other adverse events (e.g., GI intolerance), adherence, correct dosing (e.g., transition from high-intensity initiation dosing for acute VTE), duplicate therapy, and reinforce education.
- Periodic/Long-term: Reassess adherence, screen for drug interactions, monitor labs as needed. Time points, methods, and responsible staff determined locally per VHA Directive 1108.16(1).
Quality Assurance- Incorporate DOACs into ongoing quality assurance plans per VHA Directive 1108.16(1).
- Report adverse events per local protocols and P&T Committee; enter into VA ADERS.
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RANOLAZINE GRNL,EC-ORAL
ASPRUZYO SPRINKLE
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ASPRUZYO SPRINKLE |
2022-07-07 |
FDA Approved Indication- Treatment of chronic stable angina
Exclusion Criteria- Clinically significant hepatic impairment
- Receiving strong CYP 3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir)
- Receiving strong CYP 3A4 inducers (rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John’s wort)
Inclusion Criteria- Anginal episodes averaging 3 or more times per week despite maximal or maximally tolerated anti-anginal drug therapy (defined as treatment with a beta-blocker, long-acting dihydropyridine calcium channel blocker, and a long-acting nitrate)
- Active VA healthcare provider involvement in monitoring and management of ranolazine therapy, with re-assessment of therapeutic effectiveness and tolerability within 12 weeks after initiation
Precautions & Drug Interactions- QT-interval prolongation: Dose-dependent increase (mean QTc increase of 6 ms at 1000 mg twice daily); use with caution in patients with pre-existing QT interval prolongation (Normal QTc <440 ms) due to lack of safety data
- Drug-drug interactions: Ranolazine is a CYP 3A4 and P-glycoprotein inhibitor/substrate, and lesser extent CYP 2D6 substrate; carefully review medications prior to initiation; dose adjustment or avoidance may be recommended; use with caution alongside other QT-prolonging drugs (Class Ia [quinidine] or Class III [amiodarone, dofetilide, sotalol] antiarrhythmics, erythromycin, certain antipsychotic agents) due to limited safety data
Dosage & Administration- Initiate therapy at 500 mg twice daily; maximum dose 1000 mg twice daily (dose escalation not consistently shown to improve symptoms; adverse events are dose-related)
- Maximum recommended dose limited to 500 mg twice daily with concurrent moderate CYP3A inhibitors (diltiazem, verapamil, aprepitant, erythromycin, fluconazole, grapefruit-containing products)
- Down-titration may be needed when used concurrently with P-glycoprotein inhibitors (e.g., cyclosporine)
Issues for Consideration- Reserve for patients who have not received an adequate response with other antianginal drugs; use in combination with beta-blockers, nitrates, and dihydropyridine calcium channel blockers
- Not shown to be pro-arrhythmic in a high-risk ACS population
- Increases simvastatin drug levels by 2-fold; monitor and counsel for potential adverse events despite manufacturer/FDA not recommending dosing adjustment
Renewal Criteria- Therapeutic effectiveness and tolerability must be assessed within the first 12 weeks of therapy
- Documented improvement in anginal symptoms and/or reduction in sublingual nitroglycerin consumption while receiving ranolazine
- Patient is not experiencing treatment-limiting adverse effects
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VUTRISIRAN INJ,SOLN
AMVUTTRA
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AMVUTTRA |
2022-06-30 |
Indication- Polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis
Exclusion Criteria- Sensorimotor or autonomic neuropathy without also having a diagnosis of hATTR amyloidosis
- Primary amyloidosis
- Leptomeningeal amyloidosis
- Currently receiving another therapy for hATTR amyloidosis (e.g., diflunisal, tafamidis, patisiran)
- Prior liver transplant
- New York Heart Association (NYHA) Class III or IV heart failure
- Known pregnancy
Inclusion Criteria- Provider is a VA or VA Community Care neurologist or locally designated hATTR amyloidosis provider
- Diagnosis of polyneuropathy of hATTR amyloidosis including clinical symptoms and genetic testing confirming a variant in TTR
- Documented baseline Neuropathy Impairment Score (NIS) of 5 to 130, Polyneuropathy Disability Score (PND) I to IIIb, or Familial Amyloid Polyneuropathy (FAP) stage 1 or 2
- Age 18-85 years
- Anticipated survival > 2 years
- Supplementation of the recommended daily allowance of vitamin A planned to start upon approval
- Discussion with patient/caregiver/family member regarding realistic treatment expectations and discontinuation documented
Monitoring & Continuation Requirements- Continuation assessed at 9 months and periodically throughout treatment
- Therapy continued only if patient demonstrates positive clinical response (e.g., improved motor function, quality of life, ambulation, or decreased neurological impairment)
- Refer to eye clinic if ocular symptoms suggestive of vitamin A deficiency develop (e.g., night blindness)
Special Populations & Administration- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment, including risk that vutrisiran can decrease serum vitamin A levels
- Must be administered by a healthcare professional
Exclusion Criteria- Heart failure not related to transthyretin-mediated amyloidosis (ATTR)
- Patient receiving concomitant therapy for ATTR
- End stage heart disease and anticipated survival < 1 year
Diagnostic & Clinical Requirements- Diagnosis of wild type or hereditary TTR genotype ATTR-CM based on endomyocardial biopsy OR echo/MRI suggestive of amyloidosis confirmed with radionuclide imaging (e.g., technetium pyrophosphate [Tc99-PYP] scintigraphy)
- Assessment of monoclonal protein screen for and exclusion of light chain (AL) amyloidosis
- History of symptomatic heart failure (at least one hospitalization for heart failure OR clinical evidence of heart failure manifested by signs and symptoms of volume overload or elevated intracardiac pressures)
Provider & Administrative Requirements- Provider must be a VA or VA Community Care cardiologist or locally designated ATTR-CM provider
- Discussion with patient/caregiver/family member regarding realistic treatment expectations and discontinuation should be documented
Monitoring, Counseling, & Supplemental Requirements- Supplementation of the recommended daily allowance of vitamin A is advised
- Referral to eye clinic if ocular symptoms suggestive of vitamin A deficiency develop (e.g., night blindness)
- Combination disease modifying ATTR-CM therapy has not been specifically studied or determined to be superior to single agent therapy
Special Populations- Females who can become pregnant: Counseling provided on potential risks vs benefits of treatment
Indication- Treatment of cardiomyopathy of hereditary or wild-type TTR-mediated amyloidosis (ATTR-CM)
- Indicated to reduce cardiovascular (CV) death, CV hospitalization, and urgent heart failure visits
- Also indicated for treatment of polyneuropathy (PN) in hereditary ATTR
Dosage & Administration- 25 mg subcutaneous injection once every 3 months into abdomen, thighs, or upper arms
- Administered by healthcare professional
- Supplied as 25 mg per 0.5 mL solution for injection in a single dose, prefilled 1 mL syringe; stored under at room temperature
Trial Population (Inclusion Criteria)- Adults with diagnosis of ATTR-CM (wild-type or variant) and clinical heart failure
- ATTR-CM diagnosis based on tissue biopsy or validated scintigraphy-based diagnosis in absence of monoclonal gammopathy; evidence of cardiac involvement by echo and end diastolic interventricular septal wall thickness >12 mm
- Clinical heart failure determined by ≥1 prior HF hospitalization, signs/symptoms of volume overload, or HF requiring diuretic treatment
- 6MWD ≥150 m
- NT-proBNP >300 pg/mL and <8,500 pg/mL
Trial Population (Exclusion Criteria)- NYHA class IV (or NYHA class III with Amyloidosis Disease Stage 3)
- CM not due to ATTR amyloidosis
- eGFR <30 mL/min per 1.73 m²
- Polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires assistance to walk or wheelchair bound) at screening
- Elevated transaminases >1.5x ULN or total bilirubin >1.5x ULN
- Recent ACS or unstable angina
Efficacy Outcomes- Primary endpoint: composite of all-cause death and recurrent CV events (CV hospitalization or urgent visits for HF)
- Superior to placebo in overall population and monotherapy population for primary composite endpoint
- Associated with less decline from baseline in 6MWD and health status (KCCQ-OS) vs placebo
- Significantly lower all-cause death at 42 months in open label extension vs placebo
Safety & Monitoring- No boxed warnings or contraindications
- Causes reduced serum vitamin A levels; supplementation of recommended daily allowance advised
- Refer to ophthalmologist if ocular symptoms of vitamin A deficiency occur
- Adverse event rates similar to placebo (99% vs 98%); discontinuations due to AEs similar (3% vs 4%)
- No clinically relevant changes in laboratory measures, vital signs, or electrocardiograms
- Not expected to cause drug interactions via enzyme induction or modulating drug transporters
Clinical Context & Formulary Considerations- RNA silencer approved for ATTR-CM; alternative disease modifying treatments include TTR stabilizers (tafamidis, acoramidis)
- ICER determined high certainty of substantial net benefit vs no treatment or in addition to tafamidis
- Insufficient evidence to compare net health benefits among the three agents
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SORAFENIB TAB
NEXAVAR
|
NEXAVAR |
2022-06-16 |
Exclusion Criteria- Care not provided by a VA or VA purchased care (e.g., Community Care Network, Fee Basis) oncology provider
- Liver dysfunction categorized as Child-Pugh class C
- Renal dysfunction requiring hemodialysis
- Pregnancy
- Breastfeeding
Indication/Inclusion Requirements- Unresectable or metastatic hepatocellular carcinoma (HCC)
- Other indication(s) – requires supporting evidence
HCC-Specific Clinical Parameters- ECOG performance status 0, 1 or 2
- Liver dysfunction categorized as Child-Pugh class A or B
- Adequate hematologic function – defined as hemoglobin > 8.5 g/dL, platelet count > 60 x 109 /L
- Concomitant use of strong CYP3A4 inducers has been avoided OR if unavoidable, sorafenib dose adjustment considered
- For female patients of child-bearing potential: provided counseling on effective contraception and potential risks vs. benefits of treatment
- For male patients with female partners of child-bearing potential: provided counseling on effective contraception and potential risks vs. benefits of treatment
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TREPROSTINIL POWDER,INHL
TYVASO DPI
|
TYVASO DPI |
2022-06-16 |
Provider & Care Setting Requirements- Care provided by a VA or VA Community Care provider experienced in the management of PAH
Diagnostic & Hemodynamic Criteria- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis
- Mean pulmonary artery pressure greater than 20 mmHg
- Pulmonary capillary wedge pressure 15 mmHg or less
- Pulmonary vascular resistance greater than 2 Wood units
Classification & Clinical Status- World Health Organization (WHO) Group 1 PAH
- Unacceptable or deteriorating clinical status on PAH-directed therapy with, or not a candidate for, an endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5i)
- Efficacy established in patients with NYHA Functional Class III symptoms
Formulation & Dosing Preferences- Nebulized solution preferred if patient requires more than one cartridge or capsule per dose using the DPI (e.g., >64 mcg of TYVASO or >106 mcg of YUTREPIA)
- Dry powder inhalers (DPIs) reserved for patients with documented inability to use the nebulized product
Adjudication & Documentation- Individual cases that are exceptions to inclusion/exclusion criteria should be adjudicated at the local facility level per P&T committee and pharmacy services policy/procedures
- Product information should be consulted for detailed prescribing information
Provider & Care Setting Requirements- Care must be provided by a VA or VA Community Care provider experienced in the management of pulmonary hypertension (PH).
Diagnosis & Indication Criteria- Definitive, confirmed diagnosis of interstitial lung disease (ILD) (e.g., diffuse parenchymal lung disease on chest CT).
- Examples of ILD include idiopathic interstitial pneumonia, combined pulmonary fibrosis and emphysema, connective tissue disease, and chronic hypersensitivity pneumonitis.
- Definitive, confirmed diagnosis of WHO Group 3 PH associated with ILD.
Hemodynamic Criteria (via Right-Heart Catheterization)- Mean pulmonary artery pressure of at least 25 mmHg.
- Pulmonary capillary wedge pressure of 15 mmHg or less.
- Pulmonary vascular resistance greater than 3 Wood units.
Formulation & Dosing Preferences- Nebulized solution is preferred for patients requiring more than one cartridge per dose using the dry powder inhaler (DPI) (e.g., >64 mcg of TYVASO or >106 mcg of YUTREPIA).
- DPI should be reserved for patients with a documented inability to use the nebulized product.
Adjudication & Clinical Management- All inclusion criteria must be met.
- Individual cases that are exceptions to exclusion/inclusion criteria or require formulation preference adjustments should be adjudicated at the local facility level per P&T Committee and Pharmacy Services policies/procedures.
Indication & Patient Population- • Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability
- • Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability
- • PH-ILD patient criteria: ILD diagnosed by chest CT, Group 3 PH confirmed by right heart catheterization (RHC) with pulmonary vascular resistance (PVR) >3 Wood units, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, mean pulmonary arterial pressure (mPAP) ≥25 mm Hg, and baseline 6-minute walk distance (6MWD) ≥100 m
Dosing & Administration- • Dry powder inhaler (DPI) strengths: 16 mcg, 32 mcg, 48 mcg, and 64 mcg single-dose color-coded cartridges
- • Dosing frequency: 1 breath per cartridge, 4 times daily, administered about 4 hours apart
- • Titration regimen: Initial dose of 3 breaths (6 mcg per breath) 4 times daily; target dose of 9 breaths; maximum dose of 12 breaths
- • Cartridge-to-strength mapping: 6 to 7 breaths corresponds to 32 mcg, 8 to 10 breaths to 48 mcg, and 11 to 12 breaths to 64 mcg
Safety, Warnings & Monitoring- • Contraindications: None stated
- • Boxed Warnings: None stated for the drug itself
- • Warnings/Precautions: Risk of symptomatic hypotension, bleeding (due to platelet aggregation inhibition), and bronchospasm; drug interactions with CYP2C8 inhibitors (increased adverse effects) or CYP2C8 inducers (decreased effectiveness)
- • Adverse Reactions: Cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea
- • Excipient consideration: Contains fumaryl diketopiperazine (FDKP); while FDKP carries a boxed warning for acute bronchospasm risk in chronic lung disease per other products, no bronchospastic adverse events or safety signals were identified in clinical studies
Storage & Device Management- • Cartridges must be stored in a refrigerator; room temperature excursions are permitted but shorten shelf life
- • DPI should be at room temperature for 10 minutes prior to use
- • Inhaler device is reusable for 7 days, then must be replaced/discarded
Place in Therapy & Efficacy Considerations- • Indicated based on a placebo-controlled trial demonstrating improved 6MWD, NT-proBNP ratio, and reduced clinical worsening
- • May be considered as an alternative to the liquid inhalation nebulized formulation for patients with PAH or PH-ILD
- • Long-term data are lacking; European guidelines provide a weak recommendation for use in PH-ILD
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EDARAVONE SUSP,ORAL
RADICAVA ORS
|
RADICAVA ORS |
2022-06-08 |
Exclusion Criteria- Notably decreased respiratory function and dyspnea (total score of 3 or less points on ALSFRS-R items for dyspnea, orthopnea, or respiratory insufficiency)
- Bilevel positive airway pressure (BiPAP) dependent (use 24 hours per day)
- Other medical illness that will limit evaluation of motor function and efficacy (e.g., Parkinson’s disease, schizophrenia, significant dementia, other major medical morbidity)
- Other possible causes for current symptoms as applicable not ruled out (e.g., cervical spondylosis or multifocal motor neuropathy)
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist or locally designated ALS expert
- Diagnosis of ALS made or confirmed by a VA/VA Community Care neurologist or locally designated ALS expert
- Documentation of an itemized ALSFRS-R score in the electronic medical record
- Preserved function in either upper limbs (e.g., self-feed, self-dressing, typing) or lower limbs (e.g., walking)
- Discussion with patient/caregiver/family regarding realistic treatment expectations and discontinuation of therapy documented in the patient’s medical record
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TAPINAROF CREAM,TOP
VTAMA
|
VTAMA |
2022-06-02 |
Diagnosis & Patient Selection- Exclusion: Psoriasis other than the plaque variant
- Inclusion: Diagnosis of plaque psoriasis (any severity)
Provider Oversight- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated psoriasis expert.
Prior Therapy Requirements- Tried and had intolerance or inadequate response (after ≥ 1 month) to topical roflumilast unless medically inadvisable.
- ONE of the following must be met:
- Tried and had intolerance or inadequate response to ≥ 2 other classes of topical antipsoriatics unless medically inadvisable (≥ 1 month / class; e.g., corticosteroids, vitamin D analogs, calcineurin inhibitors, etc.)
- Tried and had intolerance or inadequate response to 1 other class of topical antipsoriatic, and 1 systemic therapy (phototherapy, conventional immunomodulator, or targeted immunomodulator) unless medically inadvisable, not available, or not feasible.
Pregnancy & Reproductive Counseling- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
Additional Clinical Considerations & Definitions- Roflumilast is preferred before tapinarof due to likely safety and potential cost advantages.
- Topical roflumilast is labeled for intertriginous (skin fold) areas affected by plaque psoriasis and may be preferred over tapinarof for intertriginous lesions or inverse plaque psoriasis.
- A prior trial of topical corticosteroids is not necessary and may be medically inadvisable for lesions in sensitive areas (e.g., face, intertriginous areas).
- Topical nonsteroidal treatments like tapinarof may be used alone or co-used with corticosteroids to reduce or prevent corticosteroid complications; therefore, prior trial of or inadequate response to corticosteroids is not always required.
- Examples of topical therapies (not all inclusive): Vitamin D analogs (Calcipotriene, calcipotriol), Calcineurin inhibitors (Tacrolimus, pimecrolimus), Retinoids (Tazarotene), Coal tar, Phosphodiesterase-4 Inhibitor (Roflumilast). Topical emollients and keratolytics do not count as topical antipsoriatics.
- Phototherapy is considered medically inadvisable if there is NO treatment benefit after 12 treatments or inadequate partial response after 24 treatments.
- Reasons phototherapy may be medically inadvisable include confirmed history of skin cancer, melanoma, or strong likelihood of developing them (e.g., Fitzpatrick skin type I or II = pale skin, easily sunburns).
- Conventional immunomodulator example: methotrexate.
- Systemic targeted immunomodulators examples: tumor necrosis factor inhibitors, interleukin-17A inhibitors (e.g., ixekizumab), interleukin-23 inhibitors (e.g., risankizumab-rzaa), interleukin-12/23 inhibitor (e.g., ustekinumab), and phosphodiesterase-4 inhibitors (e.g., apremilast).
Indication & Patient Population- • Topical treatment of plaque psoriasis in adults
- • Patients requiring topical nonsteroidal therapy (e.g., for treatment of lesions in sensitive areas or to limit corticosteroid use or complications)
Prior Therapy Requirements- • Inadequate response or intolerance to topical roflumilast (unless medically inadvisable)
- • AND either:
- • ≥ 2 other classes of topical antipsoriatics (e.g., topical corticosteroids, vitamin D analogs, calcineurin inhibitors, retinoids/tazarotene, or coal tar)
- • OR 1 other class of topical antipsoriatics and 1 class of systemic antipsoriatics (e.g., phototherapy, conventional immunomodulator such as methotrexate, or biologic)
Dosing & Administration- • Apply a thin layer of cream to affected areas once daily
- • Concentration: 1% cream
Safety & Clinical Considerations- • Unknown safety and efficacy when used in combination with other antipsoriatic topical, systemic (including biologic), or ultraviolet light therapies
- • Limited long-term safety data and real-world experience with topical tapinarof
- • May be more preferable than tazarotene due to low risks of skin irritation and burning/stinging, and lack of desquamating effects
- • Less preferable than alternative antipsoriatic topical therapies in patients with a significant history of folliculitis
- • Not specifically labelled for application to facial or intertriginous areas (though studied)
Diagnosis- Diagnosis of atopic dermatitis
Prescribing and Monitoring Requirements- Prescribed and monitored by a VA/VA Community Care dermatologist or locally designated expert
Prior Therapy Requirements (All must be met)- A topical corticosteroid and a topical calcineurin inhibitor (e.g., tacrolimus ointment 0.1% or 0.03% or pimecrolimus cream 1%) are medically inadvisable, not tolerated, or not adequate after trials of ≥ 1 month per drug class
Additional Prior Therapy Requirements (One must be met)- For mild to moderate atopic dermatitis: Topical crisaborole 2% ointment or roflumilast 0.15% cream is medically inadvisable, not tolerated, or not adequate after a trial of ≥ 1 month
- For moderate to severe atopic dermatitis: No prior topical agents required other than a corticosteroid and calcineurin inhibitor
Additional Patient-Specific Criteria- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
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TIRZEPATIDE INJ,SOLN
MOUNJARO, ZEPBOUND, ZEPBOUND KWIKPEN
|
MOUNJARO, ZEPBOUND, ZEPBOUND KWIKPEN |
2022-05-26 |
Exclusion Criteria- Diagnosis of Type 1 diabetes
- Personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility including gastroparesis
- History of pancreatitis (does not pertain to patients for whom the cause of pancreatitis is known and no longer presents a risk)
- Pregnancy (insulin generally preferred; use only if potential benefit justifies potential risk to fetus and mother)
- Known PDR, severe NPDR, clinically significant ME, or DME unless risks/benefits have been discussed with the patient and is documented in the EHR along with monitoring plans and follow-up with an eye specialist who is informed at the time of initiation
Relative Exclusion- Risk factors for pancreatitis (e.g., untreated fasting triglyceride level > 1000mg/dL, known gallstones with intact gallbladder, alcohol use disorder)
Inclusion Criteria- Diagnosis of Type 2 diabetes
- Inadequate glycemic control on at least 1mg of semaglutide injection plus two or more glucose lowering drugs (metformin, empagliflozin, insulin, pioglitazone, sulfonylurea) for at least 6 months
- Change needed to achieve goal A1C is less than 1% (goal based on VA/DoD Diabetes Guidelines)
- Adherent to current diabetes medications as evidenced by a review of prescription refill history during the last 6 months
- Current non-GLP 1A drugs are optimized as appropriate
Additional Inclusion Criteria- Patients with ASCVD or CKD: Receiving empagliflozin unless unable to use
- Patients of childbearing potential using oral contraceptives: Counseled to switch to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation
Additional Clinical Requirements & Restrictions- Prior GLP 1A trial required: Patients on liraglutide or exenatide must be switched to semaglutide first; patients with semaglutide intolerance should trial another GLP 1A before tirzepatide
- Empagliflozin recommendation: Recommended for overweight patients (BMI greater or equal to 27kg/m2) unless unable to use
- Insulin consideration: Consider insulin at any time prior to using tirzepatide, unless unable to use or otherwise inappropriate
- Combination restrictions: Do not use with GLP-1 agonists or DPP-4 inhibitors; concomitant use with alpha glucosidase inhibitors or meglitinides not recommended due to lack of or insufficient data
- Insulin regimen limitations: No data combining tirzepatide with both basal and prandial insulin (including premixed formulations) or with U500 insulin; concomitant use may be done on a case-by-case basis in consultation with an endocrinologist or diabetes specialist
- Retinopathy monitoring: Provider should have diabetic eye examination results within past 12 months on file; consider disease severity and activity; planned follow-up with eye provider required for progression; consult eye care specialist if concerns arise
Indication & Population- • Adults with type 2 diabetes mellitus
- • Adjunct to diet and exercise to improve glycemic control
Dosage & Administration- • Available in pre-filled single-dose pens: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg
- • Recommended starting dosage: 2.5 mg injected subcutaneously once weekly
- • After 4 weeks, increase to 5 mg injected subcutaneously once weekly
- • If additional glycemic control is needed, increase in 2.5 mg increments after at least 4 weeks on the current dose
- • Maximum dosage: 15 mg subcutaneously once weekly
- • Administer once weekly at any time of day, with or without meals
- • Inject subcutaneously in the abdomen, thigh, or upper arm
Efficacy & Place in Therapy- • Considered as an intensification option for patients with type 2 diabetes treated with semaglutide 1 mg or 2 mg in need of additional glycemic control
- • Current diabetes therapy, including diet and exercise, should be optimized as appropriate and adherence to therapy confirmed before considering tirzepatide
- • If not already using, consider adding empagliflozin or insulin if appropriate
Contraindications & Warnings/Precautions- • Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- • Known serious hypersensitivity to tirzepatide or any excipients
- • Pancreatitis: Discontinue promptly if suspected
- • Hypoglycemia with concomitant use of insulin secretagogues or insulin: Reducing dose of insulin secretagogue or insulin may be necessary
- • Hypersensitivity reactions: Discontinue tirzepatide if suspected
- • Severe gastrointestinal disease: Not recommended; has not been studied in these patients
- • Diabetic retinopathy complications: Has not been studied in non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema; monitor patients with a history of diabetic retinopathy for progression
- • Acute gallbladder disease: If cholelithiasis is suspected, perform gallbladder studies and clinical follow-up
Monitoring & Special Populations- • Acute kidney injury: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions
- • Oral hormonal contraceptives: Advise patients to switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiation and for 4 weeks after each dose escalation due to reduced Cmax/AUC and delayed Tmax; non-oral hormonal contraceptives are not affected
- • Pregnancy: Use only if potential benefit justifies potential risk to the fetus; insufficient data on drug-related risk of major birth defects or miscarriage
- • Lactation: No data on presence in milk; consider developmental/health benefits of breastfeeding along with mother’s clinical need and potential adverse effects on the breastfed infant
Indication & Patient Selection- • Indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adults.
- • Requires an initial body mass index (BMI) of ≥30 kg/m² (obesity) or ≥27 kg/m² (overweight) with at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).
Dosing & Administration- • Administered subcutaneously once weekly.
- • Initial dose is 2.5 mg/0.5 mL.
- • Weekly dose should be increased by 2.5 mg at 4-week intervals.
- • Maintenance doses are 5 mg, 10 mg, and 15 mg SC once weekly.
- • Maximum dose is 15 mg SC once weekly.
Contraindications- • Personal or family history of medullary thyroid carcinoma (MTC).
- • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- • Known serious hypersensitivity to tirzepatide or any excipients in ZEPBOUND.
Warnings & Precautions / Monitoring Criteria- • Pancreatitis: Discontinue promptly if pancreatitis is suspected.
- • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin: Concomitant use may increase the risk of severe hypoglycemia; reducing dose of insulin secretagogue or insulin may be necessary.
- • Hypersensitivity Reactions: Discontinue tirzepatide if suspected.
- • Acute Kidney Injury: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions that could lead to volume depletion.
- • Severe Gastrointestinal Disease: Not recommended in patients with severe gastrointestinal disease.
- • Diabetic Retinopathy Complications: Monitor patients with a history of diabetic retinopathy for progression; not studied in non-proliferative requiring acute therapy, proliferative, or diabetic macular edema.
- • Acute Gallbladder Disease: If cholelithiasis is suspected, perform gallbladder studies and clinical follow-up.
- • Suicide Behavior and Ideation: Avoid use in patients with a history of suicidal attempts or active suicidal ideation. Monitor for emergence or worsening of depression, suicidal thoughts/behaviors, or unusual changes in mood/behavior; discontinue if experienced.
Special Populations- • Pregnancy/Fetal Harm: Discontinue when pregnancy is recognized. Weight loss offers no benefit to a pregnant patient and may cause fetal harm.
- • Reproductive Potential: Patients using oral contraceptives should switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiating tirzepatide and for 4 weeks after each dose escalation due to delayed gastric emptying.
Exclusion Criteria- Known pregnancy
- Lactating
- Type 1 diabetes (unless followed by a diabetes/weight management specialist under careful supervision)
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History of pancreatitis (does not apply if the cause is known and no longer presents a risk)
- Known proliferative diabetic retinopathy (PDR), severe non-proliferative diabetic retinopathy (NPDR), clinically significant macular edema (ME), or diabetic macular edema (DME) unless risks/benefits are discussed with the patient, documented in the electronic health record (EHR) with monitoring plans and follow-up, and an eye specialist is informed at initiation
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention (CLI) targeting diet, physical activity, and behavioral changes
- Body mass index (BMI) ≥ 30 kg/m² with at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, metabolic dysfunction-associated steatotic liver disease)
Additional Inclusion & Counseling Requirements- For females who can become pregnant: Pregnancy must be excluded prior to receiving the medication; contraceptive counseling regarding potential risks vs. benefits of pregnancy must be provided
- Females of childbearing potential using oral contraceptives: Must be counseled to switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiation and for 4 weeks after each dose escalation
Clinical Monitoring & Management Considerations- Consider discontinuing medications that may precipitate weight gain if clinically appropriate
- For patients with diabetes: Diabetic eye exam results should be available within the past 12 months (or 24 months if no evidence of retinopathy); consider disease severity and activity; ensure planned follow-up with an eye provider for those with a history of diabetic retinopathy; consult an eye care specialist if concerns arise regarding use
- Individual cases that are exceptions to exclusion or inclusion criteria should be adjudicated at the local facility according to P&T committee and pharmacy services policy
Indications & Eligibility- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance
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DEXMEDETOMIDINE FILM,SUBLINGUAL
IGALMI
|
IGALMI |
2022-05-19 |
Indication- Acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.
Dosing & Formulation- Sublingual film: 120 mcg and 180 mcg strengths.
- Self-administered medication.
Efficacy & Place in Therapy- Efficacy established for reducing mild to moderate agitation; efficacy of the 120 mcg and 180 mcg doses is comparable, with slightly greater Positive and Negative Syndrome Scale-Excited Component (PEC) total score reduction observed with the 180 mcg dose.
- Safety and effectiveness have not been established beyond 24 hours from the first dose.
- Efficacy compared to alternative treatments has not been established.
- May be considered for patients with mild to moderate acute agitation associated with schizophrenia or bipolar disorder who cannot tolerate PRN antipsychotics or benzodiazepines.
Safety, Precautions & Contraindications- Avoid use in patients with hypotension, orthostatic hypotension, advanced heart block, severe ventricular dysfunction, or history of syncope.
- Avoid use in patients with risk factors for prolonged QT interval.
- Common adverse reactions include somnolence, paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension, and orthostatic hypotension.
- Other warnings/precautions include bradycardia, QT interval prolongation, risk of withdrawal reactions, and tolerance/tachyphylaxis.
Special Considerations- Abuse potential is not yet understood; may not be suitable for patients with comorbid substance use disorder (SUD).
- Study populations were cooperative enough for self-administration and informed consent, which may not represent typical PRN agitation populations on psychiatry units or in emergency departments.
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MAVACAMTEN CAP,ORAL
CAMZYOS
|
CAMZYOS |
2022-05-13 |
Exclusion Criteria- Left ventricular ejection fraction (e.g., per echocardiogram) < 55%
- Concomitant strong CYP2C19 inhibitors
- Concomitant moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers
- Concomitant use with disopyramide or ranolazine
Inclusion Criteria- Care provided by a VA/VA Community Care cardiologist or locally designated expert in managing obstructive hypertrophic cardiomyopathy
- Diagnosis of obstructive hypertrophic cardiomyopathy with New York Heart Association (NYHA) class II-III symptoms
- Peak left ventricular outflow tract gradient at least 50 mm Hg at rest, after Valsalva maneuver, or post-exercise
- Inadequate benefit from or unable to use a non-vasodilating beta-blocker
- Inadequate benefit from or unable to use a non-dihydropyridine calcium channel blocker
- Patient and provider enrolled in the CAMZYOS REMS program
Additional Inclusion Criteria- For patients who can become pregnant: Pregnancy excluded prior to receiving mavacamten
- For patients who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 4 months after stopping treatment
- For patients on weak-to-moderate CYP2C19 inhibitor or moderate-to-strong CYP3A4 inhibitor: Additional monitoring planned and/or mavacamten dose modified as appropriate per prescribing information
Clinical Notes & Management Considerations- Clinical trial inclusion criteria note unexplained left ventricular hypertrophy with maximal left ventricular wall thickness of ≥15 mm (or ≥13 mm if familial hypertrophic cardiomyopathy)
- If current treatment includes both a non-dihydropyridine calcium channel blocker and a beta-blocker, discontinue one agent before initiating mavacamten
- Mavacamten may reduce the effectiveness of combined hormonal contraceptives; advise patients to use an alternative contraceptive method not affected by CYP450 enzyme induction or add nonhormonal contraception
Indication & Patient Population- • Adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.
Clinical & Diagnostic Criteria- • Diagnosis of obstructive HCM defined as unexplained left ventricular hypertrophy with maximal left ventricular wall thickness ≥15 mm (or ≥13 mm if familial HCM).
- • Peak left ventricular outflow tract (LVOT) gradient ≥50 mm Hg at rest, after Valsalva maneuver, or post-exercise.
- • Left ventricular ejection fraction (LVEF) ≥55%.
Dosing & Titration Requirements- • Recommended starting dose is 5 mg once daily without regard to food.
- • Initiation or up-titration is not recommended if LVEF <55%.
- • Subsequent titration doses are 2.5 mg, 5 mg, 10 mg, or 15 mg once daily.
- • Dosing should be individualized to achieve a target reduction in LVOT to less than 30 mm Hg and a mavacamten plasma concentration between 350 to 700 ng/mL.
Monitoring & Assessment Requirements- • Echocardiogram assessments of LVEF are required prior to and during treatment.
- • Monitor LVEF and Valsalva LVOT gradient at week 4, week 8, and week 12 to appropriately adjust dose.
- • During maintenance therapy, adjust treatment dose every 12 weeks based on patient’s LVEF and Valsalva LVOT gradient.
- • Assess patient’s clinical status prior to and regularly during treatment; adjust dose accordingly.
- • Evaluate cardiac function if signs/symptoms of heart failure occur (e.g., new or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in NT-proBNP).
Treatment Interruption & Discontinuation Criteria- • Treatment must be interrupted if LVEF is <50% at any visit.
- • Treatment should be interrupted if the patient experiences heart failure symptoms or worsening clinical status.
Contraindications & Drug Interactions- • Contraindicated with moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors.
- • Contraindicated with moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.
- • Avoid concomitant use with disopyramide, ranolazine, verapamil with beta-blockers, or diltiazem with beta-blockers.
REMS & Programmatic Requirements- • Use is restricted to the CAMZYOS REMS Program.
- • Prescribers must be certified by enrolling in the program.
- • Patients must enroll and comply with ongoing monitoring requirements.
- • Pharmacies must be certified and only dispense to authorized patients.
Place in Therapy / Sequential Use- • Considered for symptomatic obstructive HCM when a non-vasodilating beta-blocker is ineffective or not tolerated, or after failure of a non-DHP CCB.
- • For patients with persistent severe symptoms despite beta-blocker or non-DHP CCB therapy, addition of disopyramide or septal reduction therapy may be considered.
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PIRFENIDONE TAB,ORAL
ESBRIET
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ESBRIET |
2022-05-13 |
Indication & Diagnostic Requirements- Diagnosis of idiopathic pulmonary fibrosis (IPF)
- Must meet ATS/ERS/JRS/ALAT diagnostic requirements
- Confirmed through formal interdisciplinary discussion (Interstitial Lung Disease Consensus Committee or similar)
- Requires exclusion of other known causes of interstitial lung disease (e.g., environmental exposures, connective tissue disease, drug toxicity)
- Requires pattern of usual interstitial pneumonia on high-resolution computed tomography (HRCT) and/or specific combinations of HRCT and surgical lung biopsy patterns
Patient Selection & Exclusion Criteria- Patient should NOT receive pirfenidone if: IPF diagnosis unconfirmed; current smoker; severe hepatic impairment (Child Pugh Class C); end-stage renal disease requiring dialysis; currently receiving nintedanib; taking combination of moderate/strong CYP1A2 inhibitors with other CYP inhibitors that cannot be altered/discontinued; or documented ongoing nonadherence
- Treatment must be initiated and followed by a VA Pulmonologist experienced in ILD diagnosis and management
Dosage & Administration- Recommended dosage: 801 mg three times daily with food (total 2403 mg/day)
- Doses should be taken at the same time each day
- Titration schedule for initiation or resumption after ≥14-day lapse over 14 days: Days 1–7: one 267mg capsule three times daily; Days 8–14: two 267mg capsules three times daily; Day 15 onward: one 801mg tablet three times daily
- Dose modifications may be required for side effects, liver function abnormalities, or drug interactions
Monitoring & Laboratory Requirements- Pulmonary specialty follow-up including pulmonary function testing at least biannually to assess drug response
- Adherence monitoring required for maximal benefit
- Liver chemistries (AST, ALT, total bilirubin): obtain at baseline, monthly for 6 months, then every 3 months thereafter
- FVC and DLCO measurements: routine monitoring at 3–6 month intervals; more frequent testing if progressive dyspnea or rapidly progressive course present
- Advise patients to avoid/minimize sunlight/UV exposure and use SPF≥50 sunblock and occlusive clothing/hats due to photosensitivity/rash risk
Management of Adverse Reactions & Liver Abnormalities- AST/ALT >3 to ≤5x ULN without symptoms/hyperbilirubinemia: discontinue confounding medications, exclude other causes, monitor closely, repeat tests as indicated; maintain full dose if appropriate or reduce/interrupt until normal, then re-titrate
- AST/ALT >3 to ≤5x ULN with symptoms/hyperbilirubinemia: permanently discontinue and do not rechallenge
- AST/ALT >5x ULN: permanently discontinue and do not rechallenge
- Strong CYP1A2 inhibitors: Co-administration of pirfenidone with strong CYP1A1 inhibitors (ex: fluvoxamine, enoxacin) is not recommended; if unavoidable, reduce dose of pirfenidone to 267mg three times daily
- Moderate CYP1A2 inhibitors: Reduce dose of pirfenidone to 534mg three times daily in combination with high-dose moderate CYP1A2 inhibitor (ex: ciprofloxacin 750mg twice daily)
- Strong/moderate CYP1A2 inhibitors combined with other CYP inhibitors: Discontinue or avoid combinations due to unpredictable clearance effect
- Strong CYP1A2 inducers: Co-administration not recommended due to expected reduction in pirfenidone exposure and loss of efficacy
- Temporary dose reductions may be required to allow resolution of symptoms
Discontinuation Guidelines- Temporarily discontinue for mildly elevated liver function tests or moderate severity adverse reactions (rash, photosensitivity, gastrointestinal, or other)
- Permanently discontinue for: severe adverse drug reactions, liver function test abnormalities per monitoring criteria, significant nonadherence to therapy, or smoking
- Consider discontinuation for perceived treatment failure based on serial pulmonary function trends
Special Populations & Clinical Considerations- Pregnancy Category C; women of childbearing potential require contraceptive counseling; use during pregnancy only if maternal benefit outweighs fetal risk
- Unknown excretion in breast milk; decide to discontinue nursing or pirfenidone based on drug importance to mother
- Limited data for severe IPF (FVC < 50%); randomized controlled trials did not enroll patients with severe disease
- Lung transplant wait list: Inadequate data; case-specific assessment of risks and benefits recommended due to short median wait times and high mortality rates among listed patients
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APOMORPHINE INJ,SOLN
APOKYN, APOMORPHINE HCL, ONAPGO
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APOKYN, APOMORPHINE HCL, ONAPGO |
2022-04-21 |
Indication- Treatment of motor fluctuations in adults with advanced Parkinson’s disease
Patient Population & Eligibility Criteria- Adults ≥30 years old
- Parkinson’s disease diagnosis >3 years prior to therapy initiation
- Stable dose of oral medications for at least 4 weeks prior to enrollment
- Mean of ≥3 hours of off time per day over 2 days at screening/baseline, with no single day recording <2 hours of off time
- Patients experiencing persistent motor fluctuations despite optimized oral or transdermal medication/levodopa therapy
- Considered when oral medications can no longer manage motor fluctuations and dyskinesias
- May be appropriate for patients who are not candidates for deep brain stimulation (DBS) or other invasive devices (e.g., elderly, non-surgical candidates)
Dosing & Administration- Administered as a continuous subcutaneous infusion via Onapgo pump using 98 mg/20 mL (4.9 mg/mL) single dose cartridges
- Initial dose: 1 mg/hour
- Titrate based on response and tolerability in 0.5 to 1 mg/hour increments at intervals ≥1 day
- Maximum continuous dosage: 6 mg/hour
- Maximum total daily dose (including continuous infusion and extra doses): 98 mg/day administered over the waking day (e.g., 16 hours)
Pretreatment & Monitoring Requirements- Due to incidence of nausea and vomiting, recommend starting trimethobenzamide 300 mg three times a day 3 days prior to initial apomorphine dose
- Alternative: Start without antiemetics and titrate slowly based on effectiveness and tolerance
- Monitor for infusion site reactions (skin nodules, erythema/pruritus, bruising), which are frequent reasons for discontinuation; mitigation strategies for skin irritation may be considered
Contraindications- Concomitant use of 5HT3 antagonists (including antiemetics such as ondansetron and alosetron)
- Hypersensitivity or allergic reaction to apomorphine or any excipients, including sulfite (sodium metabisulfite)
Warnings & Precautions- Nausea and vomiting
- Somnolence and falling asleep during activities of daily living
- Syncope/hypotension and orthostatic hypotension
- Falls
- Infusion site reactions
- Hallucinations/psychosis
- Dyskinesia
- Hemolytic anemia
- Impulse control disorder/compulsive behaviors
- Cardiac events
- QTc prolongation
- Hypersensitivity
- Fibrotic complications
- Priapism
Drug Interactions- 5HT3 antagonists (risk of hypotension)
- Antihypertensive drugs and vasodilators (risk of hypotension)
- Alcohol (risk of hypotension)
- Dopamine antagonists (may diminish efficacy)
- Drugs prolonging QT/QTc interval
Special Populations- Pregnancy: No adequate data available
- Lactation: No data available
Clinical Considerations & Place in Therapy- Device-assisted therapies considered when oral medications can no longer manage motor fluctuations and dyskinesias
- Non-motor symptoms of advanced Parkinson’s disease (e.g., severe dementia, chronic hallucinations, or psychosis) may impact therapy selection
- Indicated for use during waking hours; daytime-only pump wear may be preferred by some patients, with bolus function available for morning use to prevent morning akinesia
- Higher incidence of somnolence compared to continuous levodopa-based therapies (subcutaneous or intestinal gel)
Exclusion Criteria- Concurrent use of apomorphine injections
- Concurrent use of a 5-HT3 antagonist (e.g., ondansetron, granisetron, dolasetron, palonosetron and alosetron)
- Concurrent use of continuous subcutaneous or intrajejunal infusion of carbidopa/levodopa
- Baseline resting corrected QT interval (QTc) > 450 msec for males and > 470 msec for females on electrocardiogram (ECG) or other risk factors for a prolonged QT interval
Inclusion Criteria- Diagnosis of Idiopathic Parkinson’s Disease
- Patient is under the care of a VA or VA Community Care neurologist or locally designated expert
- Motor fluctuations (“wearing off”) that require dosing of dopaminergic medications at intervals every 4 hours or less
- Either higher frequency (≥5 times daily) carbidopa/levodopa immediate-release (IR) tablet or carbidopa/levodopa extended-release (ER) capsules throughout the day have not adequately resolved OFF periods
- Contraindication, intolerance, or inadequate therapeutic response to at least one agent from two of the following classes: dopamine agonist, catechol-O methyl transferase [COMT] inhibitor, monoamine oxidase type B [MAO B] inhibitor
- Discussion with the patient/caregiver/family regarding realistic efficacy expectations, device management, and potential device-related complications documented in the patient’s medical record
QT Prolongation Risk Factors- Electrolyte abnormalities
- Heart failure
- Congenital long QT syndrome
- Family history of long QT syndrome
- Concomitant medications known to prolong QTc interval
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DARIDOREXANT TAB,ORAL
QUVIVIQ
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QUVIVIQ |
2022-04-21 |
Exclusion Criteria- Narcolepsy
- Co-administration with strong CYP3A inhibitors
- Co-administration with moderate or strong CYP3A4 inducers
- Active substance use disorder
- Considered a high suicide risk
- Untreated significant sleep-related breathing disorder-obstructive or central sleep apnea syndrome
- Severe hepatic impairment (e.g., Child-Pugh C)
- Receiving other drugs to treat insomnia
- History of complex sleep behaviors
Inclusion Criteria- Prescribed and monitored by a VA / VA Community Care sleep specialist or locally designated expert in sleep disorders
- Documented diagnosis of insomnia characterized by difficulties with sleep onset and/or sleep maintenance
- When available, cognitive behavioral therapy for Insomnia (CBT-I) has been tried, via face to face, tele-mental health or non-VA care
- An adequate short-term trial of 2 formulary sedative hypnotics for the treatment of sleep onset and maintenance have been tried and failed to resolve symptoms or were not tolerated
Indication- • Treatment of adult patients with insomnia characterized by difficulties with sleep onset and/or sleep maintenance
Dosing & Administration- • Available as 25 mg and 50 mg tablets
- • Once daily administration
- • Clinically meaningful efficacy is supported only for the 50-mg dose based on AASM consensus criteria
Warnings & Precautions- • CNS-depressant effects and daytime impairment
- • Worsening of depression/suicidal ideation
- • Sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms
- • Complex sleep behaviors
- • Patients with compromised respiratory function
- • Need to evaluate for co-morbid diagnoses
Drug Interactions- • Avoid co-administration with strong CYP3A inhibitors
- • Avoid co-administration with moderate or strong CYP3A4 inducers
Hepatic Impairment- • Not recommended in severe hepatic impairment (Child-Pugh C)
Formulary & Regulatory Status- • Non-Formulary (NF) with Clinical Formulary Utilization (CFU)
- • Schedule IV controlled substance
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NIVOLUMAB/ RELATLIMAB-RMBW INJ,SOLN
OPDUALAG
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OPDUALAG |
2022-04-01 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Untreated unresectable or metastatic melanoma
- Patient is not expected to tolerate treatment with nivolumab and ipilimumab, the preferred first-line immunotherapy combination due to comorbidities or performance status (see Metastatic Cutaneous Melanoma Drug Sequencing Document in Clinical Recommendations)
- Consider ipilimumab 1mg/nivolumab 3mg dosing if patient unlikely to tolerate ipilimumab 3mg/nivolumab 1 mg
Additional Inclusion Criteria- Care provided by a VA/VA Community Care oncology or hematology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Reproductive Health & Counseling Requirements- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for at least 5 months after stopping treatment
Indication & Patient Population- • Treatment of unresectable metastatic melanoma
- • Previously untreated, unresctable Stage III or IV melanoma
- • Patients 12 years of age and older
- • Measurable disease by RECIST v1.1 criteria
- • ECOG performance status 0-1
Exclusion Criteria- • Requirement of >10 mg/day prednisone equivalent for 2 weeks prior to study treatment administration
- • Prior immune checkpoint inhibitor therapy (unless given as adjuvant or neoadjuvant therapy for melanoma)
- • Radiotherapy within 2 weeks
- • Active brain or leptomeningeal metastases
- • Active, known, or suspected autoimmune disease
- • History of myocarditis
- • Pregnant or breastfeeding
Dosing & Administration- • Dosage form: Single-dose vial containing 240 mg nivolumab and 80 mg relatlimab per 20 mL (12 mg/mL and 4 mg/mL)
- • Regimen: 480 mg IV nivolumab and 160 mg IV relatlimab every 4 weeks
- • Administration: Infused over 30 minutes with a 0.2-1.2 micrometer in-line filter
- • Treatment continued until disease progression, intolerable toxicity, death, or withdrawal of consent
Safety & Monitoring Considerations- • Immune-mediated adverse reactions: dermatitis, immune-mediated rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, endocrinopathies, gastrointestinal toxicity, hepatotoxicity, infusion-related reactions, nephrotoxicity, ocular toxicity, pulmonary toxicity
- • Cardiotoxicity: immune-mediated myocarditis, pericarditis, and vasculitis
- • Disease-related concerns: transplant-related complications (graft vs. host disease, hepatic veno-occlusive disease) in patients receiving allogeneic hematopoietic stem cell transplant before or after treatment; worsening or precipitation of myasthenia gravis
- • Dosage form specific: Polysorbate 80 may induce hypersensitivity reactions
- • Common adverse reactions (>10%): pruritus, fatigue, rash, arthralgia, hypothyroidism, diarrhea, vitiligo
- • Serious adverse events/toxicity leading to discontinuation noted (Grade 3-4 toxicity: 10.3%; Deaths: 0.8%; Toxicity leading to discontinuation: 8.5%)
Clinical Guidance & Place in Therapy- • NCCN-preferred category 2A recommendation for first-line treatment of metastatic or unresectable melanoma
- • Considered an alternative option for first-line combination immunotherapy if patient is eligible per VHA guidance on drug sequencing
- • Standard of care includes immunotherapy, targeted therapy against BRAF V600-activating mutations, combination therapy, or single-agent immunotherapy
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CABOTEGRAVIR INJ,SUSP,SA
APRETUDE, CABOTEGRAVIR ER (CABENUVA)
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APRETUDE, CABOTEGRAVIR ER (CABENUVA) |
2022-03-17 |
Patient Eligibility & Inclusion Criteria- • Prescribed by or in collaboration with a provider experienced or trained in PrEP administration (designated facility providers)
- • Substantial risk of HIV acquisition: sex without condoms, recent or frequent sexually transmitted infections (STIs), sexual relationship with an HIV-infected partner, injection drug abuse with equipment sharing
- • Must also meet at least one additional criterion:
- Intolerance to Truvada or Descovy
- CrCl <60 mL/min or multiple risk factors for significant renal dysfunction
- Patient-specific factors impacting adherence to daily oral PrEP (cognitive difficulties, gastrointestinal dysfunction, unstable housing, stigma, or fear of discovery)
- Very high-risk for HIV acquisition (MSM engaging in frequent condom-less receptive anal intercourse, repeated STIs, or high-risk sexual activity with partners known/likely to be HIV-infected)
Exclusion Criteria- • Significant noncompliance with follow-up appointments unless barriers to compliance have been significantly addressed by the provider
- • Drug interactions that preclude administration of CAB (UGT1A1 inducers, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifamycin derivatives, St. John’s Wort)
Dosing & Administration Criteria- • Dosing: 600mg IM monthly for 2 months, then every 2 months
- • Administration site: Gluteal muscle (absorption from other sites can be unpredictable)
Pre-Administration & Monitoring Criteria- • HIV must be excluded prior to administration of CAB
- • Clinical recommendations for monitoring should be consulted
Indication & Patient Population- Indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents.
- Recommended for individuals reporting sexual behaviors placing them at substantial ongoing risk of HIV acquisition, and persons who inject drugs (PWID) with injection practices placing them at ongoing risk.
- Particularly beneficial for patients unable to adhere to oral daily dosing due to cognitive dysfunction impacting adherence, unstable housing or homelessness, gastrointestinal dysfunction impairing absorption, previous medication non-adherence despite regular clinic visit adherence, mental illness or substance abuse impacting compliance, or concerns about stigma/discovery of PrEP use by family or friends.
- May be considered on a case-by-case basis for those at highest risk of HIV infection (e.g., frequent condom-less or unprotected sexual encounters with partners known/at high risk for HIV, frequent needle/equipment sharing with IDU).
Dosing & Administration Requirements- Dosage form: 600mg extended-release injectable suspension for intramuscular (IM) administration.
- Dosing schedule: 600mg IM repeated 4 weeks later, then every 8 weeks. Can be administered up to 7 days before or after the due date.
- Oral lead-in (30mg daily by mouth for 28 days) is OPTIONAL; if used, injection should start on the last day of oral therapy or within 3 days thereafter.
- Injectable must be administered by a healthcare professional.
- If a scheduled dose is missed by >7 days, clinical reassessment is required to ensure resumption remains appropriate; dosing schedule may need adjustment (e.g., restarting with 2 monthly doses prior to resuming every-2-month schedule).
- Oral cabotegravir (30mg daily for up to 2 months) can be used to replace one scheduled every-2-month injection if a patient is known/scheduled to miss an injection.
Testing & Monitoring Requirements- A negative HIV-1 test MUST be completed and confirmed negative prior to initiating therapy AND with each subsequent injection (at least every 2 months).
- Testing should be repeated upon diagnosis of other STIs.
- For patients with recent high-risk behaviors, evaluate for clinical symptoms compatible with acute HIV infection; if present, use an FDA-cleared/approved test for acute HIV diagnosis.
- Patients must agree to required injection dosing and testing schedules; adherence counseling and support are required.
Contraindications & Warnings/Precautions- Contraindicated in patients with unknown or positive HIV status.
- Contraindicated with previous hypersensitivity to cabotegravir.
- Contraindicated with co-administration of moderate-strong inducers of UGT1A1 due to potential loss of efficacy from decreased plasma concentrations.
- Boxed Warning: Risk of drug resistance if used as PrEP in undiagnosed HIV infection; monotherapy in undiagnosed HIV-1 may result in INSTI resistance. Patients found HIV-positive must immediately transition to a full antiretroviral regimen.
- Long-acting properties: Residual concentrations may remain for up to 12 months or longer. If discontinued, alternative PrEP should be considered for those remaining at high risk beginning within 2 months of the last injection; additional oral PrEP should be started within 4 weeks after the last dose in those continuing to engage in high-risk behaviors. Patients must reliably attend clinic visits.
- Hepatotoxicity: Clinical and lab monitoring should be considered; discontinue if suspected.
- Depressive disorders: Reported (including depression, suicide ideation/attempt).
- Hypersensitivity reactions: Oral lead-in may help identify risk prior to long-acting injection.
Special Populations & Organ Function Considerations- Renal insufficiency: No dosage adjustment for mild/moderate impairment. Increased monitoring recommended for severe impairment (CrCl 15-29 mL/min) or ESRD (CrCl <15 mL/min). Dialysis not expected to alter exposures. Particularly beneficial for patients with CrCl <30 mL/min or multiple risk factors for nephrotoxicity.
- Hepatic insufficiency: No dose adjustment for mild-moderate impairment (CTP A or B). Impact of severe impairment unknown.
- Pregnancy: Insufficient data; neural tube defects associated with other INSTIs. Animal studies showed delayed parturition, increased stillbirths/neonatal deaths at >28x RHD. Pregnancy registry exists. Consider prolonged concentrations in women of childbearing potential.
- Lactation: Unknown if present in human milk. Recommended to breastfeed only if benefits outweigh risks given potential persistence >12 months. Present in rat milk.
- Geriatric: No dose adjustment required; very limited data in patients ≥65 years.
Indications & Target Populations- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.
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DIFELIKEFALIN INJ,SOLN
KORSUVA
|
KORSUVA |
2022-03-17 |
Exclusion Criteria- Pruritus attributed to cause other than end-stage kidney disease
- Severe hepatic impairment
- Inclusion Criteria (All of the following must be met)
- Care provided by a VA / VA Community Care nephrologist
- End-stage kidney disease receiving hemodialysis three times per week
- Moderate-to-severe pruritus associated with chronic kidney disease despite optimized management of condition
- Inadequate benefit from trial of topical emollients and/or topical analgesic agents (e.g., capsaicin, pramoxine)
- Inadequate benefit from trial of gabapentin (or pregabalin, if gabapentin not tolerated)
- Weekly mean score of more than 4 points on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS)
- Optimization of dialysis, management of hyperparathyroidism and hyperphosphatemia
- Trial of oral antihistamines, and/or alternate agents (e.g., montelukast, sertraline) or phototherapy may also be useful in managing symptoms and considered on an individual basis
Indication & Patient Population- Indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis.
- Clinical trial population included patients with end-stage kidney disease receiving hemodialysis at least three times per week for at least 3 months, with moderate-to-severe pruritus defined as a weekly mean score >4 points on the WI-NRS.
Dosing & Administration- Recommended dose is 0.5 mcg/kg by intravenous (IV) bolus injection into the venous line of the dialysis circuit at the end of each hemodialysis treatment.
- Available as a 65 mcg/1.3 mL (50 mcg/mL) solution for injection.
Efficacy Criteria & Reassessment- Primary efficacy outcome defined as ≥3-point decrease from baseline in weekly mean WI-NRS score; FDA-recommended primary outcome is ≥4-point decrease.
- Treatment effect noted by week 1 and persists throughout the 12 weeks of treatment.
- Patient should be reassessed for response to treatment; therapy should be discontinued if there is not a clinically meaningful reduction in itch intensity (e.g., at least a 3 to 4-point reduction on the WI-NRS) or improvement in itch-related sleep disturbance, mood, or quality of life, or if treatment is not tolerated.
Place in Therapy / Step Requirements- Recommended for refractory uremic pruritus.
- May be considered after attempts to reduce symptoms through optimization of dialysis, management of hyperparathyroidism and hyperphosphatemia, use of topical emollients and/or analgesic agents (e.g., capsaicin, pramoxine), a trial of oral antihistamines (e.g., diphenhydramine, hydroxyzine, loratadine), and gabapentin (pregabalin if gabapentin not tolerated).
- Alternate agents (e.g., montelukast, sertraline) may be considered prior to difelikefalin on an individual basis. Phototherapy may also be considered as a treatment option.
Safety, Warnings & Precautions- No boxed warning or contraindications.
- Dizziness, somnolence, mental status changes, and gait disturbances, including falls, have occurred. Centrally-acting depressant medications, sedating antihistamines, and opioid analgesics should be used with caution.
- May impair mental or physical abilities; advise patients not to drive or operate dangerous machinery until the effect on the patient’s ability is known.
Special Populations- Not recommended for patients with severe hepatic impairment (not evaluated).
- No clinically significant difference in pharmacokinetics noted in patients with mild to moderate hepatic impairment.
- Higher incidence of somnolence in patients 65 years of age and older compared to patients <65 years.
- Abuse potential: Peripherally restricted, selective kappa opioid receptor agonist; no indication of abuse or physical dependence, and no reported adverse events related to withdrawal upon discontinuation.
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PACRITINIB CAP,ORAL
VONJO
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VONJO |
2022-03-17 |
Exclusion Criteria- Concomitant therapy with strong CYP3A4 inhibitors or inducers, moderate CYP3A4 inhibitors or inducers, sensitive substrates of CYP1A2 or CYP3A4, or sensitive substrates of P-glycoprotein, BCRP, or OCT1
- Active bleeding
- Uncontrolled diarrhea
- Baseline QTc > 480 msec
- Concomitant use of drugs with significant potential for QTc prolongation
- Untreated hypokalemia
- Uncontrolled active infection, including undrained abscess (may be started/restarted once the infection is controlled)
- Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment
- Estimated GFR < 30 mL/min
- Breastfeeding during therapy (and for 2 weeks after the last dose)
Core Inclusion Criteria- Primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis
- Prescribed and monitored by a VA / VA Community Care hematologist / oncologist or locally designated myelofibrosis expert
- Splenomegaly by palpation (≥ 5 cm below the costal margin) or imaging
- Obtained pretreatment complete blood count, coagulation testing (PT, PTT, TT, and INR), and ECG
Indication-Specific Requirements- Higher risk myelofibrosis with platelet count (PLT) < 50 × 109/L and currently not a hematopoietic stem cell transplant (HSCT) candidate
- Higher risk myelofibrosis with PLT ≥ 50 × 109/L and currently not a HSCT candidate, after no response or loss of response to one initial Janus kinase inhibitor approved for myelofibrosis (e.g., ruxolitinib or fedratinib)
- Symptomatic lower risk myelofibrosis after no response or loss of response to initial therapy and PLT < 50 × 109/L. Initial therapy may be a clinical trial, ruxolitinib, peginterferon alfa-2a, or hydroxyurea
Pre-treatment & Management Requirements- If taking another kinase inhibitor: The other kinase inhibitor has been discontinued as per its prescribing information
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
Indication & Patient Population- Treatment of adults with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet (PLT) count below 50 × 10^9/L.
- Accelerated approval based on spleen volume reduction; continued approval contingent upon verification of clinical benefit in a confirmatory trial.
Pretreatment Evaluations & Tests- Complete blood count (CBC)
- Coagulation tests
- Electrocardiogram (ECG)
- Potassium level (especially in patients with a history of low blood potassium)
- Active serious infections (delay initiation until infection has resolved)
- Prior kinase inhibitor use (taper or discontinue before initiation)
Dosage Regimen- 200 mg orally twice daily with or without food.
- Available as 100 mg capsules.
- 400 mg once daily is not recommended due to a potentially higher risk of mortality.
Dosage Modifications & Hold Conditions- Planned surgical or other invasive procedures: Hold doses for 7 days prior to procedure; restart after hemostasis is regained.
- Diarrhea, Grade 3 or 4
- Thrombocytopenia, clinically worsening and lasting more than 7 days
- Hemorrhage, moderate, severe or life-threatening
- QTc Prolongation of > 500 msec or by > 60 msec from baseline
Contraindications & Avoid Use Conditions- Strong CYP3A4 inhibitors or inducers (contraindicated)
- Moderate CYP3A4 inhibitors or inducers (avoid co-use)
- Active bleeding
- Baseline QTc > 480 msec
- Sensitive P-gp, BCRP, or OCT1 substrates (avoid co-use)
- Moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment
- Renal impairment with eGFR < 30 mL/min
- Lactation (avoid breastfeeding during therapy and for 2 weeks after discontinuation)
Place in Therapy- First-line for higher-risk primary or secondary myelofibrosis with PLT count < 50 × 10^9/L who are not hematopoietic stem cell transplant (HSCT) candidates.
- Second-line after no response or loss of response to one prior JAK inhibitor (ruxolitinib or fedratinib) in higher-risk myelofibrosis with PLT count ≥ 50 × 10^9/L who are not HSCT candidates.
- Second-line after no response or loss of response to initial therapy (clinical trial, ruxolitinib, peginterferon alfa-2a, or hydroxyurea) in symptomatic lower-risk myelofibrosis with PLT count < 50 × 10^9/L.
Safety & Monitoring Considerations Affecting Use- Monitor for diarrhea, thrombocytopenia, anemia, and peripheral edema (most common adverse events ≥20%).
- Avoid drugs with significant QTc-prolonging effects; correct hypokalemia.
- Assess for major adverse cardiac events (MACE), thrombosis, secondary malignancies, and risk of infection.
- Clinical benefits require confirmation due to accelerated approval status and uncertain overall survival benefit compared to best available therapy.
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TENAPANOR TAB
IBSRELA, XPHOZAH
|
IBSRELA, XPHOZAH |
2022-03-17 |
Exclusion Criteria- Mechanical gastrointestinal obstruction, known or suspected
- Age less than 18 years
- Presence of severe or frequent diarrhea
- Note: For purposes of these criteria and as causes of chronic constipation, irritable bowel syndrome (IBS) excludes drug-induced chronic constipation and chronic constipation due to neurogenic and non-neurogenic disorders
Inclusion Criteria- Men or women 18 years or older with a documented diagnosis of irritable bowel syndrome with constipation (IBS-C)
- Intolerance or inadequate response to a 1-month trial of either PEG-3350 powder for oral solution (17 g twice daily) or other osmotic laxative, unless there is a contraindication or risk factor(s) for serious adverse event(s)
Additional Inclusion Criteria (Sex-Specific)- For men: Intolerance or inadequate response to 1-month trials of plecanatide and linaclotide unless there is a contraindication or risk factor(s) for serious adverse event(s)
- For women: Intolerance or inadequate response to 1-month trials of lubiprostone, plecanatide and linaclotide unless there is a contraindication or risk factor(s) for serious adverse event(s). Use of lubiprostone is off-label for IBS-C in men.
Prior Therapy Doses- Lubiprostone: 8 mcg twice daily
- Plecanatide: 3 mg daily
- Linaclotide: 290 mcg daily
Clinical Recommendations & Notes- GI consultation (including e-consult) is highly recommended prior to using tenapanor for IBS-C
- Examples of osmotic laxatives include lactulose, sorbitol, magnesium citrate, magnesium hydroxide, and glycerin rectal suppositories
- During the 1-month trial, escalation/titration of therapy up to bowel-prep doses of PEG-3350 may be considered case by case to achieve the desired response
Indication & Patient Population- Hyperphosphatemia in end-stage CKD / End-Stage Renal Disease
- Adults with stable hyperphosphatemia (4–8 mg/dL) on maintenance hemodialysis (HD) or peritoneal dialysis (PD)
- Patients receiving maintenance dialysis (HD or PD) with phosphate levels >5.5 mg/dL despite phosphate binder therapy
Dosage & Administration- 30mg twice daily
- Oral tablets (20mg and 30mg available; specified regimen is 30mg)
Contraindications & Safety Warnings- Pediatric patients under 6 years of age
- Patients with known or suspected mechanical obstruction
- Risk of severe diarrhea
- Diarrhea reported in approximately 50% of clinical trials as mild-to-moderate and transient, or responding to dose reduction
Drug Interactions- Enalapril: Tenapanor interferes with oral absorption of OATP2B1 substrates
- Sodium polystyrene sulfonate: Recommend separate administration by 3 hours
Clinical Considerations for Use- Can be used in addition to traditional intraluminal phosphate binding agents, though overall result may be less than fully additive (<1 mg/dL reduction in tenapanor+binder vs. placebo+binder arms)
- Phosphate reduction is a surrogate endpoint; correlation to clinically important endpoints is unknown
- Significantly more costly than formulary phosphate reducing agents
- Different mechanism of action (NHE3 inhibitor) compared to constipating intraluminal binders; diarrhea is a common side effect
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MITAPIVAT TAB
AQVESME, PYRUKYND
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AQVESME, PYRUKYND |
2022-03-10 |
Indication & Patient Selection- Hemolytic anemia due to pyruvate kinase (PK) deficiency in adults
- Requires at least one missense variant of the PKLR gene
- Excludes patients homozygous for PKLR mutation or with only non-missense mutations in PKLR gene
Dosage & Administration- Starting dose: 5 mg twice daily for weeks 1-4
- Titrate to 20 mg twice daily if insufficient increase in hemoglobin
- Further titrate to maximum dose of 50 mg twice daily if hemoglobin is not increased and transfusion requirements are not reduced
- Available as 5 mg, 20 mg, and 50 mg oral tablets
- Dose taper packs available; abrupt cessation is not recommended
Safety & Monitoring Requirements- Avoid abrupt discontinuation to minimize risk of acute hemolysis; gradual dose reduction recommended when possible
- Avoid concomitant use with strong CYP3A4 inhibitors or inducers
- Dose adjustment recommended if co-administration with moderate CYP3A inducer or inhibitor cannot be avoided
- Monitor for loss of therapeutic effect of drugs metabolized by CYP3A, CYP2B6/2C8/2C9/2C19 enzymes (mitapivat is an inducer of these enzymes)
Clinical Context & Utilization Restrictions- Indicated for symptomatic anemia due to PK deficiency where standard supportive care includes transfusions and splenectomy
- No other drug therapies are approved for congenital hemolytic anemia due to PK deficiency
- Rare genetic condition; use within VA setting expected to be very infrequent
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ABROCITINIB TAB
CIBINQO
|
CIBINQO |
2022-02-17 |
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for infection is initiated)
- Untreated latent or active tuberculosis
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Congenital or acquired immunodeficiency
- Malignancy in the previous 5 years other than successfully treated nonmelanoma skin cancer or cervical cancer (unless dermatologist and oncologist agree risk-benefits favor use)
- Thrombosis or major adverse cardiovascular events where potential harms outweigh anticipated benefits
- Platelets < 150,000/mm3, lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once values normalize)
- Severe renal impairment (eGFR 15–29 mL/min) or end-stage renal disease (eGFR < 15 mL/min)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with other JAK inhibitors, biologic DMARDs, other immunosuppressive biologics, or potent immunosuppressants (except during treatment transition; co-use with antirheumatic doses of conventional immunomodulators like methotrexate or leflunomide is acceptable)
- Concomitant therapy with moderate to strong inhibitors of both CYP2C19 and CYP2C9 (e.g., fluconazole)
- Concomitant therapy with strong inducers of CYP2C19 or CYP2C9 (e.g., rifampin)
- Antiplatelet use in the first 3 months except low-dose aspirin (≤ 81 mg/day)
- Pregnancy
- Breastfeeding
Inclusion Criteria- Diagnosis of chronic atopic dermatitis
- Prescribed and monitored by a VA/VA Community Care dermatologist, immunologist, or allergist, OR a locally designated expert in consultation with a VA/VA Community Care dermatologist
- Assessment of moderate to severe atopic dermatitis within the last 2 weeks (gestalt assessment of “moderate” or “severe” OR EASI ≥ 16)
- Dupilumab, tralokinumab-ldrm, lebrikizumab-lbkz, OR nemolizumab-ilto therapy is medically inadvisable, not tolerated, not adequate, or lost response
Laboratory & Screening Requirements- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- Routine retesting not required for prescription renewals; retesting in high-risk patients should be considered
Vaccination & Infection Management- Offered all age-appropriate vaccinations prior to initiating therapy
- Administration of live or live-attenuated vaccines within 2 weeks before initiation is excluded
- When possible, update vaccinations before initiation; recombinant zoster vaccine should be completed or initiated by end of first year (preferably when dosage is low, disease stable, or immune response robust)
Prior Therapy Requirements- If biologic agents are contraindicated, therapies required prior to those biologics must still be tried before abrocitinib
Special Populations & Counseling- For females who can become pregnant and patients with partners who can become pregnant: Counseling on potential risks vs benefits and use of effective contraception
- For females who are breastfeeding/providing breastmilk: Counseling on potential risks vs benefits
- If HBsAg-negative but anti-HBc-positive and consult deemed indicated: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
Indication & Patient Population- Treatment of adults with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.
Pretreatment Requirements & Screening- Tuberculosis screening required.
- Viral hepatitis screening required.
- Complete blood count (CBC) required.
- Baseline lipid panel may be considered (not a US Prescribing Information recommendation).
- Guideline-recommended immunizations, including herpes zoster vaccination, should be completed prior to initiating therapy.
Contraindications & Limitations of Use- Not recommended for use in combination with other JAKIs, biologic immunomodulators, or other immunosuppressants.
- Contraindicated with antiplatelet therapy except for low-dose aspirin (≤ 81 mg daily) during the first 3 months of treatment.
- Not recommended in patients with platelet count < 150,000/mm3, absolute lymphocyte count < 500/mm3, absolute neutrophil count < 1,000/mm3, or hemoglobin < 8 g/dL.
- Not recommended in severe renal impairment (estimated glomerular filtration rate [eGFR] 15–29 mL/min) and end-stage renal disease (eGFR < 15 mL/min).
- Not recommended in severe (Child-Pugh C) hepatic impairment.
- Not recommended in patients with active hepatitis B virus (HBV) or hepatitis C virus (HCV).
Dosing & Administration- Recommended starting dose: 100 mg orally once daily with or without food.
- If there is an inadequate response after 12 weeks, the dose can be increased to 200 mg once daily.
- Discontinue therapy if there is an inadequate response to 200 mg once daily.
- Dose reduction required for patients with renal impairment per US Prescribing Information.
- Dose reduction required for known or suspected CYP2C19 poor metabolizers.
- Dose reduction required when taking strong inhibitors of CYP2C19.
Monitoring During Treatment- CBC at 4 weeks after starting therapy and 4 weeks after dose increases to monitor for hematocytopenias, especially thrombocytopenia and lymphopenia.
- Lipid panel approximately 4 weeks after starting therapy, then per clinical guidelines for hyperlipidemia.
- HBV DNA, ALT, AST per guideline recommendations to monitor for HBV reactivation.
- Annual TB screening should be considered for patients in highly endemic areas.
- Monitor patients with inactive HBV for expression of HBV DNA; consult a liver specialist if detected.
Safety Considerations & Warnings- Boxed warnings include serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis.
- Current or past smokers are at additional increased risk of malignancies and MACE.
- Avoid live vaccines immediately prior to, during, and immediately after therapy.
- Discontinuation or dosage adjustment recommended for hematologic abnormalities per US Prescribing Information.
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SUTIMLIMAB-JOME INJ,SOLN
ENJAYMO
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ENJAYMO |
2022-02-17 |
Indication- Classical complement inhibitor indicated to decrease the need for red blood cell (RBC) transfusions due to hemolysis with cold agglutinin disease (CAD).
Patient Selection/Clinical Criteria- Confirmed CAD diagnosis.
- Hemoglobin ≤10 g/dL.
- Total bilirubin above normal reference range.
- Ferritin level above the lower limit of normal.
- One or more symptoms: symptomatic anemia, acrocyanosis, Raynaud’s phenomenon, hemoglobinuria, disabling circulatory symptoms, or major adverse vascular event including thrombosis.
- Documented vaccinations against encapsulated bacterial pathogens within 5 years of enrollment.
Exclusion Criteria- Cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy.
- History of blood transfusion within 6 months or >1 transfusion within 12 months.
- Systemic lupus or other autoimmune disorder.
- Erythropoietin deficiency.
- Clinically relevant infection.
- Recent rituximab use (within 3 months) or rituximab combination therapy (within 6 months).
- Concurrent corticosteroid treatment other than a stable daily dose equivalent to ≤10 mg/d prednisone.
Dosing & Administration- Administered intravenously over 1 hour on Day 0 and Day 7, then every 2 weeks up to 26 weeks.
- Dose based on weight: <75 kg: 6500 mg in 500 mL; ≥75 kg: 7500 mg in 500 mL.
- Infusion may be extended to 2 hours if patient has underlying cardiopulmonary disease.
Safety & Monitoring Requirements- Contraindicated in patients with known hypersensitivity to sutimlimab-jome or any inactive ingredients.
- Vaccinate/revaccinate for encapsulated organisms per ACIP recommendations at least 2 weeks prior to first infusion unless urgent; vaccinate ASAP if unvaccinated.
- Monitor for serious infections caused by encapsulated bacteria (e.g., Neisseria meningitidis, Streptococcus pneumoniae, H. influenzae); monitor active systemic reactions and consider dose interruption.
- Not studied in patients with chronic systemic infections (hepatitis B, hepatitis C, or HIV).
- Interrupt infusion for infusion-related reactions; discontinue therapy and provide supportive care if signs of hypersensitivity occur (cardiovascular instability, respiratory compromise).
- Monitor for risk of autoimmune diseases (e.g., systemic lupus erythematosus) based on mechanism of action.
- Following treatment interruption, monitor for recurrent hemolysis (↑total bilirubin or LDH, ↓hemoglobin) and symptom reappearance (fatigue, dyspnea, palpitations, hemoglobinuria); consider restarting therapy if recurrent hemolysis occurs.
Place in Therapy Considerations- First FDA-approved drug for CAD; complement-directed therapies likely required for lifetime or until disease progression.
- May be considered following B-cell directed therapies (rituximab or bendamustine/rituximab) if patient is fit for immunochemotherapy.
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FARICIMAB-SVOA INJ,SOLN
VABYSMO
|
VABYSMO |
2022-02-11 |
Indications & Patient Population- Neovascular (Wet) Age-Related Macular Degeneration (nAMD)
- Diabetic Macular Edema (DME)
- Bispecific antibody acting through inhibition of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2)
Dosing Regimens & Administration- Form: Intravitreal injection, 120 mg/mL solution in a single-dose vial
- nAMD: 6 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days) for the first 4 doses
- DME: 6 mg administered by intravitreal injection either every 4 weeks for at least 4 doses, or every 4 weeks for the first 6 doses followed by every 8 weeks over the next 28 weeks
- Some patients may require every 4-week (monthly) dosing after the initial loading doses
Monitoring & Assessment Requirements- Optical coherence tomography (OCT) and visual acuity (VA) evaluations at 8 and 12 weeks following the first 4 doses to inform subsequent dosing intervals
- Central subfield thickness (CST) of the macula as measured by OCT for DME dosing interval modifications (extensions up to 4-week increments or reductions up to 8-week increments based on CST and VA evaluations through week 52)
- Regular assessment of patients throughout treatment
Contraindications & Safety Considerations- Ocular or periocular infection
- Active intraocular inflammation
- Hypersensitivity to faricimab or excipients
- Risk of endophthalmitis and retinal detachments following intravitreal injections; patients must be instructed to report suggestive symptoms without delay
- Increases in intraocular pressure may occur within 60 minutes of an intravitreal injection
- Potential risk of arterial thromboembolic events (ATEs) associated with VEGF inhibition
- Potential for immunogenicity (anti-faricimab antibodies detected in approximately 10.4% of nAMD and 8.4% of DME patients post-initiation)
Place in Therapy / Specific Use Criteria- Demonstrated non-inferiority to aflibercept administered every 8 weeks for both nAMD and DME
- Approximately 75% of patients with nAMD or DME can be maintained on dosing intervals of every 12 or 16 weeks while maintaining comparable visual gains and CST reduction
- Particularly useful for patients who would benefit from reducing treatment burden (e.g., long travel times, physical mobility limitations)
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TEBENTAFUSP-TEBN INJ
KIMMTRAK
|
KIMMTRAK |
2022-02-03 |
Indications- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
Indication & Patient Population- Metastatic or recurrent uveal melanoma that is HLA-A*02:01 positive
- Unresectable or metastatic disease
- Not a candidate for resection or radiation
- Liver-only metastases following progression on liver-directed therapy
- Metastases not limited to liver-only
Dosing & Administration- Initial 3 step-up doses in Cycle 1: 20mcg IV D1, 30mcg IV D8, 68mcg IV D15
- Subsequent dosing: 68mcg IV weekly
- Dosage form: Injection (100mcg/0.5mL single-dose vial)
Monitoring & Safety Requirements- Monitor for Cytokine Release Syndrome (CRS) at least 16 hours after the first 3 infusions
- If no Grade 2 or worse hypotension occurs during or after the third infusion, subsequent infusions require monitoring for at least 30 minutes
- Monitor for skin reactions
- Measure baseline AST/ALT/TBili and monitor for elevated LFTs
- Monitor for EF toxicity
Facility & Infrastructure Requirements- Facility must be equipped to monitor and manage Cytokine Release Syndrome (CRS) if needed
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TRALOKINUMAB-LDRM INJ,SOLN
ADBRY, ADBRY AUTOINJECTOR
|
ADBRY, ADBRY AUTOINJECTOR |
2022-01-20 |
Exclusion Criteria- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 4 weeks
- Concurrent use with targeted immunomodulators unless potential risk-benefits favor use
- Untreated parasitic (helminth) infection
Inclusion Criteria for New Starts- Diagnosis of chronic atopic dermatitis made or confirmed by a VA / VA Community Care dermatologist
- Prescribed by a VA / VA Community Care dermatologist, allergist, immunologist, or other designated expert in the management of atopic dermatitis in consultation with a VA / VA Community Care dermatologist, allergist, or immunologist
- Offered all age-appropriate vaccinations prior to initiating therapy
- Assessment of moderate to severe atopic dermatitis in the last 2 weeks as determined by either a gestalt assessment of “moderate” or “severe” OR Eczema Area and Severity Index (EASI) ≥ 16
- Refractory to ≥ 2 drug classes of topical therapies for atopic dermatitis (e.g., corticosteroids, calcineurin inhibitors, PDE4 inhibitors, JAK inhibitors) for ≥ 4 weeks total unless the therapy is medically inadvisable or not tolerated
Additional Inclusion Criteria- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits of treatment
Therapy Sequencing & Dosing Considerations- If patient weighs < 100 kg, consider tralokinumab prior to dupilumab
- First-line therapy options include dupilumab, tralokinumab-ldrm, lebrikizumab-lbkz, or nemolizumab-ilto
- Second-line therapy options include abrocitinib or upadacitinib
- Consider offering methotrexate, azathioprine, or mycophenolate mofetil in the context of shared decision-making (prior trials not required), with use conditional on risk-benefit certainty, onset speed, follow-up feasibility, comorbidities, and patient preferences
Vaccination Requirements- When possible, vaccinations should be updated before initiating therapy
- Unless contraindicated, recombinant zoster (SHINGRIX) vaccine should be completed or at least initiated by the end of the first year of treatment, preferably when dosage is low, disease is stable, or at other times when a robust immune response to vaccination can be expected
Indication- • Treatment of moderate to severe atopic dermatitis (AD) in adults whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
- • Can be used with or without topical corticosteroids (TCSs).
Pre-treatment Assessments & Requirements- • Update vaccinations prior to initiation.
- • Treat pre-existing helminth infections before initiating therapy.
- • No pretreatment screening recommended for tuberculosis, hepatitis B, hepatitis C, or HIV.
Dosing & Administration- • Initial dose: 600 mg (four 150-mg injections) subcutaneously (SC).
- • Maintenance dose: 300 mg (two 150-mg injections) SC every 2 weeks (Q2W).
- • Dose reduction option: For patients weighing less than 100 kg who achieve clear or almost clear skin after 16 weeks of treatment, a maintenance dose of 300 mg SC every 4 weeks (Q4W) may be considered.
- • Formulation: 150 mg/mL in single-dose prefilled syringes (PFS).
Place in Therapy / VHA Utilization Criteria- • Appropriate for patients with severe AD who have an inadequate response or intolerance to prescription topical therapies, phototherapy (only if available, feasible, and not medically inadvisable), and/or conventional synthetic immunomodulators.
- • May be considered for patients with severe AD who have an inadequate response or contraindication to cyclosporine A.
- • Dosing frequency reduction from Q2W to Q4W should only be considered after weighing the potential risk of loss of response and acknowledging a lack of data on recapturing response upon returning to Q2W dosing.
Safety & Contraindications- • Contraindicated in patients with hypersensitivity to tralokinumab-ldrm.
- • Monitor for conjunctivitis and keratitis.
- • Avoid use of live vaccines due to risk of infection.
- • Insufficient data to determine age-related differences in efficacy or safety for geriatric populations.
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TEZEPELUMAB-EKKO INJ,SOLN
TEZSPIRE
|
TEZSPIRE |
2022-01-13 |
Exclusion Criteria- Acute asthma exacerbation or status asthmaticus
- Concurrent use with other biologics for asthma
- Currently undergoing bronchial thermoplasty
- Untreated parasitic (helminth) infection (treat before starting tezepelumab)
- Treatment with live (attenuated) vaccines within the previous 30 days or concurrent use with live (attenuated) vaccines
Inclusion Criteria (All must be met)- Provider is a VA or VA Community Care asthma specialist (i.e., pulmonologist, allergist, immunologist)
- Diagnosis of asthma
- Receiving high-dose inhaled corticosteroid (or maximally tolerated dose) AND at least 3 months of a long-acting beta agonist and/or other controller medication such as tiotropium
- Adherent to asthma medications as evidenced by a review of prescription refill history during the last 12 months
- At least 2 exacerbations requiring systemic corticosteroids OR at least 1 hospitalization due to asthma exacerbation in the prior year OR inadequate asthma control
- Inadequate asthma control examples: short-acting beta-agonist use more than 2 days per week, nighttime awakening due to asthma more than 1 time per week, limitation with normal activity, Asthma Control Test less than 19
- Typically, pre-bronchodilator FEV1 <80%
Additional Inclusion Criteria (At least one must be met)- Baseline blood eosinophil count <150 cells/µL
- Baseline eosinophil ≥150 cells/µL and inadequate response or adverse event to 2 interleukin receptor monoclonal antibodies used for asthma (benralizumab, mepolizumab, dupilumab)
Clinical Management & Monitoring- If a live (attenuated) vaccine is needed, do not administer within 90 days after receiving a dose of tezepelumab; consider risk versus benefit of interrupting therapy versus need for vaccine.
- For patients with confirmed allergic asthma and blood eosinophils <150 cells/µL, omalizumab or tezepelumab may be considered. For patients with both allergic-eosinophilic asthma subtypes who cannot use omalizumab (e.g., inadequate response, adverse event, contraindication), a trial of benralizumab is recommended before using tezepelumab.
- A treatment period of 4-6 months is generally needed to assess response; patients showing intermediate response may need to be treated for 6-12 months for optimal response.
- Providers should observe patient’s inhaler use, as poor technique frequently is a cause of poor results in asthma.
- Exceptions to inclusion/exclusion criteria should be adjudicated at the local facility per P&T committee and pharmacy services policy/procedures.
Indication & Patient Population- • Indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma
- • Applicable regardless of eosinophilic phenotype or biomarker limitations
- • Specifically indicated for patients with severe asthma without an eosinophilic phenotype (blood eosinophil count <150 cells/µL) receiving optimal therapy (inhaled corticosteroid and long-acting beta-agonist and/or long-acting anticholinergic) who have inadequate symptom control or asthma exacerbations
- • May be used in patients with an inadequate response or adverse events to other biologics for asthma (benralizumab, mepolizumab, dupilumab, omalizumab)
Dosing & Administration- • 210 mg administered once every 4 weeks via subcutaneous injection
- • Intended for administration by a healthcare provider
- • Available in single-dose glass vial and prefilled syringe
Safety & Monitoring Requirements- • Contraindicated in patients with known hypersensitivity to tezepelumab or any excipients
- • Monitor for hypersensitivity reactions (e.g., rash, allergic conjunctivitis); initiate appropriate treatment as clinically indicated if they occur
- • Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation; decrease gradually if appropriate
- • Treat pre-existing helminth infections prior to therapy; discontinue tezepelumab until parasitic infection resolves if infected and unresponsive to anti-helminth treatment
- • Avoid concomitant use of live attenuated vaccines
Therapy Positioning & Considerations- • Did not demonstrate a statistically significant reduction in maintenance oral corticosteroids compared to placebo without loss of asthma control
- • Formulary status: TBD
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INCLISIRAN INJ,SOLN
LEQVIO
|
LEQVIO |
2022-01-06 |
Exclusion Criteria- End-stage renal disease on dialysis
- Advanced heart failure with limited prognosis
- Severe comorbid non-cardiovascular condition that is expected to limit life expectancy
- Pregnancy or lactating
- Primary Inclusion Criteria (One must be met)
- History of ASCVD
- Severe hypercholesterolemia (e.g., HeFH, LDL-C > 190 mg/dL) without ASCVD
- Additional Inclusion Criteria (All must be met)
- Contraindication, intolerance to or insufficient LDL-C reduction with maximally tolerated dose of statin and needs further LDL-C lowering to reduce ASCVD risk consistent with established guidelines
- Contraindication, intolerance to or insufficient LDL-C reduction with ezetimibe and needs further LDL-C lowering to reduce ASCVD risk consistent with established guidelines
- Contraindication, intolerance to or insufficient LDL-C reduction with a monoclonal antibody inhibitor of PCSK9 and needs further LDL-C lowering to reduce ASCVD risk consistent with established guidelines
- Willing to return for subcutaneous administration of inclisiran by a healthcare provider at the initial visit, at 3 months and every 6 months thereafter
- Pregnancy Considerations (Select if applicable)
- Evaluate pregnancy status prior to initiating treatment since inclisiran may cause fetal harm
- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy is recommended
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MOLNUPIRAVIR CAP,ORAL
LAGEVRIO (EUA)
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LAGEVRIO (EUA) |
2022-01-06 |
Indication & Patient Population- Emergency Use Authorization (EUA) for patients 18 years and older
- Mild-to-moderate COVID-19 at high risk for progression
- Use only if other alternatives are not accessible or clinically appropriate
Dosing & Administration- 800 mg (4 capsules) twice daily for 5 days
- Can be administered with or without food
Contraindications & Warnings- No contraindications listed
- Possible embryo-fetal toxicity
- Possible bone/cartilage toxicity in patients <18 years old
Adverse Reactions & Efficacy- Adverse reactions: diarrhea, nausea, dizziness
- MOVe-OUT trial data: Death or hospitalization by day 29 was 6.8% (MOV) vs. 9.7% (placebo)
Special Populations & Precautions- Not recommended in pregnancy and lactation due to potential embryo-fetal toxicity based on animal data
- If used, requires extensive discussion/documentation
- Requires reliable, consistent contraception during therapy and for 4 days after last dose in females of childbearing potential
- Requires reliable, consistent contraception for 3 months after last dose in males of reproductive potential
Renal/Hepatic Considerations- No dose adjustment required for renal or hepatic dysfunction
Indication & Patient Population- Treatment of mild to moderate laboratory confirmed COVID-19 in individuals 18 years of age and older
- Positive results of direct SARS-CoV-2 viral testing
- At high risk for progressing to severe disease
- Within 5 days of symptom onset
- Alternative FDA-authorized COVID-19 treatment options are not accessible or clinically appropriate (remdesivir is not considered an adequate alternative under the EUA due to IV infusion requirements, though NIH guidelines list it as a priority option)
High-Risk Criteria for Disease Progression- Age ≥ 65 years
- Cancer
- Chronic kidney disease
- Chronic liver disease
- Chronic lung disease
- Dementia or other neurological conditions
- Disabilities (e.g., Down syndrome, spinal cord injuries)
- Diabetes
- Cardiovascular disease
- Immunosuppressive disease or treatment
- Body mass index (BMI) > 25 kg/m2 in adults and physical inactivity
- Pregnancy
- Sickle cell disease or thalassemia
- Stroke or cerebrovascular disease
- Current or former smoking
- Mental health conditions (e.g., depression, schizophrenia, substance use disorders)
- Tuberculosis
- Other medical conditions or factors (e.g., race or ethnicity) may also place patients at high risk
Exclusions & Contraindications- Patients under 18 years of age
- Hospitalized due to COVID-19 (benefit not observed when initiated after hospitalization; patients admitted for other indications solely for infection control may be considered if all other requirements are met)
- Use for longer than 5 consecutive days
- Pre-exposure or post-exposure prophylaxis for prevention of COVID-19
- Not approved for any use, including treatment of COVID-19 (EUA only)
Dosing & Administration- Recommended dose: 800 mg (four 200 mg capsules) orally every 12 hours for 5 days
- Can be taken with or without food
- Missed dose within 10 hours of scheduled time: take as soon as possible and resume normal dosing; missed >10 hours: skip and restart normal regimen with next dose
- Should be administered as soon as possible and within 5 days of symptom onset
- No dose adjustment required for renal impairment, hepatic impairment, or geriatric patients
- Patients requiring hospitalization after starting treatment may complete the full 5-day course at provider discretion
Prescriber Requirements & Counseling- Review "Fact Sheet for Patients and Caregivers" with patient/caregiver prior to dispensing; document provision of electronic or hard copy
- Inform patient/caregiver that MOV is an unapproved drug authorized under EUA
- Inform that no adequate approved products exist for mild-moderate COVID-19 in high-risk patients
- Inform that other currently authorized products exist for the same use
- Discuss benefits and risks as outlined in the fact sheet
- Assess pregnancy status in females of childbearing potential (clinically indicated)
- Report all medication errors and serious adverse events potentially related to MOV within 7 calendar days via VA ADERS per local policy
Pregnancy, Reproductive Health & Lactation- Embryofetal toxicity noted in animal studies; not recommended during pregnancy unless benefits outweigh risks
- Females of childbearing potential: use reliable contraception correctly and consistently during treatment and for 4 days after the last dose
- Males of reproductive potential sexually active with females of childbearing potential: use reliable contraception during treatment and for at least 3 months after the last dose
- Pregnancy status does not need confirmation if surgically sterilized, using an IUD/implant, or pregnancy is impossible
- If prescribed during pregnancy: document discussion of benefits/risks, inform about Merck pregnancy surveillance program, obtain consent to share patient information with Merck (provide name and contact)
- Breastfeeding: not recommended during treatment and for 4 days after the final dose due to potential for adverse reactions in the infant
Safety Monitoring & Reporting- Monitor for hypersensitivity reactions, including anaphylaxis; immediately discontinue MOV and initiate supportive care if clinically significant reaction occurs
- Monitor for bone and cartilage toxicity (not indicated <18 years)
- Document and report all COVID-19 related adverse drug events to VA ADERS as a MedWatch report
- VHA Center for Medication Safety conducts prospective pharmacovigilance; providers should monitor closely for unusual clinical or laboratory events.
Indication & Patient Population- Laboratory confirmed mild to moderate COVID-19 in adults
- Not authorized for patients hospitalized due to COVID-19
Timing & Disease Severity- Within 5 days of symptom onset
Risk Factors & Alternative Therapies- At least one high-risk criteria for progression to severe disease as defined by the CDC
- Alternative treatments authorized for mild-moderate COVID-19 in high-risk patients are not accessible or clinically appropriate
Reproductive Health & Pregnancy Requirements- Females of childbearing potential and males sexually active with females of childbearing potential must agree to use a reliable method of contraception correctly and consistently during treatment and for 4 days (females) or 3 months (males) after the last dose
- Pregnancy status must be determined to be negative for females of childbearing potential (unless surgically sterilized, has an intrauterine device/contraceptive implant, or is unable to get pregnant)
- For pregnant patients: Provider must communicate known and potential risks of MOV during pregnancy and document; inform patient of the Merck pregnancy surveillance program; provide patient’s name to Merck if patient agrees to participate and allows disclosure
Dosing & Administration- 800mg orally q12h for 5 days (with or without food)
- No dose adjustments recommended for renal or hepatic impairment or in geriatric patients
Monitoring, Reporting & Documentation- Provider must review the “Fact Sheet for Patients and Caregivers” with the patient/caregiver prior to administration and provide an electronic or hard copy
- Report all medication errors and serious adverse drug events possibly related to MOV through the VA ADERS program
- In-line patient request form required prior to initiation capturing: patient name, last 4 of SSN, DOB, date of positive test, confirmation of mild/moderate diagnosis, timing within 5 days, high-risk status per CDC, inaccessibility/appropriateness of alternatives, fact sheet provision, and pregnancy/contraception status
- Post-dispensing tracking required: date dispensed, order number, number/dose dispensed, lot numbers, adverse events documentation, and certification of accuracy/completeness
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SILDENAFIL TAB
REVATIO, SILDENAFIL (ANTIHYPERTENSIVE), SILDENAFIL (PULM.HYPERTENSION), SILDENAFIL CITRATE, VIAGRA
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REVATIO, SILDENAFIL (ANTIHYPERTENSIVE), SILDENAFIL (PULM.HYPERTENSION), SILDENAFIL CITRATE, VIAGRA |
2022-01-01 |
Formulary Status- Avanafil is non-formulary.
- Sildenafil and tadalafil are available on the VA National Formulary (PA-F).
Prescribing & Clinical Evaluation Requirements- Prescriptions for erectile dysfunction must be written by a VA prescriber following an appropriate clinical evaluation.
- Prescribing clinician is responsible for ensuring no contraindications exist for the prescribed PDE5 inhibitor.
- Patient must understand treatment choices, associated risks, and benefits.
Quantity & Dispensing Limits- Limited to 6 doses per month for management of erectile dysfunction.
- Quantities less than 6 doses per month dispensed only at request of patient or prescriber.
- Greater quantities may be approved on a case-by-case basis (e.g., couples trying to conceive, veterans with inconsistent response).
- Quantity limit does not apply for management of pulmonary hypertension.
Adverse Event Reporting- All adverse events must be reported in the VA Adverse Drug Event Reporting System (VA ADERS/VA MedSafe).
Lost Prescription Management- Lost prescriptions will not be replaced during the intended time period; authorized refills become available at the next scheduled refill date.
Clinical Category: Monotherapy & Combination Therapy Restrictions- A PDE5I should not be used routinely for the management of LUTS-BPH as monotherapy.
- A PDE5I should not be used in combination with alpha blockers for BPH/LUTS, as it offers no symptom improvement advantage over either agent alone per American Urological Association (AUA) guidelines.
Clinical Category: Formulary PDE5I Initiation & Substitution Criteria- Consider when more established pharmacotherapies are not an option or have not demonstrated benefit.
- Initiate a formulary alpha blocker first using shared decision making and patient-specific factors. If ED is present, may consider adding a formulary PDE5I (with quantity limits) to an alpha blocker.
- Consider substituting or adding a formulary PDE5I if unable to tolerate or lack of response to an adequate trial (12 weeks) of a formulary alpha blocker titrated to maximum therapeutic dose.
- If adding a PDE5I, the patient must be on a stable dose of the alpha-blocker prior to initiation; the PDE5I should then be started at the lowest recommended dose.
Clinical Category: Clinical Scenarios for Formulary PDE5I Monotherapy Consideration- In place of an alpha blocker in the interim if cataract surgery is planned or likely (due to risk of intraoperative floppy iris syndrome).
- When an alpha blocker is contraindicated or not tolerated and an antimuscarinic is not appropriate due to post-void residual >250 mL, contraindication, ineffective trial, or substantial contribution to existing anticholinergic burden.
- (Note: The document explicitly states that only sildenafil, tadalafil, and vardenafil have been studied for BPH/LUTS; avanafil-specific criteria are not provided in the text.)
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SILDENAFIL TAB
REVATIO, SILDENAFIL (ANTIHYPERTENSIVE), SILDENAFIL (PULM.HYPERTENSION), SILDENAFIL CITRATE, VIAGRA
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REVATIO, SILDENAFIL (ANTIHYPERTENSIVE), SILDENAFIL (PULM.HYPERTENSION), SILDENAFIL CITRATE, VIAGRA |
2022-01-01 |
Formulary Status- Avanafil is non-formulary.
- Sildenafil and tadalafil are available on the VA National Formulary (PA-F).
Prescribing & Clinical Evaluation Requirements- Prescriptions for erectile dysfunction must be written by a VA prescriber following an appropriate clinical evaluation.
- Prescribing clinician is responsible for ensuring no contraindications exist for the prescribed PDE5 inhibitor.
- Patient must understand treatment choices, associated risks, and benefits.
Quantity & Dispensing Limits- Limited to 6 doses per month for management of erectile dysfunction.
- Quantities less than 6 doses per month dispensed only at request of patient or prescriber.
- Greater quantities may be approved on a case-by-case basis (e.g., couples trying to conceive, veterans with inconsistent response).
- Quantity limit does not apply for management of pulmonary hypertension.
Adverse Event Reporting- All adverse events must be reported in the VA Adverse Drug Event Reporting System (VA ADERS/VA MedSafe).
Lost Prescription Management- Lost prescriptions will not be replaced during the intended time period; authorized refills become available at the next scheduled refill date.
Clinical Category: Monotherapy & Combination Therapy Restrictions- A PDE5I should not be used routinely for the management of LUTS-BPH as monotherapy.
- A PDE5I should not be used in combination with alpha blockers for BPH/LUTS, as it offers no symptom improvement advantage over either agent alone per American Urological Association (AUA) guidelines.
Clinical Category: Formulary PDE5I Initiation & Substitution Criteria- Consider when more established pharmacotherapies are not an option or have not demonstrated benefit.
- Initiate a formulary alpha blocker first using shared decision making and patient-specific factors. If ED is present, may consider adding a formulary PDE5I (with quantity limits) to an alpha blocker.
- Consider substituting or adding a formulary PDE5I if unable to tolerate or lack of response to an adequate trial (12 weeks) of a formulary alpha blocker titrated to maximum therapeutic dose.
- If adding a PDE5I, the patient must be on a stable dose of the alpha-blocker prior to initiation; the PDE5I should then be started at the lowest recommended dose.
Clinical Category: Clinical Scenarios for Formulary PDE5I Monotherapy Consideration- In place of an alpha blocker in the interim if cataract surgery is planned or likely (due to risk of intraoperative floppy iris syndrome).
- When an alpha blocker is contraindicated or not tolerated and an antimuscarinic is not appropriate due to post-void residual >250 mL, contraindication, ineffective trial, or substantial contribution to existing anticholinergic burden.
- (Note: The document explicitly states that only sildenafil, tadalafil, and vardenafil have been studied for BPH/LUTS; avanafil-specific criteria are not provided in the text.)
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TADALAFIL TAB
ALYQ, CIALIS
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ALYQ, CIALIS |
2022-01-01 |
Formulary Status- Avanafil is non-formulary.
- Sildenafil and tadalafil are available on the VA National Formulary (PA-F).
Prescribing & Clinical Evaluation Requirements- Prescriptions for erectile dysfunction must be written by a VA prescriber following an appropriate clinical evaluation.
- Prescribing clinician is responsible for ensuring no contraindications exist for the prescribed PDE5 inhibitor.
- Patient must understand treatment choices, associated risks, and benefits.
Quantity & Dispensing Limits- Limited to 6 doses per month for management of erectile dysfunction.
- Quantities less than 6 doses per month dispensed only at request of patient or prescriber.
- Greater quantities may be approved on a case-by-case basis (e.g., couples trying to conceive, veterans with inconsistent response).
- Quantity limit does not apply for management of pulmonary hypertension.
Adverse Event Reporting- All adverse events must be reported in the VA Adverse Drug Event Reporting System (VA ADERS/VA MedSafe).
Lost Prescription Management- Lost prescriptions will not be replaced during the intended time period; authorized refills become available at the next scheduled refill date.
Clinical Category: Monotherapy & Combination Therapy Restrictions- A PDE5I should not be used routinely for the management of LUTS-BPH as monotherapy.
- A PDE5I should not be used in combination with alpha blockers for BPH/LUTS, as it offers no symptom improvement advantage over either agent alone per American Urological Association (AUA) guidelines.
Clinical Category: Formulary PDE5I Initiation & Substitution Criteria- Consider when more established pharmacotherapies are not an option or have not demonstrated benefit.
- Initiate a formulary alpha blocker first using shared decision making and patient-specific factors. If ED is present, may consider adding a formulary PDE5I (with quantity limits) to an alpha blocker.
- Consider substituting or adding a formulary PDE5I if unable to tolerate or lack of response to an adequate trial (12 weeks) of a formulary alpha blocker titrated to maximum therapeutic dose.
- If adding a PDE5I, the patient must be on a stable dose of the alpha-blocker prior to initiation; the PDE5I should then be started at the lowest recommended dose.
Clinical Category: Clinical Scenarios for Formulary PDE5I Monotherapy Consideration- In place of an alpha blocker in the interim if cataract surgery is planned or likely (due to risk of intraoperative floppy iris syndrome).
- When an alpha blocker is contraindicated or not tolerated and an antimuscarinic is not appropriate due to post-void residual >250 mL, contraindication, ineffective trial, or substantial contribution to existing anticholinergic burden.
- (Note: The document explicitly states that only sildenafil, tadalafil, and vardenafil have been studied for BPH/LUTS; avanafil-specific criteria are not provided in the text.)
Inclusion Criteria- Veteran has had insufficient response, or intolerance, to an adequate trial of sildenafil
- Tadalafil is being used for Pulmonary Arterial Hypertension (PAH)
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TADALAFIL TAB
ALYQ, CIALIS
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ALYQ, CIALIS |
2022-01-01 |
Formulary Status- Avanafil is non-formulary.
- Sildenafil and tadalafil are available on the VA National Formulary (PA-F).
Prescribing & Clinical Evaluation Requirements- Prescriptions for erectile dysfunction must be written by a VA prescriber following an appropriate clinical evaluation.
- Prescribing clinician is responsible for ensuring no contraindications exist for the prescribed PDE5 inhibitor.
- Patient must understand treatment choices, associated risks, and benefits.
Quantity & Dispensing Limits- Limited to 6 doses per month for management of erectile dysfunction.
- Quantities less than 6 doses per month dispensed only at request of patient or prescriber.
- Greater quantities may be approved on a case-by-case basis (e.g., couples trying to conceive, veterans with inconsistent response).
- Quantity limit does not apply for management of pulmonary hypertension.
Adverse Event Reporting- All adverse events must be reported in the VA Adverse Drug Event Reporting System (VA ADERS/VA MedSafe).
Lost Prescription Management- Lost prescriptions will not be replaced during the intended time period; authorized refills become available at the next scheduled refill date.
Clinical Category: Monotherapy & Combination Therapy Restrictions- A PDE5I should not be used routinely for the management of LUTS-BPH as monotherapy.
- A PDE5I should not be used in combination with alpha blockers for BPH/LUTS, as it offers no symptom improvement advantage over either agent alone per American Urological Association (AUA) guidelines.
Clinical Category: Formulary PDE5I Initiation & Substitution Criteria- Consider when more established pharmacotherapies are not an option or have not demonstrated benefit.
- Initiate a formulary alpha blocker first using shared decision making and patient-specific factors. If ED is present, may consider adding a formulary PDE5I (with quantity limits) to an alpha blocker.
- Consider substituting or adding a formulary PDE5I if unable to tolerate or lack of response to an adequate trial (12 weeks) of a formulary alpha blocker titrated to maximum therapeutic dose.
- If adding a PDE5I, the patient must be on a stable dose of the alpha-blocker prior to initiation; the PDE5I should then be started at the lowest recommended dose.
Clinical Category: Clinical Scenarios for Formulary PDE5I Monotherapy Consideration- In place of an alpha blocker in the interim if cataract surgery is planned or likely (due to risk of intraoperative floppy iris syndrome).
- When an alpha blocker is contraindicated or not tolerated and an antimuscarinic is not appropriate due to post-void residual >250 mL, contraindication, ineffective trial, or substantial contribution to existing anticholinergic burden.
- (Note: The document explicitly states that only sildenafil, tadalafil, and vardenafil have been studied for BPH/LUTS; avanafil-specific criteria are not provided in the text.)
Inclusion Criteria- Veteran has had insufficient response, or intolerance, to an adequate trial of sildenafil
- Tadalafil is being used for Pulmonary Arterial Hypertension (PAH)
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EFGARTIGIMOD ALFA-FCAB INJ,SOLN
VYVGART
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VYVGART |
2021-12-30 |
Exclusion Criteria- Concomitant therapy with other monoclonal antibody or neonatal Fc receptor antagonist (e.g., rozanolixizumab)
- Thymectomy within 3 months
- Intravenous immunoglobulin (IVIG) or plasma exchange within 1 month
- Untreated hepatitis B, hepatitis C, or HIV with low CD4 count
- Serum IgG level less than 600 mg/dL
- Active, untreated infection
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist
- Anti-acetylcholine receptor (AChR) antibody positive
- Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV
- Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) total score ≥ 5
Additional Inclusion Criteria- One of the following must be met:
- Inadequate symptom control, contraindication, or intolerance to high dose steroid burst, plasma exchange or IVIG and patient requires rapid onset or bridge therapy
- Inadequate symptom control to maximally tolerated pyridostigmine and at least two immunosuppressive agents separately trialed for at least 6 months each (e.g., azathioprine, cyclosporine, mycophenolate, etc.)
- History of intolerance or contraindication preventing trial of immunosuppressive agents (e.g., azathioprine, cyclosporine, mycophenolate, etc.)
Indication & Patient Population- Treatment of generalized myasthenia gravis in adults who are antiacetylcholine receptor (AchR) antibody positive
- May be effective for other myasthenia gravis subtypes
Dosing & Administration- 10 mg/kg IV once weekly for 4 weeks per cycle
- Maximum dose of 1.2 grams IV (1200 mg for patients weighing 120 kg or more)
- Subsequent treatment cycles may be administered based on clinical evaluation
- Treatment cycles must not be initiated sooner than 50 days from the start of the previous cycle
Safety, Monitoring & Precautions- Infections: Delay administration in patients with an active infection; monitor for signs and symptoms; withhold until resolved if a serious infection occurs
- Hypersensitivity Reactions: Discontinue infusion and institute appropriate therapy if angioedema, dyspnea, or rash occurs
- Common adverse reactions (≥10% incidence): Headache, upper respiratory tract infection, urinary tract infection
- Serious adverse events reported include thrombocytosis, rectal adenocarcinoma, myasthenia gravis worsening, depression, myocardial ischemia, atrial fibrillation, spinal ligament ossification, spinal compression fracture, and myasthenia gravis crisis
Clinical Context & Place in Therapy- Weak recommendation for patients remaining symptomatic on pyridostigmine, steroids, or nonsteroidal immunosuppressive therapy (NSISTs)
- Considered steroid-sparing with potential for additional benefit when added to other NSIST agents
- Provides rapid onset of effect (observed as early as 2 weeks in clinical trials)
- Demonstrated additional benefit in patients already receiving other immunotherapies
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MARIBAVIR TAB
LIVTENCITY
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LIVTENCITY |
2021-12-09 |
Indication/Patient Population- Treatment of adult and pediatric (>12 years and >35 kg) patients with post-transplant CMV infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir, or foscarnet.
- Post-hematopoietic-cell transplant (HSCT) or solid-organ transplant (SOT) recipients.
Dosing & Administration- 200 mg tablet; standard dose is 400 mg (two 200 mg tablets) PO BID, with or without food.
- Dose adjustment required when co-administered with CYP-inducing anticonvulsants: 800 mg PO BID with carbamazepine; 1200 mg PO BID with phenytoin or phenobarbital.
- Only available as oral dosage form.
Clinical Efficacy & Treatment Scenarios- Indicated for treatment of refractory or resistant CMV infections post-transplant.
- Not indicated for prophylaxis (Phase 2 trials failed to show efficacy).
- May be considered for patients intolerant to ganciclovir/valganciclovir (e.g., treatment-limiting cytopenias), but only in select situations with close consultation due to limited data and risk of recurrence/resistance.
- Foscarnet is generally preferred second-line over maribavir for compromised oral absorption or severe/critical illness.
- Use cautiously in CMV gastrointestinal disease due to potential reduced absorption.
- Appropriate as step-down therapy from foscarnet after clinical improvement.
- Appropriate for isolates with known or suspected resistance to foscarnet.
Safety Monitoring & Precautions- Risk of reduced antiviral activity when co-administered with ganciclovir or valganciclovir (maribavir antagonizes their activation).
- Monitor CMV DNA levels and check maribavir resistance if patient is not responding to treatment.
- Virologic failure and relapse can occur during treatment and within 4-8 weeks after discontinuation.
- Maribavir pUL97 resistance-associated substitution confers cross-resistance to ganciclovir and valganciclovir.
- Risk of adverse reactions or loss of virologic response due to drug interactions: Primarily metabolized by CYP3A4; strong inducers decrease plasma concentrations (virologic failure risk). Potential to increase concentrations of immunosuppressants that are CYP3A4 and P-gp substrates (cyclosporine, everolimus, sirolimus, tacrolimus).
- Use cautiously with moderate to strong CYP3A4 inducers.
- Common adverse effects include dysgeusia, nausea, vomiting, and diarrhea; often treatment-limiting.
Special Populations & Pharmacokinetics- No dosage adjustment required for patients >65 years.
- No dose adjustments needed for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe hepatic impairment (Child-Pugh C).
- No dose adjustments for mild, moderate, or severe kidney impairment; not studied in end-stage renal disease including dialysis.
- Absorption: 25% to 45% absorbed orally; no data to support use for CMV of the gastro-intestinal tract with compromised gut integrity.
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ROPEGINTERFERON INJ,SOLN
BESREMI
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BESREMI |
2021-12-02 |
Indication- Treatment of adults with polycythemia vera (PV).
Pretreatment Evaluations and Tests- Pregnancy testing
- Estimated GFR (eGFR)
- Liver enzyme / function tests
- Screen for subclinical thyroid dysfunction, autoimmune disorders, and neuropsychiatric disorders.
Dosage Regimen and Dosing Criteria- Patients not on hydroxyurea: Initiate at 100 mcg SC every 2 weeks. Increase dose by 50 mcg every 2 weeks up to a maximum of 500 mcg until hematologic parameters are stabilized (hematocrit less than 45%, platelets less than 400 x 109/L, and leukocytes less than 10 x 109/L).
- Patients transitioning from hydroxyurea: Initiate at 50 mcg SC every 2 weeks in combination with hydroxyurea. Increase ropegIFN by 50 mcg every 2 weeks up to a maximum of 500 mcg until hematologic stabilization. During Weeks 3–12, gradually taper off hydroxyurea by reducing the total biweekly dose by 20%–40% every 2 weeks. Discontinue hydroxyurea by Week 13.
- Maintenance: Maintain the 2-week dosing interval for at least 1 year that achieved hematologic stability. Thereafter, extend to every 4 weeks.
- Dose modifications due to adverse reactions: Refer to prescribing information.
Safety Considerations, Warnings, and Precautions- Boxed Warning: Risk of serious disorders; may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor closely and discontinue if persistently severe or worsen.
- Contraindications: Severe psychiatric disorders (particularly severe depression, suicidal ideation, or suicide attempt), hypersensitivity to IFNs including IFN alfa-2b or inactive ingredients, moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment, history or presence of active serious/untreated autoimmune disease, immunosuppressed transplant recipients.
- Other Warnings/Precautions: Depression and suicide; endocrine toxicity; cardiovascular toxicity; decreased peripheral blood counts; hypersensitivity reactions; pancreatitis; colitis; pulmonary toxicity; ophthalmologic toxicity; hyperlipidemia; hepatotoxicity; renal toxicity; dental and periodontal toxicity; dermatologic toxicity. Avoid driving and operating machinery.
- Common Adverse Events (>40%): Influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, musculoskeletal pain.
Drug Interactions- CYP450 substrates with narrow therapeutic index: Monitor for adverse reactions; adjust dose of concomitant drug if needed.
- Myelosuppressive agents: Avoid concomitant use. Monitor patients receiving concomitant myelosuppressives.
- Narcotics, hypnotics, or sedatives: Monitor for excessive central nervous system toxicity.
Specific Populations- Pregnancy: Can cause fetal harm. Advise effective contraception. May disrupt menstrual cycles. Generally avoid; use in pregnancy may be considered after weighing risks vs benefits on a case-by-case basis.
- Lactation: Advise against breastfeeding during treatment and for 8 weeks after the final dose.
- Renal Impairment: Avoid use if eGFR < 30 mL/min. No dosage adjustment necessary for eGFR ≥ 30 mL/min.
- Hepatic Impairment: Contraindicated in Child-Pugh B or C hepatic impairment. Reduce dosage if increased liver enzymes are progressive and persistent.
- Geriatric Use: Insufficient data to determine differences in response. Use cautious dosing.
Guideline Criteria for Use / Place in Therapy- NCCN Guidelines: Recommended as an alternative therapy for initial cytoreductive treatment in low-risk PV when potential indications are present (new thrombosis or disease-related major bleeding, frequent phlebotomy or intolerance to phlebotomy, splenomegaly, progressive thrombocytosis and/or leukocytosis, disease-related symptoms such as pruritus, night sweats, fatigue).
- ELN Guidelines: Cytoreductive therapy is recommended for low-risk PV with poor tolerance to phlebotomy, symptomatic progressive splenomegaly (>5-cm increase in past year), or persistent leukocytosis (leukocyte count >20 x 109/L confirmed at 3 months). Should be considered for progressive leukocytosis, extreme thrombocytosis (>1500 x 109 platelets/L) with disease-related bleeding, or inadequate hematocrit control with phlebotomies. Can be considered for high symptom burden/severe itching not relieved by standard measures, or case-by-case for relevant cardiovascular risk despite primary prevention.
- Age-based selection: Preferred in patients <60 years old; hydroxyurea is preferred in patients >60 years of age.
- VHA Place in Therapy: May be used as a less preferred (higher-cost) alternative to pegIFN alfa-2a in patients with PV, including low-risk PV (<60 years without history of thrombosis) who are symptomatic and have potential indications for cytoreductive therapy. Both should generally be avoided in pregnant patients and patients of childbearing potential not on contraception.
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ASCIMINIB TAB
SCEMBLIX
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SCEMBLIX |
2021-11-12 |
Exclusion Criteria- Presence of BCR-ABL1 A337T, P465S, or F359V/I/C mutations
- Unmanageable drug-drug interaction
- Pregnancy
- Lactation
Inclusion Criteria (All must be met)- Philadelphia chromosome-positive, chronic myeloid leukemia in chronic phase
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Additional Inclusion Criteria (One of the following must be met)- Previous treatment failure or intolerance of at least two other tyrosine kinase inhibitors (TKI)
- Presence of T315I gatekeeper mutation, previous treatment failure or intolerance to at least one other TKI, and not a candidate for ponatinib
- Patients who may not be candidates for ponatinib include those with established coronary artery disease, limb-threatening peripheral vascular disease, history of TIA and/or CVA; consider risk vs. benefit
Additional Inclusion Criteria (Select if applicable)- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
- Avoid lactation/breastfeeding during therapy and for 1 week after stopping treatment
Indications & Target Population- Adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) who have received prior treatment with 2 or more tyrosine kinase inhibitors (TKIs)
- Adult patients with Ph+ CML-CP who have the T315I mutation of BCR-ABL1
Dosing & Administration- Tablets available in 20 mg and 40 mg strengths
- For Ph+ CML after ≥2 prior TKIs: 80 mg orally once daily or 40 mg orally twice daily
- For Ph+ CML with T315I mutation: 200 mg orally twice daily
- Administer without food; avoid food at least 2 hours before or 1 hour after dosing
Monitoring Requirements- Complete blood count labs every two weeks for three months, followed by monthly labs
- Serum amylase and lipase levels monthly
- Blood pressure monitoring throughout treatment
- Assessment of cardiovascular risk factors throughout treatment
Contraindications & Warnings/Precautions- Contraindicated in patients with known A337T, P465S, or F359V/I/C mutations
- Myelosuppression (thrombocytopenia, neutropenia, anemia): May need to hold or adjust dose based on severity and occurrence
- Pancreatic toxicity (pancreatitis, elevated pancreatic enzymes): May need to hold, adjust dose, or discontinue based on severity
- Hypertension: May need to hold, adjust dose, or discontinue based on severity
- Hypersensitivity reactions: May need to hold, adjust dose, or discontinue based on severity
- Cardiovascular toxicity (cardiac dysfunction, arrhythmias, cardiac failure): May need to hold, adjust dose, or discontinue based on severity
- Embryo-fetal toxicity: Avoid in pregnancy; implement effective contraception during and one week following treatment for women of child-bearing potential
- Lactation: Advise women to avoid breastfeeding during and one week after end of treatment
- No boxed warnings
Drug Interactions- Strong CYP3A4 inhibitors: Monitor closely when used with 200 mg twice daily dosing
- Itraconazole (solution containing hydroxypropyl-β-cyclodextrin): Avoid concomitant use at all recommended doses
- CYP3A4 substrates: Monitor closely with 80 mg once daily; avoid concomitant use with 200 mg twice daily
- CYP2C9 substrates: Avoid concomitant use at all recommended doses
- P-gp substrates: Monitor concomitant use at all recommended doses
Dose Adjustments- Renal impairment: None required for estimated glomerular filtration rate (eGFR) of 15-89 mL/min/1.73 m2 without dialysis
- Hepatic impairment: None required
Formulary & Clinical Guidance- FDA indications include Ph+ CML-CP in patients previously treated with at least 2 TKIs or presence of T315I mutation
- NCCN Clinical Practice Guidelines recommend as a Category 2A treatment option for patients with treatment failure to at least 2 previous TKIs or the presence of the T315I mutation
- Considered for use in Ph+ CML-CP patients after at least two other TKI treatments or presence of the T315I gatekeeper mutation, alongside clinical judgment in selection of next-line TKI therapy
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REAL FOODS LIQUID,NUTRITIONAL SUPPLEMENT
BEEF-POTATOES-SPINACH, EGGS-APPLES-OATS, ORANGE CHICKN-CARROT-BRWN RICE, QUINOA-KALE-HEMP, SALMON-OATS-SQUASH, TURKEY-SWEET POTATOES-PEACHES
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BEEF-POTATOES-SPINACH, EGGS-APPLES-OATS, ORANGE CHICKN-CARROT-BRWN RICE, QUINOA-KALE-HEMP, SALMON-OATS-SQUASH, TURKEY-SWEET POTATOES-PEACHES |
2021-11-12 |
Exclusion Criteria- Consult to VA Registered Dietitian Nutritionist (RDN) is not completed
- Does not meet criteria for tube feeding or oral nutrition supplementation
- Commercial Blenderized Tube Feeding (CBTF) is not recommended by VA RDN
Inclusion Criteria- Veteran has a food-related allergy that excludes the trial of other standard non-blenderized formulas (including but not limited to dairy, soy, corn, nuts, or gluten)
- Standard formulary options have been attempted and were not tolerated; formulas attempted and tolerance symptoms are documented in RDN progress notes
- Specific disease states as documented by the RDN prevent the use of standard formula
Dosage and Administration- Dosing to be determined by RDN nutrition assessment and recommendation
- Dosing must be documented in request and/or RDN assessment
- Approved National NFS Dietary Supplement contract products:
- Compleat Standard 1.4 Vanilla for tube feeding or oral nutrition supplementation (Plant-based-vegan, high calorie, nutritionally complete; free of dairy, soy, nuts, wheat, corn; 250 ml, 350 calories, 18 g protein per carton)
- Kate Farms Peptide for tube feeding (Organic Plant-based Peptide, vegan; for impaired GI function or malabsorption and intolerance to other formulas; free of dairy, nuts, corn, wheat, soy; 325 ml, 500 calories, 24 g protein per carton)
- Compleat Organic Blends for tube feeding or oral consumption (Made with organic whole foods plus vitamins and minerals; plant-based/vegan or chicken blend varieties made without common allergens; 300 ml, 380 calories, 19 g protein per pouch)
Monitoring- Requires routine follow-up by RDN annually or more often as needed
- RDN documentation must include justification for CBTF, monitoring for formula tolerance and appropriateness, and progress toward meeting defined therapeutic goals
- Reassessment by an RDN is required prior to prescription renewals
Renewal and Discontinuation Considerations- When veteran no longer meets criteria for CBTF, RDN will discontinue or recommend that CBTF prescription be discontinued as appropriate
- Reassessment by RDN is required for renewal of CBTF prescription
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RANIBIZUMAB INJ,SOLN
BYOOVIZ, SUSVIMO
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BYOOVIZ, SUSVIMO |
2021-11-04 |
Indication & Patient Population- Treatment of neovascular age-related macular degeneration (nAMD)
- Previously responded to at least two intravitreal injections of a VEGF inhibitor
- Age 50 years or greater
- nAMD-related neovascular lesions involving the macula diagnosed within 9 months of screening
- At least 3 prior VEGF inhibitor intravitreal injections within 6 months of screening with anatomical and visual response
Dosing & Administration- 100 mg/mL solution for intravitreal use via SUSVIMO ocular implant
- Recommended dose: 2 mg (0.02 mL) continuously delivered via the implant with refills every 24 weeks (approximately 6 months)
- Supplemental treatment with 0.5 mg intravitreal ranibizumab injection may be administered in the affected eye if clinically necessary
Contraindications & Safety Warnings- Ocular or periocular infection
- Active intraocular inflammation
- Hypersensitivity to ranibizumab or excipients in SUSVIMO
- Boxed warning for 3-fold higher rate of endophthalmitis compared to monthly intravitreal injections
Procedural & Monitoring Requirements- Implant and refill procedure must be performed under strict aseptic conditions by an ophthalmologist experienced in vitreoretinal surgery
- Temporarily discontinue antithrombotic medication prior to implant insertion procedure to reduce risk of vitreous hemorrhage
- Close monitoring required due to frequency of adverse events and to assess need for supplemental IVT ranibizumab
- Patients instructed not to push on, rub, or touch the eye/implant area for 30 days following implant surgery and refill-exchange procedure; avoid rubbing/touching throughout treatment
Place in Therapy / Reserve Criteria- Reserved for patients with nAMD who have demonstrated response to VEGF inhibitors and who would benefit from reducing treatment burden (e.g., long travel times, physical mobility limitations)
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VARENICLINE SOLN,NASAL
TYRVAYA
|
TYRVAYA |
2021-10-28 |
Exclusion Criteria- Nasal or sinus conditions that may interfere with administration
Inclusion Criteria- Provider is a VA/VA Community Care ophthalmologist or optometrist
- Diagnosis of dry eye disease
- Documented lack of therapeutic response to at least two artificial tear agents from different categories OR documented corneal surface damage while frequently using artificial tear agent(s)
- Lack of response to an adequate trial of ophthalmic cyclosporine unless unable to use (e.g., intolerance, etc.)
- Lack of response to an adequate trial of lifitegrast unless unable to use (e.g., intolerance, etc.)
Indication- Treatment of the signs and symptoms of dry eye disease
Dosage & Administration- Nasal spray delivering 0.03 mg varenicline per spray (0.05 mL)
- One spray in each nostril twice daily, approximately 12 hours apart
- Concomitant use of artificial tears is permitted
Patient Selection Parameters- Dry eye disease defined by: anesthetized Schirmer’s score ≤10 mm/5 min; Ocular Surface Disease Index (OSDI) ≥23; corneal fluorescein staining (CFS) ≥2 in at least 1 corneal region or sum ≥4 for all corneal regions
- Patients who wish to use or are currently using artificial tears
Exclusions- Corneal epithelial defects
- Chronic or recurrent epistaxis, coagulation disorders
- Prior nasal or sinus surgery
- Vascularized polyp, severely deviated septum, chronic recurrent nosebleeds, or severe nasal obstruction
- Current treatment with nasal continuous positive airway pressure (CPAP)
- Intraocular or extraocular surgery within 3 months, or refractive surgery within 12 months
- Blepharoplasty or corneal transplant in either eye
- Contact lens use within 7 days prior to initiation or anticipated during treatment
- Any form of punctal or intracanalicular occlusion
Place in Therapy & Formulary Considerations- Projected place in therapy: Patients with dry eye disease who have not responded to or tolerated treatment with topical cyclosporine and lifitegrast
- Long-term safety data beyond 84 days are needed; development of tolerance over time is unknown
Safety & Administration Monitoring- No boxed warnings or contraindications
- Most common adverse events: sneezing (82%), cough (16%), throat irritation (13%), instillation-site (nose) irritation (8%)
- Discontinuation due to adverse events: 2% for varenicline vs 2.1% for vehicle
- Requires specific administration technique to prevent errors: insert applicator into left or right nostril, tilt tip toward top of ear on same side, do not press against nasal wall, leave space between tip and nasal wall, place tongue to roof of mouth, breathe gently while pressing/releasing applicator once
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AVACOPAN CAP,ORAL
TAVNEOS
|
TAVNEOS |
2021-10-21 |
Indication & Patient Population- Adjunctive treatment of adult patients with severe active ANCA-associated vasculitis (AAV) (GPA and MPA) in combination with standard therapy including glucocorticoids
- Not approved for eosinophilic granulomatosis with polyangiitis (EGPA / Churg-Strauss syndrome)
- VA-specific indication: Patients with severe (organ- or life-threatening), active, newly diagnosed or relapsing ANCA-positive GPA or MPA who require rapid reduction of glucocorticoid therapy due to severe, otherwise unmanageable glucocorticoid-induced complications or toxicity (e.g., glucocorticoid-related psychosis, myopathy, or herpetic keratitis)
- Not intended for adding to existing therapy with the intent of reducing relapse risk in patients already in remission
- Not intended for improving remission induction or maintenance when current guideline-recommended induction or maintenance therapy is already in place
Dosing & Administration- 30 mg (three 10-mg capsules) twice daily with food
- Capsules must not be crushed, chewed, or opened
- Reduce dosage to 30 mg once daily when coadministered with strong CYP3A4 inhibitors
- No dosage adjustment required for mild, moderate, or severe renal impairment; no data available for patients on dialysis
- No dosage adjustment required for mild or moderate hepatic impairment; no data available for severe (Child-Pugh Class C) hepatic impairment
Pretreatment Testing & Monitoring- Obtain liver function tests including serum ALT, AST, alkaline phosphatase, and total bilirubin prior to initiation
- Obtain Hepatitis B serology (HBsAg and anti-HBc titers) prior to initiation; consult HBV management expert if results indicate prior or current infection to determine need for antiviral therapy and establish monitoring plan
- Monitor liver tests every 4 weeks for the first 6 months, then as clinically indicated
- Withhold treatment if ALT or AST > 3x ULN; discontinue if AST or ALT > 5x ULN or if AST/ALT > 3x ULN with TBIL > 2x ULN until avacopan-induced liver injury is ruled out
- Monitor for evidence of HBV reactivation during therapy and for 6 months after completion of therapy
- Closely monitor for evidence of infection during and after therapy; interrupt therapy if serious or opportunistic infection develops and resume once infection is controlled
Contraindications & Precautions- Contraindicated in patients with serious hypersensitivity to avacopan or product excipients
- Not recommended for use in patients with:
- • Active, untreated and/or uncontrolled chronic liver disease and cirrhosis
- • Active, serious, systemic or localized infection (including undrained abscess); may initiate/restart once controlled
- • Untreated latent or active tuberculosis infection
- • HBsAg-positive status without antiviral prophylaxis; may initiate after starting prophylaxis
- • HBsAg-negative but anti-HBc-positive status; may initiate after starting prophylaxis or if expert approves proceeding without it
- • Hemodialysis dependence
- • Concomitant use of strong and moderate CYP3A4 inducers
- Avoid coadministration with strong and moderate CYP3A4 inducers
- Not recommended for use with methotrexate due to potential additive risk of hepatotoxicity, despite not being a formal contraindication in prescribing information
Duration of Therapy & Discontinuation- If continued during remission of severe disease, use concurrently with standard maintenance therapy (rituximab, azathioprine, or mycophenolate) for a duration based on clinician discretion (e.g., up to 1 to 2 years)
- Discontinue avacopan when current guideline-recommended maintenance therapy is withdrawn (e.g., up to 2 years)
- Efficacy of avacopan monotherapy is unknown; should not be used as a replacement for glucocorticoids
Prescriber Requirements- Must be prescribed by rheumatologists, nephrologists, or other locally designated clinicians with expertise in the management of AAV
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ATOGEPANT TAB
QULIPTA
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QULIPTA |
2021-10-07 |
Exclusion Criteria- Severe hepatic impairment (Child-Pugh C)
- Uncontrolled hypertension
- History of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- Concurrent preventive therapy with another calcitonin gene related peptide (CGRP) targeting agent (including other gepants and CGRP targeting monoclonal antibodies)
- Pregnancy
Inclusion Criteria- Completed comprehensive headache appointment prior to initiation
- Episodic migraine defined as 4 to 14 monthly migraine days
- Moderate to severe migraine intensity
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 3 of the following: beta blocker, topiramate, divalproex, SNRI or TCA, and ACE inhibitor or ARB
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks of a therapeutic dose of at least one CGRP-targeted monoclonal antibody (e.g., erenumab)
Monitoring & Clinical Management Requirements- Discontinue therapy if signs or symptoms of Raynaud’s phenomenon develop
- Monitor patients with a history of Raynaud’s phenomenon for recurrence/worsening and inform them of this possibility
- Comprehensive headache assessment must include evaluation for medication overuse headache, other secondary headache types, adherence to prior therapies, urgent/emergent features, triggers, effective acute treatment, and nonpharmacologic interventions (board certification in headache medicine is not required)
- Scheduled blood pressure check 2–4 weeks after therapy initiation
- Therapeutic dose definitions for oral preventive agents: beta blocker (e.g., metoprolol 50-100 mg BID, propranolol 20-80 mg BID), topiramate 50-200 mg BID, divalproex 500-1000 mg daily, ACE inhibitor or ARB (e.g., lisinopril 20 mg daily, enalapril 10 mg daily, telmisartan 80 mg daily), SNRI or TCA (e.g., venlafaxine SA 75-150 mg daily, amitriptyline 25-100 mg daily)
- Divalproex is not recommended in patients who can become pregnant
- Erenumab is the designated national contract agent; if failure or intolerance occurs, an alternate non-formulary CGRP-targeted monoclonal antibody (e.g., fremanezumab, galcanezumab, eptinezumab) should be tried
Exclusion Criteria- Severe hepatic impairment (Child-Pugh C)
- Creatinine clearance less than 30 mL/min
- Uncontrolled hypertension
- History of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- Concurrent use with a strong or moderate CYP3A4 inducer (e.g., carbamazepine, efavirenz)
- Concurrent preventive therapy with another calcitonin gene related peptide (CGRP) targeting agent (including other gepants and CGRP targeting monoclonal antibodies)
- Pregnancy
Inclusion Criteria- Treatment initiated by a VA/VA Community Care neurologist or locally designated headache expert
- Chronic Migraine defined as ≥15 headache days per month with ≥8 monthly migraine days
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 2 of the following: beta blocker, topiramate, divalproex, and ACE inhibitor or ARB
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks of a therapeutic dose of at least ONE CGRP-targeted monoclonal antibody (e.g., erenumab)
Monitoring & Clinical Management Requirements- Discontinue atogepant if signs or symptoms of Raynaud’s phenomenon develop; monitor and inform patients with a history of Raynaud’s phenomenon about the possibility of recurrence and worsening.
- Headache expert must perform a comprehensive headache assessment including evaluation for medication overuse headache, other secondary headache types, adherence to prior headache therapies, features requiring urgent/emergent evaluation, triggers, effective acute treatment, and nonpharmacologic interventions (board certification in headache medicine is not required).
- Scheduled blood pressure check 2-4 weeks after initiation of therapy.
- Botulinum toxin failure may be considered as one of the required oral prevention medication trials.
- If erenumab failure or intolerance occurs, an alternate non-formulary CGRP-targeted monoclonal antibody (e.g., fremanezumab, galcanezumab, eptinezumab) should be tried.
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OLANZAPINE/ SAMIDORPHAN TAB
LYBALVI
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LYBALVI |
2021-09-30 |
Indications- Schizophrenia in adults
- Bipolar I disorder in adults (acute treatment of manic or mixed episodes as monotherapy and adjunct to lithium or valproate; maintenance monotherapy treatment)
Patient Selection & Clinical Guidance- Indicated for patients where olanzapine is indicated based on individual patient characteristics who are at high risk for weight gain
- Not recommended for switching from another antipsychotic to prevent further weight gain or promote weight loss
- Requires assessment and screening for opioid use prior to initiation
- Recommended that patients have a patient identifier/medical alert identifier with them
Dosing & Administration Limits- Available tablet strengths: 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, and 20 mg/10 mg
- Maximum dose of olanzapine available in the combination tablet is 20 mg; no guidance provided for patients requiring more than 20 mg of olanzapine
Contraindications- Patients currently using opioids
- Patients undergoing acute opioid withdrawal
- Refer to lithium or valproate prescribing information for contraindications if used concomitantly
Warnings & Precautions- Increased mortality and cerebrovascular adverse reactions in elderly patients with dementia-related psychosis
- Precipitation of opioid withdrawal in opioid-dependent patients
- Vulnerability to life-threatening opioid overdose due to potential increased sensitivity to opioids and attempts to overcome samidorphan’s receptor blockade
- Neuroleptic malignant syndrome, DRESS, metabolic changes, tardive dyskinesia, orthostatic hypotension and syncope, falls, leukopenia/neutropenia/agranulocytosis, seizures, potential for cognitive and motor impairment, anticholinergic effects, hyperprolactinemia
- Most common adverse effects (>5% of patients): weight gain, somnolence, dry mouth, headache, increased appetite
Special Populations & Interactions- Renal Impairment: Not recommended for use in end-stage renal disease (eGFR <15 ml/min/1.73 m2)
- Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third-trimester exposure; pregnancy exposure registry available
- Opioid-Free Interval Requirement: 7 days for short-acting opioids and 14 days for long-acting opioids required before initiation
- Drug Interactions: Avoid use with strong CYP3A4 inducers; avoid use with levodopa and dopamine agonists
- Pharmacokinetic properties of samidorphan are not affected by smoking status or sex
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RUXOLITINIB CREAM,TOP
OPZELURA
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OPZELURA |
2021-09-30 |
Indication- Topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
Patient Selection & Place in Therapy- Recommended for short-term (up to 8 weeks) and chronic non-continuous (PRN) therapy.
- Considered second-line therapy following intolerance or inadequate response to trials of topical corticosteroids (TCSs) and a topical calcineurin inhibitor (CNI), unless medically inadvisable.
Dosage & Administration- Apply a thin layer twice daily to affected areas.
- Maximum application area: up to 20% of body surface area (BSA).
- Maximum dose: 60 grams per week.
- Discontinue use when signs and symptoms (e.g., itch, rash, redness) resolve.
- Re-examine by a health care provider if signs and symptoms do not improve within 8 weeks.
Pre-treatment Requirements- Exclude patients with active, serious infections (including localized infections).
- Screen for tuberculosis (TB); avoid therapy in untreated latent or active TB infection (may initiate after starting anti-TB therapy).
- Screen for hepatitis B (at minimum: HBsAg, total anti-HBc, and anti-HBs); if HBsAg-positive, initiate antiviral prophylaxis first; if HBsAg-negative but anti-HBc-positive, consult a hepatologist or infectious diseases expert regarding prophylaxis.
- Ensure current or past hepatitis C virus (HCV) screening.
- Update vaccinations, including for herpes zoster.
Monitoring & Safety Management- Boxed warnings apply for serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis.
- Interrupt therapy if patient develops a serious or opportunistic infection until controlled.
- Monitor patients for signs and symptoms of TB; regular re-testing is not recommended.
- Consider interrupting therapy for herpes zoster until condition resolves.
- Avoid initiation in patients with active HBV or HCV infection.
- Weigh risk-benefits for malignancy, MACE, and thrombosis, particularly in current or past smokers and patients with cardiovascular risk factors.
- Examine skin periodically to monitor for non-melanoma skin cancers (NMSC).
- Monitor complete blood count (CBC) as clinically indicated; discontinue topical ruxolitinib if clinically significant thrombocytopenia, anemia, or neutropenia occurs.
Limitations & Contraindications- Combination therapy with therapeutic biologics, other JAK inhibitors (JAKIs), or potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended.
- No specific contraindications are listed in the document.
Indication- Topical treatment of nonsegmental vitiligo in adults
Dosage & Administration- Apply a thin layer twice daily to affected areas
- Application limited to up to 10% body surface area (BSA)
- Formulation: 15 mg ruxolitinib per gram (1.5%) cream
Patient Eligibility Criteria- Diagnosis of nonsegmental vitiligo with depigmented areas involving ≤ 10% total BSA, including ≥ 0.5% facial BSA and ≥ 3% non-facial BSA
- F-VASI scores ≥ 0.5 and total VASI scores ≥ 3
- Age ≥ 12 years
- Exclusions: Complete leukotrichia within any facial lesions; prior JAKI therapy; prior biologic or investigational drug within 12 weeks or 5 half-lives; phototherapy within 8 weeks or during treatment; immunomodulators within 4 weeks; topical therapies within 1 week
VA Place in Therapy & Formulary Criteria- FDA indication requires no prior therapies, indicating first-line therapy status for nonsegmental vitiligo
- VHA use: Topical ruxolitinib monotherapy may be used in patients with stable, nonsegmental vitiligo who have tried topical corticosteroids, topical calcineurin inhibitors, and phototherapy unless these therapies are medically inadvisable, not available, or not feasible
- Application must be limited to ≤ 10% BSA
- Concurrent use with all other vitiligo therapies was not evaluated
- Combination with phototherapy, therapeutic biologics, other JAKIs, or potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended
Safety & Monitoring Considerations- Hematopoietic adverse events reported in < 1% of patients
- Nonmelanoma skin cancers (basal cell and squamous cell carcinoma) occurred in 0.15% of patients; periodic skin assessments during and after treatment are recommended
Exclusion Criteria- Active, serious, systemic or localized infection, including undrained abscess (may be started/restarted once infection is controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis
- Active hepatitis C
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless treating dermatologist and oncologist agree that risk-benefits favor using the drug)
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
- Concomitant use with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine
- Concomitant use with strong CYP3A4 inhibitors
- Breastfeeding (during treatment and for about 4 weeks after the last dose)
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care dermatologist or locally designated expert
- Diagnosis of nonsegmental vitiligo
- Application intended for ≤ 10% of total body surface area
- Tried and had an inadequate response or intolerance to topical corticosteroids and topical calcineurin inhibitors (unless medically inadvisable); requires ≥ 6 months adherence to prescribed regimens
- Tried and had an inadequate response or intolerance to phototherapy (unless medically inadvisable, not available, or not feasible)
- Vitiligo is NOT a cosmetic condition; Directive 1108.08 on Cosmetic and Enhancement Drugs does NOT apply
Pre-treatment & Management Requirements- Immunizations must be updated prior to initiation, particularly for herpes zoster
- For patients who can become pregnant or have partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
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TISOTUMAB VEDOTIN-TFTV INJ,LYPHL
TIVDAK
|
TIVDAK |
2021-09-30 |
Indication & Patient Population- Adults with recurrent or metastatic cervical cancer
- Disease progression on or after chemotherapy
- Second-line or subsequent therapy following failure of doublet chemotherapy (paclitaxel + cisplatin, carboplatin, or topotecan) plus bevacizumab (if eligible) and pembrolizumab (for PD-L1-positive tumors)
- Recurrent setting following prior systemic therapy and prior pembrolizumab per VHA Oncology Cervical Cancer Clinical Pathway
Dosing & Administration- Intravenous infusion of 2 mg/kg (maximum 200mg) every 3 weeks
- Continue until disease progression or unacceptable toxicity
Premedication & Ophthalmologic Monitoring- Topical vasoconstrictor drops immediately prior to each infusion
- Corticosteroid eye drops TID for 72 hours after each infusion
- Cold packs during infusion and frequent lubricating eye drops
- Avoid contact lenses for the entire duration of therapy
- Ophthalmologic exam prior to initiation, prior to every cycle for 9 cycles, and as clinically indicated (visual acuity, slit lamp anterior eye, eye movement)
Dose Modifications & Toxicity Management- Ocular toxicity: May require dose modification; refer new or worsening symptoms to an eye care provider
- Pneumonitis: Withhold for persistent or recurrent Grade 2; permanently discontinue for Grade 3 or 4
- Peripheral neuropathy: Withhold or reduce doses, or permanently discontinue for Grade 3 or 4
- Hemorrhage: Permanently discontinue for pulmonary or CNS hemorrhage; follow prescribing information for other bleeding types
- Severe cutaneous adverse reactions (SCAR): Permanently discontinue for confirmed Grade 3 or 4
Contraindications & Precautions- None stated
- Embryo-fetal toxicity: Advise patients of fetal risks; persons of reproductive potential must use effective contraception during treatment and for 2 months after the last dose
Drug Interactions- Monitor closely with strong CYP3A4 inhibitors due to MMAE being a CYP3A4 substrate
Exclusion Criteria- Absolute Neutrophil Count greater than or equal to 1500/mcL unless associated with Duffy-null Associated Neutrophil Count (DANC)
- Platelet count greater than or equal to 100,000/mcL
- Clinically significant cardiovascular disease (including unstable angina or acute MI within 6 months; CHF NYHA grade III/IV; reduced EF < 45%; prolonged QTc interval)
- Active or uncontrolled infection
- Clinically significant bleeding risk (coagulation defects, diffuse alveolar hemorrhage from vasculitis, known bleeding diathesis, ongoing major bleeding, trauma with increased risk of life-threatening bleeding, severe head trauma or intracranial surgery within past 8 weeks)
- History of intracerebral arteriovenous malformation, cerebral aneurysm or stroke
- Active ocular surface disease or high-risk for cicatrizing conjunctivitis (e.g. Wagner syndrome, atopic keratoconjunctivitis, autoimmune disease affecting eyes), ocular Stevens-Johnson syndrome, mucus pemphigoid or penetrating ocular transplant
- Peripheral neuropathy greater than or equal to grade 2
- Moderate or severe hepatic impairment (AST greater than 3 times upper limit of normal or total bilirubin greater than 1.5 times the upper limit of normal)
- Severe renal impairment (CrCl 15 to less than 30 ml/min) or end-stage renal disease
- Unmanageable drug-drug interaction identified
- Prior treatment with monomethyl auristatin E (MMAE)-containing drugs
- Pregnancy
- Lactating
Inclusion Criteria- Diagnosis of cervical cancer (squamous cell, adenocarcinoma or adenosquamous histology)
- Disease progression on or after at least one prior chemotherapy regimen for recurrent or metastatic disease and bevacizumab, if eligible, and pembrolizumab, if eligible
Additional Inclusion Criteria & Management Requirements- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0-1
- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 2 months after stopping treatment (4 months for male patients with female partners) for patients who can become pregnant and patients with partners who can become pregnant
- Advising patients not to breastfeed during treatment and for at least 1 week after the last dose
- Advising patients NOT to wear contact lenses throughout the course of therapy
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BELZUTIFAN TAB
WELIREG
|
WELIREG |
2021-09-11 |
Exclusion Criteria- Untreated and symptomatic central nervous system (CNS) metastases
- Unmanageable drug-drug interactions
- Moderate-Severe hepatic impairment (Total bilirubin > 1.5 X Upper Limit of Normal and any AST)
- Pregnancy
- Lactation
Inclusion Criteria- Advanced renal cell carcinoma (RCC) following a PD-1 or PD-L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) as monotherapy or in combination for locally advanced or metastatic RCC
Care Setting, Performance Status & Documentation Requirements- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Counseling & Contraception Requirements- For females who can become pregnant and males with female partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
Indication & Diagnosis- Von Hippel-Lindau (VHL) Disease, based on germline VHL alteration
Inclusion Criteria- Associated renal cell carcinoma, central nervous system (CNS) hemangioblastoma, or pancreatic neuroendocrine tumor not requiring surgery
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Exclusion Criteria- Immediate need for surgical intervention for tumor treatment
- No evidence of metastatic disease
- Pregnancy
- Lactation
Counseling & Safety Requirements- For females who can become pregnant and male patients with female partners who can become pregnant: Counseling provided on potential risks vs benefits and the use of effective contraception during therapy and for 1 week after stopping treatment
Provider & Care Setting Requirements- Care is provided by a VA/VA Community Care oncology provider
Indications & Patient Population- Adults with von Hippel Lindau (VHL) disease for associated renal cell carcinoma (RCC), CNS hemangioblastoma, or pancreatic neuroendocrine tumors not requiring immediate surgery
- Advanced Renal Cell Carcinoma following PD-1 or PD-L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI)
- Locally advanced/metastatic clear cell RCC with prior treatment with a PD-1/L1 inhibitor and VEGF TKI alone or in combination (NMT 3 prior systemic therapies), with progression, KPS ≥70%
Dosing & Administration- 120mg (3 x 40mg tablets) once daily with or without food
- Available as 40 mg film-coated tablets
Safety, Monitoring, & Adverse Events- Boxed Warning: Embryo-fetal Toxicity
- Contraindications: None
- Other Warnings: Anemia (gr 3 in 7% in VHL and 29% in advanced RCC), Hypoxia, Embryo-Fetal Toxicity
- Top Adverse Events: VHL population (anemia, fatigue, headache, dizziness, nausea); Advanced RCC population (anemia, fatigue, musculoskeletal pain, edema, nausea)
Drug Interactions- UGT2B17 inhibitors and CYP2C19 inhibitors-increased exposure of belzutifan
Clinical Pathways & Guideline Context- NCCN guidelines: No preferred therapies for subsequent therapy; Belzutifan is one choice out of 5 for subsequent therapy if patient had prior PD-1/L-1 therapy (2A)
- If only VEGF-TKI prior therapy, use belzutifan under certain circumstances (2B)
- VA Oncology Clinical Pathways: Nothing specific to VHL treatment; recurrent clear cell RCC currently recommends either of 2 combination therapies and then single-agent cabozantinib
- Note on standard of care: Everolimus alone is not considered standard treatment in this pre-treated population. Combination therapy, cabozantinib, or tivozanib would have been better comparators.
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BUPRENORPHINE FILM,BUCCAL
BELBUCA
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BELBUCA |
2021-08-26 |
Perioperative Pain Management Principles- Buprenorphine treatment should not be routinely discontinued in the perioperative period for patients on stable MOUD therapy.
- Discontinuation may confer medical risks including return to active opioid use (50-90%), risk of overdose, prolonged hospital stay, and increased patient burden.
- A buprenorphine taper to < 16 mg/day may be considered for patients prescribed higher doses (> 16 mg) with anticipated high post-surgical pain.
- Utilize a multimodal pain approach including systemic non-opioid analgesics (acetaminophen, NSAIDs, gabapentinoids, ketamine, magnesium, systemic lidocaine, alpha-2 agonists, glucocorticoids), regional/local analgesics, and psychosocial interventions.
- When a full μOR agonist is needed to adequately control perioperative pain, use opioids with similar lipophilicity and binding affinity toward μORs; fentanyl and hydromorphone are reasonable alternatives.
Pre-operative Assessment & Planning- Perform patient evaluation including pain history, physical examination, medication reconciliation, assessment of physical/psychiatric comorbidities, and urine drug monitoring (including methadone, fentanyl, buprenorphine/metabolites).
- Verify prescription adherence via PDMP database.
- Conduct universal substance use disorder screening; perform detailed questioning and appropriate referrals for positive responses.
- Provide pre-operative counseling with written instructions regarding risks of opioid exposure/undertreating pain as relapse triggers.
- Determine procedure-related pain severity (minimal/no pain vs. significant pain) to guide dose adjustment or continuation.
- Plan continuity of care: taper off short-acting opioids prior to discharge; restrict IR opioids to short-term rescue use perioperatively; coordinate with waivered provider/OUD team for outpatient post-op pain care; preschedule follow-up with OUD/chronic pain provider; ensure sufficient buprenorphine supply at discharge.
Elective Procedure Management Criteria- For most patients, continue buprenorphine throughout the operative period.
- Minimally painful surgery: Continue current home dose unchanged, or divide and administer every 6 to 8 hours. Total daily dose may be titrated up to 32 mg/day in divided doses if needed for pain management (does not apply to extended-release injection).
- Painful surgery (moderate/severe pain): Continue baseline dose > 16 mg/day, OR reduce to < 16 mg/day to allow addition of an IR full μOR agonist. Expect higher doses of full μOR agonists requiring close monitoring (e.g., ICU or step-down unit).
- Examples of minimal pain procedures: tooth extraction, endoscopy, colonoscopy, bronchoscopy.
- Examples of moderate/severe pain procedures: laparoscopic, intra-abdominal, intra-thoracic, and orthopedic procedures.
Emergent Procedure Management Criteria- Anticipated minimal to no pain: Continue buprenorphine throughout procedure with non-opioid medications. Dose may be increased until adequate pain relief is achieved. Taper off short-acting opioids prior to discharge.
- Anticipated moderate to severe pain (Continue method): Continue buprenorphine throughout operation; increase dose postoperatively (except implant or BUP XR INJ) or use short-acting opioids. Taper off short-acting opioids prior to or shortly after discharge.
- Anticipated moderate to severe pain (Discontinue method): Discontinue per specified discontinuation criteria.
Discontinuation Criteria & Management- Discontinuation is indicated only when: patient requests to stop (after discussing pros/cons with provider and OUD team); medical contraindication exists; or all other options (maximizing dose, splitting dose, multimodal therapy) are insufficient.
- Emergency procedures: Discontinue immediately upon admission in lieu of high-dose short-acting μOR agonist.
- Elective procedures: Discontinue 24-72 hours prior to surgery. Restart after resolution of acute postoperative pain.
- Monitor respiratory function when using high doses of full μOR agonists as buprenorphine clears; adjust doses to prevent opioid-induced respiratory depression (OIRD).
- Use short-acting full opioid agonists to mitigate withdrawal symptoms. Non-opioid adjuncts for withdrawal (alpha-2 receptor agonists, loperamide, ondansetron, diphenhydramine) may be used as appropriate.
Restarting Buprenorphine Criteria- Taper off short-acting opioid and convert back to previous buprenorphine dose in consultation with waivered provider/OUD team.
- Restart when initial withdrawal signs are observed (for clinic induction) or by patient (for home induction).
- Initial dosing: 2 mg or 4 mg. If withdrawal is alleviated, restart remaining prior maintenance dose on day 1.
- Re-induction protocol: Start when clear signs of opioid withdrawal are present. Begin with 2-4 mg dose or 2/0.5 to 4/1 mg buprenorphine/naloxone. After approximately 2 hours, administer additional 2-4 mg if continued withdrawal and lack of sedation.
- FDA label maximum: 8 mg on Day 1 and 16 mg on Day 2. Document clinical rationale for dosing outside FDA recommendations. Individualize dosing; some patients stabilize on lower doses.
Indications & Pharmacological Properties- Approved for management of pain severe enough to require around-the-clock, long-term opioid treatment.
- Functions as a partial agonist at mu-opioid receptors (MORs) and antagonist at kappa-opioid receptors (KORs).
- Exhibits high binding affinity toward MORs with an extremely slow dissociation rate, making it difficult to displace from receptors once bound.
Perioperative Management- Maximize all other non-opioid and non-pharmacological interventions for pain control.
- When a full MOR agonist is clinically necessary, utilize opioids with similar lipophilicity and binding affinity toward MORs (e.g., fentanyl, sufentanil, hydromorphone) to more effectively compete with buprenorphine.
- Consult waivered providers or an interdisciplinary team experienced with buprenorphine use when available.
- Communicate treatment plans directly with the buprenorphine prescriber to facilitate optimal transition of care postoperatively.
Discharge Planning & Continuity of Care- Schedule patients with their SUD provider or chronic pain provider after discharge for close follow-up.
- Provide a warm hand-off for continued buprenorphine adherence upon discharge, particularly for high-risk patients.
- Discharge patients with an adequate supply of buprenorphine to last until their next scheduled follow-up appointment.
Naloxone Education & Counseling- Evaluate the necessity of naloxone based on the specific indication for buprenorphine prescription.
- For buprenorphine buccal film prescribed for chronic pain without a history of OUD or other SUD and with minimal risk for abusing other opioids, naloxone may not be required unless immediate-release (IR) opioids are initiated postoperatively with plans to discharge on them.
- Conduct overdose education during hospitalization and prescribe naloxone at discharge for patients considered at risk for opioid overdose.
- Provide explicit instruction to patients on how to use the prescribed naloxone product.
Safety Screening- Assess all patients for suicidal ideation prior to discharge per VA strategy and facility protocol.
- Recognize that chronic pain, history of or active SUD/OUD, acute stresses to health, and behavioral health comorbidities (e.g., depression, anxiety, PTSD) significantly heighten suicide risk.
Patient Identification & Surgical Classification- Surgical team/PreOP Clinic identifies patient on buprenorphine (Butrans®, Suboxone®, Subutex®, Zubsolv®, Belbuca® , Temgesic® , Sublocade ® , Buprenex®)
- Classify surgery as minimally painful or painful
Minimally Painful Surgery Criteria- NO or minimal need for postop opioid therapy expected (e.g., endoscopy, cataracts)
- Continue home dose through procedure day and after discharge
- Avoid discontinuation or holding of buprenorphine doses
Painful Surgery & Dose Stratification- High-dose patients: > 16 mg/day Suboxone/Subutex, > 11.4 mg/day Zubsolv
- Low-dose patients: < 16 mg/day Suboxone/Subutex, < 11.4 mg/day Zubsolv, Transdermal Buprenorphine (Butrans Patch) or Buccal Film (Belbuca), ANY DOSE
- No preoperative dose adjustment required for specified doses
Pre-operative Management- Elective surgery: Contact buprenorphine prescriber to discuss dose continuation or gradual dose reduction in anticipation of elective surgery
- Pre-operative dose adjustment not possible: Schedule PreOP Clinic appointment within 2-4 weeks, not later than one week before surgery
- Management options: Continue BUP method (preferred) or Discontinue BUP method
- Anticipate need for high doses of opioids for better pain coverage, or dose reduction to <16 mg/day Suboxone/Subutex, <11.4mg/day Zubsolv by time of surgery
- Update and record prescriber name and contact information in PreOP Clinic
- Consult acute pain service IF expected inpatient stay
Day of Surgery / Intraoperative Management- Perioperative plan per OR Anesthesia team / Acute Pain Team (if available)
- Use non-opioid analgesics (gabapentin, pregabalin, acetaminophen, NSAIDS) pre-operatively if not contraindicated
- Use continuous regional anesthesia techniques if possible (epidural and peripheral nerve catheters)
- Use IV ketamine, lidocaine intra-operatively if not contraindicated
Postoperative Management- Pain Service will follow patients postoperatively if needed; pain management plan per Pain Service recommendations
- Maintenance or placement of axial or peripheral nerve catheters, or short-term nerve blocks as necessary
- Focus on non-opioid medication (gabapentinoids, acetaminophen, NSAIDs, antidepressants, α2 agonists etc.)
- Use full agonist opioid with high binding affinity (hydromorphone, fentanyl, or sufentanil) orally, IV, or by PCA
- Avoid use of long-acting opioids
- Continuation of buprenorphine at home dose, lower dose, or higher dose
- Consider Ketamine infusion protocol (1-5mcg/kg/min infusion) if applicable
- Use Non-medication/non-procedural adjuncts (acupuncture, pet therapy, PT and mechanical supports as appropriate)
Re-induction Planning- Re-induction planning should not be necessary if patients continued to take buprenorphine during hospital stay or were on buprenorphine formulations for pain management (transdermal patch or buccal film)
- If buprenorphine was discontinued, pain service attending decides, in collaboration with buprenorphine prescriber or X-waivered provider, which re-induction strategy is appropriate
Indications & Clinical Appropriateness- FDA-approved for management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period of time.
- Appropriate when there is lack of progress towards functional goals and/or inadequate analgesic benefit with full mu agonist opioid.
- Appropriate when high potential for adverse effects exists due to medical conditions, mental health, or behavioral considerations with full mu agonist LTOT.
- Preferred for patients assessed as high risk for traditional oral opioid therapy where alternate buprenorphine products are not advisable, or for patients with documented difficulty swallowing/poor or unpredictable gastrointestinal absorption.
- More appropriate than transdermal patch for moderate MEDD dosing conversions (50-90 MEDD).
Contraindications & Inappropriateness- Infrequent use of immediate-release opioid medication for episodic pain (e.g., PRN).
- Demonstrating functional improvement and expressing preference to remain on full agonist LTOT, in absence of medical, mental health, or behavioral risk for adverse effects.
- May not provide adequate analgesia for patients requiring greater than 160 mg oral morphine equivalent daily dose (MEDD); consider alternate analgesic.
- Not indicated as an as-needed (PRN) analgesic.
Dosing & Administration Guidelines- Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
- For opioid-naïve/non-tolerant patients: Initiate with 75 mcg film once daily or, if tolerated, every 12 hours for at least 4 days, then increase to 150 mcg every 12 hours.
- Titrate in increments of 150 mcg every 12 hours, no more frequently than every 4 days, to achieve adequate analgesia while minimizing adverse reactions.
- Initial dosing based on prior opioid expressed as oral MEDD: <30 mg MEDD (75 mcg qd or q12h), 30-89 mg MEDD (150 mcg q12h), 90-160 mg MEDD (300 mcg q12h).
- Discontinue all other around-the-clock opioid drugs when BUP BF therapy is initiated.
- For oral buccal use only; apply to the buccal mucosa every 12 hours.
- Wait at least one hour after taking before brushing teeth; swish gently and swallow after dissolution.
- Do not apply to areas of the mouth with open sores or lesions.
- Do not use if pouch seal is broken or film is cut/damaged.
Initiation & Transition Strategies- Follow FDA-approved labeling for new starts and standard opioid transitions.
- STOP-START method: Stop full agonist opioids for 12-24 hours and start buprenorphine in early stages of withdrawal to decrease risk of precipitated withdrawal.
- Low dose buprenorphine initiation (microdosing/overlapping dosing): Allows short-term overlap of buprenorphine titration while on full agonist to mitigate withdrawal and discomfort.
- Published conversion recommendations are highly conservative (reduced 50-75%) and already include reduction for lack of tolerance or cross-tolerance.
- Avoid rapid titrations without assessing effectiveness and tolerability at steady state; due to long half-life, takes about five days to achieve steady state.
Monitoring, Evaluation & Safety Considerations- LTOT principles should be followed: focus on functional improvement in physical, social, and psychological domains consistent with the biopsychosocial model of care.
- Assess risks versus benefits periodically; tapering or discontinuing should be considered when risks outweigh benefits or based on patient preference.
- Screen for and assess risk for OUD prior to initiation and when patterns of unhealthy medication use emerge during LTOT.
- Baseline evaluation includes: Urine drug screen (UDS), PDMP check, liver transaminases, monitor for effectiveness of pain relief/prevention of withdrawal symptoms, assess risk for physical/psychological dependence, drug diversion, sensitivity to adverse effects (particularly respiratory depression), assess mental status/respiratory status/increased risk for falls.
- Pain Management Teams (PMT) should be available for specialty care support during initiation/stabilization and transitions.
- Shared decision-making and veteran preference should guide treatment approach.
- For patients without diagnosed OUD, the encounter should indicate the pain condition diagnosis and the prescription should state “for pain management”.
Patient Counseling & Special Instructions- Caution with driving or operating heavy machinery.
- Store in secure place out of reach of children.
- Advise patients to avoid eating or drinking until film dissolves.
- Inform dentist that therapy has been started; wait at least one hour after taking before brushing teeth.
Indications- Acute pain
- Intractable pain
- Pain expected to be severe enough to require opioid management
Patient Selection (Appropriate)- Veterans who may be appropriate for a usual formulary opioid (e.g., fentanyl, hydromorphone, oxycodone, morphine) for acute pain management
- Veterans with known risk factors for hospital Opioid Related Adverse Events (ORADES)
- Veterans already on a buprenorphine pain formulation as an outpatient (e.g., buccal or transdermal)
- Veterans with impaired renal function (dose adjustment not required)
- Veterans who are opioid naïve with other medical risks (e.g., COPD, advanced age)
- Veterans at high risk for opioid dependence (e.g., co-occurring chronic pain syndromes)
- Patients more sensitive to the GI side effects of opioids and surgical procedures
Patient Selection (Inappropriate/Not Recommended)- Pain not severe enough (or expected to be severe enough) to require opioid therapy
- Patients already on high-dose opioid therapy (prescribed or illicit) or long-acting opioid antagonist treatment (e.g., Vivitrol) due to unknown exact role of pain formulations at this time
Contraindications & Precautions- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting
- Known or suspected GI obstruction including paralytic ileus
- Hypersensitivity to buprenorphine
- Additive risk with concomitant CNS depressants (similar to other full-agonist opioids)
Dosing & Administration Criteria- Pre/Peri-operative and PACU: 0.3 mg slow IV (over 2 minutes) pre-op; repeat 0.3 mg slow IV during PACU recovery PRN, may repeat x1 additional dose at 30 minutes if necessary
- PACU to Ward: If IV effective, consider continuing transmucosal formulation (e.g., Belbuca 300 to 450 mcg BID) scheduled for duration of admission; dose adjust based on observed patient response
- Discharge Home: If effective and additional discharge opioids indicated, consider continuing buprenorphine buccal 2-3 times daily PRN for expected post-surgical duration; select outpatient dose based on observed effective minimum dose during inpatient episode
- Emergency Department: Primarily transmucosal; specific use guidance outside scope but studied in renal colic and fractures
- Patients on milligram doses of buprenorphine (8-32 mg/day or LAI): Should NOT be stopped for acute pain management where FAO may be used; continue at maintenance dose and add non-opioid/high-potency FAO as needed. Dose reduction (25-50%) may be considered to allow mu-opioid receptors to “open up” in 12-24 hours, but requires close monitoring due to increased risk of overdose/withdrawals
Clinical Management & Pearls- Tapering and discontinuing buprenorphine for acute pain should not be needed; self-tapers due to long half-life. Advise patients to stop if pain is well managed with non-opioid only
- Onset of action: within 20 minutes (faster with parenteral); full effect of transmucosal products may take 1-3 hours
- Buccal formulation benefits from mucoadherence; requires no patient participation; can be administered under anesthesia; dry buccal mucosa can be moistened with a gloved finger prior to application; yellow side goes on cheek; do not eat or drink while dissolving; rinse mouth after complete dissolution
- If buprenorphine is ineffective/insufficient: may indicate opioid refractoriness; optimize non-opioid strategies and use high-potency full-agonist opioids (FAO); conventional FAO expected to be fully effective even if microgram doses prove ineffective
- Precipitated withdrawal: Microgram dosing for acute pain would not be expected to result in precipitated withdrawal; incidence <5% even when transitioning from high-dose full-agonists
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ANIFROLUMAB-FNIA INJ,SOLN
SAPHNELO
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SAPHNELO |
2021-08-13 |
Indication & Patient Population- Treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy.
- Not recommended in patients with severe active lupus nephritis or severe active central nervous system lupus due to lack of evaluated efficacy in these situations.
Dosage & Administration- 300 mg IV every 4 weeks.
- Available as injection: 300 mg/2 mL (150 mg/mL) in a single-dose vial.
Contraindications & Warnings/Precautions- Contraindicated in patients with a history of anaphylaxis to anifrolumab-fnia.
- Serious infections, including disseminated herpes zoster.
- Hypersensitivity reactions, including anaphylaxis and infusion-related reactions; consider premedication before infusions for patients with a history of these reactions.
- Malignancy risk is unknown; immunosuppressants increase the risk of malignancies.
- Not recommended for concomitant use with other biologic therapies.
Monitoring & Safety Requirements- Update immunizations prior to initiating therapy; avoid live or live attenuated vaccines during therapy.
- Consider high suspicion of tuberculosis (TB) and planned monitoring for active and latent TB, particularly in patients from endemic countries and those with high cumulative exposure to glucocorticoids.
- Potential increased risk of herpes zoster when used with immunosuppressive therapies.
- Potential increased risk of pneumonia with concomitant use of glucocorticoids.
- Potential increased risk of fatal infections, nervous system disorders, and chemistry abnormalities (e.g., increased serum glucose and gamma glutamyl transferase).
Place in Therapy & Standard of Care Alignment- Must be used as an adjunct to standard therapy; monotherapy has not been evaluated.
- Standard therapy includes oral glucocorticoids, antimalarials, and/or conventional synthetic immunosuppressants.
- Should not be used concomitantly with cyclophosphamide or other targeted biologic or synthetic immunomodulators.
- Patients should be under the care of a VA or VA Community Care rheumatologist or locally designated SLE expert.
Special Populations (Renal & Hepatic Impairment)- Not cleared renally; no dosage adjustment recommended for renal impairment.
- Clearance not expected to be affected by changes in hepatic function; no dosage adjustment recommended for hepatic impairment.
- Not studied in patients with severe renal impairment, end-stage renal disease (< 30 mL/min/1.73 m2), or urine protein-to-creatinine ratio (UPCR) > 2 mg/mg.
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BELUMOSUDIL TAB
REZUROCK
|
REZUROCK |
2021-08-05 |
Exclusion Criteria- Moderate or severe hepatic impairment (defined as Child-Pugh B or C)
- Unmanageable drug-drug-interaction
- Pregnancy
- Lactating
- Inability to monitor total bilirubin, AST and ALT at least monthly
- Inability to swallow tablets whole with a meal
Inclusion Criteria- Care provided by a VA or VA Community Care hematology provider
- Eastern Cooperative Oncology Group Performance Status 0 - 2
- Diagnosis of chronic graft-versus-host disease (cGVHD) secondary to allogeneic hematopoietic stem cell transplant
- cGVHD disease progression after at least 2 prior lines of systemic therapy
Additional Inclusion Criteria- For patients who can become pregnant: Pregnancy must be excluded prior to receiving belumosudil
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for one week after stopping treatment
Indication & Patient Population- Treatment of chronic graft vs. host disease (cGVHD)
- Patients status post allogeneic hematopoietic stem cell transplant (s/p AlloHCT)
- Persistent cGVHD in heavily pre-treated patients with progressive disease or contraindication to ibrutinib or ruxolitinib
Disease Severity & Classification Criteria- Classified per NIH Consensus Criteria for organ scoring (Score 0-3) versus host disease grading by symptoms, affected organ systems, and extent of disease involvement
- Mild: < 2 affected organs; no clinically significant functional dysfunction
- Moderate: > 3 organs with no dysfunction or > 1 organ with dysfunction but no major disability
- Severe: Major disability
Prior Therapy Requirements- Failure of at least 2 prior lines of therapy (specifically 2-5 prior lines per trial criteria)
- Applicable following prior ibrutinib and prior ruxolitinib therapy
Dosing & Administration- 200 mg tablet
- 200 mg PO once daily with food
- Dose increase to 200 mg twice daily required when coadministered with strong CYP3A inducers or proton pump inhibitors
Contraindications & Precautions- Avoid use in moderate or severe hepatic impairment
- Embryo-fetal toxicity warning
Performance Status & Supportive Care Criteria- Karnofsky Performance Scale (KPS) > 60
- On stable corticosteroid (CS) therapy for at least 2 weeks prior to initiation
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FINERENONE TAB
KERENDIA
|
KERENDIA |
2021-07-26 |
Exclusion Criteria- Concomitant treatment with strong CYP3A4 inhibitors or strong or moderate CYP3A4 inducers
- Adrenal insufficiency
- Serum potassium greater than 5.0 mEq/L
- Condition where another mineralocorticoid receptor antagonist (i.e., spironolactone or eplerenone) would be indicated (e.g., resistant hypertension, heart failure)
- Severe hepatic impairment (Child Pugh class C)
- Lactating
Inclusion Criteria- Type 2 diabetes mellitus
- Chronic kidney disease diagnosis with estimated glomerular filtration rate >= 25 ml/min/1.73m2 AND persistent albuminuria with urinary albumin-to-creatinine ratio>= 30 mg/g
- Receiving treatment containing maximum tolerated labeled dose of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) or unable to use an ACEI or ARB
- Receiving treatment with a sodium-glucose cotransporter-2 (SGLT2) inhibitor or unable to use an SGLT2 inhibitor
- Clinical trial-specific parameters for chronic kidney disease:
- FIDELIO-DKD: Persistent albuminuria (urinary albumin-to-creatinine ratio 30 to < 300 mg/g) with eGFR 25 to < 60 ml/min/1.73m2 and diabetic retinopathy; OR persistent albuminuria (UACR 300 to 5000 mg/g) with eGFR 25 to < 70 ml/min/1.73m2
- FIGARO-DKD: Persistent albuminuria (UACR 30 to < 300 mg/g) with eGFR 25 to 90 ml/min/1.73m2; OR persistent albuminuria (UACR 300 to 5000 mg/g) with eGFR >= 60 ml/min/1.73m2
- Requirement for guideline-directed medical therapy despite ACEI or ARB and SGLT2 inhibitor use
Indication- Reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes.
Dosing & Administration- Available as 10 mg and 20 mg tablets.
- Recommended starting dose is 10 mg or 20 mg orally once daily, taking into consideration eGFR and serum potassium.
- Dose may be increased after 4 weeks to the target dose of 20 mg once daily, based on eGFR and serum potassium thresholds.
Contraindications- Concomitant use with strong CYP3A4 inhibitors.
- Patients with adrenal insufficiency.
Warnings & Precautions- Hyperkalemia: Patients with decreased kidney function and higher baseline potassium levels are at increased risk.
- Do not initiate finerenone if serum potassium is > 5.0 mEq/L.
- Monitor serum potassium levels and adjust dose as needed.
Clinical Guidance / Place in Therapy- Recommended to reduce CKD progression and cardiovascular events in patients with CKD who are at increased risk for cardiovascular disease progression or CKD progression, or who are unable to use an SGLT2 inhibitor.
- Nonsteroidal, selective mineralocorticoid receptor antagonist (MRA).
Indication & Patient Population- Patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≥40% to reduce the risk of cardiovascular (CV) death, HF hospitalization, and urgent HF visits
- Applicable to HFpEF (LVEF ≥50%) and HFmrEF (LVEF 41-49%)
- Trial population criteria: ≥40 years old, symptomatic HF, LVEF ≥40%, structural heart disease, and elevated natriuretic peptides
Initiation Criteria- Required baseline labs prior to initiation: Serum potassium and estimated renal function (eGFR)
- Do not initiate if serum potassium is >5 mEq/L or eGFR <25 mL/min/1.73m2
- Initial dose determined by eGFR at time of initiation: 20 mg once daily if eGFR ≥60; 10 mg once daily if eGFR 25 to <60; not recommended for eGFR <25
Dosing & Adjustments- Dose adjustments made at 4 weeks based on serum potassium level and initial eGFR
- Target dose: 40 mg once daily for patients with initial eGFR ≥60 mL/min/1.73m2; 20 mg once daily for patients with initial eGFR ≥25 to <60 mL/min/1.73m2
Monitoring Requirements- Monitor serum potassium at 4 weeks after starting treatment and periodically thereafter
- Monitor eGFR periodically during treatment
- Dose adjustment may be required based on monitoring results
Contraindications & Warnings- Hypersensitivity to finerenone
- Concomitant use of strong CYP3A4 inhibitors
- Adrenal insufficiency
- Hyperkalemia: Increased risk with worsening renal function, higher baseline potassium levels, or other risk factors; do not initiate if potassium >5 mEq/L
- Worsening renal function: Measure eGFR before initiating and periodically; do not initiate if eGFR <25 mL/min/1.73m2
Formulary & Clinical Considerations- Nonformulary status
- FDA indicated for HF with LVEF ≥40%
- Not yet specifically included in current HF guidelines (guidelines based on spironolactone evidence)
- Primary benefit driven by reduction in HF worsening events; no improvement in CV death, all-cause mortality, or NYHA functional class observed
- Nonsteroidal, selective MRA: Not associated with gynecomastia or menstrual irregularities seen with steroidal MRAs
- No head-to-head comparisons with other MRAs (including spironolactone) for HFpEF/HFmrEF management
Exclusion Criteria- Serum potassium level greater than 5.0 mEq/L
- Estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m
- Severe hepatic impairment (e.g., Child-Pugh class C)
- Concomitant treatment with strong CYP3A4 inhibitors or strong or moderate CYP3A4 inducers
- Adrenal insufficiency
- Lactating
Inclusion Criteria- Diagnosis of symptomatic heart failure with a left ventricular ejection fraction (LVEF) of 40% or greater
- Receiving treatment with a sodium-glucose cotransporter-2 (SGLT2) inhibitor or unable to use an SGLT2 inhibitor
- Intolerance or unable to use spironolactone
Additional Inclusion Criteria- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
- Eplerenone may be considered before finerenone in patients who experience intolerance to spironolactone due to gynecomastia
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SEMAGLUTIDE INJ,SOLN
WEGOVY
|
WEGOVY |
2021-06-17 |
Exclusion Criteria- Known pregnancy
- Lactating
- Type 1 diabetes (exception: may be considered under careful supervision if followed by a diabetes/weight management specialist)
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History of pancreatitis (exception: does not apply when the cause is known and no longer presents a risk)
- Known PDR, severe NPDR, clinically significant ME, or DME unless risks/benefits discussed with patient, documented in EHR with monitoring plans/follow-up with an eye specialist informed at initiation
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention (CLI) targeting diet, physical activity, and behavioral changes
- BMI ≥ 30 kg/m² with at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, metabolic dysfunction-associated steatotic liver disease)
- Indicated to reduce a secondary cardiovascular event in patients with previous myocardial infarction, previous stroke, or symptomatic peripheral arterial disease (defined as intermittent claudication with ankle–brachial index <0.85, peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease) who have overweight or obesity
Additional Inclusion Criteria- For females who can become pregnant: Pregnancy must be excluded prior to receiving semaglutide (WEGOVY); contraceptive counseling on potential risks vs. benefits if pregnancy occurs is required
Indication & Primary Use- Primarily indicated for patients requiring weight management.
- Semaglutide (OZEMPIC) should not be used for weight management alone.
Formulary Status & Preference- Available non-formulary with criteria for use in weight management.
- No preference for semaglutide (WEGOVY) over liraglutide (SAXENDA).
- Conversion from liraglutide (SAXENDA) is not necessary for patients who are doing well and losing weight.
Conversion Criteria: Liraglutide (SAXENDA) to Semaglutide (WEGOVY)- Suggested conversion doses are off-label; selection of a more conservative dose may be considered only if clinically appropriate on a case-by-case basis.
- Conversion dose and/or titration may need adjustment based on tolerability and glucose control in patients with T2DM.
- For patients currently on 3.0 mg daily liraglutide: Initiate 0.5 mg subcutaneous once weekly for 4 weeks, then 1.0 mg subcutaneous once weekly for 4 weeks, then 1.7 mg subcutaneous once weekly for 4 weeks, followed by 2.4 mg subcutaneous once weekly for maintenance.
Conversion Criteria: Semaglutide (OZEMPIC) to Semaglutide (WEGOVY)- For patients currently receiving semaglutide (OZEMPIC) 1.0 mg subcutaneous once weekly for T2DM: Initiate 1.0 mg subcutaneous once weekly for a total of 4 weeks (combining OZEMPIC and/or WEGOVY), then 1.7 mg subcutaneous once weekly for 4 weeks, followed by 2.4 mg subcutaneous once weekly for maintenance.
- For patients receiving semaglutide (OZEMPIC) 2.0 mg subcutaneous once weekly: Consider conversion to 2.4 mg subcutaneous once weekly only if the patient has received the 2.0 mg dose for at least 4 weeks.
- When switching from semaglutide (OZEMPIC) once weekly to semaglutide (WEGOVY) once weekly, administer the first dose of semaglutide (WEGOVY) 7 days after discontinuing semaglutide (OZEMPIC).
Titration & Administration Requirements- All other patients being started on semaglutide (WEGOVY) should be titrated according to the recommended schedule available in the prescribing information.
- Patient education must be provided.
Indications & Eligibility- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance
Indication & Patient Population- Treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3) in adults
- Applicable to overweight or obese patients and lean patients with biopsy-confirmed MASH with stage 2 or 3 liver fibrosis
Dosing & Administration- Initial Dosage: 0.25 mg SC once weekly for 4 weeks
- Escalation (once weekly SC): 0.5 mg on Weeks 5–8, 1 mg on Weeks 9–12, and 1.7 mg on Weeks 13–16
- Maintenance: 2.4 mg from Week 17 onward; if not tolerated, decrease to 1.7 mg once weekly; consider reescalation to 2.4 mg
Pretreatment Requirements- Check baseline glucose in patients with type 2 diabetes (T2D) due to hypoglycemia risk
- Consider dosage reduction of concomitant insulin or insulin secretagogues (e.g., sulfonylureas) prior to initiation
Monitoring & Safety Considerations- Monitor glucose in patients with T2D
- Monitor renal function in patients with adverse reactions (e.g., vomiting, diarrhea) that could lead to volume depletion
- Monitor for diabetic retinopathy complications in patients with history of diabetic retinopathy
- Monitor for increased heart rate
- Monitor for depression or suicidal thoughts
Contraindications & Warnings- Contraindicated in personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Contraindicated in pregnancy; may cause fetal harm. Discontinue at least 2 months before a planned pregnancy
- Lactation: Likely present in human milk; weigh risks vs benefits
- Warnings include: Thyroid C-cell tumors, acute pancreatitis, acute gallbladder disease, hypoglycemia (with insulin/secretagogue), acute kidney injury, severe gastrointestinal adverse reactions, hypersensitivity reactions, diabetic retinopathy complications (in T2D), increased heart rate, suicidal behavior and ideation, pulmonary aspiration during general anesthesia or deep sedation
Lifestyle & Adjunctive Therapy Requirements- Must be used in patients with a documented plan on addressing and monitoring appropriate lifestyle interventions
- Should be combined with a reduced calorie diet and increased physical activity
- Comprehensive lifestyle intervention (CLI) should aim for 5–10% weight loss after six months; treatment should continue until long-term weight loss goals are achieved or modified if short/intermediate-term goals are not met
Exclusion Criteria- Child-Pugh score ≥ 7 (bilirubin adjustable for Gilbert syndrome; score adjusted for patients taking anticoagulants)
- Decompensated liver cirrhosis manifested by complications (noncardiac ascites, variceal hemorrhage, hepatic encephalopathy, spontaneous bacterial peritonitis)
- Most recent assessment showing: FibroScan LSM > 18 kPa or VCTE consistent with cirrhosis; MRE > 5.0 kPa; FIB-4 > 2.67 (unless LSM < 18 kPa); liver biopsy indicating cirrhosis (METAVIR stage F4)
- Hepatocellular carcinoma currently not actively managed by hepatology or multidisciplinary team
- Uncontrolled liver disease associated with condition other than metabolic dysfunction (e.g., biliary obstruction, viral hepatitis, autoimmune hepatitis, hereditary liver disease, drug-induced liver disease)
- Heavy alcohol ingestion > 3 consecutive months within the previous 1 year (≥4 drinks/day for men, ≥3 drinks/day for women; defined by specific volumes/ABV)
- Personal or first-degree family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History or presence of pancreatitis (except when cause is known and no longer presents a risk)
- Type 1 diabetes (unless followed by a diabetes specialist for careful supervision)
- Known PDR, severe NPDR, clinically significant ME, or DME (unless risks/benefits discussed, documented in EHR with monitoring plans, and eye specialist informed at initiation)
- Known pregnancy
- Lactating
Inclusion Criteria- Initiated by a VA/VA Community Care gastroenterologist/hepatologist or locally designated expert
- Documented plan for addressing and monitoring appropriate lifestyle interventions
- Documented plan to change medications that cause or exacerbate steatohepatitis to alternative agents as applicable and clinically appropriate
Diagnostic & Fibrosis Parameters- Overweight/obese patients: Documented MASH with moderate to advanced fibrosis (stage F2 or F3) diagnosed within past 6 months on noninvasive tests OR past 36 months on liver biopsy
- Lean patients with suspected MASH: Documented MASH with moderate to advanced fibrosis (stage F2 or F3) diagnosed on liver biopsy within past 36 months (exclude non-MASH diagnoses)
- Noninvasive test thresholds for MASH F2–F3: ELF score 9.2–10.5; LSM 8.0–18.0 kPa; MRE 3.1–4.4 kPa
- Weight loss targets: Slow rate (5% within 6 months, cumulative ≥10% within 18 months); ≥5% improves hepatic steatosis, ≥7% improves liver inflammation/resolves MASH, ≥10% improves/stabilizes hepatic fibrosis; lean MASLD may improve histology with 3%–5% weight loss
- FIB-4 should be used with caution in patients >65 years due to lower reliability
Specialist Initiation & Monitoring Requirements- Patients on semaglutide for MASH only must be initiated by a VA/VA Community Care gastroenterologist/hepatologist OR a locally designated expert in MASH management
- Diabetic eye exam results required on file within past 12 months (or 24 months if no evidence of retinopathy); planned follow-up with eye provider for history of diabetic retinopathy; ophthalmology consult obtained for any concerns related to use
Pregnancy & Lactation Counseling- Females who can become pregnant: Pregnancy must be excluded prior to receiving semaglutide; patient counseled on contraceptives and risks/benefits if pregnancy occurs
- Females breastfeeding/providing breastmilk: Counseling provided on potential risks vs benefits of treatment
Other- Other justification field available for clinical documentation
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ESTRADIOL/ NORETHINDRONE/ RELUGOLIX TAB
MYFEMBREE
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MYFEMBREE |
2021-06-10 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
Indication & Patient Population- Diagnosis of endometriosis (clinical or surgical) in a premenopausal patient
- Prescribed by or in consultation with a VA/VA Community Care Gynecology or Women’s Health Provider
Exclusion Criteria- High risk or history of arterial, venous thrombotic, or thromboembolic disorder
- Pregnancy
- Known osteoporosis
- Uncontrolled hypertension
- Current or history of breast cancer or other hormonally sensitive malignancies
- Known hepatic impairment or disease
- Undiagnosed abnormal uterine bleeding
- Concomitant use of hormonal contraceptives
- Concomitant use of P-glycoprotein (P-gp) inhibitors
- Concomitant use of combined P-gp and strong CYP3A inducers
- Any additional contraindication to receiving estrogen and/or progestin
- Known hypersensitivity to relugolix, estradiol, or norethindrone
Inclusion Criteria- Contraindication, intolerance, or inadequate response to one alternative treatment (e.g., NSAID, estrogen-containing or progestin-only hormonal contraceptive)
- Assessed for history of suicidal ideation, depression, and mood disorders prior to starting treatment
- Assessed for risk of bone density loss
- Planned duration of treatment not to exceed a maximum of 24 months (due to risk for bone loss)
Additional Patient-Specific Requirements- For patients who can become pregnant: Exclude pregnancy prior to receiving medication
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective nonhormonal contraception during therapy
Monitoring & Safety Requirements- Monitor for mood changes and depressive symptoms after starting treatment
- Baseline DXA (dual-energy X-ray absorptiometry) and periodic follow-up during treatment recommended
- Consider risks and benefits of treatment in patients with history of low trauma fracture or risk factors for low bone density
- If concomitant use of P-gp inhibitors is unavoidable, take the interacting medication at least 6 hours after relugolix
Indication- Heavy Menstrual Bleeding Associated with Uterine Leiomyomas (Fibroids)
Exclusion Criteria- High risk or history of arterial, venous thrombotic, or thromboembolic disorder
- Pregnancy
- Known osteoporosis
- Uncontrolled hypertension
- Current or history of breast cancer or other hormonally sensitive malignancies
- Known hepatic impairment or disease
- Undiagnosed abnormal uterine bleeding
- Concomitant use of hormonal contraceptives
- Concomitant use of P-glycoprotein (P-gp) inhibitors
- Concomitant use of combined P-gp and strong CYP3A inducers
- Any additional contraindication to receiving estrogen and/or progestin
- Known hypersensitivity to relugolix, estradiol, or norethindrone
Inclusion Criteria- Prescribed by or in consultation with a VA/VA Community Care Gynecology or Women’s Health Provider
- Confirmed diagnosis of uterine leiomyoma and heavy menstrual bleeding in a premenopausal patient
- Contraindication, intolerance, or inadequate response to one alternative treatment (e.g., estrogen-progestin hormonal contraceptives, progestin-only contraceptives, tranexamic acid, etc.)
Monitoring & Duration Requirements- Assessed for history of suicidal ideation, depression, and mood disorders prior to starting treatment
- Assessed for risk of bone density loss
- Planned duration of treatment not to exceed a maximum of 24 months (due to risk for bone loss)
- Baseline DXA (dual-energy X-ray absorptiometry) and periodic follow-up during treatment recommended; consider risks and benefits in patients with history of low trauma fracture or risk factors for low bone density
- Monitor for mood changes and depressive symptoms after starting treatment
Counseling & Safety Precautions- For patients who can become pregnant: Exclude pregnancy prior to receiving REN
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective nonhormonal contraception during therapy
- If concomitant P-gp inhibitor use is unavoidable, take the interacting medication at least 6 hours after REN
Indications- Management of heavy menstrual bleeding (HMB) associated with uterine leiomyomas (fibroids) in premenopausal women
- Management of moderate to severe pain associated with endometriosis in premenopausal women
Dosing & Administration- Fixed-dose combination oral tablet containing 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate
- One tablet orally daily at the same time each day
- Initiate as soon as possible and within 7 days after the start of menses
- Treatment duration limited to 24 months due to risk of bone loss that may not be reversible
Contraindications- Pregnancy
- Known osteoporosis
- Known hepatic impairment or hepatic disease
- High risk of arterial, venous thrombotic, or thromboembolic disorder
- Current or history of breast cancer or other hormone-sensitive malignancies
- Undiagnosed abnormal uterine bleeding
- Known hypersensitivity to ingredients
- Uncontrolled hypertension
Monitoring & Precautions- Exclude pregnancy prior to starting treatment; discontinue hormonal contraceptives before initiation
- Perform pregnancy testing during treatment if pregnancy is suspected; discontinue if confirmed
- Advise use of effective non-hormonal contraception during treatment and for one week after discontinuation
- Avoid concomitant use of estrogen-containing hormonal contraceptives
- Baseline assessment of bone mineral density (BMD) by DXA recommended; follow-up DXA annually during treatment for endometriosis and periodically during treatment for fibroids
- Monitor blood pressure; contraindicated in uncontrolled hypertension, monitor in patients with controlled hypertension
- Evaluate patients with history of mood disorders and/or suicidal ideation before initiating; monitor for mood changes and depressive symptoms after initiation
- Advise women with submucosal uterine fibroids about possible prolapse or expulsion; seek medical attention for severe bleeding or cramping
- Consider discontinuation if hair loss (alopecia) becomes a concern
- Monitor for risk of early pregnancy loss, vasomotor symptoms (hot flushes), mood disorders including depression and suicidal ideation, hypertension, abdominal pain, decreased libido, abnormal uterine bleeding, nausea, and hypersensitivity reactions (anaphylactoid reactions, urticaria, angioedema)
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SOTORASIB TAB
LUMAKRAS
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LUMAKRAS |
2021-06-10 |
Exclusion Criteria- Strong CYP 3A4 Inducers
- Proton Pump Inhibitors or H2 receptor antagonist (exception: if acid-reducing therapy is required, administer sotorasib 4 hours before or 10 hours after a local antacid)
- Inability to manage CYP3A4 or P-gp substrates
- Estimated Creatinine Clearance <30 mL/min
- Moderate or Severe Hepatic Insufficiency (AST or ALT ≥2.5 X ULN [≥5 x ULN for liver metastases] or total bilirubin ≥1.5 X ULN [≥2.0 X ULN for Gilbert’s syndrome])
- Untreated brain metastases
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult discussed and documented
- Patients of child-bearing potential or with partners of child-bearing potential: counseling on contraception and risks vs. benefits provided; effective contraception used and breastfeeding avoided during therapy and for 1 week after the last dose
Additional Inclusion Criteria- KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer who have received at least 1 prior systemic therapy
- Monitor LFTs every 3 weeks for the first 3 months then monthly as indicated
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AMIVANTAMAB-VMJW INJ,SOLN
RYBREVANT
|
RYBREVANT |
2021-06-03 |
Exclusion Criteria- Active or untreated brain metastases
- Unable to tolerate pre-medications (acetaminophen + diphenhydramine + dexamethasone or methylprednisolone)
- Pregnancy or lactating status
Inclusion Criteria- Locally advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 20 insertion mutation whose disease progressed on or after platinum-based chemotherapy
- In combination with carboplatin and pemetrexed for first-line therapy of locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutation
- In combination with Lazertinib for first-line therapy of locally advanced or metastatic non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858R substitution mutations (Give anticoagulant prophylaxis to prevent VTE during first 4 months of combination with lazertinib)
- In combination with carboplatin and pemetrexed for locally advanced or metastatic non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858R substitution mutations in patients who progressed on or after an EGFR TKI
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 3 months after stopping treatment
- Screened for Hepatitis B and Hepatitis C and managed appropriately by provider as needed including a risk/benefit discussion
- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Indication & Patient Population- • Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)
- • Must have epidermal growth factor receptor (EGFR) exon 20 insertion mutations
- • Mutation must be detected by an FDA-approved test
- • Disease must have progressed on or after platinum-based chemotherapy
Dosing & Administration Criteria- • Weight-based dosing: Under 80 kg = 1050 mg; ≥80 kg = 1400 mg
- • Dosing schedule: Weekly for 4 weeks (split Week 1 into 2 doses on Day 1 and Day 2), then every 2 weeks
- • Infusion rates are weight- and week-dependent (e.g., Week 1 Day 1 initial rate 50 mL/hr, subsequent 75 mL/hr; Week 3+ up to 125 mL/hr)
Premedication Requirements- • Acetaminophen 650 mg or 1000 mg prior to each dose
- • Diphenhydramine 25-50 mg IV or oral prior to each dose
- • Dexamethasone 10 mg or Methylprednisolone 40 mg required for initial doses (Week 1 Days 1 and 2); optional for subsequent doses
Safety Monitoring & Precautions- • Infusion-related reactions: Most common during Week 1 Day 1 and 2; premedication required; incidence lessens over time
- • Interstitial Lung Disease/Pneumonitis: Monitor (incidence 3.3%, Grade 3-4 at 0.7%)
- • Dermatologic Adverse Reactions: Rash/pruritus/dry skin in 74% (Grade 3 rash 3.3%); recommend avoiding sun exposure for 2 months, wearing protective clothing, and using UVA/UVB sunscreen daily
- • Ocular toxicity: Monitor for keratitis, uveitis, dry eye, conjunctival redness, blurred vision, visual impairment (primarily Grades 1-2)
- • Embryo-fetal toxicity warning present
Contraindications & Exclusions- • Contraindications: None stated
- • Trial exclusions (clinical context): Untreated brain metastases; clinically significant cardiovascular disease; pregnancy/breastfeeding/planning pregnancy; positive Hepatitis B surface antigen or Hepatitis C antibody; HIV positive; clinically active liver disease; interstitial lung disease
Line of Therapy / Place in Treatment- • Second-line therapy for NSCLC following progression on first-line chemotherapy
- • Alternative second-line options include mobocertinib; docetaxel is reserved for after progression on amivantamab or mobocertinib
Geriatric Use- • No important differences in efficacy or toxicity between patients ≥65 years old and younger patients
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PEGCETACOPLAN INJ,SOLN
EMPAVELI, SYFOVRE
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EMPAVELI, SYFOVRE |
2021-05-28 |
Indication- Paroxysmal nocturnal hemoglobinuria (PNH)
Dosage & Administration- 1080 mg by subcutaneous infusion twice weekly
- Infusion duration: 30 minutes if using two infusion sides, or 60 minutes if using one infusion site
- Patient can self-administer
- Obtained via specialty pharmacy
REMS Requirements- Empaveli REMS program required for both prescribers and pharmacies
- Prescribers must enroll in the REMS program
- Providers must counsel patients on the risk of serious infection
- Providers must provide patients with REMS educational materials
- Patients must be vaccinated against encapsulated bacteria (Streptococcus pneumoniae, Neisseria meningitidis, Hemophilus influenzae) prior to initiation
- Vaccination should occur at least 2 weeks before the first dose
- Pharmacies must be REMS registered and submit daily data files to the REMS coordinator; use of the program’s specialty pharmacy is recommended due to administrative requirements
Contraindications & Warnings/Precautions- Hypersensitivity to pegcetacoplan or any component of the formulation
- Patients not currently vaccinated against encapsulated bacteria (unless risks of delaying treatment outweigh the risk of infection)
- Unresolved infection caused by encapsulated bacteria
- Boxed warning for serious infections caused by encapsulated bacteria; adhere to ACIP recommendations for vaccinations in people with complement deficiencies
- Live vaccines should not be administered
- Consider restarting pegcetacoplan treatment if signs of hemolysis occur after discontinuation
- Avoid breastfeeding during treatment and up to 40 days after the last dose
Place in Therapy/Clinical Guidance- Complement C3 inhibitor indicated for the treatment of PNH
- May be reasonable to consider in patients refractory to a complement C5 inhibitor, including those experiencing breakthrough hemolysis
- European Medical Association approved for patients who remain anemic after at least three months of complement C5 inhibitor therapy
Exclusion Criteria- Geographic atrophy that is secondary to a condition other than age-related macular degeneration
- Ocular or periocular infections
- Active intraocular inflammation
Inclusion Criteria- Provider is a VA or VA Community Care ophthalmologist
- Diagnosis of geographic atrophy secondary to age-related macular degeneration
Pregnancy & Reproductive Considerations- Pregnancy should be excluded prior to receiving pegcetacoplan
- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 40 days after stopping treatment
Monitoring & Management- Monitor for signs of neovascular AMD due to increased rates associated with clinical trial use
- If anti-VEGF is required, administer separately from pegcetacoplan administration
Indication- Treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)
- Specifically indicated for dry AMD (advanced late stage)
Dosage & Administration- Intravitreal injection of 15 mg (0.1 mL of 150 mg/mL solution) to each affected eye
- Dosing interval: Once every 25 to 60 days
Contraindications- Ocular or periocular infection
- Active intraocular inflammation
Warnings & Precautions- Neovascular AMD: Associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (CNV); monitor for signs. If anti-VEGF therapy is required, administer separately from pegcetacoplan.
- Retinal vasculitis: Post-marketing reports of occlusive and non-occlusive retinal vasculitis following injection; associated with intraocular inflammation. Discontinue use of 19-gauge filter needles; utilize kits containing 18-gauge needles.
- Endophthalmitis and retinal detachments
- Intraocular inflammation
- Increased intraocular pressure
Patient Population & Special Considerations- Women of childbearing potential: Use effective contraception during treatment and for 40 days after the last dose. Assess risks and benefits for women planning pregnancy.
- Patients with a history of choroidal neovascularization (CNV) in the fellow eye have a greater risk of developing exudative AMD.
Formulary Use Restrictions- Use should be restricted to the treatment of GA secondary to AMD when no contraindications are present.
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Inclusion Criteria- Prescribed by a REMS registered VA or VA Community Care hematologist, oncologist, immunologist or genetic specialist
- Laboratory-confirmed diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH), as evidenced by detectable GPI-deficient hematopoietic clones (Type III PNH red blood cells (RBC)) via Flow Cytometry
- Evidence of clinically significant hemolysis (e.g., Hemoglobin <10g/dL) despite 6 months of stable therapy with anti-C5 inhibitor (e.g., ravulizumab or eculizumab)
- Complete or update vaccination for encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis at least 2 weeks prior to the first dose of therapy according to current Advisory Committee on Immunization Practices (ACIP)
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VILOXAZINE CAP,SPRINKLE,SA
QELBREE
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QELBREE |
2021-05-26 |
Indications- Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older.
Dosing & Administration- Extended-release capsules available in 100 mg, 150 mg, and 200 mg strengths.
- Initial dosing: 200 mg once daily for week 1.
- Titration: Increase to 400 mg once daily during week 2.
- Maintenance titration: Adjust by 200 mg per day once weekly to a minimum of 200 mg once daily and maximum of 600 mg once daily.
Contraindications- Concomitant treatment with MAOIs or within 14 days following discontinuation of an MAOI.
- Concomitant use with sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range.
Warnings & Precautions- Boxed warning for suicidal thoughts and behaviors (observed in 0.9% of pediatric patients vs 0.4% placebo; 1.6% of adults vs 0% placebo).
- Blood pressure and heart rate increases.
- Activation of mania or hypomania.
- Somnolence and fatigue.
- Pregnancy: May cause maternal harm; discontinue when pregnancy is recognized.
Formulary Status & Clinical Guidance- Non-formulary (NF) status for ADHD in adults and pediatric patients 6 years and older.
- Recommended as a second-line non-stimulant option for patients unable to tolerate or not good candidates for stimulant therapy.
- Does not appear to provide advantages over other nonstimulants (e.g., atomoxetine).
- Not addressed in current clinical guidelines due to availability timing.
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BUPRENORPHINE INJ,SOLN,SA
BRIXADI, SUBLOCADE
|
BRIXADI, SUBLOCADE |
2021-05-24 |
Indications- Treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of transmucosal buprenorphine product or who are already being treated with buprenorphine.
Dosage Forms & Dosing- Weekly: 8mg, 16mg, 24mg, and 32mg doses.
- Monthly: 64mg, 96mg, and 128mg doses.
- Weekly and monthly dosage forms are NOT interchangeable.
Contraindications- Hypersensitivity (e.g., anaphylactic shock) to buprenorphine or any other ingredients in the solution for injection.
Warnings & Precautions- Risk of serious harm or death with intravenous administration; forms a liquid crystalline gel upon contact with bodily fluids and may cause occlusion, local tissue damage, and thrombo-embolic events, including life-threatening pulmonary emboli.
- May precipitate opioid withdrawal in patients physically dependent on full-agonist opioids.
- Administer a transmucosal test-dose (e.g., 4 milligram SL buprenorphine or buprenorphine/naloxone) before administering BRIXADI.
- Needle cap is synthetically derived from natural rubber latex, which may cause allergic reactions in latex-sensitive individuals.
- Consider co-prescribing naloxone for the emergency treatment of opioid overdose based on the patient’s risk factors for overdose.
Safety & Adverse Reactions- Common treatment-emergent adverse events (TEAEs) include injection site reactions (mild to moderate severity), constipation, nausea, headache, and insomnia (>5%).
- Non-injection TEAEs occurring in >5% include headache (7.9%), nasopharyngitis (7.9%), nausea (7%), vomiting (5.3%), and urinary tract infection.
- TEAEs leading to discontinuation are rare (~2.2–2.5%).
Clinical Efficacy & Place in Therapy- Provides similar clinical benefit to sublingual buprenorphine/naloxone for moderate-to-severe opioid use disorder.
- May have benefit in patients at higher risk (e.g., history of overdose) or at risk of non-adherence.
- Cost is similar to market competitor (SUBLOCADE).
- Stored at room temperature, offers multiple sites for subcutaneous injection, and provides more dose flexibility vs. market competitor.
REMS & Administration Requirements- Only available via the BRIXADI REMS program; healthcare settings and pharmacies must be certified in this program.
- Must never be dispensed directly to a patient and must only be administered by a healthcare professional in a healthcare setting.
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RISANKIZUMAB-RZAA INJ,SOLN
SKYRIZI, SKYRIZI ON-BODY, SKYRIZI PEN
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SKYRIZI, SKYRIZI ON-BODY, SKYRIZI PEN |
2021-05-20 |
Exclusion Criteria- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (risankizumab-rzaa may be started/restarted once infection treatment has been initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients can be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless the prescriber documents that potential benefits outweigh risks
Inclusion Criteria (General & Screening)- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally designated expert
- Current or prior moderate to severe Crohn’s disease confirmed by endoscopy or imaging
- Completed tuberculosis test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Obtained pretreatment liver enzymes and bilirubin levels
Additional Inclusion Criteria (Therapeutic History & Sequencing)- ONE of the following must be met:
- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar and adalimumab are preferred TNFIs in Crohn’s disease)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of TNFI therapy in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to infliximab/biosimilar and another TNFI for Crohn’s disease despite therapeutic drug monitoring-based optimized dosing to address pharmacokinetic failure
- Drug Sequencing: First-line is Infliximab or adalimumab; Second/Third-line includes vedolizumab, upadacitinib, or risankizumab-rzaa (one drug should be risankizumab-rzaa as 2L or 3L drug); Fourth-line is mirikizumab-mrkz or ustekinumab
Special Populations & Expert Consultation- If HBsAg-negative but anti-HBc-positive, GI/liver or infectious diseases expert consulted for advice on whether to start antiviral prophylaxis or preemptively monitor for hepatitis B virus reactivation
- For women who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 5 months after stopping treatment
Monitoring & Re-testing Guidelines- Routine retesting for tuberculosis, hepatitis B, and hepatitis C screening is not required for prescription renewals; retesting in high-risk patients should be considered
- Anti-HBs titers ≥10 IU/L are generally considered protective and may help identify need for initial/booster vaccination or occult hepatitis B virus
- Infliximab may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in a first-degree relative, lupus, recurrent infections, or serious infections
Exclusion Criteria- Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection or at high risk for HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Inclusion Criteria- Prescribed and monitored by a VA / VA Community Care rheumatologist, dermatologist, or locally designated psoriasis expert
- Prescribed at the FDA-approved dose for psoriatic arthritis
- Inflammatory articular disease (joint, spine, and/or entheseal) with a definite or provisional diagnosis of psoriatic arthritis
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)
- ONE interleukin-17A inhibitor (IL-17AI; i.e., ixekizumab [preferred] or secukinumab) is medically inadvisable, not tolerated or not adequate (i.e., NO response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response)
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
Supplemental Clinical Considerations- Anti-HBs does not guarantee protection against HBV reactivation in HBsAg-negative/anti-HBc-positive patients; consult hepatologist or infectious diseases expert for prophylaxis vs preemptive monitoring
- TNFI may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent infections, serious infections, etc.
- IL-17A inhibitors (ixekizumab/secukinumab) may be medically inadvisable due to Crohn’s disease, ulcerative colitis, or recurrent/severe Candida infections
- Ustekinumab may be medically inadvisable due to history of noninfectious pneumonia (interstitial, eosinophilic, cryptogenic organizing) and severe plaque psoriasis (risankizumab-rzaa preferred)
- Ustekinumab 45 mg is preferred for PsA with concomitant psoriasis in patients weighing ≤ 100 kg and for PsA without psoriasis; cost-benefit lost with 90 mg
- Ustekinumab and IL-23 inhibitors (guselkumab, risankizumab-rzaa) are ineffective for axial psoriatic arthritis
Infection Screening & Testing- Completed tuberculosis (TB) testing using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
HIV Status- Untreated HIV infection or high risk for HIV infection is an exclusion criterion
- Treated, well-controlled, asymptomatic HIV-positive patients are eligible
Vaccination Status- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines within 2 weeks prior to initiation, are exclusion criteria
Disease Severity & Diagnosis- Chronic (≥ 6 months) moderate to severe plaque psoriasis (including nail-only involvement)
- Prescribed at the FDA-approved dose for plaque psoriasis
Prior Systemic and Topical Therapy Exclusions- Methotrexate monotherapy must be medically inadvisable, not tolerated, or not adequate (defined as no treatment benefit after 3 months with at least 2 months at standard target dose [15–25 mg once weekly], or inadequate partial response after 6 months)
- Phototherapy must be medically inadvisable (e.g., confirmed skin cancer/melanoma history or strong likelihood per Fitzpatrick skin type I/II), inadequate (no benefit after 12 treatments or inadequate partial response after 24 treatments), not available, or not feasible
- Tumor necrosis factor inhibitor (TNFI) must be medically inadvisable (e.g., heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent/serious infections), not tolerated, or not adequate
- Interleukin-17A inhibitor (ixekizumab preferred, secukinumab) must be medically inadvisable (e.g., Crohn’s disease, ulcerative colitis, recurrent/severe Candida infections), not tolerated, or not adequate (defined as no response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response)
- Ustekinumab is no longer a prerequisite
Hepatitis B Management & Consultation- HBsAg-positive status without antiviral prophylaxis is an exclusion; initiation permitted after starting prophylaxis
- If HBsAg-negative but anti-HBc-positive, consultation with a GI/liver or infectious diseases expert is required to advise on initiating antiviral prophylaxis versus preemptive monitoring for HBV reactivation
Special Populations & Counseling- For patients who can become pregnant and partners who can become pregnant: counseling on potential risks vs benefits and use of effective contraception is required
Prescribing & Monitoring Requirements- Must be prescribed and monitored by a VA/VA Community Care dermatologist or locally designated psoriasis expert
- Active, serious, systemic, or localized infection (including undrained abscess) is an exclusion; initiation/restart permitted once infection is controlled
Indication & Patient Population- • Treatment of active psoriatic arthritis (PsA) in adults
- • Active PsA defined as symptom onset ≥ 6 months, meeting classification criteria for PsA, TJC ≥ 5 of 68, SJC ≥ 5 of 66, ≥ 1 erosion in hands and/or feet or hsCRP ≥ 3.0 mg/L, and active PsO (≥ 1 plaque ≥ 2 cm diameter or nail psoriasis)
Prior Therapy Requirements & Place in Therapy- • FDA-approved indication does not require trials of any prior therapies
- • May be used as an alternative to (at the same level as) ustekinumab and guselkumab for patients with active nonaxial, nonerosive PsA who have had an inadequate response to at least one TNFI and at least one IL-17AI, unless medically inadvisable
- • Ixekizumab is preferred in new starts within the IL-17AI class
- • Supported for patients with active PsA who have had an inadequate response to conventional immunomodulators and/or biologics, or for whom these therapies are medically inadvisable
Efficacy Considerations & Disease Features- • Effective for: achievement of ACR20 response, minimal disease activity (MDA), improvement in joint/entheseal/dactylitis/nail manifestations, function, and quality of life
- • IL-23 inhibitors may be preferred over ustekinumab for severe PsA-associated plaque psoriasis
- • Ineffective or low certainty for: short-term (24-week) improvement in dactylitis, preventing radiographic progression of peripheral erosive disease, and symptomatic MRI-verified axial PsA
Safety Considerations- • Safety considerations include infections and TB
- • Safety profile generally consistent with that in plaque psoriasis
Dosing & Administration- • 150 mg subcutaneously at Weeks 0 and 4, then every 12 weeks
- • May be administered alone or in combination with nonbiologic immunomodulators
Indication- Treatment of moderately to severely active Crohn’s disease (CD) in adults.
Patient Selection & Place in Therapy- May be less preferred than TNFIs (infliximab-abda or adalimumab) as first-line treatment to induce clinical remission in patients with moderate to severe, active luminal CD who have an inadequate response to conventional therapies.
- May be preferred over vedolizumab for second-line induction therapy in biologic-exposed patients.
- May be effective for skin and joint comorbidities of CD based on FDA approvals for plaque psoriasis and psoriatic arthritis.
Dosing & Administration- Induction: 600 mg IV infusion over at least 1 hour at Weeks 0, 4, and 8.
- Maintenance: 180 mg or 360 mg SC at Week 12 then every 8 weeks thereafter; use the lowest effective dosage to maintain therapeutic response.
- On-Body Injector (wearable injector) adheres to the skin and administers each dose over up to 5 minutes; must be kept at least 12 inches away from electronic devices during administration and should not be exposed to magnetic resonance imaging.
- Duration of an adequate therapeutic trial is 12 weeks; onset of effects occurs at 4 weeks.
Monitoring & Pre-treatment Requirements- Before initiating treatment: obtain liver enzymes and bilirubin levels, evaluate for tuberculosis (TB) infection, and complete all guideline-recommended vaccinations.
- Monitor liver enzymes and bilirubin during induction for up to at least 12 weeks of therapy, then per routine patient management.
Safety, Contraindications & Warnings- Contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab-rzaa or any excipients.
- Hepatotoxicity: Drug-induced liver injury has occurred during induction therapy; consider other treatment alternatives in patients with evidence of liver cirrhosis.
- Warnings/Precautions include hypersensitivity reactions, infections (including TB), and avoiding use of live vaccines.
Limitations & Evidence Gaps- Efficacy and safety not reported in patients with fistulizing CD; not evaluated in patients with stricturing CD.
- Comparative efficacy and safety of combination therapy with conventional immunomodulators relative to risankizumab-rzaa monotherapy is unknown.
- On-Body Injector may not be suitable for patients who are blind without sighted assistance or have impaired dexterity.
Exclusion Criteria- Uncontrolled, active, severe infection (including evidence of C. difficile and undrained abscess); may start/restart once infection treatment has been initiated
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- Untreated HIV infection
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless the prescriber deems that the potential benefits outweigh the risks
Inclusion Criteria- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA/VA Community Care gastroenterologist/hepatologist or locally designated expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening
- Obtained liver panel including bilirubin
Additional Inclusion Criteria (Therapy History & Sequencing)- Must meet ONE of the following:
- Tumor necrosis factor inhibitor (TNFi) is medically inadvisable (Infliximab/biosimilar is the preferred TNFi in UC)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFi in the presence of adequate TNFi levels (mechanistic failure)
- Loss of response to a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
- Sequencing: Risankizumab-rzaa is designated as a second-line or third-line agent. First-line therapy is infliximab (preferred) or adalimumab. Fourth-line options include mirikizumab-mrkz, guselkumab, or ustekinumab.
Special Considerations & Consultations- HBsAg-negative but anti-HBc-positive: GI/hepatology or infectious diseases expert consultation required to advise on starting antiviral prophylaxis versus preemptively monitoring for HBV reactivation
- Women who can become pregnant: Counseling must be provided on potential risks vs benefits of treatment and the use of effective contraception
- Vaccinations: Update before initiation when possible; recombinant zoster (SHINGRIX) vaccine should be completed or initiated by the end of the first year, preferably when dosage is low, disease is stable, or a robust immune response can be expected
Indication- Treatment of moderately to severely active ulcerative colitis (UC)
Patient Population & Clinical Criteria- Patients with inadequate response (IR) or intolerance (INT) to oral aminosalicylates, glucocorticoids (GCs), conventional immunomodulators (cIMMs) alone; ≥ 1 biologic, Janus kinase inhibitor (JAKi), and/or sphingosine-1-phosphate receptor modulator (S1PRM); or combination of conventional and advanced therapies
- No prior exposure to ustekinumab (p40) or IL-23 (p19) inhibitors
- Disease severity: modified Mayo score (mMS) of 5–9 and endoscopy subscore (ES) of 2–3
VHA PBM Guidance & Place in Therapy- No prerequisite therapy specified for UC
- May be used for patients with medical inadvisability to, or mechanistic failure of, a TNFi, or pharmacokinetic failure of infliximab/biosimilar (the preferred TNFi in UC)
- Evidence supports efficacy in inducing and maintaining clinical remission and endoscopic remission; place in therapy remains uncertain due to lack of head-to-head trials
Pretreatment & Monitoring Requirements- Obtain liver enzymes and bilirubin levels prior to treatment
- Evaluate for tuberculosis (TB) infection prior to treatment
- Administer guideline-recommended vaccinations prior to treatment
- Monitor liver enzymes and bilirubin levels during induction (up to ≥ 12 weeks)
- Monitor liver enzymes and bilirubin levels during subsequent treatment per routine patient management
Dosage Regimen- Induction: 1200 mg IV infusion over at least 2 hours at Weeks 0, 4, and 8
- Maintenance: 180 mg or 360 mg SC at Week 12 then every 8 weeks thereafter; use the lowest effective dosage needed to maintain therapeutic response
Safety Considerations & Contraindications- Contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab-rzaa or excipients
- Warnings include hypersensitivity reactions, infections, TB, hepatotoxicity during induction, and avoidance of live vaccines
- Most common adverse events (≥3%): Arthralgia (induction); arthralgia, pyrexia, injection site reactions, rash (maintenance)
- Geriatric use: Limited data available; 103 UC patients were aged ≥ 65 years in clinical trials
- Drug interactions: No clinically significant changes observed for CYP450 substrates (caffeine, warfarin, omeprazole, metoprolol, midazolam)
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DOSTARLIMAB-GXLY INJ,SOLN
JEMPERLI
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JEMPERLI |
2021-05-06 |
Indications & Patient Populations- Primary advanced or recurrent endometrial cancer (EC)
- Mismatch repair deficient (dMMR) recurrent or advanced solid tumors with progressive disease on prior treatment and no satisfactory treatment options
- Off-label use in dMMR locally advanced rectal cancer
Dosing & Administration- Endometrial cancer combination therapy: 500 mg IV every 3 weeks for 6 cycles, then 1000 mg every 6 weeks
- Endometrial cancer single agent: 500 mg IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks
- Solid tumors (single agent): 500 mg IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks
- Neoadjuvant therapy in rectal cancer: 500 mg IV every 3 weeks x 6 cycles
- Dosage form: 500 mg/10 mL [50 mg/mL] solution in single-dose vial
VA Clinical Pathways & NCCN Guidelines- Uterine Cancer (Stage III No Residual Disease, Stage III Preop Gross Nodal Disease, Stage IV): Carcinosarcoma -> PC + dostarlimab, then dostarlimab maintenance for up to 3 years
- Rectal Cancer (Stage II and III dMMR/MSI-H): Dostarlimab x6 months as neoadjuvant therapy
- NCCN Guidelines v2.2026 Endometrial Carcinoma:
- Primary or adjuvant therapy (Stage I-IV): PC + dostarlimab for Stage III-IV (Category 1)
- Recurrent disease: PC + dostarlimab (Category 1)
- Second or subsequent line therapy: MSI-H/dMMR tumors -> Dostarlimab (Category 2A)
- NCCN Guidelines v2.2026 dMMR/MSI-H Rectal Cancer: Neoadjuvant, preferred -> Dostarlimab or nivolumab or pembrolizumab for up to 6 months (Category 2A)
Safety & Monitoring Considerations- Boxed Warnings: None
- Contraindications: None
- Other Warnings: Severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplant, embryo-fetal toxicity
- Top 5 Adverse Events (Endometrial Cancer): Decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue
- Top 5 Adverse Events (dMMR Solid Tumors): Fatigue/asthenia, anemia, diarrhea, nausea
Exclusion Criteria- Autoimmune disease
- Immunosuppression requiring a corticosteroid equivalent to > 10 mg per day of prednisone
- Primary Immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Known pregnancy
- Lactating
Inclusion Criteria- Indication is FDA-approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria (General)- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (Reproductive Health & Pregnancy)- For females who can become pregnant: Pregnancy must be excluded prior to receiving dostarlimab
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for 4 months after stopping treatment
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DROSPIRENONE/ ESTETROL TAB
NEXTSTELLIS
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NEXTSTELLIS |
2021-05-06 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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LONCASTUXIMAB TESIRINE-LPYL INJ
ZYNLONTA
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ZYNLONTA |
2021-05-06 |
Exclusion Criteria- Absolute Neutrophil Count < 1000/µL
- Platelet count < 75,000/µL (if no bone marrow involvement)
- Total bilirubin > 1.5 times upper limit of normal (unless Gilbert’s syndrome or liver involvement)
- Alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase > 2.5 times the upper limit of normal (unless liver involvement)
- Creatinine clearance < 60 ml/min
- Clinically significant third space fluid accumulation (e.g., ascites or pleural effusion requiring drainage)
- Bulky disease (tumor > 10 cm)
- Chronic or unresolved infection
- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
Inclusion Criteria- Relapsed or refractory, diffuse large B-cell lymphoma
- Previously treated with > 2 prior lines of therapy (including 1 line with anti-CD20 monoclonal antibody)
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 10 months after stopping treatment.
Indication & Approval Status- Treatment of relapsed or refractory large B-cell lymphoma (R/R DLBCL) after > 2 lines of therapy (LOT)
- Includes DLBCL arising from low-grade lymphoma and high-grade B-cell lymphoma
- Granted accelerated approval based on overall response rate (ORR); continued approval is contingent on verification and description of clinical benefit in a confirmatory trial
Patient Population & Disease Characteristics- Heavily pretreated population with R/R DLBCL following > 2 prior lines of therapy
- Includes patients with MYC and BCL2 and/or BCL6 rearrangements
- Applicable to advanced stage disease (stages III or IV)
Dosing & Administration- Intravenous administration on day 1 of a 21-day cycle
- Cycles 1 and 2: 0.15 mg/kg
- Cycles 3 and beyond: 0.075 mg/kg
- Supplied as 10 mg loncastuximab lyophilized powder in a single-dose vial (SDV) for reconstitution and dilution
VA Clinical Pathway & Guideline Recommendations- Not included in current VA Oncology Clinical Pathways for DLBCL, Relapsed, 2L
- Classified as an "Other recommended regimen (category 2A)" per NCCN guidelines for 3L and subsequent therapy
- Preferred regimens per NCCN include CAR T-cell therapy and BITE (epcoritamab, glofitamab)
- Remains an option if bispecific T-cell engagers are not available
Safety Monitoring & Warnings- Monitor for effusion and edema
- Monitor for myelosuppression including neutropenia, thrombocytopenia, anemia, and febrile neutropenia (FN)
- Monitor for infections including sepsis and pneumonia
- Monitor for cutaneous reactions including photosensitivity
- Assess for embryo-fetal toxicity risks
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PONESIMOD TAB,ORAL
PONVORY
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PONVORY |
2021-04-01 |
Indication- Relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (aSPMS) in adults
Dosing & Administration- Oral tablets taken once daily
- Starter pack includes 2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, and 10mg tablets for titration, plus 20mg maintenance tablets
- Titration starts at 2mg/d over 14 days to a target dose of 20mg/d
Contraindications- Recent myocardial infarction, unstable angina, stroke or TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure
- Mobitz type II second-degree, third-degree AV block, sick sinus syndrome, or sino-atrial block (unless patient has a functioning pacemaker)
Warnings, Precautions & Monitoring Requirements- Infections and lymphocytopenia: Do not initiate in patients with active infection; check CBC and ZVZ antibodies before treatment; monitor for infection during treatment and 1–2 weeks after discontinuation
- Bradycardia and AV conduction delays: Titration is required at initiation; check ECG to assess for preexisting cardiac conduction abnormalities before treatment; avoid use with other medications that decrease heart rate
- Missed dose: Patients should re-titrate if they miss more than three consecutive doses
- Pulmonary function: Check PFTs if clinically indicated; use with caution in patients with a history of severe respiratory disease
- Liver injury: Check LFTs before treatment initiation; discontinue if significant liver injury is confirmed (ALT or conjugated bilirubin ≥2x ULN, or combined increase of AST, AP, and total bilirubin with one >2x ULN)
- Blood pressure: Monitor BP during treatment due to risk of persistent elevations
- Cutaneous malignancy: Periodic skin examination is recommended
- Fetal risk: Patients of childbearing potential should use effective contraception during treatment and for 1 week after discontinuation; avoid during pregnancy; consider risks and benefits for lactating patients
- Macular edema: Recommend ophthalmic evaluation prior to treatment and if vision changes occur; regular ophthalmic evaluations including examination of the fundus and macula for patients with a history of diabetes or uveitis
- PRES: Caution is advised due to rare reports with other S1P receptor modulators
- Disease rebound: Severe increase in disability after stopping has been reported; caution is advised when discontinuing
Special Populations- Geriatric: Patients aged 65 years and older have been excluded from clinical trials; caution is advised
- Hepatic impairment: Avoid in patients with moderate or severe hepatic impairment (Child-Pugh class B and C); no dose adjustment recommended for mild hepatic impairment (Child-Pugh class A)
Clinical Considerations & Place in Therapy- First-dose cardiac monitoring is not required for patients with low cardiac risk
- No genotype testing is required prior to therapy initiation
- No additional concerning drug interactions beyond those described for the S1P receptor modulator class
- Shorter elimination half-life compared to other agents requires repeat dose titration if more than 3 consecutive doses are missed
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TIVOZANIB CAP,ORAL
FOTIVDA
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FOTIVDA |
2021-04-01 |
Exclusion Criteria- Active or untreated central nervous system metastases
- Hepatic insufficiency (i.e., total bilirubin > 3 to 10 x ULN with any AST)
- Significant cardiovascular disease (i.e., symptomatic left ventricular heart failure, uncontrolled hypertension with systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg, acute coronary syndrome within past 6 months)
- Pregnancy (i.e., known pregnancy or positive pregnancy test) or lactating
- Concomitant CYP3A4 inducers (strong)
Inclusion Criteria- Care provided by a VA/VA Community Care hematology or oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
Additional Inclusion Criteria- Metastatic renal cell carcinoma with a clear cell component
- Previously unsuccessful treatment with 2 or 3 systemic therapy regimens, 1 of which were vascular endothelial growth factor receptor inhibitors other than tivozanib
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for one month after stopping treatment
Indication & Patient Population- Advanced or metastatic renal cell carcinoma (RCC) with clear cell component
- Relapsed following two or more prior systemic therapies (specifically after 2 or 3 prior regimens including at least one VEGFR inhibitor other than sorafenib or tivozanib)
- ECOG performance status 0-1
- Reserved for patients ineligible for or unable to tolerate other preferred systemic therapy options (lenvatinib/everolimus, cabozantinib, nivolumab)
- Selection of 3rd or 4th line therapy may be based on patient-specific factors including comorbidities, toxicity profile, dosing frequency (once daily vs twice daily), schedule (daily vs 21 out of 28 days), and drug-drug interaction potential
Dosing & Administration- Oral capsule formulation
- Dosing schedule: Days 1 to 21 of a 28-day cycle
Monitoring & Safety Precautions- Hypertension: Monitor; median time to onset is 2 weeks. Not studied in patients with systolic BP >150 mmHg or diastolic BP >100 mmHg.
- Cardiac effects: Monitor for cardiac ischemia and failure. Not studied in patients with symptomatic cardiac failure within 6 months prior to therapy.
- Hemorrhage: Not studied in patients with significant bleeding within 6 months prior to therapy.
- Nephrotoxicity/Proteinuria: Monitor; risk of acute kidney injury noted.
- Reversible posterior leukoencephalopathy syndrome (RPLS): Evaluate by MRI if seizures, headaches, visual disturbances, confusion, or altered mental function present.
- Thromboembolism: Not studied in patients with arterial thrombotic event, myocardial infarction, or unstable angina within 6 months prior to therapy.
- Thyroid disorders: Monitor for hypothyroidism and hyperthyroidism.
- Wound healing complications: Monitor due to VEGFR inhibition mechanism.
Special Populations & Reproductive Considerations- Geriatric: No overall differences in safety observed compared to patients <65 years.
- Renal impairment: No dose modifications recommended for mild to severe impairment (CrCl 15-89 mL/min). Dosage not established for end-stage renal disease (CrCl <15 mL/min).
- Hepatic impairment: No dose modification for mild impairment (total bilirubin < ULN with AST >ULN or total bilirubin >1-1.5x ULN with any AST). Reduce dose for moderate impairment (total bilirubin >1.5-3x ULN with any AST). Dosage not established for severe impairment (total bilirubin >3-10x ULN with any AST).
- Pregnancy: Verify pregnancy status prior to treatment. Use effective contraception during therapy and for 1 month after the last dose.
- Breastfeeding: Not recommended during therapy and for 1 month after the last dose due to potential for serious adverse reactions in the breastfed infant.
Screening & Drug Interactions- Hepatitis B Virus: Consider screening prior to tivozanib due to risk of HBV infection reactivation with anti-cancer agents.
- CYP3A4 Inducers: Avoid concomitant use of strong CYP3A4 inducers. Monitor for decreased effect with moderate CYP3A4 inducers.
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CLOZAPINE (SUN) TAB
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2021-03-11 |
Indications- Treatment-resistant schizophrenia
- Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Contraindications- Hypersensitivity to clozapine or any other component of clozapine
Boxed Warnings- Severe neutropenia
- Orthostatic hypotension, bradycardia, syncope
- Seizures
- Myocarditis, pericarditis, cardiomyopathy, and mitral valve incompetence
- Increased mortality in elderly patients with dementia-related psychosis
Precautions- Eosinophilia
- QT interval prolongation
- Metabolic Changes
- Neuroleptic malignant syndrome
- Hepatotoxicity
- Fever
- Pulmonary embolism
- Anticholinergic toxicity
- Interference with cognitive and motor performance
- Use with caution in patients with decreased GI motility
- Special populations: Poor metabolizers of CYP2D6; Smokers via CYP1A2 induction – with respect to forced absence during hospitalization
Dosing- Starting Dose: 12.5 mg once daily or twice daily
- Use cautious titration and divided dosage schedule
- Titration: increase the total daily dosage in increments of 25 mg to 50 mg per day, if well-tolerated
- Target dose: 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks
- Subsequent increases: increase in increments of 100 mg or less, once, or twice weekly
- Maximum daily dose: 900 mg
ANC Monitoring Recommendations- Obtain baseline ANC before treatment initiation
- Weekly from initiation to 6 months
- Every 2 weeks from 6 to 12 months (if the ANC remains in the normal range; ANC greater than or equal to 1500/μL for the general population, ANC greater than or equal to 1000/μL for patients with Benign Ethnic Neutropenia)
- Monthly after 12 months, using shared decision making (if ANC continues to remain in the normal range)
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MARGETUXIMAB-CMKB INJ,SOLN
MARGENZA
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MARGENZA |
2021-03-11 |
Indication & Patient Population- • Treatment, in combination with chemotherapy, of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.
Dosing & Administration- • Dosage form: 250 mg/10 mL single-dose vial.
- • Dose: 15 mg/kg IV every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
- • Initial dose administered over 120 minutes; subsequent doses over a minimum of 30 minutes.
- • May be administered immediately after chemotherapy completion on days co-administered with chemotherapy.
Safety Monitoring & Dose Modifications- • Left ventricular dysfunction (LVD): Withhold for at least 4 weeks for ≥16% absolute decrease in LVEF from pretreatment values, or LVEF below institutional limits of normal (or 50% if no limits) and ≥10% absolute decrease. May resume if LVEF returns to normal limits and absolute decrease ≤15% within 8 weeks. Permanently discontinue if LVEF decline persists >8 weeks or dosing interrupted >3 occasions for LVEF decline.
- • Infusion-related reactions: Decrease infusion rate for mild or moderate reactions; interrupt for dyspnea or clinically significant hypotension; discontinue for severe or life-threatening reactions. Consider premedications (antihistamines, corticosteroids, antipyretics) for mild/moderate reactions.
- • Exclusions/Not Studied: Patients with pretreatment LVEF <50%, prior history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV.
Adverse Reactions & Warnings- • Common adverse reactions (≥20%): Fatigue/asthenia, nausea, diarrhea, vomiting, decreased hemoglobin, decreased leukocytes, decreased neutrophils, increased aPTT, decreased lymphocytes, increased INR, increased creatinine, increased ALT, increased lipase, increased AST, increased alkaline phosphatase.
- • Serious adverse events: Grade 5 fatal events reported (viral and aspiration pneumonia); none considered treatment-related. Permanent discontinuation due to adverse events occurred in 3% of patients (left ventricular dysfunction, infusion-related reaction). Dosage interruptions occurred in 11% of patients.
- • Embryo-fetal toxicity: Can cause fetal harm when administered to pregnant women.
Appropriate Use & Formulary Status- • Select patients for treatment based on the presence of ERBB-2 mutation in tumor sample.
- • Not included in the VHA clinical pathway for breast cancer due to lack of overall survival benefit compared to trastuzumab + chemotherapy, along with associated toxicity and expense.
Exclusion Criteria- Tumor tissue does not overexpress HER2 protein (Defined as IHC 3+ or FISH amplification ratio greater than or equal to 2.0)
- Known hypersensitivity to margetuximab or any of its excipients (e.g., polysorbate 80, sucrose)
- Untreated and/or unstable brain metastases
- Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months of start
- Clinically significant cardiac arrhythmia requiring treatment
- Uncontrolled hypertension (>180/100 mmHg)
- History of congestive heart failure (New York Heart Association Class 2-4)
- Baseline left ventricular ejection fraction <50%
- Pericarditis, myocarditis or significant pericardial effusion
- Severe renal impairment (defined as CrCl less than 29 ml/min)
- Moderate or severe hepatic impairment (defined as total bilirubin > 1.5 times the upper limit of normal and any AST)
- Pregnancy
- Lactating
Inclusion Criteria- Diagnosis of metastatic breast cancer
- Received 2 or more prior anti-HER2 regimens, with at least one provided in the metastatic setting
Additional Inclusion Criteria- Care for the oncologic condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
Additional Inclusion Criteria (if applicable)- For patients who may become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 7 months after the last dose of margetuximab
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EVINACUMAB-DGNB INJ,SOLN
EVKEEZA
|
EVKEEZA |
2021-02-26 |
Exclusion Criteria- History of serious hypersensitivity reactions to evinacumab-dgnb or any of its excipients
- Does not have a confirmed diagnosis of Homozygous Familial Hypercholesterolemia (HoFH)
- Patient is receiving lomitapide
- Patient is pregnant
Inclusion Criteria- Care provided by VA/VA Community Care provider specializing in Cardiology, Endocrinology or locally designed specialty provider with expertise in lipid management
- Genetic or clinical confirmation of HoFH diagnosis
- Receiving maximally tolerated low-density lipoprotein cholesterol (LDL-C) lowering therapies including statins, ezetimibe and PCSK9 inhibitors and need for further LDL-C lowering to reduce cardiovascular disease (CVD) risk (e.g., LDL-C remains > 70 mg/dL in patients with CVD, > 100 mg/dL without CVD, LDL-C reduction <50% from baseline and/or patient having recurrent CVD events)
- Receiving LDL-C apheresis if patient is a candidate for therapy and if therapy is accessible
- Patient is willing and able to travel to receive evinacumab-dgnb infusions every 4 weeks
Pregnancy & Contraception Requirements- Evaluate pregnancy status prior to initiating treatment since evinacumab-dgnb may cause fetal harm
- Contraceptive counseling on the potential risks vs. benefits of taking evinacumab-dgnb if a patient were to become pregnant is recommended
- Use of effective contraception is advised during treatment and for at least 5 months after the last dose
- Supplemental Diagnostic Criteria for HoFH (Patient must meet one or more)
- Confirmation with genetic testing (mutation in LDL receptor: true homozygote or compound heterozygote)
- Untreated LDL-C of >500 mg/dL
- LDL-C remains >300 mg/dL despite maximally tolerated, clinically indicated lipid-lowering therapy (e.g., statins, ezetimibe, PCSK9 inhibitors) and adherence is confirmed, AND presence of any of the following physical findings including tendon xanthomas at any age, arcus corneae in patients <45 years or tuberous xanthomas or xanthelasma in patients <20 years
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TRILACICLIB INJ
COSELA
|
COSELA |
2021-02-26 |
Indication- Decrease the incidence of chemotherapy-induced myelosuppression when administered prior to a platinum/etoposide containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC)
Dosing & Administration- 240 mg/m2 IV over 30 minutes completed within 4 hours prior to the start of chemotherapy
- Formulated as a 300 mg/mL single-dose vial for injection
Contraindications & Warnings/Precautions- Contraindicated in patients with a history of serious hypersensitivity to trilaciclib
- No boxed warnings
- Monitor for injection site reactions, including phlebitis and thrombophlebitis
- Withhold for moderate acute drug hypersensitivity reactions; permanently discontinue for severe or life-threatening reactions
- Permanently discontinue for recurrent symptomatic or severe/life-threatening interstitial lung disease (ILD)/pneumonitis
- May cause embryo-fetal toxicity
Special Populations- Pregnancy: May cause fetal harm; use effective contraception during therapy and for at least 3 weeks after the final dose
- Lactation: No human data; potential for serious adverse reactions in breast-fed children
- Geriatric use: No overall differences in efficacy or safety observed
- Hepatic impairment: Not recommended for moderate or severe hepatic impairment (not studied in patients with total bilirubin >1.5 X ULN irrespective of AST)
Clinical Selection Criteria- Consider for select patients with a high risk for prolonged neutropenia receiving first-line chemotherapy or second-line topotecan therapy for SCLC to prevent long durations of severe neutropenia
- Net clinical benefit is minimal; reduces duration of severe neutropenia but does not eliminate the need for granulocyte colony stimulating factor (G-CSF) use in some patients
Supportive Care & Growth Factor Guidance- Primary prophylaxis with granulocyte growth factors is generally not warranted unless the risk of febrile neutropenia with the first cycle of chemotherapy is ≥20%
- If the risk is <20%, primary prophylaxis may be used if the patient has other risk factors for febrile neutropenia
- Growth factors are generally not routinely used if the patient is neutropenic but not febrile
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TOFACITINIB SOLN,ORAL
XELJANZ
|
XELJANZ |
2021-02-22 |
Diagnosis & Monitoring- Definite or provisional diagnosis of active ankylosing spondylitis (or radiographic axial spondyloarthritis)
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Routine retesting for tuberculosis and hepatitis screening is not required for prescription renewals; consider retesting in high-risk patients
Active Infection & Immunodeficiency- Exclusion: Uncontrolled active infection (initiation/restart permitted once treatment for the infection is initiated)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (initiation permitted after starting prophylaxis)
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Exclusion: Congenital or acquired immunodeficiency
- Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Inclusion: Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Additional: If HBsAg-negative but anti-HBc-positive with consult deemed indicated, GI/liver or infectious diseases expert must advise on antiviral prophylaxis or preemptive monitoring for HBV reactivation
Malignancy- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless rheumatologist and oncologist agree that risk-benefits favor using the drug)
Hematologic & Hepatic Parameters- Exclusion: Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (initiation/restart permitted once lymphopenia, neutropenia, and/or anemia resolve)
- Exclusion: Severe hepatic impairment (Child-Pugh class C)
Cardiovascular Risk- Exclusion: At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh the anticipated benefits
Concomitant Medications & Vaccines- Exclusion: Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin) (except during treatment transition overlaps)
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Inclusion: Offered all age-appropriate vaccinations prior to initiating therapy
- Note: Recombinant zoster vaccine should be completed or at least initiated by the end of the first year, preferably when dosage is low, disease is stable, or at other times when a robust immune response to vaccination can be expected
Pregnancy, Lactation & Counseling- Exclusion: Pregnancy
- Exclusion: Breastfeeding
- Additional Inclusion (Females who can become pregnant): Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- Additional Inclusion (Females who are breastfeeding/providing breastmilk to an infant): Counseling provided on potential risks vs benefits of treatment
Prior Therapy Requirements- Inclusion: ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, not adequate after 3 months, or lost response
- Note: Criteria apply only to new starts; patients on tofacitinib who are stable (responded after 16 weeks and/or controlled on maintenance therapy) should not be switched to a criteria-required prior drug for nonmedical reasons
Dosing & Administration Considerations- Prescribed at the FDA-recommended dose for ankylosing spondylitis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Use with extreme caution in patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
Indication & Patient Population- Treatment of adult patients with active ankylosing spondylitis (AS)
- Patients must have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs)
- Active AS defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and BASDAI back pain score ≥ 4 despite ≥ 2 NSAIDs, or intolerance to NSAIDs
Dosing & Administration- Immediate-release: 5 mg twice daily
- Extended-release: 11 mg once daily
- Dose reduction required for patients receiving strong CYP3A4 inhibitors (e.g., ketoconazole) or moderate CYP3A4 inhibitors with a strong CYP2C19 inhibitor (e.g., fluconazole): immediate-release 5 mg once daily
- Dose reduction required for patients with moderate and severe renal impairment or moderate hepatic impairment: immediate-release 5 mg once daily
- Stable background therapies allowed: NSAIDs, methotrexate (≤ 25 mg/week), sulfasalazine (≤ 3 g/day), and oral glucocorticoids (≤ 10 mg/day prednisone equivalent)
Contraindications & Limitations of Use- Not recommended for use in combination with biologic disease modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine and cyclosporine
- Patients with current or prior treatment with targeted synthetic DMARDs (including JAK inhibitors) and current biologic DMARD therapy are excluded
Place in Therapy & Sequence of Use- Conditionally recommended as second-line therapy after TNFIs or IL-17AIs for active AS with inadequate response or intolerance to NSAID therapy
- Conditionally recommended as third-line therapy after IL-17AIs for active AS after primary nonresponse to TNFI
- Conditionally recommended against for active AS in secondary nonresponders to TNFI
Safety & Vaccination Requirements- Live vaccines should be administered at least 2 weeks prior to initiation of tofacitinib therapy
- All patients should complete the two-dose series of recombinant zoster vaccine (SHINGRIX) before becoming immunosuppressed
- If initiated before herpes zoster vaccination, vaccine series should preferably be given when immune response is likely strong and at least in process by the end of the first year of treatment
Infections- Exclusion: Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
Malignancy & Cardiovascular Risk- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- Exclusion: At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Laboratory & Hematologic Parameters- Exclusion: Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once resolved; requires confirmation by repeat testing)
Hepatic Screening & Management- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Exclusion: HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis; consultation with hepatologist or infectious diseases expert recommended)
- Inclusion: Current or past completion of hepatitis C screening (may initiate while waiting for results)
Concomitant Medications & Vaccines- Exclusion: Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin) [except overlaps during treatment transition]
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Pregnancy & Lactation- Exclusion: Pregnancy and females of reproductive potential not using adequate contraception
- Exclusion: Breastfeeding, unless breastfeeding occurs at least 18 hours after the most recent dose
Diagnosis, Monitoring & Prescribing Requirements- Inclusion: Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Inclusion: Tofacitinib prescribed at the FDA-recommended dose for psoriatic arthritis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Inclusion: Inflammatory articular disease (joint, spine, and/or entheseal) and a definite or provisional diagnosis of active psoriatic arthritis
- Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Inclusion: ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, or not adequate after 3 months
Exclusion Criteria- Uncontrolled active infection (initiation/restart permitted once treatment for the infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis (initiation permitted after starting prophylaxis)
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive without antiviral prophylaxis (initiation permitted after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are eligible)
- Congenital or acquired immunodeficiency
- Malignancy within the previous 5 years, excluding successfully treated nonmelanoma skin cancer or cervical cancer (unless treating rheumatologist and oncologist agree risk-benefits favor use)
- Increased risk of thrombosis or major adverse cardiovascular events where potential harms outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (initiation/restart permitted once cytopenias resolve)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin)
- Pregnancy
- Breastfeeding (unless occurring at least 18 hours after the most recent dose)
- Concomitant live or live-attenuated vaccines, or administration of inactivated/live/live-attenuated vaccines less than 2 weeks before initiation
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Moderate to severe active rheumatoid arthritis
- FDA-recommended dose for rheumatoid arthritis, with adjustments for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Tumor necrosis factor inhibitor (TNFi) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response
Clinical Precautions & Monitoring Guidelines- Extreme caution required for patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation when possible; recombinant zoster (SHINGRIX) vaccine should be completed or initiated by the end of the first year, preferably at low dosage, stable disease, or during periods expected to yield a robust immune response
Diagnosis & Indication- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging.
- Prescribed and monitored by a VA/VA Community Care gastroenterologist/hepatologist or locally-designated expert.
Screening & Laboratory Requirements- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA).
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs]).
- Current or past completion of hepatitis C screening.
- Routine retesting is not required for prescription renewals; retesting in high-risk patients should be considered.
Exclusion Criteria- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once infection treatment initiated).
- Untreated latent or active tuberculosis infection.
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis).
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated).
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer, unless treating gastroenterologist and oncologist agree risk-benefits favor use.
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits.
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once resolved).
- Severe hepatic impairment (Child-Pugh class C).
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin).
- Pregnancy and females of reproductive potential not using adequate contraception.
- Lactation/providing breastmilk to an infant unless it occurs at least 18 hours after the most recent dose.
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation.
Treatment History & Sequencing (Additional Inclusion Criteria)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar is the preferred TNFI in UC).
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in the presence of adequate TNFI levels (mechanistic failure).
- Loss of response to a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure.
Special Populations & Counseling- If HBsAg-negative but anti-HBc-positive: A GI/liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation.
- For women who can become pregnant: Pregnancy status verified. Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
Dosing & Monitoring- Prescribe at the FDA-recommended dose for UC, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias.
- Discontinue if no response after 16 weeks of induction with tofacitinib 10 mg twice daily (or extended-release tofacitinib 22 mg once daily).
- Patients achieving response or remission should have dose reduced to 5 mg twice daily (or 11 mg once daily of extended-release tofacitinib) and use the lowest effective dose needed to maintain response.
- Use of higher induction doses beyond induction should be limited to patients with loss of response for the shortest duration clinically feasible.
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CABOTEGRAVIR TAB
VOCABRIA
|
VOCABRIA |
2021-02-12 |
Indications & Target Populations- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.
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TEPOTINIB TAB
TEPMETKO
|
TEPMETKO |
2021-02-12 |
Exclusion Criteria- CrCl <30 mL/min
- Prior treatment with another MET inhibitor
- Moderate or Severe Hepatic Insufficiency: AST/ALT > 3 × ULN or total bilirubin > 1.5 × ULN. For patients with liver metastases: AST/ALT > 5 × ULN or total bilirubin > 1.5 × ULN.
- Inadequate hematologic function with one of the following: Hgb <8.5 g/dL or Neutrophils <1.5 x 109/L or Plt <100 x 109/L
- Presence of ALK mutation or sensitive EGFR mutation (exon 19 del or exon 21 alteration)
- NYHA heart failure Class III or IV
- Untreated brain metastases
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Patients of child-bearing potential and patients with partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment. Use effective contraception during therapy and for one week after the last dose.
Additional Inclusion Criteria- Patients with metastatic non-small cell lung cancer with a MET exon 14 skipping mutation
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BRIMONIDINE GEL,TOP
BRIMONIDINE TARTRATE, MIRVASO
|
BRIMONIDINE TARTRATE, MIRVASO |
2021-02-04 |
Patient Demographics & Diagnosis- Adult 18 years and older
- Diagnosis of facial rosacea
- Moderate to severe, persistent (nontransient) facial erythema of rosacea (erythematotelangiectatic [ET] rosacea)
- Not more than two facial inflammatory lesions of rosacea
- OR: 3 or more facial inflammatory lesions of rosacea (papulopustular rosacea) in addition to ET rosacea
Exclusion Criteria- Patients at risk for serious harm from vascular insufficiency, including those with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, thrombangiitis obliterans, scleroderma, or Sjögren’s syndrome
- Patients at risk for serious harm from decrease in blood pressure, such as those with severe, unstable, or uncontrolled cardiovascular disease
- Hypersensitivity to brimonidine tartrate, phenoxyethanol (preservative), or other gel ingredients
Inclusion Criteria- Inadequate response, intolerance, or contraindication to nonpharmacologic approaches for rosacea (avoidance of triggers of flushing, proper use of sun protection, and use of skin care products for sensitive skin)
- If patient has 3 or more facial inflammatory lesions of rosacea (papulopustular rosacea) in addition to ET rosacea: Documentation of inadequate response, intolerance, or contraindication to a 4-week regimen of:
- Topical metronidazole (0.75% or 1% cream, gel or lotion) or topical azelaic acid (15% gel or 20% cream)
- AND Oral doxycycline (20 to 100 mg twice daily), minocycline (50 to 100 mg twice daily), or tetracycline (250 to 500 mg twice daily)
- Patient must be receiving VA care/consultation and the initial prescription must be from a dermatologist or other locally designated provider
Monitoring & Response Assessment- High-quality photos should be taken before starting therapy to make an objective assessment of effectiveness (if possible)
- Therapy should be discontinued if there is no clinically meaningful benefit
- Prescriptions may be renewed only if there is documentation that the patient experienced a clinically meaningful benefit after 2 weeks of treatment
Safety, Warnings, & Precautions- Avoid application to eyes, lips, irritated skin, or open wounds; wash hands immediately after applying
- Not for oral, ophthalmic, or intravaginal use
- Use caution with antihypertensives/cardiac glycosides (alpha-2 agonists may reduce blood pressure)
- Consider potential additive/potentiating effects with CNS depressants (e.g., alcohol, anesthetics, barbiturates, opioids, sedatives)
- Use caution with monoamine oxidase inhibitors (may theoretically impair metabolism and potentially result in increased systemic adverse effects such as hypotension)
- Pregnancy Category B: Use only if potential benefit justifies potential risk to the fetus
- Nursing Mothers: Potential for serious adverse effects in nursing infants; help patient decide whether to discontinue nursing or brimonidine gel
- Geriatric Use: Insufficient data to determine whether patients aged 65 and over respond differently
Prescription Authorization & Limits- Initial prescriptions limited to one 30-gram tube without refill
- Subsequent prescriptions may be written for larger quantities with refills if medication is effective and tolerated
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CABOTEGRAVIR/ RILPIVIRINE INJ,SUSP,SA
CABENUVA, CABOTEGRAVIR ER (CABENUVA), RILPIVIRINE ER (CABENUVA)
|
CABENUVA, CABOTEGRAVIR ER (CABENUVA), RILPIVIRINE ER (CABENUVA) |
2021-02-04 |
Exclusion Criteria- Known hypersensitivity to any component of the treatment regimen
- Coadministration with strong UGT1A1 and/or CYP3A4 inducers (e.g., rifamycins, dexamethasone, anticonvulsants that induce UGT/CYP)
- Baseline resistance mutations to either cabotegravir or rilpivirine
- History of significant INSTI or NNRTI resistance-associated mutations (with the exception of K103N)
- Prior virologic failure to any previous antiretroviral regimen (defined as HIV-1 RNA >400 copies per mL after initial viral suppression)
- Pregnant or planning to become pregnant
- Active hepatitis B virus (HBV) infection not on active HBV therapy
- Unable to discontinue use of PPI therapy while on oral rilpivirine induction/bridge therapy
Inclusion Criteria- Virologically controlled (HIV-1 RNA <50 copies/mL) on a stable oral standard antiretroviral regimen for ≥ 6 months with two or more HIV-1 RNA labs <50 copies/mL in the past 12 months (one in the previous 6–12 months, and one 0–6 months)
- A specific indication for CAB/RPV injection exists, such as difficulty managing oral medication (e.g., cognitive deficits, homelessness), concern for oral absorption of antiretrovirals, or concern for severe stigma with discovery of oral medications
- Documented history of adherence to HIV-related clinic appointments for the past year
- Provider documents that the patient agrees to reliably show up for clinic injections and understands that failure to do so will impact clinic schedules and may result in changing back to an oral regimen
Supplemental Clarifications- A change in a prior antiretroviral regimen due to adverse events, safety concerns, ease, or convenience is NOT considered evidence of virologic failure, provided the patient remained suppressed through the change.
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RAVULIZUMAB-CWVZ INJ,SOLN
ULTOMIRIS
|
ULTOMIRIS |
2021-02-04 |
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Thymectomy within 12 months
- Concomitant therapy with rituximab, neonatal Fc receptor antagonists (e.g., efgartigimod), or any other complement inhibitor (e.g., eculizumab)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use of these treatments in exacerbations is reasonable while on ravulizumab-cwvz)
Inclusion Criteria (All must be met)- Care provided by a VA/VA Community Care neurology provider or locally designated expert
- Diagnosis of acetylcholine receptor (AChR) antibody positive generalized myasthenia gravis (gMG)
- Patient is not a candidate for or has opted against thymectomy
- Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV
- Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) total score ≥ 6
- Vaccination against pneumococcal disease and Neisseria meningitidis with both Meningococcal conjugate vaccine (MenACWY) and Meningococcal serogroup B vaccine
Additional Inclusion Criteria (One of the following must be met)- Inadequate symptom control to maximally tolerated pyridostigmine AND at least two immunosuppressive agents separately trialed for at least 6 months each (e.g., azathioprine, cyclosporine, mycophenolate, etc.)
- History of intolerance or contraindication preventing trial of immunosuppressive agents (e.g., azathioprine, cyclosporine, mycophenolate, etc.)
- Lack of symptom control despite 4 or more courses of plasma exchange, high-dose steroid bursts and/or intravenous immune globulin in a 12-month or less period
Vaccination & Prophylaxis Notes- In emergent cases where waiting to initiate ravulizumab-cwvz at least two weeks after completion of vaccination is not possible, patients should begin the vaccination series at the time of initial dosing and be provided with appropriate prophylaxis
Indication & Patient Population- • Treatment of Neuromyelitis optica spectrum disorder (NMOSD)
- • Restricted to patients who are anti-aquaporin-4 (AQP4) antibody-positive
Dosing & Administration- • Dosage form: Injection (300 mg/mL in a single dose vial)
- • Route and frequency: Intravenous infusion every 8 weeks
- • Dosing is weight-based:
- Loading dose: 2,400 mg (40 kg to <60 kg), 2,700 mg (60 kg to <100 kg), 3,000 mg (≥100 kg)
- Maintenance dose: 3,000 mg (40 kg to <60 kg), 3,300 mg (60 kg to <100 kg), 3,600 mg (≥100 kg), starting 2 weeks after loading dose
REMS & Safety Requirements- • Prescribers must enroll in the Ultomiris REMS program
- • Patients must be counseled regarding the risk of meningococcal infections/sepsis
- • Patients must be provided with REMS educational materials
- • Patients must be vaccinated with meningococcal vaccines prior to starting therapy
Clinical Considerations- • Appropriate as a biologic therapy option for NMOSD
- • Disease severity, risks, and patient-specific considerations should be taken into account when choosing which therapy to start
Exclusion Criteria- Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae active infection
- Active, clinically significant infection
- Concomitant biologic therapy for neuromyelitis optica spectrum disorder (NMOSD)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use of these treatments in exacerbations is reasonable)
Inclusion Criteria- Care provided by VA or VA Community Care neurology provider or locally designated expert
- Diagnosis of aquaporin-4 antibody positive NMOSD
- Patient is vaccinated against pneumococcal disease
- Patient is vaccinated with BOTH the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
- Contraindication, intolerance, or lack of therapeutic response to rituximab
Exclusion Criteria- Shiga toxin E. coli-related hemolytic uremic syndrome (STEC-HUS)
- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Concomitant therapy with rituximab or any other complement inhibitor such as eculizumab
- Concomitant chronic therapy with plasma exchange
- Inclusion Criteria (All must be met)
- Prescribed by or in consultation with a VA or VA Community Care nephrology or hematology provider or locally designated expert
- Patient is vaccinated against pneumococcal disease
- Patient is vaccinated with BOTH the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
- Additional Inclusion Criteria (One of the following must be met)
- Patient requires treatment of aHUS with documentation ruling out Shiga toxin E. coli-related hemolytic uremic syndrome (STEC-HUS) and thrombotic thrombocytopenia purpura (TTP) (e.g., clinical evaluation and/or rule out of ADAMTS13 deficiency)
- Patient requires prophylaxis in renal transplant to ensure aHUS does not recur in the transplanted kidney
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Inclusion Criteria- Must be prescribed by or in consultation with a VA or VA Community Care hematology, oncology, immunology provider or locally designated expert
- Patient is vaccinated against pneumococcal disease
- Patient is vaccinated with BOTH the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
- Laboratory-confirmed diagnosis of PNH, as evidenced by detectable GPI-deficient hematopoietic clones (Type III PNH red blood cells [RBC]) via Flow Cytometry
- Documentation of Flow Cytometry pathology report must indicate presence of PNH-type RBC
- Must have a lactate dehydrogenase (LDH) level of 1.5 times the upper limit of the normal range (unless switching from eculizumab; laboratory results with reference range must be available for review)
Indication & Patient Population- • Generalized Myasthenia Gravis (gMG) in patients who are anti-acetylcholine receptor antibody-positive (AChR+)
- • Not supported for use in other antibody types including MuSK+, LRP4+, or seronegative disease
Dosing & Administration- • Only the IV formulation is currently approved for myasthenia gravis
- • Dosing is weight-based with a loading dose followed by maintenance doses every 8 weeks starting 2 weeks after the loading dose
- • Weight-based dosing:
- 40 kg to less than 60 kg: Loading 2,400 mg; Maintenance 3,000 mg
- 60 kg to less than 100 kg: Loading 2,700 mg; Maintenance 3,300 mg
- 100 kg or more: Loading 3,000 mg; Maintenance 3,600 mg
Safety & REMS Requirements- • Prescribers must enroll in the Ultomiris REMS program
- • Must counsel patients about the risk of meningococcal infections/sepsis and provide REMS educational materials
- • Patients must be vaccinated with meningococcal vaccines prior to therapy
- • Monitor for infusion-related reactions, severe meningococcal infection, other infections, diarrhea, and headache
Place in Therapy & Treatment Context- • Steroid-sparing treatment option for AChR+ gMG
- • Considered as add-on therapy when traditional oral immunosuppressants (azathioprine, mycophenolate, steroids) with or without acetylcholinesterase inhibitor (pyridostigmine) are ineffective
- • Offers a less frequent infusion schedule compared to eculizumab
- • Not studied in combination with plasma exchange, intravenous immunoglobulin (IVIg), rituximab, efgartigimod, or other complement inhibitors
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VERICIGUAT TAB
VERQUVO
|
VERQUVO |
2021-02-04 |
Exclusion Criteria- Symptomatic hypotension
- Concomitant use of other soluble guanylate cyclase stimulators (e.g., riociguat)
- Concomitant use of a PDE-5 inhibitor
- Pregnancy (i.e., known pregnancy or positive pregnancy test)
Inclusion Criteria- Restricted to VA/VA Community Care cardiology provider or locally designated expert in the management of heart failure
- Left ventricular ejection fraction less than 45% with New York Heart Association class II-IV heart failure symptoms
- Recent evidence of worsening heart failure (e.g., hospitalization for heart failure within the past 6 months despite optimal medical therapy, or outpatient intravenous diuretic therapy within the previous 3 months)
- On guideline-directed therapy for heart failure with an ACEI, ARB, or ARNI; a beta-blocker; and a mineralocorticoid receptor antagonist (or unable to use these agents)
- Female patients of child-bearing potential: provided counseling on contraception and potential risks vs. benefits of treatment
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TIRBANIBULIN OINT,TOP
KLISYRI
|
KLISYRI |
2021-01-28 |
Exclusion Criteria- None
- Inclusion Criteria (All criteria must be fulfilled)
- Care is provided by a VA / VA Community Care dermatologist or locally designated expert in actinic keratosis (AK)
- Clinically typical AK of the face or scalp
- Inadequate response or intolerance to two of three topical field therapies (5-fluorouracil, imiquimod, or diclofenac 3%) unless the treatment is medically inadvisable
- Inadequate response or intolerance to aminolevulinic acid with photodynamic therapy unless the treatment is medically inadvisable, unfeasible, or unavailable
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RELUGOLIX TAB
ORGOVYX
|
ORGOVYX |
2021-01-07 |
Exclusion Criteria- Unmanageable drug interaction identified
- End stage renal disease (with or without hemodialysis)
- Child-Pugh class C
- QTc > 470 msec, Q-wave infarction or congenital long QT syndrome
- Uncontrolled or symptomatic ventricular arrhythmias in the prior 6 months
- Congestive heart failure (NYHA Class 3 or 4) in the prior 6 months
- A thromboembolic event in the prior 6 months
- Gastrointestinal condition that may interfere with relugolix absorption or inability to swallow tablets whole
- Known history of non-adherence with oral medication, follow-up appointments or laboratory visits
Inclusion Criteria- Care provided by a VA or VA Community Care provider of urology or hematology/oncology services
- Goals of care and role of Palliative Care consult have been discussed and documented
- Hormone-sensitive, advanced adenocarcinoma of the prostate
- Additional Inclusion Criteria (One must be fulfilled)
- Inability to maintain castrate levels of serum testosterone on LHRH agonist therapy (taking into consideration the initial time required to reach castrate level)
- Known hypersensitivity to LHRH agonist analogs or their components
- Rapid decrease in testosterone levels needed due to organ-threatening disease
- Cardiovascular benefit alone (i.e. reduction in Major Cardiovascular Events) is not an appropriate indication for use
Reproductive Safety Considerations- Advise male patients with female partners of childbearing potential to use effective contraception during and for 2 weeks following the last dose of relugolix
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REMIMAZOLAM INJ
BYFAVO
|
BYFAVO |
2021-01-07 |
Indications & Approval Status- FDA approved for induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.
- Induction of general anesthesia is off-label; optimal dosing has not been established.
Dosing & Administration Criteria- Procedural Sedation (FDA Approved):
- Induction: Administer 5 mg IV over 1 minute for adult patients. For ASA III and IV patients, administer 2.5 to 5 mg IV over 1 minute based on general condition.
- Maintenance: Administer 2.5 mg IV over 15 seconds as needed. At least 2 minutes must elapse before any supplemental dose. For ASA III and IV patients, administer 1.25 to 2.5 mg IV over 15 seconds with the same 2-minute interval requirement.
- General Anesthesia (Off-Label):
- Dosing varies across studies; includes IV bolus or infusion for induction.
- Approved dosing in Japan and South Korea: Initial infusion of 6-12 mg/kg/h for induction, followed by 1 mg/kg/h for maintenance (maximum rate 2 mg/kg/h).
- Study dosing ranges: Bolus 0.2-0.4 mg/kg; Infusion 6, 9, or 12 mg/kg/h for induction; Maintenance 1-2 mg/kg/h.
Efficacy & Clinical Outcomes- Time to loss of consciousness (LOC), depth of anesthesia during maintenance, and recovery from anesthesia are generally similar between remimazolam and propofol, though some differences favor propofol for time to LOC, depth of anesthesia (measured by BIS index 40-60), and recovery.
- Use of BIS index target values (40-60) may not be reliable for measuring appropriate depth of anesthesia with remimazolam or other benzodiazepines.
- Evidence does not support replacing propofol with remimazolam for maintenance of anesthesia.
Safety, Adverse Events & Monitoring Requirements- Post-induction hypotension (PIH) and need for vasoactive medications are significantly lower with remimazolam compared to propofol in most studies.
- Hemodynamic changes during anesthesia maintenance are not statistically different between groups.
- Injection site pain is reported more frequently with propofol. Post-op delirium, PONV, dizziness, and respiratory depression show no consistent differences between remimazolam and propofol.
- Risk of delayed emergence due to variable CES1 metabolism (affected by inter-ethnic variability, genetic polymorphisms, hepatic impairment, age, BMI, low albumin, flavonoids, fatty acids, alcohol).
- Risk of re-sedation after reversal with flumazenil; flumazenil should be reserved for delayed emergence or awakening. Initial dose 0.2 mg recommended; monitor for two hours after reversal.
- Post-induction hypotension is generally defined as MAP <60-65 mmHg, >30% change from baseline, and need for vasoactive medications.
Contraindications & Precautions- Contraindicated in patients with known hypersensitivity to Dextran 40 or products containing Dextran 40.
- Several perioperative medications/fluids are incompatible with remimazolam, resulting in precipitation; consult product labeling for compatible fluids.
- Use caution in elderly, frail, patients with multiple co-morbidities, shock states, at risk for cardiopulmonary collapse, or ASA III-IV status due to vulnerability to post-induction hypotension (though remimazolam may reduce this risk).
Appropriate Use Cases / Place in Therapy- May offer an advantage over propofol for induction of anesthesia in patients vulnerable to post-induction hypotension (e.g., elderly, frail, multiple co-morbidities, shock states, at risk for cardiopulmonary collapse, ASA III-IV).
- Should not be used for maintenance of anesthesia or ICU sedation based on current evidence.
- Off-label use for induction of general anesthesia requires consideration of reduced post-induction hypotension risk and potential complications.
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OXYBUTYNIN CHLORIDE TAB
|
|
2021-01-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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VENLAFAXINE TAB
VENLAFAXINE HCL
|
VENLAFAXINE HCL |
2021-01-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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ACETAMINOPHEN INJ
|
|
2020-12-18 |
Exclusion Criteria- Severe hepatic impairment or severe active liver disease
- Hypersensitivity to acetaminophen or any components of the injectable formulation
Inclusion Criteria- Acute Postoperative Pain Management
- Requires management of acute postoperative pain AND either patient is medically unable to take analgesics orally (NPO) or is unlikely to have sufficient gastrointestinal absorption to achieve benefit from ingested acetaminophen
- Patients with one or more hours available before the induction of general anesthesia for intraabdominal or oropharyngeal surgery (and likely adequate gastrointestinal absorption) should be preferentially prescribed ingestible oral liquid acetaminophen
- Patients having non-abdominal or non-oropharyngeal surgery and likely adequate gastrointestinal absorption may be given acetaminophen oral formulations at any time before induction of general anesthesia
- Non-Surgical Setting (Acute Pain or Fever Management)
- Requires management of acute pain or management of fever AND patient is medically unable to take analgesics orally (NPO) or is unlikely to have sufficient gastrointestinal absorption to achieve benefit from ingested acetaminophen AND (for pain control only) IV/IM ketorolac is contraindicated
- Patients with difficulty swallowing but likely to have adequate gastrointestinal absorption may be given oral liquid acetaminophen or ibuprofen suspension unless contraindicated
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BEROTRALSTAT CAP,ORAL
ORLADEYO
|
ORLADEYO |
2020-12-18 |
Exclusion Criteria- Angioedema or abdominal pain not associated with C1 inhibitor deficiency
Inclusion Criteria (ALL must be met)- Restricted to VA / VA Community Care allergy/immunology or dermatology provider; or for use in Emergency Medicine/Urgent Care
- Diagnosis of Hereditary Angioedema due to C1 inhibitor deficiency (HAE-C1INH) as established by laboratory testing
Additional Inclusion Criteria (ONE must be met)- Long-term prophylaxis for HAE-C1INH attacks after consideration of either an attenuated androgen or antifibrinolytic
Clinical Context & Decision-Making Requirements- Prior consideration of an attenuated androgen or antifibrinolytic must be discussed with the patient using shared decision-making, including efficacy, routes of administration, and side effects of each therapy
- Baseline attack rate criteria may include at least 2 attacks per month or baseline attack rate in clinical trials
- Need for long-term prophylaxis should be determined using shared decision-making
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CLASCOTERONE CREAM,TOP
WINLEVI
|
WINLEVI |
2020-12-18 |
Indications & Patient Population- • Topical treatment of acne vulgaris in patients 12 years of age and older
- • FDA-approved for the treatment of acne without regard to severity or affected body area
Safety & Monitoring Considerations- • HPA axis suppression occurred in 5% of evaluated adults; incidence was higher in adolescents (9%) and pediatric patients aged 9–11 years (15%)
- • Hyperkalemia risk was not increased in study patients ≥12 years old, but risk in actual clinical practice, elderly patients, or with concurrent hyperkalemia-causing drugs remains unknown
- • Local skin reactions occurred at similar rates to vehicle
- • Adverse events of special interest include hyperkalemia, gynecomastia, and menstrual irregularities (polycystic ovaries/amenorrhea noted in long-term study)
- • Geriatric use: Insufficient data; extent of systemic absorption and risk of HPA axis suppression in patients >58 years are unknown
Contraindications & Precautions- • Not approved for children aged 9 to 11 years due to lack of efficacy in that subgroup and increased risks of HPA axis suppression (10%) and hyperkalemia (33.3%)
- • No data in pregnant women; teratogenic in animals
- • No human data for lactation
Place in Therapy- • May be used as an alternative topical treatment option for patients with acne vulgaris who have had an inadequate response or intolerance to two- or three-drug topical combination therapy including benzoyl peroxide, a retinoid and/or antibiotic
- • Safety and efficacy of clascoterone cream in combination therapy have not been evaluated
- • Topical therapies are generally used for mild to moderate acne and can serve as adjuncts to systemic antibiotics for severe acne
Storage & Handling- • Pharmacy storage: Refrigerate between 36°F and 46°F (2°C and 8°C)
- • Storage after dispensing: Room temperature between 68°F and 77°F (20°C and 25°C); do not freeze. Discard unused product 180 days after dispensing or 1 month after first opening, whichever is sooner
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ALVIMOPAN CAP,ORAL
|
|
2020-12-10 |
Exclusion Criteria- Complete bowel obstruction or having surgery for correction of complete bowel obstruction
- Patients scheduled for total colectomy, ileostomy, colostomy, pancreatic anastomosis or gastric anastomosis
- Inflammatory bowel disease
- Therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking alvimopan
- Intrathecal or epidural opioids or anesthetics are scheduled to be used during surgery
- Recent treatment with alvimopan in current episode of care (No studies evaluated safety and efficacy of more than one treatment course)
- Situations where pre-operative dose cannot be administered
- Severe hepatic impairment (Child-Pugh C)
- End-stage renal disease
- Any non-FDA approved indication (Alvimopan Shared System REMS applies)
Inclusion Criteria- Undergoing surgery that includes partial bowel resection with primary anastomosis (including resection of intra-abdominal organs with large or small bowel resection / anastomoses, e.g. radical cystectomy)
- Intravenous postoperative opioid pain management is planned
- Particular consideration for patients at risk for prolonged post operative ileus (PPOI):
- Prior occurrence of PPOI after any surgical procedure
- Anticipation of extensive (over 2 hours) adhesiolysis associated with a small or large bowel resection
- Significant en bloc resection of intraabdominal organs including large or small bowel
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ICOSAPENT ETHYL CAP,ORAL
VASCEPA
|
VASCEPA |
2020-11-13 |
Exclusion Criteria- History of hypersensitivity to icosapent ethyl or to any of its components
- Not on a statin or unable to tolerate statins
- Severe NYHA Class IV congestive heart failure
- Severe renal insufficiency (e.g., creatinine clearance <30 mL/min) or on dialysis
- Severe comorbid non-cardiovascular condition(s) expected to limit life expectancy to <2 years
- Uncontrolled or poorly controlled diabetes (e.g., HGB A1C > 10 %)
Inclusion Criteria- > 45 years of age with established cardiovascular disease (history of acute coronary syndrome, myocardial infarction, ischemic stroke and/or symptomatic peripheral arterial disease)
- Receiving a moderate to high dose statin (or maximally tolerated statin) and LDL is between 41 mg/dL and 100 mg/dL
- Fasting triglyceride level of > 150 mg/dL
- Secondary causes of hypertriglyceridemia have been considered and managed as appropriate before considering addition of icosapent ethyl
- Lifestyle and dietary changes have been discussed with the patient
Dosing & Administration- Icosapent ethyl 2 grams twice daily
- Available in 500 mg capsules (4 caps twice daily) if capsule size is a problem for some patients
- Statin doses should be maximized (as tolerated) prior to adding icosapent ethyl
Concomitant Medication Management- Patients on other omega-3 fatty acids, dietary supplements containing OM-3 FA, niacin or fibrates must stop these medications for at least 28 days prior
- If currently receiving niacin, fibrates or other OM-3 FA/supplements for reducing elevated triglyceride levels, consider stopping them and rechecking a fasting triglyceride level after 1-3 months to determine eligibility based upon repeat value
Secondary Cause & Lifestyle Management- Manage secondary causes of hypertriglyceridemia: hypothyroidism, uncontrolled diabetes, nephrotic syndrome, alcohol abuse, obesity, metabolic syndrome, and medications (e.g., tamoxifen, oral estrogens, systemic corticosteroids, thiazide diuretics, non-cardioselective beta-blockers [except carvedilol], clozapine, olanzapine)
- Encourage lifestyle and dietary changes: adoption of a healthy diet, weight loss in obese patients, aerobic exercise, smoking cessation, limiting alcohol intake
Restrictions & Safety Warnings- Use is restricted to patients meeting criteria for reducing cardiovascular risk; evidence does not support a greater triglyceride lowering response between various fish oil products and icosapent ethyl
- For patients with severe hypertriglyceridemia > 500 mg/dL who do not meet CFU for reducing CV risk, refer to the Omega-3-Acid Ethyl Esters (Lovaza and Lovaza generics) CFU
- Statistically higher incidence of hospitalization for atrial fibrillation or flutter reported in the icosapent ethyl group versus placebo-mineral oil
- Trend towards a higher risk of serious bleeding events reported with icosapent ethyl vs placebo
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REMDESIVIR INJ,SOLN
VEKLURY INJECTION
|
VEKLURY INJECTION |
2020-11-13 |
Indication & Patient Population- Emergency Use Authorization (EUA) for patients 18 years and older
- Mild-to-moderate COVID-19 at high risk for progression
- Use only if other alternatives are not accessible or clinically appropriate
Dosing & Administration- 800 mg (4 capsules) twice daily for 5 days
- Can be administered with or without food
Contraindications & Warnings- No contraindications listed
- Possible embryo-fetal toxicity
- Possible bone/cartilage toxicity in patients <18 years old
Adverse Reactions & Efficacy- Adverse reactions: diarrhea, nausea, dizziness
- MOVe-OUT trial data: Death or hospitalization by day 29 was 6.8% (MOV) vs. 9.7% (placebo)
Special Populations & Precautions- Not recommended in pregnancy and lactation due to potential embryo-fetal toxicity based on animal data
- If used, requires extensive discussion/documentation
- Requires reliable, consistent contraception during therapy and for 4 days after last dose in females of childbearing potential
- Requires reliable, consistent contraception for 3 months after last dose in males of reproductive potential
Renal/Hepatic Considerations- No dose adjustment required for renal or hepatic dysfunction
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EMTRICITABINE/ TENOFOVIR TAB
EMTRICITABINE-TENOFOVIR DISOP, TRUVADA
|
EMTRICITABINE-TENOFOVIR DISOP, TRUVADA |
2020-10-16 |
Indications & Target Populations- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.
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FOSFOMYCIN GRNL,RCNST-ORAL
FOSFOMYCIN TROMETHAMINE
|
FOSFOMYCIN TROMETHAMINE |
2020-10-16 |
Indications & Clinical Situations- FDA approved for treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.
- Not indicated for pyelonephritis or perinephric abscess.
- Off-label uses include management of cystitis in males, acute and chronic prostatitis, pre-operative prophylaxis (e.g., pre-transrectal prostate biopsy), and rarely as chronic suppressive therapy for recurrent symptomatic cystitis.
Microbiological & Susceptibility Requirements- CLSI breakpoint (≤ 64 ug/mL) applies only to E. coli and Enterococcus faecalis in urine cultures.
- Susceptibility testing is not routinely performed; must be specifically requested.
- Approved testing methods are disk diffusion and agar dilution MIC method (agar media supplemented with 25 ug/mL glucose-6-phosphate); broth microdilution MIC should not be performed.
- Breakpoints apply only to E. coli urinary tract isolates and should not be extrapolated to other Enterobacterales species.
- IDSA guidance recommends limiting oral fosfomycin to E. coli cystitis due to the intrinsic fosA gene in other gram-negative organisms (moderate to high risk of AmpC production), which may lead to clinical failure.
- Clinical data indicate worse outcomes and higher emergence of resistance with non-E. coli gram-negative isolates, particularly Klebsiella pneumoniae and Pseudomonas aeruginosa.
Dosing & Administration Parameters- FDA approved regimen: Single 3-gram dose dissolved in water for uncomplicated cystitis.
- Off-label dosing varies by clinical scenario:
- • Cystitis in males: 3 grams every 24–72 hours for 3–4 doses (1–3 weeks total).
- • Prostatitis: 3 grams daily for one week, followed by 3 grams every 48 hours OR 3 grams orally every 48–72 hours for 2–4 weeks (acute) or 4–6 weeks or longer (chronic).
- • Pre-transrectal prostate biopsy prophylaxis: Single 3-gram dose.
- Oral dosing does not achieve systemic concentrations required for upper urinary tract infections or systemic manifestations.
Safety & Monitoring Considerations- Diarrhea is the most frequently reported adverse event (9% in prescribing information; up to 18% in longer treatment case series), occasionally necessitating discontinuation, dose interval prolongation, or dietary modification.
- Other reported adverse events include vaginitis, nausea, headache, dizziness, asthenia, and dyspepsia.
- One case of C. difficile infection was reported; no other studies noted it.
- Indiscriminate use may result in treatment failure, adverse events (especially diarrhea), and emergence of resistance.
Place in Therapy & Rational Use Parameters- Ideal use is for lower urinary tract infections (e.g., cystitis) without signs of upper tract infection or systemic signs (e.g., fever, leukocytosis) caused by ESBL-producing E. coli resistant to other oral options.
- Appropriate when other oral agents are unavailable or inappropriate due to resistance, allergy, or route of administration.
- Aims to prevent hospital admission or outpatient parenteral antibiotic therapy.
- Most studies excluded patients with fever, leukocytosis, and upper tract infection symptoms; pharmacokinetic data does not support efficacy for systemic or upper urinary tract infections.
- Male sex has been identified as an independent risk factor for treatment failure in at least one study.
- Susceptibility testing is often unavailable at therapy initiation, and few VA laboratories routinely test for fosfomycin susceptibility.
Exclusion Criteria- Treatment of systemic infections beyond the urinary tract or prostate
- History of hypersensitivity reaction to fosfomycin
- Pyelonephritis or perinephric abscess
- Asymptomatic bacteriuria unless the patient is scheduled to undergo significant urinary manipulation or is pregnant
- Inclusion Criteria (At least one must be fulfilled)
- Cystitis with Escherichia coli or Enterococcus spp. in urine culture which is non-susceptible to other appropriate oral agents (e.g., nitrofurantoin, beta-lactams, trimethoprim-sulfamethoxazole) OR have a severe allergy or contraindication to other susceptible oral agents
- Acute/chronic prostatitis with Escherichia coli or Enterococcus spp. in culture which is non-susceptible to other appropriate oral agents (e.g., trimethoprim-sulfamethoxazole, doxycycline, fluoroquinolones) OR have a severe allergy or contraindication to other susceptible oral agents
- Other locally-approved indication or patient situation
Dosing and Administration- Acute uncomplicated cystitis in females (FDA-approved): 3 grams orally once with or without food
- Complicated cystitis in females or males: 3 grams orally once every 2-3 days for 3 doses (utilized for multi-drug resistant UTI)
- Acute/chronic prostatitis (off-label): 3 g orally daily for one week, followed by 3 g orally every 48 hours; OR 3 g orally every 48 to 72 hours. Durations: acute – 2 to 4 weeks, chronic – 4 to 6 weeks
Clinical Considerations & Supplemental Information- FDA-approved for Escherichia coli and Enterococcus faecalis uncomplicated UTI (by definition excludes males), but likely safe and efficacious for complicated UTI in males only involving the bladder
- ESBL E. coli fosfomycin resistance rates are low (susceptibility rates 81-100%)
- Reserve for E. coli; avoid for other gram-negative organisms (Klebsiella spp., Enterobacter spp., Serratia marcescens, Pseudomonas aeruginosa) due to intrinsic fosA gene leading to hydrolysis and clinical failure
- Does not achieve adequate concentration in the renal parenchyma; avoid for pyelonephritis and complicated UTI
- May be considered (off-label) for bacterial prostatitis, but fluoroquinolones are generally preferred if susceptible due to more robust evidence for chronic prostatitis
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FACTOR VIIA,RECOMBINANT-JNCW INJ,LYPHL
SEVENFACT
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SEVENFACT |
2020-09-24 |
Indications & Patient Population- Indicated for the treatment and control of bleeding episodes in adults and adolescents aged > 12 years with hemophilia A or B with inhibitors.
- Evaluated for on-demand treatment of mild/moderate bleeding events (BEs) and perioperative management/hemostasis.
Dosing & Administration- Supplied as a lyophilized powder in 1 mg or 5 mg single-use vials; reconstituted to a final concentration of 1 mg/mL.
- Dosing regimens include 75 mcg/kg and 225 mcg/kg as initial doses, with additional 75 mcg/kg doses administered until objective and refractory response.
- Perioperative administration includes preoperative dosing followed by up to 75 mcg/kg postoperative doses as directed by the surgeon/investigator.
Safety, Contraindications & Warnings- Boxed warning for thrombosis; serious arterial and venous thrombotic events have been reported.
- Contraindicated in patients with known allergy to rabbits or rabbit proteins, or severe hypersensitivity reaction to rFVIIa or its components.
- Patients with other risk factors for thrombosis may be at increased risk of serious arterial or venous thrombotic events.
- Hypersensitivity reactions, including anaphylaxis, are possible.
Formulary & Clinical Guidance- Indicated for treatment/control of bleeding episodes in adults and adolescents > 12 years with hemophilia A or B with inhibitors.
- Derived from genetically engineered rabbits; risk of thrombosis with emicizumab is unknown.
- For patients on emicizumab prophylaxis, eptacog beta is a reasonable option alongside eptacog alfa.
- May be less costly and require fewer doses per bleed event compared to alternatives in congenital hemophilia A or B with inhibitors.
- Recommended for availability on the VA National Formulary (VANF) without restrictions.
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AZACITIDINE TAB
ONUREG
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ONUREG |
2020-09-10 |
Exclusion Criteria- Using oral azacitidine as a substitute for parenteral azacitidine (oral and IV formulations are not interchangeable)
- Using oral azacitidine to treat myelodysplastic syndrome (MDS)
- Secondary acute myeloid leukemia (AML) with prior treatment using a hypomethylating agent (i.e., for MDS)
- History of hypersensitivity to azacitidine or mannitol
- Inability to swallow whole tablets
- Baseline absolute neutrophil count < 0.5x10^9/L and platelets < 20x10^9/L
- Renal insufficiency (serum creatinine > 2.5 x upper level of normal [ULN])
- Hepatic insufficiency (total bilirubin > 1.5 x ULN, AST and ALT > 2.5 x ULN)
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care provided by a VA/VA Community Care hematology provider
- Goals of care and role of palliative care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 to 3
Additional Inclusion Criteria- Age > 55 with newly diagnosed de novo or secondary AML
- Achievement of complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy
- Not a candidate or unable to complete intensive curative therapy (consolidation therapy, candidate for allogeneic hematopoietic stem cell transplant)
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FERRIC DERISOMALTOSE INJ
MONOFERRIC
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MONOFERRIC |
2020-09-10 |
Indications & Patient Population- Treatment of iron deficiency anemia (IDA) in adult patients
- Patients with intolerance to oral iron or unsatisfactory response to oral iron
- Patients with non-hemodialysis dependent chronic kidney disease (NDD-CKD)
Dosing & Administration Criteria- Available as 1000 mg/10 mL single-dose vial
- For patients weighing ≥50 kg: Administer 1,000 mg as a single IV infusion over at least 20 minutes
- For patients weighing <50 kg: Administer 20 mg/kg actual body weight as a single IV infusion over at least 20 minutes
- Dilute in 100 mL to 500 mL of 0.9% Sodium Chloride Injection, USP
- Repeat dose if IDA reoccurs
Contraindications- History of serious hypersensitivity to ferric derisomaltose or any of its components
Warnings & Precautions- Hypersensitivity reactions: Serious, life-threatening, and fatal anaphylactic-type reactions have been reported (including shock, clinically significant hypotension, loss of consciousness, collapse)
- Iron overload: Excess iron storage, iatrogenic hemosiderosis, or hemochromatosis can occur with excessive IV iron therapy; do not administer to patients with iron overload
Monitoring Requirements- Monitor for signs and symptoms of hypersensitivity during and after administration for at least 30 minutes until clinically stable
- Monitor hemoglobin, hematocrit, serum ferritin, and transferrin saturation during IV iron therapy
Clinical Decision Criteria- Decision to manage IDA with oral versus IV iron therapy depends on etiology of anemia, response/tolerability to iron supplementation, convenience of administration, and cost
- May be considered as preferred therapy based on economic considerations or convenience on a case-by-case basis at the local level
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DIMETHYL FUMARATE CAP,EC
TECFIDERA
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TECFIDERA |
2020-08-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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SATRALIZUMAB-MWGE INJ,SOLN
ENSPRYNG
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ENSPRYNG |
2020-08-27 |
Exclusion Criteria- Untreated active hepatitis B infection
- Untreated latent or active tuberculosis infection
- Active, clinically significant infection
- Active hepatic disease or hepatic impairment
- Baseline ALT and/or AST > 1.5 times the upper limit of normal (ULN)
- Concomitant therapy with another biologic therapy for neuromyelitis optica spectrum disorder (NMOSD)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use in exacerbations is reasonable)
- Pregnancy
Inclusion Criteria- Care provided by VA or VA Community Care neurology provider or locally designated expert
- Diagnosis of aquaporin-4 antibody positive NMOSD
- Completed hepatitis B screening (HBsAg, total anti-HBc and anti-HBs) with consult referral for hepatitis B management if either HBsAg or total anti-HBc positive
- All guideline recommended eligible immunizations administered at least 4 weeks prior to treatment start for live or live-attenuated vaccines, and whenever possible, at least 2 weeks prior for inactivated vaccines
- Contraindication, intolerance, or lack of therapeutic response to rituximab OR patient not a candidate for IV rituximab due to inability to access an infusion center or poor venous access
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and to inform provider of a known or suspected pregnancy
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CEDAZURIDINE/ DECITABINE TAB
INQOVI
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INQOVI |
2020-08-20 |
Indication & Patient Population- Adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS
- French-American-British subtypes: refractory anemia (RA), RA with ringed sideroblasts, RA with excess blasts, and chronic myelomonocytic leukemia (CMML)
- Intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System Groups
- Palliative intent for MDS and CMML; may serve as bridge therapy to allogeneic hematopoietic stem cell transplant (alloHSCT)
Dosing & Administration- Tablet strength: 35mg decitabine and 100mg cedazuridine
- Regimen: One tablet taken orally once daily on Day 1 through 5 of each 28-day cycle
- Dose reductions are accomplished by reducing the number of days of the treatment cycle rather than using an alternative tablet size
Monitoring & Clinical Management- Recommended minimum of 4 cycles prior to determining disease response
- Close monitoring required for infections, bleeding, and transfusion needs due to hematologic adverse reactions (more common in the first cycle)
- Renal/Hepatic insufficiency: No current dose recommendations; consider risks versus benefits. Clinical trial inclusion criteria specified Scr < 1.5 or CrCl > 50ml/min/1.73m2 and AST/ALT < 2.5 x ULN, Bilirubin < 2 x ULN
- Avoid coadministration with other drugs metabolized by cytidine deaminase (CDA). Proton pump inhibitors have no clinically meaningful effect on exposure
Contraindications & Warnings/Precautions- Boxed warnings: None
- Contraindications: None
- Fatal and serious myelosuppression
- Embryo-fetal toxicity; can cause fetal harm when administered to a pregnant woman. Advise patients not to breastfeed
- Can impair fertility
Formulary & Clinical Guidance- Appropriate for patients diagnosed with MDS or CMML who would be appropriate for azacitidine or IV decitabine
- Consider patient-specific factors including travel time, reliability, degree of social support, access to emergency services, and local VA CBOCs
- May avoid CITC consults and allow continued care provision
- Not adding additional indications beyond hypomethylating agents for MDS/CMML
- Equivalence has not been established with azacitidine IV, SQ, or PO
Exclusion Criteria- Hypersensitivity reaction to azacitidine, decitabine or cedazuridine
- Previous use of at least four cycles of decitabine IV or azacitidine without clinical response or benefit
- Concurrent treatment with lenalidomide, injectable azacitidine or injectable decitabine
- Renal dysfunction – Creatinine Clearance <30 mL/min (for Creatinine Clearance 30 – 59 mL/min monitor frequently for adverse reactions)
- Hepatic dysfunction – AST/ALT > 2.5 x upper limit of normal (ULN), Bilirubin > 2 x ULN
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Patients of child-bearing potential and patients with partners of child-bearing potential: counseling provided on contraception and risks vs benefits of treatment. Use effective contraception during therapy and for 6 months after the last dose.
Additional Inclusion Criteria- Diagnosis of myelodysplastic syndrome (MDS), including previously treated or untreated, de novo and secondary MDS (RA, RA-RS, RA-EB and CMML) and intermediate-1, intermediate-2, and high-Risk IPSS-R groups
- Parenteral therapy refused by patient or impractical (due to travel or healthcare setting exposure risk)
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BUDESONIDE/ GLYCOPYRROLATE/ FORMOTEROL INHL,ORAL
BREZTRI AEROSPHERE
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BREZTRI AEROSPHERE |
2020-08-14 |
Inclusion Criteria (All must be fulfilled)- Initial prescription is by or in consult with a VA/VA Community Care pulmonologist or designated expert
- Diagnosis of chronic obstructive pulmonary disease (post-bronchodilator ratio of FEV1/FVC less than 70%)
- Receiving ICS/LABA or LAMA/LABA but requires additional maintenance treatment for uncontrolled COPD symptoms and/or exacerbations
- If currently receiving an ICS, patient is NOT a candidate for ICS de-escalation
Additional Inclusion Criteria (At least one must be met)- Documented difficulty adhering to 3-drug therapy via 2 separate inhalers (ICS/LABA + LAMA or LABA/LAMA + ICS)
- Unable to use multiple inhalers due to underlying conditions (e.g., cognitive deficits, dexterity or visual impairment, etc.)
- Uncontrolled COPD symptoms and/or exacerbations while using formulary LABA/LAMA + ICS or ICS/LABA + LAMA
Adjudication & Clinical Considerations- Additional inclusion criteria do not apply to patients already using 3 different/separate inhalation products
- Patients doing well on 3-drug therapy via 2 separate inhalers should not be switched solely for convenience; cases adjudicated case-by-case
- Assess adherence and inhaler technique and provide any needed patient education before switching to Breztri
→ Full criteria details
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DEFERASIROX GRANULES
JADENU SPRINKLE
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JADENU SPRINKLE |
2020-08-14 |
Exclusion Criteria- Creatinine clearance <40 mL/min/1.73m2
- Severe (Child-Pugh C) hepatic impairment
- Terminal high-risk Myelodysplastic Syndrome (MDS-excess blasts)
- Unmanageable CYP2C8, CYP1A2, UGT, bile sequestrant, or aluminum-containing antacid drug interactions
- Baseline ophthalmology exam not completed
- Known hypersensitivity to deferasirox or any of its components
- Breastfeeding
Inclusion Criteria- Chronic iron overload due to red blood cell transfusion dependence
- Chronic iron overload in patients with non-transfusion-dependent thalassemia (NTDT) syndromes, and a liver iron concentration (LIC) of at least 5 mg Fe per gram of dry weight and a serum ferritin greater than 300 mcg/L
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Pregnancy Counseling Requirement- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective non-hormonal contraception during therapy
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TAFASITAMAB-CXIX INJ
MONJUVI
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MONJUVI |
2020-08-14 |
Exclusion Criteria- Absolute neutrophil count < 1500/µL or platelet count < 90,000/µL (if no bone marrow involvement)
- Total bilirubin > 2.5 times upper limit of normal (unless Gilbert’s syndrome or liver involvement)
- Alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase > 3 times upper limit of normal (unless liver involvement)
- Creatinine clearance < 60 ml/min
- Unmanageable drug-drug interaction
- Not a candidate for concomitant lenalidomide therapy
- Contraindication to thromboprophylaxis while receiving tafasitamab and lenalidomide
- Pregnancy
- Lactating
Inclusion Criteria- Previously treated, relapsed or refractory, diffuse large B-cell lymphoma in combination with lenalidomide
- Not eligible for autologous stem cell transplant
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 3 months after stopping treatment.
Indication & Disease State- Relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
Patient Eligibility & Treatment History- Not eligible for autologous stem cell transplant (ASCT)
- Not a candidate for CAR T-cell therapy
- Relapsed/refractory DLBCL following 1–3 prior systemic therapies, including anti-CD20 monoclonal antibody (i.e., rituximab)
- Second-line (2L) treatment setting
Exclusions & Population Limitations- Primary refractory DLBCL (i.e., fail to achieve a CR or relapse within 6 mos)
- Double or triple hit genetics (i.e., MYC, BCL2, and/or BCL6 translocations)
- Efficacy unknown in patients meeting the above exclusion criteria per L-MIND trial data
VA/NCCN Clinical Pathway & Guideline Recommendations- Preferred 2L option (Category 2A) in combination with lenalidomide
- VA Oncology Clinical Pathway specifies use in the 2L setting for patients not eligible for ASCT and not a candidate for CAR T-cell therapy
- Unclear if anti-CD19-directed therapy could have a negative impact on efficacy of subsequent CAR T-cell therapy
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MITOMYCIN SOLN,URH
JELMYTO
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JELMYTO |
2020-08-05 |
Exclusion Criteria- Perforation of the bladder or upper urinary tract
- Contraindication or known sensitivity to mitomycin
- Glomerular Filtration Rate of <30 mL/minute
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
- CBC at baseline (i.e. WBC ≥3 X109/L, ANC ≥1.5 x 109/L, Platelets ≥100,000 x 109/L, Hgb ≥9.0 mg/dL)
Inclusion Criteria- Care is provided by a VA/VA Community Care urology or oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Patients of child-bearing potential and patients with partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment; effective contraception used during therapy and for 6 months after the last dose (patients) or 3 months after the last dose (partners)
Additional Inclusion Criteria- Treatment naïve, residual disease, or recurrent low-grade Upper Tract Urothelial Carcinoma: treat weekly for 6 weeks
- Monthly maintenance therapy (for 1 year) after complete response can be considered on a case-by-case basis (data on monthly maintenance therapy is not robust)
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ETHINYL ESTRADIOL/ LEVONORGESTREL PATCH
TWIRLA
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TWIRLA |
2020-07-09 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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PERTUZUMAB/ TRASTUZUMAB/ HYALURONIDASE-ZZXF INJ,SOLN
PHESGO
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PHESGO |
2020-07-09 |
Indications- Neoadjuvant therapy for HER2+, locally advanced, inflammatory or early stage breast cancer (EBC) as part of a treatment regimen for early breast cancer
- Adjuvant therapy in HER2+ EBC at high risk of recurrence
- With docetaxel for HER2+ metastatic breast cancer (MBC) who have not received prior HER2-directed therapy or chemotherapy for metastatic disease
Patient Selection & Inclusion Criteria- Age > 18 years
- ECOG PS 0-1
- HER2+ status (IHC 3+ and/or ISH+)
- Locally advanced, inflammatory, or early stage breast cancer (operable) stage II-IIIC
- LVEF > 55%
Dosage & Administration- Subcutaneous injection formulation containing pertuzumab, trastuzumab, and hyaluronidase for subcutaneous dispersion
- Loading dose: 1200 mg pertuzumab, 600 mg trastuzumab, 30,000 units hyaluronidase/15ml SDV
- Maintenance dose: 600 mg pertuzumab, 600 mg trastuzumab, 20,000 units hyaluronidase/10ml SDV
Safety Monitoring & Precautions- Perform cardiac assessment with LVEF at baseline and throughout therapy
- Following completion of therapy in EBC, monitor for cardiomyopathy every 6 months for at least 2 years
- Verify pregnancy status prior to start of therapy; advise effective contraception during treatment and for 7 months after last dose
- Monitor patients during and for 30 minutes following the initial injection, then during and for 15 minutes following subsequent maintenance injections
- Consider pre-medications (analgesic, anti-pyretic, or antihistamine) for reversible Grade 1 or 2 hypersensitivity reactions
Contraindications & Exclusions- Known hypersensitivity to pertuzumab, trastuzumab, hyaluronidase, or any excipients
- Not studied in patients with baseline LVEF < 55% (EBC) or < 50% (MBC)
- Exclude patients with prior history of CHF, uncontrolled HTN, recent MI, cumulative anthracycline exposure > 360 mg/m2 doxorubicin equivalent, or serious cardiac arrhythmia requiring treatment
Transition & Place in Therapy- Patients currently receiving IV pertuzumab and trastuzumab can transition to the subcutaneous formulation
- Depending on time since last dose, patient may require a loading vs. maintenance dose
- Fixed-dose combination minimizes medication error potential from miscalculations and minimizes drug waste
- Shortened drug infusion time reduces clinic time and chair space; less drug preparation time and ancillary equipment required
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INEBILIZUMAB-CDON INJ,SOLN
UPLIZNA
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UPLIZNA |
2020-07-02 |
Exclusion Criteria- Untreated active hepatitis B infection
- Untreated latent or active tuberculosis infection
- Active, clinically significant infection
- Concomitant therapy with another biologic therapy for neuromyelitis optica spectrum disorder (NMOSD)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use during exacerbations is reasonable)
- Pregnancy
Inclusion Criteria- Care provided by VA or VA Community Care neurology provider or locally designated expert
- Diagnosis of aquaporin-4 antibody positive NMOSD
- Completed hepatitis B screening (HBsAg, total anti-HBc and anti-HBs) with consult/referral for hepatitis B management if either HBsAg or total anti-HBc is positive
- Quantitative serum immunoglobulins tested; if low, neurologist has documented risk/benefit assessment and/or an immunology expert was consulted prior to start
- All guideline recommended eligible immunizations administered at least 4 weeks prior to the start of treatment for live or live-attenuated vaccines, and whenever possible, at least 2 weeks prior to the start of treatment for inactivated vaccines
- Contraindication, intolerance, or lack of therapeutic response to rituximab
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 6 months after stopping treatment
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LURBINECTEDIN INJ
ZEPZELCA
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ZEPZELCA |
2020-07-02 |
Exclusion Criteria- Immunocompromised patients including known HIV (unless HIV with normal CD-4 counts)
- Absolute neutrophil count (ANC) < 1500 cells/mm3 and platelet count <100,000/mm3
- Unmanageable strong or moderate CYP3A Inhibitor drug interaction identified (including grapefruit and Seville oranges)
- Concomitant strong CYP3A inducers
- Moderate-severe hepatic impairment (T bili > 1.5 times the upper limit of normal and any AST)
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Lactating
Inclusion Criteria- Care is provided by a VA/VA purchased care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Baseline CBC then prior to each administration; baseline LFT’s then periodically as indicated
Additional Inclusion Criteria- Evidence of disease progression on or after platinum-based chemotherapy for metastatic small cell lung cancer (SCLC)
- Prophylaxis with antiemetic regimen for moderately emetogenic agent
- Use of granulocyte colony stimulating factor (GCSF) is recommended for ANC < 500 cells/mm3 as secondary prophylaxis
Reproductive Safety & Counseling Requirements- Female patients of child-bearing potential: counseling provided on risks vs benefits of treatment and use of effective contraception during therapy and for 6 months after the last dose
- Male partners: counseling provided on risks vs benefits of treatment and use of effective contraception during therapy and for 4 months after the last dose
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SELINEXOR TAB
XPOVIO
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XPOVIO |
2020-07-02 |
Exclusion Criteria- Inability to reliably take drug according to prescribed schedule
- Malabsorption syndrome or other condition affecting oral absorption
- Patient is not a candidate for dexamethasone therapy
- Active CNS disease
- Active, unstable cardiovascular function
- Ongoing or active systemic infection including hepatitis B or C, or known HIV
- ANC < 1000/mm3
- Platelet count < 75,000/mm3 (< 50,000/mm3 if myeloma involvement in bone marrow > 50%)
- Hemoglobin < 8 g/dL; Must transfuse to hemoglobin above 8 g/dL prior to initiation
- Total bilirubin > 2 x ULN (Gilbert’s syndrome > 3 x ULN) and AST and ALT > 2.5x ULN
- Estimated creatinine clearance < 15 ml/min
- Sodium level < 130 mmol/L
- Patient with evidence of anorexia and/or dehydration
- Concomitant therapy with antiplatelet drugs
- Unable to take antiemetic prophylaxis & breakthrough regimen for highly emetogenic therapy
- Pregnancy
- Breastfeeding
Inclusion Criteria (Indications)- Multiple myeloma: In combination with bortezomib and dexamethasone after at least one prior line of therapy
- Relapsed or refractory multiple myeloma: In combination with dexamethasone after at least 4 prior myeloma therapies (unless contraindicated or patient is unable to tolerate), with disease refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody
- Relapsed or refractory Diffuse Large B-cell lymphoma: After at least 2 prior lines of therapy
Additional Inclusion Criteria- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult discussed and documented
- ECOG performance status < 2
- Patients of child-bearing potential or with partners of child-bearing potential: Counseling provided on risk vs. benefit regarding pregnancy; Continue effective contraception until 1 week after last dose
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TECOVIRIMAT CAP,ORAL
TPOXX (NATIONAL STOCKPILE)
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TPOXX (NATIONAL STOCKPILE) |
2020-07-02 |
Indications & Patient Selection- JYNNEOS (Vaccine for Prevention)
- Indicated for pre- or post-exposure prophylaxis against monkeypox and smallpox in adults at high risk.
- Pre-exposure prophylaxis (PrEP): Recommended for laboratory workers handling orthopoxviruses; broader vaccination may be recommended when supply increases.
- Post-exposure prophylaxis (PEP): Indicated after high-risk exposure to monkeypox virus; ideally given within 4 days of exposure to prevent infection. Between 4–14 days post-exposure may be less effective. Beyond 14 days, benefits may outweigh risks in specific clinical situations (e.g., severely immunosuppressed patient with recent confirmed partner).
- Not expected to provide benefit if administered after onset of signs or symptoms of monkeypox.
- PEP++ (Enhanced PEP) criteria: Multiple sexual partners in the past 14 days in a jurisdiction with known monkeypox transmission.
- TPOXX / TECOVIRIMAT (Treatment)
- FDA approved for treatment of smallpox based on animal models; available under EA-IND protocol for non-variola orthopoxvirus infections including monkeypox during an outbreak.
- Consider for patients with severe disease: hemorrhagic disease, confluent lesions, sepsis, encephalitis, or conditions requiring hospitalization.
- Consider for persons at HIGH risk for severe disease: immunocompromised; pregnant/breastfeeding women; persons with complications (secondary skin infections, gastroenteritis with severe nausea/vomiting, diarrhea/dehydration, bronchopneumonia, concurrent disease/comorbidities); history or presence of atopic dermatitis or other exfoliative skin disorders.
- Consider for monkeypox virus aberrant infections: accidental implantation in eyes, mouth, genitals, or anus.
Dosing & Administration- JYNNEOS
- Standard (FDA-approved) regimen: 2 subcutaneous (SQ) doses of 0.5 mL each, 4 weeks apart, into fatty tissue over the triceps in the upper arm. Minimum interval is 28 days; may be given up to 4 days before or 7 days after. If delayed >7 days, administer ASAP without restarting series.
- Alternative (EUA) regimen: 0.1 mL administered intradermally (ID) on the volar surface of the forearm, second dose 28 days later. Preferred in VHA for most patients to maximize supply.
- Interchangeability: Adults who received standard SQ dosing may receive the second dose ID if no history of keloid development.
- TPOXX / TECOVIRIMAT
- Oral (Preferred): 600 mg every 12 hours for 14 days. Increase to 600 mg every 8 hours for patients weighing ≥120 kg. Must be given within 30 minutes of a full moderate or high fat meal.
- Intravenous (If unable to tolerate oral): Dilute with 0.9% sodium chloride or 5% dextrose. <120 kg: 20 mL (200 mg) + 40 mL diluent. ≥120 kg: 30 mL (300 mg) + 60 mL diluent. NOT diluted into prefilled infusion bags or given as IV bolus. Administer over 6 hours every 12 hours via syringe pump.
- Duration: 14 days. Modifications to dose, frequency, and duration may be necessary based on clinical condition, disease progression, therapeutic response, or clinical judgment (consult CDC EOC/FDA).
Contraindications- JYNNEOS: History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose.
- TPOXX / TECOVIRIMAT INJECTION: Severe renal impairment (CrCl < 30 mL/min). No contraindications to oral tecovirimat.
Precautions & Warnings- JYNNEOS
- History of severe allergic reaction (anaphylaxis) following gentamicin or ciprofloxacin (contains trace amounts).
- History of severe allergic reaction (anaphylaxis) to chicken or egg protein AND currently avoiding exposure to all chicken/egg products.
- Moderate to severe acute illness with or without fever (defer until improved).
- Immunocompromised patients may have a diminished immune response.
- Appropriate medical treatment must be available to manage possible anaphylactic reactions; weigh risk of severe reaction against disease risk.
- TPOXX / TECOVIRIMAT
- Use with caution in mild or moderate renal impairment (injection due to reduced clearance of hydroxypropyl-β-Cyclodextrin vehicle).
- Hypoglycemia when co-administered with repaglinide.
- Weak inducer of CYP3A and weak inhibitor of CYP2C8/CYP2C19; effects not clinically relevant for most substrates except increased repaglinide and decreased midazolam concentrations.
Storage, Handling & Monitoring- JYNNEOS
- Frozen: Thaw to room temperature before use. Use vials before date marked on carton. Once thawed, store refrigerated (36–46°F) for up to 8 weeks. Do not re-freeze.
- Room Temperature: Unpunctured vials up to 6 consecutive hours (46–77°F). Punctured vials must be stored refrigerated and discarded within 8 hours of first puncture.
- Monitoring: Observe after vaccination for immediate adverse reactions including syncope. Observation duration is 30 minutes for persons with history of anaphylaxis to gentamicin, ciprofloxacin, or chicken/egg protein (and avoiding exposure); 15 minutes for all others.
- TPOXX / TECOVIRIMAT
- Diluted IV solution: Store refrigerated up to 24 hours, or 4 hours at room temperature.
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ELAGOLIX/ ESTRADIOL/ NORETHRINDRONE CAP,ORAL
ORIAHNN
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ORIAHNN |
2020-06-11 |
Indication & Patient Population- Heavy Menstrual Bleeding Associated with Uterine Leiomyomas (Fibroids)
- Premenopausal patient
Exclusion Criteria- High risk or history of arterial, venous thrombotic, or thromboembolic disorder
- Pregnancy
- Known osteoporosis
- Uncontrolled hypertension
- Current or history of breast cancer or other hormonally sensitive malignancies
- Known hepatic impairment or disease
- Undiagnosed abnormal uterine bleeding
- Concomitant use of hormonal contraceptives
- Concomitant use of organic anion transporting polypeptide (OATP) 1B1 (e.g., gemfibrozil, cyclosporine)
- Any additional contraindication to receiving estrogen and/or progestin
- Known hypersensitivity to elagolix, estradiol, or norethindrone
Inclusion Criteria- Prescribed by or in consultation with a VA/VA Community Care Gynecology or Women’s Health Provider
- Confirmed diagnosis of uterine leiomyoma and heavy menstrual bleeding
- Contraindication, intolerance, or inadequate response to one alternative treatment (e.g., estrogen-progestin hormonal contraceptives, progestin-only contraceptives, tranexamic acid)
Monitoring, Duration, & Safety Requirements- Assessed for history of suicidal ideation, depression, and mood disorders prior to starting treatment
- Assessed for risk of bone density loss
- Planned duration of treatment not to exceed a maximum of 24 months (due to risk for bone loss)
- Monitor for mood changes and depressive symptoms after starting treatment
- Baseline DXA (dual-energy X-ray absorptiometry) and periodic follow-up during treatment; consider risks and benefits in patients with history of low trauma fracture or risk factors for low bone density
Pregnancy Prevention & Counseling- Exclude pregnancy prior to receiving EEN or start within 7 days of menses onset
- Counseling provided on potential risks vs. benefits of treatment
- Use of effective nonhormonal contraception during treatment and for 28 days after stopping treatment
Indication & Patient Population- Management of heavy menstrual bleeding (HMB) associated with uterine leiomyomas (fibroids) in premenopausal women
- Applicable to premenopausal women 18 to 51 years old with ultrasound-confirmed diagnosis of uterine fibroids and HMB defined as > 80 ml menstrual blood loss per cycle for ≥ 2 cycles
Dosing & Administration- One oral capsule taken twice daily, packaged in weekly blister packs
- Morning dose: elagolix 300 mg, estradiol 1 mg, norethindrone 0.5 mg
- Evening dose: elagolix 300 mg
Contraindications- High risk of arterial, venous thrombotic, or thromboembolic disorders
- Pregnancy
- Known osteoporosis
- Current or history of breast cancer or other hormonally sensitive malignancies
- Known hepatic impairment or disease
- Undiagnosed abnormal uterine bleeding
- Known anaphylactic reaction to EEN
- Concomitant use of organic anion transporting polypeptide (OATP)1B1 inhibitors (e.g., cyclosporine, gemfibrozil)
Warnings & Precautions- Boxed warning: Risk of thromboembolic disorders and vascular events
- Bone loss
- Suicidal ideation and exacerbation of mood disorders
- Transaminase elevations
- Elevated blood pressure
- Change in menstrual bleeding pattern and reduced ability to recognize pregnancy
- Alopecia
- Allergy to FD&C Yellow No. 5
- Additional standard warnings for estrogen and progestin
Treatment Duration & Limitations- Maximum treatment duration of 24 months due to concerns of bone loss
- Add-back therapy (estrogen plus progestin) combined with elagolix to lessen bone loss and improve overall tolerability
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BEMPEDOIC ACID/ EZETIMIBE TAB,ORAL
NEXLIZET
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NEXLIZET |
2020-06-04 |
Exclusion Criteria- End stage renal disease on dialysis
- Advanced heart failure with limited prognosis
- Severe comorbid non-cardiovascular condition expected to limit life expectancy
- Pregnant or lactating status
Primary Inclusion Criteria (Patient must meet at least one)- History of ASCVD (Atherosclerotic cardiovascular disease)
- Severe primary hypercholesterolemia (e.g., HeFH, LDL-C > 190 mg/dL) without ASCVD
Additional Required Inclusion Criteria (All must be met)- Contraindication, intolerance to, or insufficient LDL-C reduction with maximally tolerated dose of statin, requiring further LDL-C lowering per established guidelines
- Contraindication, intolerance to, or insufficient LDL-C reduction with ezetimibe, requiring further LDL-C lowering per established guidelines
- Contraindication, intolerance to, or insufficient LDL-C reduction with a monoclonal antibody inhibitor of PCSK9, requiring further LDL-C lowering per established guidelines
- Provider acknowledges potential for adverse events with bempedoic acid and will monitor as clinically appropriate
Pregnancy & Reproductive Considerations- Evaluate pregnancy status prior to initiating treatment due to potential fetal harm
- Provide contraceptive counseling on risks vs. benefits if pregnancy occurs during treatment
- Discontinue therapy if pregnancy occurs unless benefits outweigh potential risk to the fetus
Statin Intolerance Definition & Clinical Context- Documented intolerance requires a trial of at least 2 statins causing intolerable unexplained skeletal muscle-related complaints (pain/ache, weakness/cramping) that start or worsen during treatment and resolve upon cessation
- One statin trial must be at the lowest approved dose with alternate day dosing attempted
- Address factors increasing risk for statin intolerance or non-statin causes of muscle symptoms (e.g., hypothyroidism, vitamin D deficiency, drug-drug interactions, excessive alcohol use)
Stepwise Therapy & PCSK9 Preference Guidance- Patients on lower than optimal statin doses should receive ezetimibe as second-line treatment
- For patients on suboptimal statin dosing + ezetimibe with insufficient LDL reduction or unmet goals despite confirmed adherence, consider monoclonal antibody inhibitors of PCSK9
- For completely statin-intolerant patients where ezetimibe is insufficient or not expected to provide desired LDL-C reduction, a monoclonal antibody inhibitor of PCSK9 is preferred over bempedoic acid due to greater expected LDL-C reduction magnitude (50-60% vs 16-36%) and adverse event potential
- For patients with statin intolerance without established ASCVD and LDL-C <190 mg/dL, utilize ezetimibe, bile acid sequestrant (BAS), or combination in appropriate candidates
- For high-risk patients (e.g., diabetes mellitus, 10-year risk score >20%, subclinical atherosclerosis by imaging) without established ASCVD and LDL-C <190 mg/dL: If ezetimibe/BAS/combination fails to achieve clinically meaningful LDL-C reduction (>30% or >50%) or meet goals despite adherence, consider monoclonal antibody inhibitors of PCSK9 or bempedoic acid; PCSK9 inhibitors are preferred due to greater expected reduction and adverse event profile
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RIPRETINIB TAB
QINLOCK
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QINLOCK |
2020-06-01 |
Exclusion Criteria- CrCl <30 mL/min
- Moderate Hepatic Insufficiency defined as total bilirubin > 1.5 × ULN and any AST
- Clinically significant cardiovascular disease such as CHF (NYHA Class II to IV), active ischemia and/or angina Pectoris, baseline Left Ventricular Ejection Fraction < 50%
- Uncontrolled hypertension, ensure blood pressure control prior to starting therapy
- Major surgical procedure within prior 14 days or presence of active wound
- Pre-existing bleeding or coagulopathy
- Untreated brain metastases
- Hypersensitivity to ripretinib
- Unmanageable drug interaction with CYP3A inducers and/or inhibitors
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Patients of child-bearing potential and patients with partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment. Use effective contraception during therapy and for one week after the last dose.
Additional Inclusion Criteria- Patients with gastrointestinal stromal tumors who have progressed or have unacceptable toxicity on three prior lines of therapy that includes imatinib, sunitinib, and regorafenib
Indication & Patient Population- Adult patients with advanced gastrointestinal stromal tumor (GIST)
- Patients who have received prior treatment with 3 or more kinase inhibitors, including imatinib
- Patients who have progressed on or are intolerant to three or more tyrosine kinase inhibitors (TKIs), including imatinib
Dosing & Administration- Tablets: 50 mg
- Standard dose: 150 mg orally once daily with or without food
- Dose escalation: 150 mg twice daily for patients previously treated with 150 mg daily (fifth-line and beyond)
Pre-Treatment Requirements & Monitoring- Assess cardiac function prior to initiating therapy
- Assess ejection fraction by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) prior to initiation
- Monitor blood pressure prior to starting therapy
- Ensure hypertension is adequately controlled before starting treatment
- Withhold ripretinib at least 1 week prior to elective surgery; do not administer for at least 2 weeks following surgery or until wound is healed
- Monitor frequently for adverse reactions when coadministered with strong CYP3A4 inhibitors
Safety Warnings & Contraindications- Do not initiate in patients with uncontrolled hypertension
- Discontinue if Grade 3 or 4 left ventricular systolic dysfunction occurs
- Advise women of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose due to embryo-fetal toxicity risk
- Advise patients not to breastfeed during treatment and for one week after the final dose
- Withhold ripretinib and resume at the same or reduced dose based on severity for palmar-plantar erythrodysesthesia syndrome (PPES)
- Advise patients to immediately report any change in or development of new skin lesions due to risk of new primary cutaneous malignancies
Clinical Guidance & Place in Therapy- NCCN guidelines: Preferred fourth-line therapy (Category 1) for GIST after three prior regimens including imatinib
- UpToDate: Recommended for patients with GIST who have progressed on or are intolerant to three or more TKIs, including imatinib
- Formulary status: TBD
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TOLVAPTAN TAB
JYNARQUE, SAMSCA
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JYNARQUE, SAMSCA |
2020-06-01 |
Exclusion Criteria- History, signs or symptoms of significant liver impairment or injury (does not apply to uncomplicated polycystic liver disease)
- Use of strong CYP 3A inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, indinavir/ritonavir, ritonavir, conivaptan)
- Uncorrected abnormal blood sodium concentrations
- Inability to sense or respond to thirst
- Hypovolemia
- Hypersensitivity (e.g., anaphylaxis, rash) to tolvaptan or any component of the product
- Uncorrected urinary outflow obstruction
- Anuria
- Advanced diabetes (e.g., glycosylated hemoglobin > 7.5%)
- Significant kidney disease (currently active glomerulonephritides), renal cancer, single kidney, recent (within past 6 months) renal surgery or acute kidney injury
- Chronic kidney disease stage 5 (eGFR < 15 ml/min/1.73m2) or end-stage kidney disease
- Inability to adhere to a twice daily treatment regimen
Inclusion Criteria- Prescribed by a VA authorized Nephrologist
- Enrolled in JYNARQUE REMS Program and VA Specific Ordering Process
- Diagnosis of autosomal dominant polycystic kidney disease (ADPKD)
- AND one of the following indicating high risk of progression:
- Age > 18 to 50 years with eGFR > 60 ml/min/1.73m2 AND total kidney volume (TKV) > 750 ml
- Age > 18 to 55 years with eGFR > 25 to < 65 ml/min/1.73m2
- Age > 56 to < 66 years with eGFR > 25 to < 44 ml/min AND eGFR decline > 2ml/min/1.73m2 per year
Monitoring Requirements- ALT, AST, and bilirubin prior to initiation, at 2 and 4 weeks after initiation, monthly for 18 months, and every 3 months thereafter
- Serum sodium monitoring to detect increases above normal range
- Assessment of hydration and volume status
Discontinuation Criteria- Inability to adhere to liver function test monitoring schedule (at 2 and 4 weeks after initiation, monthly for 18 months, then every 3 months)
- Inability to adhere to twice daily therapy
- Inability to tolerate treatment
- Development of chronic kidney disease stage 5 (eGFR < 15 ml/min/1.73m2) or end-stage kidney disease
Dosage & Administration Guidelines- Initial recommended dosage: 60 mg orally per day divided as 45 mg upon awakening and 15 mg taken 8 hours later
- Titrate to 60 mg + 30 mg, then 90 mg + 30 mg per day if tolerated, with at least weekly interval between titrations
- Dose may be down-titrated based on tolerability; tablets are not scored
- If a dose is missed, take the next dose at the scheduled time
- Dose adjustments required for patients taking moderate CYP 3A inhibitors (specific reduced doses provided)
Safety & Clinical Considerations- Indicated to slow kidney function decline in adults at risk for rapidly progressing ADPKD
- Avoid concomitant use with strong CYP 3A inducers, grapefruit juice, OATP1B1/3 and OAT3 substrates, BCRP substrates, and V2-receptor agonists (e.g., desmopressin)
- Patients must be instructed to drink water when thirsty throughout the day and night while awake
- Limit dietary salt intake to < 5 grams/day; ingest at least 2 to 3 liters of fluid per day (including 1 to 2 cups of water at bedtime regardless of perceived thirst, and replenish fluids after each episode of nocturia)
- Temporarily suspend therapy if serum sodium increases above normal, or if patient becomes hypovolemic/dehydrated and fluid intake cannot be increased
- For women of childbearing potential: Insufficient data on fetal risk; breastfeeding is not recommended
Exclusion Criteria- Use for autosomal dominant polycystic kidney disease (ADPKD)
- Underlying liver disease including cirrhosis
- Unable to sense or respond to thirst
- Hypovolemic hyponatremia
- Urgent need to raise serum sodium acutely
- Anuria
- Strong CYP 3A inhibitors (e.g., ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, clarithromycin, and telithromycin) or moderate CYP 3A inhibitors (e.g., erythromycin, fluconazole, aprepitant, diltiazem, and verapamil)
Inclusion Criteria- Care provided by a VA / VA Community Care endocrinologist, nephrologist, or other locally designated expert
- Diagnosis of clinically significant hypervolemic or euvolemic hyponatremia (serum sodium less than 125 mEq/L or less marked hyponatremia that is symptomatic and unresponsive to fluid restriction)
- Initiation and re-initiation conducted in a hospital setting for close serum sodium monitoring and avoidance of excessively rapid correction
- Duration of treatment limited to 30 days due to the risk of hepatotoxicity
- Avoid fluid restriction during the first 24 hours; advise patients to continue to ingest fluids in response to thirst
Additional Inclusion Criteria- For women of childbearing potential: Use during pregnancy only if potential benefit justifies potential risk to the fetus based on animal data indicating possible fetal harm
- Breastfeeding is not recommended
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CAPMATINIB TAB
TABRECTA
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TABRECTA |
2020-05-21 |
Exclusion Criteria- EGFR mutation (exon 19 or exon 21 mutation) or ALK rearrangement
- Neurologically unstable CNS metastases
- Unmanageable Strong or Moderate CYP3A4 inducer drug interaction identified
- Current interstitial lung disease or interstitial pneumonitis including radiation pneumonitis
- Creatinine clearance < 30 mL/min
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care is provided by a VA/VA purchased care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Female patients of child-bearing potential or male with female partner of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment; use effective contraception during therapy and for 1 week after the last dose
- Additional Inclusion Criteria (at least one must be fulfilled)
- Patient with metastatic non-small cell lung cancer whose tumor has a mutation that leads to MET exon 14 skipping as detected by an FDA-approved test
- Patient-specific recommendation for capmatinib from the National Precision Oncology Program for the minimal duration needed to assess for efficacy (in most cases 8-12 weeks)
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DARATUMUMAB/ HYALURONIDASE-FIHJ INJ,SOLN
DARZALEX FASPRO
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DARZALEX FASPRO |
2020-05-15 |
Exclusion Criteria- Known hypersensitivity to daratumumab
- Unable to be observed in clinic for an extended period following the first dose
- Absolute Neutrophil Count (ANC) < 1000/mm3
- Hemoglobin < 8 g/dL; must transfuse to hemoglobin > 8 g/dL prior to therapy initiation
- Platelet count < 50,000/mm3 (< 30,000/mm3 if myeloma involvement in bone marrow > 50%)
- Estimated creatinine clearance (CrCl) < 15 ml/min
- New York Heart Association (NYHA) Class III or IV heart failure
- Ongoing or active systemic infection including active hepatitis B or C or known HIV infection
- Patient has not been screened for Hepatitis B Virus (HBV)
- Pregnancy (e.g. known or positive pregnancy test)
- Breastfeeding
Indications- Multiple myeloma
- Light chain amyloidosis
Pre-treatment & Clinical Management Requirements- Care is provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Type and screen patients for Red Blood Cell antibodies PRIOR to starting therapy
- Provider has informed Blood Bank that patient will be starting daratumumab
- Antiviral prophylaxis to prevent herpes zoster reactivation to start within 1 week after starting daratumumab and continue for 3 months following the end of treatment
- Female patients of child-bearing potential and male patients with female partners of child-bearing potential: counseling provided on contraception (use during treatment and 3 months after) and risks vs. benefits of treatment
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LEMBOREXANT TAB
DAYVIGO
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DAYVIGO |
2020-05-15 |
Exclusion Criteria- Narcolepsy
- Co-administration with strong or moderate CYP3A4 inhibitors and inducers
- Active substance use disorder
- Actively suicidal or evaluated as being a high suicide risk
- Untreated significant sleep-related breathing disorder-obstructive or central sleep apnea syndrome
- Severe hepatic impairment (e.g., Child-Pugh C)
- History of complex sleep behaviors
Inclusion Criteria- Prescribed and monitored by a VA / VA Community Care sleep specialist or locally designated expert in sleep disorders
- Documented diagnosis of insomnia characterized by difficulties with sleep onset and/or sleep maintenance
- When available, cognitive behavioral therapy for Insomnia (CBT-I) has been tried, via face to face, tele-mental health or non-VA care
- An adequate short-term trial of 2 formulary sedative hypnotics for the treatment of sleep onset and maintenance have been tried and failed to resolve symptoms or were not tolerated
- An adequate trial of daridorexant has been tried and failed or was not tolerated
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PEMIGATINIB TAB
PEMAZYRE
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PEMAZYRE |
2020-04-30 |
Exclusion Criteria- Care not provided by a VA or VA Community Care provider of hematology/oncology services
- Unmanageable CYP3A inhibitor/inducer drug interaction identified
- Clinically significant corneal or retinal disorder identified by ophthalmologic exam
- Serum phosphate level greater than ULN
- Untreated, clinically unstable brain and/or CNS metastases
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Diagnosis of advanced/metastatic or surgically unresectable cholangiocarcinoma
- Documented disease progression after at least one prior systemic therapy
- Confirmed tumor expression of FGFR2 fusion or select rearrangement by FDA-approved next generation sequencing
- Baseline ophthalmology exam, including optical coherence tomography (OCT), performed
- Goals of care and role of Palliative Care consult have been discussed and documented
- ECOG Performance Status 0-2
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SACITUZUMAB GOVITECAN-HZIY INJ,LYPHL
TRODELVY
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TRODELVY |
2020-04-30 |
Indications & Patient Population- Unresectable locally advanced (LA) or metastatic triple-negative breast cancer (mTNBC)
- Unresectable locally advanced or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer
Prior Therapy Requirements- mTNBC: Received > 2 prior therapies, with at least one therapy administered in the metastatic setting
- HR+, HER2- BC: Received prior endocrine-based therapy (including a CDK4/6 inhibitor) and > 2 additional systemic therapies in the metastatic setting (one of which must be a taxane)
Dosing & Administration- 10 mg/kg administered once weekly on Days 1 and 8 of a 21-day cycle
- Continue treatment until disease progression or unacceptable toxicity
Monitoring & Safety Considerations- Significant toxicity profile (risk of neutropenia, diarrhea, nausea, vomiting) requires appropriate pre-medication, pertinent labs, and monitoring tailored to the patient's clinical context
- Patients homozygous for the UGT1A1*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia; reduced UGT1A1 activity warrants caution
- Avoid concomitant use of UGT1A1 inhibitors or inducers
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TUCATINIB TAB
TUKYSA
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TUKYSA |
2020-04-30 |
Exclusion Criteria- Neurologically unstable Central Nervous System (CNS) metastases requiring urgent local intervention
- Unmanageable drug interaction identified
- Known pregnancy
- Lactating
Inclusion Criteria (Indications & Regimens)- In combination with trastuzumab and capecitabine for advanced unresectable or metastatic HER2+ breast cancer who received two or more lines of anti-HER2-based therapy in the metastatic setting
- In combination with trastuzumab and capecitabine for metastatic HER2+ breast cancer with brain metastases who received one or more lines of anti-HER2-based therapy
- In combination with trastuzumab for RAS wild-type HER2+ unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan- based chemotherapy
Additional Inclusion Criteria (General & Administrative)- Care for the oncologic condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
Additional Inclusion Criteria (Pregnancy & Contraception)- For females who can become pregnant: Pregnancy must be excluded prior to receiving tucatinib
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for one week after stopping treatment
Indication & Patient Population- Adult patients with advanced unresectable or metastatic HER2-positive breast cancer
- Patients who have received one or more prior anti-HER2-based regimens in the metastatic setting
- Includes patients with brain metastases (active brain metastases permitted if urgent local intervention not needed)
Line of Therapy & Regimen- Used in combination with trastuzumab and capecitabine
- VA formulary guidance: Reserved for patients who have received two or more previous lines of therapy for HER2-positive metastatic breast cancer
- Specifically considered as a third-line option for patients who previously received trastuzumab deruxtecan as second-line therapy, particularly those with active brain metastases
Dosing Criteria- Recommended dosage: 300 mg taken orally twice daily with or without food
- Severe hepatic impairment: 200 mg taken orally twice daily
Monitoring & Management Criteria- Hepatotoxicity monitoring: Monitor ALT, AST, and bilirubin prior to starting tucatinib, every 3 weeks during treatment, and as clinically indicated; interrupt dose, reduce dose, or permanently discontinue based on severity
- Diarrhea management: Administer antidiarrheal treatment as clinically indicated; interrupt dose, reduce dose, or permanently discontinue based on severity
- Renal function monitoring: Consider alternative markers of renal function if persistent elevations in serum creatinine are observed (due to inhibition of renal tubular secretion without affecting glomerular filtration)
Drug Interaction Criteria- Avoid concomitant use with strong CYP3A inducers or moderate CYP2C8 inducers
- Avoid concomitant use with strong CYP2C8 inhibitors; reduce tucatinib dose if concomitant use cannot be avoided
- Avoid concomitant use with CYP3A substrates where minimal concentration changes may lead to serious or life-threatening toxicities
- Consider reducing the dose of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities
Special Populations & Safety Criteria- Pregnancy: Females of reproductive potential should use effective contraception during tucatinib therapy and for ≥1 week after the last dose
- Male partners: Males with female partners of reproductive potential should use effective contraception during tucatinib therapy and for ≥1 week after the last dose
- Lactation: Breastfeeding is not recommended during tucatinib treatment or for ≥1 week after the last dose due to potential for serious adverse reactions in the breastfed infant
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TRASTUZUMAB-DTTB INJ
ONTRUZANT
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ONTRUZANT |
2020-04-23 |
Exclusion Criteria- Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Interstitial lung disease or pneumonitis
- Pregnancy
- Lactating
- Primary Inclusion Criteria (One must be fulfilled)
- HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
- HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
- Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
- Care provided by VA or VA Community Care provider of oncology
- Goals of care and role of Palliative Care consult discussed and documented, if appropriate
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception Requirements (Select if applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose
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ETHINYL ESTRADIOL/ ETONOGESTREL RING,VAG
ELURYNG, ENILLORING, ETONOGESTREL-ETHINYL ESTRADIOL, HALOETTE, NUVARING
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ELURYNG, ENILLORING, ETONOGESTREL-ETHINYL ESTRADIOL, HALOETTE, NUVARING |
2020-04-21 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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TRASTUZUMAB-PKRB INJ
HERZUMA
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HERZUMA |
2020-03-26 |
Exclusion Criteria- Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Interstitial lung disease or pneumonitis
- Pregnancy
- Lactating
- Primary Inclusion Criteria (One must be fulfilled)
- HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
- HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
- Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
- Care provided by VA or VA Community Care provider of oncology
- Goals of care and role of Palliative Care consult discussed and documented, if appropriate
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception Requirements (Select if applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose
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BEMPEDOIC ACID TAB,ORAL
NEXLETOL
|
NEXLETOL |
2020-03-12 |
Exclusion Criteria- End stage renal disease on dialysis
- Advanced heart failure with limited prognosis
- Severe comorbid non-cardiovascular condition expected to limit life expectancy
- Pregnant or lactating status
Primary Inclusion Criteria (Patient must meet at least one)- History of ASCVD (Atherosclerotic cardiovascular disease)
- Severe primary hypercholesterolemia (e.g., HeFH, LDL-C > 190 mg/dL) without ASCVD
Additional Required Inclusion Criteria (All must be met)- Contraindication, intolerance to, or insufficient LDL-C reduction with maximally tolerated dose of statin, requiring further LDL-C lowering per established guidelines
- Contraindication, intolerance to, or insufficient LDL-C reduction with ezetimibe, requiring further LDL-C lowering per established guidelines
- Contraindication, intolerance to, or insufficient LDL-C reduction with a monoclonal antibody inhibitor of PCSK9, requiring further LDL-C lowering per established guidelines
- Provider acknowledges potential for adverse events with bempedoic acid and will monitor as clinically appropriate
Pregnancy & Reproductive Considerations- Evaluate pregnancy status prior to initiating treatment due to potential fetal harm
- Provide contraceptive counseling on risks vs. benefits if pregnancy occurs during treatment
- Discontinue therapy if pregnancy occurs unless benefits outweigh potential risk to the fetus
Statin Intolerance Definition & Clinical Context- Documented intolerance requires a trial of at least 2 statins causing intolerable unexplained skeletal muscle-related complaints (pain/ache, weakness/cramping) that start or worsen during treatment and resolve upon cessation
- One statin trial must be at the lowest approved dose with alternate day dosing attempted
- Address factors increasing risk for statin intolerance or non-statin causes of muscle symptoms (e.g., hypothyroidism, vitamin D deficiency, drug-drug interactions, excessive alcohol use)
Stepwise Therapy & PCSK9 Preference Guidance- Patients on lower than optimal statin doses should receive ezetimibe as second-line treatment
- For patients on suboptimal statin dosing + ezetimibe with insufficient LDL reduction or unmet goals despite confirmed adherence, consider monoclonal antibody inhibitors of PCSK9
- For completely statin-intolerant patients where ezetimibe is insufficient or not expected to provide desired LDL-C reduction, a monoclonal antibody inhibitor of PCSK9 is preferred over bempedoic acid due to greater expected LDL-C reduction magnitude (50-60% vs 16-36%) and adverse event potential
- For patients with statin intolerance without established ASCVD and LDL-C <190 mg/dL, utilize ezetimibe, bile acid sequestrant (BAS), or combination in appropriate candidates
- For high-risk patients (e.g., diabetes mellitus, 10-year risk score >20%, subclinical atherosclerosis by imaging) without established ASCVD and LDL-C <190 mg/dL: If ezetimibe/BAS/combination fails to achieve clinically meaningful LDL-C reduction (>30% or >50%) or meet goals despite adherence, consider monoclonal antibody inhibitors of PCSK9 or bempedoic acid; PCSK9 inhibitors are preferred due to greater expected reduction and adverse event profile
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ISATUXIMAB-IRFC INJ,SOLN
SARCLISA
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SARCLISA |
2020-03-12 |
Exclusion Criteria- Unable to be observed in clinic for an extended period following the first dose
- Absolute neutrophil count (ANC) < 1000/mm3
- Hemoglobin < 8 g/dL; Must transfuse to hemoglobin above 8 g/dL prior to therapy initiation
- Platelet count < 50,000/mm3 (<30,000/mm3 if myeloma involvement in bone barrow >50%)
- Active or uncontrolled infection
- Known pregnancy
- Lactating
Inclusion Criteria (Indications & Regimens)- Previously treated multiple myeloma, as part of a pomalidomide- or carfilzomib-based regimen
- Newly diagnosed multiple myeloma, in combination with bortezomib, lenalidomide and dexamethasone, in transplant ineligible patients
Additional Inclusion Criteria (All Must Be Met)- Care is provided by a VA or VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult has been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Type and screen patients for Red Blood Cell antibodies PRIOR to starting therapy
- Provider has informed Blood Bank that patient will be starting isatuximab
Additional Inclusion Criteria (Select if Applicable)- Female patients of child-bearing potential: counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for 5 months after stopping treatment
- Male patients with female partners of child-bearing potential: counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for 5 months after stopping treatment
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RIMEGEPANT TAB,ORAL DISINTEGRATING
NURTEC ODT
|
NURTEC ODT |
2020-03-12 |
Exclusion Criteria- Concurrent therapy with a strong CYP3A4 inhibitor
- Concurrent therapy with inhibitors of P-gp
- Concurrent therapy with strong and moderate CYP3A4 inducers
- Uncontrolled hypertension
- History of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- For abortive therapy: concurrent therapy with a triptan or another gepant once rimegepant is initiated
- Pregnancy
Inclusion Criteria- Treatment initiated by a VA/VA Community Care neurologist or locally designated headache expert
- Diagnosis of migraine, with or without aura, per the International Classification of Headache Disorders (ICHD-3)
- Moderate to severe migraine intensity
- Currently receiving preventive therapy for migraine if indicated
- Contraindication, intolerance, or lack of response to trial of two different triptans at a clinically effective dose
Additional Inclusion Criteria- If using rimegepant for abortive therapy in combination with a calcitonin gene related peptide (CGRP)-targeted monoclonal antibody for preventative therapy: patient has been evaluated and counseled on risks of concomitant therapy
Clinical Monitoring & Safety Requirements- Discontinue rimegepant if signs or symptoms of Raynaud’s phenomenon develop
- All patients with a history of Raynaud’s phenomenon should be monitored for and informed about the possibility of recurrence and worsening
- Locally designated headache expert must perform a comprehensive headache assessment including evaluation for medication overuse headache, other secondary headache types, adherence to prior headache therapies, and features that require urgent/emergent evaluation; patient’s headache history should be reviewed to identify triggers, effective preventive treatment (if indicated), and nonpharmacologic interventions
- Patients started on rimegepant must have a scheduled blood pressure check 2-4 weeks after initiation of therapy
- Vascular contraindications to all triptans include ischemic coronary artery disease, previous stroke or transient ischemic attack, peripheral vascular disease, or ischemic bowel disease
- Other contraindications with triptans may be drug interaction related such as concurrent use of a MAO inhibitor
- Safety evidence of concomitant CGRP acting agents is limited; patients may be prone to CGRP-related adverse events involving vasodilation and GI motor-stimulation/prosecretory effects; alternative therapies may benefit patients at high risk for adverse outcomes from this combination (e.g., high risk for ischemic events, severe constipation)
Exclusion Criteria- Concurrent therapy with a strong CYP3A4 inhibitor
- Concurrent therapy with inhibitors of P-gp
- Concurrent therapy with strong and moderate CYP3A4 inducers
- Uncontrolled hypertension
- History of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- For preventive therapy: concurrent preventative therapy with another calcitonin gene related peptide (CGRP) targeting agent (including other gepants and CGRP targeting monoclonal antibodies)
- Pregnancy
Inclusion Criteria- Treatment initiated by a VA/VA Community Care neurologist or locally designated headache expert
- Episodic Migraine defined as 4 to 14 monthly migraine days
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 3 of the following: beta blocker, topiramate, divalproex, SNRI or TCA, and ACE inhibitor or ARB
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks of a therapeutic dose of at least one CGRP-targeted monoclonal antibody
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks of a therapeutic dose of atogepant
Monitoring & Clinical Management Requirements- Discontinue rimegepant if signs or symptoms of Raynaud’s phenomenon develop
- Monitor patients with a history of Raynaud’s phenomenon for and inform about the possibility of recurrence and worsening
- Locally designated headache expert must perform a comprehensive headache assessment including evaluation for medication overuse headache, other secondary headache types, adherence to prior headache therapies, and features requiring urgent/emergent evaluation; review headache history to identify triggers, effective acute treatment, and nonpharmacologic interventions
- Scheduled blood pressure check required 2-4 weeks after initiation of therapy
- If failure or intolerance to erenumab occurs, an alternate non-formulary CGRP-targeted monoclonal antibody must be tried
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TRASTUZUMAB-QYYP INJ
TRAZIMERA
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TRAZIMERA |
2020-02-27 |
Exclusion Criteria- Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Interstitial lung disease or pneumonitis
- Pregnancy
- Lactating
- Primary Inclusion Criteria (One must be fulfilled)
- HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
- HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
- Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
- Care provided by VA or VA Community Care provider of oncology
- Goals of care and role of Palliative Care consult discussed and documented, if appropriate
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception Requirements (Select if applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose
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GLUCERNA LIQUID,NUTRITIONAL SUPPLEMENT
GLUCERNA THERAPEUTIC NUTRITION
|
GLUCERNA THERAPEUTIC NUTRITION |
2020-02-12 |
Inclusion Criteria- VA / VA Community Care provider or Registered Dietitian
- The patient has diabetes or has a documented need requiring an oral dietary supplement designed to assist with glucose control
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TEPROTUMUMAB-TRBW INJ,LYPHL
TEPEZZA
|
TEPEZZA |
2020-01-30 |
Indications & Disease Severity- Diagnosis of Graves’ disease
- Active thyroid eye disease with Clinical Activity Score (CAS) of 4 or greater
- Moderate-severe thyroid eye disease with at least one of the following: lid retraction ≥ 2mm, moderate or severe soft-tissue involvement, proptosis ≥3 mm above normal for race and sex, periodic or constant diplopia
Exclusion Criteria- Urgent surgical ophthalmological intervention needed (e.g., compressive optic neuropathy, severe exposure keratopathy)
- Pregnant or planning to become pregnant during treatment or for 6 months following treatment
Contraception & Pregnancy Management- Patients who can become pregnant: Implement effective contraception prior to initiation and continue for at least 6 months after stopping treatment; discontinue if pregnancy occurs during therapy
- Patients with partners who can become pregnant: Use a barrier contraceptive during treatment and for 6 months after treatment (unless surgically sterile)
Monitoring & Clinical Management- Monitor patients with diabetes or pre-diabetes for hyperglycemia during the course of treatment
- Correct hypo- or hyperthyroidism in patients who are not euthyroid
- Address smoking cessation due to increased risk of disease progression and severity
- Insufficient data to support retreatment after a full 8-infusion course; subsequent courses require local case-by-case adjudication
Provider Requirements- Restricted to VA/VA Community Care provider who is a neuro-ophthalmologist or ophthalmologist with oculoplastic training (generally co-managed with an endocrinologist)
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AVAPRITINIB TAB
AYVAKIT
|
AYVAKIT |
2020-01-23 |
Exclusion Criteria- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
Diagnosis & Indication- Histologically confirmed gastrointestinal stromal tumor (GIST)
- GIST is unresectable or metastatic
Clinical Status- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2
Treatment History & Mutational Profile- Mutational testing shows platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation insensitive to imatinib including PDGFRA D842V
- Progressive disease on prior trials of imatinib, sunitinib, regorafenib AND dose-escalated ripretinib
Care Coordination & Documentation- Prescribed and monitored by a VA / VA Community Care oncologist
- Goals of care and role of Palliative Care consult have been discussed and documented
Reproductive Safety & Counseling- For patients who can become pregnant or whose partners can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- For patients who are breastfeeding/lactating: Advised to avoid providing breastmilk during therapy and for 2 weeks after the final dose
Exclusion Criteria- Platelet count < 50 × 109/L
- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
- Inclusion Criteria (All must be met)
- Documented diagnosis of one of the following subtypes of advanced systemic mastocytosis: aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, or mast cell leukemia
- Prescribed and monitored by a VA / VA Community Care hematologist / oncologist
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3
- Additional Inclusion Criteria (Select if appropriate)
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- For patients who are breastfeeding/lactating: Advised to avoid providing breastmilk during therapy and for 2 weeks after the final dose
Exclusion Criteria- Platelets < 50 × 109/L
- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
Inclusion Criteria- Documented diagnosis of indolent systemic mastocytosis (ISM)
- Care provided by a VA or VA Community Care hematology/oncology provider
Additional Inclusion Criteria- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
- For patients who are breastfeeding/lactating: Advised to avoid providing breastmilk during therapy and for 2 weeks after the final dose.
Indication & Patient Population- Adults with unresectable or metastatic GIST (umGIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations
- Unresectable or metastatic GISTs harboring PDGFRA exon 18 mutations insensitive to imatinib including PDGFRA D842V
Line of Therapy & Prior Treatment Requirements- First-line therapy for unresectable, progressive, or advanced/metastatic GISTs (upmGISTs; amGIST) with PDGFRA exon 18 D842V mutation
- Additional (5th-line) option after progression on approved therapies (imatinib, sunitinib, regorafenib, ripretinib) for upmGISTs with sensitive mutations excluding PDGFRA exon 18 mutations that are insensitive to imatinib including D842V
- Progressive GIST after trials of imatinib and 3 other kinase inhibitors such as sunitinib, regorafenib, and dose-escalated ripretinib
Dosing Regimen- 300 mg PO once daily
- Available in 100 mg, 200 mg, and 300 mg tablets
Safety Considerations & Contraindications- No boxed warnings or contraindications
- Monitor for intracranial hemorrhage (ICH), cognitive effects (e.g., memory impairment, amnesia, somnolence, speech disorder), photosensitivity, and embryofetal toxicity
- Avoid strong CYP3A inhibitors; avoid or reduce dose for moderate CYP3A inhibitors; avoid strong or moderate CYP3A inducers
Guideline Recommendations- FDA: 1st-line therapy for umGIST with PDGFRA exon 18 mutations including recurrent GIST post-resection
- NCCN: Preferred (1st-line) option for unresectable, progressive, or advanced/metastatic GISTs with PDGFRA exon 18 D842V mutation; may be considered for neoadjuvant therapy of localized GIST with PDGFRA D842V mutation
- ESMO: Standard 1st-line therapy for recurrent GIST post-resection or metastatic GISTs with PDGFRA exon 18 D842V mutation; may be considered for neoadjuvant therapy of localized GIST with PDGFRA D842V mutation
Indications- Advanced Systemic Mastocytosis (AdvSM): Treatment of adults with AdvSM, including aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL).
- Indolent Systemic Mastocytosis (ISM): Treatment of adults with ISM.
Limitations & VA Formulary Criteria- Not recommended for treatment of patients with platelet count (PLT) < 50 × 109/L.
- VA formulary use is restricted to:
- AdvSM (ASM, SM-AHN, or MCL) with PLT ≥ 50 × 109/L
- Symptomatic ISM with PLT ≥ 50 × 109/L in patients with an absolute contraindication or unmanageable intolerance to midostaurin.
Dosage & Administration- AdvSM: 200 mg PO QD; continue treatment until disease progression or unacceptable toxicity.
- ISM: 25 mg PO QD.
- Dosage modifications are indicated for adverse reactions, strong or moderate CYP3A inhibitors, and severe hepatic impairment.
Safety & Precautions- Boxed Warnings: None.
- Contraindications: None.
- Other Warnings/Precautions: Intracranial hemorrhage, cognitive effects, photosensitivity, embryofetal toxicity.
- Drug Interactions: Avoid strong CYP3A inhibitors; avoid or reduce dose with moderate CYP3A inhibitors; avoid strong or moderate CYP3A inducers.
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UBROGEPANT TAB
UBRELVY
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UBRELVY |
2020-01-23 |
Exclusion Criteria- Concurrent therapy with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin)
- Uncontrolled hypertension
- History of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- Concurrent therapy with a triptan agent once ubrogepant is initiated
- Concurrent therapy with another gepant prescribed for abortive treatment
- Pregnancy
Inclusion Criteria- Treatment initiated by a VA/VA Community Care neurologist or locally designated headache expert
- Diagnosis of migraine, with or without aura, per the International Classification of Headache Disorders (ICHD-3)
- Moderate to severe migraine intensity
- Currently receiving preventive therapy for migraine if indicated
- Contraindication, intolerance, or lack of response to trial of two different triptans at a clinically effective dose
Additional Inclusion Criteria- If using a combination of a calcitonin gene related peptide (CGRP)-targeted monoclonal antibody for preventative therapy and ubrogepant for abortive therapy: patient has been evaluated and counseled on risks of concomitant therapy
Clinical Monitoring & Safety Requirements- Discontinue ubrogepant if signs or symptoms of Raynaud’s phenomenon develop
- Monitor patients with a history of Raynaud’s phenomenon for recurrence/worsening and inform them about the possibility
- Locally designated headache expert must perform a comprehensive headache assessment, including evaluation for medication overuse headache, other secondary headache types, adherence to prior headache therapies, features requiring urgent/emergent evaluation, identification of triggers, effective preventive treatment (if indicated), and nonpharmacologic interventions
- Scheduled blood pressure check required 2-4 weeks after initiation of therapy
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BUDESONIDE/ FORMOTEROL INHL,ORAL
BREYNA, BUDESONIDE-FORMOTEROL FUMARATE, SYMBICORT
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BREYNA, BUDESONIDE-FORMOTEROL FUMARATE, SYMBICORT |
2020-01-16 |
Exclusion Criteria- Diagnosis of COPD without a concomitant diagnosis of asthma
- Inability to properly use a metered dose inhaler (MDI) (e.g., issues with dexterity)
Inclusion Criteria- Diagnosis of Asthma
- Diagnosis of COPD with concomitant Asthma (Asthma-COPD overlap syndrome [ACOS])
Additional Inclusion Criteria & Clinical Management Guidance- Preference for use of Maintenance and Reliever Therapy (MART) with budesonide/formoterol inhaler
- Patient is unable to tolerate or use a dry powder inhaler (DPI)
- Switching from formulary ICS/LABA (fluticasone/salmeterol) maintenance plus SABA reliever therapy to MART with budesonide/formoterol is generally not encouraged for patients whose symptoms are well controlled
- If switching to MART occurs (e.g., for step-down per GINA Track 1, steps 1-2), educate patients on using a single MDI for MART and discontinue the SABA inhaler
- If the patient prefers continued use of a SABA inhaler for symptom relief, continuation of formulary ICS/LABA is recommended instead
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AMOXICILLIN/ OMEPRAZOLE/ RIFABUTIN CAP,EC
TALICIA
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TALICIA |
2020-01-02 |
Exclusion Criteria- Concomitant rilpivirine, voriconazole or other serious drug-drug interactions that cannot be managed (e.g. other azoles, rifampin, some HIV protease inhibitors, high-dose methotrexate)
- Pregnancy
- History of severe hypersensitivity to penicillins, proton pump inhibitors or rifamycins
- Inability to swallow capsules whole
Inclusion Criteria- Documented H.pylori by laboratory test or pathology
- Failure to at least one course of bismuth quadruple therapy or vonoprazan dual therapy or contraindication to BOTH
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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ENFORTUMAB VEDOTIN-EJFV INJ
PADCEV
|
PADCEV |
2020-01-02 |
Exclusion Criteria- Symptomatic CNS metastases
- Pre-existing sensory or motor neuropathy ≥ Grade 2
- Baseline active keratitis or corneal ulceration
- Moderate or severe hepatic impairment (total bilirubin > 1.5 times the ULN and any AST)
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult discussed and documented
- Patients of child-bearing potential or with partners of child-bearing potential: counseling on contraception and risks vs. benefits provided; effective contraception used during therapy and for 2 months after the last dose
Additional Inclusion Criteria- Locally advanced or metastatic urothelial carcinoma in patients who had previous PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy
- Locally advanced or metastatic urothelial carcinoma in patients ineligible for platinum-containing chemotherapy and received at least 1 prior line of therapy
Monitoring & Management Requirements- Monitor blood glucose in all patients prior to each dose and manage hyperglycemia
- Hold dose until blood glucose is < 250mg/dL
- Hyperglycemia and diabetic ketoacidosis occurred in patients with and without pre-existing diabetes mellitus
Indication & Clinical Setting- Metastatic urothelial carcinoma
- Cisplatin-ineligible patients
Patient Eligibility Criteria (Cisplatin Ineligibility)- Creatinine clearance <60 ml/min
- New York Heart Association (NYHA) Class III or higher
- Grade-2 or higher peripheral neuropathy or hearing impairment
- Eastern Cooperative Oncology Group (ECOG) performance status ≥2
Line of Therapy- First-line therapy in combination with pembrolizumab for cisplatin-ineligible patients
- Single agent enfortumab vedotin remains an option for patients who have progressed on at least one other line of systemic therapy
Formulary & Administrative Requirements- Recommended for addition to the national formulary with PA-F (Prior Authorization)
- VA Clinical Pathways updated to include enfortumab vedotin plus pembrolizumab as an option for patients determined to be ineligible for cisplatin
Dosing & Administration- Enfortumab vedotin 1.25 mg/kg (maximum 125mg) IV over 30 minutes on Days 1 & 8 of a 21-day cycle
- Pembrolizumab 200mg IV on day 1 of a 21-day cycle
Exclusion Criteria- Symptomatic CNS metastases
- Pre-existing sensory or motor neuropathy ≥ Grade 2
- Baseline active keratitis or corneal ulceration
- Moderate or severe hepatic impairment (total bilirubin > 1.5 times the ULN and any AST)
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Active Autoimmune Disease requiring systemic treatment
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Locally advanced or metastatic urothelial carcinoma in combination with Pembrolizumab
Pregnancy & Contraception Requirements- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 2 months after stopping treatment
Monitoring & Management Notes- Monitor blood glucose in all patients prior to each dose and manage hyperglycemia; hold dose of enfortumab vedotin until blood glucose is < 250mg/dL
- Hyperglycemia and diabetic ketoacidosis occurred in patients with and without pre-existing diabetes mellitus.
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FAM-TRASTUZUMAB DERUXTECAN-NXKI INJ
ENHERTU
|
ENHERTU |
2020-01-02 |
Exclusion Criteria- Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Interstitial lung disease or pneumonitis
- Pregnancy
- Lactating
- Primary Inclusion Criteria (One must be fulfilled)
- HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
- HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
- Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
- Care provided by VA or VA Community Care provider of oncology
- Goals of care and role of Palliative Care consult discussed and documented, if appropriate
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception Requirements (Select if applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose
Exclusion Criteria- Known hypersensitivity to fam-trastuzumab deruxtecan or its excipients (L-histidine, sucrose, polysorbate 80)
- Clinically significant cardiovascular disease* (Baseline Left Ventricular Ejection Fraction < 50% via MUGA or echocardiography; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; symptomatic Congestive Heart Failure New York Heart Association Class 2-4)
- History of, current, or suspected interstitial lung disease/pneumonitis
- Clinically active (untreated and symptomatic) Central Nervous System metastases
- Uncontrolled HIV or active hepatitis B or C infection
- Absolute Neutrophil Count < 1500/mm3 and/or platelet count < 100,000/mm3
- Creatinine clearance < 30 ml/min
- Total bilirubin > 3 – 10 times Upper Limit of Normal and any AST
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria (Select one)- Unresectable or metastatic HER2-positive breast cancer with prior anti-HER2-based regimen in metastatic, neoadjuvant, or adjuvant setting
- Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma with prior trastuzumab-based regimen
- Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+ and ISH negative) breast cancer with at least one prior line of chemotherapy for metastatic disease or disease recurrence within 6 months of adjuvant chemotherapy
Additional Inclusion Criteria (Must be fulfilled)- Oncologic care provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
Additional Inclusion Criteria (Select if applicable)- For patients who can become pregnant or have partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months following the last dose
Indications & Patient Population- • Adults with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior anti-HER2 therapies in the metastatic setting
- • Adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen
Dosing & Administration- • Breast cancer: 5.4 mg/kg IV once every 3 weeks
- • Gastric cancer: 6.4 mg/kg IV once every 3 weeks
- • Do NOT substitute for or with trastuzumab, trastuzumab biosimilars, or ado-trastuzumab emtansine
Safety Monitoring & Management Requirements- • Interstitial lung disease (ILD) and pneumonitis: Closely monitor for cough, dyspnea, fever, and other new or worsening respiratory symptoms; permanently discontinue in patients with Grade 2 or higher ILD/pneumonitis
- • Neutropenia: Monitor CBC at baseline, prior to each dose, and as clinically indicated
- • Left Ventricular Dysfunction: Evaluate LVEF at baseline and at regular intervals as clinically indicated; permanently discontinue in symptomatic CHF
- • Moderately emetogenic: Ensure appropriate antiemetics are provided to prevent acute and delayed nausea/vomiting
Contraindications & Warnings- • Embryo-fetal harm: Advise patients of the risk and need for effective contraception
- • Contraindications: None
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DEFERASIROX TAB,ORAL
JADENU
|
JADENU |
2019-12-12 |
Exclusion Criteria- Creatinine clearance <40 mL/min/1.73m2
- Severe (Child-Pugh C) hepatic impairment
- Terminal high-risk Myelodysplastic Syndrome (MDS-excess blasts)
- Unmanageable CYP2C8, CYP1A2, UGT, bile sequestrant, or aluminum-containing antacid drug interactions
- Baseline ophthalmology exam not completed
- Known hypersensitivity to deferasirox or any of its components
- Breastfeeding
Inclusion Criteria- Chronic iron overload due to red blood cell transfusion dependence
- Chronic iron overload in patients with non-transfusion-dependent thalassemia (NTDT) syndromes, and a liver iron concentration (LIC) of at least 5 mg Fe per gram of dry weight and a serum ferritin greater than 300 mcg/L
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Pregnancy Counseling Requirement- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective non-hormonal contraception during therapy
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GIVOSIRAN INJ,SOLN
GIVLAARI
|
GIVLAARI |
2019-12-05 |
Exclusion Criteria- History of or anticipated liver transplantation
Inclusion Criteria- Provider/Specialty Restriction: Restricted to VA / VA Community Care provider in dermatology, gastroenterology, gynecology, hematology, hepatology, or neurology, or in consultation with one of these specialties
- Diagnosis Requirements: Diagnosis of acute hepatic porphyria by at least ONE of the following:
- Genetic testing confirming mutation for acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, or aminolevulinic acid (ALA) dehydratase deficient porphyria
- OR confirmation of acute hepatic porphyria by documentation of clinical features (e.g., severe abdominal pain or other neurovisceral symptoms) and laboratory parameters (e.g., urinary or plasma porphobilinogen [PBG] or ALA at least four times the upper limit normal) during an acute attack
- Disease Activity & Attack History: Active disease with at least 2 porphyria attacks requiring hospitalization, urgent healthcare visit, or intravenous hemin administered within the past 6 months despite avoidance of potential precipitating factors AND intravenous hemin prophylaxis administered more than once weekly or documented intolerance to hemin
- Women with Menstrual Cycle-Related Attacks: Intolerance to or ineffective prophylaxis with a gonadotropin-releasing hormone analogue
Continuation & Evaluation Criteria- Evaluate continuation of therapy based on patient response as evidenced by improvement (e.g., reduction in number of attacks requiring hospitalization, urgent care visit, or administration of intravenous hemin), disease stabilization or absence of disease progression, and ability to tolerate treatment
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DEFERASIROX TAB,SUSP,ORAL
EXJADE
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EXJADE |
2019-11-25 |
Exclusion Criteria- Creatinine clearance <40 mL/min/1.73m2
- Severe (Child-Pugh C) hepatic impairment
- Terminal high-risk Myelodysplastic Syndrome (MDS-excess blasts)
- Unmanageable CYP2C8, CYP1A2, UGT, bile sequestrant, or aluminum-containing antacid drug interactions
- Baseline ophthalmology exam not completed
- Known hypersensitivity to deferasirox or any of its components
- Breastfeeding
Inclusion Criteria- Chronic iron overload due to red blood cell transfusion dependence
- Chronic iron overload in patients with non-transfusion-dependent thalassemia (NTDT) syndromes, and a liver iron concentration (LIC) of at least 5 mg Fe per gram of dry weight and a serum ferritin greater than 300 mcg/L
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Pregnancy Counseling Requirement- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective non-hormonal contraception during therapy
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DIROXIMEL FUMARATE CAP,EC
VUMERITY
|
VUMERITY |
2019-11-14 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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TRASTUZUMAB-DKST INJ
OGIVRI
|
OGIVRI |
2019-11-14 |
Exclusion Criteria- Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Interstitial lung disease or pneumonitis
- Pregnancy
- Lactating
- Primary Inclusion Criteria (One must be fulfilled)
- HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
- HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
- Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
- Care provided by VA or VA Community Care provider of oncology
- Goals of care and role of Palliative Care consult discussed and documented, if appropriate
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception Requirements (Select if applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose
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IVERMECTIN CREAM,TOP
SOOLANTRA
|
SOOLANTRA |
2019-10-24 |
Prescriber Requirements- Provider must be a VA dermatologist or other provider locally designated to prescribe ivermectin 1% cream
Patient Diagnosis & Clinical Presentation- Documented diagnosis of papulopustular rosacea (may be mixed presentation with other rosacea subtype)
Treatment History & Medication Response- Inadequate response despite appropriate trials of at least two alternative topical treatments alone
- Inadequate response despite one trial of an alternative topical treatment in combination with an oral antibiotic
Additional Clinical Notes- Oral antibiotics used for rosacea include doxycycline, minocycline, azithromycin, and clarithromycin
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DAUNORUBICIN/ CYTARABINE INJ,LYPHL
VYXEOS
|
VYXEOS |
2019-10-09 |
Exclusion Criteria- Hypersensitivity to daunorubicin, cytarabine or any of its components
- Pregnancy (known pregnancy or positive pregnancy test) and/or actively breastfeeding
- Prior cumulative anthracycline exposure > 368 mg/m2 daunorubicin or equivalent
- Class III or IV heart failure symptoms (NYHA staging system)
- Left Ventricular Ejection Fraction < 50% (via echo, MUGA, MRI, etc.)
- Uncontrolled infection
- History of Wilson’s disease or another copper-metabolism disorder
- Tbili > 2.0 mg/dL (unless with Gilbert’s Syndrome); ALT or AST > 3x ULN
- Severe renal impairment or end-stage renal disease, defined as Clcr < 30 ml/min
Inclusion Criteria- Diagnosis of therapy-related AML (t-AML) OR diagnosis of AML with myelodysplasia-related changes (AML-MRC) OR diagnosis of AML with antecedent MDS or CMML
- Patient has not received treatment for newly-diagnosed t-AML, AML-MRC or with antecedent MDS or CMML
- Goals of care and role of Palliative Care Consult have been discussed and documented
- ECOG Performance Status 0-2
- For women of childbearing potential: Pregnancy must be excluded prior to receiving; contraceptive counseling on risks vs. benefits provided; effective contraception advised during treatment and for at least 6 months after last dose; males with female partners of reproductive potential advised to use effective contraception during treatment and for at least 6 months after last dose, with counseling that fertility may be compromised; women advised not to breastfeed during treatment and for at least 2 weeks after last dose.
Monitoring- Prior to induction: evaluate cardiac function, renal and liver function tests
- TLS parameters for those at risk
- Prior to each consolidation cycle: evaluate cardiac function, CBC, renal and liver function tests
- Pregnancy test (in women of childbearing potential) at baseline
Discontinuation Criteria- Signs or symptoms of acute copper toxicity
- Severe infusion reaction or any life-threatening hypersensitivity reaction
- Worsening cardiac function, unless benefit outweighs risk (consider cardiology consultation)
- Decline in ECOG performance status to level unacceptable to maintain quality of life
Dosage & Administration / Clinical Considerations- Refer to Product Information for dosing, dose modifications and administration details
- Boxed warning: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-CONTAINING PRODUCTS
- Antiemetic potential per ASCO Clinical Practice Guidelines 2017: moderate
- Use appropriate measure to prevent Tumor Lysis Syndrome (TLS)
- Due to prolonged neutropenia expected following treatment, provide standard antimicrobial prophylaxis for induction of acute leukemia
- Consider risks vs. benefits in patients with Wilson’s disease, as use in this population has not been studied
- Concomitant cardiotoxic drugs may increase risk of cardiotoxicity, necessitating more frequent cardiac function assessment
- Concomitant hepatotoxic drugs may affect liver function, increasing toxicity and necessitating more frequent liver function assessment
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ISTRADEFYLLINE TAB
NOURIANZ
|
NOURIANZ |
2019-10-04 |
Exclusion Criteria- Patient is taking a strong CYP3A4 inducer
- Severe hepatic impairment (Child-Pugh Class C)
- End-stage renal disease (CrCl less than 15 mL/min) or hemodialysis
- Pregnancy
Inclusion Criteria- Patient is under the care of a VA or VA Community Care neurologist or locally designated expert
- Diagnosis of Parkinson’s disease (PD) with at least 2 hours of OFF time per day
- Patient is receiving carbidopa/levodopa at least four times daily, with dose stable for at least 4 weeks prior to request
- Attempts to reduce dosing intervals of carbidopa/levodopa have not adequately resolved OFF periods
- Use of carbidopa/levodopa extended-release (ER) capsule formulation (RYTARY) or controlled-release (CR) tablet formulation throughout the day has not adequately resolved OFF periods
- Contraindication, intolerance, or inadequate therapeutic response to at least one agent from two of the following classes: dopamine agonist, catechol-O methyl transferase [COMT] inhibitor, monoamine oxidase type B [MAO B] inhibitor
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
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PITOLISANT TAB
WAKIX
|
WAKIX |
2019-10-04 |
Exclusion Criteria- Excessive daytime sleepiness associated with OSA not receiving primary therapy (e.g., CPAP)
- Severe hepatic impairment (e.g., Child-Pugh C)
- Known hypersensitivity to pitolisant
- Receiving a drug known to prolong the QT interval
- End-stage renal disease (e.g., eGFR < 15 ml/min)
- Patient with known QT prolongation
- Symptomatic bradycardia
- Hypokalemia
- Hypomagnesemia
- Receiving a centrally acting histamine-1 receptor antagonist
Inclusion Criteria- Treatment of excessive daytime sleepiness (EDS) OR cataplexy associated with narcolepsy
- Epworth Sleepiness Scale (EES) is > 14
- Documented lack of efficacy with, is intolerant of, or has contraindications to modafinil OR armodafinil
- Prescribed and monitored by a VA/VA Community Care sleep specialist / pulmonologist / neurologist or locally designated expert in sleep disorders
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SEMAGLUTIDE TAB
RYBELSUS, WEGOVY
|
RYBELSUS, WEGOVY |
2019-10-04 |
Indications & Eligibility- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance
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TAFAMIDIS CAP,ORAL
VYNDAMAX
|
VYNDAMAX |
2019-09-11 |
Indication- Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Provider Requirements- Provider is a VA or VA Community Care cardiologist or locally designated ATTR-CM provider
Diagnostic & Laboratory Criteria- Diagnosis of wild type or hereditary TTR genotype ATTR-CM based on 1) endomyocardial biopsy OR 2) echo/MRI suggestive of amyloidosis confirmed with radionuclide imaging (e.g., technetium-pyrophosphate [Tc99-PYP] scintigraphy)
- Assessment of monoclonal protein screen for and exclusion of light chain (AL) amyloidosis
Clinical Presentation- History of symptomatic heart failure (at least one hospitalization for heart failure OR clinical evidence of heart failure manifested by signs and symptoms of volume overload or elevated intracardiac pressures)
Counseling & Documentation- Discussion with patient/caregiver/family member regarding realistic treatment expectations and discontinuation should be documented
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment
Exclusion Criteria- Heart failure without definitive evidence of transthyretin-mediated amyloidosis (ATTR) (e.g., heart failure secondary to ischemic heart disease)
- Patient receiving concomitant therapy for ATTR amyloidosis (e.g., patisiran, eplontersen, inotersen, vutrisiran, acoramidis)
- End stage heart disease and anticipated survival < 1 year
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ENTRECTINIB CAP,ORAL
ROZLYTREK
|
ROZLYTREK |
2019-08-29 |
Exclusion Criteria- Prior history of prolonged QTc interval (repeated QTc interval >450 msec) or risk factors for torsade de pointes
- Gastrointestinal condition that may interfere with entrectinib absorption
- Interstitial lung disease, interstitial fibrosis, or tyrosine kinase inhibitor-induced pneumonitis
- Prior ROS1 or NTRK tyrosine kinase inhibitor therapy
- Unmanageable drug interaction identified
- Creatinine clearance <30 mL/min
- Total bilirubin >1.5 times the ULN (unless with Gilbert’s syndrome)
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Female patients of child-bearing potential or male patients with female partner of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment; use effective contraception during therapy and for at least 5 weeks (female patients) or 3 months (males and female partners) after the final dose
- Additional Inclusion Criteria (At least one must be met)
- Patient with metastatic non-small cell lung cancer whose tumor is ROS1-positive
- Patient with solid tumor that is metastatic or unresectable AND:
- Has a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation AND
- Has progressed following treatment or has no satisfactory alternative therapy
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FEDRATINIB CAP,ORAL
INREBIC
|
INREBIC |
2019-08-29 |
Diagnosis & Indication- Intermediate (INT)-2- or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera or post-essential thrombocythemia)
- Splenomegaly by palpation (at least 5 cm below costal margin) or imaging
- ECOG performance status of 0 to 2
Laboratory & Hematologic Parameters- Absolute neutrophil count less than 1.0 x 109/L
- Platelet count less than 50 x 109/L
- Thiamine level within the normal reference range used by local laboratory; if deficient, replete thiamine prior to initiating fedratinib
- Ruxolitinib medically inadvisable due to absolute neutrophil count persisting below 0.75 x 109/L (note: to give fedratinib, neutropenia should be grade ≤ 2 and platelet count ≥ 50 x 109/L)
- Fedratinib prescribed at the FDA-approved dose for myelofibrosis, modified as recommended for severe renal impairment (CrCl 15–29 mL/min), Grade 3 or 4 toxicities, and treatment-emergent transfusion dependence
Infectious Disease Screening & Management- History of recurrent Wernicke’s encephalopathy
- Active, uncontrolled systemic or localized infection
- Untreated latent or active tuberculosis infection
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Active hepatitis A
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis
- Antiviral prophylaxis for HBV: Agents with high genetic barrier to resistance such as entecavir or tenofovir should be used
- Completed hepatitis B screening (at minimum, HBsAg, anti-HBc and anti-HBs)
- Anti-HBs may help to identify patients who require initial or booster vaccination (anti-HBs titers >= 10 IU/L are generally considered protective) or HBsAg-negative patients without past vaccination who have occult HBV from past infection (anti-HBs positive and lost anti-HBc)
- Untreated hepatitis C
- Completed hepatitis C screening
- Untreated HIV infection or at high risk for HIV infection
Hepatic & Renal Function- Severe liver impairment (Child-Pugh Class C)
- Total bilirubin ≥ 3.0 x ULN
- AST or ALT ≥ 2.5 x ULN
- History of chronic liver disease, unless a hepatologist documents that fedratinib may be initiated safely
- Serum amylase or lipase > 1.5 x ULN
Cardiac Status- Uncontrolled NYHA Class 3 or 4 heart failure, unless a cardiologist documents that fedratinib may be initiated safely
Concomitant Medications & Vaccinations- Strong or moderate CYP3A4 inDUCers (e.g., rifampin)
- Dual CYP3A4 and CYP2C19 inhibitors (e.g., fluvoxamine)
- Concomitant fluconazole required at doses greater than 200 mg daily
- Fedratinib prescribed with modifications recommended for CYP3A4 inhibitor drug interactions
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Reproductive Health & Counseling- Breastfeeding
- For women of childbearing age and men who partner with women of childbearing potential: Provided counseling on use of effective contraception to prevent pregnancy and on risks and benefits of treatment
Monitoring & Care Coordination- Unable to comply with recommended laboratory monitoring
- Patient able and willing to have hemoglobin monitored for transfusion requirement
- Patient able and willing to have thiamine levels monitored
- Care provided by a VA / VA Community Care hematologist or locally designated myelofibrosis expert
- Goals of care and role of Palliative Care consult discussed and documented
- Ruxolitinib is medically inadvisable, not tolerated despite dosage modifications, or not adequate
- For patients on ruxolitinib: Ruxolitinib has been tapered and discontinued before initiation of fedratinib
- Not adequate refers to NO spleen size reduction or myelofibrosis symptom improvement, or worsening of spleen size or myelofibrosis symptoms after 6 months of ruxolitinib therapy, or loss of initial response
Supportive Care & Administration- Uncontrolled alcohol use disorder
- Patient will receive antiemetics (e.g., ondansetron) to prevent or treat fedratinib-induced nausea or vomiting
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LEFAMULIN INJ,SOLN
XENLETA
|
XENLETA |
2019-08-29 |
Exclusion Criteria- Prolonged QT interval
- Patients with history of ventricular arrhythmias
- Pregnancy (pregnancy status should be verified in women of childbearing potential) or lactation
- Concomitant receipt of strong CYP3A4 inducers (e.g. rifampin, applies to both oral and injection) or strong CYP3A4 inhibitors (applies to oral only)
- Concomitant receipt of sensitive 3A4 substrates that prolong the QT interval (e.g. pimozide)
- Concomitant receipt of Class 1a or class III antiarrhythmic agents
Inclusion Criteria- Prescriber is an VA/VA Community Care Infectious Diseases or other facility authorized provider
- Patient has a diagnosis of community acquired bacterial pneumonia
- PORT (PSI) classification of II, III or IV
- Women of childbearing age agree to a pregnancy test and to use appropriate contraception until at least 2 days after the last dose
- Additional Inclusion Criteria (Must meet one of the following)
- Intolerance to fluoroquinolones, macrolides AND doxycycline
- Severe beta-lactam allergy AND high risk for FQ adverse events
Special Considerations/Exceptions- Lactating women may be considered if they discard milk during treatment and for 2 days after final dose
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LEFAMULIN TAB,ORAL
XENLETA
|
XENLETA |
2019-08-29 |
Exclusion Criteria- Prolonged QT interval
- Patients with history of ventricular arrhythmias
- Pregnancy (pregnancy status should be verified in women of childbearing potential) or lactation
- Concomitant receipt of strong CYP3A4 inducers (e.g. rifampin, applies to both oral and injection) or strong CYP3A4 inhibitors (applies to oral only)
- Concomitant receipt of sensitive 3A4 substrates that prolong the QT interval (e.g. pimozide)
- Concomitant receipt of Class 1a or class III antiarrhythmic agents
Inclusion Criteria- Prescriber is an VA/VA Community Care Infectious Diseases or other facility authorized provider
- Patient has a diagnosis of community acquired bacterial pneumonia
- PORT (PSI) classification of II, III or IV
- Women of childbearing age agree to a pregnancy test and to use appropriate contraception until at least 2 days after the last dose
- Additional Inclusion Criteria (Must meet one of the following)
- Intolerance to fluoroquinolones, macrolides AND doxycycline
- Severe beta-lactam allergy AND high risk for FQ adverse events
Special Considerations/Exceptions- Lactating women may be considered if they discard milk during treatment and for 2 days after final dose
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UPADACITINIB TAB,SA (EXTENDED RELEASE)
RINVOQ
|
RINVOQ |
2019-08-29 |
Infections & Screening Requirements- Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Must complete tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Must complete hepatitis B screening (at minimum, HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs])
- Must have current or past completion of hepatitis C screening
Malignancy & Cardiovascular/Thrombotic Risk- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Laboratory & Organ Function Parameters- Lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once resolved)
- Severe hepatic impairment (Child-Pugh class C)
Concomitant Medications, Vaccines & Reproductive Health- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics or potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), except overlaps during treatment transition
- Concomitant therapy with strong CYP3A4 inducers (e.g., rifampin)
- Pregnancy
- Breastfeeding
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Provider Oversight & Diagnostic Requirements- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Has inflammatory articular disease (joint, spine, and/or entheseal) and a definite or provisional diagnosis of active psoriatic arthritis
Prior Biologic Therapy & Adjudication Considerations- ONE tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, or not adequate after 3 months
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- TNFI may be medically inadvisable for reasons including heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent/serious infections, or aversity to injections/barriers to in-clinic administration (adjudicated case-by-case)
- IL-17A inhibitor (ixekizumab preferred) may be medically inadvisable due to inflammatory bowel disease (IBD), as they can worsen IBD
- Ustekinumab may be medically inadvisable for axial psoriatic arthritis, as it is ineffective for ankylosing spondylitis
Indication & Disease Severity- Diagnosis of chronic atopic dermatitis
- Within 2 weeks of starting upadacitinib therapy, determination of severity by Gestalt Assessment (GA) of “moderate” or “severe” OR Eczema Area and Severity Index (EASI) ≥ 16 (scale 0–72)
- When practical, SCORing Atopic Dermatitis (SCORAD) index and Patient Oriented Eczema Measure (POEM) may be considered
Exclusion Criteria & Contraindications- Uncontrolled active infection (may start/restart once treatment for the infection is initiated)
- Untreated latent or active tuberculosis
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis; agents with high genetic barrier to resistance such as entecavir or tenofovir should be used)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients can be treated)
- Congenital or acquired immunodeficiency
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless dermatologist and oncologist agree risk-benefits favor use)
- Thrombosis or major adverse cardiovascular events in which potential harms are expected to outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once values normalize)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, or potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus) [except overlaps during treatment transition; co-use with antirheumatic doses of conventional immunomodulators such as methotrexate or leflunomide is acceptable]
- Pregnancy
- Breastfeeding
- Administration of inactivated, live, or live-attenuated vaccines within 2 weeks before initiation
Infectious Disease Screening & Monitoring- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Routine retesting not required for prescription renewals; consider in high-risk patients
Prior Therapy Requirements- Dupilumab OR tralokinumab-ldrm therapy is medically inadvisable, not tolerated, not adequate, or lost response (NO response after 12 weeks or inadequate response after 16 weeks)
- If dupilumab or tralokinumab-ldrm is contraindicated, therapies required prior to those biologic agents must still be tried
Vaccination Requirements- Offered all age-appropriate vaccinations prior to initiating therapy
- When possible, vaccinations should be updated before initiation
- Unless contraindicated, recombinant zoster (SHINGRIX equivalent) vaccine should be completed or at least initiated by the end of the first year of treatment, preferably when dosage is low, disease is stable, or at other times when a robust immune response can be expected
Special Populations & Counseling- For females who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits
- If HBsAg-negative but anti-HBc-positive and consult deemed indicated: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
Provider Oversight- Prescribed and monitored by a VA/VA Community Care dermatologist OR an immunologist, allergist, or locally designated expert in the management of atopic dermatitis in consultation with a VA/VA Community Care dermatologist
Indication & Patient Population- • Adults with refractory, moderate to severe atopic dermatitis
- • Patients who are candidates for systemic therapy
Treatment History & Place in Therapy- • Indicated when other systemic drug products, including biologics, have provided an inadequate response or when use of those therapies is medically inadvisable
- • May be used following inadequate response or intolerance to other systemic therapies, including but not limited to phototherapy, short-term induction therapy with cyclosporine or a systemic corticosteroid (if indicated), two conventional maintenance therapies, and dupilumab
- • Place in therapy is equivalent to abrocitinib
Limitations of Use- • Not recommended for co-administration with other JAK inhibitors (JAKIs)
- • Not recommended for co-administration with biologic immunomodulators
- • Not recommended for co-administration with other immunosuppressants
Dosing & Administration- • Adults < 65 years: Initiate at 15 mg once daily; if response is inadequate, increase to 30 mg once daily; discontinue if response to 30 mg is inadequate; use the lowest effective dose to maintain response
- • Adults ≥ 65 years: 15 mg once daily
- • Severe renal impairment (CrCL < 30 mL/min): 15 mg once daily
- • Mild or moderate renal impairment (CrCL > 30 mL/min): No dosage adjustment is needed
Pre-treatment Requirements- • Refer to the prescribing information for important pre-treatment assessments
Indication & Patient Population- • Adults with active psoriatic arthritis (PsA)
- • Patients who have had an inadequate response or intolerance to one or more TNFIs
- • Patients who refuse TNFI therapy due to safety concerns
Treatment History & Sequencing- • Placed after TNFIs in the treatment sequence
- • May be used despite therapy with one TNFI
- • May be preferred over ustekinumab, IL-23 inhibitors, apremilast, and abatacept for patients requiring treatment for axial PsA or ankylosing spondylitis
- • May be less preferable than tofacitinib and other agents (except abatacept) for patients with psoriatic nail involvement
- • Tofacitinib may be preferred over upadacitinib when a JAKI is indicated due to cost considerations
Dosing & Administration- • 15 mg once daily (only dose approved for PsA; escalation to 30 mg is only approved for atopic dermatitis)
- • No dosage adjustment required for renal impairment in PsA
- • May be used as monotherapy
Treatment Duration & Response Assessment- • A 12-week trial may be adequate; if nonresponse occurs by 12 weeks, an alternative treatment may be considered. For partial responders at 12 weeks, therapy may continue up to 24 weeks to improve response.
Limitations & Safety Considerations- • Not recommended in combination with other JAKIs, biologic DMARDs, or potent immunosuppressants (e.g., azathioprine, cyclosporine)
- • Not recommended in severe (Child-Pugh class C) liver disease
- • Carries Boxed Warnings for mortality, malignancy, major adverse cardiovascular events, and thrombosis regardless of indication
Pre-treatment Requirements- • Refer to the prescribing information for important pre-treatment assessments
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for the infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are permitted)
- Congenital or acquired immunodeficiency
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless treating rheumatologist and oncologist agree risk-benefits favor use)
- At increased risk of thrombosis where potential harms are expected to outweigh anticipated benefits
- Lymphopenia, neutropenia, or anemia (may start/restart once resolved; defined as lymphocyte count <500 cells/mm3, absolute neutrophil count <1000 cells/mm3, hemoglobin <8 g/dL)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, or potent immunosuppressants (except during treatment transition overlaps)
- Concomitant therapy with strong CYP3A4 inducers (e.g., rifampin)
- Pregnancy
- Breastfeeding
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Moderate to severe active rheumatoid arthritis
- Prescribed at the FDA-recommended dose for rheumatoid arthritis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response
Additional Inclusion/Justification Criteria- If HBsAg-negative but anti-HBc-positive and consult is deemed indicated: Consultation with a GI/liver or infectious diseases expert for advice on starting antiviral prophylaxis or preemptively monitoring for HBV reactivation
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 5 months after stopping treatment
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits of treatment
Indication & Diagnosis- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA/VA Community Care gastroenterologist or UC expert
Exclusion Criteria- Uncontrolled, active, severe infection (including C. difficile and undrained abscess) [may start/restart once infection treatment initiated]
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis [may initiate after starting antiviral prophylaxis]
- Untreated HIV infection [treated, well-controlled, asymptomatic HIV-positive patients may be treated]
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or cervical cancer (unless treating gastroenterologist and oncologist agree risk-benefits favor use)
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL [may start/restart once values normalize]
- End stage renal disease (eGFR < 15 mL/min/1.73 m2)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant live or live-attenuated vaccines, or administration of inactivated/live/live-attenuated vaccines < 2 weeks before initiation
- Concomitant JAK inhibitors, biologic immunomodulators, or potent immunosuppressants (e.g., azathioprine, cyclosporine)
- Concomitant strong CYP3A4 inducers
- Pregnancy (during therapy and for 4 weeks after last dose)
- Breastfeeding/providing breastmilk to an infant (during therapy and for 6 days after last dose)
Inclusion Criteria (All Must Be Met)- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, anti-HBs)
- Current or past completion of hepatitis C screening [may initiate while waiting for results]
Additional Inclusion Criteria (One Must Be Met)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar is preferred TNFI in UC)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in presence of adequate TNFI levels (mechanistic failure)
- Loss of response to a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
Additional Inclusion Criteria (Select if Appropriate)- If HBsAg-negative but anti-HBc-positive: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis vs. preemptive monitoring for HBV reactivation
- For women who can become pregnant: Pregnancy status verified; counseling provided on risks vs benefits and use of effective contraception during therapy and for 4 weeks after discontinuation
Dosing & Sequencing Requirements- Prescribe at FDA-recommended dose for UC, adjusting for severe renal impairment (eGFR 15 to <30 mL/min/1.73 m2), mild/moderate hepatic impairment (Child-Pugh A or B), and strong CYP3A4 inhibitors
- Sequencing: 1L Infliximab (preferred) or adalimumab; 2L/3L includes upadacitinib (one drug must be risankizumab-rzaa as 2L or 3L); 4L Mirikizumab-mrkz, guselkumab, or ustekinumab
- Routine retesting for TB, HBV, HCV not required for prescription renewals; retest in high-risk patients
Indications & Patient Population- • Treatment of adults with active ankylosing spondylitis (AS) who have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs).
- • Treatment of adults with active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have had an inadequate response or intolerance to TNFIs.
- • Limitations of Use: Not recommended for use in combination with other JAKIs, biologic immunomodulators, or potent immunosuppressants such as azathioprine and cyclosporine.
Dosage & Administration- • 15 mg once daily.
- • Form: Extended-release tablets.
Dose Modifications & Interruptions- • Renal impairment: No dosage adjustment recommended for mild, moderate, or severe renal impairment in patients treated for AS or nr-axSpA.
- • Hepatic impairment: Use is not recommended in severe hepatic impairment. No dosage adjustment needed for mild or moderate hepatic impairment (Child-Pugh A or B) in patients treated for AS or nr-axSpA.
- • Strong CYP3A4 inducers: Use is not recommended.
- • Strong CYP3A4 inhibitors: No dosage modification recommendation for AS or nr-axSpA.
- • Infections: Interrupt treatment; may restart when infection is controlled.
- • Hematologic parameters: Interrupt treatment if absolute neutrophil count < 1000 cells/mm3, absolute lymphocyte count < 500 cells/mm3, or hemoglobin < 8 g/dL; may restart once values return to above these thresholds.
- • Hepatic transaminases: Interrupt treatment for elevated hepatic transaminases or suspected drug-induced liver injury until diagnosis is excluded.
Safety Monitoring & Precautions- • Pretreatment tests and evaluations are similar to those for previously approved indications.
- • Boxed warnings, contraindications, and other warnings/precautions are the same as for other approved indications.
- • Common adverse events (≥1%): Upper respiratory tract infections, acne, herpes simplex, headache, blood creatine phosphokinase increased, cough, hypersensitivity, folliculitis, nausea, abdominal pain, pyrexia, increased weight, herpes zoster, influenza, fatigue, neutropenia, myalgia, and influenza-like illness.
Place in Therapy / Clinical Context- • May be used for active AS/r-axSpA or active nr-axSpA with objective signs of inflammation who have an inadequate response or intolerance to TNFIs or for whom TNFIs are medically inadvisable.
- • For active nr-axSpA candidates for JAKI therapy, upadacitinib may be preferred over tofacitinib due to lack of evidence supporting tofacitinib's off-label use for nr-axSpA.
- • JAKIs may be used as alternatives to IL-17AIs when TNFI therapy is inadequate, not tolerated, or medically inadvisable.
- • Evidence does not support use of targeted biologic or synthetic immunomodulators for treatment of patients without inflammatory disease; objective signs of inflammation (e.g., elevated high-sensitivity CRP and/or sacroiliitis on MRI) are required.
Infectious Disease- Active, serious systemic or localized infection (including undrained abscess)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are permitted)
Malignancy & Hematology- Malignancy in the previous 5 years (except successfully treated nonmelanoma skin cancer or cervical cancer, unless rheumatologist and oncologist agree risk-benefit favors use)
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL
Hepatic Function- Severe hepatic impairment (Child-Pugh class C)
Cardiovascular & Thrombotic Risk- Increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Concomitant Medications & Vaccines- Concomitant JAK inhibitors, biologic immunomodulators, or potent immunosuppressants (azathioprine, cyclosporine), except during treatment transitions
- Concomitant strong CYP3A4 inducers (e.g., rifampin)
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Diagnosis & Provider Requirements- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Definite or provisional diagnosis of active axial spondyloarthritis (ankylosing spondylitis/radiographic axial spondyloarthritis or nonradiographic axial spondyloarthritis) made by a VA/VA Community Care rheumatologist
Prior Therapy Requirements- One tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated, or not adequate after 3 months
Laboratory & Screening Requirements- Completed tuberculosis test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening
Additional Inclusion Criteria- If HBsAg-negative but anti-HBc-positive and consult indicated: GI/liver or ID expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- For patients who can become pregnant: Pregnancy status verified; counseling provided on potential risks vs benefits of treatment and use of effective contraception
Clinical Context & Monitoring Notes- Use with extreme caution in patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
- Upadacitinib may be used with methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine
- Vaccinations should be updated before initiation; recombinant zoster vaccine should be completed or initiated by end of first year, preferably when dosage is low, disease is stable, or immune response can be expected
- Applies only to new starts; stable patients should not be switched for nonmedical reasons
Indication & Patient Population- Adults with moderately to severely active Crohn’s disease
- Patients who have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs)
- Limited to second-line use
Dosage & Administration Criteria- Induction: 45 mg once daily for 12 weeks
- Maintenance: 15 mg once daily; a dosage of 30 mg once daily may be considered for refractory, severe, or extensive disease
- Discontinue upadacitinib if an adequate response is not achieved with 30 mg daily
- Use the lowest effective dosage needed to maintain response
- Formulation: Extended-release tablets (15 mg, 30 mg, 45 mg)
Limitations & Contraindications- Not recommended for use in combination with other JAKIs
- Not recommended for use in combination with biologic therapies for Crohn’s disease
- Not recommended for use in combination with potent immunosuppressants such as azathioprine and cyclosporine
Laboratory Monitoring Requirements- Lipid panel (total cholesterol, LDL, HDL) about 12 weeks after initiation of therapy, then per lipid guidelines
- Complete blood count as per routine management
- Latent TB testing and TB activation screening
- Liver panel as per routine management
- Viral hepatitis reactivation screening per guidelines
Efficacy & Clinical Response Criteria- Clinical remission: CDAI < 150; stool frequency ≤ 2.8 daily and average daily abdominal pain score ≤ 1.0 with neither worse than baseline (PRO-2)
- Endoscopic response: >50% decrease from baseline in SES-CD, or ≥2-point reduction from baseline if baseline SES-CD is 4
- Clinical response: ≥30% decrease in stool frequency and/or abdominal pain, or ≥100-point decrease from baseline in CDAI
- Onset of clinical response (CDAI-100) observed at Week 2
Safety Considerations- Monitor for gastrointestinal perforations
- Safety profile is consistent with other approved indications
Place in Therapy & Selection Criteria- Appropriate for induction and maintenance therapy of moderate to severe, active luminal CD
- May be less preferred than risankizumab-rzaa and ustekinumab in patients with co-existing plaque psoriasis
- Preferred over vedolizumab in patients with extraintestinal involvement
Exclusion Criteria- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once infection treatment initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or cervical cancer unless treating gastroenterologist and oncologist agree risk-benefits favor use
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once values normalize)
- End stage renal disease (eGFR < 15 mL/min/1.73 m2)
- Severe hepatic impairment (Child-Pugh C)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Concomitant JAK inhibitors, biologic immunomodulators, or potent immunosuppressants such as azathioprine and cyclosporine
- Concomitant strong CYP3A4 inducers
- Pregnancy (during therapy and for 4 weeks after the last dose)
- Breastfeeding / providing breastmilk to an infant (during therapy and for 6 days after the last dose)
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally designated Crohn’s disease expert
- Current or prior moderate to severe Crohn’s disease (CD) confirmed by endoscopy or imaging
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
Additional Inclusion Criteria (One Required)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar and adalimumab/biosimilar are preferred TNFIs in CD)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of TNFI in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to infliximab/biosimilar and another TNFI for CD despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
Adjudication & Supplemental Considerations- HBsAg-negative but anti-HBc-positive: GI/liver or infectious diseases expert must be consulted for advice on starting antiviral prophylaxis vs preemptive monitoring for HBV reactivation
- Women who can become pregnant: Pregnancy status must be verified; counseling provided on risks vs benefits and use of effective contraception during therapy and for 4 weeks after discontinuation
- Routine retesting for TB, Hepatitis B, and Hepatitis C screening is not required for prescription renewals (retesting in high-risk patients should be considered)
- Drug Sequencing: First-line = Infliximab or adalimumab; Second/Third-line = Vedolizumab, upadacitinib, or risankizumab-rzaa (one drug must be risankizumab-rzaa as 2L or 3L); Fourth-line = Mirikizumab-mrkz or ustekinumab
- Dosing: Prescribe at FDA-recommended dose for ulcerative colitis, adjusting for severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m2), mild to moderate hepatic impairment (Child-Pugh A or B), and strong CYP3A4 inhibitors
- Vaccinations: Update before initiation when possible; recombinant zoster vaccine should be completed/initiated by end of first year, preferably at low dose/stable disease/robust immune response expected
Indication & Patient Selection- • Treatment of adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs)
- • Limitation of Use: Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs, or potent immunosuppressants such as azathioprine and cyclosporine
Pretreatment Tests & Evaluations- • Tuberculosis (TB) screening
- • Viral hepatitis screening (hepatitis B, hepatitis C)
- • Complete blood count (noting neutrophils, lymphocytes, hemoglobin)
- • Liver panel
- • Pregnancy status
- • Update immunizations, including for varicella zoster or herpes zoster prophylaxis per immunization guidelines
Dosing & Administration- • Induction: 45 mg once daily for 8 weeks (extended-release tablets)
- • Maintenance: 15 mg once daily; a dose of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease
- • Discontinue upadacitinib if an adequate response is not achieved with 30 mg
- • Use the lowest effective dosage needed to maintain response
Monitoring During Therapy- • Lipid panel (total cholesterol, LDL, HDL) approximately 12 weeks after initiation of therapy, then per lipid guidelines
- • Complete blood count per routine management
- • Latent TB testing and TB activation monitoring
- • Liver panel per routine management
- • Viral hepatitis reactivation monitoring per guidelines
Efficacy & Response Criteria- • Clinical remission defined as Adapted Mayo score ≤ 2, with stool frequency score (SFS) ≤ 1 and not greater than baseline, rectal bleeding score (RBS) = 0, and endoscopic subscore ≤ 1 without friability
- • Onset of treatment benefit: Earliest significant treatment difference occurred at Week 2; post hoc analysis demonstrated significant differences as early as Day 1 based on SFS ≤ 1/0, RBS = 0, and a 2-item patient-reported outcome (SFS ≤ 1 and RBS = 0)
- • Duration of an adequate therapeutic trial: Approximately 16 weeks (based on extended induction substudy where 58.4% of Week 8 nonresponders achieved clinical response at Week 16); no FDA-approved extended induction dosage regimen is available
Safety Considerations & Warnings- • Boxed warnings, contraindications, and other warnings/precautions are consistent with other approved indications for upadacitinib
- • Common adverse events (≥5%): Induction therapy (upper respiratory tract infection, acne, increased blood creatine phosphokinase, neutropenia); Maintenance therapy (upper respiratory tract infection, increased blood creatine phosphokinase, neutropenia, elevated liver enzymes, rash)
- • Specific safety risks noted: Venous thromboembolism, herpes zoster infection, hepatic disorder (mostly transaminase elevations), neutropenia, and CPK elevation
- • Avoid pregnancy during upadacitinib therapy and for 4 weeks after the end of therapy
Place in Therapy Context- • Alternative to tofacitinib for patients with moderate to severely active UC who have an inadequate response to vedolizumab (if TNFIs are medically inadvisable) or nonresponse, inadequate response, loss of response, or intolerance to TNFIs
- • Network meta-analyses indicate upadacitinib may be significantly more effective than tofacitinib in inducing clinical remission, with similar efficacy for maintenance of clinical remission and glucocorticoid-free remission
- • Associated with the lowest probability of discontinuations due to adverse events relative to infliximab, vedolizumab, and adalimumab, but a higher risk of adverse events than all other drugs except adalimumab 80/40 mg
Infection & Screening- Uncontrolled active infection, including undrained abscess; upadacitinib may be started/restarted once the infection treatment has been initiated
- Untreated latent or active tuberculosis infection
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis; upadacitinib may be initiated after starting antiviral prophylaxis
- Untreated HIV infection; treated, well-controlled, asymptomatic HIV-positive patients can be treated with upadacitinib
- Current or past completion of hepatitis C screening; upadacitinib may be initiated while waiting for test results
- If HBsAg-negative but anti-HBc-positive and patient’s practitioner deems consult is indicated, a GI/liver or infectious diseases expert has been (e-)consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
Malignancy & Cardiovascular Risk- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or cervical cancer, unless it is documented that the treating rheumatologist and oncologist agree that risk-benefits favor using the drug
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh the anticipated benefits
Laboratory Values & Organ Function- Lymphocytes < 500 cells/mm3 confirmed by repeat testing, neutrophils < 1000 cells/mm3 , or hemoglobin < 8 g/dL; upadacitinib may be started/restarted once values normalize
- Severe hepatic impairment (Child-Pugh class C)
Gastrointestinal Risk- At increased risk of gastrointestinal perforation (e.g., history of diverticulitis, concomitant glucocorticoids) where potential harms of therapy are expected to outweigh the anticipated benefits
Concomitant Medications & Vaccinations- Concomitant JAK inhibitors, biologic immunomodulators (e.g., tocilizumab, abatacept), or potent immunosuppressants such as azathioprine and cyclosporine
- Concomitant methotrexate at antirheumatic doses (≤25 mg/WEEK) is allowable but may increase risks of immunosuppression and infection
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation of upadacitinib; when possible, vaccinations should be updated before the patient initiates upadacitinib, with recombinant zoster (SHINGRIX) vaccine completed or at least initiated by the end of the first year of treatment
- Concomitant strong CYP3A4 inDUCers
Pregnancy & Lactation- Pregnancy (during therapy and for 4 weeks after the last dose of upadacitinib)
- Breastfeeding/providing breastmilk to an infant (during therapy and for 6 days after the last dose)
- For females who can become pregnant: pregnancy status verified; counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 weeks after discontinuation of therapy
Dietary Restrictions- Ingestion of food or drink containing grapefruit during therapy
Diagnosis & Clinical Monitoring- Definite or provisional diagnosis of active giant cell arteritis
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Initiated concurrently or after glucocorticoid therapy unless glucocorticoids are medically inadvisable
Screening & Renewal Procedures- Routine rescreening for hepatitis B or hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
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TRASTUZUMAB-ANNS INJ
KANJINTI
|
KANJINTI |
2019-08-01 |
Exclusion Criteria- Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Interstitial lung disease or pneumonitis
- Pregnancy
- Lactating
- Primary Inclusion Criteria (One must be fulfilled)
- HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
- HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
- Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
- Care provided by VA or VA Community Care provider of oncology
- Goals of care and role of Palliative Care consult discussed and documented, if appropriate
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception Requirements (Select if applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose
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ETHINYL ESTRADIOL/ SEGESTERONE RING,VAG
ANNOVERA
|
ANNOVERA |
2019-07-25 |
Indication & Patient Population- • Prevention of pregnancy in females of reproductive potential
- • Not adequately studied in females with a body mass index (BMI) greater than 29 kg/m²
Contraindications- • High risk of arterial or venous thrombotic disease
- • Current or history of breast cancer or other estrogen- or progestin-sensitive cancer
- • Liver tumors, acute hepatitis, or severe (decompensated) cirrhosis
- • Undiagnosed abnormal uterine bleeding
- • Hypersensitivity to ingredients
- • Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir
Warnings & Precautions- • Risk of venous thromboembolic events (VTE) and arterial events (e.g., stroke, myocardial infarction)
- • Liver enzyme elevations
- • Hypertension
- • Potential for gall bladder disease
- • Abnormal uterine bleeding
- • Depression
- • Toxic shock syndrome (TSS)
- • Vaginal and cervical erosion and/or ulceration
- • Risk of vaginal infection with prolonged use
Administration & Storage Requirements- • Patient-inserted into vagina; must remain continuously for 3 weeks (21 days) followed by a 1-week (7-day) ring-free interval
- • Reusable ring stored in provided case during the ring-free interval
- • Provides contraception for 13 cycles (1 year)
- • Must be cleaned with mild soap and water before storage and prior to re-insertion
Special Populations & Interactions- • Pregnancy: No indication for use
- • Lactation: Hormones and metabolites are found in human milk and may reduce milk production; alternative contraception recommended for breastfeeding females
- • Does not protect against sexually transmitted infections including HIV
- • Oil-based (including silicone-based) vaginal lubricants and medications will alter the vaginal system/exposure and should not be used
- • Compatible with water-based vaginal lubricants/creams and male condoms
Clinical Selection Criteria- • Considered when a 12-month product is preferred due to clinical or patient-specific needs (e.g., extended travel or deployment, limited or no access to refrigeration, history of or potential difficulties with obtaining timely refills)
- • Not studied for indications other than pregnancy prevention or dosing regimens outside the product label
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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ICATIBANT INJ,SOLN
FIRAZYR, SAJAZIR
|
FIRAZYR, SAJAZIR |
2019-07-25 |
Exclusion Criteria- Angioedema or abdominal pain not associated with C1 inhibitor deficiency
Inclusion Criteria (ALL must be met)- Restricted to VA / VA Community Care allergy/immunology or dermatology provider; or for use in Emergency Medicine/Urgent Care
- Diagnosis of Hereditary Angioedema due to C1 inhibitor deficiency (HAE-C1INH) as established by laboratory testing
Additional Inclusion Criteria (ONE must be met)- Long-term prophylaxis for HAE-C1INH attacks after consideration of either an attenuated androgen or antifibrinolytic
Clinical Context & Decision-Making Requirements- Prior consideration of an attenuated androgen or antifibrinolytic must be discussed with the patient using shared decision-making, including efficacy, routes of administration, and side effects of each therapy
- Baseline attack rate criteria may include at least 2 attacks per month or baseline attack rate in clinical trials
- Need for long-term prophylaxis should be determined using shared decision-making
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DROSPIRENONE TAB
SLYND
|
SLYND |
2019-07-18 |
Indication(s)- Prevention of pregnancy in females of reproductive potential
- Progestin-only contraceptive pill (POP)
Contraindications- Renal impairment
- Adrenal insufficiency
- Liver tumors (benign or malignant) or hepatic impairment
- Presence or history of cervical cancer or progestin-sensitive cancers
- Undiagnosed abnormal uterine bleeding
- Conditions predisposing to hyperkalemia
Warnings & Precautions- Hyperkalemia: Monitor serum potassium in patients receiving concomitant daily/chronic medications that increase potassium, strong CYP3A4 inhibitors, or who develop conditions increasing hyperkalemia risk
- Thromboembolic disorders: Consider increased risk in postpartum period and history of thromboembolism; consider discontinuation during prolonged immobilization due to surgery or illness
- Bone loss: Unclear if causes clinically significant bone loss; FDA requires post-marketing study
- Uterine bleeding irregularities/amenorrhea: Evaluate for pregnancy or malignancy if bleeding persists or occurs after previously regular cycles; consider pregnancy if scheduled bleeding does not occur
- Liver disease: Discontinue if jaundice or symptoms of liver function disturbances develop
- Risk of hyperglycemia in patients with diabetes
- Ectopic pregnancy
- Cervical cancer
- Depression
Dosing & Administration- 24 active tablets followed by 4 inert tablets daily (24-day on, 4-day off regimen)
- Take one tablet daily at about the same time each day to maintain a 24-hour interval
- 24-hour pill forgiveness for missed or late doses
- If more than one tablet is missed, use backup contraception for 7 days
Patient Selection & Clinical Context- Desirable for breastfeeding women and those with contraindications or desire to avoid estrogen-containing products (e.g., history of venous thromboembolism, migraine with aura, smokers >35 years)
- May be considered in patients desiring a daily POP but unable to use or intolerant of norethindrone POP
- Patient examples include: tolerance issues on norethindrone (unscheduled bleeding/spotting); contraindication to estrogen with poor candidacy for progestin shot/implant/IUD or history of failure/intolerance to norethindrone; indication for ovulation suppression (e.g., recurrent ovarian cysts) with contraindications/intolerance to other options; difficulties adhering to the 3-hour window for norethindrone despite reasonable efforts
Efficacy Considerations- Prevents pregnancy primarily by suppressing ovulation
- Pearl Index: 4.0 (95% CI: 2.3–6.4) pregnancies per 100 woman-years in non-breastfeeding women ≤35 years
- Subgroup analyses of higher BMI did not suggest greater pregnancy risk
- Effectiveness may be less than combination products with real-world use due to strict dosing schedule, though DRSP POP offers a 24-hour forgiveness window
Safety & Adverse Reactions- Most common adverse reactions (≥1%): Acne, metrorrhagia, headache, breast pain, weight increased, dysmenorrhea, nausea, vaginal hemorrhage, libido decreased, breast tenderness, menstruation irregular
- Discontinuations due to adverse events: 11% in pooled data; most frequent: acne, metrorrhagia, irregular menstruation, increased weight, vaginal hemorrhage, decreased libido
- Hyperkalemia: Most common serious adverse event (0.2%); typically isolated, mild, and returns to normal despite continued treatment
- Unscheduled bleeding/spotting: Decreased over time but reported in 40% of patients in cycle 13; amenorrhea reported by nearly three-quarters by end of study
Drug Interactions- CYP3A4 inducers (e.g., phenytoin, carbamazepine, barbiturates) may decrease DRSP concentrations, potentially reducing contraceptive effectiveness and increasing breakthrough bleeding
- CYP3A4 inhibitors (e.g., ketoconazole) may increase DRSP systemic exposure
- Caution with drugs that increase serum potassium (ACE inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, potassium supplements, heparin, aldosterone antagonists, NSAIDs)
Special Populations- Pregnancy: Discontinue if pregnancy occurs; epidemiologic studies/meta-analysis show no increased risk of birth defects from early inadvertent use
- Lactation: Negligible amounts excreted in breast milk; no adverse effects on milk production or infant health/development found
- Renal impairment: Mild (CrCL 50-80 ml/min) has comparable DRSP concentrations to CrCL >80 ml/min; increased by 37% in CrCL 30-49 ml/min
- Hepatic impairment: DRSP exposure increased 3-fold in moderate hepatic impairment
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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FEBUXOSTAT TAB
ULORIC
|
ULORIC |
2019-07-18 |
Exclusion Criteria- Hypersensitivity or history of intolerance to febuxostat (or inactive tablet ingredients)
- Asymptomatic hyperuricemia
- Concomitant administration of drugs that are metabolized by xanthine oxidase (e.g., theophylline, mercaptopurine, azathioprine)
Inclusion Criteria- Patient is a candidate for chronic treatment of gout (hyperuricemic with recurrent gouty attacks ≥ 2 acute attacks/year or other manifestations of chronic gout including tophaceous disease, erosive gouty arthritis, or uric acid urolithiasis)
- Documentation of lack of adequate response, contraindication, or inability to tolerate appropriately dose-maximized trials of allopurinol and/or probenecid
- For patients with known cardiovascular disease: encourage use of low-dose aspirin (if no contraindications exist) and discontinue NSAIDs if possible or use at the lowest dose for the shortest possible duration
Dosage and Administration- Initial recommended starting dose: 40 mg daily
- Dose of 80 mg daily recommended if serum urate < 6 mg/dL is not achieved after 2 weeks of treatment at the lower dose
- Doses >80 mg daily are not approved for use in the United States
- Severe renal impairment (CrCl 10-29 mL/min): dose should be limited to 40 mg daily
- Mild to moderate hepatic impairment (Child-Pugh Class A or B): no dose adjustment needed; caution advised for severe hepatic disease due to lacking evidence
- May be administered without regard to food or antacid use
- Prophylaxis against acute gout flare (with colchicine or NSAIDs) is recommended during the first 6 months of urate lowering therapy
Monitoring- Baseline liver function testing upon initiation and periodically thereafter in patients with symptoms suggestive of liver toxicity (fatigue, anorexia, right upper abdominal discomfort, darkened urine, or jaundice)
- If liver injury is confirmed: withhold febuxostat and investigate cause; do not restart if no other etiology is found
- Serum uric acid target of < 6 mg/dL for effective gout management; a target of < 5 mg/dL may be recommended for selected patients with more severe disease until urate crystals and symptoms resolve
- Monitor for signs and symptoms of myocardial infarction and stroke due to observed higher rate of cardiovascular thromboembolic events in clinical development
- Discontinue febuxostat if serious skin reactions are suspected (e.g., Stevens-Johnson syndrome, DRESS, toxic epidermal necrolysis)
Renewal Criteria- Patient is tolerating febuxostat and adherent to therapy
- Patient has achieved a clinically significant reduction in serum urate within 6 months of initiation (reached serum urate < 6 mg/dL to reduce frequency of acute gout flares and/or favorably alter other manifestations of chronic gout)
Issues for Consideration & Provider Recommendations- CARES trial demonstrated higher rates of cardiovascular death and all-cause mortality with febuxostat compared to allopurinol, with heterogeneity observed regarding NSAID use or lack of daily low-dose aspirin
- Engage in shared decision-making with the patient regarding CARES trial findings to determine the best course of therapy
- Options include: reevaluating treatment to replace febuxostat with allopurinol (with appropriate dose titration) OR continuing febuxostat while emphasizing low-dose aspirin use in patients with known/high-risk cardiovascular disease, discontinuing NSAIDs if possible, and considering a Rheumatology referral to assess ongoing necessity
- Caution is advised for patients without known cardiovascular disease due to unknown risk profile compared to allopurinol
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SOLRIAMFETOL TAB
SUNOSI
|
SUNOSI |
2019-07-11 |
Exclusion Criteria- OSA not receiving primary OSA therapy (e.g., CPAP, or other OSA therapy for patients for whom CPAP was intolerable or ineffective (dental appliance, hypoglossal nerve stimulator, OSA surgery, or other)
- Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or use of a MAOI within the preceding 14 days
- Patient has uncontrolled hypertension, unstable non medically controlled angina or coronary artery disease, non medically controlled heart arrhythmias, or other clinically relevant unstable or untreated heart problems
- End Stage Renal Disease (eGFR less than 15 ml/min/1.73m2)
Inclusion Criteria & Indications- Treatment of excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA)
- Documented lack of efficacy with, is intolerant of, or has contraindications to modafinil OR armodafinil
Diagnostic Requirements- If narcolepsy is the indication, the diagnosis of narcolepsy has been confirmed by Multiple Sleep Latency Test (MSLT) or hypocretin-1 deficiency
- Documented excessive daytime sleepiness (Epworth Sleepiness Scale score > 10)
Monitoring & Prescribing Requirements- Prescribed and monitored by a VA/VA Community Care sleep specialist/pulmonologist/neurologist or locally designated expert in sleep disorders.
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MEPOLIZUMAB INJ,SOLN
NUCALA
|
NUCALA |
2019-06-21 |
Indication & Patient Population- Add-on maintenance therapy in adults with inadequately controlled chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype.
- Patients must have an eosinophilic phenotype defined as EOS > 300 microL.
Prior Therapy & Treatment Requirements- Must be continuing to experience exacerbations despite adherence to maximal inhaled therapies (LAMA+LABA+ICS) with documented proper inhaler use technique.
- A trial of azithromycin and/or roflumilast should be considered prior to mepolizumab in certain patients with exacerbations of COPD.
Dosing & Administration- 100 mg subcutaneously (SQ) every 4 weeks.
- Available as 100 mg single dose vial, 100 mg single dose prefilled syringe, or prefilled autoinjector.
Contraindications & Precautions- Contraindicated in patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.
- Not indicated for treating acute symptoms or exacerbations of asthma or COPD.
- Pre-existing parasitic infection (Helminth) must be treated prior to initiating therapy.
- Monitor for risk of hypersensitivity reactions and opportunistic infections (e.g., herpes zoster).
Exclusion Criteria- Untreated acute bronchospasm or acute exacerbation of chronic obstructive pulmonary disease (COPD)
- Untreated parasitic (helminth) infection (infection must be treated prior to initiating mepolizumab)
- Concurrent use with therapeutic biologics unless potential benefit-risk favors use
- Inclusion Criteria (All criteria must be met)
- Provider is a VA or VA Community Care pulmonologist or designated expert
- Moderate to severe COPD (post-bronchodilator FEV1 30-70% predicted and FEV1/FVC <0.7, confirmed by pulmonary function testing)
- Blood eosinophils ≥300 cells/µL obtained prior to treatment (e.g., within the 3 months prior)
- Signs or symptoms of chronic bronchitis (chronic productive cough) for at least 3 months during the past year
- Receiving concurrent triple inhaled therapy with a long-acting beta-agonist (LABA), long-acting anticholinergic (LAMA), and inhaled corticosteroid (ICS) (unless ICS is contraindicated) for at least 3 months
- At least 2 moderate COPD exacerbations (requiring systemic steroids and/or antibiotics) or at least 1 severe COPD exacerbation (requiring hospitalization) in the previous 12 months
- Inadequate symptom control (e.g., mMRC dyspnea scale score > 2) or impaired health status (e.g., CAT score > 15)
- Unable to tolerate or had an inadequate response to a 6-month trial of roflumilast and a 6-month trial of azithromycin, unless not clinically appropriate for either agent
- Adherent to COPD medications as evidenced by prescription refill history review
- Demonstrated correct inhaler technique (documented in chart)
Additional Inclusion Criteria & Clinical Guidance- Patient is non-smoking or enrolled in a smoking cessation program/on cessation medications; current smokers may be considered if unable or refusing to quit
- Modifiable environmental triggers for Type 2 inflammation should be addressed, if not already done
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
Other Justification- Hypereosinophilic syndrome (HES) to reduce eosinophilia and minimize exposure to glucocorticoids, prescribed by a specialty provider experienced in managing HES
- Non-severe active eosinophilic granulomatosis with polyangiitis (EGPA) to induce remission, prevent relapse, and minimize exposure to glucocorticoids, prescribed by a specialty provider experienced in managing EGPA with an inadequate response to benralizumab
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POLATUZUMAB VEDOTIN-PIIQ INJ,LYPHL
POLIVY
|
POLIVY |
2019-06-21 |
Exclusion Criteria- Absolute Neutrophil Count < 1000/µL
- Platelet count < 75,000/µL (if no bone marrow involvement)
- Moderate or severe hepatic impairment [Total bilirubin > 1.5 times upper limit of normal (unless Gilbert’s syndrome or liver involvement)]
- Creatinine clearance < 40 ml/min
- Baseline peripheral neuropathy > Grade 2
- Chronic or unresolved infection
- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
Inclusion Criteria- Care provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Indications & Regimens- In combination with rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHP) for previously untreated diffuse large B-cell lymphoma with International Prognostic Index score 2-5
- In combination with bendamustine and rituximab (BR) for relapsed or refractory, diffuse large B-cell lymphoma previously treated with > 2 prior lines of therapy
Pregnancy Counseling- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 5 months after stopping treatment.
Indications- Previously untreated diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL) with an International Prognostic Index (IPI) score > 2, in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP).
- Relapsed or refractory DLBCL after at least 2 prior lines of therapy (LOT), in combination with bendamustine and a rituximab product.
Patient Population & Eligibility Criteria- Untreated DLBCL: IPI score 2-5; ECOG performance status 0-2.
- Excluded populations: Transformed lymphoma, primary mediastinal large B-cell lymphoma, known CNS lymphoma, peripheral neuropathy (grade > 2).
- Relapsed/refractory DLBCL: Transplant-ineligible patients; ineligible for hematopoietic stem cell transplant (HSCT) due to age (40%), insufficient response to salvage therapy (26%), or prior HSCT failure (20%).
- Populations not demonstrating clear benefit with polatuzumab-R-CHP: Age < 60 years, germinal-center B-cell-like subtype of DLBCL, bulky (>7 cm) disease, lower IPI score.
VA Oncology Clinical Pathway Recommendations- First-line Advanced stage (III, IV), ECOG 0-2, IPI 2-5, non-germinal center origin: Pola-R-CHP.
- Relapsed DLBCL: Pola-BR in patients who are not candidates for autologous stem cell transplant (ASCT) or CAR T-cell therapy.
Bridging Therapy & CAR T-Cell Considerations- Recommended as bridging therapy to CAR T-cell therapy during the CAR T-cell manufacture period.
- Bridging therapy with polatuzumab ± rituximab ± bendamustine is category 2A per NCCN guidelines.
- Must be administered only after leukapheresis, as it may impact cell collection.
- Recommendations are per the cellular therapy team.
Dosing & Administration- Polatuzumab: 1.8 mg/kg IV every 21 days for 6 cycles.
- Administered in combination with either R-CHP or bendamustine + rituximab (BR) per specified cycle schedules.
Safety & Monitoring Requirements for Use- Peripheral neuropathy: Monitor for new or worsening symptoms; onset typically ~2 months.
- Infusion-related reactions: Administer antihistamine and antipyretic prior to administration; monitor during infusion.
- Myelosuppression: Primary prophylaxis with G-CSF recommended for neutropenia due to Pola-R-CHP; consider for Pola-BR. Monitor for neutropenia, thrombocytopenia, and anemia.
- Infections: Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus; monitor for serious and opportunistic infections.
- Progressive multifocal leukoencephalopathy (PML): Monitor for new or worsening neurologic, cognitive symptoms, or behavioral changes.
- Tumor lysis syndrome: Monitor closely in patients with high tumor burden; provide prophylaxis to those at risk.
- Hepatotoxicity: Monitor liver function tests and bilirubin; use caution in patients with pre-existing liver disease, elevated baseline liver enzymes, or concomitant medications.
- Embryo-fetal toxicity: Advise effective contraception due to potential fetal harm.
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PRABOTULINUMTOXINA-XVFS INJ,PWDR
JEUVEAU
|
JEUVEAU |
2019-05-31 |
Exclusion Criteria- Hypersensitivity to botulinum toxins or any components in the formulation (e.g., human serum albumin, lactose, sucrose, disodium succinate)
- Co-administration with neuromuscular blockade
- Neurologic condition where botulinum toxins pose risk for additive neuromuscular compromise (e.g., myasthenia gravis, amyotrophic lateral sclerosis), unless risks/benefits have been discussed with the patient and documented in the medical record
- Use for cosmetic purposes
Inclusion Criteria (Indications)- Cervical dystonia or focal dystonia
- Blepharospasm or hemifacial spasm
- Severe focal hyperhidrosis with inadequate response or unmanageable intolerance to prescription topical therapy (e.g., aluminum chloride hexahydrate 20% topical solution)
- Upper or lower limb spasticity
- Overactive bladder or neurogenic bladder dysfunction with contraindication, intolerance, or inefficacy to behavioral therapy and at least one pharmacotherapy (e.g., antimuscarinic agent, beta-3 adrenergic agonist)
- Chronic migraine prevention with contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 2 of the following: beta blocker, topiramate, divalproex, and ACE inhibitor or ARB
- Pharyngoesophageal segment spasm (PES)
- Sialorrhea with contraindication, intolerance, or lack of therapeutic response to anticholinergics and/or speech therapy
- Chronic anal fissure refractory to conservative treatment including supportive measures (e.g., dietary fiber, sitz bath) and topical vasodilator (e.g., topical nitrates)
- Esophageal achalasia if patient is not a candidate for surgery
- Idiopathic (primary or genetic) or symptomatic (acquired) torsion dystonia
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BOSENTAN TAB
TRACLEER
|
TRACLEER |
2019-05-23 |
Exclusion Criteria- Known pregnancy
- Baseline hepatic transaminase elevations >3 times the upper limit of normal
- Moderate or severe liver impairment (e.g., Child-Pugh Class B or C)
Inclusion Criteria- Care provided by a VA/VA Community Care provider experienced in the management of pulmonary arterial hypertension (PAH) (certified and enrolled in the bosentan REMS Program)
- World Health Organization (WHO) Group 1 PAH
- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis: mean pulmonary artery pressure >25 mmHg, pulmonary artery wedge pressure ≤15 mm Hg, and pulmonary vascular resistance >3 Wood Units
- Baseline hepatic transaminase testing and commitment to monthly testing
- Intolerance, inadequate response, or unable to use ambrisentan (ambrisentan is the preferred endothelin receptor antagonist when clinically appropriate)
Reproductive Safety & Counseling- Females who can become pregnant: Pregnancy must be excluded prior to receiving bosentan; counseling on potential risk vs benefit and effective contraception use prior to, during, and one month after stopping treatment is required
- Males of reproductive potential: Counseling provided on the potential risk of bosentan to adversely affect spermatogenesis and impair fertility
Hemodynamic & Clinical Context Considerations- Hemodynamic definition applies to the majority of PAH patients and is recommended by the 7th World Symposium for Pulmonary Hypertension for consideration of PAH-specific drug therapy including endothelin receptor antagonists
- Decisions for hemodynamic parameters outside specified thresholds should be made by PAH specialists in the context of the individual patient's entire presentation
- mPAP and PVR thresholds have been expanded to include mPAP >20 mmHg and PVR >2 Wood Units, though most PAH therapies were studied in populations meeting the older definition
- Consensus is lacking on whether PAH treatment should be considered in patients with mildly elevated pressures per the 7th World Symposium
- PAWP ≤15 mm Hg is traditionally used to rule out pulmonary hypertension due to left-heart disease, where PAH-specific therapies have not been shown to benefit and may result in harm
- REVEAL U.S. registry data suggests PAH may exist in patients with PAWP 16-18 mmHg; survival did not significantly differ from those with PAWP ≤15 mm Hg at diagnosis
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ERDAFITINIB TAB
BALVERSA
|
BALVERSA |
2019-04-25 |
Exclusion Criteria- Serum phosphate above the upper limit of normal
- Symptomatic CNS metastases
- Any corneal or retinal abnormality identified by ophthalmologic exam
- Unmanageable CYP2C9 or CYP3A4 drug interaction
- Unmanageable CYP3A4, OAT2, or P-glycoprotein substrate drug interaction
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Baseline ophthalmologic exam, including Optical Coherence Tomograph (OCT) where available
- Patients of child-bearing potential and patients with partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment; use effective contraception during therapy and for 1 month after the last dose
- Known Poor Metabolizer genotype (CYP2C93/3): monitor for increased risk of adverse events
Indication & Prior Therapy Requirements- Locally advanced (unresectable) or metastatic urothelial carcinoma
- FGFR3 alteration based on companion diagnostic or next generation sequencing
- Progressed during or following at least 1 prior line of systemic therapy
- Not recommended if patient is eligible for or has not received prior PD-1 or PD-L1 inhibitor therapy
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AMBRISENTAN TAB
LETAIRIS
|
LETAIRIS |
2019-04-18 |
Exclusion Criteria- Known pregnancy
- Moderate or severe liver impairment (e.g., Child-Pugh Class B or C)
Inclusion Criteria- Care provided by a VA/VA Community Care provider experienced in the management of pulmonary arterial hypertension (PAH)
- World Health Organization (WHO) Group 1 PAH
- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis: mean pulmonary artery pressure >25 mmHg, pulmonary artery wedge pressure ≤15 mm Hg, and pulmonary vascular resistance >3 Wood Units
Additional Inclusion Criteria- Females who can become pregnant: Excluded pregnancy prior to receiving ambrisentan. Provided counseling on potential risk vs benefit of treatment and use of effective contraception prior to, during, and one month after stopping treatment.
- For males of reproductive potential: Counseling provided on the potential risk of ambrisentan to adversely affect spermatogenesis and impair fertility.
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ROMOSOZUMAB-AQQG INJ,SOLN
EVENITY, EVENITY (2 SYRINGES)
|
EVENITY, EVENITY (2 SYRINGES) |
2019-04-18 |
Exclusion Criteria- Patient had a myocardial infarction or stroke within the past year
- Pregnancy (known pregnancy or positive pregnancy test), or lactating
- Hypocalcemia or pre-existing disturbance of mineral metabolism that has not been effectively corrected or treated (e.g., hypoparathyroidism, thyroid or parathyroid surgery, vitamin D deficiency, malabsorption syndromes, excision of small intestine)
- Exception: Patients with secondary or tertiary hyperparathyroidism due to chronic kidney disease and low bone mineral density who are nonsurgical candidates
- Documentation of the need for an invasive dental procedure (e.g., tooth extraction, dental implant, and/or dental infection treatment) or recent procedure that has not fully healed
- Acute dental issue identified by history or clinician mouth examination
- Previous cumulative 12-month exposure to romosozumab
Inclusion Criteria- Patient has a diagnosis of osteoporosis
- Prescriber is a VA or VA Community Care endocrinologist, rheumatologist, nephrologist, geriatrician, or locally designated expert
- Patient’s total daily dietary and supplemental calcium intake is 1000 to 1200 mg/day
- Has a 25-hydroxyvitamin D concentration >30 ng/mL or > 20 ng/ml with appropriate intake (e.g., cholecalciferol >800 international units per day)
- Following a one-year course of romosozumab, start antiresorptive therapy to maintain bone density gains
- Additional Inclusion Criteria (One of the following must be met)
- Osteoporotic fracture and a T-score at the hip or spine of < -2.5
- Very high fracture probability by the Fracture Risk Assessment Tool (FRAX) (e.g., major osteoporosis fracture >30%, hip fracture >4.5%)
- Patient has a T-score < -3.0
- More than 2 osteoporotic fractures
- Continuing to lose bone mineral density or sustained an osteoporotic fracture while on approved osteoporosis therapy
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ESKETAMINE SOLN,SPRAY,NASAL
SPRAVATO
|
SPRAVATO |
2019-03-21 |
Exclusion Criteria- Allergy or previous serious adverse effects to ketamine or esketamine
- Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation
- History of intracerebral hemorrhage
- Uncontrolled seizures
- Dementia
- Current or recent (within 30 days) delirium
- Current uncontrolled hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg)
- Severe cardiac decompensation (Class IV heart failure or unstable angina)
- Severe hepatic impairment (Child-Pugh class C)
- Current or previous interstitial or ulcerative cystitis
- Comorbid psychiatric condition is present (schizophrenia, schizoaffective disorder, bipolar disorder)
- History of non-response to ketamine or esketamine
- Current or previous abuse of ketamine or esketamine
- Clinical evidence for current substance abuse except tobacco
- Current barbiturate, cannabis, or opioid use
- Current moderate or severe substance use disorder (SUD)
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding/providing breastmilk to an infant
Primary Inclusion Criteria- Remission not achieved from 2 antidepressant trials including a trial of an augmentation strategy in the current episode of depression and 4 total adequate antidepressant trials in the patient’s lifetime
- Patient is hospitalized with TRD with acute suicidal ideation/behavior
- One augmentation trial could be an adequate course of evidence-based psychotherapy (EBP)
Additional Inclusion Criteria- All REMS requirements have been met
- Adults <65 years of age with current diagnosis of unipolar major depressive disorder by DSM-5
- Patient in current episode of depression is experiencing moderate to severe depressive symptomatology (i.e., PHQ-9 >15 within the last 30 days)
- Antidepressant treatment trials are considered unsuccessful if the patient has not responded to at least 6 weeks of an antidepressant at half maximum dose or greater
- A VA psychiatrist or a VA licensed health-care provider (i.e., CPP, NP, PA) has evaluated the patient and determined and documented in the patient’s medical records that the patient qualifies for esketamine treatment
- The prescriber is a VA psychiatrist or a VA licensed health-care provider (i.e., CPP, NP, PA)
- The patient agrees to stay and be monitored after esketamine administration and agrees not to drive or operate heavy machinery and not to make critical decisions for the remainder of the day in which esketamine is administered
- The patient or their legal representative can provide signed informed consent
- The patient has an adult who can accompany him/her and assist with transportation, or another method of safe transport has been arranged and documented
Specific Population Requirements- For women of childbearing potential: Pregnancy should be excluded prior to receiving esketamine and the patient provided contraceptive counseling on potential risks vs. benefits of taking esketamine if patient were to become pregnant
Indications & Patient Selection- Treatment of treatment-resistant depression (TRD) or depressive symptoms in major depressive disorder (MDD) with acute suicidal ideation or behavior
- Adults <65 years of age with current diagnosis of unipolar major depressive disorder by DSM-5
- Patient in current episode of depression experiencing moderate to severe depressive symptomatology (PHQ-9 >15 within the last 30 days)
Inclusion Criteria- Remission not achieved from 2 antidepressant trials including a trial of an augmentation strategy in the current episode of depression AND 4 total adequate antidepressant trials in the patient’s lifetime
- OR hospitalized with TRD with acute suicidal ideation/behavior
- All REMS requirements have been met
- Antidepressant treatment trials considered unsuccessful if patient has not responded to at least 6 weeks of an antidepressant at half maximum dose or greater
- Evaluated and documented by a VA psychiatrist or VA licensed Mental Health-care provider (CPP, NP, PA) as qualifying for esketamine treatment
- Prescriber is a VA psychiatrist or VA licensed Mental Health-care provider (CPP, NP, PA)
- Patient agrees to stay/be monitored after administration and agrees not to drive/operate heavy machinery/equipment or make major financial/legal decisions for the remainder of the day
- Patient or legal representative provides signed informed consent
- Patient has an adult who can accompany/assist with transportation, or another method of safe transport arranged/documented
- For women of childbearing potential: Pregnancy excluded prior to receiving; provided contraceptive counseling on risks vs benefits if pregnant
Exclusion Criteria- Allergy or previous serious adverse effects to ketamine or esketamine
- Aneurysmal vascular disease (thoracic/abdominal aorta, intracranial, peripheral arterial vessels) or arteriovenous malformation
- History of intracerebral hemorrhage
- Uncontrolled seizures
- Dementia
- Current or recent (within 30 days) delirium
- Current uncontrolled hypertension (SBP >140 mm Hg or DBP >90 mm Hg)
- Severe cardiac decompensation (Class IV heart failure or unstable angina)
- Severe hepatic impairment (Child-Pugh class C)
- Current or previous interstitial or ulcerative cystitis
- Comorbid psychiatric condition (schizophrenia, schizoaffective disorder, bipolar disorder)
- History of non-response to ketamine or esketamine
- Current or previous abuse of ketamine or esketamine
- Clinical evidence for current substance abuse (except tobacco)
- Current moderate or severe substance use disorder (SUD)
- Pregnancy (known pregnancy or positive pregnancy test)
- Patient is breastfeeding
Screening & Pre-treatment Requirements- Screening completed no more than 60 days prior to acceptance/administration of first dose
- Signed informed consent
- Psychiatric examination including assessment of inclusion/exclusion criteria
- PHQ-9 depression rating scale required at screening and prior to each treatment
- Evaluation of cognitive status (e.g., M-ACE)
- Assessment of suicide risk: C-SSRS at intake/initial evaluation (and within 24 hours of discharge/clinically indicated); CSRE completed if first ever, otherwise updated as clinically indicated
- Physical examination including vitals (BP, heart rate)
- Relevant laboratory measures, urine toxicology, and pregnancy screens
- Medical clearance from PCP or consultation from cardiologist/specialist based on risk factors (provider responsibility)
- REMS Patient Enrollment Form completed and submitted
Dosing & Administration Parameters- Self-administered intranasally under direct observation of a Mental Health care provider in a certified medical facility
- Ordering VA psychiatrist or VA licensed Mental Health-care provider physically present during dosing procedure
- Induction Phase (Weeks 1-4): 56 mg or 84 mg twice per week
- Maintenance Phase (Weeks 5-8): 56 mg or 84 mg once weekly
- Maintenance Phase (Week 9 and after): 56 mg or 84 mg every 2 weeks or once weekly (individualized to least frequent dosing to maintain remission/response)
- For MDD with acute suicidal ideation/behavior: 84 mg twice weekly x 4 weeks (may reduce to 56 mg twice weekly based on tolerability; use beyond 4 weeks not evaluated)
- Stop dosing if pallor/cyanosis/poor perfusion, respiratory symptoms (shortness of breath/wheezing), chest/jaw/arm pain, or patient desire to stop
Monitoring & Recovery Requirements- Monitor for at least two hours after receiving dose
- Esketamine cannot be dispensed directly to patient for home use
- Monitoring location must be private, large enough for reclining head at 45 degrees, have crash cart/rapid access code team, monitor cardiovascular (ECG, BP) and respiratory function (O2 sat or end-tidal CO2), capable of administering oxygen/medications/restraints
- Vital signs checks: T+20 min, T+40 min, T+90 min, T+120 min
- At T+120 min: Check vital signs, C-SSRS Screener, readiness for discharge assessment (Modified Aldrete or bCAM)
- REMS Patient Monitoring Form completed after every treatment session and submitted to Janssen
- Longitudinal monitoring: PHQ-9 prior to each dose; PHQ-9 and cognitive evaluation at end of induction, every 6 months, and end of treatment course
Discontinuation & Treatment Failure Criteria- Do not move to maintenance therapy if no response after four weeks
- Adequate response defined as ≥50% decline in PHQ-9 score from baseline
- Stop drug and counsel on risks/benefits if woman becomes pregnant
- Consider discontinuing if positive urine drug screen for specified drugs of abuse (cannabinoids, barbiturates, methadone, opioids, cocaine, phencyclidine, amphetamine/methamphetamine)
- Discontinue if signs/symptoms of new or recurrent SUD emerge; refer to SUD specialty care
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CAPLACIZUMAB-YHDP INJ,LYPHL
CABLIVI
|
CABLIVI |
2019-03-07 |
Exclusion Criteria- Congenital Thrombotic Thrombocytopenic Purpura
- Concurrent antiplatelet agents or anticoagulants
- Active bleeding or history of bleeding disorder
- Platelet count greater than or equal to 100,000/uL
- Pregnancy
- Lactating
Inclusion Criteria- Acquired/Immune Thrombotic Thrombocytopenic Purpura (iTTP) along with plasma exchange and immunosuppression
- ADAMTS13 activity <10% or pending
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care hematology or oncology provider
- Goals of care have been discussed and documented in the electronic health record
Discontinuation Criteria- Stop caplacizumab when ADAMTS13 activity is >10% on 2 consecutive weeks or >30% on one occasion
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RANOLAZINE TAB,SA
RANOLAZINE ER
|
RANOLAZINE ER |
2019-03-07 |
FDA Approved Indication- Treatment of chronic stable angina
Exclusion Criteria- Clinically significant hepatic impairment
- Receiving strong CYP 3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir)
- Receiving strong CYP 3A4 inducers (rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John’s wort)
Inclusion Criteria- Anginal episodes averaging 3 or more times per week despite maximal or maximally tolerated anti-anginal drug therapy (defined as treatment with a beta-blocker, long-acting dihydropyridine calcium channel blocker, and a long-acting nitrate)
- Active VA healthcare provider involvement in monitoring and management of ranolazine therapy, with re-assessment of therapeutic effectiveness and tolerability within 12 weeks after initiation
Precautions & Drug Interactions- QT-interval prolongation: Dose-dependent increase (mean QTc increase of 6 ms at 1000 mg twice daily); use with caution in patients with pre-existing QT interval prolongation (Normal QTc <440 ms) due to lack of safety data
- Drug-drug interactions: Ranolazine is a CYP 3A4 and P-glycoprotein inhibitor/substrate, and lesser extent CYP 2D6 substrate; carefully review medications prior to initiation; dose adjustment or avoidance may be recommended; use with caution alongside other QT-prolonging drugs (Class Ia [quinidine] or Class III [amiodarone, dofetilide, sotalol] antiarrhythmics, erythromycin, certain antipsychotic agents) due to limited safety data
Dosage & Administration- Initiate therapy at 500 mg twice daily; maximum dose 1000 mg twice daily (dose escalation not consistently shown to improve symptoms; adverse events are dose-related)
- Maximum recommended dose limited to 500 mg twice daily with concurrent moderate CYP3A inhibitors (diltiazem, verapamil, aprepitant, erythromycin, fluconazole, grapefruit-containing products)
- Down-titration may be needed when used concurrently with P-glycoprotein inhibitors (e.g., cyclosporine)
Issues for Consideration- Reserve for patients who have not received an adequate response with other antianginal drugs; use in combination with beta-blockers, nitrates, and dihydropyridine calcium channel blockers
- Not shown to be pro-arrhythmic in a high-risk ACS population
- Increases simvastatin drug levels by 2-fold; monitor and counsel for potential adverse events despite manufacturer/FDA not recommending dosing adjustment
Renewal Criteria- Therapeutic effectiveness and tolerability must be assessed within the first 12 weeks of therapy
- Documented improvement in anginal symptoms and/or reduction in sublingual nitroglycerin consumption while receiving ranolazine
- Patient is not experiencing treatment-limiting adverse effects
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LEVODOPA CAP,INHL
INBRIJA
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INBRIJA |
2019-02-21 |
Exclusion Criteria- Concomitant use of a nonselective monoamine oxidase inhibitor (MAOI), such as phenelzine or tranylcypromine (must be >14 days post discontinuing therapy)
- Asthma or chronic obstructive pulmonary disease (COPD)
- Presence of psychotic disorder
- Glaucoma with uncontrolled intraocular pressure (IOP)
Inclusion Criteria- Patient is under the care of a VA/VA-authorized Neurologist or locally designated expert who is responsible for prescribing and monitoring therapy
- Patient has Parkinson’s Disease and is receiving at least four times daily carbidopa/levodopa
- Patient will continue to receive oral carbidopa/levodopa therapy
- Patient has OFF time of >2 hours/day
- Contraindication to or inadequate therapeutic response to use of a dopamine agonist, catechol-O-methyl transferase [COMT] inhibitor, monoamine oxidase type B [MAO B] inhibitor, ER capsule formulation or CR tablet formulation
- Attempts to reduce dosing intervals have not adequately resolved OFF periods
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FACTOR XA,INACTIVATED-ZHZO INJ,LYPHL
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2019-01-25 |
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
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CINACALCET TAB
CINACALCET HCL, SENSIPAR
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CINACALCET HCL, SENSIPAR |
2019-01-15 |
Exclusion Criteria- Serum calcium less than the lower limit normal (e.g., < 8.4 mg/dL, corrected for serum albumin)
Inclusion Criteria- Secondary hyperparathyroidism in a patient with chronic kidney disease (CKD) on chronic dialysis with elevated intact plasma parathyroid hormone (iPTH) level (e.g., greater than 400 pg/ml or significant trend upwards within two to nine times the upper limit normal for the assay) despite management with standard therapy as appropriate (e.g., dietary phosphate restriction, phosphate binders [calcium-based or non-calcium based], calcitriol or vitamin D analogs)
- Hypercalcemia (e.g., > 12.5 mg/dl, or symptomatic and > 11.3 mg/dl; corrected for serum albumin) in a patient with primary hyperparathyroidism who is not a surgical candidate or with recurrence despite surgical intervention
- Hypercalcemia (e.g., > 12.5 mg/dl, corrected for serum albumin) in a patient with parathyroid carcinoma despite standard therapy to control hypercalcemia prior to surgical intervention, or who is not a surgical candidate, or who has recurrence despite surgical intervention
FDA Indications & Limitations- Secondary hyperparathyroidism in adult patients with CKD on dialysis (Limitation: Not indicated for use in patients with CKD not on dialysis)
- Hypercalcemia in adult patients with parathyroid carcinoma
- Hypercalcemia in adult patients with primary hyperparathyroidism for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy
Hypocalcemia Management & Monitoring- Both agents lower serum calcium, leading to potentially severe hypocalcemia (can cause paresthesias, myalgias, muscle spasms, seizures, QT interval prolongation and ventricular arrhythmia); patients predisposed to QT interval prolongation, ventricular arrhythmias, or seizures are at increased risk
- Close monitoring recommended for development of hypocalcemia, with adjustment of other therapies (e.g., phosphate binders, calcitriol or vitamin D analogs) as indicated
- For secondary hyperparathyroidism with CKD on dialysis: Monitor serum calcium approximately monthly if receiving maintenance dose
- For parathyroid carcinoma or primary hyperparathyroidism: Monitor corrected serum calcium every 2 months
- If calcium is between 8.4 mg/dL and 7.5 mg/dL: Calcium-based phosphate binders and/or vitamin D sterols can be used to increase calcium
- If calcium is below 7.5 mg/dL or patient has symptoms of hypocalcemia: Hold cinacalcet dose until calcium is 8.0 mg/dL; may resume at a lower dose once calcium is corrected
Dosing & Administration Considerations- Refer to Product Information for detailed prescribing information
- Selection between oral cinacalcet and IV etelcalcetide should depend on treatment response, tolerability, adherence, and cost
- Patients adequately controlled on cinacalcet, who are tolerating therapy and adherent to the oral once daily treatment regimen, should remain on cinacalcet
- Concurrent use of calcimimetics could result in severe, life-threatening hypocalcemia; cinacalcet and etelcalcetide should not be used as concomitant therapy
Off-Label Use- Long-term safety and efficacy in patients with CKD not on dialysis has not been established; however, individual cases treating a non-dialysis patient with markedly elevated iPTH might be considered
- Patients treated with cinacalcet who are not on dialysis may be at increased risk for the development of hypocalcemia
- Limited data show reduction in hypercalcemia and iPTH with cinacalcet in patients with hyperparathyroidism after kidney transplantation; appropriate treatment should be determined on a case by case basis
Pregnancy & Reproductive Safety- Refer to prescribing information for animal reproduction studies data to determine use in patients of child-bearing potential, and the need for contraceptive counseling and education on potential risk vs. benefit if patient were to become pregnant
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AMIFAMPRIDINE TAB,ORAL
FIRDAPSE
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FIRDAPSE |
2018-12-28 |
Exclusion Criteria- History of seizures
- Forced vital capacity < 1500 ml
Inclusion Criteria- Must be prescribed by or in consultation with a VA or VA-authorized neurologist
- Diagnosis of Lambert-Eaton myasthenic syndrome via nerve conduction studies or positive anti-P/Q type voltage-gated calcium channel antibody test
- Patient has the ability to swallow 4 ounces of water without coughing or throat clearing
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CENEGERMIN-BKBJ SOLN,OPH
OXERVATE
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OXERVATE |
2018-12-06 |
Exclusion Criteria- Active ocular infection
- Active ocular inflammation not related to neurotrophic keratitis
- Non-approved conditions (e.g., dry eye, glaucoma, retinitis pigmentosa)
Inclusion Criteria- Provider is an ophthalmologist (VA or VA authorized community care)
- Diagnosis of stage 2 or stage 3 neurotrophic keratitis
- Refractory to treatment to regularly scheduled preservative-free artificial tears, gels, or ointments
- Refractory to treatment with topical cyclosporin (if use is appropriate)
- Refractory to treatment with at least ONE of the following: corneal or scleral therapeutic contact lenses, punctal-occlusion, non-surgical (e.g., patching, botulinum induced ptosis) or surgical (tarsorrhaphy) eyelid closure, or other intervention
- Willingness to comply with cenegermin administration schedule (6 times a day at 2-hour intervals for eight weeks)
- One-time renewal may be considered on a case-by-case basis for recurrence in a patient who had demonstrated compliance with the administration regimen
- Discontinue benzalkonium chloride (BAK)-preserved topical ophthalmic medications where feasible
- Discuss with patient the use of alarms or other reminders to support adherence to therapy
- No data on outcomes for retreatment of recurrences defined as Stage 2 or 3 NK after complete healing has occurred and treatment has been stopped
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GILTERITINIB TAB,ORAL
XOSPATA
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XOSPATA |
2018-12-06 |
Patient Demographics & Reproductive Status- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
- Female patients of child-bearing potential: provided counseling on effective contraception and risk vs. benefit of treatment; continue contraception for at least 6 months after the final dose
- Male patients with partners of child-bearing potential: provided counseling on effective contraception and potential risk vs. benefit of treatment; continue contraception for at least 4 months after the final dose
Clinical Diagnosis & Performance Status- Relapsed or refractory acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3) mutation (i.e. ITD or TKD) as detected by an FDA-approved test
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Laboratory & Monitoring Requirements- Unable to comply with recommended laboratory monitoring
- Baseline QTc > 500 msec
Medical Conditions & Organ Function- Severe renal impairment (CrCl <30 ml/min) - has not been studied
- Severe hepatic impairment (Child-Pugh Class C) – has not been studied
Prescriber Qualifications & Documentation- Prescriber is a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
Drug Interactions & Medication Profile Review- Patient is on chronic therapy with a combined P-gp and strong CYP3A inducer (e.g. rifampin)
- Medication profile reviewed for concomitant CYP3A inhibitors which may increase gilteritinib concentrations and potential toxicity
- Medication profile reviewed for chronic SSRI therapy (e.g. escitalopram, fluoxetine, sertraline) as gilteritinib may reduce their effectiveness
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GLASDEGIB TAB,ORAL
DAURISMO
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DAURISMO |
2018-12-06 |
Exclusion Criteria- Unable to comply with recommended laboratory monitoring
- Baseline QTc > 470 msec
- Severe renal impairment (<30 mL/min) – has not been studied
- Severe hepatic impairment (LFT>3x ULN) – has not been studied
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Prescriber is a VA or VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- ECOG performance status 0-2
- New diagnosis of previously untreated, acute myeloid leukemia (AML)
- Not eligible (or declines) intensive induction chemotherapy
- No actionable mutations (e.g. FLT3 mutation)
- Able to receive concurrent low-dose subcutaneous cytarabine
- Medication profile reviewed for concomitant CYP3A inducers, inhibitors and QTc prolonging drugs for glasdegib dose adjustment
- For female patients of child-bearing potential: provided counseling on effective contraception, and risk vs. benefit of treatment. Continue contraception for at least 30 days after final dose.
- For male patients with partners of child-bearing potential: provided counseling on effective contraception and potential risks vs. benefit of treatment. Continue contraception for at least 30 days after final dose.
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LAROTRECTINIB CAP,ORAL
VITRAKVI
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VITRAKVI |
2018-12-06 |
Exclusion Criteria- Malabsorption syndrome or other condition affecting oral absorption
- Unmanageable drug interaction
- Known pregnancy
- Lactating
Inclusion Criteria- Patient has a metastatic solid tumor that is unresectable with an NTRK gene fusion without a known acquired resistance mutation (G595R, G623R, G696A, and F617L)
- Patient has progression on standard treatment(s) or no standard alternative treatment exists
- Baseline hepatic function (AST, ALT, Tbili) evaluated for larotrectinib dose adjustment
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Additional Inclusion Criteria, if applicable- For female patients who can become pregnant: Pregnancy must be excluded prior to receiving Larotrectinib.
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for at least 1 week after the final dose.
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LAROTRECTINIB SOLN,ORAL
VITRAKVI
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VITRAKVI |
2018-12-06 |
Exclusion Criteria- Malabsorption syndrome or other condition affecting oral absorption
- Unmanageable drug interaction
- Known pregnancy
- Lactating
Inclusion Criteria- Patient has a metastatic solid tumor that is unresectable with an NTRK gene fusion without a known acquired resistance mutation (G595R, G623R, G696A, and F617L)
- Patient has progression on standard treatment(s) or no standard alternative treatment exists
- Baseline hepatic function (AST, ALT, Tbili) evaluated for larotrectinib dose adjustment
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Additional Inclusion Criteria, if applicable- For female patients who can become pregnant: Pregnancy must be excluded prior to receiving Larotrectinib.
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for at least 1 week after the final dose.
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SILODOSIN CAP,ORAL
RAPAFLO
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RAPAFLO |
2018-12-06 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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SOFOSBUVIR/ VELPATASVIR TAB,ORAL
EPCLUSA
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EPCLUSA |
2018-12-06 |
Exclusion Criteria- Limited life expectancy
- Documented ongoing nonadherence to prescribed medications or medical treatment
- Concurrent use of drugs not recommended with SOF/VEL (e.g., amiodarone, apalutamide, modafinil, rifamycins, CYP450 inducers, St John’s Wort, > 10mg/day of rosuvastatin, efavirenz, etravirine)
- Hepatitis B surface antigen (HBsAg) positive and not on antiviral treatment with entecavir or tenofovir
- Contraindication to ribavirin (RBV) if RBV is indicated
Inclusion Criteria- Care provided by and/or in consultation with a VA/VA Community Care Hepatitis C virus (HCV) specialist
- HCV Genotype (GT) 1-6 or ungenotyped with detectable HCV RNA
- Treatment regimen and duration consistent with HCV GT and patient characteristics
- Completed hepatitis B screening: at minimum HBsAg, HBV core antibody (anti-HBc), and HBV surface antibody (anti-HBs)
- Adherence counseling performed including laboratory follow-up and documented understanding by patient
- Additional Inclusion Criteria (One of the following must be met)
- GT 1-6 or ungenotyped with detectable HCV RNA and treatment naïve with or without compensated cirrhosis (CTP A)
- GT 1-6 and treatment experienced (PEG-IFN/RBV +/- NS3/4A inhibitor but NS5A and SOF naïve) with or without compensated cirrhosis (CTP A)
- GT 1b, treatment-experienced (NS5A naïve and SOF-experienced)
- GT 1-6 with decompensated cirrhosis (CTP B or C): 12 weeks with RBV or 24 weeks without RBV if NS5A naïve; 24 weeks with RBV if NS5A-experienced
Specific Clinical & Regimen Notes- Contraindication to RBV includes history of significant cardiac disease, significant anemia, pregnancy, and men whose female partner is pregnant or plans to become pregnant
- Ribavirin should be added if GT 3 with compensated cirrhosis and Y93H is present
- If GT 1a, add RBV or use SOF/VEL/VOX
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LEDIPASVIR/ SOFOSBUVIR TAB,ORAL
HARVONI
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HARVONI |
2018-11-29 |
Exclusion Criteria- Limited life expectancy
- Documented ongoing nonadherence to prescribed medications or medical treatment
- Concurrent use of drugs not recommended with LDV/SOF (e.g., cytochrome P450 inducers, amiodarone/dronaderone, rosuvastatin > 10mg/day, high-dose proton pump inhibitors)
- Hepatitis B surface antigen (HBsAg) positive and not on antiviral treatment with entecavir or tenofovir
- Contraindication to ribavirin (RBV) if RBV is indicated
Inclusion Criteria- Care provided by and/or in consultation with a VA/VA Community Care Hepatitis C specialist
- HCV genotype (GT) 1, 4, 5 or 6
- Treatment regimen and duration consistent with HCV GT and patient characteristics
- Completed hepatitis B screening: at minimum HBsAg, HBV core antibody (anti-HBc), and HBV surface antibody (anti-HBs)
- Adherence counseling performed including laboratory follow-up and documented understanding by patient
- Additional Inclusion Criteria (One of the following must be met)
- GT 1, 4, 5 or 6, treatment-naïve with or without compensated cirrhosis
- GT 1, 4, 5 or 6, treatment-naïve with decompensated cirrhosis and no contraindication to ribavirin
- GT 1, treatment-experienced (pegylated interferon or NS3/4A inhibitor only) with decompensated cirrhosis and no contraindication to ribavirin
Ribavirin Contraindications- History of significant cardiac disease
- Significant anemia
- Pregnancy
- Men whose female partner is pregnant or plans to become pregnant
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LORLATINIB TAB,ORAL
LORBRENA
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LORBRENA |
2018-11-15 |
Exclusion Criteria- Concurrent use of strong CYP3A inducers
- History of interstitial fibrosis or interstitial lung disease
- Severe renal impairment (i.e. CrCl < 15 ml/min using Cockroft-Gault or ESRD requiring dialysis)
- Baseline moderate to severe hepatic impairment [i.e. total bilirubin ≥ 1.5 x ULN with any AST OR AST/ALT > 2.5 x ULN (>5 x ULN in patients with liver metastases)]
- Inadequate bone marrow function (i.e. ANC < 1,500/mm3, PLT < 100,000/mm3, Hgb < 9 g/dL)
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care provided by a VA/VA Community Care oncology provider
- Goals of care and role of Palliative Care consult discussed and documented
- ECOG Performance Status 0-2
Additional Inclusion Criteria (Clinical Indications)- Metastatic non-small cell lung cancer (NSCLC) with a confirmed ALK mutation AND progressive disease or intolerance to at least one prior ALK TKI (e.g. crizotinib, alectinib, brigatinib, ceritinib)
- Metastatic NSCLC with a confirmed ROS1 rearrangement AND progressive disease or intolerance to entrectinib or crizotinib
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OMALIZUMAB INJ,SOLN
XOLAIR
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XOLAIR |
2018-11-15 |
Exclusion Criteria- Prior severe hypersensitivity reaction to omalizumab or any of its ingredients
- Do not use to treat acute exacerbation of asthma or status asthmaticus
Inclusion Criteria- Care provided by a VA/VA Community Care pulmonologist, immunologist, allergist, or designated expert in the management of asthma
- Diagnosis of moderate to severe persistent asthma
- Pre-treatment serum IgE is 30 to 700 IU/mL
- Positive skin tests or in vitro reactivity to common aeroallergens (e.g., dust mites, pet dander, cockroach)
- Receiving medium to high dose inhaled corticosteroids and long-acting beta-agonist or other controller medication(s)
- Inadequate symptom control (e.g., short-acting beta-agonist use, nighttime awakening due to asthma more than once weekly, limitation with normal activity, Asthma Control Test less than 19) OR asthma exacerbation(s) requiring systemic corticosteroids in the last 12 months
- Adherent to asthma medications as evidenced by a review of prescription refill history during the last 12 months
- Should be nonsmoking or receiving smoking cessation treatment if smoking
- Has an epinephrine pen available at time of injection and for at least 24 hours after injection
- Therapy to be initiated in a healthcare setting
Additional Inclusion Criteria for Self-Administration- Provider has determined that self-administration with prefilled syringe by patient or caregiver is appropriate
- No previous history of anaphylaxis to omalizumab or other agents (e.g. food, drugs, biologics, etc.)
- At least 3 doses were administered in healthcare setting with no hypersensitivity reactions
- The patient and/or caregiver must be trained in and demonstrate the correct subcutaneous injection technique
- The patient and/or caregiver are taught to recognize signs and symptoms of anaphylaxis and is able to treat anaphylaxis appropriately
Other Justification- Patient has confirmed Ig-E mediated food allergy and a need for treatment with omalizumab to reduce the risk of type 1 allergic reactions, including anaphylaxis, and prescribed by a specialist in Allergy and Immunology.
Clinical Notes & Local Adjudication- Data for use in patients with baseline IgE serum levels up to 1500 IU/mL are available (considered off-label in the US). Use of omalizumab in such patients should be adjudicated locally.
- There is limited information on the efficacy and safety of omalizumab in patients who smoke. The decision to use omalizumab in patients who have had unsuccessful attempts at smoking cessation should be made on a case-by-case basis.
Exclusion Criteria- Prior severe hypersensitivity reaction to omalizumab or any of its ingredients
Inclusion Criteria (All must be fulfilled)- Diagnosis of severe chronic spontaneous urticaria (e.g., UAS7 >28 and/or UCT <12)
- Unacceptable symptoms despite a therapeutic trial of 1 non-sedating H antihistamine titrated up to 4 times the usual daily dose
- Has an epinephrine rescue device available at the time of injection and for at least 24 hours after the injection
- Omalizumab therapy is initiated in a healthcare setting
Provider Requirements- Provider is a VA or VA Community Care allergy specialist, dermatologist or designated expert in the management of allergic conditions
Additional Inclusion Criteria for Self-Administration- Provider has determined that self-administration with prefilled syringe by patient or caregiver is appropriate
- No previous history of anaphylaxis to omalizumab or other agents (e.g., food, drugs, biologics, etc.)
- At least 3 doses were administered in healthcare setting with no hypersensitivity reactions
- Patient and/or caregiver are taught to recognize signs and symptoms of anaphylaxis and able to treat anaphylaxis appropriately
Dosing/Pharmacology Notes- Dose is not dependent upon free or total serum IgE levels or body weight
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TESTOSTERONE AUTO-INJECTOR
XYOSTED
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XYOSTED |
2018-11-15 |
Exclusion Criteria- Active prostate cancer
- Active breast cancer
- Uncontrolled or untreated erythrocytosis (e.g., Hematocrit >48%)
- Severe, untreated Obstructive Sleep Apnea (OSA)
- Unevaluated Prostate Specific Antigen (PSA) level greater than 4 ng/mL or PSA greater than 3 ng/mL in individuals with risk factors for prostate cancer
- Severe lower urinary tract symptoms (International Prostate Symptom Score [IPSS] >19)
- Inadequately controlled congestive heart failure
- Acute Coronary syndrome (ACS), stroke (CVA), or revascularization procedure in the last 4 months
- Thrombophilia or history of unprovoked venous thromboembolism
- Severe liver disease or renal failure
- Desire for future fertility
- Active, unaddressed anabolic steroid misuse
Inclusion Criteria- Hypogonadism diagnosed by at least one clinical sign or symptom consistent with androgen deficiency
- HIV infected men with low testosterone levels and weight loss
- Receiving high doses of glucocorticoids who have low testosterone levels (daily dose greater than 5mg of prednisone or equivalent for at least 6 months)
- Status post bilateral orchiectomy or unilateral orchiectomy (with documented atrophy of second testicle)
- Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism and signs/symptoms of hypogonadism
Additional Pre-Initiation Requirements- Document that other potential treatable causes of symptoms of low testosterone levels and their suspected etiologies have been addressed
- Two, unequivocally low baseline, fasting, total testosterone levels (determined based on local laboratory assay and patient specific factors), at least one week apart, between 8am - 10am
- Prior to initiation, potential risks and benefits discussed and documented in the medical record
- Baseline Hemoglobin and Hematocrit, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and prolactin levels assessed
- Discussion regarding prostate cancer screening and monitoring occurred; if shared decision-making results in screening, PSA is measured
Clinical & Laboratory Considerations- For patients with Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism, a single baseline testosterone level is sufficient
- Free testosterone assessment recommended if concern for Sex Hormone Binding Globulin (SHBG) alterations exists (e.g., elderly, obesity, diabetes, liver or HIV disease, medications such as anticonvulsants/anabolic steroids/progestins, thyroid disease); acceptable measurement methods include equilibrium dialysis or calculation using total testosterone, SHBG, and albumin levels
- For patients on long-standing TRT (>1 year) without documentation, the requirement for two low baseline serum total testosterone levels may be waived case-by-case
- Risk factors for prostate cancer include African-American background, first-degree relative with prostate cancer, and exposure to Agent Orange
Indications for Evaluation- • Men presenting with specific symptoms: erectile dysfunction, low libido, decreased frequency of morning erections, new unexplained gynecomastia, decreased body hair, eunuchoid features on exam, small testes, loss of male hair and gynecomastia
- • Men with findings associated with hypogonadism: infertility, unexplained anemia, fractures
- • Men with a history of conditions likely to cause hypogonadism: traumatic brain injury, orchiectomy, pituitary dysfunction, testicular trauma, chronic opioid use
Laboratory & Biochemical Assessment Criteria- • Serum total and/or free testosterone must be unequivocally and consistently low
- • Measurements must be obtained in the early morning (6–10 am), fasting state, and confirmed on at least two separate occasions
- • Total testosterone levels <150 ng/dL require evaluation for secondary/central hypogonadism
- • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must be measured to distinguish primary from secondary hypogonadism
- • Abnormal immunoassay results must be confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS)
- • Free testosterone should be measured when conditions affecting sex hormone-binding globulin (SHBG) are present: obesity, diabetes mellitus, glucocorticoid use, nephrotic syndrome, thyroid disease, acromegaly, androgen/estrogen use, liver disease
- • Harmonized lower limit of normal for total testosterone is 264 ng/dL for CDC-certified assays with normal SHBG
Contraindications to Testosterone Replacement Therapy (TRT)- • Active prostate or breast cancer
- • Uncontrolled/untreated erythrocytosis (initial hematocrit >48% or 54% on TRT)
- • Severe, untreated obstructive sleep apnea
- • Elevated prostate-specific antigen (PSA) (>4 ng/mL)
- • Severe lower urinary tract symptoms
- • Inadequately controlled congestive heart failure
- • Acute coronary syndrome, stroke, or revascularization procedure within 4 months
- • Thrombophilia or history of unprovoked venous thromboembolism
- • Severe liver disease or renal failure
- • Active, unaddressed anabolic steroid misuse
- • Desire for future fertility
Initiation, Monitoring, & Dosing Parameters- • Discontinue TRT if symptoms do not significantly and consistently improve after 6–12 months despite testosterone levels within the reference range
- • Monitor testosterone (including free/bioavailable), hemoglobin, hematocrit, and PSA at 3–6 months after initiation, again at 12 months
- • Dose adjustments indicated if testosterone falls outside laboratory limits or total testosterone exceeds 900 ng/dL
- • Discontinue testosterone if hematocrit exceeds 54%
- • Blood draw timing: midway between injections for injectable formulations; 2–8 hours after application for gel once steady-state is achieved (typically after ≥1 week)
- • PSA monitoring: baseline, repeated at 12 months, then annually (or sooner if clinically indicated)
Specialist Referral Criteria- • Endocrinology: Total testosterone <150 ng/dL with inappropriately normal or decreased LH/FSH; new/established contraindications to TRT; gynecomastia due to hypogonadism
- • Urology (for males receiving TRT): PSA rising >1.4 ng/mL from baseline or >4 ng/mL at any time; lack of improvement or intolerance of PDE-5 inhibitors
Alternative Therapies & Specific Clinical Scenarios- • Human chorionic gonadotropin (HCG) reserved for hypogonadotropic hypogonadism in men seeking to maintain fertility (restricted to endocrinology and infertility specialists)
- • Clomiphene may be considered on a case-by-case basis in males with hypogonadotropic hypogonadism desiring fertility prior to HCG use
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CEMIPLIMAB-RWLC INJ,SOLN
LIBTAYO
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LIBTAYO |
2018-11-08 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Indication is FDA approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria- Care provided by a VA/VA Community Care oncology or hematology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Female patients of child-bearing potential and male patients with female partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment; use effective contraception during therapy and for 4 months after the last dose
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VARDENAFIL TAB
LEVITRA, VARDENAFIL HCL
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LEVITRA, VARDENAFIL HCL |
2018-11-08 |
Formulary Status- Avanafil is non-formulary.
- Sildenafil and tadalafil are available on the VA National Formulary (PA-F).
Prescribing & Clinical Evaluation Requirements- Prescriptions for erectile dysfunction must be written by a VA prescriber following an appropriate clinical evaluation.
- Prescribing clinician is responsible for ensuring no contraindications exist for the prescribed PDE5 inhibitor.
- Patient must understand treatment choices, associated risks, and benefits.
Quantity & Dispensing Limits- Limited to 6 doses per month for management of erectile dysfunction.
- Quantities less than 6 doses per month dispensed only at request of patient or prescriber.
- Greater quantities may be approved on a case-by-case basis (e.g., couples trying to conceive, veterans with inconsistent response).
- Quantity limit does not apply for management of pulmonary hypertension.
Adverse Event Reporting- All adverse events must be reported in the VA Adverse Drug Event Reporting System (VA ADERS/VA MedSafe).
Lost Prescription Management- Lost prescriptions will not be replaced during the intended time period; authorized refills become available at the next scheduled refill date.
Clinical Category: Monotherapy & Combination Therapy Restrictions- A PDE5I should not be used routinely for the management of LUTS-BPH as monotherapy.
- A PDE5I should not be used in combination with alpha blockers for BPH/LUTS, as it offers no symptom improvement advantage over either agent alone per American Urological Association (AUA) guidelines.
Clinical Category: Formulary PDE5I Initiation & Substitution Criteria- Consider when more established pharmacotherapies are not an option or have not demonstrated benefit.
- Initiate a formulary alpha blocker first using shared decision making and patient-specific factors. If ED is present, may consider adding a formulary PDE5I (with quantity limits) to an alpha blocker.
- Consider substituting or adding a formulary PDE5I if unable to tolerate or lack of response to an adequate trial (12 weeks) of a formulary alpha blocker titrated to maximum therapeutic dose.
- If adding a PDE5I, the patient must be on a stable dose of the alpha-blocker prior to initiation; the PDE5I should then be started at the lowest recommended dose.
Clinical Category: Clinical Scenarios for Formulary PDE5I Monotherapy Consideration- In place of an alpha blocker in the interim if cataract surgery is planned or likely (due to risk of intraoperative floppy iris syndrome).
- When an alpha blocker is contraindicated or not tolerated and an antimuscarinic is not appropriate due to post-void residual >250 mL, contraindication, ineffective trial, or substantial contribution to existing anticholinergic burden.
- (Note: The document explicitly states that only sildenafil, tadalafil, and vardenafil have been studied for BPH/LUTS; avanafil-specific criteria are not provided in the text.)
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BALOXAVIR TAB,ORAL
XOFLUZA
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XOFLUZA |
2018-11-01 |
Exclusion Criteria- Severe influenza requiring hospitalization unless oseltamivir/zanamivir is contraindicated or not tolerated
- Pregnancy
Inclusion Criteria- Patient with documented influenza by PCR/rapid flu test OR strongly suspected influenza during a time of significant influenza activity in the community (as evidenced by at least fever PLUS one or more of the following: severe fatigue, muscle aches, severe respiratory symptoms)
- Presenting within 48 hours of onset of flu-like symptoms
- Was exposed to influenza as a household contact who is within 48 hours of symptom onset
- AND at least one of the following additional conditions:
- Prior intolerance and/or allergy to oseltamivir and/or zanamivir
- Documented oseltamivir-resistant influenza in the community
- Inability to receive oseltamivir within the 48-hour time window from symptom onset (such as CBOCs, or after pharmacy hours, shortages of oseltamivir limiting supply)
Dosing and Administration- Given as a single oral dose taken with or without food
- Should be separated from dairy products or di/trivalent cations
- Recommended dosage: 40 mg for patients weighing < 80 kg and 80 mg for those weighing ≥ 80 kg
Additional Clinical Considerations- Emergence of mutants with reduced susceptibility to baloxavir emerged in 3-11% of subjects receiving baloxavir in clinical trials
- Use may be considered in situations where oseltamivir and zanamivir are contraindicated or not tolerated, or cannot be used due to logistical constraints which prevent adherence to or timely receipt of oseltamivir or zanamivir (such as homelessness, inability to fill prescription in a timely manner due to distance or after pharmacy hours, or other situations where directly observed therapy is preferred)
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TALAZOPARIB CAP,ORAL
TALZENNA
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TALZENNA |
2018-10-25 |
Exclusion Criteria- Absolute Neutrophil Count < 1500/µL
- Platelet count < 75,000/µL
- Hemoglobin < 9 g/dL (unless caused by bone marrow invasion)
- Unmanageable drug-drug interaction
- History of Myelodysplastic Syndrome or Acute Myeloid Leukemia
- Pregnancy
- Lactating
Inclusion Criteria- Care provided by a VA/VA purchased care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria- Locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutation (gBRCAm)
- Metastatic Castration-Resistant Prostate Cancer (mCRPC) with Homologous Recombination Repair (HRR) gene mutation, in combination with enzalutamide, for patients without prior novel androgen receptor inhibitor therapy in the mCRPC setting
Additional Inclusion Criteria if Applicable- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 7 months after stopping treatment.
Indications & Patient Population- Breast cancer: Single agent for patients with deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced (LA) or metastatic breast cancer (MBC).
- Prostate cancer: In combination with enzalutamide for treatment of homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
Dosing Regimen- Breast cancer: 1 mg PO once daily.
- Prostate cancer: 0.5 mg PO once daily in combination with enzalutamide.
Formulary Status & Pathway Restrictions- Breast cancer: Remains non-formulary due to Olaparib being the preferred PARP inhibitor on the VA Breast Cancer Pathway. Available via non-formulary processes for patients experiencing adherence issues with olaparib.
- Prostate cancer: Remains non-formulary as Olaparib is the preferred agent on the VA Oncology Prostate Cancer Pathway. Use in combination with enzalutamide may be adjudicated at the local level for off-pathway use.
Safety & Monitoring Considerations- Boxed warnings: None.
- Warnings/Precautions: Myelodysplastic syndrome/Acute Myeloid Leukemia (MDS/AML), myelosuppression, embryo-fetal toxicity.
- Drug Interactions: Reduce dose with select P-gp inhibitors and monitor for adverse events. Monitor for increased adverse events with BRCP inhibitors.
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BUPRENORPHINE INJ
BUPRENORPHINE HCL
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BUPRENORPHINE HCL |
2018-10-23 |
Perioperative Pain Management Principles- Buprenorphine treatment should not be routinely discontinued in the perioperative period for patients on stable MOUD therapy.
- Discontinuation may confer medical risks including return to active opioid use (50-90%), risk of overdose, prolonged hospital stay, and increased patient burden.
- A buprenorphine taper to < 16 mg/day may be considered for patients prescribed higher doses (> 16 mg) with anticipated high post-surgical pain.
- Utilize a multimodal pain approach including systemic non-opioid analgesics (acetaminophen, NSAIDs, gabapentinoids, ketamine, magnesium, systemic lidocaine, alpha-2 agonists, glucocorticoids), regional/local analgesics, and psychosocial interventions.
- When a full μOR agonist is needed to adequately control perioperative pain, use opioids with similar lipophilicity and binding affinity toward μORs; fentanyl and hydromorphone are reasonable alternatives.
Pre-operative Assessment & Planning- Perform patient evaluation including pain history, physical examination, medication reconciliation, assessment of physical/psychiatric comorbidities, and urine drug monitoring (including methadone, fentanyl, buprenorphine/metabolites).
- Verify prescription adherence via PDMP database.
- Conduct universal substance use disorder screening; perform detailed questioning and appropriate referrals for positive responses.
- Provide pre-operative counseling with written instructions regarding risks of opioid exposure/undertreating pain as relapse triggers.
- Determine procedure-related pain severity (minimal/no pain vs. significant pain) to guide dose adjustment or continuation.
- Plan continuity of care: taper off short-acting opioids prior to discharge; restrict IR opioids to short-term rescue use perioperatively; coordinate with waivered provider/OUD team for outpatient post-op pain care; preschedule follow-up with OUD/chronic pain provider; ensure sufficient buprenorphine supply at discharge.
Elective Procedure Management Criteria- For most patients, continue buprenorphine throughout the operative period.
- Minimally painful surgery: Continue current home dose unchanged, or divide and administer every 6 to 8 hours. Total daily dose may be titrated up to 32 mg/day in divided doses if needed for pain management (does not apply to extended-release injection).
- Painful surgery (moderate/severe pain): Continue baseline dose > 16 mg/day, OR reduce to < 16 mg/day to allow addition of an IR full μOR agonist. Expect higher doses of full μOR agonists requiring close monitoring (e.g., ICU or step-down unit).
- Examples of minimal pain procedures: tooth extraction, endoscopy, colonoscopy, bronchoscopy.
- Examples of moderate/severe pain procedures: laparoscopic, intra-abdominal, intra-thoracic, and orthopedic procedures.
Emergent Procedure Management Criteria- Anticipated minimal to no pain: Continue buprenorphine throughout procedure with non-opioid medications. Dose may be increased until adequate pain relief is achieved. Taper off short-acting opioids prior to discharge.
- Anticipated moderate to severe pain (Continue method): Continue buprenorphine throughout operation; increase dose postoperatively (except implant or BUP XR INJ) or use short-acting opioids. Taper off short-acting opioids prior to or shortly after discharge.
- Anticipated moderate to severe pain (Discontinue method): Discontinue per specified discontinuation criteria.
Discontinuation Criteria & Management- Discontinuation is indicated only when: patient requests to stop (after discussing pros/cons with provider and OUD team); medical contraindication exists; or all other options (maximizing dose, splitting dose, multimodal therapy) are insufficient.
- Emergency procedures: Discontinue immediately upon admission in lieu of high-dose short-acting μOR agonist.
- Elective procedures: Discontinue 24-72 hours prior to surgery. Restart after resolution of acute postoperative pain.
- Monitor respiratory function when using high doses of full μOR agonists as buprenorphine clears; adjust doses to prevent opioid-induced respiratory depression (OIRD).
- Use short-acting full opioid agonists to mitigate withdrawal symptoms. Non-opioid adjuncts for withdrawal (alpha-2 receptor agonists, loperamide, ondansetron, diphenhydramine) may be used as appropriate.
Restarting Buprenorphine Criteria- Taper off short-acting opioid and convert back to previous buprenorphine dose in consultation with waivered provider/OUD team.
- Restart when initial withdrawal signs are observed (for clinic induction) or by patient (for home induction).
- Initial dosing: 2 mg or 4 mg. If withdrawal is alleviated, restart remaining prior maintenance dose on day 1.
- Re-induction protocol: Start when clear signs of opioid withdrawal are present. Begin with 2-4 mg dose or 2/0.5 to 4/1 mg buprenorphine/naloxone. After approximately 2 hours, administer additional 2-4 mg if continued withdrawal and lack of sedation.
- FDA label maximum: 8 mg on Day 1 and 16 mg on Day 2. Document clinical rationale for dosing outside FDA recommendations. Individualize dosing; some patients stabilize on lower doses.
Indications & Pharmacological Properties- Approved for management of pain severe enough to require around-the-clock, long-term opioid treatment.
- Functions as a partial agonist at mu-opioid receptors (MORs) and antagonist at kappa-opioid receptors (KORs).
- Exhibits high binding affinity toward MORs with an extremely slow dissociation rate, making it difficult to displace from receptors once bound.
Perioperative Management- Maximize all other non-opioid and non-pharmacological interventions for pain control.
- When a full MOR agonist is clinically necessary, utilize opioids with similar lipophilicity and binding affinity toward MORs (e.g., fentanyl, sufentanil, hydromorphone) to more effectively compete with buprenorphine.
- Consult waivered providers or an interdisciplinary team experienced with buprenorphine use when available.
- Communicate treatment plans directly with the buprenorphine prescriber to facilitate optimal transition of care postoperatively.
Discharge Planning & Continuity of Care- Schedule patients with their SUD provider or chronic pain provider after discharge for close follow-up.
- Provide a warm hand-off for continued buprenorphine adherence upon discharge, particularly for high-risk patients.
- Discharge patients with an adequate supply of buprenorphine to last until their next scheduled follow-up appointment.
Naloxone Education & Counseling- Evaluate the necessity of naloxone based on the specific indication for buprenorphine prescription.
- For buprenorphine buccal film prescribed for chronic pain without a history of OUD or other SUD and with minimal risk for abusing other opioids, naloxone may not be required unless immediate-release (IR) opioids are initiated postoperatively with plans to discharge on them.
- Conduct overdose education during hospitalization and prescribe naloxone at discharge for patients considered at risk for opioid overdose.
- Provide explicit instruction to patients on how to use the prescribed naloxone product.
Safety Screening- Assess all patients for suicidal ideation prior to discharge per VA strategy and facility protocol.
- Recognize that chronic pain, history of or active SUD/OUD, acute stresses to health, and behavioral health comorbidities (e.g., depression, anxiety, PTSD) significantly heighten suicide risk.
Patient Identification & Surgical Classification- Surgical team/PreOP Clinic identifies patient on buprenorphine (Butrans®, Suboxone®, Subutex®, Zubsolv®, Belbuca® , Temgesic® , Sublocade ® , Buprenex®)
- Classify surgery as minimally painful or painful
Minimally Painful Surgery Criteria- NO or minimal need for postop opioid therapy expected (e.g., endoscopy, cataracts)
- Continue home dose through procedure day and after discharge
- Avoid discontinuation or holding of buprenorphine doses
Painful Surgery & Dose Stratification- High-dose patients: > 16 mg/day Suboxone/Subutex, > 11.4 mg/day Zubsolv
- Low-dose patients: < 16 mg/day Suboxone/Subutex, < 11.4 mg/day Zubsolv, Transdermal Buprenorphine (Butrans Patch) or Buccal Film (Belbuca), ANY DOSE
- No preoperative dose adjustment required for specified doses
Pre-operative Management- Elective surgery: Contact buprenorphine prescriber to discuss dose continuation or gradual dose reduction in anticipation of elective surgery
- Pre-operative dose adjustment not possible: Schedule PreOP Clinic appointment within 2-4 weeks, not later than one week before surgery
- Management options: Continue BUP method (preferred) or Discontinue BUP method
- Anticipate need for high doses of opioids for better pain coverage, or dose reduction to <16 mg/day Suboxone/Subutex, <11.4mg/day Zubsolv by time of surgery
- Update and record prescriber name and contact information in PreOP Clinic
- Consult acute pain service IF expected inpatient stay
Day of Surgery / Intraoperative Management- Perioperative plan per OR Anesthesia team / Acute Pain Team (if available)
- Use non-opioid analgesics (gabapentin, pregabalin, acetaminophen, NSAIDS) pre-operatively if not contraindicated
- Use continuous regional anesthesia techniques if possible (epidural and peripheral nerve catheters)
- Use IV ketamine, lidocaine intra-operatively if not contraindicated
Postoperative Management- Pain Service will follow patients postoperatively if needed; pain management plan per Pain Service recommendations
- Maintenance or placement of axial or peripheral nerve catheters, or short-term nerve blocks as necessary
- Focus on non-opioid medication (gabapentinoids, acetaminophen, NSAIDs, antidepressants, α2 agonists etc.)
- Use full agonist opioid with high binding affinity (hydromorphone, fentanyl, or sufentanil) orally, IV, or by PCA
- Avoid use of long-acting opioids
- Continuation of buprenorphine at home dose, lower dose, or higher dose
- Consider Ketamine infusion protocol (1-5mcg/kg/min infusion) if applicable
- Use Non-medication/non-procedural adjuncts (acupuncture, pet therapy, PT and mechanical supports as appropriate)
Re-induction Planning- Re-induction planning should not be necessary if patients continued to take buprenorphine during hospital stay or were on buprenorphine formulations for pain management (transdermal patch or buccal film)
- If buprenorphine was discontinued, pain service attending decides, in collaboration with buprenorphine prescriber or X-waivered provider, which re-induction strategy is appropriate
Indications & Clinical Appropriateness- FDA-approved for management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period of time.
- Appropriate when there is lack of progress towards functional goals and/or inadequate analgesic benefit with full mu agonist opioid.
- Appropriate when high potential for adverse effects exists due to medical conditions, mental health, or behavioral considerations with full mu agonist LTOT.
- Preferred for patients assessed as high risk for traditional oral opioid therapy where alternate buprenorphine products are not advisable, or for patients with documented difficulty swallowing/poor or unpredictable gastrointestinal absorption.
- More appropriate than transdermal patch for moderate MEDD dosing conversions (50-90 MEDD).
Contraindications & Inappropriateness- Infrequent use of immediate-release opioid medication for episodic pain (e.g., PRN).
- Demonstrating functional improvement and expressing preference to remain on full agonist LTOT, in absence of medical, mental health, or behavioral risk for adverse effects.
- May not provide adequate analgesia for patients requiring greater than 160 mg oral morphine equivalent daily dose (MEDD); consider alternate analgesic.
- Not indicated as an as-needed (PRN) analgesic.
Dosing & Administration Guidelines- Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
- For opioid-naïve/non-tolerant patients: Initiate with 75 mcg film once daily or, if tolerated, every 12 hours for at least 4 days, then increase to 150 mcg every 12 hours.
- Titrate in increments of 150 mcg every 12 hours, no more frequently than every 4 days, to achieve adequate analgesia while minimizing adverse reactions.
- Initial dosing based on prior opioid expressed as oral MEDD: <30 mg MEDD (75 mcg qd or q12h), 30-89 mg MEDD (150 mcg q12h), 90-160 mg MEDD (300 mcg q12h).
- Discontinue all other around-the-clock opioid drugs when BUP BF therapy is initiated.
- For oral buccal use only; apply to the buccal mucosa every 12 hours.
- Wait at least one hour after taking before brushing teeth; swish gently and swallow after dissolution.
- Do not apply to areas of the mouth with open sores or lesions.
- Do not use if pouch seal is broken or film is cut/damaged.
Initiation & Transition Strategies- Follow FDA-approved labeling for new starts and standard opioid transitions.
- STOP-START method: Stop full agonist opioids for 12-24 hours and start buprenorphine in early stages of withdrawal to decrease risk of precipitated withdrawal.
- Low dose buprenorphine initiation (microdosing/overlapping dosing): Allows short-term overlap of buprenorphine titration while on full agonist to mitigate withdrawal and discomfort.
- Published conversion recommendations are highly conservative (reduced 50-75%) and already include reduction for lack of tolerance or cross-tolerance.
- Avoid rapid titrations without assessing effectiveness and tolerability at steady state; due to long half-life, takes about five days to achieve steady state.
Monitoring, Evaluation & Safety Considerations- LTOT principles should be followed: focus on functional improvement in physical, social, and psychological domains consistent with the biopsychosocial model of care.
- Assess risks versus benefits periodically; tapering or discontinuing should be considered when risks outweigh benefits or based on patient preference.
- Screen for and assess risk for OUD prior to initiation and when patterns of unhealthy medication use emerge during LTOT.
- Baseline evaluation includes: Urine drug screen (UDS), PDMP check, liver transaminases, monitor for effectiveness of pain relief/prevention of withdrawal symptoms, assess risk for physical/psychological dependence, drug diversion, sensitivity to adverse effects (particularly respiratory depression), assess mental status/respiratory status/increased risk for falls.
- Pain Management Teams (PMT) should be available for specialty care support during initiation/stabilization and transitions.
- Shared decision-making and veteran preference should guide treatment approach.
- For patients without diagnosed OUD, the encounter should indicate the pain condition diagnosis and the prescription should state “for pain management”.
Patient Counseling & Special Instructions- Caution with driving or operating heavy machinery.
- Store in secure place out of reach of children.
- Advise patients to avoid eating or drinking until film dissolves.
- Inform dentist that therapy has been started; wait at least one hour after taking before brushing teeth.
Indications- Acute pain
- Intractable pain
- Pain expected to be severe enough to require opioid management
Patient Selection (Appropriate)- Veterans who may be appropriate for a usual formulary opioid (e.g., fentanyl, hydromorphone, oxycodone, morphine) for acute pain management
- Veterans with known risk factors for hospital Opioid Related Adverse Events (ORADES)
- Veterans already on a buprenorphine pain formulation as an outpatient (e.g., buccal or transdermal)
- Veterans with impaired renal function (dose adjustment not required)
- Veterans who are opioid naïve with other medical risks (e.g., COPD, advanced age)
- Veterans at high risk for opioid dependence (e.g., co-occurring chronic pain syndromes)
- Patients more sensitive to the GI side effects of opioids and surgical procedures
Patient Selection (Inappropriate/Not Recommended)- Pain not severe enough (or expected to be severe enough) to require opioid therapy
- Patients already on high-dose opioid therapy (prescribed or illicit) or long-acting opioid antagonist treatment (e.g., Vivitrol) due to unknown exact role of pain formulations at this time
Contraindications & Precautions- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting
- Known or suspected GI obstruction including paralytic ileus
- Hypersensitivity to buprenorphine
- Additive risk with concomitant CNS depressants (similar to other full-agonist opioids)
Dosing & Administration Criteria- Pre/Peri-operative and PACU: 0.3 mg slow IV (over 2 minutes) pre-op; repeat 0.3 mg slow IV during PACU recovery PRN, may repeat x1 additional dose at 30 minutes if necessary
- PACU to Ward: If IV effective, consider continuing transmucosal formulation (e.g., Belbuca 300 to 450 mcg BID) scheduled for duration of admission; dose adjust based on observed patient response
- Discharge Home: If effective and additional discharge opioids indicated, consider continuing buprenorphine buccal 2-3 times daily PRN for expected post-surgical duration; select outpatient dose based on observed effective minimum dose during inpatient episode
- Emergency Department: Primarily transmucosal; specific use guidance outside scope but studied in renal colic and fractures
- Patients on milligram doses of buprenorphine (8-32 mg/day or LAI): Should NOT be stopped for acute pain management where FAO may be used; continue at maintenance dose and add non-opioid/high-potency FAO as needed. Dose reduction (25-50%) may be considered to allow mu-opioid receptors to “open up” in 12-24 hours, but requires close monitoring due to increased risk of overdose/withdrawals
Clinical Management & Pearls- Tapering and discontinuing buprenorphine for acute pain should not be needed; self-tapers due to long half-life. Advise patients to stop if pain is well managed with non-opioid only
- Onset of action: within 20 minutes (faster with parenteral); full effect of transmucosal products may take 1-3 hours
- Buccal formulation benefits from mucoadherence; requires no patient participation; can be administered under anesthesia; dry buccal mucosa can be moistened with a gloved finger prior to application; yellow side goes on cheek; do not eat or drink while dissolving; rinse mouth after complete dissolution
- If buprenorphine is ineffective/insufficient: may indicate opioid refractoriness; optimize non-opioid strategies and use high-potency full-agonist opioids (FAO); conventional FAO expected to be fully effective even if microgram doses prove ineffective
- Precipitated withdrawal: Microgram dosing for acute pain would not be expected to result in precipitated withdrawal; incidence <5% even when transitioning from high-dose full-agonists
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AMIKACIN SUSP,INHL
ARIKAYCE
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ARIKAYCE |
2018-10-12 |
Exclusion Criteria- Indication other than refractory Mycobacterium avium (MAC) pulmonary disease
Inclusion Criteria- Prescriber is an Infectious Diseases or Pulmonary Specialist
- Patient has been treated with at least 6 months of guideline-based therapy without converting sputum cultures to negative (≥6-month final cultures remain positive)
- Patient has failed or is intolerant of parenteral aminoglycoside therapy or is not a candidate for such therapy
Discontinuation Criteria- If the patient does not convert sputum cultures to negative with 6 months of ALIS + guideline-based therapy for refractory disease (≥6 month final culture results), therapy should be discontinued
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GALCANEZUMAB-GNLM INJ,SOLN
EMGALITY PEN, EMGALITY SYRINGE
|
EMGALITY PEN, EMGALITY SYRINGE |
2018-10-12 |
Indication & Patient Definition- Episodic Cluster Headache defined as attacks lasting from 7 days to one year, separated by pain-free periods lasting 3 months or more
Exclusion Criteria- Uncontrolled hypertension
- History of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- Concurrent preventative therapy with another CGRP targeting agent (including other CGRP-targeting monoclonal antibodies and gepants)
- Diagnosis of hemiplegic migraine or tension headache
Inclusion Criteria- Treatment initiated by a VA/VA Community Care neurologist or locally designated headache expert
- Contraindication, intolerance, or lack of therapeutic response to a therapeutic dose of either verapamil 240-960 mg/day or lithium 600-1500 mg/day
Monitoring & Safety Requirements- Discontinue galcanezumab if signs or symptoms of Raynaud’s phenomenon develop
- Monitor patients with a history of Raynaud’s phenomenon and inform them about the possibility of recurrence and worsening
- Scheduled blood pressure check 2-4 weeks after initiation of therapy
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PIMAVANSERIN CAP,ORAL
NUPLAZID
|
NUPLAZID |
2018-09-13 |
Exclusion Criteria- Diagnosis of dementia-related psychosis due to Alzheimer’s disease, Lewy Body Dementia or other dementia not secondary to Parkinson disease
- Known QTc prolongation, history of cardiac arrhythmias, or circumstances increasing risk of torsade de pointes and/or sudden death (including symptomatic bradycardia, hypokalemia or hypomagnesemia, congenital prolongation of the QT interval)
- Taking other medications known to prolong the QT interval
- Taking another antipsychotic
- Taking a moderate or strong CYP3A4 inducer
Inclusion Criteria- Meets diagnostic criteria for Parkinson Disease Psychosis (PDP):
- Presence of at least one PDP symptom: illusions, false sense of presence, hallucinations or delusions
- Primary diagnosis of Parkinson disease (PD)
- PDP symptoms occur after the onset of PD
- Duration of PDP symptoms is recurrent or continuous for 1 month
- Symptoms are not better accounted for by another cause (e.g., dementia with Lewy bodies, psychiatric disorders such as schizophrenia/schizoaffective disorder/delusional disorder/mood disorder with psychotic features, or a general medical condition including delirium)
- Prescriber is a psychiatrist, neurologist or geriatric medicine specialist
Renewal Criteria- Assess effectiveness within 3 months after initiation via in-person or telephone interview with the patient and/or caregiver
- Discontinue if ineffective
Dosage & Administration- Recommended dose: 34 mg, taken orally once daily, without titration
- Can be taken with or without food
- When coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole), recommended dose is 10 mg, taken orally as one tablet once daily
Clinical Considerations & Warnings- Indicated for treatment of hallucinations and delusions associated with Parkinson disease psychosis
- Box Warning: Increased mortality in elderly patients with dementia-related psychosis; not approved for dementia-related psychosis unrelated to PD psychosis
- Avoid combination with another antipsychotic due to increased mortality rate and serious adverse events; discontinue current antipsychotics before starting pimavanserin
- Prolongs the QT interval; avoid in patients with known QT prolongation, history of cardiac arrhythmias, or those taking drugs that prolong QT (including Class 1A/3A antiarrhythmics, certain antipsychotics, and certain antibiotics)
- Failed to demonstrate efficacy as an augmentation treatment for schizophrenia
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LUSUTROMBOPAG TAB
MULPLETA
|
MULPLETA |
2018-08-30 |
Indication & Mechanism- Small-molecule thrombopoietin receptor agonist (TPORA)
- Used in patients with thrombocytopenia due to chronic liver disease
- Indicated to prophylactically and temporarily increase platelet counts prior to invasive procedures
- Goal is to decrease prophylactic platelet transfusion and the need for rescue therapy for bleeding
Exclusion Criteria- Past or present arterial or venous thrombotic or thromboembolic event(s) or prothrombotic condition(s), including portal or splenic mesenteric systemic thrombosis
- Thrombocytopenia (< 150 x 109/L) due to a cause other than chronic liver disease
- Uncontrolled generalized infection
- Exposure to eltrombopag or romiplostim in the previous 90 days or avatrombopag within the previous 35 days
- Planned invasive procedure is one for which routine preprocedural platelet transfusion is not recommended (e.g., bone marrow aspiration or biopsy, traction removal of tunneled central venous catheter, paracentesis)
- Attempting to normalize platelet counts with lusutrombopag
Inclusion Criteria- Care provided by a VA / VA Community Care hepatologist or locally designated expert in chronic liver disease
- Pretreatment platelet count less than 50 x 109/L (i.e., severe thrombocytopenia) in the 2 weeks prior to initiation of lusutrombopag
- Chronic liver disease (Child-Pugh class C is conditionally not recommended)
- Scheduled to undergo an elective invasive procedure within the next 29 days
- Use of platelet transfusions is medically inadvisable (e.g., risk of transfusion reaction, volume overload, platelet refractoriness, acute lung injury), or the patient declines any blood products
- In the previous 6 months: (1) Absence of portal vein thrombosis on computed tomography (CT) or magnetic resonance imaging (MRI) OR (2) Presence of hepatopetal portal vein blood flow on doppler ultrasonography
Special Clinical Considerations- Child-Pugh class C chronic liver disease is conditionally not recommended due to limited data; Cmax and AUC0–Τ decreased by 20%–30% relative to mild to moderate hepatic impairment
- Hepatopetal refers to normal direction of blood flow towards the liver
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MOGAMULIZUMAB-KPKC INJ,SOLN
POTELIGEO
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POTELIGEO |
2018-08-30 |
Exclusion Criteria- Care not provided by a VA or VA Community Care hematology/oncology provider
- Evidence of large cell transformation (LCT)
- Evidence of central nervous system (CNS) metastasis
- History of allogeneic or autologous hematopoietic stem cell transplant (HSCT) within past 90 days
- Plan to undergo allogeneic HSCT within the next 6 months
- Chronic or unresolved infection
- Active autoimmune disease (e.g., Graves’ disease, SLE, RA, Crohn’s, psoriasis)
- ANC < 1500 cells/mm3, platelets < 100,000 cells/mm3 (if marrow involvement, then ANC <1000 and platelets < 75,000)
- Severe hepatic impairment (Child-Pugh Class C), as drug has not been evaluated in this population
- Pregnancy (i.e., known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Diagnosis of mycosis fungoides (MF) or Sézary syndrome (SS)
- Relapsed or refractory disease after at least two prior courses of systemic therapy (patients received 2-5 prior treatments in MAVORIC)
- Mogamulizumab will be used as a single agent therapy (not to be given in combination with other systemic therapies)
- ECOG Performance Status 0-1 (ECOG Eastern Cooperative Oncology Group)
- Counseling provided to advise female patients of reproductive potential OR male patients and their female partners of reproductive potential to use effective contraception during treatment with mogamulizumab-kpkc and for at least 3 months following last dose of mogamulizumab-kpkc
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TILDRAKIZUMAB-ASMN INJ,SOLN
ILUMYA
|
ILUMYA |
2018-08-30 |
Exclusion Criteria- Active, serious, systemic or localized infection, including undrained abscess (may be started/restarted once the infection is controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may be initiated after starting antiviral prophylaxis)
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may be initiated after starting antiviral prophylaxis)
- Untreated HIV infection (Treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care dermatologist or locally designated psoriasis expert
- Prescribed at the FDA-approved dose for plaque psoriasis
- Adult with chronic (≥ 6 months) moderate to severe plaque psoriasis (including involvement of nails only)
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may be initiated while waiting for test results)
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- Methotrexate monotherapy is medically inadvisable, not tolerated, or not adequate
- Phototherapy is medically inadvisable, inadequate, not available or not feasible
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, or not adequate (i.e., NO response to ONE TNFI after 3 months, partial response to 3-month trials of TWO TNFIs = total 6 months, or loss of initial response)
Additional Inclusion Criteria- ONE of the following criteria must be met:
- Interleukin-17A inhibitor (i.e., ixekizumab [preferred] or secukinumab) is medically inadvisable, not tolerated or not adequate (i.e., NO response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response)
- Ustekinumab is medically inadvisable, not tolerated or not adequate (i.e., NO response after 16 weeks, inadequate partial response after 32 weeks, or loss of initial response)
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PATISIRAN INJ,SOLN
ONPATTRO
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ONPATTRO |
2018-08-23 |
Exclusion Criteria- Sensorimotor or autonomic neuropathy (including diabetic neuropathy) without also having a diagnosis of hereditary transthyretin-mediated (hATTR) amyloidosis
- Primary amyloidosis
- Leptomeningeal amyloidosis
- Currently receiving another therapy for hATTR amyloidosis (e.g., diflunisal, tafamidis, vutrisiran)
- Prior liver transplant
- New York Heart Association (NYHA) Class III or IV heart failure
- Known pregnancy
Inclusion Criteria- Provider is a VA or VA Community Care neurologist or locally designated hATTR amyloidosis provider
- Diagnosis of polyneuropathy of hATTR amyloidosis including clinical symptoms and genetic testing that confirms a variant in TTR
- Documented baseline Neuropathy Impairment Score (NIS) of 5 to 130, Polyneuropathy Disability Score (PND) I to IIIb or Familial Amyloid Polyneuropathy (FAP) stage 1 or 2
- Age 18-85 years
- Anticipated survival > 2 years
- Contraindication, intolerance, or lack of clinical response to at least a 9-month trial of vutrisiran
- Supplementation of the recommended daily allowance of vitamin A is planned to start upon approval
- Discussion with patient/caregiver/family member regarding realistic treatment expectations and discontinuation should be documented
Additional Inclusion Criteria- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment including the risk that patisiran can decrease serum vitamin A levels
Monitoring & Continuation Requirements- Continuation of therapy assessed at 9 months and then periodically throughout treatment
- Therapy continued only if patient continues to demonstrate positive clinical response (e.g., improved motor function, quality of life, or ambulation or decreased neurological impairment)
- Refer to eye clinic if ocular symptoms suggestive of vitamin A deficiency develop (e.g., night blindness)
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ELAGOLIX TAB
ORILISSA
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ORILISSA |
2018-08-02 |
Exclusion Criteria- Pregnancy
- Known osteoporosis
- Severe hepatic impairment (Child-Pugh C)
- Concomitant use of organic anion transporting polypeptide (OATP)1B1 (e.g., gemfibrozil, cyclosporine)
- Known hypersensitivity
- Concomitant use of hormonal contraceptives
Inclusion Criteria- Prescribed by or in consultation with a VA/VA Community Care Gynecology or Women’s Health Provider
- Diagnosis of endometriosis (clinical or surgical) in a premenopausal patient
- Contraindication, intolerance, or inadequate response to one alternative treatment (e.g., NSAID, estrogen-containing or progestin-only hormonal contraceptive)
- Assessed for history of suicidal ideation, depression, and mood disorders prior to starting treatment
- Assessed for risk of bone density loss
- Planned duration of treatment not to exceed a maximum of 6 months for high dose (200 mg twice daily) or 24 months for low dose (150 mg once daily) elagolix due to risk for bone loss
Additional Inclusion Criteria- For patients who can become pregnant: Exclude pregnancy prior to receiving elagolix or start within 7 days of menses onset
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective nonhormonal contraception during treatment and for 28 days after stopping treatment
Safety Monitoring & Risk Assessment- Monitor for mood changes and depressive symptoms after starting treatment due to association with mood disorders, depression, and suicidal ideation
- Consider bone mineral density (BMD) assessment in patients with history of low trauma fracture or risk factors for low bone density
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IVOSIDENIB TAB
TIBSOVO
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TIBSOVO |
2018-08-02 |
Exclusion Criteria- Inability to swallow whole tablets
- Severe renal impairment (CrCl < 30 ml/min)
- Severe hepatic impairment (Child-Pugh C)
- Baseline QTc > 450 msec and/or history of long QT syndrome
- Clinically significant cardiovascular disease (uncontrolled or symptomatic arrhythmias, CHF NYHA Class 3 or 4, myocardial infarction in prior 6 months)
- Unmanageable CYP3A4 inducer/inhibitor and/or QTc-prolonging drug interaction
- Chronic or unresolved infection
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
General Inclusion Criteria- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult discussed and documented
- ECOG performance status 0-2
- Presence of an isocitrate dehydrogenase-1 (IDH-1) mutation
Disease-Specific Indications- Relapsed/refractory acute myeloid leukemia: Relapsed disease after 2 previous inductions OR relapsed disease after 1 induction and not suitable for intensive chemotherapy
- Newly diagnosed acute myeloid leukemia: Age > 75 years OR not a candidate for intensive induction therapy
- Locally advanced or metastatic cholangiocarcinoma: After 1 prior gemcitabine-based or fluorouracil-based regimen
Reproductive & Safety Requirements- Pregnancy must be excluded prior to receiving ivosidenib
- Provide contraceptive counseling on potential risks vs. benefits of taking ivosidenib if patient were to become pregnant
- Advise against breastfeeding during treatment and for at least 1 month after the last dose
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PIMAVANSERIN TAB
NUPLAZID
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NUPLAZID |
2018-08-02 |
Exclusion Criteria- Diagnosis of dementia-related psychosis due to Alzheimer’s disease, Lewy Body Dementia or other dementia not secondary to Parkinson disease
- Known QTc prolongation, history of cardiac arrhythmias, or circumstances increasing risk of torsade de pointes and/or sudden death (including symptomatic bradycardia, hypokalemia or hypomagnesemia, congenital prolongation of the QT interval)
- Taking other medications known to prolong the QT interval
- Taking another antipsychotic
- Taking a moderate or strong CYP3A4 inducer
Inclusion Criteria- Meets diagnostic criteria for Parkinson Disease Psychosis (PDP):
- Presence of at least one PDP symptom: illusions, false sense of presence, hallucinations or delusions
- Primary diagnosis of Parkinson disease (PD)
- PDP symptoms occur after the onset of PD
- Duration of PDP symptoms is recurrent or continuous for 1 month
- Symptoms are not better accounted for by another cause (e.g., dementia with Lewy bodies, psychiatric disorders such as schizophrenia/schizoaffective disorder/delusional disorder/mood disorder with psychotic features, or a general medical condition including delirium)
- Prescriber is a psychiatrist, neurologist or geriatric medicine specialist
Renewal Criteria- Assess effectiveness within 3 months after initiation via in-person or telephone interview with the patient and/or caregiver
- Discontinue if ineffective
Dosage & Administration- Recommended dose: 34 mg, taken orally once daily, without titration
- Can be taken with or without food
- When coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole), recommended dose is 10 mg, taken orally as one tablet once daily
Clinical Considerations & Warnings- Indicated for treatment of hallucinations and delusions associated with Parkinson disease psychosis
- Box Warning: Increased mortality in elderly patients with dementia-related psychosis; not approved for dementia-related psychosis unrelated to PD psychosis
- Avoid combination with another antipsychotic due to increased mortality rate and serious adverse events; discontinue current antipsychotics before starting pimavanserin
- Prolongs the QT interval; avoid in patients with known QT prolongation, history of cardiac arrhythmias, or those taking drugs that prolong QT (including Class 1A/3A antiarrhythmics, certain antipsychotics, and certain antibiotics)
- Failed to demonstrate efficacy as an augmentation treatment for schizophrenia
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BUDESONIDE TAB,SA
BUDESONIDE ER, UCERIS
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BUDESONIDE ER, UCERIS |
2018-07-20 |
Exclusion Criteria- Hypersensitivity to budesonide or any tablet ingredients (anaphylactic reactions have occurred)
- Concomitant therapy with CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin)
- Acute, severe ulcerative colitis
- Glucocorticoid-refractory ulcerative colitis (defined as no meaningful clinical response to induction therapy using prednisone 30 to 60 mg/day for 2 weeks with a 2-week taper, or IV equivalent for 1 to 1.5 weeks)
- Stable quiescent ulcerative colitis without evidence of recent exacerbation (not indicated for maintenance of remission)
- Untreated or uncontrolled fungal, bacterial, systemic viral, or parasitic infections
- Crohn’s disease or microscopic/collagenous colitis
Inclusion Criteria- Patient receives VA care/consultation and initial prescription is from a gastroenterologist or other ulcerative colitis treatment expert
- Intolerance or relative contraindication to orally administered prednisone, prednisolone, methylprednisolone, or other glucocorticoids with higher systemic bioavailability (e.g., unstable/uncontrolled diabetes mellitus, hypertension, heart failure, osteoporosis)
- Requires treatment to induce remission in newly diagnosed or recurrent active mild to moderate ulcerative colitis
- OR requires rapid-onset treatment for recurrence of active, mild to moderate ulcerative colitis as an adjunct to 5-ASA maintenance therapy
Dosage and Administration- Initial/subsequent dosage: 9 mg orally once daily in the morning with or without food (excluding grapefruit/juice) for up to 8 weeks
- Tablets must not be chewed, crushed, or broken
- Avoid grapefruit/grapefruit juice due to hypercorticism risk
- Discontinuation: Tapering is not required; only one tablet strength (9 mg) is available
- Switching from other systemic glucocorticoids: Taper slowly off the prior glucocorticoid to reduce adrenal insufficiency risk; clinically equivalent doses are uncertain
Monitoring- Increased signs/symptoms of hypercorticism, particularly in patients with moderate/severe liver disease or those taking CYP3A4 inhibitors (consider discontinuation)
- Signs/symptoms of adrenal insufficiency or benign intracranial hypertension, particularly when switching from higher systemic effect glucocorticoids or during surgery/stress situations (supplementation recommended)
- General glucocorticoid complications: HPA axis suppression, Cushing’s syndrome, hyperglycemia, new infections/exacerbations/reactivation of latent infection/masking of infection signs, increased blood pressure, sodium/water retention, hypokalemia, gastrointestinal perforation (signs may be masked), behavioral/mood disturbances, decreased bone density, cataracts/eye infections/glaucoma, weight gain
Clinical Considerations & Indications- FDA indication: Induction of remission in patients with active, mild to moderate ulcerative colitis
- Not evaluated for isolated ulcerative proctitis (rectal foam is approved for this)
- Pregnancy Category C: Use only if potential benefit justifies potential risk to the fetus
- Nursing Mothers: Secreted in human milk; discontinue nursing or drug based on clinical importance
- Elderly: Use caution; insufficient data on age-related responses
- Gastric acid reducing agents (PPIs, H2-receptor antagonists, antacids) may affect pH-dependent dissolution/coating breakdown at pH ≥7.0; no specific management recommendations
- Liver Impairment: Cirrhosis causes 2.5-fold increase in systemic bioavailability; severe dysfunction effects unstudied; mild disease causes minimal effects
- Tuberculosis: Active or latent TB requires concomitant anti-TB therapy
- Formulation distinction: MMX technology releases drug throughout colon for UC; ENTOCORT (CIR) releases in ileum/ascending colon for Crohn’s, may be used off-label for microscopic/collagenous colitis
Renewal Criteria- Each course of therapy limited to 8 weeks
- Inadequate response within 4 weeks indicates steroid-refractory disease requiring alternative therapies
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BINIMETINIB TAB
MEKTOVI
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MEKTOVI |
2018-07-05 |
Indication & Patient Population- • Unresectable or metastatic melanoma (locally advanced Stage IIIB, IIIC, or IV)
- • BRAF V600E or V600K mutation positive
- • Indicated specifically in combination with encorafenib
Exclusion Criteria / Patient Selection Constraints- • Untreated CNS lesions
- • Uveal or mucosal melanoma
- • Positive serology for HIV
- • Active Hepatitis B or C infection
- • Leptomeningeal metastases
- • History of bone marrow transplant or solid organ transplant
- • Prior BRAF or MEK inhibitor therapy
- • Clinically significant cardiovascular disease
- • Uncontrolled arterial hypertension
- • Pregnancy
Safety & Monitoring Requirements- • Assess baseline ejection fraction by echocardiogram or MUGA; no safety data available if baseline EF is below 50% or below the institutional lower limit of normal (LLN)
- • Monitor for cardiomyopathy (asymptomatic or symptomatic decrease in LVEF)
- • Assess for vision changes at each visit due to risks of serous retinopathy, retinal vein occlusion, and uveitis
- • Monitor liver function tests prior to therapy and monthly during treatment due to hepatotoxicity risk
- • Monitor CPK and creatinine prior to initiation and periodically during treatment due to rhabdomyolysis risk
- • Use effective contraception due to embryo-fetal toxicity risk
Administration & Pharmacologic Considerations- • Dosage form: 15 mg tablet
- • May be taken with or without food; store at room temperature
- • Functions as a BRAF inhibitor plus MEK inhibitor combination for first-line treatment of metastatic melanoma
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ENCORAFENIB CAP,ORAL
BRAFTOVI
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BRAFTOVI |
2018-07-05 |
Indication & Patient Population- • Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
- • Not indicated for the treatment of wild-type BRAF melanoma
Dosing & Administration- • 75 mg capsule
- • Encorafenib 300 mg QD plus binimetinib 45 mg BID
Inclusion Criteria- • Locally advanced (Stage IIIB, IIIC, or IV) unresectable or metastatic BRAF V600-mutant melanoma
- • BRAF V600E or V600K mutation or both
- • Adequate organ function and baseline labs
- • At least 1 measurable lesion
- • Treatment naïve or 1 previous immunotherapy
Exclusion Criteria- • Untreated CNS lesions
- • Uveal or mucosal melanoma
- • Positive serology for HIV
- • Active HepB or C or both
- • Leptomeningeal mets
- • Risk for retinal vein occlusion
- • History of BMT or solid organ transplant
- • Prior BRAF or MEK inhibitor therapy
- • Previous systemic chemo other than immunotherapy
- • Clinically significant CV disease
- • Uncontrolled arterial hypertension
- • Pregnancy
Safety Considerations & Monitoring- • Boxed warnings: None
- • Contraindications: None
- • Monitor for new primary malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma, new primary melanoma)
- • Assess for hemorrhage (most frequently gastrointestinal; fatal intracranial hemorrhage in brain metastases)
- • Assess for uveitis at each visit
- • Correct hypokalemia and hypomagnesemia prior to initiation due to QT prolongation risk
- • Monitor for embryo-fetal toxicity
- • Common adverse reactions: fatigue, nausea, vomiting, abdominal pain, arthralgia
- • Discontinuation rate 5% (most common reasons: headache, hemorrhage)
Efficacy Outcomes- • Primary endpoint: Progression-free survival (PFS) by blinded independent review committee (BIRC)
- • Secondary endpoints: PFS encorafenib vs vemurafenib; best objective response rate (ORR); disease control rate; duration of response; time to response
- • Median OS and 1, 2, and 3 year OS rates reported
- • Quality of life favored combination over vemurafenib
Clinical Guidance & Place in Therapy- • Metastatic melanoma
- • Unresectable/metastatic BRAF V600E or K mutated melanoma in combination with binimetinib
- • Versus vemurafenib (NCCN Category 1)
- • Standard of care for first-line metastatic melanoma includes immunotherapy alone/in combination or BRAF inhibitor plus MEK inhibitor
- • Combination BRAF/MEK inhibitors show no statistically significant difference in PFS and OS based on indirect comparisons
- • Encorafenib + binimetinib is clinically thought to be better tolerated
- • Nivolumab + ipilimumab is likely the preferred 1st choice independent of BRAF mutation status if patient is a candidate for immunotherapy and does not require immediate results due to bulky disease
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BUPRENORPHINE/ NALOXONE FILM,SUBLINGUAL
SUBOXONE
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SUBOXONE |
2018-07-01 |
Perioperative Pain Management Principles- Buprenorphine treatment should not be routinely discontinued in the perioperative period for patients on stable MOUD therapy.
- Discontinuation may confer medical risks including return to active opioid use (50-90%), risk of overdose, prolonged hospital stay, and increased patient burden.
- A buprenorphine taper to < 16 mg/day may be considered for patients prescribed higher doses (> 16 mg) with anticipated high post-surgical pain.
- Utilize a multimodal pain approach including systemic non-opioid analgesics (acetaminophen, NSAIDs, gabapentinoids, ketamine, magnesium, systemic lidocaine, alpha-2 agonists, glucocorticoids), regional/local analgesics, and psychosocial interventions.
- When a full μOR agonist is needed to adequately control perioperative pain, use opioids with similar lipophilicity and binding affinity toward μORs; fentanyl and hydromorphone are reasonable alternatives.
Pre-operative Assessment & Planning- Perform patient evaluation including pain history, physical examination, medication reconciliation, assessment of physical/psychiatric comorbidities, and urine drug monitoring (including methadone, fentanyl, buprenorphine/metabolites).
- Verify prescription adherence via PDMP database.
- Conduct universal substance use disorder screening; perform detailed questioning and appropriate referrals for positive responses.
- Provide pre-operative counseling with written instructions regarding risks of opioid exposure/undertreating pain as relapse triggers.
- Determine procedure-related pain severity (minimal/no pain vs. significant pain) to guide dose adjustment or continuation.
- Plan continuity of care: taper off short-acting opioids prior to discharge; restrict IR opioids to short-term rescue use perioperatively; coordinate with waivered provider/OUD team for outpatient post-op pain care; preschedule follow-up with OUD/chronic pain provider; ensure sufficient buprenorphine supply at discharge.
Elective Procedure Management Criteria- For most patients, continue buprenorphine throughout the operative period.
- Minimally painful surgery: Continue current home dose unchanged, or divide and administer every 6 to 8 hours. Total daily dose may be titrated up to 32 mg/day in divided doses if needed for pain management (does not apply to extended-release injection).
- Painful surgery (moderate/severe pain): Continue baseline dose > 16 mg/day, OR reduce to < 16 mg/day to allow addition of an IR full μOR agonist. Expect higher doses of full μOR agonists requiring close monitoring (e.g., ICU or step-down unit).
- Examples of minimal pain procedures: tooth extraction, endoscopy, colonoscopy, bronchoscopy.
- Examples of moderate/severe pain procedures: laparoscopic, intra-abdominal, intra-thoracic, and orthopedic procedures.
Emergent Procedure Management Criteria- Anticipated minimal to no pain: Continue buprenorphine throughout procedure with non-opioid medications. Dose may be increased until adequate pain relief is achieved. Taper off short-acting opioids prior to discharge.
- Anticipated moderate to severe pain (Continue method): Continue buprenorphine throughout operation; increase dose postoperatively (except implant or BUP XR INJ) or use short-acting opioids. Taper off short-acting opioids prior to or shortly after discharge.
- Anticipated moderate to severe pain (Discontinue method): Discontinue per specified discontinuation criteria.
Discontinuation Criteria & Management- Discontinuation is indicated only when: patient requests to stop (after discussing pros/cons with provider and OUD team); medical contraindication exists; or all other options (maximizing dose, splitting dose, multimodal therapy) are insufficient.
- Emergency procedures: Discontinue immediately upon admission in lieu of high-dose short-acting μOR agonist.
- Elective procedures: Discontinue 24-72 hours prior to surgery. Restart after resolution of acute postoperative pain.
- Monitor respiratory function when using high doses of full μOR agonists as buprenorphine clears; adjust doses to prevent opioid-induced respiratory depression (OIRD).
- Use short-acting full opioid agonists to mitigate withdrawal symptoms. Non-opioid adjuncts for withdrawal (alpha-2 receptor agonists, loperamide, ondansetron, diphenhydramine) may be used as appropriate.
Restarting Buprenorphine Criteria- Taper off short-acting opioid and convert back to previous buprenorphine dose in consultation with waivered provider/OUD team.
- Restart when initial withdrawal signs are observed (for clinic induction) or by patient (for home induction).
- Initial dosing: 2 mg or 4 mg. If withdrawal is alleviated, restart remaining prior maintenance dose on day 1.
- Re-induction protocol: Start when clear signs of opioid withdrawal are present. Begin with 2-4 mg dose or 2/0.5 to 4/1 mg buprenorphine/naloxone. After approximately 2 hours, administer additional 2-4 mg if continued withdrawal and lack of sedation.
- FDA label maximum: 8 mg on Day 1 and 16 mg on Day 2. Document clinical rationale for dosing outside FDA recommendations. Individualize dosing; some patients stabilize on lower doses.
Indications & Pharmacological Properties- Approved for management of pain severe enough to require around-the-clock, long-term opioid treatment.
- Functions as a partial agonist at mu-opioid receptors (MORs) and antagonist at kappa-opioid receptors (KORs).
- Exhibits high binding affinity toward MORs with an extremely slow dissociation rate, making it difficult to displace from receptors once bound.
Perioperative Management- Maximize all other non-opioid and non-pharmacological interventions for pain control.
- When a full MOR agonist is clinically necessary, utilize opioids with similar lipophilicity and binding affinity toward MORs (e.g., fentanyl, sufentanil, hydromorphone) to more effectively compete with buprenorphine.
- Consult waivered providers or an interdisciplinary team experienced with buprenorphine use when available.
- Communicate treatment plans directly with the buprenorphine prescriber to facilitate optimal transition of care postoperatively.
Discharge Planning & Continuity of Care- Schedule patients with their SUD provider or chronic pain provider after discharge for close follow-up.
- Provide a warm hand-off for continued buprenorphine adherence upon discharge, particularly for high-risk patients.
- Discharge patients with an adequate supply of buprenorphine to last until their next scheduled follow-up appointment.
Naloxone Education & Counseling- Evaluate the necessity of naloxone based on the specific indication for buprenorphine prescription.
- For buprenorphine buccal film prescribed for chronic pain without a history of OUD or other SUD and with minimal risk for abusing other opioids, naloxone may not be required unless immediate-release (IR) opioids are initiated postoperatively with plans to discharge on them.
- Conduct overdose education during hospitalization and prescribe naloxone at discharge for patients considered at risk for opioid overdose.
- Provide explicit instruction to patients on how to use the prescribed naloxone product.
Safety Screening- Assess all patients for suicidal ideation prior to discharge per VA strategy and facility protocol.
- Recognize that chronic pain, history of or active SUD/OUD, acute stresses to health, and behavioral health comorbidities (e.g., depression, anxiety, PTSD) significantly heighten suicide risk.
Patient Identification & Surgical Classification- Surgical team/PreOP Clinic identifies patient on buprenorphine (Butrans®, Suboxone®, Subutex®, Zubsolv®, Belbuca® , Temgesic® , Sublocade ® , Buprenex®)
- Classify surgery as minimally painful or painful
Minimally Painful Surgery Criteria- NO or minimal need for postop opioid therapy expected (e.g., endoscopy, cataracts)
- Continue home dose through procedure day and after discharge
- Avoid discontinuation or holding of buprenorphine doses
Painful Surgery & Dose Stratification- High-dose patients: > 16 mg/day Suboxone/Subutex, > 11.4 mg/day Zubsolv
- Low-dose patients: < 16 mg/day Suboxone/Subutex, < 11.4 mg/day Zubsolv, Transdermal Buprenorphine (Butrans Patch) or Buccal Film (Belbuca), ANY DOSE
- No preoperative dose adjustment required for specified doses
Pre-operative Management- Elective surgery: Contact buprenorphine prescriber to discuss dose continuation or gradual dose reduction in anticipation of elective surgery
- Pre-operative dose adjustment not possible: Schedule PreOP Clinic appointment within 2-4 weeks, not later than one week before surgery
- Management options: Continue BUP method (preferred) or Discontinue BUP method
- Anticipate need for high doses of opioids for better pain coverage, or dose reduction to <16 mg/day Suboxone/Subutex, <11.4mg/day Zubsolv by time of surgery
- Update and record prescriber name and contact information in PreOP Clinic
- Consult acute pain service IF expected inpatient stay
Day of Surgery / Intraoperative Management- Perioperative plan per OR Anesthesia team / Acute Pain Team (if available)
- Use non-opioid analgesics (gabapentin, pregabalin, acetaminophen, NSAIDS) pre-operatively if not contraindicated
- Use continuous regional anesthesia techniques if possible (epidural and peripheral nerve catheters)
- Use IV ketamine, lidocaine intra-operatively if not contraindicated
Postoperative Management- Pain Service will follow patients postoperatively if needed; pain management plan per Pain Service recommendations
- Maintenance or placement of axial or peripheral nerve catheters, or short-term nerve blocks as necessary
- Focus on non-opioid medication (gabapentinoids, acetaminophen, NSAIDs, antidepressants, α2 agonists etc.)
- Use full agonist opioid with high binding affinity (hydromorphone, fentanyl, or sufentanil) orally, IV, or by PCA
- Avoid use of long-acting opioids
- Continuation of buprenorphine at home dose, lower dose, or higher dose
- Consider Ketamine infusion protocol (1-5mcg/kg/min infusion) if applicable
- Use Non-medication/non-procedural adjuncts (acupuncture, pet therapy, PT and mechanical supports as appropriate)
Re-induction Planning- Re-induction planning should not be necessary if patients continued to take buprenorphine during hospital stay or were on buprenorphine formulations for pain management (transdermal patch or buccal film)
- If buprenorphine was discontinued, pain service attending decides, in collaboration with buprenorphine prescriber or X-waivered provider, which re-induction strategy is appropriate
Indications & Clinical Appropriateness- FDA-approved for management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period of time.
- Appropriate when there is lack of progress towards functional goals and/or inadequate analgesic benefit with full mu agonist opioid.
- Appropriate when high potential for adverse effects exists due to medical conditions, mental health, or behavioral considerations with full mu agonist LTOT.
- Preferred for patients assessed as high risk for traditional oral opioid therapy where alternate buprenorphine products are not advisable, or for patients with documented difficulty swallowing/poor or unpredictable gastrointestinal absorption.
- More appropriate than transdermal patch for moderate MEDD dosing conversions (50-90 MEDD).
Contraindications & Inappropriateness- Infrequent use of immediate-release opioid medication for episodic pain (e.g., PRN).
- Demonstrating functional improvement and expressing preference to remain on full agonist LTOT, in absence of medical, mental health, or behavioral risk for adverse effects.
- May not provide adequate analgesia for patients requiring greater than 160 mg oral morphine equivalent daily dose (MEDD); consider alternate analgesic.
- Not indicated as an as-needed (PRN) analgesic.
Dosing & Administration Guidelines- Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
- For opioid-naïve/non-tolerant patients: Initiate with 75 mcg film once daily or, if tolerated, every 12 hours for at least 4 days, then increase to 150 mcg every 12 hours.
- Titrate in increments of 150 mcg every 12 hours, no more frequently than every 4 days, to achieve adequate analgesia while minimizing adverse reactions.
- Initial dosing based on prior opioid expressed as oral MEDD: <30 mg MEDD (75 mcg qd or q12h), 30-89 mg MEDD (150 mcg q12h), 90-160 mg MEDD (300 mcg q12h).
- Discontinue all other around-the-clock opioid drugs when BUP BF therapy is initiated.
- For oral buccal use only; apply to the buccal mucosa every 12 hours.
- Wait at least one hour after taking before brushing teeth; swish gently and swallow after dissolution.
- Do not apply to areas of the mouth with open sores or lesions.
- Do not use if pouch seal is broken or film is cut/damaged.
Initiation & Transition Strategies- Follow FDA-approved labeling for new starts and standard opioid transitions.
- STOP-START method: Stop full agonist opioids for 12-24 hours and start buprenorphine in early stages of withdrawal to decrease risk of precipitated withdrawal.
- Low dose buprenorphine initiation (microdosing/overlapping dosing): Allows short-term overlap of buprenorphine titration while on full agonist to mitigate withdrawal and discomfort.
- Published conversion recommendations are highly conservative (reduced 50-75%) and already include reduction for lack of tolerance or cross-tolerance.
- Avoid rapid titrations without assessing effectiveness and tolerability at steady state; due to long half-life, takes about five days to achieve steady state.
Monitoring, Evaluation & Safety Considerations- LTOT principles should be followed: focus on functional improvement in physical, social, and psychological domains consistent with the biopsychosocial model of care.
- Assess risks versus benefits periodically; tapering or discontinuing should be considered when risks outweigh benefits or based on patient preference.
- Screen for and assess risk for OUD prior to initiation and when patterns of unhealthy medication use emerge during LTOT.
- Baseline evaluation includes: Urine drug screen (UDS), PDMP check, liver transaminases, monitor for effectiveness of pain relief/prevention of withdrawal symptoms, assess risk for physical/psychological dependence, drug diversion, sensitivity to adverse effects (particularly respiratory depression), assess mental status/respiratory status/increased risk for falls.
- Pain Management Teams (PMT) should be available for specialty care support during initiation/stabilization and transitions.
- Shared decision-making and veteran preference should guide treatment approach.
- For patients without diagnosed OUD, the encounter should indicate the pain condition diagnosis and the prescription should state “for pain management”.
Patient Counseling & Special Instructions- Caution with driving or operating heavy machinery.
- Store in secure place out of reach of children.
- Advise patients to avoid eating or drinking until film dissolves.
- Inform dentist that therapy has been started; wait at least one hour after taking before brushing teeth.
Indications- Acute pain
- Intractable pain
- Pain expected to be severe enough to require opioid management
Patient Selection (Appropriate)- Veterans who may be appropriate for a usual formulary opioid (e.g., fentanyl, hydromorphone, oxycodone, morphine) for acute pain management
- Veterans with known risk factors for hospital Opioid Related Adverse Events (ORADES)
- Veterans already on a buprenorphine pain formulation as an outpatient (e.g., buccal or transdermal)
- Veterans with impaired renal function (dose adjustment not required)
- Veterans who are opioid naïve with other medical risks (e.g., COPD, advanced age)
- Veterans at high risk for opioid dependence (e.g., co-occurring chronic pain syndromes)
- Patients more sensitive to the GI side effects of opioids and surgical procedures
Patient Selection (Inappropriate/Not Recommended)- Pain not severe enough (or expected to be severe enough) to require opioid therapy
- Patients already on high-dose opioid therapy (prescribed or illicit) or long-acting opioid antagonist treatment (e.g., Vivitrol) due to unknown exact role of pain formulations at this time
Contraindications & Precautions- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting
- Known or suspected GI obstruction including paralytic ileus
- Hypersensitivity to buprenorphine
- Additive risk with concomitant CNS depressants (similar to other full-agonist opioids)
Dosing & Administration Criteria- Pre/Peri-operative and PACU: 0.3 mg slow IV (over 2 minutes) pre-op; repeat 0.3 mg slow IV during PACU recovery PRN, may repeat x1 additional dose at 30 minutes if necessary
- PACU to Ward: If IV effective, consider continuing transmucosal formulation (e.g., Belbuca 300 to 450 mcg BID) scheduled for duration of admission; dose adjust based on observed patient response
- Discharge Home: If effective and additional discharge opioids indicated, consider continuing buprenorphine buccal 2-3 times daily PRN for expected post-surgical duration; select outpatient dose based on observed effective minimum dose during inpatient episode
- Emergency Department: Primarily transmucosal; specific use guidance outside scope but studied in renal colic and fractures
- Patients on milligram doses of buprenorphine (8-32 mg/day or LAI): Should NOT be stopped for acute pain management where FAO may be used; continue at maintenance dose and add non-opioid/high-potency FAO as needed. Dose reduction (25-50%) may be considered to allow mu-opioid receptors to “open up” in 12-24 hours, but requires close monitoring due to increased risk of overdose/withdrawals
Clinical Management & Pearls- Tapering and discontinuing buprenorphine for acute pain should not be needed; self-tapers due to long half-life. Advise patients to stop if pain is well managed with non-opioid only
- Onset of action: within 20 minutes (faster with parenteral); full effect of transmucosal products may take 1-3 hours
- Buccal formulation benefits from mucoadherence; requires no patient participation; can be administered under anesthesia; dry buccal mucosa can be moistened with a gloved finger prior to application; yellow side goes on cheek; do not eat or drink while dissolving; rinse mouth after complete dissolution
- If buprenorphine is ineffective/insufficient: may indicate opioid refractoriness; optimize non-opioid strategies and use high-potency full-agonist opioids (FAO); conventional FAO expected to be fully effective even if microgram doses prove ineffective
- Precipitated withdrawal: Microgram dosing for acute pain would not be expected to result in precipitated withdrawal; incidence <5% even when transitioning from high-dose full-agonists
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ESTRADIOL INSERT,VAG
IMVEXXY
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IMVEXXY |
2018-07-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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BARICITINIB TAB
OLUMIANT
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OLUMIANT |
2018-06-14 |
Patient Selection & Diagnosis- Moderate to severe active rheumatoid arthritis
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Dosing at the FDA-recommended dose for rheumatoid arthritis, adjusting for strong organic anion transporter 3 inhibitor interactions, moderate renal impairment (GFR 30 to 60 mL/min/1.73 m2), and hematocytopenias
Infectious Disease Screening & Management- Exclusion: Uncontrolled active infection (may start/restart once treatment for the infection is initiated)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Exclusion: HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Exclusion: Congenital or acquired immunodeficiency
- Exclusion: Malignancy in the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless treating rheumatologist and oncologist agree risk-benefits favor use)
- Inclusion: Completed tuberculosis test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Inclusion: Current or past completion of hepatitis C screening (may initiate while waiting for test results)
Laboratory Parameters & Organ Function- Exclusion: Lymphocytes < 500 cells/mm3 confirmed by repeat testing, absolute neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once lymphopenia, neutropenia, and/or anemia resolve)
- Exclusion: Severe renal impairment (GFR < 30 mL/min/1.73 m2)
- Exclusion: Severe hepatic impairment (Child-Pugh class C)
Concomitant Medications & Interactions- Exclusion: Concomitant therapy with immunosuppressive biologics or potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus) except during overlaps in treatment transition
- Exclusion: Concomitant therapy with strong CYP3A4 inducers (e.g., rifampin)
Vaccination Requirements- Inclusion: Offered all age-appropriate vaccinations prior to initiating therapy
- Unless contraindicated, recombinant zoster (SHINGRIX) vaccine should be completed or at least initiated by the end of the first year of treatment, preferably when dosage is low, disease is stable, or at other times when a robust immune response can be expected
TNF-Inhibitor Prerequisites- Inclusion: Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, or not adequate (NO response to ONE TNFI after 3 months, partial response to 3-month trials of TWO TNFIs = total 6 months, or loss of initial response)
Special Populations & Counseling- Exclusion: Pregnancy
- Exclusion: Breastfeeding
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits
- For HBsAg-negative but anti-HBc-positive patients where consult is deemed indicated: GI/liver or infectious diseases expert consultation for advice on starting antiviral prophylaxis or preemptive monitoring for HBV reactivation
Monitoring & Retesting- Routine retesting is not required for prescription renewals; retesting in high-risk patients should be considered
Indication & Patient Selection- Treatment of adults with severe alopecia areata (AA)
- Patients should have a SALT score ≥ 50
- Current episode of alopecia > 6 months to < 8 years without spontaneous improvement (≤ 10-point reduction in SALT score) in the previous 6 months, or episodes lasting ≥ 8 years if episodes of hair regrowth were observed on affected areas in the previous 8 years
Dosing Regimen- Recommended dose: 2 mg orally once daily with or without food
- If response is inadequate, increase to 4 mg once daily
- For patients with nearly complete or complete scalp hair loss (with or without substantial eyelash or eyebrow hair loss), consider treating with 4 mg once daily
- After an adequate response is obtained with 4 mg once daily, decrease to 2 mg once daily
- Available dosage forms: 1 mg, 2 mg, and 4 mg tablets
Dosage Modifications & Interruptions- Hematocytopenias: Dosage interruptions recommended for absolute lymphocyte counts < 500 cells/μL, absolute neutrophil count < 1000 cells/μL, or hemoglobin < 8 g/dL
- Renal Impairment: Dosage modification recommended for moderate renal impairment (eGFR 30 to ≤ 60 mL/min/1.73 m2); not recommended in severe renal impairment (eGFR < 30 mL/min/1.73 m2)
- Hepatic Impairment: Dosage interruption recommended if increases in ALT or AST occur and drug-induced liver disease is suspected; not recommended in severe hepatic impairment
- Strong OAT3 Inhibitors (e.g., probenecid): Dosage reduction recommended if recommended daily dosage is 2 mg or 4 mg; if recommended dose is 1 mg daily, consider discontinuing the inhibitor
Contraindications & Limitations of Use- Not recommended for use in combination with other JAKIs, biologic immunomodulators, cyclosporine, or other potent immunosuppressants
- Boxed warnings, contraindications, and other warnings/precactions are the same as for rheumatoid arthritis
VA-Specific Formulary Criteria- May be used in patients with severe AA (≥ 50% scalp hair loss)
- Patients should have tried and had intolerance or an inadequate response to a systemic corticosteroid unless it is medically inadvisable
- Should not be used in patients with severe AA who had no hair regrowth with previous systemic JAKI therapy
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Congenital or acquired immunodeficiency
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless treating dermatologist and oncologist agree risk-benefits favor use)
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3, absolute neutrophils < 1000 cells/mm3, or hemoglobin < 8 g/dL (may start/restart once lymphopenia, neutropenia, and/or anemia resolve)
- Severe renal impairment (eGFR < 30 mL/min/1.73 m2)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with immunosuppressive biologics or potent immunosuppressants (except overlaps during treatment transition)
- Concomitant therapy with strong CYP3A4 inducers (e.g., rifampin)
- Pregnancy
- Breastfeeding
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- NO hair regrowth with previous use of a systemic Janus kinase inhibitor
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care dermatologist or locally designated expert
- Diagnosis of severe alopecia areata based on ≥ 50% scalp hair loss
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
Additional Inclusion Criteria- If HBsAg-negative but anti-HBc-positive and consult deemed indicated: GI/liver or infectious diseases expert consulted for advice on starting antiviral prophylaxis or preemptively monitoring for HBV reactivation
- For females who can become pregnant: Pregnancy status checked; counseling provided on potential risks vs benefits of treatment and use of effective contraception
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits of treatment
Dosing & Monitoring Requirements- Prescribed at the FDA-recommended dose for severe alopecia areata, adjusting for strong organic anion transporter 3 inhibitor drug interactions, moderate renal impairment (eGFR 30 to < 60 mL/min/1.73 m2), and hematocytopenias
- Routine retesting is not required for prescription renewals; retesting in high-risk patients should be considered
- Antiviral prophylaxis for HBV should use agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated before initiation when possible; recombinant zoster vaccine should be completed or initiated by the end of the first year, preferably at low dosage, stable disease, or times when robust immune response is expected
Clinical Policy & Context- Alopecia areata is NOT a cosmetic condition; Directive 1108.08 policy on Cosmetic and Enhancement Drugs does NOT apply
- Individual cases that are exceptions to exclusion and inclusion criteria should be adjudicated at the local facility according to P&T Committee and Pharmacy Services policy
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OMEPRAZOLE TAB,ORAL DISINTEGRATING
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2018-06-14 |
Pharmacology & Drug Interaction- Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
- Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.
Gastrointestinal Risk Management- PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
- For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.
Cardiovascular Risk Management- Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
- No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.
Prescribing Criteria- Deprescribe PPIs as much as possible per established de-prescribing guidelines.
- Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.
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SARILUMAB AUTO-INJECTOR
KEVZARA
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KEVZARA |
2018-06-14 |
Exclusion Criteria- Uncontrolled, active, severe infection (including undrained abscess)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis
- Untreated HIV infection
- Concomitant live or live-attenuated vaccines, or administration of such vaccines less than 2 weeks prior to initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 (unless associated with Duffy-null Associated Neutrophil Count)
- Baseline platelet count < 150,000/mm3
- Baseline alanine transaminase (ALT) and/or aspartate transaminase (AST) > 1.5x the upper limit of normal (ULN)
Inclusion Criteria- Diagnosis of polymyalgia rheumatica (PMR)
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening
- Initiated concurrently with or after glucocorticoid therapy (unless glucocorticoids are medically inadvisable)
Additional Inclusion Criteria- For HBsAg-negative, anti-HBc-positive patients where consult is indicated: E-consult with GI/liver or infectious diseases expert for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- Patients capable of pregnancy: Counseling provided on treatment risks vs benefits and requirement for effective contraception during therapy
- Lactating patients/providing breastmilk: Counseling provided on potential risks and benefits of treatment
Monitoring & Safety Considerations- Antiviral prophylaxis for hepatitis B should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed or initiated by the end of the first year, preferably when dosage is low or disease is stable
- Routine rescreening for hepatitis B or C is not required for prescription renewals; retesting in high-risk patients should be considered
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for infection has been initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Congenital or acquired immunodeficiency
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 unless associated with Duffy-null Associated Neutrophil Count
- Baseline platelet count <150,000/mm3
- Baseline ALT and/or AST > 1.5x the upper limit of normal (ULN)
Inclusion Criteria- Diagnosis of moderate to severe rheumatoid arthritis
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response
Additional Inclusion Criteria & Clinical Precautions- If HBsAg-negative but anti-HBc-positive and consult is indicated: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- Females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
- Females who are lactating/providing breastmilk: Counseling provided on potential risks and benefits of treatment
- Antiviral prophylaxis for hepatitis B virus should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed or initiated by end of first year, preferably when dosage is low, disease is stable, or immune response is robust
- May be used with methotrexate, other nonbiologic DMARDs, mycophenolate, hydroxychloroquine, or glucocorticoids; concomitant use of potent immunosuppressives should generally be avoided
- Routine rescreening for hepatitis B or C is not required for prescription renewals; retesting in high-risk patients should be considered
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AVATROMBOPAG TAB
DOPTELET
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DOPTELET |
2018-06-07 |
Exclusion Criteria- Anticipated antiviral treatment includes a direct-acting antiviral (DAA) for chronic HCV
- Currently receiving peginterferon and ribavirin with or without DAA for chronic HCV
- Any contraindications to peginterferon and ribavirin apply
- Active malignancy or stem cell disorder
- Prior history of arterial or venous thrombosis plus ≥2 risk factors (hereditary thrombophilic disorders, estrogen hormone replacement therapy, systemic contraception therapy containing estrogen, smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer)
- Serious cardiac, cerebrovascular, or pulmonary disease
- Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin
- Known hypersensitivity, intolerance, or allergy to peginterferon and ribavirin, eltrombopag tablets, or ingredients
- Evidence of decompensated liver disease (Child-Pugh score ≥7 and/or clinical manifestations)
- Patient infected with HIV
Inclusion Criteria- Under care of and/or in collaboration with an experienced VA HCV practitioner
- Provider has discussed risks/benefits with patient; shared decision made for use
- Diagnosis of chronic HCV infection
- Baseline platelet count <75,000/μL
- Appropriate candidates for peginterferon and ribavirin combination antiviral therapy
- Treatment with peginterferon and ribavirin (dual therapy) anticipated after reaching target platelet goal
- Abdominal imaging negative for portal vein thrombosis within past 3 months
Dosing & Administration- Initiate prior to peginterferon and ribavirin therapy to obtain target platelet count
- Initial dose: 25 mg once daily on empty stomach (1 hour before or 2 hours after meal)
- Adjust by 25 mg increments every 2 weeks to achieve target platelet count (≥90,000/μL for peginterferon alfa-2a; ≥100,000/μL for peginterferon alfa-2b)
- Use lowest dose to achieve/maintain necessary platelet count
- Maintain same pre-treatment dose when starting antiviral therapy; modify during therapy to maintain counts between 50,000-150,000/μL
- Dose reduction NOT needed solely based on East Asian ethnicity
- Maximum dose: 100 mg/day
- If platelets <50,000/μL after ≥2 weeks: increase by 25 mg; wait 2 weeks to assess
- If platelets ≥150,000-200,000/μL: decrease by 25 mg; wait 2 weeks
- If platelets >200,000/μL: stop eltrombopag; monitor twice weekly; reinitiate at dose reduced by 25 mg (or 12.5 mg if previously on 25 mg) when count <100,000/μL
Monitoring Requirements- Prior to initiation: CBC with differential (including platelet), ocular exam for cataracts, Liver Function Panel (Total/Direct bilirubin, AST, ALT, albumin, total protein)
- During therapy: CBC weekly until stable then monthly; Serum liver tests (ALT, AST, bilirubin) every 2 weeks during adjustment then monthly; fractionate bilirubin if elevated; repeat tests within 3-5 days if abnormal; monitor weekly until resolved/stabilized/baseline; regular ocular exams for cataracts
- Upon discontinuation: CBCs weekly for at least four weeks
Safety & Risk Considerations- Box warnings for hepatotoxicity and risk of hepatic decompensation (ascites, hepatic encephalopathy, variceal hemorrhage, spontaneous bacterial peritonitis, hepatocellular carcinoma, death)
- Patients with albumin <3.5g/dL or MELD scores ≥10 at baseline have greatest risk of hepatic decompensation
- High thromboembolism risk: may increase risk; consider risk vs benefit
- Cataracts developed/worsened in 8% of treated patients
Discontinuation Guidelines- Discontinue when antiviral therapy is discontinued
- Discontinue for hepatotoxicity if ALT increases to ≥3X ULN (normal liver) or ≥3X baseline (pre-treatment elevations) and is progressive, persistent ≥4 weeks, accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury/hepatic decompensation
- Non-response: Consider discontinuing after 9 weeks at maximum dose (100 mg/day) if platelet count not increased sufficiently to initiate antiviral therapy
Specific Populations & Interactions- HIV: No safety/efficacy data; limited drug-drug interaction studies
- Renal insufficiency (CrCl<50ml/min): Not studied; use with caution
- Hepatic insufficiency: Clearance reduced in moderate-severe impairment; initial dose 25 mg daily; monitor serum liver tests; AUC ~2-fold higher; half-life prolonged 2-fold
- Pregnancy: Category C; discuss risks/benefits; consider enrollment in Promacta Pregnancy Registry
- Interactions: Substrate of CYP1A2/CYP2C8; inhibitor of OATP1B1/UGTs; chelates polyvalent cations. Separate administration from iron, calcium, aluminum, magnesium, selenium, zinc-containing meds/supplements/food by at least 4 hours.
Exclusion Criteria- Stem cell disorder (i.e., myelodysplastic syndrome)
- Patient has not received prior therapy with steroids to increase platelet counts
- Thrombocytopenia secondary to bone marrow suppressive anti-cancer therapy, antibiotics, or other drugs
- Thromboembolic events within the past year (unless evaluated by a hematology provider and deemed an appropriate candidate)
- Pregnancy and/or breastfeeding
Inclusion Criteria- Diagnosis of chronic Immune Thrombocytopenia (ITP)
- Platelet count < 30,000 mm³ and/or persistent bleeding resistant/refractory to glucocorticoids
- Relapse after second-line therapies (unless contraindicated or patient is not a candidate): Splenectomy, Rituximab
Counseling & Management Requirements- For patients who can become pregnant: Counseling provided on potential risks vs. benefits of taking drug if patient were to become pregnancy
- Advise patients not to breastfeed during treatment and for 2 weeks following
Indication & Clinical Purpose- Thrombocytopenia due to chronic liver disease (CLD)
- Small-molecule thrombopoietin receptor agonist (TPORA) used to prophylactically and temporarily increase platelet counts prior to invasive procedures
- Aims to decrease prophylactic platelet transfusion and the need for rescue therapy for bleeding
Exclusion Criteria- Thrombocytopenia due to a cause other than CLD (e.g., Immune Thrombocytopenia)
- Past or present arterial or venous thrombotic or thromboembolic event(s) or prothrombotic condition(s), including portal, splenic, mesenteric, or systemic thrombosis
- Uncontrolled generalized infection
- Exposure to eltrombopag or romiplostim in the previous 90 days, or lusutrombopag within the previous 35 days
- Planned invasive procedure where routine preprocedural platelet transfusion is not recommended (bone marrow aspiration/biopsy, traction removal of tunneled central venous catheter, paracentesis)
- Attempting to normalize platelet counts
Inclusion Criteria- Care provided by a VA/VA Community Care hepatologist or locally designated expert in CLD
- Pretreatment platelet count less than 50 x 10^9/L (severe thrombocytopenia) within the 2 weeks prior to initiation
- CLD (Child-Pugh class C is conditionally not recommended due to limited data and exclusion from clinical trials; no clinically meaningful pharmacokinetic effects observed)
- Scheduled to undergo an elective invasive procedure within the next 27 days
- Use of platelet transfusions is medically inadvisable (e.g., risk of transfusion reaction, volume overload, platelet refractoriness, acute lung injury) or patient declines blood products
- In the previous 6 months: Absence of portal vein thrombosis on computed tomography (CT) or magnetic resonance imaging (MRI) OR presence of hepatopetal portal vein blood flow on doppler ultrasonography
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FINGOLIMOD CAP,ORAL
GILENYA
|
GILENYA |
2018-06-07 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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ERENUMAB-AOOE INJ
AIMOVIG AUTOINJECTOR
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AIMOVIG AUTOINJECTOR |
2018-06-01 |
Exclusion Criteria- Uncontrolled hypertension
- History of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- Concurrent preventive therapy with another calcitonin gene-related peptide (CGRP) targeting agent (including other CGRP-targeting monoclonal antibodies and gepants)
- Diagnosis of hemiplegic migraine or tension headache
Inclusion Criteria- Chronic Migraine defined as at least 15 headache days per month with at least 8 migraine days per month
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 2 of the following: beta blocker, topiramate, divalproex, and ACE inhibitor or ARB
- If using a combination of a CGRP-targeted monoclonal antibody for preventive therapy and a CGRP receptor antagonist (gepant) for abortive therapy, patient must be evaluated and counseled on risks of concomitant therapy
Clinical Monitoring & Safety- Discontinue erenumab if signs or symptoms of Raynaud’s phenomenon develop; patients with a history of Raynaud’s phenomenon should be monitored and informed about the possibility of recurrence and worsening
- Scheduled blood pressure check required 2-4 weeks after initiation of therapy
- Botulinum toxin with demonstrated no response may be considered as one of the required prevention medication trials
- Therapeutic dose definitions: beta blocker (e.g., metoprolol 50-100 mg BID, propranolol 20-80 mg BID), topiramate 50-200 mg BID, divalproex 500-1000 mg daily, ACE inhibitor or ARB (e.g., lisinopril 20 mg daily, enalapril 10 mg daily, telmisartan 80 mg daily)
- Divalproex is not recommended in patients who can become pregnant
- Safety evidence of concomitant CGRP acting agents is limited; patients may be prone to CGRP-related adverse events (vasodilation, GI motor-stimulation, prosecretory effects); alternative therapies may benefit patients at high risk for ischemic events or severe constipation
Provider Requirements & Assessment- Treatment must be initiated by a VA/VA Community Care neurologist or locally designated headache expert
- Headache expert must perform a comprehensive headache assessment including evaluation for medication overuse headache, other secondary headache types, adherence to prior headache therapies, features requiring urgent/emergent evaluation, triggers, effective acute treatment, and nonpharmacologic interventions
- Board certification in headache medicine is not required to meet the provider criterion
Exclusion Criteria- Uncontrolled hypertension
- History of Raynaud’s phenomenon with ischemia (e.g., digital ulcers, tissue necrosis, or other critical ischemia)
- Concurrent preventive therapy with another calcitonin gene related peptide (CGRP) targeting agent (including other CGRP-targeting monoclonal antibodies and gepants)
- Diagnosis of hemiplegic migraine or tension headache
Inclusion Criteria- Treatment initiated by a VA/VA Community Care neurologist or locally designated headache expert
- Episodic migraine defined as 4 to 14 monthly headache days
- Contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 3 of the following: beta blocker, topiramate, divalproex, SNRI or TCA, and ACE inhibitor or ARB
Monitoring & Clinical Management Requirements- Scheduled blood pressure check required 2–4 weeks after initiation of therapy
- Discontinue erenumab if signs or symptoms of Raynaud’s phenomenon develop
- Monitor patients with a history of Raynaud’s phenomenon and inform them about the possibility of recurrence and worsening
- Comprehensive headache assessment required by prescribing clinician (evaluation for medication overuse headache, other secondary headache types, adherence to prior therapies, features requiring urgent/emergent evaluation; review of headache history for triggers, effective acute treatment, and nonpharmacologic interventions)
- If using a combination of a CGRP-targeted monoclonal antibody for preventive therapy and a CGRP receptor antagonist (gepant) for abortive therapy, patient must be evaluated and counseled on risks of concomitant therapy
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ETHINYL ESTRADIOL/ FERROUS BISGLYCINATE/ LEVONORGESTREL TAB
BALCOLTRA, JOYEAUX, LEVONORG-ETH ESTRAD-FE BISGLYC, MINZOYA
|
BALCOLTRA, JOYEAUX, LEVONORG-ETH ESTRAD-FE BISGLYC, MINZOYA |
2018-06-01 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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FOSTAMATINIB TAB
TAVALISSE
|
TAVALISSE |
2018-06-01 |
Exclusion Criteria- Care not provided by a VA or VA purchased care hematology provider
- History of non-adherence with oral medication, follow-up appointments, or laboratory visits
- Unable to comply with dosing instructions
- Chronic therapy with a strong CYP3A4 inducer that cannot be interrupted
- Has not received prior therapy to increase platelet counts
- Thrombocytopenia secondary to bone marrow suppressive anti-cancer therapy, antibiotics, or other medication
- Thrombocytopenia secondary to chronic liver disease
- Pregnancy and/or breastfeeding
Inclusion Criteria- Documented diagnosis of chronic ITP per American Society of Hematology (ASH) guidelines: diagnosis based upon history, PE, CBC and exam of peripheral smear
- Platelet count < 30,000 mm3
- Inadequate response or contraindication to at least 2 prior treatment categories: splenectomy; rituximab; thrombopoietin agonists (eltrombopag or romiplostim); danazol or immune suppressants (azathioprine, cyclosporine or mycophenolate mofetil)
- For women of childbearing potential: Pregnancy excluded prior to receiving fostamatinib; provided contraceptive counseling on potential risks vs. benefits if patient were to become pregnant; awareness that fostamatinib may affect female fertility
Dosage and Administration- 100 mg taken orally twice daily with or without food
- After 4 weeks, if platelet count has not increased to at least 50 x 109/L, increase dose to 150 mg twice daily
- Dosing regimen should be interrupted, reduced, or discontinued to manage adverse effect profile (HTN, hepatotoxicity, diarrhea, neutropenia)
- Concomitant use with a strong CYP3A4 inhibitor increases exposure; monitor for toxicity as doses may need adjustment
Monitoring Requirements- Baseline labs prior to initiation: CBC with differential (ANC, platelets), LFTs (AST, ALT, bilirubin), baseline stable BP
- During treatment: CBC with differential monthly, LFTs monthly, BP every 2 weeks until stabilized dose then monthly thereafter, severity and duration of diarrhea, fever and signs/symptoms of infection, unusual bleeding and/or bruising
Adverse Effects and Management- Hypertension (all grades 28%; > grade 3: 2%): Monitor; management may require addition and/or adjustment of antihypertensive therapies
- Hepatotoxicity: Monitor; manage by fostamatinib dose adjustment or discontinuation
- Diarrhea: Monitor; manage with supportive measures and dose adjustment
- Neutropenia: Monitor for infection; manage with supportive measures and dose adjustment
Discontinuation Recommendations- Non-compliance with therapy, laboratory, or follow-up requests
- Discontinue after 12 weeks of therapy if platelets have not increased to a level sufficient to avoid clinically important bleeding
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IBRUTINIB TAB,ORAL
IMBRUVICA
|
IMBRUVICA |
2018-04-01 |
Exclusion Criteria- Patient has not been screened for Hepatitis B Virus (HBV)
- Unmanageable drug-drug or drug-food interaction
- Active or uncontrolled infection
- History of stroke or intracranial hemorrhage in prior 6 months
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (NYHA Class 3 or 4) or myocardial infarction in prior 6 months
- Severe hepatic impairment (Child-Pugh C) or total bilirubin > 3x Upper Limit of Normal (unless non-hepatic origin or Gilbert syndrome)
- Known pregnancy
- Lactating
Inclusion Criteria- Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) if acalabrutinib is not clinically appropriate for patient
- Waldenstrom Macroglobulinemia
- Previously treated chronic Graft versus Host Disease (cGVHD) after Hematopoietic Stem Cell Transplant
Additional Inclusion Criteria- Care for the oncologic condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 - 2
Pregnancy and Lactation Counseling Requirements- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 month after stopping treatment
- Advise patients not to breastfeed/provide breastmilk during treatment and for 1 week after last dose
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ESTRADIOL CREAM,VAG
ESTRACE
|
ESTRACE |
2018-03-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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GEMTUZUMAB INJ
MYLOTARG
|
MYLOTARG |
2018-03-01 |
Indications & Patient Selection- Exclusion Criteria: Do not administer if any of the following are present: hypersensitivity to gemtuzumab or components; pregnancy (known/positive test) and/or actively breastfeeding; Tbili > 2x ULN, AST > 2.5x ULN, and ALT > 2.5x ULN; hyperleukocytosis (leukocyte count > 30 Gi/L); adverse-risk cytogenetics.
- Inclusion Criteria: Fulfillment of one of the following is required: previously untreated CD-33 positive AML in adults fit for intensive induction (in combination with standard 7+3 induction of daunorubicin and cytarabine); previously untreated CD-33 positive AML in adults age > 60 years (as monotherapy if not a candidate for or declines intensive induction); relapsed or refractory CD-33 positive AML in adults (as monotherapy).
Reproductive Health & Contraception- Exclude pregnancy prior to receiving gemtuzumab; provide contraceptive counseling on potential risks vs. benefits if pregnancy occurs during treatment.
- Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the last dose.
- Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose.
- Advise women not to breastfeed during treatment and for at least 1 month after the last dose.
Pre-medication & Infusion Management- Premedicate with acetaminophen 650 mg PO and diphenhydramine 50 mg PO or IV given 1 hour prior to gemtuzumab.
- AND administer methylprednisolone 1 mg/kg (or equivalent corticosteroid) within 30 minutes prior to gemtuzumab.
- Additional acetaminophen and diphenhydramine may be administered every 4 hours after the initial pre-treatment dose.
- Repeat methylprednisolone or equivalent corticosteroid for any sign of infusion reaction during infusion or within 4 hours afterwards.
- Use appropriate measures to prevent Tumor Lysis Syndrome (TLS).
Monitoring Requirements- Check ALT, AST, total bilirubin, and alkaline phosphatase prior to each dose.
- Monitor for signs/symptoms of Veno-Occlusive Disease (VOD) following treatment.
- Monitor TLS parameters for those at risk.
- Monitor for infusion-related reactions during or within 24 hours following a dose; premedicate prior to each infusion; monitor vital signs frequently during infusion; continue monitoring for at least 1 hour post-infusion or until signs/symptoms completely resolve.
- Check CBC prior to each dose and frequently throughout treatment until resolution of cytopenias; monitor for signs/symptoms of bleeding (cytopenias can be prolonged).
- Obtain ECG and electrolytes prior to therapy start and as needed if patient has history/predisposition for QTc prolongation or is taking QT-prolonging medications.
- Perform pregnancy test in women of childbearing potential at baseline.
Discontinuation Criteria- Severe infusion reaction or any life-threatening infusion reaction.
- Persistent thrombocytopenia and/or neutropenia if blood counts do not recover within 14 days after hematologic recovery from the previous cycle (or within 14 days following the planned start date of consolidation cycle).
- Evidence of VOD.
Special Considerations & Risk Management- Hyperleukocytosis: Recommend cytoreduction prior to initiating gemtuzumab.
- Hepatotoxicity/VOD Risk: Boxed warning for VOD/SOS, particularly with higher monotherapy doses, mod/severe hepatic impairment at baseline, or pre/post-HSCT (ALFA-0701 utilized a 2-month interval between last dose and HSCT).
- Bleed Risk: Prolonged thrombocytopenia may increase bleed risk; evaluate blood counts prior to each dose and throughout therapy; monitor for bleeding.
- QT Interval Prolongation: Associated with calicheamicin; evaluate patient risk prior to initiation and monitor appropriately.
- Adverse-Risk Cytogenetics: No improvement in EFS noted; for newly diagnosed disease treated with gemtuzumab + chemotherapy, consider whether potential benefit outweighs risks when cytogenetic results become available.
- Other Targeted Therapies: Not tested in combination with target therapy for specific AML mutations (e.g., FLT3); refer to respective CFU for those regimens.
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BENRALIZUMAB INJ,SOLN
FASENRA, FASENRA PEN
|
FASENRA, FASENRA PEN |
2018-01-01 |
Exclusion Criteria- Acute exacerbation of asthma or status asthmaticus
- Concurrent use with other biologics for asthma
- Currently undergoing bronchial thermoplasty
- Untreated parasitic (helminth) infection (treat before starting benralizumab)
- Inclusion Criteria (All must be met)
- Provider is a VA or VA Community Care asthma specialist (pulmonologist, allergist, immunologist) or designated expert
- Diagnosis of asthma with an eosinophilic phenotype
- Blood eosinophil count > 150 cells/microliter obtained prior to treatment (does not apply if switching from another interleukin modifying drug for asthma)
- Receiving high-dose inhaled corticosteroid (or maximally tolerated dose) AND at least 3 months of a long-acting beta agonist and/or other controller medication such as tiotropium if appropriate, with or without an oral corticosteroid
- Adherent to asthma medications as evidenced by a review of prescription refill history
- Patient has demonstrated correct inhaler technique (documented in chart)
- Additional Inclusion Criteria (At least one must be met)
- Two or more asthma exacerbations requiring systemic corticosteroids OR one or more hospitalizations in the prior year
- Requires maintenance with oral corticosteroids
- Inadequate symptom control (e.g., short-acting beta-agonist use > 2 days/week, nighttime awakening due to asthma > once/week, limitation of normal activity, Asthma Control Test <19)
Other Justification- Patient with non-severe active eosinophilic granulomatosis with polyangiitis (EGPA) to induce remission, prevent relapse and to minimize exposure to glucocorticoids and prescribed by a specialty provider experienced in managing EGPA
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CLOZAPINE (MAYNE) TAB
|
|
2018-01-01 |
Indications- Treatment-resistant schizophrenia
- Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Contraindications- Hypersensitivity to clozapine or any other component of clozapine
Boxed Warnings- Severe neutropenia
- Orthostatic hypotension, bradycardia, syncope
- Seizures
- Myocarditis, pericarditis, cardiomyopathy, and mitral valve incompetence
- Increased mortality in elderly patients with dementia-related psychosis
Precautions- Eosinophilia
- QT interval prolongation
- Metabolic Changes
- Neuroleptic malignant syndrome
- Hepatotoxicity
- Fever
- Pulmonary embolism
- Anticholinergic toxicity
- Interference with cognitive and motor performance
- Use with caution in patients with decreased GI motility
- Special populations: Poor metabolizers of CYP2D6; Smokers via CYP1A2 induction – with respect to forced absence during hospitalization
Dosing- Starting Dose: 12.5 mg once daily or twice daily
- Use cautious titration and divided dosage schedule
- Titration: increase the total daily dosage in increments of 25 mg to 50 mg per day, if well-tolerated
- Target dose: 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks
- Subsequent increases: increase in increments of 100 mg or less, once, or twice weekly
- Maximum daily dose: 900 mg
ANC Monitoring Recommendations- Obtain baseline ANC before treatment initiation
- Weekly from initiation to 6 months
- Every 2 weeks from 6 to 12 months (if the ANC remains in the normal range; ANC greater than or equal to 1500/μL for the general population, ANC greater than or equal to 1000/μL for patients with Benign Ethnic Neutropenia)
- Monthly after 12 months, using shared decision making (if ANC continues to remain in the normal range)
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LETERMOVIR INJ,SOLN
PREVYMIS
|
PREVYMIS |
2018-01-01 |
Exclusion Criteria- Treatment of cytomegalovirus (CMV) infection
- Coadministration of medications not recommended with letermovir (e.g., nafcillin, phenytoin, phenobarbital, carbamazepine, rifamycins, bosentan, St. John’s wort, efavirenz, etravirine, modafinil)
Inclusion Criteria- Prescribed by Infectious Diseases, Solid organ or Hematopoietic stem cell transplant, or other facility authorized providers
Additional Inclusion Criteria (Indications)- ONE of the following must be met:
- Prevention of infection in high-risk (CMV Recipient positive, R+) allogeneic hematopoietic stem cell transplant recipient for up to 200 days
- Prevention of CMV infection in high-risk (CMV donor positive / recipient negative, D+/R-) solid-organ transplant recipients when valganciclovir cannot be used due to tolerability, difficulty dosing due to changing renal function or resistance
Indication & Patient Population- Cytomegalovirus (CMV) prophylaxis for high-risk kidney transplant recipients
- Approved for CMV prophylaxis after allogeneic hematopoietic stem-cell transplant (HSCT)
- High-risk HSCT defined by donor properties, stem cell source, receipt of anti-thymocyte globulin or alemtuzumab, or graft vs. host disease requiring ongoing corticosteroids
- Excluded populations: end-stage renal disease, severe hepatic insufficiency/disease, drug interactions, prior solid organ transplant, double kidney transplant, CMV disease within 6 months prior to randomization
Dosing & Administration- 480 mg daily (PO or IV)
- Dose decreased to 240 mg if concomitant cyclosporine A is used
- Available as tablets and injection for intravenous use
- IV formulation contains hydroxypropyl betadex; recommend changing to oral formulation as soon as possible
Efficacy & Clinical Outcomes- Non-inferior to valganciclovir for prevention of CMV in high-risk kidney transplant recipients through week 52
- Consistently reduced CMV infection and clinically significant CMV infection in HSCT patients across trials and observational studies
- Primary endpoint discontinuation of study drug for any reason was lower with letermovir (38%) vs placebo (61%)
- Clinically significant CMV infection rates: 18% vs 41% (letermovir vs placebo) in initial HSCT trial
- Extended prophylaxis to 200 days showed similar efficacy and safety to the initial 100-day trial
- Impact on all-cause mortality was less consistent; lower at week 24 but not week 48 in initial trial
Safety & Tolerability- GI adverse events most common (vomiting, abdominal pain)
- Cardiac adverse events reported (tachycardia, atrial fibrillation), mostly mild-moderate
- Hematologic parameters not different from placebo in HSCT trials
- In kidney transplant vs valganciclovir: lower drug-related AEs, significant decrease in leukopenia and neutropenia, lower discontinuation due to AEs (4% vs 14%)
- Real-world cohorts note improvement/resolution of cytopenias and reduced need for immunosuppression modification when switching from valganciclovir
Resistance & Monitoring Considerations- No cross-resistance with other anti-CMV agents
- Not active against HSV or VZV; additional prophylaxis for these viruses is necessary
- Resistance-associated substitutions not identified in letermovir-treated subjects in Phase 3 trials, unlike 12% in the valganciclovir group
- Theoretical risk that prolonged prophylaxis might delay CMV-specific cellular reconstitution; optimal strategy and duration remain unclear
Formulary Status & Place in Therapy- Formulary status: NF/TBD
- Can be used as primary prophylaxis in very-high-risk allo-HSCT patients vs pre-emptive therapy
- Offers an option to continue prophylaxis in high-risk solid organ transplant patients who develop cytopenias on valganciclovir or have CMV resistant to valganciclovir, minimizing adverse events of valganciclovir
- Currently not indicated for treatment of CMV disease
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LETERMOVIR TAB,ORAL
PREVYMIS
|
PREVYMIS |
2018-01-01 |
Exclusion Criteria- Treatment of cytomegalovirus (CMV) infection
- Coadministration of medications not recommended with letermovir (e.g., nafcillin, phenytoin, phenobarbital, carbamazepine, rifamycins, bosentan, St. John’s wort, efavirenz, etravirine, modafinil)
Inclusion Criteria- Prescribed by Infectious Diseases, Solid organ or Hematopoietic stem cell transplant, or other facility authorized providers
Additional Inclusion Criteria (Indications)- ONE of the following must be met:
- Prevention of infection in high-risk (CMV Recipient positive, R+) allogeneic hematopoietic stem cell transplant recipient for up to 200 days
- Prevention of CMV infection in high-risk (CMV donor positive / recipient negative, D+/R-) solid-organ transplant recipients when valganciclovir cannot be used due to tolerability, difficulty dosing due to changing renal function or resistance
Indication & Patient Population- Cytomegalovirus (CMV) prophylaxis for high-risk kidney transplant recipients
- Approved for CMV prophylaxis after allogeneic hematopoietic stem-cell transplant (HSCT)
- High-risk HSCT defined by donor properties, stem cell source, receipt of anti-thymocyte globulin or alemtuzumab, or graft vs. host disease requiring ongoing corticosteroids
- Excluded populations: end-stage renal disease, severe hepatic insufficiency/disease, drug interactions, prior solid organ transplant, double kidney transplant, CMV disease within 6 months prior to randomization
Dosing & Administration- 480 mg daily (PO or IV)
- Dose decreased to 240 mg if concomitant cyclosporine A is used
- Available as tablets and injection for intravenous use
- IV formulation contains hydroxypropyl betadex; recommend changing to oral formulation as soon as possible
Efficacy & Clinical Outcomes- Non-inferior to valganciclovir for prevention of CMV in high-risk kidney transplant recipients through week 52
- Consistently reduced CMV infection and clinically significant CMV infection in HSCT patients across trials and observational studies
- Primary endpoint discontinuation of study drug for any reason was lower with letermovir (38%) vs placebo (61%)
- Clinically significant CMV infection rates: 18% vs 41% (letermovir vs placebo) in initial HSCT trial
- Extended prophylaxis to 200 days showed similar efficacy and safety to the initial 100-day trial
- Impact on all-cause mortality was less consistent; lower at week 24 but not week 48 in initial trial
Safety & Tolerability- GI adverse events most common (vomiting, abdominal pain)
- Cardiac adverse events reported (tachycardia, atrial fibrillation), mostly mild-moderate
- Hematologic parameters not different from placebo in HSCT trials
- In kidney transplant vs valganciclovir: lower drug-related AEs, significant decrease in leukopenia and neutropenia, lower discontinuation due to AEs (4% vs 14%)
- Real-world cohorts note improvement/resolution of cytopenias and reduced need for immunosuppression modification when switching from valganciclovir
Resistance & Monitoring Considerations- No cross-resistance with other anti-CMV agents
- Not active against HSV or VZV; additional prophylaxis for these viruses is necessary
- Resistance-associated substitutions not identified in letermovir-treated subjects in Phase 3 trials, unlike 12% in the valganciclovir group
- Theoretical risk that prolonged prophylaxis might delay CMV-specific cellular reconstitution; optimal strategy and duration remain unclear
Formulary Status & Place in Therapy- Formulary status: NF/TBD
- Can be used as primary prophylaxis in very-high-risk allo-HSCT patients vs pre-emptive therapy
- Offers an option to continue prophylaxis in high-risk solid organ transplant patients who develop cytopenias on valganciclovir or have CMV resistant to valganciclovir, minimizing adverse events of valganciclovir
- Currently not indicated for treatment of CMV disease
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ETELCALCETIDE INJ,SOLN
PARSABIV
|
PARSABIV |
2017-12-01 |
Exclusion Criteria- Serum calcium less than the lower limit normal (e.g., < 8.4 mg/dL, corrected for serum albumin)
Inclusion Criteria- Secondary hyperparathyroidism in a patient with chronic kidney disease (CKD) on chronic dialysis with elevated intact plasma parathyroid hormone (iPTH) level (e.g., greater than 400 pg/ml or significant trend upwards within two to nine times the upper limit normal for the assay) despite management with standard therapy as appropriate (e.g., dietary phosphate restriction, phosphate binders [calcium-based or non-calcium based], calcitriol or vitamin D analogs)
- Hypercalcemia (e.g., > 12.5 mg/dl, or symptomatic and > 11.3 mg/dl; corrected for serum albumin) in a patient with primary hyperparathyroidism who is not a surgical candidate or with recurrence despite surgical intervention
- Hypercalcemia (e.g., > 12.5 mg/dl, corrected for serum albumin) in a patient with parathyroid carcinoma despite standard therapy to control hypercalcemia prior to surgical intervention, or who is not a surgical candidate, or who has recurrence despite surgical intervention
FDA Indications & Limitations- Secondary hyperparathyroidism in adult patients with CKD on dialysis (Limitation: Not indicated for use in patients with CKD not on dialysis)
- Hypercalcemia in adult patients with parathyroid carcinoma
- Hypercalcemia in adult patients with primary hyperparathyroidism for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy
Hypocalcemia Management & Monitoring- Both agents lower serum calcium, leading to potentially severe hypocalcemia (can cause paresthesias, myalgias, muscle spasms, seizures, QT interval prolongation and ventricular arrhythmia); patients predisposed to QT interval prolongation, ventricular arrhythmias, or seizures are at increased risk
- Close monitoring recommended for development of hypocalcemia, with adjustment of other therapies (e.g., phosphate binders, calcitriol or vitamin D analogs) as indicated
- For secondary hyperparathyroidism with CKD on dialysis: Monitor serum calcium approximately monthly if receiving maintenance dose
- For parathyroid carcinoma or primary hyperparathyroidism: Monitor corrected serum calcium every 2 months
- If calcium is between 8.4 mg/dL and 7.5 mg/dL: Calcium-based phosphate binders and/or vitamin D sterols can be used to increase calcium
- If calcium is below 7.5 mg/dL or patient has symptoms of hypocalcemia: Hold cinacalcet dose until calcium is 8.0 mg/dL; may resume at a lower dose once calcium is corrected
Dosing & Administration Considerations- Refer to Product Information for detailed prescribing information
- Selection between oral cinacalcet and IV etelcalcetide should depend on treatment response, tolerability, adherence, and cost
- Patients adequately controlled on cinacalcet, who are tolerating therapy and adherent to the oral once daily treatment regimen, should remain on cinacalcet
- Concurrent use of calcimimetics could result in severe, life-threatening hypocalcemia; cinacalcet and etelcalcetide should not be used as concomitant therapy
Off-Label Use- Long-term safety and efficacy in patients with CKD not on dialysis has not been established; however, individual cases treating a non-dialysis patient with markedly elevated iPTH might be considered
- Patients treated with cinacalcet who are not on dialysis may be at increased risk for the development of hypocalcemia
- Limited data show reduction in hypercalcemia and iPTH with cinacalcet in patients with hyperparathyroidism after kidney transplantation; appropriate treatment should be determined on a case by case basis
Pregnancy & Reproductive Safety- Refer to prescribing information for animal reproduction studies data to determine use in patients of child-bearing potential, and the need for contraceptive counseling and education on potential risk vs. benefit if patient were to become pregnant
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LANTHANUM TAB,CHEWABLE
FOSRENOL, LANTHANUM CARBONATE
|
FOSRENOL, LANTHANUM CARBONATE |
2017-12-01 |
Inclusion Criteria- Provider is a VA / VA Community Care Nephrologist
- Patient has an inadequate response or intolerance to sevelamer carbonate tablets
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PAROXETINE CAP,ORAL
PAROXETINE MESYLATE
|
PAROXETINE MESYLATE |
2017-12-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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PRASUGREL TAB
EFFIENT, PRASUGREL HCL
|
EFFIENT, PRASUGREL HCL |
2017-12-01 |
Exclusion Criteria- Active pathologic bleeding
- Clinically important anemia or thrombocytopenia
- History of prior transient ischemic attack (TIA), stroke, or intracranial hemorrhage (ICH)
- Body weight less than 60 kg
- Age 75 or older unless at high risk of ischemic events (e.g., diabetes mellitus or prior myocardial infarction) and otherwise low bleeding risk
- Planned or recent fibrinolytic therapy (e.g., within past 24 hours)
- Concomitant anticoagulant therapy (clopidogrel is preferred P2Y12 inhibitor for use in combination with an oral anticoagulant)
- Severe hepatic impairment
- Anticipated urgent coronary artery bypass graft (CABG) surgery (e.g., within 7 days)
Inclusion Criteria- ST-elevation myocardial infarction acute coronary syndrome (STEMI-ACS) and undergoing PCI
- Non-ST elevation ACS with planned PCI after coronary anatomy identified and deemed suitable for PCI, ischemic symptoms lasting ≥10 min and occurring within 72 hrs of presentation, TIMI risk score of ≥3, and either ST segment deviation of ≥1 mm or positive cardiac biomarkers
- Definite or probable acute stent thrombosis (Academic Research Consortium definition) in patients documented to be compliant with aspirin and clopidogrel
- Reduced clopidogrel response (e.g., any documented CYP2C19 intermediate or poor metabolizer phenotypes or high on-treatment platelet reactivity by P2Y12 reaction units [PRU] testing) and continued indication for P2Y12 inhibitor therapy
- Extended duration dual antiplatelet therapy (DAPT=aspirin plus P2Y12 inhibitor) beyond 12 months following an ACS event as per Cardiology re-evaluation
- Undergoing PCI with or without ACS in patients with clopidogrel allergy or true aspirin allergy
Dosing and Duration Considerations- If no other antiplatelet is appropriate, standard dose prasugrel may be considered but is associated with no net clinical benefit in patients 75 and older or who weigh less than 60 kg; alternatively, the lower dose of 5 mg of prasugrel daily may be considered
- Extended durations of therapy: DAPT for at least 12 months is guideline recommended therapy after ACS; longer or shorter durations may be considered with the understanding that DAPT reduces ischemic risk but increases bleeding risk
- Routine pharmacogenomic or platelet function screening for reduced clopidogrel response is not currently guideline recommended, and the ultimate clinical benefit of a guided-use strategy is unknown
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COPANLISIB INJ,LYPHL
ALIQOPA
|
ALIQOPA |
2017-11-01 |
Exclusion Criteria- Care not provided by a VA/VA Community Care hematology/oncology provider
- CrCl <15 mL/minute
- Severe hepatic impairment (Child-Pugh class C or total bilirubin 3 to 10x ULN)
- Patients receiving concomitant therapy with strong CYP3A inducers
- Uncontrolled hypertension with blood pressure ≥ 150/90 mmHg despite optimal medical management
- History or concurrent condition of interstitial lung disease
- Ongoing or active systemic infection, including hepatitis B or C or known HIV
- Pregnancy
- Breastfeeding
Inclusion Criteria- Diagnosis of follicular lymphoma
- Relapsed or refractory disease after ≥ 2 prior lines of therapy (patients must have received rituximab and alkylating agents unless contraindicated)
- ECOG performance status 0, 1, or 2
- Patients with diabetes mellitus are willing and able to have close monitoring due to risk of hyperglycemia
Reproductive Health & Contraception Requirements- Women of childbearing potential: Pregnancy must be excluded prior to receiving copanlisib; provide contraceptive counseling on potential risks vs. benefits if pregnancy occurs during therapy; advise use of highly effective contraception during treatment and for at least one month after the last dose.
- Men with partners of childbearing potential: Advise use of highly effective contraception during treatment and for at least one month after the last dose.
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| ▸ |
ENASIDENIB TAB
IDHIFA
|
IDHIFA |
2017-11-01 |
Exclusion Criteria- Pregnancy (i.e., known pregnancy or positive pregnancy test) and/or actively breastfeeding
- Inability to swallow whole tablets
Inclusion Criteria- Diagnosis of relapsed/refractory acute myeloid leukemia
- Defined as relapsed disease after 2 previous inductions OR
- Relapsed disease after 1 induction and not suitable for intensive chemotherapy
- Presence of an isocitrate dehydrogenase-2 (IDH2) mutation
- ECOG performance status 0-2
- For women of childbearing potential: Pregnancy must be excluded prior to receiving enasidenib; patient provided contraceptive counseling on potential risks vs. benefits if pregnancy occurs. Note may include men with female partners of childbearing potential if adequate contraception should be practiced.
Dosage and Administration- Recommended starting dose: 100 mg taken orally once daily with or without food until disease progression or unacceptable toxicity
- Treat for a minimum of 6 months to allow time for clinical response (if no disease progression or unacceptable toxicity)
- Refer to Product Information for dosing modification based on adverse events
Monitoring- Blood counts and blood chemistries for leukocytosis and tumor lysis syndrome prior to initiation; monitor at minimum every 2 weeks for at least the first 3 months during treatment
- Liver function tests including bilirubin level: evaluate at least monthly or when clinically indicated
- Pregnancy test (in women with childbearing potential) at baseline
- Monitor for signs and symptoms of differentiation syndrome (fever, cough, dyspnea, bone pain, rapid weight gain, edema, lymphadenopathy) and tumor lysis syndrome; differentiation syndrome noted as early as 10 days and up to 5 months after therapy initiation
Issues for Consideration- FDA-approved indication: Treatment of adult patients with relapsed or refractory AML with an IDH2 mutation as detected by an FDA-approved test
- Off-label uses in other hematologic malignancies with IDH2-positive mutations require local adjudication processes
- Differentiation syndrome: Boxed warning highlights risk (reported in 14% of patients); if suspected, initiate oral or IV corticosteroids with hemodynamic monitoring until improvement
Renewal Criteria- Documented benefit (defined as no disease progression or RBC and/or platelet transfusion independence)
- ECOG performance status has not declined to a level unacceptable to maintain quality of life
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GLECAPREVIR/ PIBRENTASVIR TAB
MAVYRET
|
MAVYRET |
2017-11-01 |
Exclusion Criteria- Limited life expectancy
- Documented ongoing nonadherence to prescribed medications or medical treatment
- Concurrent use of drugs not recommended with GLE/PIB (e.g., rifampin, atazanavir, darunavir, efavirenz, etravirine or ritonavir)
- Severe hepatic impairment (Child-Pugh B/C or history of hepatic decompensation)
- Prior hepatitis C virus (HCV) treatment failure of both an NS3/4A protease inhibitor AND an NS5A inhibitor
- Hepatitis B surface antigen (HBsAg) positive and not on antiviral treatment with entecavir or tenofovir
- Contraindication to ribavirin (RBV) IF RBV is indicated (includes history of significant cardiac disease, significant anemia, pregnancy, and men whose female partner is pregnant or plans to become pregnant)
Inclusion Criteria- Care is provided by or in consultation with a VA/VA Community Care Hepatitis C Specialist
- Treatment regimen and duration consistent with HCV genotype (GT) and patient characteristics according to VA HCV Treatment considerations
- HCV GT 1-6 or ungenotyped but detectable HCV RNA
- Completed hepatitis B screening: at minimum HBsAg, HBV core antibody (anti-HBc) and HBV surface antibody (anti-HBs)
- Adherence counseling performed including laboratory follow-up and documented understanding by patient
- Additional Inclusion Criteria (One of the following must be true)
- GT 1-6 or ungenotyped but detectable HCV RNA with or without compensated cirrhosis and are treatment naïve
- GT 1-6 with or without compensated cirrhosis with prior treatment experience with pegylated interferon, ribavirin +/- sofosbuvir (SOF)
- GT 1 with or without compensated cirrhosis and prior NS3/4A experience (but SOF and NS5A naïve)
- GT 1 with or without compensated cirrhosis and prior NS5A inhibitor experience but NS3/4A naïve
- With SOF and RBV for GT 1-6 with or without compensated cirrhosis and treatment experienced with sofosbuvir / velpatasvir / voxilaprevir or SOF plus GLE/PIB
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NALDEMEDINE TAB,ORAL
SYMPROIC
|
SYMPROIC |
2017-11-01 |
Exclusion Criteria- Age less than 18 years
- Known or suspected gastrointestinal obstruction or at risk of recurrent obstruction
- Concomitant use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s Wort)
- Concomitant use with other opioid antagonists
- Severe hepatic impairment (Child-Pugh class C)
- Hypersensitivity to naldemedine or product excipients
- Presence of severe or frequent diarrhea
Inclusion Criteria- Patient is taking opioids for chronic, non-cancer pain (including chronic pain related to prior cancer or its treatment)
- Does not require frequent opioid dose escalation
- Documented opioid-induced constipation (OIC)
- Documentation of attempts to reduce constipation by change to less constipating analgesics or reduction of opioid dose OR medical justification why changes are unable to be made in current regimen
- Documentation that benefits of opioid therapy exceed risks for the patient
- All VA/DOD Directives/guidelines for prescribing and monitoring long-term opioids are being followed
Laxative Trial Requirements- Intolerance or inadequate response to 1-month trials of:
- One stimulant laxative (e.g., bisacodyl, sennosides) AND
- MIRALAX equivalent (twice daily) or other osmotic laxative (e.g., sorbitol, lactulose, magnesium citrate, Mg hydroxide, glycerin rectal suppositories)
- Maintenance laxative therapy does not need to be discontinued before starting naldemedine
- Bulk forming laxatives are relatively contraindicated in OIC
- Stool softeners (e.g., docusate) are considered low benefit and low harm for OIC; may be used but are not required prior to use of naldemedine
Dosage and Administration- Adults: 0.2 mg once daily with or without food
- Alteration of analgesic dosing regimen prior to initiating naldemedine is not required
- Patients receiving opioids for less than 4 weeks may be less responsive to naldemedine
Monitoring, Safety, and Special Populations- OIC clinical trial definition: ≤3 spontaneous bowel movements (SBMs) per week during a 2-week run-in period with a total of ≤4 SBMs; ≥1 symptom (straining, lumpy/hard stools, sensation of incomplete evacuation, or anorectal obstruction/blockage) for ≥25% of bowel movements; ≥78% compliance with daily diary entries
- SBMs defined as bowel movements without rescue laxatives taken within the past 24 hours
- Response defined as ≥3 SBMs per week and an increase from baseline of ≥1 SBM per week for at least 9 of 12 study weeks and 3 of the last 4 weeks
- Monitor for opioid withdrawal symptoms (e.g., abdominal pain, diarrhea, nausea, vomiting, hyperhidrosis, pyrexia, anxiety); disruptions in the blood-brain barrier may increase risk
- GI perforation warning: Use with caution in patients at risk for gastrointestinal perforation (e.g., peptic ulcer disease, diverticular disease, infiltrative gastrointestinal malignancy, peritoneal metastases, Crohn’s disease)
- Drug interactions: Avoid concomitant use with strong CYP3A inducers and other opioid antagonists; monitor for naldemedine-related adverse reactions during concomitant use with moderate/strong CYP3A4 inhibitors (e.g., fluconazole, itraconazole) and P-gp inhibitors (e.g., cyclosporine)
- Pregnancy: No human data; potential for fetal opioid withdrawal; weigh risks vs benefits
- Nursing Mothers: No human data; weigh risks vs benefits; breastfeeding may be resumed 3 days after the final dose of naldemedine
Initial Prescription SupplyRenewal Criteria- Patient experiences clinically important benefit (improved constipation and abdominal pain) after an adequate therapeutic trial and tolerates treatment
- Adequate therapeutic trial is defined as 1 week
- Discontinue naldemedine if treatment with the opioid pain medication is discontinued
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OLAPARIB TAB
LYNPARZA
|
LYNPARZA |
2017-11-01 |
Exclusion Criteria- Creatinine clearance less than or equal to 30 mL/min
- Concomitant strong or moderate CYP3A inducers
- Concomitant strong or moderate CYP3A inhibitors (if unavoidable, reduce olaparib dose per labeling)
- Untreated or uncontrolled brain metastases
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
General Inclusion Criteria- Care provided by a VA/VA purchased care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult discussed and documented
- Male patients with partners of reproductive potential or who are pregnant must use effective contraception during treatment and for 3 months following the last dose
Additional Inclusion Criteria (Metastatic Castration-Resistant Prostate Cancer)- Radiographic disease progression following treatment with enzalutamide or abiraterone/prednisone (prior docetaxel allowed)
- Mutation in Homologous Recombination Repair (HRR) gene confirmed by FDA-approved companion diagnostic
- Ongoing castration with prior surgical castration or concomitant LHRH analogue
Other Indications- Provide evidence to support use
Additional Considerations- For HRR gene mutations other than BRCA2, consider a clinical trial if available and patient is eligible
Patient Population & Indication- • Adult patients with metastatic castration-resistant prostate cancer (mCRPC)
- • Deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated
Prior Therapy Requirements- • Disease must have progressed following prior treatment with enzalutamide or abiraterone
Diagnostic & Testing Requirements- • Selection for therapy must be based on an FDA-approved companion diagnostic for olaparib
Additional VA-Specific Considerations- • Patients with non-BRCA2 HRR mutations may consider a clinical trial if available and the patient is eligible
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C1 INHIBITOR INJ,SOLN
HAEGARDA
|
HAEGARDA |
2017-09-01 |
Exclusion Criteria- Angioedema or abdominal pain not associated with C1 inhibitor deficiency
Inclusion Criteria (ALL must be met)- Restricted to VA / VA Community Care allergy/immunology or dermatology provider; or for use in Emergency Medicine/Urgent Care
- Diagnosis of Hereditary Angioedema due to C1 inhibitor deficiency (HAE-C1INH) as established by laboratory testing
Additional Inclusion Criteria (ONE must be met)- Long-term prophylaxis for HAE-C1INH attacks after consideration of either an attenuated androgen or antifibrinolytic
Clinical Context & Decision-Making Requirements- Prior consideration of an attenuated androgen or antifibrinolytic must be discussed with the patient using shared decision-making, including efficacy, routes of administration, and side effects of each therapy
- Baseline attack rate criteria may include at least 2 attacks per month or baseline attack rate in clinical trials
- Need for long-term prophylaxis should be determined using shared decision-making
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ESTRADIOL TAB,VAG
VAGIFEM, YUVAFEM
|
VAGIFEM, YUVAFEM |
2017-09-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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GUSELKUMAB INJ,SOLN
TREMFYA, TREMFYA ONE-PRESS, TREMFYA PEN, TREMFYA PEN INDUCTION (2 PEN)
|
TREMFYA, TREMFYA ONE-PRESS, TREMFYA PEN, TREMFYA PEN INDUCTION (2 PEN) |
2017-09-01 |
Exclusion Criteria- Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients can be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- General Inclusion Criteria (All must be met)
- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated psoriasis expert
- Prescribed at the FDA-approved dose for plaque psoriasis
- Adult with chronic (≥ 6 months) moderate to severe plaque psoriasis (including involvement of nails only)
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- For patients who can become pregnant and partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- Prior Therapy Requirements (All must be met)
- Methotrexate monotherapy is medically inadvisable, not tolerated, or not adequate (i.e., NO treatment benefit after 3 months, of which at least 2 months is at the standard target dose), or inadequate partial response after 6 months
- Phototherapy is medically inadvisable, not available, not feasible, or inadequate (i.e., NO treatment benefit after 12 treatments or inadequate partial response after 24 treatments)
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, or not adequate (i.e., NO response to ONE TNFI after 3 months, partial response to 3-month trials of TWO TNFIs = total 6 months, or loss of initial response)
- Additional Biologic Failure/Inadvisability Criteria (One must be met)
- Interleukin-17A inhibitor (i.e., ixekizumab [preferred] or secukinumab) is medically inadvisable, not tolerated or not adequate (i.e., NO response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response)
- Ustekinumab is medically inadvisable, not tolerated or not adequate (i.e., NO response after 16 weeks, inadequate partial response after 32 weeks, or loss of initial response)
Indication & Diagnosis- Definite or provisional diagnosis of psoriatic arthritis
- Inflammatory articular disease (joint, spine, and/or entheseal)
Prior Therapy Requirements- One tumor necrosis factor inhibitor (TNFI) must be medically inadvisable, not tolerated, or not adequate (defined as no/partial response after 12 weeks or loss of initial response)
- One interleukin-17A inhibitor (IL-17AI; ixekizumab [preferred] or secukinumab) must be medically inadvisable, not tolerated, or not adequate (defined as no response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response)
- Methotrexate monotherapy must be medically inadvisable, not tolerated, or not adequate (defined as no treatment benefit after 3 months with at least 2 months at standard target dose, or inadequate partial response after 6 months; target dose: 15–25 mg once weekly orally, subcutaneously, or intramuscularly)
- Phototherapy must be medically inadvisable or inadequate (defined as no treatment benefit after 12 treatments or inadequate partial response after 24 treatments)
Infection Screening & Management- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, and anti-HBs)
- Current or past completion of hepatitis C screening (initiation may occur while awaiting results)
- Antiviral prophylaxis is required for patients with active HBV infection or those who are HBsAg-negative but anti-HBc-positive; initiation may proceed after starting prophylaxis
Contraindications & Exclusions- Active, serious, systemic, or localized infection (including undrained abscess); therapy may start/restart once infection is controlled
- Untreated latent or active tuberculosis infection
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are eligible)
- Concomitant live or live-attenuated vaccines, or administration of inactivated/live/attenuated vaccines less than 2 weeks before initiation
- TNFI may be medically inadvisable for heart failure, demyelinating disease, multiple sclerosis in a first-degree relative, lupus, recurrent infections, or serious infections
- IL-17A inhibitors may be medically inadvisable for Crohn’s disease, ulcerative colitis, or recurrent/severe Candida infections
Monitoring, Counseling & Administration- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Administered at the FDA-approved dose for psoriatic arthritis
- For patients who can become pregnant or whose partners can become pregnant: counseling on potential risks vs benefits and use of effective contraception is required
Disease Indication & Diagnosis- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA / VA Community Care gastroenterologist / hepatologist or locally designated expert
Infection Screening & Laboratory Requirements- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum: HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Obtained liver panel including bilirubin
Exclusion Criteria- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once treatment initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are eligible)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless prescriber determines potential benefits outweigh risks
Prior Therapy Requirements- One of the following must be tried (unless medically inadvisable) and found not tolerated, not adequate, or lost response: vedolizumab, tofacitinib, upadacitinib, etrasimod, or ozanimod
- Risankizumab-rzaa must be tried (unless medically inadvisable) and found not tolerated, not adequate, or lost response
Additional Inclusion Criteria (One Required)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (infliximab / biosimilar is the preferred TNFI in UC)
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to a TNFI (infliximab / biosimilar preferred) despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
Special Populations & Expert Consultations- If HBsAg-negative but anti-HBc-positive: GI / liver or infectious diseases expert consulted for advice on antiviral prophylaxis vs preemptive monitoring for HBV reactivation
- Women who can become pregnant: Counseling provided on treatment risks vs benefits and use of effective contraception
Sequencing & Retesting Policies- 1L therapy: Infliximab (preferred) or adalimumab
- 2L / 3L therapy: Vedolizumab, tofacitinib, upadacitinib, etrasimod, ozanimod, or risankizumab-rzaa (one must be risankizumab-rzaa)
- 4L therapy: Mirikizumab-mrkz, guselkumab, or ustekinumab
- Routine retesting for TB, hepatitis B, and hepatitis C screening is not required for prescription renewals; retesting in high-risk patients should be considered
- Applies only to new starts; stable patients should not be switched to a criteria-required prior agent for nonmedical reasons
Indication- Treatment of adults with moderately to severely active ulcerative colitis (UC)
Dosing & Administration- Induction: 200 mg IV infusion over at least one hour at Weeks 0, 4, and 8
- Maintenance: Either 100 mg SC at Week 16 then every 8 weeks, or 200 mg SC at Week 12 then every 4 weeks
Therapeutic Placement & Guideline Recommendations- Placed as early as second-line (2L) therapy per VA/Clinical Guidance
- Not specifically mentioned in 2020 AGA or 2019 ACG guidelines; FDA-approved for UC in September 2024
Patient Selection Criteria- Inadequate response (IR), loss of response (LOR), secondary nonresponse (SNR), primary nonresponse (PNR), or intolerance (INT) to corticosteroids (CS), immunomodulators (IMM), and/or advanced tx
- Advanced tx include ≥1 TNFi, vedolizumab (VEDO), and/or JAKi (tofacitinib/TOFA)
- Guselkumab monotherapy may be used for induction and maintenance in patients with medical inadvisability, IR, INT, or LOR to a TNFi, plus two of the following: vedolizumab, tofacitinib, upadacitinib, etrasimod, ozanimod, or risankizumab (one must be risankizumab)
Combination Therapy Considerations- Guselkumab is the first IL-23i evaluated in combination with a TNFi (golimumab) versus monotherapy
- Combination induction followed by guselkumab monotherapy maintenance may be considered on a case-by-case basis
- Golimumab is noted as currently the costliest TNFi; safety and efficacy of other TNFis combined with guselkumab have not been evaluated
Exclusion Criteria- Uncontrolled, active, severe infection (may start/restart once infection treatment is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Liver cirrhosis unless prescriber deems potential benefits outweigh risks
Inclusion Criteria (All Required)- Current or prior moderate to severe Crohn’s disease (CD) confirmed by endoscopy or imaging
- Prescribed and monitored by a VA / VA Community Care gastroenterologist or locally designated expert
- Completed tuberculosis test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Obtained liver panel including bilirubin
- One of vedolizumab or upadacitinib was tried (unless medically inadvisable) and not tolerated, not adequate, or lost response
- Risankizumab-rzaa was tried (unless medically inadvisable) and not tolerated, not adequate, or lost response
Additional Inclusion Criteria (One Required)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in the presence of adequate TNFI levels (mechanistic failure)
- Loss of response to a TNFI despite therapeutic drug monitoring-based optimized dosing to address pharmacokinetic failure
Additional Clinical Requirements- If HBsAg-negative but anti-HBc-positive: GI/liver or infectious diseases expert consulted for advice on starting antiviral prophylaxis vs preemptive monitoring for HBV reactivation
- For women who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception
Drug Sequencing & Positioning- First-line (1L): Infliximab/biosimilar or adalimumab/biosimilar; vedolizumab may be used 1L for “moderate” CD, absence of extraintestinal manifestations, or pouchitis
- Second/Third-line (2L/3L): Vedolizumab, upadacitinib, or risankizumab-rzaa (one drug must be risankizumab-rzaa)
- Fourth-line (4L): Mirikizumab-mrkz, guselkumab, or ustekinumab/biosimilar
Testing & Monitoring Guidelines- Routine retesting for tuberculosis, hepatitis B, and hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
- Anti-HBs titers >= 10 IU/L are generally considered protective
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SOFOSBUVIR/ VELPATASVIR/ VOXILAPREVIR TAB,ORAL
VOSEVI
|
VOSEVI |
2017-09-01 |
Exclusion Criteria- Limited life expectancy
- Documented ongoing nonadherence to prescribed medications or medical treatment
- Concurrent use of drugs not recommended with SOF/VEL/VOX (e.g., rifamycins, amiodarone, dabigatran, CYP450 inducers, cyclosporine, some antineoplastics, efavirenz, etravirine, lovastatin or simvastatin)
- Decompensated cirrhosis (Child-Pugh B/C or history of hepatic decompensation)
- Prior hepatitis C virus (HCV) treatment failure of both an NS3/4A protease inhibitor AND an NS5A inhibitor
- Hepatitis B surface antigen (HBsAg) positive and not on antiviral treatment with entecavir or tenofovir
- Contraindication to ribavirin (RBV) IF RBV is indicated
Inclusion Criteria- Care provided by or in consultation with a VA/VA Community Care Hepatitis C Specialist
- Treatment regimen and duration consistent with HCV genotype (GT) and patient characteristics according to VA HCV Treatment considerations
- Completed hepatitis B screening: at minimum HBsAg, HBV core antibody (anti-HBc) and HBV surface antibody (anti-HBs)
- Adherence counseling performed including laboratory follow-up and documented understanding by patient
Additional Inclusion Criteria- GT 1, 2, 4, 5 or 6, NS5A-experienced, with or without compensated cirrhosis
- GT 1-6, SOF experienced, NS3/4A PI naïve, with or without compensated cirrhosis
Ribavirin (RBV) Specific Considerations- Contraindications to RBV include history of significant cardiac disease, significant anemia, pregnancy, and men whose female partner is pregnant or plans to become pregnant
- For GT 3, add RBV if cirrhosis and no contraindication, or extend duration to 24 weeks
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| ▸ |
BUPRENORPHINE PATCH
BUTRANS
|
BUTRANS |
2017-08-01 |
Perioperative Pain Management Principles- Buprenorphine treatment should not be routinely discontinued in the perioperative period for patients on stable MOUD therapy.
- Discontinuation may confer medical risks including return to active opioid use (50-90%), risk of overdose, prolonged hospital stay, and increased patient burden.
- A buprenorphine taper to < 16 mg/day may be considered for patients prescribed higher doses (> 16 mg) with anticipated high post-surgical pain.
- Utilize a multimodal pain approach including systemic non-opioid analgesics (acetaminophen, NSAIDs, gabapentinoids, ketamine, magnesium, systemic lidocaine, alpha-2 agonists, glucocorticoids), regional/local analgesics, and psychosocial interventions.
- When a full μOR agonist is needed to adequately control perioperative pain, use opioids with similar lipophilicity and binding affinity toward μORs; fentanyl and hydromorphone are reasonable alternatives.
Pre-operative Assessment & Planning- Perform patient evaluation including pain history, physical examination, medication reconciliation, assessment of physical/psychiatric comorbidities, and urine drug monitoring (including methadone, fentanyl, buprenorphine/metabolites).
- Verify prescription adherence via PDMP database.
- Conduct universal substance use disorder screening; perform detailed questioning and appropriate referrals for positive responses.
- Provide pre-operative counseling with written instructions regarding risks of opioid exposure/undertreating pain as relapse triggers.
- Determine procedure-related pain severity (minimal/no pain vs. significant pain) to guide dose adjustment or continuation.
- Plan continuity of care: taper off short-acting opioids prior to discharge; restrict IR opioids to short-term rescue use perioperatively; coordinate with waivered provider/OUD team for outpatient post-op pain care; preschedule follow-up with OUD/chronic pain provider; ensure sufficient buprenorphine supply at discharge.
Elective Procedure Management Criteria- For most patients, continue buprenorphine throughout the operative period.
- Minimally painful surgery: Continue current home dose unchanged, or divide and administer every 6 to 8 hours. Total daily dose may be titrated up to 32 mg/day in divided doses if needed for pain management (does not apply to extended-release injection).
- Painful surgery (moderate/severe pain): Continue baseline dose > 16 mg/day, OR reduce to < 16 mg/day to allow addition of an IR full μOR agonist. Expect higher doses of full μOR agonists requiring close monitoring (e.g., ICU or step-down unit).
- Examples of minimal pain procedures: tooth extraction, endoscopy, colonoscopy, bronchoscopy.
- Examples of moderate/severe pain procedures: laparoscopic, intra-abdominal, intra-thoracic, and orthopedic procedures.
Emergent Procedure Management Criteria- Anticipated minimal to no pain: Continue buprenorphine throughout procedure with non-opioid medications. Dose may be increased until adequate pain relief is achieved. Taper off short-acting opioids prior to discharge.
- Anticipated moderate to severe pain (Continue method): Continue buprenorphine throughout operation; increase dose postoperatively (except implant or BUP XR INJ) or use short-acting opioids. Taper off short-acting opioids prior to or shortly after discharge.
- Anticipated moderate to severe pain (Discontinue method): Discontinue per specified discontinuation criteria.
Discontinuation Criteria & Management- Discontinuation is indicated only when: patient requests to stop (after discussing pros/cons with provider and OUD team); medical contraindication exists; or all other options (maximizing dose, splitting dose, multimodal therapy) are insufficient.
- Emergency procedures: Discontinue immediately upon admission in lieu of high-dose short-acting μOR agonist.
- Elective procedures: Discontinue 24-72 hours prior to surgery. Restart after resolution of acute postoperative pain.
- Monitor respiratory function when using high doses of full μOR agonists as buprenorphine clears; adjust doses to prevent opioid-induced respiratory depression (OIRD).
- Use short-acting full opioid agonists to mitigate withdrawal symptoms. Non-opioid adjuncts for withdrawal (alpha-2 receptor agonists, loperamide, ondansetron, diphenhydramine) may be used as appropriate.
Restarting Buprenorphine Criteria- Taper off short-acting opioid and convert back to previous buprenorphine dose in consultation with waivered provider/OUD team.
- Restart when initial withdrawal signs are observed (for clinic induction) or by patient (for home induction).
- Initial dosing: 2 mg or 4 mg. If withdrawal is alleviated, restart remaining prior maintenance dose on day 1.
- Re-induction protocol: Start when clear signs of opioid withdrawal are present. Begin with 2-4 mg dose or 2/0.5 to 4/1 mg buprenorphine/naloxone. After approximately 2 hours, administer additional 2-4 mg if continued withdrawal and lack of sedation.
- FDA label maximum: 8 mg on Day 1 and 16 mg on Day 2. Document clinical rationale for dosing outside FDA recommendations. Individualize dosing; some patients stabilize on lower doses.
Indications & Pharmacological Properties- Approved for management of pain severe enough to require around-the-clock, long-term opioid treatment.
- Functions as a partial agonist at mu-opioid receptors (MORs) and antagonist at kappa-opioid receptors (KORs).
- Exhibits high binding affinity toward MORs with an extremely slow dissociation rate, making it difficult to displace from receptors once bound.
Perioperative Management- Maximize all other non-opioid and non-pharmacological interventions for pain control.
- When a full MOR agonist is clinically necessary, utilize opioids with similar lipophilicity and binding affinity toward MORs (e.g., fentanyl, sufentanil, hydromorphone) to more effectively compete with buprenorphine.
- Consult waivered providers or an interdisciplinary team experienced with buprenorphine use when available.
- Communicate treatment plans directly with the buprenorphine prescriber to facilitate optimal transition of care postoperatively.
Discharge Planning & Continuity of Care- Schedule patients with their SUD provider or chronic pain provider after discharge for close follow-up.
- Provide a warm hand-off for continued buprenorphine adherence upon discharge, particularly for high-risk patients.
- Discharge patients with an adequate supply of buprenorphine to last until their next scheduled follow-up appointment.
Naloxone Education & Counseling- Evaluate the necessity of naloxone based on the specific indication for buprenorphine prescription.
- For buprenorphine buccal film prescribed for chronic pain without a history of OUD or other SUD and with minimal risk for abusing other opioids, naloxone may not be required unless immediate-release (IR) opioids are initiated postoperatively with plans to discharge on them.
- Conduct overdose education during hospitalization and prescribe naloxone at discharge for patients considered at risk for opioid overdose.
- Provide explicit instruction to patients on how to use the prescribed naloxone product.
Safety Screening- Assess all patients for suicidal ideation prior to discharge per VA strategy and facility protocol.
- Recognize that chronic pain, history of or active SUD/OUD, acute stresses to health, and behavioral health comorbidities (e.g., depression, anxiety, PTSD) significantly heighten suicide risk.
Patient Identification & Surgical Classification- Surgical team/PreOP Clinic identifies patient on buprenorphine (Butrans®, Suboxone®, Subutex®, Zubsolv®, Belbuca® , Temgesic® , Sublocade ® , Buprenex®)
- Classify surgery as minimally painful or painful
Minimally Painful Surgery Criteria- NO or minimal need for postop opioid therapy expected (e.g., endoscopy, cataracts)
- Continue home dose through procedure day and after discharge
- Avoid discontinuation or holding of buprenorphine doses
Painful Surgery & Dose Stratification- High-dose patients: > 16 mg/day Suboxone/Subutex, > 11.4 mg/day Zubsolv
- Low-dose patients: < 16 mg/day Suboxone/Subutex, < 11.4 mg/day Zubsolv, Transdermal Buprenorphine (Butrans Patch) or Buccal Film (Belbuca), ANY DOSE
- No preoperative dose adjustment required for specified doses
Pre-operative Management- Elective surgery: Contact buprenorphine prescriber to discuss dose continuation or gradual dose reduction in anticipation of elective surgery
- Pre-operative dose adjustment not possible: Schedule PreOP Clinic appointment within 2-4 weeks, not later than one week before surgery
- Management options: Continue BUP method (preferred) or Discontinue BUP method
- Anticipate need for high doses of opioids for better pain coverage, or dose reduction to <16 mg/day Suboxone/Subutex, <11.4mg/day Zubsolv by time of surgery
- Update and record prescriber name and contact information in PreOP Clinic
- Consult acute pain service IF expected inpatient stay
Day of Surgery / Intraoperative Management- Perioperative plan per OR Anesthesia team / Acute Pain Team (if available)
- Use non-opioid analgesics (gabapentin, pregabalin, acetaminophen, NSAIDS) pre-operatively if not contraindicated
- Use continuous regional anesthesia techniques if possible (epidural and peripheral nerve catheters)
- Use IV ketamine, lidocaine intra-operatively if not contraindicated
Postoperative Management- Pain Service will follow patients postoperatively if needed; pain management plan per Pain Service recommendations
- Maintenance or placement of axial or peripheral nerve catheters, or short-term nerve blocks as necessary
- Focus on non-opioid medication (gabapentinoids, acetaminophen, NSAIDs, antidepressants, α2 agonists etc.)
- Use full agonist opioid with high binding affinity (hydromorphone, fentanyl, or sufentanil) orally, IV, or by PCA
- Avoid use of long-acting opioids
- Continuation of buprenorphine at home dose, lower dose, or higher dose
- Consider Ketamine infusion protocol (1-5mcg/kg/min infusion) if applicable
- Use Non-medication/non-procedural adjuncts (acupuncture, pet therapy, PT and mechanical supports as appropriate)
Re-induction Planning- Re-induction planning should not be necessary if patients continued to take buprenorphine during hospital stay or were on buprenorphine formulations for pain management (transdermal patch or buccal film)
- If buprenorphine was discontinued, pain service attending decides, in collaboration with buprenorphine prescriber or X-waivered provider, which re-induction strategy is appropriate
Indications & Clinical Appropriateness- FDA-approved for management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period of time.
- Appropriate when there is lack of progress towards functional goals and/or inadequate analgesic benefit with full mu agonist opioid.
- Appropriate when high potential for adverse effects exists due to medical conditions, mental health, or behavioral considerations with full mu agonist LTOT.
- Preferred for patients assessed as high risk for traditional oral opioid therapy where alternate buprenorphine products are not advisable, or for patients with documented difficulty swallowing/poor or unpredictable gastrointestinal absorption.
- More appropriate than transdermal patch for moderate MEDD dosing conversions (50-90 MEDD).
Contraindications & Inappropriateness- Infrequent use of immediate-release opioid medication for episodic pain (e.g., PRN).
- Demonstrating functional improvement and expressing preference to remain on full agonist LTOT, in absence of medical, mental health, or behavioral risk for adverse effects.
- May not provide adequate analgesia for patients requiring greater than 160 mg oral morphine equivalent daily dose (MEDD); consider alternate analgesic.
- Not indicated as an as-needed (PRN) analgesic.
Dosing & Administration Guidelines- Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
- For opioid-naïve/non-tolerant patients: Initiate with 75 mcg film once daily or, if tolerated, every 12 hours for at least 4 days, then increase to 150 mcg every 12 hours.
- Titrate in increments of 150 mcg every 12 hours, no more frequently than every 4 days, to achieve adequate analgesia while minimizing adverse reactions.
- Initial dosing based on prior opioid expressed as oral MEDD: <30 mg MEDD (75 mcg qd or q12h), 30-89 mg MEDD (150 mcg q12h), 90-160 mg MEDD (300 mcg q12h).
- Discontinue all other around-the-clock opioid drugs when BUP BF therapy is initiated.
- For oral buccal use only; apply to the buccal mucosa every 12 hours.
- Wait at least one hour after taking before brushing teeth; swish gently and swallow after dissolution.
- Do not apply to areas of the mouth with open sores or lesions.
- Do not use if pouch seal is broken or film is cut/damaged.
Initiation & Transition Strategies- Follow FDA-approved labeling for new starts and standard opioid transitions.
- STOP-START method: Stop full agonist opioids for 12-24 hours and start buprenorphine in early stages of withdrawal to decrease risk of precipitated withdrawal.
- Low dose buprenorphine initiation (microdosing/overlapping dosing): Allows short-term overlap of buprenorphine titration while on full agonist to mitigate withdrawal and discomfort.
- Published conversion recommendations are highly conservative (reduced 50-75%) and already include reduction for lack of tolerance or cross-tolerance.
- Avoid rapid titrations without assessing effectiveness and tolerability at steady state; due to long half-life, takes about five days to achieve steady state.
Monitoring, Evaluation & Safety Considerations- LTOT principles should be followed: focus on functional improvement in physical, social, and psychological domains consistent with the biopsychosocial model of care.
- Assess risks versus benefits periodically; tapering or discontinuing should be considered when risks outweigh benefits or based on patient preference.
- Screen for and assess risk for OUD prior to initiation and when patterns of unhealthy medication use emerge during LTOT.
- Baseline evaluation includes: Urine drug screen (UDS), PDMP check, liver transaminases, monitor for effectiveness of pain relief/prevention of withdrawal symptoms, assess risk for physical/psychological dependence, drug diversion, sensitivity to adverse effects (particularly respiratory depression), assess mental status/respiratory status/increased risk for falls.
- Pain Management Teams (PMT) should be available for specialty care support during initiation/stabilization and transitions.
- Shared decision-making and veteran preference should guide treatment approach.
- For patients without diagnosed OUD, the encounter should indicate the pain condition diagnosis and the prescription should state “for pain management”.
Patient Counseling & Special Instructions- Caution with driving or operating heavy machinery.
- Store in secure place out of reach of children.
- Advise patients to avoid eating or drinking until film dissolves.
- Inform dentist that therapy has been started; wait at least one hour after taking before brushing teeth.
Indications- Acute pain
- Intractable pain
- Pain expected to be severe enough to require opioid management
Patient Selection (Appropriate)- Veterans who may be appropriate for a usual formulary opioid (e.g., fentanyl, hydromorphone, oxycodone, morphine) for acute pain management
- Veterans with known risk factors for hospital Opioid Related Adverse Events (ORADES)
- Veterans already on a buprenorphine pain formulation as an outpatient (e.g., buccal or transdermal)
- Veterans with impaired renal function (dose adjustment not required)
- Veterans who are opioid naïve with other medical risks (e.g., COPD, advanced age)
- Veterans at high risk for opioid dependence (e.g., co-occurring chronic pain syndromes)
- Patients more sensitive to the GI side effects of opioids and surgical procedures
Patient Selection (Inappropriate/Not Recommended)- Pain not severe enough (or expected to be severe enough) to require opioid therapy
- Patients already on high-dose opioid therapy (prescribed or illicit) or long-acting opioid antagonist treatment (e.g., Vivitrol) due to unknown exact role of pain formulations at this time
Contraindications & Precautions- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting
- Known or suspected GI obstruction including paralytic ileus
- Hypersensitivity to buprenorphine
- Additive risk with concomitant CNS depressants (similar to other full-agonist opioids)
Dosing & Administration Criteria- Pre/Peri-operative and PACU: 0.3 mg slow IV (over 2 minutes) pre-op; repeat 0.3 mg slow IV during PACU recovery PRN, may repeat x1 additional dose at 30 minutes if necessary
- PACU to Ward: If IV effective, consider continuing transmucosal formulation (e.g., Belbuca 300 to 450 mcg BID) scheduled for duration of admission; dose adjust based on observed patient response
- Discharge Home: If effective and additional discharge opioids indicated, consider continuing buprenorphine buccal 2-3 times daily PRN for expected post-surgical duration; select outpatient dose based on observed effective minimum dose during inpatient episode
- Emergency Department: Primarily transmucosal; specific use guidance outside scope but studied in renal colic and fractures
- Patients on milligram doses of buprenorphine (8-32 mg/day or LAI): Should NOT be stopped for acute pain management where FAO may be used; continue at maintenance dose and add non-opioid/high-potency FAO as needed. Dose reduction (25-50%) may be considered to allow mu-opioid receptors to “open up” in 12-24 hours, but requires close monitoring due to increased risk of overdose/withdrawals
Clinical Management & Pearls- Tapering and discontinuing buprenorphine for acute pain should not be needed; self-tapers due to long half-life. Advise patients to stop if pain is well managed with non-opioid only
- Onset of action: within 20 minutes (faster with parenteral); full effect of transmucosal products may take 1-3 hours
- Buccal formulation benefits from mucoadherence; requires no patient participation; can be administered under anesthesia; dry buccal mucosa can be moistened with a gloved finger prior to application; yellow side goes on cheek; do not eat or drink while dissolving; rinse mouth after complete dissolution
- If buprenorphine is ineffective/insufficient: may indicate opioid refractoriness; optimize non-opioid strategies and use high-potency full-agonist opioids (FAO); conventional FAO expected to be fully effective even if microgram doses prove ineffective
- Precipitated withdrawal: Microgram dosing for acute pain would not be expected to result in precipitated withdrawal; incidence <5% even when transitioning from high-dose full-agonists
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PRASTERONE INSERT,VAG
INTRAROSA
|
INTRAROSA |
2017-08-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
Exclusion Criteria- Undiagnosed abnormal genital bleeding
- Inclusion Criteria (All must be met)
- Moderate to severe dyspareunia and/or vaginal dryness as a symptom of vulvar or vaginal atrophy due to menopause
- Intolerance, inadequate response, or unable to use vaginal estrogen
Additional Inclusion Criteria- For patients with known or suspected history of breast cancer: Use a multidisciplinary, shared decision-making approach considering potential unknown risk and benefit.
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ABALOPARATIDE INJ,SOLN
TYMLOS
|
TYMLOS |
2017-07-01 |
Exclusion Criteria- History of hypersensitivity reaction or contraindication to abaloparatide (including Paget’s disease, hyper or hypocalcemia, hypercalciuria, bone cancer, bone metastases, radiation treatment to the skeleton, and hyperparathyroidism)
- Pregnancy or lactating status
- Lifetime receipt of 2 years of treatment with abaloparatide
Inclusion Criteria (All must be met)- Diagnosis of osteoporosis or at risk for glucocorticoid-induced osteoporosis
- Prescriber is a VA/Community Care endocrinologist, rheumatologist, nephrologist, geriatrician, or locally designated expert
- Total daily dietary and supplemental calcium intake of 1000 to 1200 mg/day
- 25-hydroxyvitamin D concentration >30 ng/mL or >20 ng/mL with appropriate intake (e.g., cholecalciferol >800 international units per day)
Additional Inclusion Criteria (One must be met)- Osteoporotic fracture and a T-score at the hip or spine of < -2.5
- Very high fracture probability by Fracture Risk Assessment Tool (FRAX) (e.g., major osteoporosis fracture >30%, hip fracture >4.5%)
- T-score < -3.0
- More than 2 osteoporotic fractures
- Continued loss of bone mineral density or sustained osteoporotic fracture despite treatment with an approved osteoporosis therapy (e.g., bisphosphonate or denosumab)
Post-Treatment Requirement- Following a 2-year course of abaloparatide, initiate antiresorptive therapy to maintain bone density gains.
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DURVALUMAB INJ,SOLN
IMFINZI
|
IMFINZI |
2017-07-01 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Indication is FDA approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria- Care provided by a VA/VA Community Care oncology or hematology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Counseling provided on contraception and risks vs. benefits of treatment for female patients of child-bearing potential and male patients with female partners of child-bearing potential; effective contraception required during therapy and for 3 months after the last dose
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MIDOSTAURIN CAP,ORAL
RYDAPT
|
RYDAPT |
2017-07-01 |
Exclusion Criteria- Hypersensitivity to midostaurin or any of the excipients
- Inability to swallow whole capsules
- Pregnancy (known pregnancy or positive pregnancy test)
- Lactating
Inclusion Criteria- Newly diagnosed FLT3 mutation positive Acute Myeloid Leukemia (AML) and eligible for standard induction and consolidation chemotherapy regimens
- Diagnosis of Aggressive Systemic Mastocytosis (ASM), Indolent Systemic Mastocytosis (ISM), Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) or Mast Cell Leukemia (MCL)
Additional Inclusion Criteria- Care for the condition provided by VA or VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3
Pregnancy & Contraception Counseling Requirements- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risk vs. benefit of taking midostaurin if they were to become pregnant
- For patients who can become pregnant and patients with partners who can become pregnant: Counsel on effective contraception use during treatment and for 4 months following the last dose
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SARILUMAB INJ,SOLN
KEVZARA
|
KEVZARA |
2017-07-01 |
Exclusion Criteria- Uncontrolled, active, severe infection (including undrained abscess)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis
- Untreated HIV infection
- Concomitant live or live-attenuated vaccines, or administration of such vaccines less than 2 weeks prior to initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 (unless associated with Duffy-null Associated Neutrophil Count)
- Baseline platelet count < 150,000/mm3
- Baseline alanine transaminase (ALT) and/or aspartate transaminase (AST) > 1.5x the upper limit of normal (ULN)
Inclusion Criteria- Diagnosis of polymyalgia rheumatica (PMR)
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening
- Initiated concurrently with or after glucocorticoid therapy (unless glucocorticoids are medically inadvisable)
Additional Inclusion Criteria- For HBsAg-negative, anti-HBc-positive patients where consult is indicated: E-consult with GI/liver or infectious diseases expert for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- Patients capable of pregnancy: Counseling provided on treatment risks vs benefits and requirement for effective contraception during therapy
- Lactating patients/providing breastmilk: Counseling provided on potential risks and benefits of treatment
Monitoring & Safety Considerations- Antiviral prophylaxis for hepatitis B should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed or initiated by the end of the first year, preferably when dosage is low or disease is stable
- Routine rescreening for hepatitis B or C is not required for prescription renewals; retesting in high-risk patients should be considered
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for infection has been initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Congenital or acquired immunodeficiency
- Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 unless associated with Duffy-null Associated Neutrophil Count
- Baseline platelet count <150,000/mm3
- Baseline ALT and/or AST > 1.5x the upper limit of normal (ULN)
Inclusion Criteria- Diagnosis of moderate to severe rheumatoid arthritis
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response
Additional Inclusion Criteria & Clinical Precautions- If HBsAg-negative but anti-HBc-positive and consult is indicated: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- Females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
- Females who are lactating/providing breastmilk: Counseling provided on potential risks and benefits of treatment
- Antiviral prophylaxis for hepatitis B virus should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation; recombinant zoster vaccine should be completed or initiated by end of first year, preferably when dosage is low, disease is stable, or immune response is robust
- May be used with methotrexate, other nonbiologic DMARDs, mycophenolate, hydroxychloroquine, or glucocorticoids; concomitant use of potent immunosuppressives should generally be avoided
- Routine rescreening for hepatitis B or C is not required for prescription renewals; retesting in high-risk patients should be considered
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TRASTUZUMAB INJ
HERCEPTIN
|
HERCEPTIN |
2017-07-01 |
Exclusion Criteria- Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Interstitial lung disease or pneumonitis
- Pregnancy
- Lactating
- Primary Inclusion Criteria (One must be fulfilled)
- HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
- HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
- Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
- Care provided by VA or VA Community Care provider of oncology
- Goals of care and role of Palliative Care consult discussed and documented, if appropriate
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception Requirements (Select if applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose
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VALBENAZINE CAP,ORAL
INGREZZA, INGREZZA INITIATION PK(TARDIV)
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INGREZZA, INGREZZA INITIATION PK(TARDIV) |
2017-07-01 |
Exclusion Criteria- Active suicidality or untreated/inadequately treated depression
- Congenital long QT interval or QTc >450 ms (men) / >470 ms (women)
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB/RBBB), or presence of a cardiac device (requires cardiology evaluation for consideration)
- Concurrent use of monoamine oxidase inhibitors (MAOIs)
- Current or recent reserpine use within the past 20 days
- Concurrent use of another VMAT2 inhibitor
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnancy or lactation
- Concurrent use of strong CYP3A4 inducers
Inclusion Criteria- Documented diagnosis of Huntington disease in the medical record
- Disabling or painful chorea that interferes with functional status (self-care, ambulation), quality of life, or causes social stigma/isolation/embarrassment
- Documentation of specific movement(s) (facial, oral, extremity, trunk) and their impact on function, quality of life, or socialization
- Verification by an attending psychiatrist or neurologist if the initial prescriber is a resident, fellow, or other trainee
Indications- Management of chorea associated with Huntington disease (HD)
- Management of tardive dyskinesia (TD)
Dosage & Administration- Dosage form: Oral tablets (6 mg, 9 mg, 12 mg); non-formulary status
- Administer with food; swallow tablets whole (do not crush, chew, or break)
- HD dosing: 6 mg once daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day. If total daily dose is ≥12 mg, administer in two divided doses. Maximum recommended dose: 48 mg/day.
- TD dosing: 6 mg twice daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day. If total daily dose is ≥12 mg, administer in two divided doses. Maximum recommended dose: 48 mg/day.
Contraindications- Suicidal/untreated depression
- Hepatic impairment
- Taking reserpine
- Taking MAOI (monoamine oxidase inhibitor)
- Taking another VMAT-2 inhibitor
Warnings & Precautions- Box warning for depression and suicidality
- Neuroleptic malignant syndrome
- Akathisia, restlessness, agitation
- Parkinsonism
- Sedation and somnolence
- QTc prolongation
Adverse Reactions- HD: Somnolence, diarrhea, dry mouth, fatigue, insomnia
- TD: Insomnia, nasopharyngitis, depression, akathisia
Drug Interactions- Strong CYP2D6 inhibitors
- Reserpine
- MAOIs
- Alcohol/Sedating drugs
- Drugs causing QTc prolongation
- Neuroleptic drugs
- Concomitant VMAT-2 inhibitors
Efficacy- HD: Demonstrated reduction in Total Chorea Score compared to placebo (p<0.0001) in a 12-week randomized, double-blind, placebo-controlled study.
- TD: Demonstrated reduction in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo at week 12 in the AIM-TD and ARM-TD trials.
Place in Therapy & Utilization- VMAT-2 inhibitor utilized for management of HD chorea and TD.
- Indirect evidence suggests better tolerability compared to tetrabenazine, though VA ADERS data does not fully support this finding.
- Sequencing of VMAT-2 inhibitors is not warranted based on current evidence and utilization data.
Exclusion Criteria- Patient is actively suicidal or has untreated/inadequately treated depression
- Congenital long QT interval, or QTc >450 ms (men) / >470 ms (women)
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB/RBBB), or cardiac device (candidates may be considered with cardiology evaluation)
- Concurrent use of a monoamine oxidase inhibitor (MAOI)
- Current or recent reserpine use within the past 20 days
- Concurrent use of another VMAT2 inhibitor
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnant or lactating
- Concurrent use of a strong CYP3A4 inducer
Inclusion Criteria- Diagnosis of tardive dyskinesia secondary to a dopaminergic blocking agent (e.g., antipsychotic or metoclopramide)
- TD interferes with functional status (self-care, ambulation), quality of life, or causes social stigma/isolation/embarrassment
- Prescriber has documented specific movement(s) (facial, oral, extremity, trunk) in medical record along with impact on function, quality of life, or socialization
- Recent Abnormal Involuntary Movement Scale (AIMS) score recorded in medical record
- ECG performed to confirm QTc <450 ms (men) / <470 ms (women)
- If initial prescriber is a resident/fellow/trainee, attending psychiatrist or neurologist must verify diagnosis and need for valbenazine
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CLOZAPINE (ACCORD) TAB
|
|
2017-06-01 |
Indications- Treatment-resistant schizophrenia
- Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Contraindications- Hypersensitivity to clozapine or any other component of clozapine
Boxed Warnings- Severe neutropenia
- Orthostatic hypotension, bradycardia, syncope
- Seizures
- Myocarditis, pericarditis, cardiomyopathy, and mitral valve incompetence
- Increased mortality in elderly patients with dementia-related psychosis
Precautions- Eosinophilia
- QT interval prolongation
- Metabolic Changes
- Neuroleptic malignant syndrome
- Hepatotoxicity
- Fever
- Pulmonary embolism
- Anticholinergic toxicity
- Interference with cognitive and motor performance
- Use with caution in patients with decreased GI motility
- Special populations: Poor metabolizers of CYP2D6; Smokers via CYP1A2 induction – with respect to forced absence during hospitalization
Dosing- Starting Dose: 12.5 mg once daily or twice daily
- Use cautious titration and divided dosage schedule
- Titration: increase the total daily dosage in increments of 25 mg to 50 mg per day, if well-tolerated
- Target dose: 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks
- Subsequent increases: increase in increments of 100 mg or less, once, or twice weekly
- Maximum daily dose: 900 mg
ANC Monitoring Recommendations- Obtain baseline ANC before treatment initiation
- Weekly from initiation to 6 months
- Every 2 weeks from 6 to 12 months (if the ANC remains in the normal range; ANC greater than or equal to 1500/μL for the general population, ANC greater than or equal to 1000/μL for patients with Benign Ethnic Neutropenia)
- Monthly after 12 months, using shared decision making (if ANC continues to remain in the normal range)
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CLOZAPINE (AUROBINDO) TAB
|
|
2017-06-01 |
Indications- Treatment-resistant schizophrenia
- Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Contraindications- Hypersensitivity to clozapine or any other component of clozapine
Boxed Warnings- Severe neutropenia
- Orthostatic hypotension, bradycardia, syncope
- Seizures
- Myocarditis, pericarditis, cardiomyopathy, and mitral valve incompetence
- Increased mortality in elderly patients with dementia-related psychosis
Precautions- Eosinophilia
- QT interval prolongation
- Metabolic Changes
- Neuroleptic malignant syndrome
- Hepatotoxicity
- Fever
- Pulmonary embolism
- Anticholinergic toxicity
- Interference with cognitive and motor performance
- Use with caution in patients with decreased GI motility
- Special populations: Poor metabolizers of CYP2D6; Smokers via CYP1A2 induction – with respect to forced absence during hospitalization
Dosing- Starting Dose: 12.5 mg once daily or twice daily
- Use cautious titration and divided dosage schedule
- Titration: increase the total daily dosage in increments of 25 mg to 50 mg per day, if well-tolerated
- Target dose: 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks
- Subsequent increases: increase in increments of 100 mg or less, once, or twice weekly
- Maximum daily dose: 900 mg
ANC Monitoring Recommendations- Obtain baseline ANC before treatment initiation
- Weekly from initiation to 6 months
- Every 2 weeks from 6 to 12 months (if the ANC remains in the normal range; ANC greater than or equal to 1500/μL for the general population, ANC greater than or equal to 1000/μL for patients with Benign Ethnic Neutropenia)
- Monthly after 12 months, using shared decision making (if ANC continues to remain in the normal range)
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DEUTETRABENAZINE TAB
AUSTEDO
|
AUSTEDO |
2017-06-01 |
Exclusion Criteria- Actively suicidal or has untreated or inadequately treated depression
- Congenital long QT interval, or a QTc >450 ms for men or QTc >470 ms for women
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB or RBBB), or cardiac device (can be considered candidates with cardiology evaluation)
- Concurrent use of a monoamine oxidase inhibitor (MAOI) or within 14 days of discontinuing therapy with an MAOI
- Current or use of reserpine within the past 20 days
- Concurrent use of another VMAT2 inhibitor (i.e., tetrabenazine, valbenazine)
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnant or lactating
- Hepatic impairment
Inclusion Criteria: Treatment of Huntington Disease- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
- Diagnosis of Huntington disease documented in the medical record
- Chorea is disabling or painful and interferes with functional status (including self-care and ambulation), quality of life, or creates a social stigma sufficient to cause social isolation or embarrassment
- Prescriber has documented specific movement(s) (e.g., facial, oral, extremity, or trunk) in the medical record along with how the chorea is affecting function, quality of life, or socialization
Inclusion Criteria: Treatment of Dystonia- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
- No response or intolerant to alternative agents (local botulinum toxin injections, anticholinergics, or benzodiazepines)
Inclusion Criteria: Treatment of Tardive Dyskinesia- Diagnosis of tardive dyskinesia (TD) secondary to a dopaminergic blocking agent (e.g., antipsychotic or metoclopramide)
- TD interferes with functional status (including self-care and ambulation), quality of life, or creates a social stigma sufficient to cause social isolation or embarrassment
- Prescriber has documented specific movement(s) (e.g., facial, oral, extremity, or trunk) in the medical record along with how TD is affecting function, quality of life, or socialization
- Recent Abnormal Involuntary Movement Scale (AIMS) score is recorded in the medical record
- ECG performed to confirm a QTc <450 ms for men or QTc <470 ms for women
- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
Indications- Management of chorea associated with Huntington disease (HD)
- Management of tardive dyskinesia (TD)
Dosage & Administration- Dosage form: Oral tablets (6 mg, 9 mg, 12 mg); non-formulary status
- Administer with food; swallow tablets whole (do not crush, chew, or break)
- HD dosing: 6 mg once daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day. If total daily dose is ≥12 mg, administer in two divided doses. Maximum recommended dose: 48 mg/day.
- TD dosing: 6 mg twice daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day. If total daily dose is ≥12 mg, administer in two divided doses. Maximum recommended dose: 48 mg/day.
Contraindications- Suicidal/untreated depression
- Hepatic impairment
- Taking reserpine
- Taking MAOI (monoamine oxidase inhibitor)
- Taking another VMAT-2 inhibitor
Warnings & Precautions- Box warning for depression and suicidality
- Neuroleptic malignant syndrome
- Akathisia, restlessness, agitation
- Parkinsonism
- Sedation and somnolence
- QTc prolongation
Adverse Reactions- HD: Somnolence, diarrhea, dry mouth, fatigue, insomnia
- TD: Insomnia, nasopharyngitis, depression, akathisia
Drug Interactions- Strong CYP2D6 inhibitors
- Reserpine
- MAOIs
- Alcohol/Sedating drugs
- Drugs causing QTc prolongation
- Neuroleptic drugs
- Concomitant VMAT-2 inhibitors
Efficacy- HD: Demonstrated reduction in Total Chorea Score compared to placebo (p<0.0001) in a 12-week randomized, double-blind, placebo-controlled study.
- TD: Demonstrated reduction in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo at week 12 in the AIM-TD and ARM-TD trials.
Place in Therapy & Utilization- VMAT-2 inhibitor utilized for management of HD chorea and TD.
- Indirect evidence suggests better tolerability compared to tetrabenazine, though VA ADERS data does not fully support this finding.
- Sequencing of VMAT-2 inhibitors is not warranted based on current evidence and utilization data.
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AVELUMAB INJ,SOLN
BAVENCIO
|
BAVENCIO |
2017-05-01 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy (i.e., known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Indication is FDA approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria- Care provided by a VA/VA Community Care oncology or hematology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Counseling on contraception and risks vs. benefits of treatment provided for female patients of child-bearing potential and male patients with female partners of child-bearing potential; effective contraception required during therapy and for 1 month after the last dose
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BRODALUMAB INJ,SOLN
SILIQ
|
SILIQ |
2017-05-01 |
Exclusion Criteria- Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients can be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- History of suicidal ideation or behavior or risk factors for suicide (e.g., depression, bipolar disorder) – relative contraindication when potential risks outweigh benefits; available only through the restricted SILIQ REMS Program
- Crohn’s disease
Inclusion Criteria for Plaque Psoriasis- Meets requirements of the SILIQ REMS Program
- Prescribed and monitored by a VA/VA Community Care dermatologist or locally designated psoriasis expert
- Prescribed at FDA-approved dose for plaque psoriasis
- Adult with chronic (≥ 6 months) moderate to severe plaque psoriasis (including involvement of nails only)
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
- Methotrexate monotherapy is medically inadvisable, not tolerated, or not adequate (inadequate response defined as NO treatment benefit after 3 months with at least 2 months at standard target dose [15–25 mg ONCE WEEKLY], or inadequate partial response after 6 months)
- Phototherapy is medically inadvisable, inadequate, not available or not feasible (inadequate defined as NO treatment benefit after 12 treatments or inadequate partial response after 24 treatments; medically inadvisable for confirmed history of skin cancer/melanoma or strong likelihood [Fitzpatrick I/II])
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, or not adequate (NO response to ONE TNFI after 3 months, partial response to 3-month trials of TWO TNFIs = total 6 months, or loss of initial response; may be inadvisable for heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent infections, serious infections)
- Interleukin-17A inhibitor (ixekizumab [preferred] or secukinumab) is medically inadvisable, not tolerated or not adequate (NO response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response; may be inadvisable for Crohn’s disease, ulcerative colitis, or recurrent/severe Candida infections)
- Interleukin-23 inhibitor (e.g., guselkumab, risankizumab-rzaa, or tildrakizumab-asmn) is medically inadvisable, not tolerated or not adequate (NO response after 12 weeks, inadequate partial response after 24 weeks, or loss of initial response)
- Ustekinumab is medically inadvisable, not tolerated or not adequate (NO response after 16 weeks, inadequate partial response after 32 weeks, or loss of initial response; may be inadvisable for history of noninfectious pneumonia)
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DESVENLAFAXINE TAB,SA
DESVENLAFAXINE ER, DESVENLAFAXINE SUCCINATE ER, PRISTIQ
|
DESVENLAFAXINE ER, DESVENLAFAXINE SUCCINATE ER, PRISTIQ |
2017-05-01 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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DUPILUMAB INJ,SOLN
DUPIXENT PEN, DUPIXENT SYRINGE
|
DUPIXENT PEN, DUPIXENT SYRINGE |
2017-05-01 |
Exclusion Criteria- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 4 weeks.
- Concurrent use with targeted immunomodulators unless potential risk-benefits favor use.
- Untreated parasitic (helminth) infection.
- Existing diagnosis of cutaneous T-cell lymphoma (CTCL), mycosis fungoides, or Sézary syndrome unless potential benefits outweigh risks (relative contraindication).
Inclusion Criteria (New Starts)- Diagnosis of chronic atopic dermatitis made or confirmed by a VA / VA Community Care dermatologist.
- Prescribed by a VA / VA Community Care dermatologist, allergist, or immunologist, or other designated expert in the management of atopic dermatitis in consultation with a VA / VA Community Care dermatologist, allergist, or immunologist.
- Offered all age-appropriate vaccinations prior to initiating therapy.
- Assessment of moderate to severe atopic dermatitis in the last 2 weeks as determined by either a gestalt assessment of “moderate” or “severe” OR Eczema Area and Severity Index (EASI) ≥ 16 (scale 0–72).
- Refractory to ≥ 2 classes of topical therapies for atopic dermatitis (e.g., corticosteroids, calcineurin inhibitors, PDE4 inhibitors, JAK inhibitors) for ≥ 4 weeks total unless the therapy is medically inadvisable or not tolerated.
Additional Inclusion Criteria- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits of treatment.
Sequencing & Therapy Considerations- If patient weighs < 100 kg, consider tralokinumab prior to dupilumab.
- First-line therapies include dupilumab, tralokinumab-ldrm, lebrikizumab-lbkz, or nemolizumab-ilto.
- Second-line therapies include abrocitinib or upadacitinib.
- Consider offering methotrexate, azathioprine, mycophenolate mofetil in the context of shared decision-making (prior trials not required), with use conditional on factors such as lower certainty of risk-benefits, slower onset, feasibility of adhering to follow-ups, comorbidities, and patient values/preferences.
Exclusion Criteria- History of hypersensitivity to dupilumab or any of its excipients
- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 12 weeks
- Currently treated with omalizumab or another biologic agent
- Untreated parasitic (helminth) infection
Inclusion Criteria- Care provided by a VA / VA Community Care (Allergy, Immunology or Otolaryngology [ear, nose and throat] specialist) or locally designated expert in managing CRSwNP
- Diagnosis of CRSwNP is confirmed
- Symptoms of CRSwNP are uncontrolled and persistent despite use of ALL of the following:
- Daily use and adherence to topical corticosteroid (CS) nasal spray (e.g., fluticasone)
- Daily use and adherence to nasal saline spray/irrigations
- Trial of nasal CS irrigation (e.g., 4-6 weeks budesonide added to topical CS and nasal saline sprays/irrigations)
- Short-term course of systemic CS within the past 2 years (unless contraindicated)
- Sinonasal surgery has been performed (e.g., surgical/endoscopic intervention(s) to remove nasal polyps/tissue, unless patient is not a surgical candidate or surgery is not indicated) and continued adherence to maximal medical therapies after surgery has been confirmed with the patient
Dosing & Administration- FDA-approved dosing schedule for CRSwNP is every 2 weeks
- Clinical trials (SINUS-24 and SINUS-52) showed no statistically different outcomes between administering dupilumab every 2 weeks vs. every 4 weeks
Safety & Clinical Management- Hypersensitivity reactions reported in <1% of patients in clinical trials (e.g., generalized urticaria, rash, erythema nodosum and serum sickness or serum sickness-like events)
- If a hypersensitivity reaction occurs, appropriate therapy should be instituted and dupilumab discontinued
Exclusion Criteria- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 12 weeks
- Untreated parasitic (helminth) infection
Inclusion Criteria- Diagnosis of eosinophilic esophagitis (EoE) including histologic evidence of eosinophilic inflammation (≥ 15 eosinophils / high power field) made or confirmed by a VA / VA Community Care gastroenterologist
- Prescribed by a VA / VA Community Care gastroenterologist OR an immunologist, allergist, or other designated expert in the management of EoE in consultation with a VA / VA Community Care gastroenterologist
- Tried a swallowed topical glucocorticoid (e.g., swallowed aerosolized fluticasone or commercially available budesonide oral suspension) for at least 8 to 12 weeks, unless medically inadvisable, and had an inadequate response or intolerance
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Indication- Treatment of adults with eosinophilic esophagitis (EoE)
Patient Selection & Clinical Criteria- Histologic confirmation of eosinophilic inflammation (≥ 15 intraepithelial eosinophils per high-power field [eos/hpf])
- Significant symptoms: average ≥ 2 episodes of dysphagia with intake of solids per week in the previous 4 weeks
- Inadequate response or intolerance to prior trials of proton pump inhibitors (PPIs) administered twice daily for ≥ 8 weeks
- Prior trials of swallowed topical glucocorticoids (STGs) (≥ 8 weeks) and dietary therapy are considered, though a prior trial of systemic glucocorticoids is not required
- Patients should be strongly motivated/adherent with access to dietitian support if dietary therapy is utilized
Dosing & Administration- 300 mg subcutaneous (SC) every week (QW)
- Dose is higher and more frequent than for other approved indications
Place in Therapy- Third-line pharmacologic treatment alternative for EoE
Safety Considerations & Monitoring- Adverse events observed include injection site reactions, upper respiratory tract infections, arthralgia, and herpes viral infections (≥ 2% incidence)
- Conjunctivitis and keratitis were reported at 0% in the dupilumab group
- Long-term safety and risk of loss of efficacy require further assessment beyond short-term trials
- Symptomatic remission does not reliably correlate with histologic remission; both histologic end points (reduction in eosinophilic inflammation) and clinical signs/symptoms are important outcome measures
Un-Evaluated Populations & Precautions- Safety and efficacy have not been evaluated in patients in complete symptomatic remission
- Safety and efficacy have not been evaluated in patients with prior esophageal surgery
- Safety and efficacy have not been evaluated in patients with an esophageal stricture unable to be passed with a 9- to 10-mm standard diagnostic endoscope
- Safety and efficacy have not been evaluated in patients with a critical esophageal stricture requiring dilation
- Use in the above un-evaluated populations should be adjudicated on a case-by-case basis
Indication & Patient Population- • Treatment of adult patients with prurigo nodularis (PN)
- • Patients with a documented diagnosis of PN and ≥ 20 nodules
- • Patients presenting with severe itch despite use of topical therapies
Treatment Prerequisites & Step Therapy Requirements- • Inadequate response (after ≥ 2 weeks per therapy) or intolerance to one of the following:
- – Two topical therapies (e.g., medium, high, or super-high corticosteroids [where different strengths count as different therapies], calcipotriene, or calcineurin inhibitor)
- – One topical therapy and an intralesional corticosteroid
- • Applicable unless these prior therapies are medically inadvisable
Dosing & Administration- • Initial: 600 mg (two 300-mg injections) subcutaneously (SC)
- • Maintenance: 300 mg SC every 2 weeks
- • Formulation: Single-dose prefilled syringe or single-dose prefilled pen: 300 mg/2 mL
Safety & Clinical Considerations- • Boxed warnings, contraindications, and other warnings/precautions apply as for previous indications
- • Common adverse events (≥ 2% of dupilumab group and greater than placebo): Nasopharyngitis, conjunctivitis, herpes infection, dizziness, myalgia, diarrhea
- • Patients with atopic dermatitis-related PN require more weeks of treatment to achieve response compared to non-atopic dermatitis-related PN patients
- • Complete remission is rarely observed before 4 months of therapy; 2 months of therapy are required before itch is relieved
Provider & Care Setting- Provider must be a VA or VA Community Care pulmonologist or designated expert.
Disease Severity & Phenotype- Moderate to severe COPD (post-bronchodilator FEV 30-70% predicted and FEV /FVC <0.7, confirmed by pulmonary function testing).
- Signs or symptoms of chronic bronchitis (chronic productive cough) for at least 3 months during the past year.
Exacerbation History & Symptom Control- At least 2 moderate COPD exacerbations (requiring systemic steroids and/or antibiotics) or at least 1 severe COPD exacerbation (requiring hospitalization) in the previous 12 months.
- Inadequate symptom control (e.g., mMRC dyspnea scale score > 2.) or impaired health status (e.g., CAT score > 15).
Biomarkers- Blood eosinophils ≥300 cells/µL obtained prior to treatment (e.g., within the prior 3 months).
Prior Therapy & Treatment Trials- Receiving concurrent triple inhaled therapy with a long-acting beta-agonist (LABA) AND a long-acting anticholinergic (LAMA) AND an inhaled corticosteroid (unless inhaled corticosteroid is contraindicated) for at least 3 months.
- Unable to tolerate or had an inadequate response to a (6-month) trial of roflumilast and to a (6-month) trial of azithromycin, unless not clinically appropriate for either agent.
Adherence & Technique- Adherent to COPD medications as evidenced by a review of prescription refill history.
- Demonstrated correct inhaler technique (documented in chart).
Safety & Contraindications (Exclusion Criteria)- Untreated acute bronchospasm or an acute exacerbation of chronic obstructive pulmonary disease (COPD).
- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 4 weeks.
- Untreated parasitic (helminth) infection (treat infection prior to initiating dupilumab).
- Concurrent use with therapeutic biologics unless potential benefit-risk favors use.
Special Populations & Additional Considerations- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
- Patient is non-smoking or, if not, enrolled in a quit smoking program or on medications to assist with smoking cessation (current smokers may be considered if unable or refuse to quit).
- Address modifiable environmental triggers for Type 2 inflammation, if not already done.
Indication & Patient Population- Adults with bullous pemphigoid (BP)
- Moderate to severe BP or patients requiring systemic therapy
- Refractory/resistant to combined topical corticosteroids (TCS) and oral corticosteroids (OCS)
- Histopathologically, immunopathologically, and serologically confirmed diagnosis
- Bullous Pemphigoid Disease Area Index (BPDAI) activity score ≥ 24
- Weekly average Peak Pruritus NRS (PP-NRS) score ≥ 4
Dosing & Administration- 600 mg SC once, then 300 mg SC every 2 weeks
- Use in combination with a tapering course of OCS
- Once disease control occurs, gradually taper OCS and continue dupilumab as monotherapy
- Add corticosteroids if medically advisable in case of relapse
Pretreatment & Monitoring- No pretreatment procedures required
- No laboratory monitoring required
- Monitor for keratoconjunctivitis
Safety Considerations- Nonimmunosuppressant (advantageous for older patients with comorbidities)
- Top 5 adverse events: arthralgia, conjunctivitis, blurred vision, herpes viral infections, keratitis
Place in Therapy- FDA-approved for BP
- Potential first-line (1L) treatment in combination with a tapering course of OCS for moderate to severe BP or when systemic therapy is indicated
- Considered for BP resistant to combined TCS and OCS; once disease controlled, OCS may be tapered before continuing dupilumab as monotherapy
Indication & Patient Population- Adults and pediatric patients > 12 years with chronic spontaneous urticaria (CSU)
- Patients who remain symptomatic despite treatment with H1 antihistamines (up to 4x usual daily dose)
- Not indicated for patients with inducible urticaria, diseases other than urticaria associated with hives or angioedema, active atopic dermatitis, or other skin conditions that could interfere with outcome assessments
Dosing & Administration- Initial dose: 600 mg
- Maintenance dose: 300 mg every 2 weeks
- Continue H1 antihistamines; titrate up to 4x usual daily dose as needed
- Rescue therapy with oral corticosteroids is permitted
Safety, Monitoring & Precautions- Contraindicated in patients with known hypersensitivity to dupilumab or any excipients
- Monitor for and report: Hypersensitivity; conjunctivitis and keratitis (report new eye symptoms); eosinophilic conditions (especially upon reducing oral corticosteroid dose); psoriasis (new onset); arthralgia and psoriatic arthritis (report new onset joint symptoms)
- Steroid withdrawal precautions: Do not abruptly discontinue oral, topical, or inhaled corticosteroids upon initiation; if needed, gradually decrease steroids
- Parasitic (Helminth) infections: Treat preexisting infections before initiating treatment
- Vaccines: Avoid use of live vaccines
- Pregnancy: Monitor via pregnancy registry; case reports and series have not identified a dupilumab-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
- Lactation: Weigh benefits of breastfeeding against mother’s clinical need and potential adverse drug events on the breastfed child
Place in Therapy & Step-Down Criteria- Recommended as a second-line therapy for patients remaining symptomatic on H1 antihistamines (up to 4x daily dose)
- Maximum doses of H1 antihistamines should be continued in combination with second-line therapies
- Not recommended for patients who have not had an adequate response to omalizumab, as they are unlikely to show a greater response to dupilumab
- Therapy can be stepped down by reducing doses or extending dosing intervals when the urticaria control test (UCT) score equals 16
Exclusion Criteria- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 4 weeks
- Concurrent use with therapeutic biologics unless potential risk-benefits favor use
- Untreated parasitic (helminth) infection
Inclusion Criteria (Prerequisites)- Prescribed by a VA / VA Community Care dermatologist or other designated expert in the management of bullous pemphigoid in consultation with a VA / VA Community Care dermatologist
- Medications potentially implicated as causing bullous pemphigoid have been discontinued or switched if clinically possible (but this should not necessarily delay initiation of therapy)
Inclusion Criteria (Disease Severity & Treatment History)- One of the following must be selected:
- Documented biopsy and/or serology-confirmed, moderate–severe bullous pemphigoid with moderate–very severe pruritus AND concomitant tapering course of oral corticosteroids unless medically inadvisable
- Documented mild bullous pemphigoid AND had an inadequate response (after ≥ 4 weeks), intolerance, or medical inadvisability to either high potency topical corticosteroids or oral corticosteroids and either doxycycline/tetracycline or dapsone
Additional Inclusion Criteria (Special Populations)- Select if applicable:
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
- For females who are lactating/providing breastmilk to an infant: Counseling provided on the potential risks vs benefits of treatment
Exclusion Criteria- Concurrent use of live or live attenuated vaccines (within the past 4 weeks)
- Untreated parasitic (helminth) infection (treat infection prior to initiating dupilumab)
- Concurrent use with therapeutic biologics unless potential benefit-risk favors use
Inclusion Criteria- Provider is a VA or VA Community Care allergy specialist, dermatologist or designated expert in the management of allergic conditions
- Diagnosis of severe chronic spontaneous urticaria (e.g., UAS7 >28 and/or UCT <12)
- Unacceptable symptoms despite a therapeutic trial of 1 non-sedating H antihistamine titrated up to 4 times the usual daily dose
- Inadequate response to a 3-month trial of omalizumab 300 mg every 4 weeks (minimum of 3 doses), unable to tolerate or not a candidate for omalizumab
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy; if pregnancy occurs, enrollment in a pregnancy register is recommended
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| ▸ |
OCRELIZUMAB INJ,SOLN
OCREVUS
|
OCREVUS |
2017-05-01 |
Indication & Clinical Status- Diagnosis of primary progressive multiple sclerosis (PPMS) has been established
- Expanded Disability Status Scale (EDSS) score of 6.5 or less
Provider & Care Setting Requirements- Care is provided by a VA/VA Community Care neurologist or locally designated MS expert (e.g., Spinal Cord Injury)
Screening & Laboratory Monitoring- Patient has been screened for hepatitis B virus (HBV) including HBsAg, HBsAb and HBcAb; if HBsAb negative and HBcAb positive or HBsAg positive, a liver disease expert must be consulted first
- Quantitative serum immunoglobulins tested; if low, neurologist has documented risk/benefit assessment and/or an immunology expert was consulted prior to start
Contraindications & Exclusions- History of life-threatening infusion reaction to another anti-CD20 antibody (e.g., ublituximab, rituximab)
- Untreated active hepatitis B infection
- Untreated latent or active tuberculosis infection
- Active infection or receiving chemotherapy
- Concurrent use of another disease modifying therapy (DMT) to treat multiple sclerosis (MS) unless the previous agent will be discontinued when ocrelizumab is initiated
Pre-treatment & Vaccination Requirements- All guideline recommended eligible immunizations administered at least 4 weeks prior to the start of treatment for live or live-attenuated vaccines, and whenever possible, at least 2 weeks prior to the start of treatment for inactivated vaccines
Reproductive & Pregnancy Considerations- For patients who can become pregnant: Pregnancy should be excluded prior to receiving ocrelizumab
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 6 months after stopping treatment
Exclusion Criteria- Diagnosis of primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis without activity (non-active SPMS)
- History of life-threatening infusion reaction to another anti-CD20 antibody (e.g., ublituximab, rituximab)
- Untreated active hepatitis B infection
- Untreated latent or active tuberculosis infection
- Concurrent use of another disease modifying therapy (DMT) to treat multiple sclerosis (MS) unless the previous agent will be discontinued when ocrelizumab is initiated
- Active infection or receiving chemotherapy
- Pregnancy
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist or locally designated MS expert (e.g., Spinal Cord Injury)
- Diagnosis of a relapsing form of multiple sclerosis (relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome) has been established
- Intolerance or inadequate therapeutic response to ublituximab
- Patient screened for hepatitis B virus (HBV) including HBsAg, HBsAb and HBcAb; if HBsAb negative and HBcAb positive or HBsAg positive, liver disease expert must be consulted first
- Quantitative serum immunoglobulins tested; if low, neurologist has documented risk/benefit assessment and/or an immunology expert was consulted prior to start
- All guideline recommended eligible immunizations administered at least 4 weeks prior to the start of treatment for live or live-attenuated vaccines, and whenever possible at least 2 weeks prior to the start of treatment for inactivated vaccines
Additional Inclusion Criteria (One of the following must be met)- Current treatment with natalizumab and patient has elevated risk factors for PML (anti-JC virus antibody positive, duration of therapy > 24 months or received immunosuppressant therapy prior to natalizumab)
- Ineffectiveness with at least one other MS DMT defined as continued clinical relapses, central nervous system (CNS) lesion progression on MRI, or continued worsening of disability
- Highly active disease demonstrated by heavy burden of gadolinium enhancing and/or T2 lesions on MRI at onset of disease, high accumulation of CNS lesions on MRI, or rapid accrual of disability
Pregnancy Management Criteria- For patients who can become pregnant: Pregnancy should be excluded prior to receiving ocrelizumab
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 6 months after stopping treatment
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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TELOTRISTAT TAB
XERMELO
|
XERMELO |
2017-05-01 |
Inclusion Criteria- Diagnosis of neuroendocrine tumor
- Diarrhea secondary to carcinoid syndrome, inadequately managed with somatostatin analog (SSA) therapy alone; can be used in combination with short-acting SSA
Exclusion Criteria- Patient has not been on a stable sandostatin analog (SSA) regimen defined as a long-acting release, depot or infusion pump for > 3 months
- More than 12 watery BMs per day associated with volume contraction, dehydration or hypotension
- Evidence of enteric infection
- Eastern Cooperative Oncology Group Performance Status > 2
- History of short bowel syndrome
- Moderate to severe hepatic impairment (Child-Pugh class B or C)
- Unmanageable drug-drug interaction
- Known pregnancy
Additional Inclusion Criteria- For females who can become pregnant: Pregnancy should be excluded prior to receiving telotristat
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
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TENOFOVIR ALAFENAMIDE ORAL TABLET
VEMLIDY
|
VEMLIDY |
2017-05-01 |
Exclusion Criteria- Patient prescribed combination product containing tenofovir disoproxil fumarate or tenofovir alafenamide fumarate for HBV and/or HIV infection
- Inclusion Criteria (Must meet at least one)
- Patient with calculated CrCl or eGFR of 15-59 mL/min or has end stage renal disease (ESRD) and is receiving dialysis
- Patient prescribed concomitant nephrotoxic medications (eg: ACE-inhibitors, calcineurin inhibitors, certain chemotherapy agents, diuretics, etc.)
- Patient at risk of fracture or with evidence of bone mineral destruction (including, but not limited to: active treatment for osteoporosis or osteopenia, history of stress fracture, oral glucocorticoid use within past 3 months at a prednisolone dose ≥7.5 mg daily, currently smoking, etc.)
Dosage and Administration- One 25 mg tablet orally once daily taken with food
Dosing Considerations- No dose adjustment is needed for patients with a CrCl 15-59 mL/min OR CrCl <15mL/min AND receiving hemodialysis
- Not recommended in patients with ESRD (CrCl < 15 mL/min who are NOT receiving dialysis)
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NALOXONE KIT
NALOXONE INTRANASAL KIT, NALOXONE KIT IM
|
NALOXONE INTRANASAL KIT, NALOXONE KIT IM |
2017-04-01 |
Indications & Patient Populations- All patients at risk of an opioid overdose
- Veterans prescribed or using opioids, including those unknowingly exposed to opioids (e.g., illicit drugs/pills containing fentanyl)
- Patients with increased risk for opioid overdose or where provider clinical judgment indicates indication for readily available naloxone
- Active substance use disorder (excluding tobacco)
- Diagnosis of opioid use disorder (OUD)
- Diagnosis of stimulant use disorder (e.g., amphetamines, cocaine)
- >50 MEDD
- Long-acting or extended-release formulations (e.g., morphine SA, fentanyl)
- Concomitant use of CNS depressants
- Identified as very-high risk per VHA’s Stratification Tool for Opioid Risk Mitigation (STORM)
- History of opioid or stimulant overdose in the past year
- Use of illicit or non-prescribed substances that could contain opioids
- Loss of tolerance and/or at risk of non-prescribed use (during/after recently completed opioid taper, after detoxification/withdrawal treatment/residential treatment/abstinence, recent incarceration/release)
- Higher risk for suicide/overdose based on predictive modeling tools (e.g., STORM, RIOSORD)
- Prescriber determines individual is at risk of a potential overdose
Exclusions & Special Populations- Tramadol: Low-risk patients on single-agent tramadol generally do not warrant naloxone prescription due to low mu-opioid receptor affinity, non-opioid mechanism, lack of reversibility, and lack of significant withdrawal; high-risk patients remain candidates
- Hospice: Not routinely used for comfort-oriented goals receiving opioids toward end-of-life suffering due to overlapping signs/symptoms with the dying process; may be considered based on clinical conditions, prognosis, goals of care, home environment, opioid dose, and prior opioid history
Prescribing & Dispensing Parameters- Requires a prescription but provided at zero copay to any Veteran enrolled in VHA care
- Each prescription order contains 2 dose units
- Prescriptions processed with a 1-day supply marked with at least one refill
- Standing orders may be utilized, but overdose education and Veteran agreement must occur prior to dispensation
- Reassessment of OEND need should occur at least annually
Product Selection & Administration- Preferred products: Nasal preparations (4 mg nasal spray)
- Alternative routes: IM kit/injection available for patients with contraindications to nasal products
- Higher dose options: 8 mg naloxone nasal spray (KLOXXADO) for concerns requiring higher dose; nalmefene (OPVEE) for higher potency antagonist need or rare true naloxone allergy (accessed via routine non-formulary request)
- All products are FDA-approved and designed for layperson use without assembly
- Administration generally includes: place patient on back, administer dose, repeat after 2-3 minutes if no/minimal response, obtain emergency medical help (call 911), place in recovery position if breathing normally
Documentation & Monitoring Requirements- Use “Overdose Education and Naloxone” CPRS note or “Naloxone Overdose Education” Oracle Powerform for education/order process
- Document whether Veteran accepts, declines, or reports having in-date product on hand (document “has current naloxone” if applicable)
- Report all overdoses within the past 12 months using national standardized documentation (e.g., Suicidal Behavior and Overdose Report template)
- If naloxone was used on someone other than the Veteran, use the Naloxone Use Note
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NALOXONE SOLN,SPRAY,NASAL
KLOXXADO, NARCAN, REXTOVY
|
KLOXXADO, NARCAN, REXTOVY |
2017-04-01 |
Indications & Patient Populations- All patients at risk of an opioid overdose
- Veterans prescribed or using opioids, including those unknowingly exposed to opioids (e.g., illicit drugs/pills containing fentanyl)
- Patients with increased risk for opioid overdose or where provider clinical judgment indicates indication for readily available naloxone
- Active substance use disorder (excluding tobacco)
- Diagnosis of opioid use disorder (OUD)
- Diagnosis of stimulant use disorder (e.g., amphetamines, cocaine)
- >50 MEDD
- Long-acting or extended-release formulations (e.g., morphine SA, fentanyl)
- Concomitant use of CNS depressants
- Identified as very-high risk per VHA’s Stratification Tool for Opioid Risk Mitigation (STORM)
- History of opioid or stimulant overdose in the past year
- Use of illicit or non-prescribed substances that could contain opioids
- Loss of tolerance and/or at risk of non-prescribed use (during/after recently completed opioid taper, after detoxification/withdrawal treatment/residential treatment/abstinence, recent incarceration/release)
- Higher risk for suicide/overdose based on predictive modeling tools (e.g., STORM, RIOSORD)
- Prescriber determines individual is at risk of a potential overdose
Exclusions & Special Populations- Tramadol: Low-risk patients on single-agent tramadol generally do not warrant naloxone prescription due to low mu-opioid receptor affinity, non-opioid mechanism, lack of reversibility, and lack of significant withdrawal; high-risk patients remain candidates
- Hospice: Not routinely used for comfort-oriented goals receiving opioids toward end-of-life suffering due to overlapping signs/symptoms with the dying process; may be considered based on clinical conditions, prognosis, goals of care, home environment, opioid dose, and prior opioid history
Prescribing & Dispensing Parameters- Requires a prescription but provided at zero copay to any Veteran enrolled in VHA care
- Each prescription order contains 2 dose units
- Prescriptions processed with a 1-day supply marked with at least one refill
- Standing orders may be utilized, but overdose education and Veteran agreement must occur prior to dispensation
- Reassessment of OEND need should occur at least annually
Product Selection & Administration- Preferred products: Nasal preparations (4 mg nasal spray)
- Alternative routes: IM kit/injection available for patients with contraindications to nasal products
- Higher dose options: 8 mg naloxone nasal spray (KLOXXADO) for concerns requiring higher dose; nalmefene (OPVEE) for higher potency antagonist need or rare true naloxone allergy (accessed via routine non-formulary request)
- All products are FDA-approved and designed for layperson use without assembly
- Administration generally includes: place patient on back, administer dose, repeat after 2-3 minutes if no/minimal response, obtain emergency medical help (call 911), place in recovery position if breathing normally
Documentation & Monitoring Requirements- Use “Overdose Education and Naloxone” CPRS note or “Naloxone Overdose Education” Oracle Powerform for education/order process
- Document whether Veteran accepts, declines, or reports having in-date product on hand (document “has current naloxone” if applicable)
- Report all overdoses within the past 12 months using national standardized documentation (e.g., Suicidal Behavior and Overdose Report template)
- If naloxone was used on someone other than the Veteran, use the Naloxone Use Note
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PLECANATIDE TAB,ORAL
TRULANCE
|
TRULANCE |
2017-04-01 |
Exclusion Criteria- Mechanical gastrointestinal obstruction, known or suspected
- Age less than 18 years
- Presence of severe or frequent diarrhea
- Chronic constipation due to drug-induced causes, neurogenic disorders, or non-neurogenic disorders (excluded from IBS definition)
Inclusion Criteria- Men or women 18 years or older with a documented diagnosis of irritable bowel syndrome with constipation (IBS-C)
- Intolerance or inadequate response to a 1-month trial of either PEG-3350 powder for oral solution (17 g twice daily) or other osmotic laxative, unless contraindication or risk factor(s) for serious adverse event(s)
- For women: Intolerance or inadequate response to a 1-month trial of lubiprostone (8 mcg twice daily)
Additional Clinical Recommendations & Notes- GI consultation (including e-consult) is highly recommended prior to using plecanatide for IBS-C
- Osmotic laxatives include lactulose, sorbitol, magnesium citrate, magnesium hydroxide, and glycerin rectal suppositories
- Escalation/titration of therapy up to bowel-prep doses of PEG-3350 may be considered case by case during the 1-month trial
Indication- Chronic idiopathic constipation (CIC)
- Note: CIC excludes drug-induced chronic constipation and chronic constipation due to neurogenic and non-neurogenic disorders.
Exclusion Criteria- Mechanical gastrointestinal obstruction, known or suspected
- Age less than 18 years
- Presence of severe or frequent diarrhea
Inclusion Criteria & Prerequisites- Men or women 18 years or older with CIC
- Intolerance or inadequate response to a 1-month trial of at least one bulk forming laxative (e.g., psyllium, oxidized cellulose, calcium polycarbophil) with fluids, unless there is a contraindication or risk factor(s) for serious adverse event(s)
- Intolerance or inadequate response to a 1-month trial of either PEG-3350 powder for oral solution (17 g twice daily) or other osmotic laxative, unless there is a contraindication or risk factor(s) for serious adverse event(s)
- Intolerance or inadequate response to a 1-month trial of lubiprostone (24 mcg twice daily)
Laxative Trial Specifications- Examples of osmotic laxatives: lactulose, sorbitol, magnesium citrate, magnesium hydroxide, glycerin rectal suppositories
- During the 1-month trial, escalation/titration of therapy up to bowel-prep doses of PEG-3350 may be considered case by case
Consultation Recommendations- GI consultation (including e-consult) is highly recommended prior to using plecanatide for CIC.
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ABOBOTULINUMTOXINA INJ,LYPHL
DYSPORT
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DYSPORT |
2017-02-27 |
Exclusion Criteria- Hypersensitivity to botulinum toxins or any components in the formulation (e.g., human serum albumin, lactose, sucrose, disodium succinate)
- Co-administration with neuromuscular blockade
- Neurologic condition where botulinum toxins pose risk for additive neuromuscular compromise (e.g., myasthenia gravis, amyotrophic lateral sclerosis), unless risks/benefits have been discussed with the patient and documented in the medical record
- Use for cosmetic purposes
Inclusion Criteria (Indications)- Cervical dystonia or focal dystonia
- Blepharospasm or hemifacial spasm
- Severe focal hyperhidrosis with inadequate response or unmanageable intolerance to prescription topical therapy (e.g., aluminum chloride hexahydrate 20% topical solution)
- Upper or lower limb spasticity
- Overactive bladder or neurogenic bladder dysfunction with contraindication, intolerance, or inefficacy to behavioral therapy and at least one pharmacotherapy (e.g., antimuscarinic agent, beta-3 adrenergic agonist)
- Chronic migraine prevention with contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 2 of the following: beta blocker, topiramate, divalproex, and ACE inhibitor or ARB
- Pharyngoesophageal segment spasm (PES)
- Sialorrhea with contraindication, intolerance, or lack of therapeutic response to anticholinergics and/or speech therapy
- Chronic anal fissure refractory to conservative treatment including supportive measures (e.g., dietary fiber, sitz bath) and topical vasodilator (e.g., topical nitrates)
- Esophageal achalasia if patient is not a candidate for surgery
- Idiopathic (primary or genetic) or symptomatic (acquired) torsion dystonia
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ADO-TRASTUZUMAB INJ
KADCYLA
|
KADCYLA |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity to ado-trastuzumab emtansine or its excipients (sodium succinate, sucrose, polysorbate 20)
- Baseline Left Ventricular Ejection Fraction (LVEF) < 50%
- Uncontrolled hypertension or arrhythmia requiring treatment
- Myocardial infarction within prior 6 months
- History of Congestive Heart Failure (New York Heart Association Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Breast tissue does not overexpress HER2 protein (HER2 positive status defined as IHC 3+ or FISH amplification ratio > 2.0)
- Platelet count < 100,000/ mm3
- Grade 3 or higher peripheral neuropathy
- Serum transaminases (ALT/AST) > 2.5x ULN and/or Total bilirubin > 1.5x ULN or active hepatitis B or C virus
- Interstitial Lung Disease or pneumonitis
Inclusion Criteria- Metastatic setting: Patient received prior treatment for metastatic breast cancer that includes trastuzumab and taxane (separately or in combo) OR disease recurred during or within 6 months of completing adjuvant therapy
- Adjuvant therapy: Patient with early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment
Additional Inclusion Criteria- Care for the condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0-2
Reproductive & Pregnancy Considerations- Pregnancy must be excluded prior to receiving therapy for patients who can become pregnant
- Counseling on potential risks vs benefits and use of effective contraception during therapy and for 7 months after stopping treatment for patients who can become pregnant
- Counseling on potential risks vs benefits and use of effective contraception during therapy and for 4 months after stopping treatment for patients with partners who can become pregnant
Exclusion Criteria- Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Interstitial lung disease or pneumonitis
- Pregnancy
- Lactating
- Primary Inclusion Criteria (One must be fulfilled)
- HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
- HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
- Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
- Care provided by VA or VA Community Care provider of oncology
- Goals of care and role of Palliative Care consult discussed and documented, if appropriate
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception Requirements (Select if applicable)
- For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose
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ALEMTUZUMAB INJ,SOLN
LEMTRADA
|
LEMTRADA |
2017-02-27 |
Exclusion Criteria- Secondary progressive MS with no clinical or MRI evidence of relapses
- Concurrent use of immune system modifying drugs (DMT) to treat MS (interferon beta-1B, glatiramer acetate, interferon beta 1A, natalizumab, mitoxantrone), unless the previous agent is discontinued when alemtuzumab is initiated
- Infection with Human Immunodeficiency Virus
- No documented baseline testing within 30 days prior to initiation: CBC with differential, LFT, and skin exam
- Positive test for tuberculosis
Inclusion Criteria- Patients with relapsing MS characterized by clearly defined acute attacks with full or partial recovery
- Must be prescribed and monitored by a VA neurologist or locally designated MS Specialist
- AND meet at least one of the following conditions:
- Loss of clinical response or intolerance to at least two DMTs (injectable: interferon beta 1a, interferon beta 1b, glatiramer; oral: dimethyl fumarate, fingolimod, teriflunomide); if serum JCV Ab negative, a trial of natalizumab is required
- Currently on natalizumab therapy with development of risk factors for PML (duration > 24 months, anti JC virus antibody positive, or received immunosuppressant therapy prior to natalizumab)
- Highly aggressive disease demonstrated by heavy burden of MRI T2 lesions, presence of multiple enhancing lesions at onset, high burden of gadolinium enhancing lesions, or rapid accrual of disability
Dosage & Administration- Recommended dosage: 12 mg/day administered by intravenous infusion for 5 consecutive days, followed by three consecutive daily infusions 1 year later
- Subsequent treatment courses: 12 mg per day on 3 consecutive days (36 mg total dose) may be administered as needed, at least 12 months after the last dose of any prior treatment course
- Must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions
- Monitor patients for 2 hours after each infusion; inform patients that serious infusion reactions can also occur after the 2-hour monitoring period
Premedication Requirements- High dose corticosteroids (1,000 mg methylprednisolone or equivalent) immediately prior to alemtuzumab infusion and for the first 3 days of each treatment course
- Anti-viral prophylaxis for herpetic viral infections starting on the first day of each treatment course, continuing for a minimum of two months following treatment or until CD4+ lymphocyte count is > 200 cells per microliter (whichever occurs later)
Monitoring Requirements- CBC with differential, serum creatinine levels, and urinalysis with urine cell counts and urine protein to creatinine ratio: prior to initiation and monthly until 48 months after the last infusion
- Thyroid function tests: prior to initiation and every 3 months until 48 months after the last infusion (monitoring may continue past 48 months based on clinical findings)
- Skin examination for melanoma: prior to treatment and yearly thereafter
- HPV screening for female patients: annually
- Annual brain MRI by CMSC Protocol
Safety, Black Box Warnings & REMS Restrictions- Available only through restricted distribution under a Risk Evaluation Mitigation Strategy (REMS) program due to risks of autoimmunity, infusion reactions, and malignancies
- Black Box Warning for serious, sometimes fatal autoimmune conditions such as immune thrombocytopenia and antiglomerular basement membrane disease (anti-GBM)
- Anti-GBM disease may develop end-stage renal disease requiring dialysis or renal transplantation; alveolar hemorrhage (hemoptysis) is a common component; cases diagnosed up to 40 months after the last dose
- Associated with increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders
Infection Risks & Clinical Considerations- Serious and life-threatening stroke (ischemic and hemorrhagic) reported within 3 days; instruct patients to seek immediate medical attention if symptoms occur
- Evaluate for varicella zoster virus infection history or vaccination prior to initiation; if negative, vaccinate with live varicella virus product (Varivax®), wait at least six weeks after completing two doses before initiating therapy
- Do not administer live viral vaccines for at least 2 months after a course or until CD4+ lymphocyte count is > 200 cells per microliter
- Consider delaying alemtuzumab in persons with active infection until the infection is fully controlled
- Fungal infections and Listeria meningitis occur with increased frequency; counsel patients to not consume foods associated with Listeria prior to infusion
- Symptoms of Listeria infection can be difficult to distinguish from infusion reactions
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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ALIROCUMAB INJ,SOLN
PRALUENT PEN
|
PRALUENT PEN |
2017-02-27 |
Exclusion Criteria- End-stage renal disease on dialysis
- Advanced heart failure with limited prognosis
- Severe comorbid non-cardiovascular condition that is expected to limit life expectancy
- Pregnant or lactating status
- Primary Inclusion Criteria (One must be met)
- History of atherosclerotic cardiovascular disease (ASCVD)
- Severe primary hypercholesterolemia (e.g., heterozygous familial hypercholesterolemia [HeFH], LDL-C > 190 mg/dL) without ASCVD
- Additional Inclusion Criteria (All must be met)
- Contraindication, intolerance to, or insufficient LDL-C reduction with maximally tolerated dose of statin, requiring further LDL-C lowering to reduce ASCVD risk consistent with established guidelines
- Contraindication, intolerance to, or insufficient LDL-C reduction with ezetimibe, requiring further LDL-C lowering to reduce ASCVD risk consistent with established guidelines
Additional Inclusion Criteria (Select if Applicable)- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Statin Intolerance & Management Guidelines- Statins remain the treatment of choice; PCSK9 inhibitors augment LDL-C lowering when used with statins
- Documented statin intolerance requires a trial of at least 2 statins resulting in intolerable unexplained skeletal muscle-related complaints (pain/ache, weakness, or cramping) that resolve upon discontinuation
- One statin causing symptoms must be trialed at the lowest approved dose; alternate day dosing should be attempted
- Evaluate and address factors increasing risk for statin intolerance or non-statin causes of muscle symptoms (e.g., hypothyroidism, vitamin D deficiency, drug-drug interactions, excessive alcohol use)
- Patients on lower than optimal statin doses should receive ezetimibe as second-line therapy
- For patients on suboptimal statin doses plus ezetimibe: Consider PCSK9 inhibitor if LDL reduction from untreated baseline is less than clinically desired and/or LDL-C goal is not achieved despite confirmed adherence
- For completely statin-intolerant patients: Consider PCSK9 inhibitor if ezetimibe has not/is not expected to provide clinically desired LDL-C reduction or achieve LDL-C goal despite confirmed adherence
High-Risk Patients Without Established ASCVD- Utilize ezetimibe, bile acid sequestrant (BAS), or combination in appropriate candidates
- For high-risk patients (e.g., diabetes mellitus, 10-year risk score > 20%, presence of subclinical atherosclerosis by imaging including coronary artery calcium assessment and coronary CT): Consider PCSK9 inhibitor if LDL-C is not reduced by a clinically meaningful percentage from baseline (>30% or >50% based on risk/need) and/or goals are not reached despite confirmed adherence
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ANAKINRA INJ,SOLN
KINERET
|
KINERET |
2017-02-27 |
Indication & Patient Population- Hospitalized patients with severe COVID-19
- Positive SARS-CoV-2 direct viral test
- Requirement for supplemental oxygen (low or high-flow)
- At risk for progressing to severe respiratory failure
- Likely to have elevated plasma soluble urokinase plasminogen activator receptor (suPAR)
Dosing & Administration- Adults: 100 mg subcutaneously daily for up to 10 days
- Renal insufficiency (severe or end-stage renal disease): 100 mg every other day for a total of 5 doses over 10 days
- Supplied as prefilled syringe (100 mg/0.67 mL) intended for single use; discard any unused portion after dosing
- Do not administer if solution is discolored, cloudy, or contains particulate matter
Surrogate Markers for Elevated suPAR (≥ 6 ng/mL)- At least 3 of the following criteria: Age ≥ 75 years, severe pneumonia by WHO criteria, SOFA score ≥ 3, neutrophil to lymphocyte ratio ≥ 7, hemoglobin ≥ 10.5 g/dL, medical history of ischemic stroke, blood urea ≥ 50 mg/dL and/or history of renal disease
- Predictors of favorable response (at least 2 of the following): CRP > 50 mg/L, neutrophil to lymphocyte ratio > 5.5, ferritin > 700 ng/mL, AST > 44 U/L
Contraindications- Known hypersensitivity to E.coli derived proteins, anakinra, or any components of the product
Warnings & Precautions- Serious infections: Monitor for signs and symptoms of new infections during and after treatment; limited data available for patients with concomitant active serious infections
- TNF blocking agents: Not recommended for concurrent use due to increased risk of serious infections
- Hypersensitivity reactions (including anaphylaxis and angioedema): Discontinue anakinra and initiate appropriate therapy if severe reaction occurs
- Immunosuppression: Impact on development of malignancies is unknown
- Immunizations: Avoid use of live vaccines; no data available for other inactivated vaccines or effects of live vaccination on secondary transmission
Monitoring & Safety Requirements- Assess neutrophil counts prior to initiation; monitor for neutropenia per current clinical practices (patients with ANC < 1500 cells/mm3 were excluded from trials)
- Monitor closely for unusual clinical or laboratory events, record per local policy, and report to VA ADERS
Special Populations- Pregnancy: Insufficient data to identify drug-associated risk of maternal or fetal adverse events; animal studies showed no evidence of fetal harm at doses up to 25 times the maximum recommended human dose
- Lactation: No data on presence in human or animal milk; risk to infant during lactation is unclear
- Geriatric: Higher incidence of infections in elderly population; use caution
EUA Administrative & Prescribing Requirements- Patient must meet all criteria outlined in the FDA Emergency Use Authorization
- Healthcare providers must communicate information from the "Fact Sheet for Patients, Parents and Caregivers" prior to administration (unless delay endangers life)
- Patient or surrogate decision maker has the option to accept or refuse therapy
- All medication errors and adverse drug events must be documented per local policy and reported to VA ADERS within 7 calendar days
Indication & Patient Population- Hospitalized adults requiring supplemental oxygen (low or high-flow) for COVID-19
- Patients at risk of progressing to severe respiratory failure
Diagnostic & Clinical Status Requirements- Laboratory confirmed COVID-19 diagnosis
- Requiring supplemental oxygen (low- or high-flow oxygen)
- At risk for progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR)
Contraindications & Precautions- Known hypersensitivity to ANA, E.coli derived proteins, or any component of the product
- Concurrent use of TNF blocking agents
Risk Stratification for Elevated suPAR- Likely to have suPAR levels ≥ 6 ng/mL at baseline if meeting at least 3 of the following criteria: age ≥ 75 years, severe pneumonia by WHO criteria, current/previous smoker, SOFA score ≥ 3, neutrophil-to-lymphocyte ratio (NLR) ≥ 7, hemoglobin ≤ 10.5 g/dL, history of ischemic stroke, blood urea ≥ 50 mg/dL, and/or history of renal disease
Dosing & Administration- 100mg as a subcutaneous injection daily for 10 days
- Consider reducing the dose to 100mg every other day in patients with severe renal insufficiency or end-stage renal disease (CrCl < 30 mL/min)
Counseling, Documentation & Safety Monitoring- Counseling provided and documented per EUA, including: communication consistent with the “Fact Sheet for Patients and Parents/Caregivers,” documentation of fact sheet provision, informing patient it is an unapproved drug authorized under EUA, discussing alternatives/risks/benefits, and right to refuse/accept
- Exception: If providing fact sheet information delays administration to endanger life, provide to caregiver as soon as feasible after administration (document in record)
- Patient advised to notify provider if any adverse drug event (ADE) occurs
- All ADEs and medication errors (with interventions) must be recorded per local policy AND placed in VA ADERS within 7 calendar days of notification, with MedWatch reporting selection
- Appropriate storage maintained until administration consistent with authorization terms
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APIXABAN TAB,ORAL
ELIQUIS
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ELIQUIS |
2017-02-27 |
Indications- Atrial fibrillation/flutter (AF)
- Acute venous thromboembolism (VTE), or prevention of recurrent VTE
- Primary prophylaxis of VTE in patients undergoing hip or knee replacement surgery
- Other indication for anticoagulation (local adjudication required)
Exclusions- Mechanical heart valve
- Moderate to severe rheumatic mitral valve stenosis (for AF/flutter only)
- Antiphospholipid syndrome (APS)
- Known significant liver disease (e.g., acute clinical hepatitis, cirrhosis [Child-Pugh C], or hepatic disease associated with coagulopathy)
- Pregnancy
- Breastfeeding
Pre-Treatment Assessment & Monitoring- Assessment of renal function (CrCl) and hemoglobin, hematocrit, and platelets
- Consider liver function testing in patients with a history of or risk for hepatic insufficiency
- Provider must assess DOAC choice, dose, and duration considering patient’s age, renal function, liver function, concurrent medications, and indication
- Identify and address modifiable risk factors for bleeding (e.g., NSAIDs, antiplatelet therapy)
- Document the treatment plan including duration in the patient’s chart
Dosing & Administration Requirements- For acute VTE: Administer 10 mg twice daily for 7 days as oral loading dose BEFORE starting maintenance doses
- Review drug dosing errors and drug-drug interactions, especially with new starts
Special Populations & Clinical Considerations- Bioprosthetic heart valve placement in the past 3 months: Appropriate based on shared decision-making process between provider and patient
- Severe renal impairment (CrCl <25-30 ml/min) or hemodialysis: Individual evaluation of risks and benefits recommended; net clinical benefit unclear
- Apixaban may be the preferred DOAC when CrCl is less than 30 ml/min
- For patients who can become pregnant: Counsel on potential risks vs benefits of treatment and use of effective contraception during therapy
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
FDA Approved Adult Indications- Non-valvular atrial fibrillation
- Treatment of DVT and PE (after 5-10 days of parenteral anticoagulant)
- Reduction in the risk of recurrent DVT and PE following initial therapy
- Post-surgical VTE prophylaxis following hip replacement surgery
- Post-surgical VTE prophylaxis following knee replacement surgery
Oversight & Initiation- Chronic DOAC therapy requires initial assessment, education, and follow-up by locally designated staff (e.g., anticoagulation management program or other designees).
- Facilities should utilize decision support tools and/or anticoagulation staff for upfront review to verify appropriate candidate selection, agent choice, and dosing upon initiation.
- Short-term treatment (e.g., post-surgical VTE prophylaxis) or very low dose regimens should follow education/monitoring protocols similar to alternative agents in that setting.
Laboratory Monitoring- Baseline: Serum creatinine (SCr) to estimate creatinine clearance (CrCl); CrCl estimated using Cockcroft-Gault equation with actual body weight for apixaban trials. Hemoglobin, hematocrit, and platelets required. Liver function tests may be considered for patients with history/risk of hepatic insufficiency. PT/aPTT may be obtained for emergency reference. Baseline values drawn within 1-3 months are acceptable per provider clinical judgment based on age/health status/comorbidities.
- Follow-up: SCr monitored at least annually (more frequently if CrCl < 60 ml/min, concomitant illness worsening renal function, or age ≥ 75 years). Hemoglobin, hematocrit, and platelets monitored at least annually or as clinically dictated. Liver function testing considered for underlying liver disease or clinical indication.
Patient Education- Initial and periodic education must cover: capsule/tablet identification, proper storage, therapy indication, risks/benefits, anticipated duration, daily dose/dosing changes (e.g., loading doses), administration considerations, drug interactions, monitoring requirements, adherence importance, management of missed/extra doses, signs/symptoms of bleeding/thromboembolic events, avoidance of major bleeding risk medications (e.g., NSAIDs, antiplatelets) unless instructed, non-bleeding adverse events, fall risks/mitigation, medication supply acquisition, pre-procedure provider notification for peri-procedural management, anticoagulation provider contact information, and gender-specific considerations for women of childbearing age (menstrual difficulties, pregnancy, contraception).
Adherence Monitoring- Monitor adherence, refill history, and medication tolerance, especially at therapy initiation.
- Utilize population management tools, telephone follow-up, face-to-face visits, secure messaging, or combinations based on site resources.
Follow-up Care- Initial: Within 2-4 weeks of initiation (or sooner if clinically indicated) to assess tolerance, bleeding, thromboembolic events, other adverse events (e.g., GI intolerance), adherence, correct dosing (e.g., transition from high-intensity initiation dosing for acute VTE), duplicate therapy, and reinforce education.
- Periodic/Long-term: Reassess adherence, screen for drug interactions, monitor labs as needed. Time points, methods, and responsible staff determined locally per VHA Directive 1108.16(1).
Quality Assurance- Incorporate DOACs into ongoing quality assurance plans per VHA Directive 1108.16(1).
- Report adverse events per local protocols and P&T Committee; enter into VA ADERS.
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APREMILAST TAB,ORAL
OTEZLA
|
OTEZLA |
2017-02-27 |
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy of apremilast
- Untreated or unstable depression or suicidality, unless a mental health consultant concurs with apremilast treatment
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Adult (18 years of age or older) with recurrence of 2 or more oral ulcers associated with Behçet's disease
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy of apremilast.
- Untreated or unstable depression or suicidality unless mental health consultation concurs with apremilast treatment.
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care dermatologist or locally-designated expert.
- Diagnosis of plaque psoriasis.
- Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate.
Additional Inclusion Criteria (One must be met)- Documented mild to moderate disease AND tried and had an inadequate response to ≥ 3 classes of topical therapies (≥ 1 month per class) or intolerance unless medically inadvisable (prior trials not required).
- Documented moderate to severe disease, impaired function or quality of life, or involvement of special areas AND 1 conventional immunomodulator and 2 classes of targeted immunomodulators are medically inadvisable (prior trials not required).
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
Indication- Treatment of adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy
- FDA-approved for mild to moderate plaque psoriasis (expanded indication December 2021)
Patient Eligibility & Diagnosis- Documented diagnosis of plaque psoriasis for ≥ 6 months
- Patients must be cared for by a VA or VA Community Care dermatologist
Prior Therapy Requirements- Inadequate response to 2 or more topical therapies (e.g., corticosteroids in different potencies, vitamin D analogs such as calcipotriene or calcitriol, calcineurin inhibitors such as tacrolimus or pimecrolimus for sensitive areas, or retinoids such as tazarotene)
- Phototherapy is medically inadvisable, not available, not feasible, not tolerated, or not adequate
Dosing & Administration- Initiated with a 5-day upward dosage titration to a maintenance dose of 30 mg orally twice daily starting on Day 6
- Slowly up-titrate dosage
Safety & Monitoring Considerations- No routine lab monitoring required
- Decrease dose for renal impairment
- Monitor for GI AEs/diarrhea (risk of dehydration in elderly)
- Avoid strong CYP3A4 inducers
Place in Therapy Considerations- Used as monotherapy
- Appropriate for patients who prefer to avoid frequent injections and lab monitoring and are willing to accept delayed onset and lower chance of skin clearance
- Alternative systemic therapies (methotrexate, cyclosporine, retinoids, targeted biologic agents including TNF inhibitors, IL-12/23 inhibitors, IL-17A inhibitors, IL-17A receptor inhibitor, and IL-23 inhibitors) may be considered for mild to moderate psoriasis recalcitrant to therapies approved for mild–moderate plaque psoriasis including apremilast
Exclusion Criteria- Concomitant therapy with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy
- Untreated or unstable depression or suicidality, unless a mental health consultant concurs with apremilast treatment
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Nonsevere or predominantly oligoarticular peripheral inflammatory disease and a definite or provisional diagnosis of active psoriatic arthritis (note: ineffective for joint erosions and axial disease)
- Conventional synthetic immunomodulator (methotrexate, leflunomide or sulfasalazine) is medically inadvisable, not tolerated, or not adequate after 12 weeks
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable
Additional Inclusion Criteria for Patients Who Can Become Pregnant- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Clinical Adjudication & Supplemental Considerations- Conventional synthetic immunomodulator: Adequate trial requires NO or partial treatment benefit after 12 weeks at doses of 15–25 mg/wk (or lower if limited by toxicity); for inadequate responders, consider switching to subcutaneous methotrexate. For other immunomodulators, require NO or partial treatment benefit after 12 weeks at recommended doses (or lower if limited by toxicity).
- TNFI therapy: Prior trial is not required but should be recommended if medically advisable. For TNFI inadequate/nonresponders, consider switching to a second TNFI, another biologic, or tofacitinib rather than apremilast monotherapy.
- TNFI may be medically inadvisable due to heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent infections, serious infections, etc.
- Aversity to injections or barriers to in-clinic administration (e.g., travel) should be adjudicated case by case as a reason why a TNFI is medically inadvisable.
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ARIPIPRAZOLE INJ,SUSP,SA
ABILIFY ASIMTUFII, ABILIFY MAINTENA, ARISTADA, ARISTADA INITIO
|
ABILIFY ASIMTUFII, ABILIFY MAINTENA, ARISTADA, ARISTADA INITIO |
2017-02-27 |
Transitioning Veteran Criteria- Veteran is transitioning care from the Department of Defense to VHA.
- A VA prescriber has assessed and consulted with the Veteran, determining that continuing the medication is safe and clinically appropriate.
- Exclusion Criteria (Patient should NOT receive a long-acting injectable antipsychotic if any apply)
- Patient has never taken the ordered long-acting injectable antipsychotic in any formulation (e.g., oral).
- Patient has a hypersensitivity to the ordered antipsychotic.
- For Aripiprazole: Patient is taking a CYP3A4 inducer.
- For Aripiprazole: Patient is taking a CYP2D6 AND CYP3A4 inhibitor.
- Inclusion Criteria – Mandatory Requirements (All must be met)
- Diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder.
- Prescriber is a VA Mental Health Provider.
- Patient has taken and tolerated the ordered antipsychotic prior to receiving it as a LAI for an adequate length of time.
- Patient will be transitioned from oral medication to the long-acting injectable per guidelines/manufacturer recommendations.
- Inclusion Criteria – Conditional Requirements (One must be met)
- Patient has relapsed or been hospitalized for the intended indication or complications due to nonadherence when treated with oral antipsychotics.
- Patient’s care environment makes a LAI a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely).
Transitioning Veteran- Veteran is transitioning care from the Department of Defense to VHA, and a VA prescriber has determined continuing the medication is safe and clinically appropriate. (If met, remainder of criteria does not apply)
- Exclusion Criteria (Patient should NOT receive a long-acting injectable antipsychotic if any are met)
- Patient has never taken the ordered long-acting injectable antipsychotic in any formulation (e.g., oral)
- Patient has hypersensitivity to the ordered antipsychotic
- For Aripiprazole (Aristada Initio only): Patient is a known CYP2D6 poor metabolizer, or is receiving a benzodiazepine, antihypertensive drugs, strong CYP3A4 inducers, a strong CYP3A4 inhibitor, or a strong CYP2D6 inhibitor
- Inclusion Criteria (Patient must meet ALL of the following)
- Diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder
- Prescriber is a VA Mental Health Provider
- Patient has taken and tolerated the ordered antipsychotic prior to receiving it as a long-acting injectable for an adequate length of time
- Patient will be transitioned from oral medication to the long-acting injectable per guidelines/manufacturer recommendations
- Inclusion Criteria (Patient must meet ONE of the following)
- Patient has relapsed or been hospitalized for the intended indication or complications due to nonadherence when treated with oral antipsychotics
- Patient’s care environment makes a long-acting injectable a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely)
Transitioning Veteran- Veteran is transitioning care from the Department of Defense to VHA
- VA prescriber has assessed and consulted with the Veteran and determined that continuing the medication is safe and clinically appropriate
- (Note: If met, remainder of criteria for use is not applicable)
- Exclusion Criteria (Patient should NOT receive a long-acting injectable antipsychotic if ANY are met)
- Patient has never taken the long-acting injectable antipsychotic ordered in any formulation (e.g., oral)
- Patient has a hypersensitivity to the antipsychotic ordered
- For Aripiprazole (Abilify Maintena): patient is taking a CYP3A4 inducer
- Inclusion Criteria (ALL of the following must be met)
- Diagnosis of schizophrenia or schizoaffective disorder, or bipolar disorder
- Prescriber is a VA Mental Health Provider
- Patient has taken and tolerated the antipsychotic ordered prior to receiving it as a LAI for an adequate length of time
- Patient will be transitioned from oral medication to the long-acting injectable per guidelines/manufacturer recommendations
- Inclusion Criteria (ONE of the following must be met)
- Patient has relapsed or been hospitalized for the intended indication or complications of the intended indication because of nonadherence when treated with oral antipsychotics
- Patient’s care environment is such that a LAI is a more reliable route of administration (e.g., homeless, lack of medication supervision, or the medication cannot be stored safely)
Indications- • Treatment of schizophrenia in adults
- • Maintenance monotherapy treatment of bipolar I disorder in adults
Patient Selection & Clinical Context- • Typically reserved for patients who are nonadherent with or do not prefer oral medications
- • May be an appropriate choice for patients who have responded to oral aripiprazole and require a long-acting injectable (LAI) antipsychotic for adherence
Administration & Dosing Requirements- • Intramuscular (IM) gluteal injection every 2 months
- • Available as 720 mg/2.4 mL or 960 mg/3.2 mL injections
- • Requires oral supplementation for 14 days after the initial injection
- • Early maintenance dose is allowed up to 2 weeks before the next scheduled dose due
Safety, Warnings & Precautions- • Not approved for elderly patients with dementia-related psychosis (increased risk of death)
- • Monitor for: Cerebrovascular adverse reactions in elderly patients with dementia-related psychosis, Neuroleptic Malignant Syndrome, Tardive Dyskinesia, Metabolic Changes, Pathological Gambling and Other Compulsive Behaviors, Orthostatic Hypotension and Syncope, Leukopenia/Neutropenia/Agranulocytosis, Seizures, Potential for Cognitive and Motor Impairment
- • Adverse reactions observed in ≥2% of adult patients with schizophrenia (vs. placebo): Constipation, Dry Mouth, Diarrhea, Vomiting, Abdominal Discomfort, Injection Site Pain, Upper Respiratory Tract Infection, Increased Weight, Decreased Weight, Arthralgia, Back Pain, Myalgia, Musculoskeletal pain, Akathisia, Sedation, Dizziness, Tremor, Nasal Congestion
Specific Populations- • Pregnancy: Insufficient data to inform drug-associated risk. Neonates exposed during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorder). Monitor neonates exhibiting these symptoms and manage appropriately. Consider benefits/risks to fetus when prescribing.
- • Lactation: Present in human breast milk; insufficient data on amount, effects on breastfed infant, or effects on milk production. Weigh development/health benefits of breastfeeding against the mother's clinical need and potential adverse effects on the infant.
Place in Therapy & Use Considerations- • Chief advantage: Lower risk for metabolic effects (e.g., weight gain) compared to other atypical antipsychotics; convenient every-2-month dosing may aid patients with scheduling difficulties
- • Disadvantages/Barriers: May be unsuitable for patients unable or unwilling to receive a gluteal injection; requirement for 2-week oral overlap may lead to non-adherence, mistaken continuation past the 2-week period (increasing side effect risk), or decreased treatment efficacy/relapse risk; no manufacturer-recommended conversions when switching from oral to this formulation
Indications- Schizophrenia in adults
- Maintenance monotherapy treatment of bipolar I disorder in adults
Administration & Preparation- Route: Intramuscular (IM) injection into deltoid or gluteal muscle
- Refrigeration: Not required
- Reconstitution/Shaking Requirements:
- Aripiprazole Maintena: Room temperature; shake 20 seconds (pre-filled syringe) or 30 seconds (vial)
- Aripiprazole Aristada: Tap 10x + shake 30 seconds (syringe)
- Aripiprazole Asimtufii: Tap 10x + shake 10 seconds (syringe)
Dosing & Scheduling- Aripiprazole Maintena: Monthly dosing; conversions include 15mg oral to 300mg IM monthly, and 20mg oral to 400mg IM monthly
- Aripiprazole Aristada: Monthly, q6 weeks, or q2 months dosing; conversions include 10mg oral to 441mg IM monthly, 15mg oral to 662mg IM monthly/882mg q6wks/1064mg q2months IM, and 20mg oral to 882mg IM monthly
- Aripiprazole Asimtufii: Q2 months dosing; conversion includes 400mg IM qmonth to 960mg q2months
Oral Overlap Requirements- Maintena and Asimtufii: Require 14-day oral overlap
- Aristada: Requires 21-day oral overlap unless administered with Initio (675mg) plus a 30 mg oral dose, which eliminates the need for oral overlap
Formulary & Logistical Considerations- Formulary status: PA-F with CFU for all three dosage forms
- Medication selection should be based on patient-specific characteristics, patient preferences, and medication side effect profiles per the 2023 VA/DoD CPG for Schizophrenia
- Aristada represents 41% market share among aripiprazole LAIs, has a high PADR approval rate, and is the least expensive LAI among the aripiprazole products
- To avoid oral overlap, Aristada should be administered with Initio for maximum benefit and may be administered monthly or q2months (1064mg only)
- Reported adverse drug events (ADEs) are low, pharmacologically expected, and similar across all aripiprazole LAI dosage forms
- Logistical considerations include route of administration, oral overlap requirements, staff education for administration (duration product must be shaken, injection speed, injection location), refrigeration requirements, and cost
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ATEZOLIZUMAB INJ,SOLN
TECENTRIQ
|
TECENTRIQ |
2017-02-27 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy (i.e., known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Indication is FDA approved
- Off-label use supported by high-level published data
Additional Inclusion & Practice Requirements- Care provided by a VA/VA Community Care oncology or hematology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Contraception counseling for female patients of child-bearing potential and male patients with female partners of child-bearing potential regarding risks vs. benefits; effective contraception required during therapy and for 5 months after the last dose
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Lactating
Inclusion Criteria- Indications & Administration
- Indication is FDA approved
- Off-label use supported by high-level published data
- If administering with chemotherapy and/or bevacizumab, administer prior to chemotherapy and/or bevacizumab if given on the same day
- Care Coordination & Documentation
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Performance Status
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Reproductive Health & Contraception
- Female patients of child-bearing potential and male patients with female partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment. Use effective contraception during therapy and for 5 months after the last dose.
- Product Substitution/Transition
- Do not substitute atezolizumab/hyaluronidase SubQ for atezolizumab IV on a mg per mg basis. Patients may transition products at the next dose.
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AXITINIB TAB
INLYTA
|
INLYTA |
2017-02-27 |
Exclusion Criteria- Major surgery in the previous 4 weeks
- Active (unstable) CNS metastasis (stable brain metastases not requiring steroids is allowed)
- Uncontrolled hypertension
- Current serious wound that is not healing
- Clinically significant gastrointestinal disorder (e.g., active GI bleeding, intraluminal metastatic disease with suspected bleeding, inflammatory bowel disease, ulcerative colitis, other GI conditions associated with an increased risk of perforation)
- Uncontrolled active infection
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
- Caution with use in untreated deep vein thrombosis or pulmonary embolism
Inclusion Criteria- Care provided by a VA/VA purchased care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Goals of care and role of Palliative Care consult have been discussed and documented
- Female patients of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment
- Males with female partners of child-bearing potential: use effective contraception during therapy and for 1 week after the last dose
Indications & Regimens (Additional Inclusion Criteria)- In combination with pembrolizumab for first-line treatment of advanced renal cell carcinoma
- As a single agent for treatment of advanced renal cell carcinoma after failure of 1 prior systemic therapy
Monitoring & Safety Cautions- Avoid concomitant CYP3A/4 inhibitors (including grapefruit juice); if unavoidable, reduce axitinib dose. Avoid strong CYP3A/4 inducers.
- At baseline, assess blood pressure and dipstick urine for protein; monitor both periodically during therapy.
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AZACITIDINE INJ,LYPHL
VIDAZA
|
VIDAZA |
2017-02-27 |
Diagnosis & Initial Therapy- Initial therapy for myelodysplastic subtypes: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), chronic myelomonocytic leukemia (CMMoL)
- Must be accompanied by neutropenia OR thrombocytopenia OR clinical hemorrhage requiring platelet transfusions OR anemia requiring red blood cell transfusions
- Restricted to use by VA Hematologists and Oncologists
Exclusion Criteria- ECOG Performance Status >2
- Serum Creatinine > 1.5 X ULN
- Diagnosis of metabolic acidosis
- Total bilirubin > 1.5 X ULN
- AST/ALT > 2 X ULN
- Extensive hepatic tumor burden due to metastatic disease
- Uncontrolled congestive heart failure
- Hypersensitivity to mannitol
- Life expectancy < 4 months
- Pregnancy
- Women actively breastfeeding
Discontinuation Criteria- Progression of disease during initial 4 months of treatment
- Stable disease after initial 4 months of treatment
- Unacceptable toxicity
- Relapse after initial response:
- • >5% myeloblasts in bone marrow (from complete response)
- • >30% bone marrow blasts (from partial response)
- • Return of peripheral blood counts to pretreatment values or recurrence of transfusion requirements (from improvement)
- Transformation to Acute Myelogenous Leukemia
Monitoring- Complete blood counts and assessment of renal function prior to each cycle and as needed
- Premedicate with oral prochlorperazine or oral ondansetron
- If no beneficial bone marrow effect from initial dose by day 57 without significant toxicity, increase dose to 100mg/m2/day for 7 days (optional)
- Assess effect on bone marrow after fourth cycle (day 113) (optional)
- Reduce dose by 50% on next course for unexplained reductions in serum bicarbonate to < 20 mEq/L; assess for renal tubular acidosis (alkaline urine, hypokalemia to <3 mEq/L along with drop in serum bicarbonate)
- If unexplained increase in BUN or serum creatinine, delay dose until values return to normal or baseline, then resume at 50% dose reduction on next course
Additional Definitions & Requirements- Neutropenia defined as ANC <1.0 x 109/L and thrombocytopenia defined as platelets ≤50 x 109/L
- Women of child-bearing potential and men with the potential to father a child should use adequate contraception methods
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BAZEDOXIFENE/ ESTROGENS TAB,ORAL
DUAVEE
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DUAVEE |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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BELATACEPT INJ,LYPHL
NULOJIX
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NULOJIX |
2017-02-27 |
General Criteria Structure- All mandatory inclusion criteria must be met.
- At least one additional inclusion criterion must also be met.
Transplant Recipient Status & Clinical Indications- Veteran is a kidney transplant recipient
- Chronic allograft nephropathy or calcineurin inhibitor (CNI) toxicity on biopsy
- Unmanageable CNI intolerance (e.g., tremors, headache, thrombotic microangiopathy, post-transplant diabetes)
- Preference for avoidance or minimization of long-term CNI exposure
- Chronic antibody-mediated rejection or donor-specific antibody suppression
Provider & Care Coordination Requirements- Requesting provider must be a nephrologist or post-kidney transplant designee (e.g., locally designated expert)
- Documentation must show concurrent communication with the transplant team
Infectious Disease Screening & Safety- Veteran must be Epstein-Barr seropositive
- No active or untreated infections
- Tuberculosis screening completed within the past year (e.g., QuantiFERON gold)
Special Populations & Pregnancy Considerations- For women of childbearing age: Confirm no alternative treatment exists and benefits outweigh risks due to limited/conflicting information regarding fetal harm risk.
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BISMUTH SUBSALICYLATE SUSP,ORAL
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2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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BISMUTH SUBSALICYLATE TAB,CHEWABLE
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2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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BLINATUMOMAB INJ,LYPHL
BLINCYTO
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BLINCYTO |
2017-02-27 |
Indications- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
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BOOST LIQUID,NUTRITIONAL SUPPLEMENT
BOOST BREEZE
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BOOST BREEZE |
2017-02-27 |
Inclusion Criteria- VA / VA Community Care provider or Registered Dietitian
- Patient requires a fat-restricted, fat-malabsorptive, or clear liquid diet
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BUDESONIDE INHL,NASAL
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2017-02-27 |
Inclusion Criteria- Patient had an inadequate response to or is unable to tolerate fluticasone propionate nasal inhaler/spray
→ Full criteria details
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BUPRENORPHINE TAB,SUBLINGUAL
BUPRENORPHINE HCL, SUBUTEX
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BUPRENORPHINE HCL, SUBUTEX |
2017-02-27 |
Perioperative Pain Management Principles- Buprenorphine treatment should not be routinely discontinued in the perioperative period for patients on stable MOUD therapy.
- Discontinuation may confer medical risks including return to active opioid use (50-90%), risk of overdose, prolonged hospital stay, and increased patient burden.
- A buprenorphine taper to < 16 mg/day may be considered for patients prescribed higher doses (> 16 mg) with anticipated high post-surgical pain.
- Utilize a multimodal pain approach including systemic non-opioid analgesics (acetaminophen, NSAIDs, gabapentinoids, ketamine, magnesium, systemic lidocaine, alpha-2 agonists, glucocorticoids), regional/local analgesics, and psychosocial interventions.
- When a full μOR agonist is needed to adequately control perioperative pain, use opioids with similar lipophilicity and binding affinity toward μORs; fentanyl and hydromorphone are reasonable alternatives.
Pre-operative Assessment & Planning- Perform patient evaluation including pain history, physical examination, medication reconciliation, assessment of physical/psychiatric comorbidities, and urine drug monitoring (including methadone, fentanyl, buprenorphine/metabolites).
- Verify prescription adherence via PDMP database.
- Conduct universal substance use disorder screening; perform detailed questioning and appropriate referrals for positive responses.
- Provide pre-operative counseling with written instructions regarding risks of opioid exposure/undertreating pain as relapse triggers.
- Determine procedure-related pain severity (minimal/no pain vs. significant pain) to guide dose adjustment or continuation.
- Plan continuity of care: taper off short-acting opioids prior to discharge; restrict IR opioids to short-term rescue use perioperatively; coordinate with waivered provider/OUD team for outpatient post-op pain care; preschedule follow-up with OUD/chronic pain provider; ensure sufficient buprenorphine supply at discharge.
Elective Procedure Management Criteria- For most patients, continue buprenorphine throughout the operative period.
- Minimally painful surgery: Continue current home dose unchanged, or divide and administer every 6 to 8 hours. Total daily dose may be titrated up to 32 mg/day in divided doses if needed for pain management (does not apply to extended-release injection).
- Painful surgery (moderate/severe pain): Continue baseline dose > 16 mg/day, OR reduce to < 16 mg/day to allow addition of an IR full μOR agonist. Expect higher doses of full μOR agonists requiring close monitoring (e.g., ICU or step-down unit).
- Examples of minimal pain procedures: tooth extraction, endoscopy, colonoscopy, bronchoscopy.
- Examples of moderate/severe pain procedures: laparoscopic, intra-abdominal, intra-thoracic, and orthopedic procedures.
Emergent Procedure Management Criteria- Anticipated minimal to no pain: Continue buprenorphine throughout procedure with non-opioid medications. Dose may be increased until adequate pain relief is achieved. Taper off short-acting opioids prior to discharge.
- Anticipated moderate to severe pain (Continue method): Continue buprenorphine throughout operation; increase dose postoperatively (except implant or BUP XR INJ) or use short-acting opioids. Taper off short-acting opioids prior to or shortly after discharge.
- Anticipated moderate to severe pain (Discontinue method): Discontinue per specified discontinuation criteria.
Discontinuation Criteria & Management- Discontinuation is indicated only when: patient requests to stop (after discussing pros/cons with provider and OUD team); medical contraindication exists; or all other options (maximizing dose, splitting dose, multimodal therapy) are insufficient.
- Emergency procedures: Discontinue immediately upon admission in lieu of high-dose short-acting μOR agonist.
- Elective procedures: Discontinue 24-72 hours prior to surgery. Restart after resolution of acute postoperative pain.
- Monitor respiratory function when using high doses of full μOR agonists as buprenorphine clears; adjust doses to prevent opioid-induced respiratory depression (OIRD).
- Use short-acting full opioid agonists to mitigate withdrawal symptoms. Non-opioid adjuncts for withdrawal (alpha-2 receptor agonists, loperamide, ondansetron, diphenhydramine) may be used as appropriate.
Restarting Buprenorphine Criteria- Taper off short-acting opioid and convert back to previous buprenorphine dose in consultation with waivered provider/OUD team.
- Restart when initial withdrawal signs are observed (for clinic induction) or by patient (for home induction).
- Initial dosing: 2 mg or 4 mg. If withdrawal is alleviated, restart remaining prior maintenance dose on day 1.
- Re-induction protocol: Start when clear signs of opioid withdrawal are present. Begin with 2-4 mg dose or 2/0.5 to 4/1 mg buprenorphine/naloxone. After approximately 2 hours, administer additional 2-4 mg if continued withdrawal and lack of sedation.
- FDA label maximum: 8 mg on Day 1 and 16 mg on Day 2. Document clinical rationale for dosing outside FDA recommendations. Individualize dosing; some patients stabilize on lower doses.
Indications & Pharmacological Properties- Approved for management of pain severe enough to require around-the-clock, long-term opioid treatment.
- Functions as a partial agonist at mu-opioid receptors (MORs) and antagonist at kappa-opioid receptors (KORs).
- Exhibits high binding affinity toward MORs with an extremely slow dissociation rate, making it difficult to displace from receptors once bound.
Perioperative Management- Maximize all other non-opioid and non-pharmacological interventions for pain control.
- When a full MOR agonist is clinically necessary, utilize opioids with similar lipophilicity and binding affinity toward MORs (e.g., fentanyl, sufentanil, hydromorphone) to more effectively compete with buprenorphine.
- Consult waivered providers or an interdisciplinary team experienced with buprenorphine use when available.
- Communicate treatment plans directly with the buprenorphine prescriber to facilitate optimal transition of care postoperatively.
Discharge Planning & Continuity of Care- Schedule patients with their SUD provider or chronic pain provider after discharge for close follow-up.
- Provide a warm hand-off for continued buprenorphine adherence upon discharge, particularly for high-risk patients.
- Discharge patients with an adequate supply of buprenorphine to last until their next scheduled follow-up appointment.
Naloxone Education & Counseling- Evaluate the necessity of naloxone based on the specific indication for buprenorphine prescription.
- For buprenorphine buccal film prescribed for chronic pain without a history of OUD or other SUD and with minimal risk for abusing other opioids, naloxone may not be required unless immediate-release (IR) opioids are initiated postoperatively with plans to discharge on them.
- Conduct overdose education during hospitalization and prescribe naloxone at discharge for patients considered at risk for opioid overdose.
- Provide explicit instruction to patients on how to use the prescribed naloxone product.
Safety Screening- Assess all patients for suicidal ideation prior to discharge per VA strategy and facility protocol.
- Recognize that chronic pain, history of or active SUD/OUD, acute stresses to health, and behavioral health comorbidities (e.g., depression, anxiety, PTSD) significantly heighten suicide risk.
Patient Identification & Surgical Classification- Surgical team/PreOP Clinic identifies patient on buprenorphine (Butrans®, Suboxone®, Subutex®, Zubsolv®, Belbuca® , Temgesic® , Sublocade ® , Buprenex®)
- Classify surgery as minimally painful or painful
Minimally Painful Surgery Criteria- NO or minimal need for postop opioid therapy expected (e.g., endoscopy, cataracts)
- Continue home dose through procedure day and after discharge
- Avoid discontinuation or holding of buprenorphine doses
Painful Surgery & Dose Stratification- High-dose patients: > 16 mg/day Suboxone/Subutex, > 11.4 mg/day Zubsolv
- Low-dose patients: < 16 mg/day Suboxone/Subutex, < 11.4 mg/day Zubsolv, Transdermal Buprenorphine (Butrans Patch) or Buccal Film (Belbuca), ANY DOSE
- No preoperative dose adjustment required for specified doses
Pre-operative Management- Elective surgery: Contact buprenorphine prescriber to discuss dose continuation or gradual dose reduction in anticipation of elective surgery
- Pre-operative dose adjustment not possible: Schedule PreOP Clinic appointment within 2-4 weeks, not later than one week before surgery
- Management options: Continue BUP method (preferred) or Discontinue BUP method
- Anticipate need for high doses of opioids for better pain coverage, or dose reduction to <16 mg/day Suboxone/Subutex, <11.4mg/day Zubsolv by time of surgery
- Update and record prescriber name and contact information in PreOP Clinic
- Consult acute pain service IF expected inpatient stay
Day of Surgery / Intraoperative Management- Perioperative plan per OR Anesthesia team / Acute Pain Team (if available)
- Use non-opioid analgesics (gabapentin, pregabalin, acetaminophen, NSAIDS) pre-operatively if not contraindicated
- Use continuous regional anesthesia techniques if possible (epidural and peripheral nerve catheters)
- Use IV ketamine, lidocaine intra-operatively if not contraindicated
Postoperative Management- Pain Service will follow patients postoperatively if needed; pain management plan per Pain Service recommendations
- Maintenance or placement of axial or peripheral nerve catheters, or short-term nerve blocks as necessary
- Focus on non-opioid medication (gabapentinoids, acetaminophen, NSAIDs, antidepressants, α2 agonists etc.)
- Use full agonist opioid with high binding affinity (hydromorphone, fentanyl, or sufentanil) orally, IV, or by PCA
- Avoid use of long-acting opioids
- Continuation of buprenorphine at home dose, lower dose, or higher dose
- Consider Ketamine infusion protocol (1-5mcg/kg/min infusion) if applicable
- Use Non-medication/non-procedural adjuncts (acupuncture, pet therapy, PT and mechanical supports as appropriate)
Re-induction Planning- Re-induction planning should not be necessary if patients continued to take buprenorphine during hospital stay or were on buprenorphine formulations for pain management (transdermal patch or buccal film)
- If buprenorphine was discontinued, pain service attending decides, in collaboration with buprenorphine prescriber or X-waivered provider, which re-induction strategy is appropriate
Indications & Clinical Appropriateness- FDA-approved for management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period of time.
- Appropriate when there is lack of progress towards functional goals and/or inadequate analgesic benefit with full mu agonist opioid.
- Appropriate when high potential for adverse effects exists due to medical conditions, mental health, or behavioral considerations with full mu agonist LTOT.
- Preferred for patients assessed as high risk for traditional oral opioid therapy where alternate buprenorphine products are not advisable, or for patients with documented difficulty swallowing/poor or unpredictable gastrointestinal absorption.
- More appropriate than transdermal patch for moderate MEDD dosing conversions (50-90 MEDD).
Contraindications & Inappropriateness- Infrequent use of immediate-release opioid medication for episodic pain (e.g., PRN).
- Demonstrating functional improvement and expressing preference to remain on full agonist LTOT, in absence of medical, mental health, or behavioral risk for adverse effects.
- May not provide adequate analgesia for patients requiring greater than 160 mg oral morphine equivalent daily dose (MEDD); consider alternate analgesic.
- Not indicated as an as-needed (PRN) analgesic.
Dosing & Administration Guidelines- Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
- For opioid-naïve/non-tolerant patients: Initiate with 75 mcg film once daily or, if tolerated, every 12 hours for at least 4 days, then increase to 150 mcg every 12 hours.
- Titrate in increments of 150 mcg every 12 hours, no more frequently than every 4 days, to achieve adequate analgesia while minimizing adverse reactions.
- Initial dosing based on prior opioid expressed as oral MEDD: <30 mg MEDD (75 mcg qd or q12h), 30-89 mg MEDD (150 mcg q12h), 90-160 mg MEDD (300 mcg q12h).
- Discontinue all other around-the-clock opioid drugs when BUP BF therapy is initiated.
- For oral buccal use only; apply to the buccal mucosa every 12 hours.
- Wait at least one hour after taking before brushing teeth; swish gently and swallow after dissolution.
- Do not apply to areas of the mouth with open sores or lesions.
- Do not use if pouch seal is broken or film is cut/damaged.
Initiation & Transition Strategies- Follow FDA-approved labeling for new starts and standard opioid transitions.
- STOP-START method: Stop full agonist opioids for 12-24 hours and start buprenorphine in early stages of withdrawal to decrease risk of precipitated withdrawal.
- Low dose buprenorphine initiation (microdosing/overlapping dosing): Allows short-term overlap of buprenorphine titration while on full agonist to mitigate withdrawal and discomfort.
- Published conversion recommendations are highly conservative (reduced 50-75%) and already include reduction for lack of tolerance or cross-tolerance.
- Avoid rapid titrations without assessing effectiveness and tolerability at steady state; due to long half-life, takes about five days to achieve steady state.
Monitoring, Evaluation & Safety Considerations- LTOT principles should be followed: focus on functional improvement in physical, social, and psychological domains consistent with the biopsychosocial model of care.
- Assess risks versus benefits periodically; tapering or discontinuing should be considered when risks outweigh benefits or based on patient preference.
- Screen for and assess risk for OUD prior to initiation and when patterns of unhealthy medication use emerge during LTOT.
- Baseline evaluation includes: Urine drug screen (UDS), PDMP check, liver transaminases, monitor for effectiveness of pain relief/prevention of withdrawal symptoms, assess risk for physical/psychological dependence, drug diversion, sensitivity to adverse effects (particularly respiratory depression), assess mental status/respiratory status/increased risk for falls.
- Pain Management Teams (PMT) should be available for specialty care support during initiation/stabilization and transitions.
- Shared decision-making and veteran preference should guide treatment approach.
- For patients without diagnosed OUD, the encounter should indicate the pain condition diagnosis and the prescription should state “for pain management”.
Patient Counseling & Special Instructions- Caution with driving or operating heavy machinery.
- Store in secure place out of reach of children.
- Advise patients to avoid eating or drinking until film dissolves.
- Inform dentist that therapy has been started; wait at least one hour after taking before brushing teeth.
Indications- Acute pain
- Intractable pain
- Pain expected to be severe enough to require opioid management
Patient Selection (Appropriate)- Veterans who may be appropriate for a usual formulary opioid (e.g., fentanyl, hydromorphone, oxycodone, morphine) for acute pain management
- Veterans with known risk factors for hospital Opioid Related Adverse Events (ORADES)
- Veterans already on a buprenorphine pain formulation as an outpatient (e.g., buccal or transdermal)
- Veterans with impaired renal function (dose adjustment not required)
- Veterans who are opioid naïve with other medical risks (e.g., COPD, advanced age)
- Veterans at high risk for opioid dependence (e.g., co-occurring chronic pain syndromes)
- Patients more sensitive to the GI side effects of opioids and surgical procedures
Patient Selection (Inappropriate/Not Recommended)- Pain not severe enough (or expected to be severe enough) to require opioid therapy
- Patients already on high-dose opioid therapy (prescribed or illicit) or long-acting opioid antagonist treatment (e.g., Vivitrol) due to unknown exact role of pain formulations at this time
Contraindications & Precautions- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting
- Known or suspected GI obstruction including paralytic ileus
- Hypersensitivity to buprenorphine
- Additive risk with concomitant CNS depressants (similar to other full-agonist opioids)
Dosing & Administration Criteria- Pre/Peri-operative and PACU: 0.3 mg slow IV (over 2 minutes) pre-op; repeat 0.3 mg slow IV during PACU recovery PRN, may repeat x1 additional dose at 30 minutes if necessary
- PACU to Ward: If IV effective, consider continuing transmucosal formulation (e.g., Belbuca 300 to 450 mcg BID) scheduled for duration of admission; dose adjust based on observed patient response
- Discharge Home: If effective and additional discharge opioids indicated, consider continuing buprenorphine buccal 2-3 times daily PRN for expected post-surgical duration; select outpatient dose based on observed effective minimum dose during inpatient episode
- Emergency Department: Primarily transmucosal; specific use guidance outside scope but studied in renal colic and fractures
- Patients on milligram doses of buprenorphine (8-32 mg/day or LAI): Should NOT be stopped for acute pain management where FAO may be used; continue at maintenance dose and add non-opioid/high-potency FAO as needed. Dose reduction (25-50%) may be considered to allow mu-opioid receptors to “open up” in 12-24 hours, but requires close monitoring due to increased risk of overdose/withdrawals
Clinical Management & Pearls- Tapering and discontinuing buprenorphine for acute pain should not be needed; self-tapers due to long half-life. Advise patients to stop if pain is well managed with non-opioid only
- Onset of action: within 20 minutes (faster with parenteral); full effect of transmucosal products may take 1-3 hours
- Buccal formulation benefits from mucoadherence; requires no patient participation; can be administered under anesthesia; dry buccal mucosa can be moistened with a gloved finger prior to application; yellow side goes on cheek; do not eat or drink while dissolving; rinse mouth after complete dissolution
- If buprenorphine is ineffective/insufficient: may indicate opioid refractoriness; optimize non-opioid strategies and use high-potency full-agonist opioids (FAO); conventional FAO expected to be fully effective even if microgram doses prove ineffective
- Precipitated withdrawal: Microgram dosing for acute pain would not be expected to result in precipitated withdrawal; incidence <5% even when transitioning from high-dose full-agonists
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BUPRENORPHINE/ NALOXONE TAB,SUBLINGUAL
ZUBSOLV
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ZUBSOLV |
2017-02-27 |
Perioperative Pain Management Principles- Buprenorphine treatment should not be routinely discontinued in the perioperative period for patients on stable MOUD therapy.
- Discontinuation may confer medical risks including return to active opioid use (50-90%), risk of overdose, prolonged hospital stay, and increased patient burden.
- A buprenorphine taper to < 16 mg/day may be considered for patients prescribed higher doses (> 16 mg) with anticipated high post-surgical pain.
- Utilize a multimodal pain approach including systemic non-opioid analgesics (acetaminophen, NSAIDs, gabapentinoids, ketamine, magnesium, systemic lidocaine, alpha-2 agonists, glucocorticoids), regional/local analgesics, and psychosocial interventions.
- When a full μOR agonist is needed to adequately control perioperative pain, use opioids with similar lipophilicity and binding affinity toward μORs; fentanyl and hydromorphone are reasonable alternatives.
Pre-operative Assessment & Planning- Perform patient evaluation including pain history, physical examination, medication reconciliation, assessment of physical/psychiatric comorbidities, and urine drug monitoring (including methadone, fentanyl, buprenorphine/metabolites).
- Verify prescription adherence via PDMP database.
- Conduct universal substance use disorder screening; perform detailed questioning and appropriate referrals for positive responses.
- Provide pre-operative counseling with written instructions regarding risks of opioid exposure/undertreating pain as relapse triggers.
- Determine procedure-related pain severity (minimal/no pain vs. significant pain) to guide dose adjustment or continuation.
- Plan continuity of care: taper off short-acting opioids prior to discharge; restrict IR opioids to short-term rescue use perioperatively; coordinate with waivered provider/OUD team for outpatient post-op pain care; preschedule follow-up with OUD/chronic pain provider; ensure sufficient buprenorphine supply at discharge.
Elective Procedure Management Criteria- For most patients, continue buprenorphine throughout the operative period.
- Minimally painful surgery: Continue current home dose unchanged, or divide and administer every 6 to 8 hours. Total daily dose may be titrated up to 32 mg/day in divided doses if needed for pain management (does not apply to extended-release injection).
- Painful surgery (moderate/severe pain): Continue baseline dose > 16 mg/day, OR reduce to < 16 mg/day to allow addition of an IR full μOR agonist. Expect higher doses of full μOR agonists requiring close monitoring (e.g., ICU or step-down unit).
- Examples of minimal pain procedures: tooth extraction, endoscopy, colonoscopy, bronchoscopy.
- Examples of moderate/severe pain procedures: laparoscopic, intra-abdominal, intra-thoracic, and orthopedic procedures.
Emergent Procedure Management Criteria- Anticipated minimal to no pain: Continue buprenorphine throughout procedure with non-opioid medications. Dose may be increased until adequate pain relief is achieved. Taper off short-acting opioids prior to discharge.
- Anticipated moderate to severe pain (Continue method): Continue buprenorphine throughout operation; increase dose postoperatively (except implant or BUP XR INJ) or use short-acting opioids. Taper off short-acting opioids prior to or shortly after discharge.
- Anticipated moderate to severe pain (Discontinue method): Discontinue per specified discontinuation criteria.
Discontinuation Criteria & Management- Discontinuation is indicated only when: patient requests to stop (after discussing pros/cons with provider and OUD team); medical contraindication exists; or all other options (maximizing dose, splitting dose, multimodal therapy) are insufficient.
- Emergency procedures: Discontinue immediately upon admission in lieu of high-dose short-acting μOR agonist.
- Elective procedures: Discontinue 24-72 hours prior to surgery. Restart after resolution of acute postoperative pain.
- Monitor respiratory function when using high doses of full μOR agonists as buprenorphine clears; adjust doses to prevent opioid-induced respiratory depression (OIRD).
- Use short-acting full opioid agonists to mitigate withdrawal symptoms. Non-opioid adjuncts for withdrawal (alpha-2 receptor agonists, loperamide, ondansetron, diphenhydramine) may be used as appropriate.
Restarting Buprenorphine Criteria- Taper off short-acting opioid and convert back to previous buprenorphine dose in consultation with waivered provider/OUD team.
- Restart when initial withdrawal signs are observed (for clinic induction) or by patient (for home induction).
- Initial dosing: 2 mg or 4 mg. If withdrawal is alleviated, restart remaining prior maintenance dose on day 1.
- Re-induction protocol: Start when clear signs of opioid withdrawal are present. Begin with 2-4 mg dose or 2/0.5 to 4/1 mg buprenorphine/naloxone. After approximately 2 hours, administer additional 2-4 mg if continued withdrawal and lack of sedation.
- FDA label maximum: 8 mg on Day 1 and 16 mg on Day 2. Document clinical rationale for dosing outside FDA recommendations. Individualize dosing; some patients stabilize on lower doses.
Indications & Pharmacological Properties- Approved for management of pain severe enough to require around-the-clock, long-term opioid treatment.
- Functions as a partial agonist at mu-opioid receptors (MORs) and antagonist at kappa-opioid receptors (KORs).
- Exhibits high binding affinity toward MORs with an extremely slow dissociation rate, making it difficult to displace from receptors once bound.
Perioperative Management- Maximize all other non-opioid and non-pharmacological interventions for pain control.
- When a full MOR agonist is clinically necessary, utilize opioids with similar lipophilicity and binding affinity toward MORs (e.g., fentanyl, sufentanil, hydromorphone) to more effectively compete with buprenorphine.
- Consult waivered providers or an interdisciplinary team experienced with buprenorphine use when available.
- Communicate treatment plans directly with the buprenorphine prescriber to facilitate optimal transition of care postoperatively.
Discharge Planning & Continuity of Care- Schedule patients with their SUD provider or chronic pain provider after discharge for close follow-up.
- Provide a warm hand-off for continued buprenorphine adherence upon discharge, particularly for high-risk patients.
- Discharge patients with an adequate supply of buprenorphine to last until their next scheduled follow-up appointment.
Naloxone Education & Counseling- Evaluate the necessity of naloxone based on the specific indication for buprenorphine prescription.
- For buprenorphine buccal film prescribed for chronic pain without a history of OUD or other SUD and with minimal risk for abusing other opioids, naloxone may not be required unless immediate-release (IR) opioids are initiated postoperatively with plans to discharge on them.
- Conduct overdose education during hospitalization and prescribe naloxone at discharge for patients considered at risk for opioid overdose.
- Provide explicit instruction to patients on how to use the prescribed naloxone product.
Safety Screening- Assess all patients for suicidal ideation prior to discharge per VA strategy and facility protocol.
- Recognize that chronic pain, history of or active SUD/OUD, acute stresses to health, and behavioral health comorbidities (e.g., depression, anxiety, PTSD) significantly heighten suicide risk.
Patient Identification & Surgical Classification- Surgical team/PreOP Clinic identifies patient on buprenorphine (Butrans®, Suboxone®, Subutex®, Zubsolv®, Belbuca® , Temgesic® , Sublocade ® , Buprenex®)
- Classify surgery as minimally painful or painful
Minimally Painful Surgery Criteria- NO or minimal need for postop opioid therapy expected (e.g., endoscopy, cataracts)
- Continue home dose through procedure day and after discharge
- Avoid discontinuation or holding of buprenorphine doses
Painful Surgery & Dose Stratification- High-dose patients: > 16 mg/day Suboxone/Subutex, > 11.4 mg/day Zubsolv
- Low-dose patients: < 16 mg/day Suboxone/Subutex, < 11.4 mg/day Zubsolv, Transdermal Buprenorphine (Butrans Patch) or Buccal Film (Belbuca), ANY DOSE
- No preoperative dose adjustment required for specified doses
Pre-operative Management- Elective surgery: Contact buprenorphine prescriber to discuss dose continuation or gradual dose reduction in anticipation of elective surgery
- Pre-operative dose adjustment not possible: Schedule PreOP Clinic appointment within 2-4 weeks, not later than one week before surgery
- Management options: Continue BUP method (preferred) or Discontinue BUP method
- Anticipate need for high doses of opioids for better pain coverage, or dose reduction to <16 mg/day Suboxone/Subutex, <11.4mg/day Zubsolv by time of surgery
- Update and record prescriber name and contact information in PreOP Clinic
- Consult acute pain service IF expected inpatient stay
Day of Surgery / Intraoperative Management- Perioperative plan per OR Anesthesia team / Acute Pain Team (if available)
- Use non-opioid analgesics (gabapentin, pregabalin, acetaminophen, NSAIDS) pre-operatively if not contraindicated
- Use continuous regional anesthesia techniques if possible (epidural and peripheral nerve catheters)
- Use IV ketamine, lidocaine intra-operatively if not contraindicated
Postoperative Management- Pain Service will follow patients postoperatively if needed; pain management plan per Pain Service recommendations
- Maintenance or placement of axial or peripheral nerve catheters, or short-term nerve blocks as necessary
- Focus on non-opioid medication (gabapentinoids, acetaminophen, NSAIDs, antidepressants, α2 agonists etc.)
- Use full agonist opioid with high binding affinity (hydromorphone, fentanyl, or sufentanil) orally, IV, or by PCA
- Avoid use of long-acting opioids
- Continuation of buprenorphine at home dose, lower dose, or higher dose
- Consider Ketamine infusion protocol (1-5mcg/kg/min infusion) if applicable
- Use Non-medication/non-procedural adjuncts (acupuncture, pet therapy, PT and mechanical supports as appropriate)
Re-induction Planning- Re-induction planning should not be necessary if patients continued to take buprenorphine during hospital stay or were on buprenorphine formulations for pain management (transdermal patch or buccal film)
- If buprenorphine was discontinued, pain service attending decides, in collaboration with buprenorphine prescriber or X-waivered provider, which re-induction strategy is appropriate
Indications & Clinical Appropriateness- FDA-approved for management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period of time.
- Appropriate when there is lack of progress towards functional goals and/or inadequate analgesic benefit with full mu agonist opioid.
- Appropriate when high potential for adverse effects exists due to medical conditions, mental health, or behavioral considerations with full mu agonist LTOT.
- Preferred for patients assessed as high risk for traditional oral opioid therapy where alternate buprenorphine products are not advisable, or for patients with documented difficulty swallowing/poor or unpredictable gastrointestinal absorption.
- More appropriate than transdermal patch for moderate MEDD dosing conversions (50-90 MEDD).
Contraindications & Inappropriateness- Infrequent use of immediate-release opioid medication for episodic pain (e.g., PRN).
- Demonstrating functional improvement and expressing preference to remain on full agonist LTOT, in absence of medical, mental health, or behavioral risk for adverse effects.
- May not provide adequate analgesia for patients requiring greater than 160 mg oral morphine equivalent daily dose (MEDD); consider alternate analgesic.
- Not indicated as an as-needed (PRN) analgesic.
Dosing & Administration Guidelines- Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
- For opioid-naïve/non-tolerant patients: Initiate with 75 mcg film once daily or, if tolerated, every 12 hours for at least 4 days, then increase to 150 mcg every 12 hours.
- Titrate in increments of 150 mcg every 12 hours, no more frequently than every 4 days, to achieve adequate analgesia while minimizing adverse reactions.
- Initial dosing based on prior opioid expressed as oral MEDD: <30 mg MEDD (75 mcg qd or q12h), 30-89 mg MEDD (150 mcg q12h), 90-160 mg MEDD (300 mcg q12h).
- Discontinue all other around-the-clock opioid drugs when BUP BF therapy is initiated.
- For oral buccal use only; apply to the buccal mucosa every 12 hours.
- Wait at least one hour after taking before brushing teeth; swish gently and swallow after dissolution.
- Do not apply to areas of the mouth with open sores or lesions.
- Do not use if pouch seal is broken or film is cut/damaged.
Initiation & Transition Strategies- Follow FDA-approved labeling for new starts and standard opioid transitions.
- STOP-START method: Stop full agonist opioids for 12-24 hours and start buprenorphine in early stages of withdrawal to decrease risk of precipitated withdrawal.
- Low dose buprenorphine initiation (microdosing/overlapping dosing): Allows short-term overlap of buprenorphine titration while on full agonist to mitigate withdrawal and discomfort.
- Published conversion recommendations are highly conservative (reduced 50-75%) and already include reduction for lack of tolerance or cross-tolerance.
- Avoid rapid titrations without assessing effectiveness and tolerability at steady state; due to long half-life, takes about five days to achieve steady state.
Monitoring, Evaluation & Safety Considerations- LTOT principles should be followed: focus on functional improvement in physical, social, and psychological domains consistent with the biopsychosocial model of care.
- Assess risks versus benefits periodically; tapering or discontinuing should be considered when risks outweigh benefits or based on patient preference.
- Screen for and assess risk for OUD prior to initiation and when patterns of unhealthy medication use emerge during LTOT.
- Baseline evaluation includes: Urine drug screen (UDS), PDMP check, liver transaminases, monitor for effectiveness of pain relief/prevention of withdrawal symptoms, assess risk for physical/psychological dependence, drug diversion, sensitivity to adverse effects (particularly respiratory depression), assess mental status/respiratory status/increased risk for falls.
- Pain Management Teams (PMT) should be available for specialty care support during initiation/stabilization and transitions.
- Shared decision-making and veteran preference should guide treatment approach.
- For patients without diagnosed OUD, the encounter should indicate the pain condition diagnosis and the prescription should state “for pain management”.
Patient Counseling & Special Instructions- Caution with driving or operating heavy machinery.
- Store in secure place out of reach of children.
- Advise patients to avoid eating or drinking until film dissolves.
- Inform dentist that therapy has been started; wait at least one hour after taking before brushing teeth.
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BUPROPION/ NALTREXONE TAB,SA
CONTRAVE
|
CONTRAVE |
2017-02-27 |
Exclusion Criteria- Pregnancy
- Lactating
- Uncontrolled hypertension
- History of seizure disorder, bulimia, or anorexia nervosa
- Concurrent opioid use or use of opioids within the last 7 to 10 days
- Undergoing abrupt discontinuation of alcohol, benzodiazepines, barbitates, and antiepileptic drugs
- Major depressive disorder especially in patients 24 years of age or younger (unless a mental health consultation supports benefits for patients at risk for suicidal thoughts or behaviors)
Inclusion Criteria- Verifiable participation in a comprehensive lifestyle intervention (CLI) that targets all three aspects of weight management: diet, physical activity, behavioral changes
- BMI greater than or equal to 30 kg/m² OR BMI greater than or equal to 27 kg/m² with at least one weight-related comorbidity
- Weight-related comorbidities include: hypertension, type 2 diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, nonalcoholic fatty liver disease (aka metabolic dysfunction-associated steatotic liver disease)
- Discontinuation of medications that may precipitate weight gain if clinically appropriate
Additional Inclusion Criteria- For patients who can become pregnant: Pregnancy must be excluded prior to receiving treatment; patient must receive contraceptive counseling regarding potential risks vs. benefits if pregnancy occurs during treatment
Indications & Eligibility- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance
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C1 INHIBITOR INJ,PWDR
BERINERT, CINRYZE, RUCONEST
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BERINERT, CINRYZE, RUCONEST |
2017-02-27 |
Exclusion Criteria- Angioedema or abdominal pain not associated with C1 inhibitor deficiency
Inclusion Criteria (ALL must be met)- Restricted to VA / VA Community Care allergy/immunology or dermatology provider; or for use in Emergency Medicine/Urgent Care
- Diagnosis of Hereditary Angioedema due to C1 inhibitor deficiency (HAE-C1INH) as established by laboratory testing
Additional Inclusion Criteria (ONE must be met)- Long-term prophylaxis for HAE-C1INH attacks after consideration of either an attenuated androgen or antifibrinolytic
Clinical Context & Decision-Making Requirements- Prior consideration of an attenuated androgen or antifibrinolytic must be discussed with the patient using shared decision-making, including efficacy, routes of administration, and side effects of each therapy
- Baseline attack rate criteria may include at least 2 attacks per month or baseline attack rate in clinical trials
- Need for long-term prophylaxis should be determined using shared decision-making
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CABAZITAXEL INJ,SOLN
JEVTANA
|
JEVTANA |
2017-02-27 |
Exclusion Criteria- History of severe hypersensitivity reactions to drugs formulated with polysorbate 80
- Absolute Neutrophil Count (ANC) < 1500/mm3 or hemoglobin < 10 g/dL or platelets < 100,000/mm3
- Radiotherapy to 40% or more of bone marrow
- Hepatic impairment (bilirubin greater than 3x upper limit of normal)
- Active Grade 2 or higher peripheral neuropathy
- Inability or contraindication to taking prednisone
Inclusion Criteria- Diagnosis of metastatic prostate cancer with documented disease progression during or after completion of docetaxel-based therapy
Additional Inclusion Criteria & Clinical Requirements- Care is provided by a VA/VA Community Care oncology provider
- The goals of care and role of Palliative Care consult has been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Prior and ongoing castrate levels of testosterone (less than 50 ng/dL) by either medical or surgical castration
- Patients with female partners of childbearing potential advised to use effective contraception during therapy and for 3 months following the last dose
Prophylaxis Considerations- Consider primary prophylaxis with a Granulocyte-Colony Stimulating Factor (G-CSF) product for patients at high risk for neutropenia and those receiving a dose 25mg/m2
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CARBIDOPA/ LEVODOPA SUSP,INTESTINAL
DUOPA
|
DUOPA |
2017-02-27 |
Exclusion Criteria- Currently taking or taken within 14 days a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine)
- Patient is not an appropriate candidate for PEG J placement
- Patient has not demonstrated a response to prior levodopa use
Inclusion Criteria- Diagnosis of Idiopathic Parkinson’s disease
- Patient is under the care of a VA or VA Community Care neurologist
- Motor fluctuations (“wearing off”) that require dosing of dopaminergic medications at intervals every 4 hours or less
- Either combination of carbidopa/levodopa controlled-release (CR) and immediate-release (IR) tablet formulations or carbidopa/levodopa extended-release (ER) capsules throughout the day have not adequately resolved OFF periods
- Contraindication, intolerance, or inadequate therapeutic response to at least one agent from two of the following classes: dopamine agonist, catechol-O methyl transferase [COMT] inhibitor, monoamine oxidase type B [MAO B] inhibitor
Documentation & Clinical Management Requirements- Discussion with patient/caregiver/family regarding realistic efficacy expectations, device management, and potential device-related complications should be documented in the patient’s medical record
- Recommended dosing should be determined based on the patient’s current carbidopa/levodopa dose and other Parkinson’s disease therapies per product prescribing information
Device Placement Considerations- Absolute contraindications to J-tube placement include: known or suspected intestinal obstruction, serious coagulation disorders, sepsis or active peritonitis
- Relative contraindications include: ascites and neoplastic, inflammatory and infiltrative disease of the gastric and abdominal walls
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CARFILZOMIB INJ
KYPROLIS
|
KYPROLIS |
2017-02-27 |
Exclusion Criteria- Absolute neutrophil count < 1000/µL and/or platelet count < 50,000/µL (<30,000/mm³ if myeloma involvement in bone marrow > 50%)
- Total bilirubin > 1.5x upper limit of normal (unless Gilbert’s syndrome or liver involvement) and/or alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase > 3x upper limit of normal (unless liver involvement)
- Clinically significant cardiovascular disease, including: baseline left ventricular ejection fraction < 50% via MUGA or echocardiography; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; symptomatic congestive heart failure (New York Heart Assoc Class 3-4)
- Grade 3 or 4 peripheral neuropathy
- Active or uncontrolled infection
- Unmanageable drug-drug interaction
- Known pregnancy
- Lactating
Inclusion Criteria- Previously treated multiple myeloma
- Care provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Goals of care and role of Palliative Care consult have been discussed and documented
- Venous thromboembolism (VTE) risk scoring (i.e. SAVED, IMPEDE) performed for consideration of VTE prophylaxis
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 6 months after stopping treatment
- For patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 3 months after stopping treatment
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CICLESONIDE AEROSOL,ORAL
ALVESCO
|
ALVESCO |
2017-02-27 |
Indications & Clinical Context- Recommended for conversion during mometasone inhaler (Asmanex) shortage due to favorable pricing.
- Dose comparison table explicitly provided for asthma.
- Clinically used as add-on therapy to bronchodilators for COPD, though not FDA-approved for COPD.
Dosing & Administration- Frequency of administration: Twice daily.
- Total daily dose categories (based on product labeling):
- Low: ≤160 mcg
- Medium: >160-320 mcg
- High: >320 mcg
Strengths & Formulation- Ciclesonide HFA MDI (Alvesco) available in 80 mcg and 160 mcg strengths.
Clinical Considerations & Monitoring- Consider disease control and severity when switching.
- Monitor patient response and adjust dose as appropriate.
- Refer to product package insert for further dosing information.
- Table provides suggested total daily doses based on product labeling, not equivalence or potency equivalence.
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CICLESONIDE INHL,ORAL
ALVESCO
|
ALVESCO |
2017-02-27 |
Indications & Clinical Context- Recommended for conversion during mometasone inhaler (Asmanex) shortage due to favorable pricing.
- Dose comparison table explicitly provided for asthma.
- Clinically used as add-on therapy to bronchodilators for COPD, though not FDA-approved for COPD.
Dosing & Administration- Frequency of administration: Twice daily.
- Total daily dose categories (based on product labeling):
- Low: ≤160 mcg
- Medium: >160-320 mcg
- High: >320 mcg
Strengths & Formulation- Ciclesonide HFA MDI (Alvesco) available in 80 mcg and 160 mcg strengths.
Clinical Considerations & Monitoring- Consider disease control and severity when switching.
- Monitor patient response and adjust dose as appropriate.
- Refer to product package insert for further dosing information.
- Table provides suggested total daily doses based on product labeling, not equivalence or potency equivalence.
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CILOSTAZOL TAB
PLETAL, PLETAL 100MG TAB
|
PLETAL, PLETAL 100MG TAB |
2017-02-27 |
Exclusion Criteria- Heart failure with reduced ejection fraction (FDA labeling does not specify the classification or degree of heart failure severity that should be avoided; concern is based on extrapolated data from oral milrinone where patients with class III and IV heart failure with reduced ejection fraction had lower survival)
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CITALOPRAM TAB
CELEXA, CELEXA 40MG TABLET, CITALOPRAM HBR
|
CELEXA, CELEXA 40MG TABLET, CITALOPRAM HBR |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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CLADRIBINE INJ
LEUSTATIN
|
LEUSTATIN |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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CLARITHROMYCIN TAB
BIAXIN
|
BIAXIN |
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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CLONAZEPAM TAB,ORAL DISINTEGRATING
|
|
2017-02-27 |
Continuity of Care Inclusion Criteria- Veteran is transitioning care from the Department of Defense to VHA
- Additional Inclusion Criteria (Select ONE if appropriate)
- The medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making.
- The medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making.
Non-Continuity of Care Inclusion Criteria- Difficulty swallowing oral tablet.
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CLOPIDOGREL TAB
PLAVIX
|
PLAVIX |
2017-02-27 |
Pharmacology & Drug Interaction- Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
- Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.
Gastrointestinal Risk Management- PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
- For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.
Cardiovascular Risk Management- Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
- No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.
Prescribing Criteria- Deprescribe PPIs as much as possible per established de-prescribing guidelines.
- Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.
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CLOZAPINE (CARACO) TAB
|
|
2017-02-27 |
Indications- Treatment-resistant schizophrenia
- Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Contraindications- Hypersensitivity to clozapine or any other component of clozapine
Boxed Warnings- Severe neutropenia
- Orthostatic hypotension, bradycardia, syncope
- Seizures
- Myocarditis, pericarditis, cardiomyopathy, and mitral valve incompetence
- Increased mortality in elderly patients with dementia-related psychosis
Precautions- Eosinophilia
- QT interval prolongation
- Metabolic Changes
- Neuroleptic malignant syndrome
- Hepatotoxicity
- Fever
- Pulmonary embolism
- Anticholinergic toxicity
- Interference with cognitive and motor performance
- Use with caution in patients with decreased GI motility
- Special populations: Poor metabolizers of CYP2D6; Smokers via CYP1A2 induction – with respect to forced absence during hospitalization
Dosing- Starting Dose: 12.5 mg once daily or twice daily
- Use cautious titration and divided dosage schedule
- Titration: increase the total daily dosage in increments of 25 mg to 50 mg per day, if well-tolerated
- Target dose: 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks
- Subsequent increases: increase in increments of 100 mg or less, once, or twice weekly
- Maximum daily dose: 900 mg
ANC Monitoring Recommendations- Obtain baseline ANC before treatment initiation
- Weekly from initiation to 6 months
- Every 2 weeks from 6 to 12 months (if the ANC remains in the normal range; ANC greater than or equal to 1500/μL for the general population, ANC greater than or equal to 1000/μL for patients with Benign Ethnic Neutropenia)
- Monthly after 12 months, using shared decision making (if ANC continues to remain in the normal range)
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CLOZAPINE (CLOZARIL) TAB
CLOZARIL
|
CLOZARIL |
2017-02-27 |
Indications- Treatment-resistant schizophrenia
- Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Contraindications- Hypersensitivity to clozapine or any other component of clozapine
Boxed Warnings- Severe neutropenia
- Orthostatic hypotension, bradycardia, syncope
- Seizures
- Myocarditis, pericarditis, cardiomyopathy, and mitral valve incompetence
- Increased mortality in elderly patients with dementia-related psychosis
Precautions- Eosinophilia
- QT interval prolongation
- Metabolic Changes
- Neuroleptic malignant syndrome
- Hepatotoxicity
- Fever
- Pulmonary embolism
- Anticholinergic toxicity
- Interference with cognitive and motor performance
- Use with caution in patients with decreased GI motility
- Special populations: Poor metabolizers of CYP2D6; Smokers via CYP1A2 induction – with respect to forced absence during hospitalization
Dosing- Starting Dose: 12.5 mg once daily or twice daily
- Use cautious titration and divided dosage schedule
- Titration: increase the total daily dosage in increments of 25 mg to 50 mg per day, if well-tolerated
- Target dose: 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks
- Subsequent increases: increase in increments of 100 mg or less, once, or twice weekly
- Maximum daily dose: 900 mg
ANC Monitoring Recommendations- Obtain baseline ANC before treatment initiation
- Weekly from initiation to 6 months
- Every 2 weeks from 6 to 12 months (if the ANC remains in the normal range; ANC greater than or equal to 1500/μL for the general population, ANC greater than or equal to 1000/μL for patients with Benign Ethnic Neutropenia)
- Monthly after 12 months, using shared decision making (if ANC continues to remain in the normal range)
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CLOZAPINE (MYLAN) TAB
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2017-02-27 |
Indications- Treatment-resistant schizophrenia
- Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Contraindications- Hypersensitivity to clozapine or any other component of clozapine
Boxed Warnings- Severe neutropenia
- Orthostatic hypotension, bradycardia, syncope
- Seizures
- Myocarditis, pericarditis, cardiomyopathy, and mitral valve incompetence
- Increased mortality in elderly patients with dementia-related psychosis
Precautions- Eosinophilia
- QT interval prolongation
- Metabolic Changes
- Neuroleptic malignant syndrome
- Hepatotoxicity
- Fever
- Pulmonary embolism
- Anticholinergic toxicity
- Interference with cognitive and motor performance
- Use with caution in patients with decreased GI motility
- Special populations: Poor metabolizers of CYP2D6; Smokers via CYP1A2 induction – with respect to forced absence during hospitalization
Dosing- Starting Dose: 12.5 mg once daily or twice daily
- Use cautious titration and divided dosage schedule
- Titration: increase the total daily dosage in increments of 25 mg to 50 mg per day, if well-tolerated
- Target dose: 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks
- Subsequent increases: increase in increments of 100 mg or less, once, or twice weekly
- Maximum daily dose: 900 mg
ANC Monitoring Recommendations- Obtain baseline ANC before treatment initiation
- Weekly from initiation to 6 months
- Every 2 weeks from 6 to 12 months (if the ANC remains in the normal range; ANC greater than or equal to 1500/μL for the general population, ANC greater than or equal to 1000/μL for patients with Benign Ethnic Neutropenia)
- Monthly after 12 months, using shared decision making (if ANC continues to remain in the normal range)
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CLOZAPINE (VERSACLOZ) SUSP,ORAL
VERSACLOZ
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VERSACLOZ |
2017-02-27 |
Indications- Treatment-resistant schizophrenia
- Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Contraindications- Hypersensitivity to clozapine or any other component of clozapine
Boxed Warnings- Severe neutropenia
- Orthostatic hypotension, bradycardia, syncope
- Seizures
- Myocarditis, pericarditis, cardiomyopathy, and mitral valve incompetence
- Increased mortality in elderly patients with dementia-related psychosis
Precautions- Eosinophilia
- QT interval prolongation
- Metabolic Changes
- Neuroleptic malignant syndrome
- Hepatotoxicity
- Fever
- Pulmonary embolism
- Anticholinergic toxicity
- Interference with cognitive and motor performance
- Use with caution in patients with decreased GI motility
- Special populations: Poor metabolizers of CYP2D6; Smokers via CYP1A2 induction – with respect to forced absence during hospitalization
Dosing- Starting Dose: 12.5 mg once daily or twice daily
- Use cautious titration and divided dosage schedule
- Titration: increase the total daily dosage in increments of 25 mg to 50 mg per day, if well-tolerated
- Target dose: 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks
- Subsequent increases: increase in increments of 100 mg or less, once, or twice weekly
- Maximum daily dose: 900 mg
ANC Monitoring Recommendations- Obtain baseline ANC before treatment initiation
- Weekly from initiation to 6 months
- Every 2 weeks from 6 to 12 months (if the ANC remains in the normal range; ANC greater than or equal to 1500/μL for the general population, ANC greater than or equal to 1000/μL for patients with Benign Ethnic Neutropenia)
- Monthly after 12 months, using shared decision making (if ANC continues to remain in the normal range)
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COLCHICINE TAB
LODOCO
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LODOCO |
2017-02-27 |
Indication- Reduce risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease (ASCVD) or multiple risk factors for cardiovascular disease.
Dosage & Administration- 0.5 mg tablet taken once daily.
Patient Selection & Clinical Context- Adults with stable cardiovascular disease (CVD) or chronic coronary disease (CCD).
- Patients within 30 days of an MI.
- Patients presenting with acute coronary syndrome (ACS) with evidence of CAD on coronary angiography, managed with percutaneous coronary intervention (PCI) or medical therapy.
- High-risk patients who remain at risk despite maximally tolerated guideline directed medical therapies (GDMT).
Contraindications & Precautions- Avoid concurrent use of strong CYP3A4 inhibitors or P-glycoprotein (P-gp) inhibitors due to risk of life-threatening and fatal colchicine toxicity.
- Avoid use in patients with renal failure (CrCl <15 mL/min) and severe hepatic impairment.
- Avoid use in patients with pre-existing blood dyscrasias or hypersensitivity to colchicine or any ingredients.
- Avoid moderate CYP3A4 inhibitors in patients with any degree of hepatic or renal impairment.
- Avoid use in patients with eGFR <30 mL/min/m2 per 2023 AHA/ACC guidelines.
Monitoring & Safety Considerations- Determine hepatic and renal function prior to initiating therapy.
- Assess all medications for potential drug-drug interactions before initiation.
- Closely monitor patients reporting gastrointestinal symptoms (e.g., diarrhea, nausea, vomiting, abdominal cramping) as they may be the initial sign of colchicine toxicity.
- Monitor closely for myopathy or rhabdomyolysis when used with statins or fibrates.
Special Populations- Pregnancy: Animal data indicate embryofetal toxicity and altered postnatal development; observational studies do not suggest increased risk for birth defects or miscarriage in pregnant women with rheumatic disease.
- Lactation: Weigh developmental health benefits of breastfeeding against the mother’s clinical need and potential for adverse events in the infant.
- Renal/Hepatic Impairment: Use with caution in any degree of impairment; avoid if severe/failure or when combined with moderate CYP3A4 inhibitors.
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CRIZOTINIB CAP,ORAL
XALKORI
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XALKORI |
2017-02-27 |
Exclusion Criteria- History of interstitial fibrosis or interstitial lung disease
- History of congenital long QT syndrome
- Unmanageable drug-drug interactions
- Inadequate bone marrow function (Absolute Neutrophil Count < 1000/mm3, platelets < 50,000/mm3, hemoglobin < 8g/dL), unless due to marrow involvement
- Pregnancy
- Lactating
Inclusion Criteria- Care provided by a VA/VA Community Care hematology or oncology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Relapsed or refractory systemic Anaplastic Lymphoma Kinase (ALK)-positive anaplastic large cell lymphoma (ALCL)
- Unresectable, recurrent or refractory ALK-positive inflammatory myofibroblastic tumor (IMT)
Reproductive Health & Pregnancy Management- Pregnancy must be excluded prior to receiving crizotinib for patients who can become pregnant
- Counseling on potential risks vs benefits of treatment and use of effective contraception during therapy and for 45 days after stopping treatment for patients who can become pregnant
- Counseling on potential risks vs benefits of treatment and use of effective contraception during therapy and for 90 days after stopping treatment for patients with partners who can become pregnant
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DARATUMUMAB INJ,SOLN
DARZALEX
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DARZALEX |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity to daratumumab
- Unable to be observed in clinic for an extended period following the first dose
- Absolute Neutrophil Count (ANC) < 1000/mm3
- Hemoglobin < 8 g/dL; must transfuse to hemoglobin > 8 g/dL prior to therapy initiation
- Platelet count < 50,000/mm3 (< 30,000/mm3 if myeloma involvement in bone marrow > 50%)
- Estimated creatinine clearance (CrCl) < 15 ml/min
- New York Heart Association (NYHA) Class III or IV heart failure
- Ongoing or active systemic infection including active hepatitis B or C or known HIV infection
- Patient has not been screened for Hepatitis B Virus (HBV)
- Pregnancy (e.g. known or positive pregnancy test)
- Breastfeeding
Indications- Multiple myeloma
- Light chain amyloidosis
Pre-treatment & Clinical Management Requirements- Care is provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Type and screen patients for Red Blood Cell antibodies PRIOR to starting therapy
- Provider has informed Blood Bank that patient will be starting daratumumab
- Antiviral prophylaxis to prevent herpes zoster reactivation to start within 1 week after starting daratumumab and continue for 3 months following the end of treatment
- Female patients of child-bearing potential and male patients with female partners of child-bearing potential: counseling provided on contraception (use during treatment and 3 months after) and risks vs. benefits of treatment
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DENOSUMAB INJ,SOLN
PROLIA, XGEVA
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PROLIA, XGEVA |
2017-02-27 |
Exclusion Criteria- Hypocalcemia or pre-existing disturbance of mineral metabolism not effectively corrected or treated
- Documentation of need for invasive dental procedure (e.g., tooth extraction, dental implant, dental infection treatment) or recent unhealed procedure
- Acute dental issue identified by history or clinician mouth examination
- Receiving denosumab (XGEVA)
- Pregnancy or lactating
- Exception: Patients with secondary or tertiary hyperparathyroidism due to chronic kidney disease and low bone mineral density who are nonsurgical candidates
- Inclusion Criteria (All must be met)
- Diagnosis of osteoporosis or at risk for glucocorticoid-induced osteoporosis
- Prescriber is a VA/VA Community Care endocrinologist, rheumatologist, nephrologist, geriatrician, or locally designated expert
- Patient’s total daily dietary and supplemental calcium intake is 1000 to 1200 mg/day
- 25-hydroxyvitamin D concentration >30 ng/mL or > 20 ng/ml with appropriate intake (e.g., cholecalciferol >800 international units per day)
- Prescriber has documented discussion of severe hypocalcemia risk and need for close monitoring if eGFR < 30ml/min
- For patients with eGFR < 35 ml/min, risks and benefits of indefinite denosumab discussed due to inability to transition to bisphosphonates
- Requirement to transition to another antiresorptive agent upon discontinuation to prevent rebound fractures
- Additional Criteria (One of the following must be met)
- Allergy, contraindication, unsatisfactory response, or intolerable adverse events with bisphosphonate therapy
- Osteoporotic fracture and T-score at hip or spine < -2.5
- Very high fracture probability by Fracture Risk Assessment Tool (FRAX) (e.g., major osteoporosis fracture >30%, hip fracture >4.5%)
- T-score < -3.0
- More than 2 osteoporotic fractures
- Continued bone mineral density loss or sustained osteoporotic fracture while on other approved osteoporosis therapy
Exclusion Criteria- Hypocalcemia (corrected calcium at or below lower limit of normal) that has not been effectively corrected
- Documentation of the need for an invasive dental procedure (e.g., tooth extraction, dental implant, and/or dental infection treatment) or recent procedure that has not fully healed
- Acute dental issue identified by history or clinician mouth examination
- Receiving denosumab (PROLIA), zoledronic acid, or pamidronate
- Pregnancy
Inclusion Criteria (Cancer-Related Indications)- Prevention of skeletal-related events in patients with multiple myeloma refractory or intolerant to zoledronic acid (or if zoledronic acid contraindicated based on renal function)
- Prevention of skeletal-related events in patients with bone metastases from solid tumors refractory or intolerant to zoledronic acid (or if zoledronic acid contraindicated based on renal function)
- Treatment of unresectable giant cell tumor of the bone
- Treatment of hypercalcemia of malignancy refractory to zoledronic acid therapy (or if zoledronic acid contraindicated based on renal function)
Additional Inclusion Criteria- Prescriber must be a VA/VA Community Care hematologist, oncologist, urologist, hospitalist, or endocrinologist
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 5 months after stopping treatment
Dosing & Safety Considerations- Dose: 120 mg subcutaneous every 4 weeks (do not confuse with denosumab Prolia)
- Patients with an eGFR <30 ml/minute are at increased risk of hypocalcemia
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DESOGESTREL/ ETHINYL ESTRADIOL TAB
APRI, AVERI, CYRED, CYRED EQ, ENSKYCE, ISIBLOOM, JULEBER, KALLIGA, RECLIPSEN
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APRI, AVERI, CYRED, CYRED EQ, ENSKYCE, ISIBLOOM, JULEBER, KALLIGA, RECLIPSEN |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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DESOGESTREL/ ETHINYL ESTRADIOL TAB
AZURETTE, CAZIANT, DESOGESTR-ETH ESTRAD ETH ESTRA, KARIVA, SIMLIYA, VELIVET, VIORELE, VOLNEA
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AZURETTE, CAZIANT, DESOGESTR-ETH ESTRAD ETH ESTRA, KARIVA, SIMLIYA, VELIVET, VIORELE, VOLNEA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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DEXAMETHASONE IMPLANT
OZURDEX
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OZURDEX |
2017-02-27 |
Inclusion Criteria- Inadequate response, contraindication, or adverse event to VEGF-inhibitors for diabetic macular edema or macular edema following branch or central retinal vein occlusion
- Inadequate response, contraindication, or adverse event to first-line treatments for posterior uveitis
Additional Inclusion Criteria- Provider is a VA/VA Community Care ophthalmologist
- Inadequate response or adverse event to intravitreal triamcinolone or a trial of triamcinolone is not appropriate (must document as adverse event in record/provide reason)
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DEXMEDETOMIDINE INJ,SOLN
DEXMEDETOMIDINE HCL, DEXMEDETOMIDINE-0.9% NACL, DEXMEDETOMIDINE-D5W, PRECEDEX
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DEXMEDETOMIDINE HCL, DEXMEDETOMIDINE-0.9% NACL, DEXMEDETOMIDINE-D5W, PRECEDEX |
2017-02-27 |
Indications & Inclusion Criteria- Patient must be receiving continuous respiratory monitoring and cardiac monitoring while receiving dexmedetomidine.
- Short-term sedation anticipated (<24 hours) as an alternative to propofol.
- Intermediate-term sedation (e.g., 24-72 hours) as an alternative to propofol or benzodiazepines where avoidance is desired.
- Transitioning from another sedative agent to facilitate ventilator weaning; may be continued during and post-extubation (typically 24-48 hours).
Exclusion Criteria- Advanced heart block.
- Baseline bradycardia (e.g., <50 bpm).
- Known hypersensitivity.
- Concurrent use of or anticipated need for neuromuscular blockade where dexmedetomidine would be the sole sedative agent used.
- Active myocardial ischemia.
- Severe hypotension (e.g., systolic blood pressure <90 mmHg with the use of 2 or more vasopressors).
Dosage & Administration- FDA approved dosing: Optional loading dose of 1 mcg/kg over 10 min (commonly omitted in ICU setting due to potential for hypotension and/or bradycardia) followed by a continuous infusion of 0.4 mcg/kg/hr, titrated to desired level of sedation (usual range 0.2-0.7 mcg/kg/hr), for up to 24 hours.
- Additional dosing: Omission, reduction, or slower infusions of the loading dose have been studied/observed. Maintenance doses up to 1.4 mcg/kg/hour (most patients requiring ≤1 mcg/kg/hr) and longer infusion durations (~3-5 days) used in clinical trials. Use beyond 24 hours associated with withdrawal symptoms, tolerance, tachyphylaxis, and dose-related increase in adverse reactions.
- Special Populations: Dose reductions should be considered in the elderly and in patients with hepatic impairment.
Monitoring Requirements- Administration restricted to personnel privileged to provide care in ICU/intensive-care level, procedural, or operating room settings.
- Continuous respiratory and cardiac monitoring recommended (e.g., heart rate, pulse oximetry).
- Monitor for loss of oropharyngeal muscle tone resulting in airway obstruction in nonintubated patients.
- Monitor for clinically significant bradycardia, hypotension, and sinus arrest requiring intervention (dose reduction, discontinuation, fluids, pressors, or anticholinergic agents).
- Routinely evaluate patient’s level and need for sedation using a validated assessment tool.
- Routinely assess for pain and treat when needed (analgesic properties are not primary use).
Clinical Considerations & Special Populations- Withdrawal: Potential withdrawal syndrome similar to clonidine if administered >24 hours. ~5% experience symptoms within 24 hours of discontinuation after up to 7 days use. Commonly reported: nausea, vomiting, agitation; hypertension and tachycardia also reported.
- Hemodynamic Risks: Reduces sympathetic nervous system activity. Use with caution in states where bradycardia/hypotension risk is pronounced (severe ventricular dysfunction, hypovolemia, advanced age, diabetes, chronic hypertension, significant aortic stenosis or left ventricular outflow tract obstruction).
- Serious CNS Pathology: Limited data for trauma, acute stroke, active seizures. Lacks anti-seizure activity. Consider potential for hypotension impacting cerebral hemodynamics when maintaining arterial blood pressure is critical.
- Drug Interactions: Additive effects may occur with co-administration of anesthetics, sedatives, hypnotics, opioids, negative chronotropic agents, and vasodilators.
- Adjunctive Treatment of Alcohol Withdrawal: Evidence limited to small RCTs/observational studies. May have benzodiazepine-sparing properties but unclear effect on intubation rates/duration or LOS. Should not be used alone (lacks antiseizure activity/effectiveness for delirium tremens). Case-by-case basis.
- ICU Delirium: Evidence limited/inconsistent for minimizing delirium, though guidelines endorse use to shorten duration. Produces lighter sedation, reduces need for benzodiazepines. Reasonable option for appropriately selected patients.
- Hepatic Impairment: Clearance decreases with increasing severity. Consider dose reduction despite titration to effect.
- Pregnancy: No adequate/well-controlled studies. Crosses placenta. Teratogenic effects not observed but adverse effects in rats found. Use only if benefit outweighs potential risks.
- Perioperative/Periprocedural Use: Addressed in separate guidance; operational details determined at facility level.
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DIHYDROERGOTAMINE SOLN,NASAL
DIHYDROERGOTAMINE MESYLATE, MIGRANAL, TRUDHESA
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DIHYDROERGOTAMINE MESYLATE, MIGRANAL, TRUDHESA |
2017-02-27 |
Exclusion Criteria- Concomitant use of strong CYP3A4 inhibitors (ritonavir, cobicistat, amiodarone, or others)
- Ischemic heart disease or coronary artery vasospasm
- Deviated septum or other nasal anatomical abnormality that could interfere with drug delivery
- Uncontrolled hypertension, peripheral arterial diseases, sepsis, following vascular surgery, or severe hepatic or renal impairment
- Hypersensitivity to ergot alkaloids
- Concomitant use of other 5-HT1 agonists (e.g., sumatriptan) or ergotamine containing/ergot-type medications within 24 hours
- Concomitant use of peripheral and central vasoconstrictors (midodrine, phenylephrine, pseudoephedrine, or others)
- Pregnancy
Inclusion Criteria- Diagnosis of Post traumatic headache, Cluster headache, Status migrainosous, or Medication overuse headache
- Lack of therapeutic response (after at least 3 migraine episodes and a minimum of a 30-day trial), contraindication, or intolerance to generic dihydroergotamine nasal spray
Additional Inclusion Criteria- For patients who can become pregnant: Pregnancy must be excluded prior to receiving dihydroergotamine nasal spray
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Indication & Therapeutic Use- Acute treatment of migraine with or without aura in adults
Dosage and Administration- Recommended dose: 1.45 mg (administered as one metered spray of 0.725 mg into each nostril)
- Dose may be repeated if needed, with a minimum interval of 1 hour after the first dose
- Maximum dosing limit: Do not exceed 2 doses within a 24-hour period or 3 doses within 7 days
- Device must be discarded after one complete dose (1 spray in each nostril)
Contraindications- Concomitant use of strong CYP3A4 inhibitors
- Ischemic heart disease or coronary artery vasospasm
- Uncontrolled hypertension, peripheral arterial diseases, sepsis, following vascular surgery, or severe hepatic or renal impairment
- Hypersensitivity to ergot alkaloids
- Recent use of other 5-HT1 agonists (e.g., sumatriptan) or ergotamine-containing/ergot-type medications within 24 hours
- Concomitant use of peripheral and central vasoconstrictors
Warnings and Precautions- Consider first dose administration under medical supervision with electrocardiogram in patients with risk factors
- Discontinue if cerebral hemorrhage, subarachnoid hemorrhage, or stroke is suspected
- Discontinue if signs or symptoms of vasoconstriction develop (may cause vasospasm or elevation in blood pressure)
- Medication Overuse Headache: Detoxification may be necessary
- Preterm Labor: Advise pregnant women of the risk
- Pleural and retroperitoneal fibrosis reported following prolonged daily use
- Administration should not exceed dosing guidelines or be used for chronic daily administration
- Suspend if severe local irritation occurs for no other attributable reasons
Special Populations- Pregnancy: May cause fetal harm based on animal data
- Lactation: Advise not to use during breastfeeding
Drug Interactions- Beta Blockers/Nicotine: May potentiate/provoke vasoconstriction
- Selective Serotonin Reuptake Inhibitors: Weakness, hyperreflexia, and incoordination may occur with coadministration
Clinical Efficacy Parameters- Pain freedom at 2 hours after dose: 38.0% (compared to 30.1% with best usual care)
- Most bothersome symptom (MBS) freedom at 2 hours after dose: 52.1% (compared to 46.4% with best usual care)
- Migraine recurrence incidence among patients reporting pain freedom at 2 hours: 7.1% at 24 hours and 14.3% at 48 hours
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DOFETILIDE CAP,ORAL
TIKOSYN
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TIKOSYN |
2017-02-27 |
Exclusion Criteria- Congenital or acquired long QT syndromes
- Baseline QT interval or QTc > 440 msec (or > 500 msec in patients with ventricular conduction abnormalities e.g., bundle branch blocks or intraventricular conduction delays)
- Severe renal impairment (calculated creatinine clearance per Cockcroft-Gault using actual body weight < 20 ml/min)
- Concomitant use with verapamil, cimetidine, trimethoprim (alone or in combination with sulfamethoxazole), ketoconazole, prochlorperazine, dolutegravir, megestrol, hydrochlorothiazide (alone or in combination with triamterene)
- Concomitant use with drugs that prolong the QT interval, or Class I or other Class III antiarrhythmic drug therapy
Inclusion Criteria- Atrial fibrillation / atrial flutter (highly symptomatic) in patients who require cardioversion to normal sinus rhythm
- Maintenance of normal sinus rhythm in patients with highly symptomatic atrial fibrillation/atrial flutter who have been converted to normal sinus rhythm
- Reserved for patients in whom atrial fibrillation/atrial flutter is highly symptomatic due to risk of life-threatening ventricular arrhythmias
Provider & Initiation Restrictions- Initial prescription restricted to VA / VA Community Care Cardiology provider or other locally designated provider
- Initiation, re-initiation, or dose increase restricted to inpatient admission for appropriate monitoring and dose adjustments
Monitoring & Dosing Requirements- Place patient on telemetry
- Check baseline QTc (use QT interval if heart rate < 60 beats per minute)
- Calculate creatinine clearance using Cockcroft-Gault formula based on actual body weight and serum creatinine
- Initial dosing based on calculated CrCl: >60 ml/min (500 mcg twice daily), 40 to 60 ml/min (250 mcg twice daily), 20 to <40 ml/min (125 mcg twice daily)
- Check QTc 2 to 3 hours after first dose; continue current dose if increase <15%, decrease dose if increase >15% or is >500 msec
- Determine QTc at 2 to 3 hours after each subsequent in-hospital dose (doses 2 to 5)
- Discontinue dofetilide if QTc increases to >500 msec (or >550 msec with ventricular conduction abnormalities) after the second dose
- Continuous ECG monitoring required for minimum of 3 days, or minimum of 12 hours after electrical or pharmacologic conversion to normal sinus rhythm, whichever is longer
- Only one down titration suggested for QTc prolongation
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DOXAZOSIN TAB
DOXAZOSIN MESYLATE
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DOXAZOSIN MESYLATE |
2017-02-27 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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DOXAZOSIN TAB,ORAL
CARDURA, DOXAZOSIN MESYLA, DOXAZOSIN MESYLATE
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CARDURA, DOXAZOSIN MESYLA, DOXAZOSIN MESYLATE |
2017-02-27 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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DOXAZOSIN TAB,SA
CARDURA XL
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CARDURA XL |
2017-02-27 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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DOXYCYCLINE CAP,ORAL
DOXYCYCLINE HYCLATE, DOXYCYCLINE MONOHYDRATE, MONDOXYNE NL, MORGIDOX
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DOXYCYCLINE HYCLATE, DOXYCYCLINE MONOHYDRATE, MONDOXYNE NL, MORGIDOX |
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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DOXYCYCLINE PWDR,RENST-ORAL
DOXYCYCLINE MONOHYDRATE
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DOXYCYCLINE MONOHYDRATE |
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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DOXYCYCLINE TAB
AVIDOXY, DOXYCYCLINE HYCLATE, DOXYCYCLINE MONOHYDRATE, TARGADOX
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AVIDOXY, DOXYCYCLINE HYCLATE, DOXYCYCLINE MONOHYDRATE, TARGADOX |
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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DRONEDARONE TAB
MULTAQ
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MULTAQ |
2017-02-27 |
Exclusion Criteria- Recently decompensated heart failure (HF) requiring hospitalization or Class IV HF
- Permanent atrial fibrillation (patients in whom normal sinus rhythm will not or cannot be restored)
- Second or third-degree atrioventricular block, or sick sinus syndrome (except in conjunction with a pacemaker)
- Significant bradycardia (e.g., less than 50 beats per minute)
- Concomitant use of a strong CYP3A inhibitor
- Concomitant use of drugs or herbal products that prolong the QT interval and may induce Torsade de Pointes
- QTc Bazett greater than or equal to 500 milliseconds with appropriate correction for prolongation of QRS interval in patients with intraventricular conduction delay and ventricular pacing
- Uncorrected hypokalemia or hypomagnesemia
- Liver or lung toxicity related to the previous use of amiodarone
- Severe hepatic impairment (i.e., Child-Pugh Grade C or baseline liver function tests greater than 2 times upper limit normal)
- Pregnancy (i.e., known pregnancy or positive pregnancy test; Category X)
- Nursing mothers
Inclusion Criteria- Restricted to VA / VA Community Care Cardiology provider or other locally designated provider for initial prescription
- Symptomatic recurrent paroxysmal or persistent atrial fibrillation documented by electrocardiogram (ECG) within the past 6 months, with a second ECG in sinus rhythm or pending cardioversion
- Intolerance (e.g., unmanageable significant adverse event), contraindication to, or ineffective therapy with at least one other antiarrhythmic agent used for the rhythm management of atrial fibrillation
- Female patients of child-bearing potential: pregnancy must be excluded prior to receiving dronedarone and patient provided counseling on use of an effective method of contraception and risks vs. benefits of taking dronedarone if patient were to become pregnant
Discontinuation Criteria- Consider discontinuation if the patient does not experience adequate symptom control (e.g., no or inadequate change in frequency or duration of palpitations or irregular heartbeat; no or inadequate increase in time to recurrence atrial fibrillation or flutter)
- Discontinue in patients who develop permanent atrial fibrillation, unless cardioversion is planned
- Discontinue if cardioversion fails or is not planned
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DROSPIRENONE/ ESTRADIOL TAB
ANGELIQ
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ANGELIQ |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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DROSPIRENONE/ ETHINYL ESTRADIOL TAB
ZARAH
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ZARAH |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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DROSPIRENONE/ ETHINYL ESTRADIOL TAB
JASMIEL, LORYNA, LO-ZUMANDIMINE, NIKKI, OCELLA, SYEDA, VESTURA, YASMIN 28, YAZ, ZUMANDIMINE
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JASMIEL, LORYNA, LO-ZUMANDIMINE, NIKKI, OCELLA, SYEDA, VESTURA, YASMIN 28, YAZ, ZUMANDIMINE |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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DROSPIRENONE/ ETHINYL ESTRADIOL/ LEVOMEFOLATE TAB
BEYAZ, DROSPIRENONE-ETH ESTRA-LEVOMEF, SAFYRAL
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BEYAZ, DROSPIRENONE-ETH ESTRA-LEVOMEF, SAFYRAL |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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ECALLANTIDE INJ
KALBITOR
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KALBITOR |
2017-02-27 |
Exclusion Criteria- Angioedema or abdominal pain not associated with C1 inhibitor deficiency
Inclusion Criteria (ALL must be met)- Restricted to VA / VA Community Care allergy/immunology or dermatology provider; or for use in Emergency Medicine/Urgent Care
- Diagnosis of Hereditary Angioedema due to C1 inhibitor deficiency (HAE-C1INH) as established by laboratory testing
Additional Inclusion Criteria (ONE must be met)- Long-term prophylaxis for HAE-C1INH attacks after consideration of either an attenuated androgen or antifibrinolytic
Clinical Context & Decision-Making Requirements- Prior consideration of an attenuated androgen or antifibrinolytic must be discussed with the patient using shared decision-making, including efficacy, routes of administration, and side effects of each therapy
- Baseline attack rate criteria may include at least 2 attacks per month or baseline attack rate in clinical trials
- Need for long-term prophylaxis should be determined using shared decision-making
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ECULIZUMAB INJ,SOLN
SOLIRIS
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SOLIRIS |
2017-02-27 |
Exclusion Criteria- Shiga toxin E. coli-related hemolytic uremic syndrome (STEC-HUS)
- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Concomitant therapy with rituximab or any other complement inhibitor such as ravulizumab
- Concomitant chronic therapy with plasma exchange
Inclusion Criteria- Must be prescribed by or in consultation with a VA or VA Community Care nephrology or hematology provider or locally designated expert
- Intolerance, contraindication, or inadequate symptom control to ravulizumab over at least a 2-month period
- Patient is vaccinated against pneumococcal disease
- Patient is vaccinated with BOTH the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
Additional Inclusion Criteria- Requires treatment of aHUS with documentation ruling out Shiga toxin E. coli-related hemolytic uremic syndrome (STEC-HUS) and thrombotic thrombocytopenia purpura (TTP) (e.g., clinical evaluation and/or rule out of ADAMTS13 deficiency)
- Requires prophylaxis in renal transplant to ensure aHUS does not recur in the transplanted kidney
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Concomitant therapy with rituximab, neonatal Fc receptor antagonists (e.g., efgartigimod), or any other complement inhibitor (e.g., ravulizumab)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (these treatments may be used for exacerbations)
- Thymectomy within 12 months
Inclusion Criteria- Care provided by a VA or VA Community Care neurology provider or locally designated expert
- Diagnosis of acetylcholine receptor (AChR) antibody positive generalized myasthenia gravis (gMG)
- Not a candidate for thymectomy
- Patient has a Myasthenia Gravis Foundation of America (MGFA) Clinical Classification of class II to IV
- Patient has a Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) total score ≥ 6
- Patient is vaccinated against pneumococcal disease and Neisseria meningitidis with both Meningococcal conjugate vaccine (MenACWY) and Meningococcal serogroup B vaccine
- Intolerance, contraindication, or inadequate symptom control to ravulizumab or zilucoplan over at least a 6-month period
- Additional Inclusion Criteria (One of the following must be met)
- Inadequate symptom control to maximally tolerated pyridostigmine AND at least two immunosuppressive agents separately trialed for at least 6 months each [e.g., azathioprine, cyclosporine, mycophenolate, etc.]
- History of intolerance or contraindication preventing trial of immunosuppressive agents [e.g., azathioprine, cyclosporine, mycophenolate, etc.]
- Lack of symptom control despite 4 or more courses of plasma exchange, high-dose steroid bursts and/or intravenous immune globulin within a 12 month or less period
Emergency/Prophylaxis Protocol- In emergent cases where waiting to initiate eculizumab at least two weeks after completion of vaccination is not possible, patients should begin the vaccination series at the time of initial eculizumab dosing and be provided with appropriate prophylaxis.
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Concomitant therapy with rituximab or any other complement inhibitor (such as ravulizumab)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use of these treatments during exacerbations is reasonable while on eculizumab)
Inclusion Criteria- Care provided by VA or VA Community Care neurology provider
- Vaccination against pneumococcal disease and Haemophilus influenzae type B
- Vaccination with both the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases, begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
Exclusion Criteria- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Inclusion Criteria- Prescribed by or in consultation with a VA or VA Community Care hematology, oncology, immunology provider or locally designated expert
- Vaccinated against pneumococcal disease
- Vaccinated with both the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases, begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
- Laboratory-confirmed diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), evidenced by detectable glycosylphosphatidylinositol (GPI)-deficient hematopoietic clones (Type III PNH red blood cells [RBC]) via Flow Cytometry, with pathology report documentation indicating presence of PNH-type RBC
- Lactate dehydrogenase (LDH) level of 1.5 times the upper limit of the normal range (laboratory results with reference range must be available for review)
- Documentation that a meningococcal vaccine was administered at least two weeks prior to the first dose of eculizumab
Exclusion Criteria- Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae active infection
- Active, clinically significant infection
- Concomitant biologic therapy for neuromyelitis optica spectrum disorder (NMOSD)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use of these treatments in exacerbations is reasonable)
Inclusion Criteria- Care provided by VA or VA Community Care neurology provider or locally designated expert
- Diagnosis of aquaporin-4 antibody positive NMOSD
- Patient is vaccinated against pneumococcal disease
- Patient is vaccinated with BOTH the protein conjugate ACWY meningococcal vaccine and the type B meningococcal vaccine (in emergent cases begin vaccination series at initial dosing and provide antibiotic prophylaxis until 2 weeks after vaccination)
- Contraindication, intolerance, or lack of therapeutic response to rituximab
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EDOXABAN TAB
SAVAYSA
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SAVAYSA |
2017-02-27 |
Indications- Atrial fibrillation/flutter (AF)
- Acute venous thromboembolism (VTE), or prevention of recurrent VTE
- Primary prophylaxis of VTE in patients undergoing hip or knee replacement surgery
- Other indication for anticoagulation (local adjudication required)
Exclusions- Mechanical heart valve
- Moderate to severe rheumatic mitral valve stenosis (for AF/flutter only)
- Antiphospholipid syndrome (APS)
- Known significant liver disease (e.g., acute clinical hepatitis, cirrhosis [Child-Pugh C], or hepatic disease associated with coagulopathy)
- Pregnancy
- Breastfeeding
Pre-Treatment Assessment & Monitoring- Assessment of renal function (CrCl) and hemoglobin, hematocrit, and platelets
- Consider liver function testing in patients with a history of or risk for hepatic insufficiency
- Provider must assess DOAC choice, dose, and duration considering patient’s age, renal function, liver function, concurrent medications, and indication
- Identify and address modifiable risk factors for bleeding (e.g., NSAIDs, antiplatelet therapy)
- Document the treatment plan including duration in the patient’s chart
Dosing & Administration Requirements- For acute VTE: Administer 10 mg twice daily for 7 days as oral loading dose BEFORE starting maintenance doses
- Review drug dosing errors and drug-drug interactions, especially with new starts
Special Populations & Clinical Considerations- Bioprosthetic heart valve placement in the past 3 months: Appropriate based on shared decision-making process between provider and patient
- Severe renal impairment (CrCl <25-30 ml/min) or hemodialysis: Individual evaluation of risks and benefits recommended; net clinical benefit unclear
- Apixaban may be the preferred DOAC when CrCl is less than 30 ml/min
- For patients who can become pregnant: Counsel on potential risks vs benefits of treatment and use of effective contraception during therapy
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
FDA Approved Adult Indications- Non-valvular atrial fibrillation
- Treatment of DVT and PE (after 5-10 days of parenteral anticoagulant)
- Reduction in the risk of recurrent DVT and PE following initial therapy
- Post-surgical VTE prophylaxis following hip replacement surgery
- Post-surgical VTE prophylaxis following knee replacement surgery
Oversight & Initiation- Chronic DOAC therapy requires initial assessment, education, and follow-up by locally designated staff (e.g., anticoagulation management program or other designees).
- Facilities should utilize decision support tools and/or anticoagulation staff for upfront review to verify appropriate candidate selection, agent choice, and dosing upon initiation.
- Short-term treatment (e.g., post-surgical VTE prophylaxis) or very low dose regimens should follow education/monitoring protocols similar to alternative agents in that setting.
Laboratory Monitoring- Baseline: Serum creatinine (SCr) to estimate creatinine clearance (CrCl); CrCl estimated using Cockcroft-Gault equation with actual body weight for apixaban trials. Hemoglobin, hematocrit, and platelets required. Liver function tests may be considered for patients with history/risk of hepatic insufficiency. PT/aPTT may be obtained for emergency reference. Baseline values drawn within 1-3 months are acceptable per provider clinical judgment based on age/health status/comorbidities.
- Follow-up: SCr monitored at least annually (more frequently if CrCl < 60 ml/min, concomitant illness worsening renal function, or age ≥ 75 years). Hemoglobin, hematocrit, and platelets monitored at least annually or as clinically dictated. Liver function testing considered for underlying liver disease or clinical indication.
Patient Education- Initial and periodic education must cover: capsule/tablet identification, proper storage, therapy indication, risks/benefits, anticipated duration, daily dose/dosing changes (e.g., loading doses), administration considerations, drug interactions, monitoring requirements, adherence importance, management of missed/extra doses, signs/symptoms of bleeding/thromboembolic events, avoidance of major bleeding risk medications (e.g., NSAIDs, antiplatelets) unless instructed, non-bleeding adverse events, fall risks/mitigation, medication supply acquisition, pre-procedure provider notification for peri-procedural management, anticoagulation provider contact information, and gender-specific considerations for women of childbearing age (menstrual difficulties, pregnancy, contraception).
Adherence Monitoring- Monitor adherence, refill history, and medication tolerance, especially at therapy initiation.
- Utilize population management tools, telephone follow-up, face-to-face visits, secure messaging, or combinations based on site resources.
Follow-up Care- Initial: Within 2-4 weeks of initiation (or sooner if clinically indicated) to assess tolerance, bleeding, thromboembolic events, other adverse events (e.g., GI intolerance), adherence, correct dosing (e.g., transition from high-intensity initiation dosing for acute VTE), duplicate therapy, and reinforce education.
- Periodic/Long-term: Reassess adherence, screen for drug interactions, monitor labs as needed. Time points, methods, and responsible staff determined locally per VHA Directive 1108.16(1).
Quality Assurance- Incorporate DOACs into ongoing quality assurance plans per VHA Directive 1108.16(1).
- Report adverse events per local protocols and P&T Committee; enter into VA ADERS.
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ELBASVIR/ GRAZOPREVIR TAB
ZEPATIER
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ZEPATIER |
2017-02-27 |
Patient Eligibility & Characteristics- Genotype (GT) 1 or 4, treatment naïve, with or without compensated cirrhosis
- Limited life expectancy
- Severe hepatic impairment (Child-Pugh B/C or history of hepatic decompensation)
- Prior hepatitis C virus (HCV) treatment failure to a non-structural protein 5A (NS5A) inhibitor containing regimen
Specialist Consultation & Regimen Planning- Care provided by and/or in consultation with a VA/VA Community Care Hepatitis C Specialist
- Treatment regimen and duration consistent with HCV genotype (GT) and patient characteristics
Screening & Laboratory Requirements- Completed hepatitis B screening: at minimum HBsAg, HBV core antibody (anti-HBc) and HBV surface antibody (anti-HBs)
- Hepatitis B surface antigen (HBsAg) positive and not on antiviral treatment with entecavir or tenofovir
Adherence & Counseling- Documented ongoing nonadherence to prescribed medications or medical treatment
- Adherence counseling performed including laboratory follow-up and documented understanding by patient
Drug Interactions & Contraindications- Concurrent use of drugs not recommended with EBR/GZR (e.g., rifamycins, strong CYP3A inducers, cobicistat, cyclosporine, boosted HIV protease inhibitors, efavirenz) Recommend full drug-drug interaction check.
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ELOTUZUMAB INJ,LYPHL
EMPLICITI
|
EMPLICITI |
2017-02-27 |
Laboratory & Hematologic Criteria- Exclusion: Hemoglobin < 8 g/dL; Must transfuse to hemoglobin above 8 gm/dL prior to therapy initiation
- Exclusion: Absolute neutrophil count (ANC) < 1000/mm3
- Exclusion: Platelet count < 50,000/mm3 (<30,000/mm3 if myeloma involvement in bone marrow > 50%)
- Exclusion: Total bilirubin > 2x the upper limit of the normal range (except for Gilbert Syndrome: direct bilirubin > 2 mg/dL) or ALT and AST > 3x upper limit of normal
Clinical Status & Performance- Exclusion: Eastern Cooperative Oncology Group performance status > 2
Infection, Pregnancy & Lactation- Exclusion: Active or uncontrolled infection
- Exclusion: Known pregnancy
- Exclusion: Lactating
Diagnosis & Care Setting- Inclusion: Diagnosis of relapsed or refractory multiple myeloma, following at least one prior line of therapy
- Inclusion: Care is provided by a VA or VA Community Care hematology/oncology provider
Palliative Care- Inclusion: Goals of care and role of Palliative Care consult have been discussed and documented
Contraception & REMS Compliance- Inclusion: Patients who can become pregnant and patients with partners who can become pregnant must comply with pregnancy testing and contraception requirements for lenalidomide or pomalidomide under their REMS programs
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EMTRICITABINE/ TENOFOVIR TAB
DESCOVY
|
DESCOVY |
2017-02-27 |
Inclusion Criteria- Prescribed by, or in collaboration with, a provider with experience or training in the administration of PrEP (designated facility PrEP providers)
- Adult male (as assigned at birth) at substantial risk of HIV acquisition (e.g., sex without condoms, recent or frequent sexually transmitted infections, sexual relationship with HIV-infected partner, injection drug abuse with equipment sharing)
- Intolerance to Truvada or contraindication (e.g., CrCl 30–59 mL/min or CrCl ≥60 mL/min with multiple risk factors for significant renal dysfunction OR osteoporosis/osteopenia/prior stress fracture)
Exclusion Criteria- Significant noncompliance with follow-up HIV testing unless barriers to compliance have been significantly addressed by provider
- Individuals at risk from receptive vaginal sex (female at birth)
- Concomitant contraindicated medications (Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifamycin derivatives, St. John’s Wort)
Supplemental & Monitoring Information- HIV must be excluded prior to administration of FTC/TAF
- Maximum 90-day supply with NO REFILLS
- FTC/TAF associated with hyperlipidemia, increased body mass index, and atherosclerotic cardiovascular disease (ASCVD) risk score; FTC/TDF may be preferred in patients with increased metabolic risk
- Additional monitoring requirements per PBM VHA Clinical Recommendations
Indications & Target Populations- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.
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| ▸ |
ESTRADIOL GEL,TOP
DIVIGEL
|
DIVIGEL |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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ESTRADIOL PATCH
CLIMARA, DOTTI, ESTRADIOL (ONCE WEEKLY), ESTRADIOL (TWICE WEEKLY), LYLLANA, MENOSTAR, MINIVELLE, VIVELLE-DOT
|
CLIMARA, DOTTI, ESTRADIOL (ONCE WEEKLY), ESTRADIOL (TWICE WEEKLY), LYLLANA, MENOSTAR, MINIVELLE, VIVELLE-DOT |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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| ▸ |
ESTRADIOL RING,VAG
ESTRING
|
ESTRING |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
|
| ▸ |
ESTRADIOL RING,VAG
FEMRING
|
FEMRING |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
|
| ▸ |
ESTRADIOL SPRAY,TOP
EVAMIST
|
EVAMIST |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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| ▸ |
ESTRADIOL TAB
|
|
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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| ▸ |
ESTRADIOL/ LEVONORGESTREL PATCH
CLIMARA PRO
|
CLIMARA PRO |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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| ▸ |
ESTRADIOL/ NORETHINDRONE FILM,CONT REL
COMBIPATCH
|
COMBIPATCH |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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ESTRADIOL/ NORETHINDRONE TAB
ABIGALE, ABIGALE LO, ACTIVELLA, ESTRADIOL-NORETHINDRONE ACETAT, MIMVEY
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ABIGALE, ABIGALE LO, ACTIVELLA, ESTRADIOL-NORETHINDRONE ACETAT, MIMVEY |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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| ▸ |
ESTROGENS CREAM,VAG
PREMARIN
|
PREMARIN |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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| ▸ |
ESTROGENS TAB
MENEST
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MENEST |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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| ▸ |
ESTROGENS/ MEDROXYPROGESTERONE TAB
PREMPHASE, PREMPRO
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PREMPHASE, PREMPRO |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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ETHINYL ESTRADIOL / NORETHINDRONE ORAL TABLET
NORETHINDRON-ETHINYL ESTRADIOL
|
NORETHINDRON-ETHINYL ESTRADIOL |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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ETHINYL ESTRADIOL/ ETHYNODIOL DIACETATE TAB
ETHYNODIOL-ETHINYL ESTRADIOL, KELNOR 1-35, VALTYA, ZOVIA 1-35
|
ETHYNODIOL-ETHINYL ESTRADIOL, KELNOR 1-35, VALTYA, ZOVIA 1-35 |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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| ▸ |
ETHINYL ESTRADIOL/ FERROUS FUMARATE/ NORETHINDRONE CAP,ORAL
GEMMILY, NORETHINDRONE-E.ESTRADIOL-IRON, TAYTULLA
|
GEMMILY, NORETHINDRONE-E.ESTRADIOL-IRON, TAYTULLA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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| ▸ |
ETHINYL ESTRADIOL/ FERROUS FUMARATE/ NORETHINDRONE TAB
AUROVELA 24 FE, AUROVELA FE, BLISOVI 24 FE, BLISOVI FE, FEIRZA, HAILEY 24 FE, HAILEY FE, JUNEL FE 24, LARIN 24 FE, LARIN FE, LO LOESTRIN FE, LOESTRIN FE, MICROGESTIN FE, NORETHINDRONE-E.ESTRADIOL-IRON, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TILIA FE, TRI-LEGEST FE, XARAH FE
|
AUROVELA 24 FE, AUROVELA FE, BLISOVI 24 FE, BLISOVI FE, FEIRZA, HAILEY 24 FE, HAILEY FE, JUNEL FE 24, LARIN 24 FE, LARIN FE, LO LOESTRIN FE, LOESTRIN FE, MICROGESTIN FE, NORETHINDRONE-E.ESTRADIOL-IRON, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TILIA FE, TRI-LEGEST FE, XARAH FE |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
|
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ETHINYL ESTRADIOL/ FERROUS FUMARATE/ NORETHINDRONE TAB,CHEWABLE
CHARLOTTE 24 FE, FINZALA, GALBRIELA, KAITLIB FE, MIBELAS 24 FE, NORETHINDRONE-E.ESTRADIOL-IRON, NORETHIN-ETH ESTRA-FERROUS FUM, WYMZYA FE, XELRIA FE
|
CHARLOTTE 24 FE, FINZALA, GALBRIELA, KAITLIB FE, MIBELAS 24 FE, NORETHINDRONE-E.ESTRADIOL-IRON, NORETHIN-ETH ESTRA-FERROUS FUM, WYMZYA FE, XELRIA FE |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
|
| ▸ |
ETHINYL ESTRADIOL/ LEVONORGESTREL TAB
AMETHYST, DOLISHALE, LEVONORGESTREL-ETH ESTRADIOL
|
AMETHYST, DOLISHALE, LEVONORGESTREL-ETH ESTRADIOL |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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| ▸ |
ETHINYL ESTRADIOL/ LEVONORGESTREL TAB
AFIRMELLE, ALTAVERA, AUBRA, AUBRA EQ, AVIANE, AYUNA, CHATEAL (28), CHATEAL EQ, ENPRESSE, FALMINA, ICLEVIA, JOLESSA, KURVELO, LESSINA, LEVONEST, LEVONORGESTREL-ETH ESTRADIOL, LUTERA, MARLISSA, PORTIA, RIVELSA, ROSYRAH, SETLAKIN, TYBLUME, VIENVA
|
AFIRMELLE, ALTAVERA, AUBRA, AUBRA EQ, AVIANE, AYUNA, CHATEAL (28), CHATEAL EQ, ENPRESSE, FALMINA, ICLEVIA, JOLESSA, KURVELO, LESSINA, LEVONEST, LEVONORGESTREL-ETH ESTRADIOL, LUTERA, MARLISSA, PORTIA, RIVELSA, ROSYRAH, SETLAKIN, TYBLUME, VIENVA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
|
| ▸ |
ETHINYL ESTRADIOL/ LEVONORGESTREL TAB,ORAL
AMETHIA, ASHLYNA, CAMRESE, CAMRESE LO, DAYSEE, JAIMIESS, LOJAIMIESS, SIMPESSE
|
AMETHIA, ASHLYNA, CAMRESE, CAMRESE LO, DAYSEE, JAIMIESS, LOJAIMIESS, SIMPESSE |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
|
| ▸ |
ETHINYL ESTRADIOL/ NORELGESTROMIN PATCH
NORELGESTROMIN-ETH ESTRADIOL, XULANE, ZAFEMY
|
NORELGESTROMIN-ETH ESTRADIOL, XULANE, ZAFEMY |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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| ▸ |
ETHINYL ESTRADIOL/ NORETHINDRONE TAB
ARANELLE, BALZIVA, BRIELLYN, FEIRZA, FYAVOLV, HAILEY FE, JUNEL FE, MICROGESTIN FE, NECON, NORETHINDRON-ETHINYL ESTRADIOL, NORTREL, PHILITH, VYFEMLA, WERA
|
ARANELLE, BALZIVA, BRIELLYN, FEIRZA, FYAVOLV, HAILEY FE, JUNEL FE, MICROGESTIN FE, NECON, NORETHINDRON-ETHINYL ESTRADIOL, NORTREL, PHILITH, VYFEMLA, WERA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
|
| ▸ |
ETHINYL ESTRADIOL/ NORETHINDRONE TAB
ARANELLE, BALZIVA, BRIELLYN, FEIRZA, FYAVOLV, HAILEY FE, JUNEL FE, MICROGESTIN FE, NECON, NORETHINDRON-ETHINYL ESTRADIOL, NORTREL, PHILITH, VYFEMLA, WERA
|
ARANELLE, BALZIVA, BRIELLYN, FEIRZA, FYAVOLV, HAILEY FE, JUNEL FE, MICROGESTIN FE, NECON, NORETHINDRON-ETHINYL ESTRADIOL, NORTREL, PHILITH, VYFEMLA, WERA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
|
| ▸ |
ETHINYL ESTRADIOL/ NORETHINDRONE TAB
ALYACEN, AUROVELA, DASETTA, FYAVOLV, HAILEY, JINTELI, JUNEL, LARIN, LOESTRIN, LUIZZA, MICROGESTIN, NORETHINDRON-ETHINYL ESTRADIOL, NORTREL, NYLIA
|
ALYACEN, AUROVELA, DASETTA, FYAVOLV, HAILEY, JINTELI, JUNEL, LARIN, LOESTRIN, LUIZZA, MICROGESTIN, NORETHINDRON-ETHINYL ESTRADIOL, NORTREL, NYLIA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
|
| ▸ |
ETHINYL ESTRADIOL/ NORETHINDRONE TAB
ALYACEN, AUROVELA, DASETTA, FYAVOLV, HAILEY, JINTELI, JUNEL, LARIN, LOESTRIN, LUIZZA, MICROGESTIN, NORETHINDRON-ETHINYL ESTRADIOL, NORTREL, NYLIA
|
ALYACEN, AUROVELA, DASETTA, FYAVOLV, HAILEY, JINTELI, JUNEL, LARIN, LOESTRIN, LUIZZA, MICROGESTIN, NORETHINDRON-ETHINYL ESTRADIOL, NORTREL, NYLIA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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ETHINYL ESTRADIOL/ NORGESTIMATE TAB
ESTARYLLA, MILI, MONO-LINYAH, NORGESTIMATE-ETHINYL ESTRADIOL, ORTHO TRI-CYCLEN, SPRINTEC, TRI-ESTARYLLA, TRI-LINYAH, TRI-MILI, TRI-SPRINTEC, TRI-VYLIBRA, VYLIBRA
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ESTARYLLA, MILI, MONO-LINYAH, NORGESTIMATE-ETHINYL ESTRADIOL, ORTHO TRI-CYCLEN, SPRINTEC, TRI-ESTARYLLA, TRI-LINYAH, TRI-MILI, TRI-SPRINTEC, TRI-VYLIBRA, VYLIBRA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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ETHINYL ESTRADIOL/ NORGESTIMATE TAB
NORGESTIMATE-ETHINYL ESTRADIOL, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-VYLIBRA LO
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NORGESTIMATE-ETHINYL ESTRADIOL, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-VYLIBRA LO |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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ETHINYL ESTRADIOL/ NORGESTREL TAB
CRYSELLE, ELINEST, LOW-OGESTREL, TURQOZ
|
CRYSELLE, ELINEST, LOW-OGESTREL, TURQOZ |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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ETONOGESTREL IMPLANT
NEXPLANON
|
NEXPLANON |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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EVOLOCUMAB INJ,SOLN
REPATHA PUSHTRONEX, REPATHA SURECLICK, REPATHA SYRINGE
|
REPATHA PUSHTRONEX, REPATHA SURECLICK, REPATHA SYRINGE |
2017-02-27 |
Exclusion Criteria- End-stage renal disease on dialysis
- Advanced heart failure with limited prognosis
- Severe comorbid non-cardiovascular condition that is expected to limit life expectancy
- Pregnant or lactating status
- Primary Inclusion Criteria (One must be met)
- History of atherosclerotic cardiovascular disease (ASCVD)
- Severe primary hypercholesterolemia (e.g., heterozygous familial hypercholesterolemia [HeFH], LDL-C > 190 mg/dL) without ASCVD
- Additional Inclusion Criteria (All must be met)
- Contraindication, intolerance to, or insufficient LDL-C reduction with maximally tolerated dose of statin, requiring further LDL-C lowering to reduce ASCVD risk consistent with established guidelines
- Contraindication, intolerance to, or insufficient LDL-C reduction with ezetimibe, requiring further LDL-C lowering to reduce ASCVD risk consistent with established guidelines
Additional Inclusion Criteria (Select if Applicable)- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Statin Intolerance & Management Guidelines- Statins remain the treatment of choice; PCSK9 inhibitors augment LDL-C lowering when used with statins
- Documented statin intolerance requires a trial of at least 2 statins resulting in intolerable unexplained skeletal muscle-related complaints (pain/ache, weakness, or cramping) that resolve upon discontinuation
- One statin causing symptoms must be trialed at the lowest approved dose; alternate day dosing should be attempted
- Evaluate and address factors increasing risk for statin intolerance or non-statin causes of muscle symptoms (e.g., hypothyroidism, vitamin D deficiency, drug-drug interactions, excessive alcohol use)
- Patients on lower than optimal statin doses should receive ezetimibe as second-line therapy
- For patients on suboptimal statin doses plus ezetimibe: Consider PCSK9 inhibitor if LDL reduction from untreated baseline is less than clinically desired and/or LDL-C goal is not achieved despite confirmed adherence
- For completely statin-intolerant patients: Consider PCSK9 inhibitor if ezetimibe has not/is not expected to provide clinically desired LDL-C reduction or achieve LDL-C goal despite confirmed adherence
High-Risk Patients Without Established ASCVD- Utilize ezetimibe, bile acid sequestrant (BAS), or combination in appropriate candidates
- For high-risk patients (e.g., diabetes mellitus, 10-year risk score > 20%, presence of subclinical atherosclerosis by imaging including coronary artery calcium assessment and coronary CT): Consider PCSK9 inhibitor if LDL-C is not reduced by a clinically meaningful percentage from baseline (>30% or >50% based on risk/need) and/or goals are not reached despite confirmed adherence
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FENTANYL PATCH
|
|
2017-02-27 |
Patient Eligibility & Indications- Requires around-the-clock analgesia for moderate to severe, persistent chronic pain
- Must be opioid-tolerant: taking ≥60 mg oral morphine daily, ≥20 mg oral methadone daily, ≥30 mg oral oxycodone daily, ≥8 mg oral hydromorphone daily, or an equianalgesic dose of another opioid for ≥1 week
- Must meet at least one condition: unable to swallow/tolerate/absorb oral preparations; unable to adhere to oral opioid regimen due to cognitive/psychiatric impairment; requires chronic/stable pain management as part of end-of-life care where twice-daily or more frequent oral administration is problematic; or documented current/past history of intolerable adverse effects to long-acting morphine and oxycodone (e.g., constipation unresponsive to aggressive laxatives, nausea inadequately controlled by antiemetics/dose titration)
- Applies to new starts only; stable patients should not be required to discontinue unless clinically indicated
Exclusion Criteria- Mild pain
- Breakthrough or intermittent pain (as-needed/p.r.n. analgesia)
- Postoperative pain, including outpatient or day surgeries
- Pain due to acute clinical conditions/situations (e.g., acute trauma, new onset herpes zoster/shingles)
- Hypersensitivity to fentanyl or local hypersensitivity reaction not adequately controlled with topical medications
- Contraindication to opioids (significant respiratory depression, acute/severe bronchial asthma/hypercarbia, known/suspected paralytic ileus)
Dosing & Administration Requirements- Initial dose is an initial conversion dose; must be individualized based on medical condition, potency/dose/type of previous opioid, degree of tolerance/exposure, past analgesic response/adverse experiences, and accuracy of conversion factors
- Conversion table is unidirectional (other opioids TO transdermal fentanyl only); do not use to convert FROM transdermal fentanyl to other opioids due to risk of overdose/toxicity
- Dose increases generally should not be sooner than 3 days after initial dose or more frequently than every 6 days thereafter
- Dosage increments based on daily supplemental opioid use: morphine 45 mg/d orally equals a 12 mcg/h increase in transdermal fentanyl dose
- Patches may be applied every 48 hours instead of 72 hours for some patients; evaluate dose increase before changing interval to maintain 72-hour regimen
- Short-acting analgesics should be provided on an as-needed basis until sufficient analgesic effects are achieved (1–2 days) and considered for predictable, incident breakthrough pain
- Patches available in strengths: 12.5, 25, 50, 75, 100 mcg/h
- Do not cut, damage, or alter patches prior to application; use alternate opioid therapy if fractions are needed
- Remove previous patch before applying next dose (especially in inpatient settings); check skin folds
- Avoid external heat on patch site (heating pads, electric blankets, saunas, hot tubs, heated water beds, hot baths, sunbathing); monitor for toxicity if fever/increased core temperature develops
- Remove patch prior to MRI; replace after procedure
Safety Monitoring & Risk Mitigation- Verify doses during medication reconciliation for hospitalized patients using patches at home
- Implement risk mitigation strategies per VA/DOD Clinical Practice Guideline on Management of Opioid Therapy for Chronic Pain (2017): informed consent conversation, ongoing random urine drug testing with confirmatory testing, checking state prescription drug monitoring programs, monitoring for overdose potential and suicidality, providing overdose education, prescribing naloxone rescue with education
- Assess concomitant use of other opioids to reduce overdose risk
- Reduce dose of fentanyl or CNS depressants when used concomitantly; VA/DOD guideline recommends against concurrent use of opioids and benzodiazepines; consider tapering one or both if risks exceed benefits and obtain specialty consultation
- Use caution with concomitant CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, nefazodone, ritonavir, troleandomycin); monitor carefully for extended period and adjust dosage if warranted
- Allow adequate time for recovery from toxicity; monitor and treat for at least 24 hours after patch removal due to mean elimination half-life of 17 hours
- Provide and document mandatory patient/caregiver education on use, indications, high potency, dose, safety precautions, application/removal/disposal, signs of toxicity, secure storage (locked place, out of reach of children/pets), risk of fatal respiratory depression from used patches, and avoiding application in front of children
Special Populations & Precautions- Elderly, cachectic, or debilitated patients: use caution due to altered pharmacokinetics (poor fat stores, muscle wasting, altered clearance)
- Pregnant women: Pregnancy Category C; use only if potential benefit justifies potential risk to fetus. Not recommended for analgesia during labor and delivery
- Lactating women: Not recommended due to potential risks to infants
Provider Management & Follow-up- Initiation and adjustments restricted to Pain Clinic, Addiction Medicine, Addiction Psychiatry Specialists with pain management expertise, Oncology (for advanced cancer pain), Hospice and Palliative Specialty Care, or consultation with a practitioner having relevant knowledge/expertise (e.g., CARA mandated Pain Team, local facility-designated pain SME, Pain Clinic providers, Clinical Pharmacy Specialist with pain management scope)
- Patient must be followed by a VA or VA-contracted provider for management of transdermal fentanyl therapy
- For doses >50 mcg/h: evaluate by specialist in pain management, anesthesiology, palliative care, or hematology/oncology
- Perioperative use: Pain experts suggest continuing patch throughout perioperative period to avoid withdrawal or uncontrolled post-op pain; abrupt discontinuation not recommended
- Provider initiation/continuation follows VA/DOD guideline against initiating long-term opioid therapy for chronic pain; ongoing risk mitigation, assessment for OUD, and tapering when risks exceed benefits
- Tapering: Screen/treat complicating conditions first (mental health disorders, OUD/SUD, medical complications, sleep disorders). Dose reductions typically 5% to 20% every 4 weeks
- OUD management: If suspected, refer to addiction-focused medical management in PACT or Interdisciplinary Pain Management Team with Addiction Medicine expertise/MAT access, or Primary Care Mental Health/specialty care
Transitioning Veteran Provision- If transitioning care from DoD to VHA and VA prescriber determines continuing medication is safe/clinically appropriate after assessment/consultation, the remainder of criteria does not apply
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FINASTERIDE TAB
PROSCAR
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PROSCAR |
2017-02-27 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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FLUPHENAZINE INJ
FLUPHENAZINE DECANOATE
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FLUPHENAZINE DECANOATE |
2017-02-27 |
Transitioning Veteran Status- Veteran is transitioning care from the Department of Defense to VHA
- VA prescriber has determined that continuing the medication is safe and clinically appropriate (remainder of criteria not applicable if met)
Exclusion Criteria- Patient has never taken the long-acting injectable antipsychotic ordered in any formulation (e.g., oral)
- Patient has a hypersensitivity to the antipsychotic ordered
Required Inclusion Criteria (All Must Be Met)- Diagnosis of schizophrenia or schizoaffective disorder, or bipolar disorder
- Prescriber is a VA Mental Health Provider
- Patient has taken and tolerated the antipsychotic ordered prior to receiving it as a LAI for an adequate length of time
- Patient will be transitioned from oral/short-acting injection medication to the long-acting injectable per guidelines/manufacturer recommendations
Alternative Inclusion Criteria (One Must Be Met)- Patient has relapsed or been hospitalized for the intended indication or complications of the intended indication because of nonadherence when treated with oral antipsychotics
- Patient’s care environment is such that a LAI is a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely)
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GABAPENTIN CAP,ORAL
NEURONTIN, RELGAABI
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NEURONTIN, RELGAABI |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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GABAPENTIN TAB
NEURONTIN
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NEURONTIN |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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GLATIRAMER INJ,SOLN
COPAXONE, GLATIRAMER ACETATE, GLATOPA
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COPAXONE, GLATIRAMER ACETATE, GLATOPA |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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HALOPERIDOL INJ
HALOPERIDOL DECANOATE
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HALOPERIDOL DECANOATE |
2017-02-27 |
Transitioning Veteran- Veteran is transitioning care from the Department of Defense to VHA, and a VA prescriber has determined continuing the medication is safe and clinically appropriate after assessing and consulting with the Veteran. (If met, remainder of criteria for use is not applicable.)
Exclusion Criteria- Patient has never taken the long-acting injectable antipsychotic ordered in any formulation (e.g., oral).
- Patient has a hypersensitivity to the antipsychotic ordered.
Inclusion Criteria (All Must Be Met)- Diagnosis of schizophrenia or schizoaffective disorder, or bipolar disorder.
- Prescriber is a VA Mental Health Provider.
- Patient has taken and tolerated the antipsychotic ordered prior to receiving it as a LAI for an adequate length of time.
- Patient will be transitioned from oral/short-acting injection medication to the long-acting injectable per guidelines/manufacturer recommendations.
Inclusion Criteria (One Must Be Met)- Patient has relapsed or been hospitalized for the intended indication or complications of the intended indication because of nonadherence when treated with oral antipsychotics.
- Patient’s care environment is such that a LAI is a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely).
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HYALURONATE SODIUM INJ
DUROLANE, EUFLEXXA, GEL-ONE, HYALGAN
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DUROLANE, EUFLEXXA, GEL-ONE, HYALGAN |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity or allergy to hyaluronate or hylan preparations
- Knee joint infection
- Skin disease or infection in the area of the injection site
Inclusion Criteria- Documented symptomatic (pain/stiffness) osteoarthritis (OA) of the knee that interferes with functional activities (e.g., ambulation, prolonged standing) and/or is associated with significant pain
- Inadequate improvement in pain/function following an adequate trial (2 to 3 months) of non-pharmacologic measures (e.g., cane/crutches, bracing/orthotics, weight loss, physical therapy/exercise)
- Inadequate improvement in pain/function following a therapeutic trial of at least 3 analgesics (e.g., acetaminophen, topical capsaicin or topical NSAIDs, oral NSAIDs or duloxetine), OR patient is unable to tolerate or is not a candidate for NSAIDs or other oral therapies
- Patient and/or provider have elected to continue conservative (nonsurgical) treatment for OA
Practice Restrictions & Administration Guidelines- Use limited to specialists in Orthopedics, Rheumatology, and Physical Medicine and Rehabilitation
- Patients with more advanced stages of OA and near complete loss of joint space may be less likely to benefit
- All hyaluronic acid (HA) or hylan products are for intra-articular (IA) use only
- Avian source products (Gel-One, Hyalgan, Supartz, Synvisc, Synvisc-One): Administer with caution in patients with a known allergy to avian proteins, feathers, or eggs
- Non-avian source products (Durolane, Euflexxa, Gel-Syn 3, GenVisc 850, Hymovis, Monovisc, Orthovisc, Synojoynt, Trivisc): Can be used in patients with an allergy to avian proteins
- Refer to product labeling for specific warnings (e.g., Gel-One should be used with caution in patients with an allergy to cinnamon)
- Safety/efficacy of concomitant administration with other IA agents has not been established
- Pseudosepsis or severe acute inflammatory reactions (SAIR) have been reported with Synvisc, typically occurring with the second or third injection in a course or with subsequent courses
- Repeat courses should not be administered within 6 months of the last injection
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HYALURONATE SODIUM INJ
GENVISC 850, HYMOVIS, MONOVISC, ORTHOVISC, SUPARTZ FX, TRILURON, TRIVISC, VISCO-3
|
GENVISC 850, HYMOVIS, MONOVISC, ORTHOVISC, SUPARTZ FX, TRILURON, TRIVISC, VISCO-3 |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity or allergy to hyaluronate or hylan preparations
- Knee joint infection
- Skin disease or infection in the area of the injection site
Inclusion Criteria- Documented symptomatic (pain/stiffness) osteoarthritis (OA) of the knee that interferes with functional activities (e.g., ambulation, prolonged standing) and/or is associated with significant pain
- Inadequate improvement in pain/function following an adequate trial (2 to 3 months) of non-pharmacologic measures (e.g., cane/crutches, bracing/orthotics, weight loss, physical therapy/exercise)
- Inadequate improvement in pain/function following a therapeutic trial of at least 3 analgesics (e.g., acetaminophen, topical capsaicin or topical NSAIDs, oral NSAIDs or duloxetine), OR patient is unable to tolerate or is not a candidate for NSAIDs or other oral therapies
- Patient and/or provider have elected to continue conservative (nonsurgical) treatment for OA
Practice Restrictions & Administration Guidelines- Use limited to specialists in Orthopedics, Rheumatology, and Physical Medicine and Rehabilitation
- Patients with more advanced stages of OA and near complete loss of joint space may be less likely to benefit
- All hyaluronic acid (HA) or hylan products are for intra-articular (IA) use only
- Avian source products (Gel-One, Hyalgan, Supartz, Synvisc, Synvisc-One): Administer with caution in patients with a known allergy to avian proteins, feathers, or eggs
- Non-avian source products (Durolane, Euflexxa, Gel-Syn 3, GenVisc 850, Hymovis, Monovisc, Orthovisc, Synojoynt, Trivisc): Can be used in patients with an allergy to avian proteins
- Refer to product labeling for specific warnings (e.g., Gel-One should be used with caution in patients with an allergy to cinnamon)
- Safety/efficacy of concomitant administration with other IA agents has not been established
- Pseudosepsis or severe acute inflammatory reactions (SAIR) have been reported with Synvisc, typically occurring with the second or third injection in a course or with subsequent courses
- Repeat courses should not be administered within 6 months of the last injection
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HYALURONATE SODIUM INJ
GELSYN-3
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GELSYN-3 |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity or allergy to hyaluronate or hylan preparations
- Knee joint infection
- Skin disease or infection in the area of the injection site
Inclusion Criteria- Documented symptomatic (pain/stiffness) osteoarthritis (OA) of the knee that interferes with functional activities (e.g., ambulation, prolonged standing) and/or is associated with significant pain
- Inadequate improvement in pain/function following an adequate trial (2 to 3 months) of non-pharmacologic measures (e.g., cane/crutches, bracing/orthotics, weight loss, physical therapy/exercise)
- Inadequate improvement in pain/function following a therapeutic trial of at least 3 analgesics (e.g., acetaminophen, topical capsaicin or topical NSAIDs, oral NSAIDs or duloxetine), OR patient is unable to tolerate or is not a candidate for NSAIDs or other oral therapies
- Patient and/or provider have elected to continue conservative (nonsurgical) treatment for OA
Practice Restrictions & Administration Guidelines- Use limited to specialists in Orthopedics, Rheumatology, and Physical Medicine and Rehabilitation
- Patients with more advanced stages of OA and near complete loss of joint space may be less likely to benefit
- All hyaluronic acid (HA) or hylan products are for intra-articular (IA) use only
- Avian source products (Gel-One, Hyalgan, Supartz, Synvisc, Synvisc-One): Administer with caution in patients with a known allergy to avian proteins, feathers, or eggs
- Non-avian source products (Durolane, Euflexxa, Gel-Syn 3, GenVisc 850, Hymovis, Monovisc, Orthovisc, Synojoynt, Trivisc): Can be used in patients with an allergy to avian proteins
- Refer to product labeling for specific warnings (e.g., Gel-One should be used with caution in patients with an allergy to cinnamon)
- Safety/efficacy of concomitant administration with other IA agents has not been established
- Pseudosepsis or severe acute inflammatory reactions (SAIR) have been reported with Synvisc, typically occurring with the second or third injection in a course or with subsequent courses
- Repeat courses should not be administered within 6 months of the last injection
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HYDROCODONE/ IBUPROFEN TAB
REPREXAIN, XYLON 10
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REPREXAIN, XYLON 10 |
2017-02-27 |
Continuity of Care- Veteran is transitioning care from the Department of Defense to VHA
- Must also meet one of the following Additional Inclusion Criteria:
- The medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making
- The medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making
Non-Continuity of Care- Inadequate response, contraindication or intolerance to hydrocodone/acetaminophen combination product and clinical need for hydrocodone containing product
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HYLAN G-F 20
SYNVISC
|
SYNVISC |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity or allergy to hyaluronate or hylan preparations
- Knee joint infection
- Skin disease or infection in the area of the injection site
Inclusion Criteria- Documented symptomatic (pain/stiffness) osteoarthritis (OA) of the knee that interferes with functional activities (e.g., ambulation, prolonged standing) and/or is associated with significant pain
- Inadequate improvement in pain/function following an adequate trial (2 to 3 months) of non-pharmacologic measures (e.g., cane/crutches, bracing/orthotics, weight loss, physical therapy/exercise)
- Inadequate improvement in pain/function following a therapeutic trial of at least 3 analgesics (e.g., acetaminophen, topical capsaicin or topical NSAIDs, oral NSAIDs or duloxetine), OR patient is unable to tolerate or is not a candidate for NSAIDs or other oral therapies
- Patient and/or provider have elected to continue conservative (nonsurgical) treatment for OA
Practice Restrictions & Administration Guidelines- Use limited to specialists in Orthopedics, Rheumatology, and Physical Medicine and Rehabilitation
- Patients with more advanced stages of OA and near complete loss of joint space may be less likely to benefit
- All hyaluronic acid (HA) or hylan products are for intra-articular (IA) use only
- Avian source products (Gel-One, Hyalgan, Supartz, Synvisc, Synvisc-One): Administer with caution in patients with a known allergy to avian proteins, feathers, or eggs
- Non-avian source products (Durolane, Euflexxa, Gel-Syn 3, GenVisc 850, Hymovis, Monovisc, Orthovisc, Synojoynt, Trivisc): Can be used in patients with an allergy to avian proteins
- Refer to product labeling for specific warnings (e.g., Gel-One should be used with caution in patients with an allergy to cinnamon)
- Safety/efficacy of concomitant administration with other IA agents has not been established
- Pseudosepsis or severe acute inflammatory reactions (SAIR) have been reported with Synvisc, typically occurring with the second or third injection in a course or with subsequent courses
- Repeat courses should not be administered within 6 months of the last injection
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HYLAN G-F 20 INJ
SYNVISC-ONE
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SYNVISC-ONE |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity or allergy to hyaluronate or hylan preparations
- Knee joint infection
- Skin disease or infection in the area of the injection site
Inclusion Criteria- Documented symptomatic (pain/stiffness) osteoarthritis (OA) of the knee that interferes with functional activities (e.g., ambulation, prolonged standing) and/or is associated with significant pain
- Inadequate improvement in pain/function following an adequate trial (2 to 3 months) of non-pharmacologic measures (e.g., cane/crutches, bracing/orthotics, weight loss, physical therapy/exercise)
- Inadequate improvement in pain/function following a therapeutic trial of at least 3 analgesics (e.g., acetaminophen, topical capsaicin or topical NSAIDs, oral NSAIDs or duloxetine), OR patient is unable to tolerate or is not a candidate for NSAIDs or other oral therapies
- Patient and/or provider have elected to continue conservative (nonsurgical) treatment for OA
Practice Restrictions & Administration Guidelines- Use limited to specialists in Orthopedics, Rheumatology, and Physical Medicine and Rehabilitation
- Patients with more advanced stages of OA and near complete loss of joint space may be less likely to benefit
- All hyaluronic acid (HA) or hylan products are for intra-articular (IA) use only
- Avian source products (Gel-One, Hyalgan, Supartz, Synvisc, Synvisc-One): Administer with caution in patients with a known allergy to avian proteins, feathers, or eggs
- Non-avian source products (Durolane, Euflexxa, Gel-Syn 3, GenVisc 850, Hymovis, Monovisc, Orthovisc, Synojoynt, Trivisc): Can be used in patients with an allergy to avian proteins
- Refer to product labeling for specific warnings (e.g., Gel-One should be used with caution in patients with an allergy to cinnamon)
- Safety/efficacy of concomitant administration with other IA agents has not been established
- Pseudosepsis or severe acute inflammatory reactions (SAIR) have been reported with Synvisc, typically occurring with the second or third injection in a course or with subsequent courses
- Repeat courses should not be administered within 6 months of the last injection
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IBRUTINIB CAP,ORAL
IMBRUVICA
|
IMBRUVICA |
2017-02-27 |
Exclusion Criteria- Patient has not been screened for Hepatitis B Virus (HBV)
- Unmanageable drug-drug or drug-food interaction
- Active or uncontrolled infection
- History of stroke or intracranial hemorrhage in prior 6 months
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (NYHA Class 3 or 4) or myocardial infarction in prior 6 months
- Severe hepatic impairment (Child-Pugh C) or total bilirubin > 3x Upper Limit of Normal (unless non-hepatic origin or Gilbert syndrome)
- Known pregnancy
- Lactating
Inclusion Criteria- Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) if acalabrutinib is not clinically appropriate for patient
- Waldenstrom Macroglobulinemia
- Previously treated chronic Graft versus Host Disease (cGVHD) after Hematopoietic Stem Cell Transplant
Additional Inclusion Criteria- Care for the oncologic condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 - 2
Pregnancy and Lactation Counseling Requirements- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 month after stopping treatment
- Advise patients not to breastfeed/provide breastmilk during treatment and for 1 week after last dose
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IDARUCIZUMAB INJ,SOLN
PRAXBIND
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PRAXBIND |
2017-02-27 |
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
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IDELALISIB TAB,ORAL
ZYDELIG
|
ZYDELIG |
2017-02-27 |
Exclusion Criteria- Unable to swallow oral capsules whole and intact
- History of non-adherence with oral medication, follow-up appointments or laboratory visits
- Unmanageable drug interaction identified
- History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis
- Gastrointestinal condition that may interfere with absorption
- Chronic or unresolved infection
- Severe renal impairment defined as CrCl < 15 ml/min (drug has not been studied in this setting)
- AST (SGOT) or ALT (SGPT) > 2.5x ULN, bilirubin > 1.5x ULN, or with moderate-severe hepatic impairment (Child-Pugh B or C)
- Absolute Neutrophil Count (ANC) < 1000 cells/µL, and/or platelet count < 50,000 cells/µL unless bone marrow involvement
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care provided by VA or VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 – 2
Indication- Relapsed Chronic Lymphocytic Leukemia (CLL) with rituximab (if rituximab alone is appropriate due to comorbidities)
Reproductive Health & Contraception Requirements- Pregnancy should be excluded prior to receiving idelalisib and the patient provided contraceptive counseling on potential risk vs. benefit of taking idelalisib if patient were to become pregnant
- Effective contraception should be used during treatment and for 1 month after the last dose
- Partners should use effective contraception for 3 months after last dose
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INCOBOTULINUMTOXINA INJ,LYPHL
XEOMIN
|
XEOMIN |
2017-02-27 |
Exclusion Criteria- Hypersensitivity to botulinum toxins or any components in the formulation (e.g., human serum albumin, lactose, sucrose, disodium succinate)
- Co-administration with neuromuscular blockade
- Neurologic condition where botulinum toxins pose risk for additive neuromuscular compromise (e.g., myasthenia gravis, amyotrophic lateral sclerosis), unless risks/benefits have been discussed with the patient and documented in the medical record
- Use for cosmetic purposes
Inclusion Criteria (Indications)- Cervical dystonia or focal dystonia
- Blepharospasm or hemifacial spasm
- Severe focal hyperhidrosis with inadequate response or unmanageable intolerance to prescription topical therapy (e.g., aluminum chloride hexahydrate 20% topical solution)
- Upper or lower limb spasticity
- Overactive bladder or neurogenic bladder dysfunction with contraindication, intolerance, or inefficacy to behavioral therapy and at least one pharmacotherapy (e.g., antimuscarinic agent, beta-3 adrenergic agonist)
- Chronic migraine prevention with contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 2 of the following: beta blocker, topiramate, divalproex, and ACE inhibitor or ARB
- Pharyngoesophageal segment spasm (PES)
- Sialorrhea with contraindication, intolerance, or lack of therapeutic response to anticholinergics and/or speech therapy
- Chronic anal fissure refractory to conservative treatment including supportive measures (e.g., dietary fiber, sitz bath) and topical vasodilator (e.g., topical nitrates)
- Esophageal achalasia if patient is not a candidate for surgery
- Idiopathic (primary or genetic) or symptomatic (acquired) torsion dystonia
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INDOMETHACIN SUPP,RTL
INDOCIN
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INDOCIN |
2017-02-27 |
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INSULIN INHL,ORAL
AFREZZA
|
AFREZZA |
2017-02-27 |
Pre-Considerations & Prerequisites- • Patient training with a VA Diabetes Educator
- • Offer a trial of insulin pens, smaller gauge needles, and other assistive devices
- • Patient must demonstrate competency with and agree to self-monitoring of blood glucose
- • If basal insulin is required, conversion from pre-meal inhaled to injectable insulin should occur once the patient is stabilized on basal insulin and comfortable with administering injections
Exclusion Criteria- • COPD, asthma, or other chronic lung disorders
- • Patients who smoke or have recently quit smoking within the last six months
- • Active lung cancer, prior history of lung cancer, or risk factors (other than smoking) for lung cancer
- • History of a serious hypersensitivity reaction to regular human insulin or excipients of Afrezza
- • Treatment of diabetic ketoacidosis
Inclusion Criteria- • Patient has diabetes and requires insulin (inhaled insulin must be used in combination with long-acting insulin in patients with type 1 diabetes)
- • Provider is experienced in managing insulin therapy in patients with diabetes (e.g., endocrinologists, diabetologists, practices in a diabetes management team)
- • Patient must have baseline spirometry (FEV1) within the last 6 months to identify potential underlying lung disease
- • AND at least one of the following:
- Severe persistent injection site reactions (e.g., lipohypertrophy)
- Works in an environment that does not allow needles
Special Circumstances- • Psychological aversion to needles may warrant case-by-case consideration for inhaled insulin use
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INSULIN,DEGLUDEC,HUMAN 100 UNIT/ ML
TRESIBA, TRESIBA FLEXTOUCH U-100
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TRESIBA, TRESIBA FLEXTOUCH U-100 |
2017-02-27 |
Exclusion Criteria- Hypersensitivity to insulin degludec
Inclusion Criteria – Insulin Degludec 100 u/mL Only- Instability of glucose levels (e.g., insulin-sensitive type 1 diabetes) resulting in hypoglycemia while receiving lower doses of insulin glargine 100 units/mL
- Wide fluctuation in glucose levels due to an inability to take basal insulin at a consistent time (e.g., variability in shift work, dialysis, inconsistent routines), documented in the Federal EHR
- Fluctuation in glucose levels must be documented in a glucose diary or continuous glucose monitor (CGM) and included in the Federal electronic health record (EHR)
Inclusion Criteria – Insulin Degludec 200 u/mL Only- Insulin resistance (e.g., requires >1 unit/kg/day)
- Recurrent episodes of hypoglycemia on insulin glargine 100 u/mL (e.g., > three Level 2 or one Level 3 hypoglycemic event within a one-month period) despite use of CGM and adjustments made to current insulin regimen
Product Specifications & Clinical Definitions- Concentrated degludec 200 u/mL can be given in 2-unit increments, delivering up to 160 units per single injection; preferred for patients who are insulin resistant receiving high doses of insulin
- Degludec 100 u/mL can be given in 1-unit increments, delivering up to 80 units per single injection
- Level 2 hypoglycemia: glucose level <54 mg/dL
- Level 3 hypoglycemia: severe event requiring assistance for management, regardless of glucose level
- CGM: Continuous glucose monitor
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INSULIN,DEGLUDEC,HUMAN 200 UNIT/ ML
TRESIBA FLEXTOUCH U-200
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TRESIBA FLEXTOUCH U-200 |
2017-02-27 |
Exclusion Criteria- Hypersensitivity to insulin degludec
Inclusion Criteria – Insulin Degludec 100 u/mL Only- Instability of glucose levels (e.g., insulin-sensitive type 1 diabetes) resulting in hypoglycemia while receiving lower doses of insulin glargine 100 units/mL
- Wide fluctuation in glucose levels due to an inability to take basal insulin at a consistent time (e.g., variability in shift work, dialysis, inconsistent routines), documented in the Federal EHR
- Fluctuation in glucose levels must be documented in a glucose diary or continuous glucose monitor (CGM) and included in the Federal electronic health record (EHR)
Inclusion Criteria – Insulin Degludec 200 u/mL Only- Insulin resistance (e.g., requires >1 unit/kg/day)
- Recurrent episodes of hypoglycemia on insulin glargine 100 u/mL (e.g., > three Level 2 or one Level 3 hypoglycemic event within a one-month period) despite use of CGM and adjustments made to current insulin regimen
Product Specifications & Clinical Definitions- Concentrated degludec 200 u/mL can be given in 2-unit increments, delivering up to 160 units per single injection; preferred for patients who are insulin resistant receiving high doses of insulin
- Degludec 100 u/mL can be given in 1-unit increments, delivering up to 80 units per single injection
- Level 2 hypoglycemia: glucose level <54 mg/dL
- Level 3 hypoglycemia: severe event requiring assistance for management, regardless of glucose level
- CGM: Continuous glucose monitor
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INTERFERON BETA-1A AUTO-INJECTOR
REBIF REBIDOSE
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REBIF REBIDOSE |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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INTERFERON BETA-1A INJ,SOLN
REBIF, REBIF REBIDOSE
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REBIF, REBIF REBIDOSE |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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INTERFERON BETA-1A INJ,SOLN
AVONEX, AVONEX (4 PACK), AVONEX PEN, AVONEX PEN (4 PACK)
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AVONEX, AVONEX (4 PACK), AVONEX PEN, AVONEX PEN (4 PACK) |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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INTERFERON BETA-1B INJ,LYPHL
BETASERON
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BETASERON |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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IPILIMUMAB INJ,SOLN
YERVOY
|
YERVOY |
2017-02-27 |
Exclusion Criteria- Active autoimmune disease (excluding diabetes and history of thyroid disease)
- Active or untreated brain metastases
- Primary ocular or mucosal melanoma
- Concomitant treatment with immunosuppressants including systemic corticosteroids (prednisone equivalent > 5mg/day)
- Child-Pugh Class B or C liver dysfunction
- Known pregnancy
- Lactating
Inclusion Criteria (Indications & Regimens)- Monotherapy or in combination with nivolumab for treatment of unresectable or metastatic melanoma
- Adjuvant treatment of cutaneous melanoma with pathologic involvement of regional lymph nodes (> 1mm) after complete resection
- In combination with nivolumab as first-line treatment of intermediate or poor risk advanced renal cell carcinoma
- In combination with nivolumab in unresectable or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer
- In combination with nivolumab as first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC) or in those previously treated with sorafenib
- In combination with nivolumab as first-line treatment of metastatic non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations and PD-L1 expression > 1%
- In combination with nivolumab and 2 cycles of a platinum-doublet as first-line treatment of metastatic non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations
- In combination with nivolumab as first-line treatment of unresectable malignant pleural mesothelioma
- In combination with nivolumab as first-line treatment of unresectable advanced or metastatic esophageal squamous cell carcinoma
Additional Inclusion Criteria- Pregnancy & Fertility Management
- For females who can become pregnant: Pregnancy must be excluded prior to receiving ipilimumab.
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 3 months after stopping treatment.
- Oncology Care & Performance Status
- Care for the oncologic condition provided by VA or VA community care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
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IVERMECTIN TAB
STROMECTOL
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STROMECTOL |
2017-02-27 |
Exclusion Criteria- Use as a treatment for COVID-19 infection without another appropriate indication
- Known hypersensitivity to ivermectin
- Pregnancy
Inclusion Criteria- Treatment of a parasitic infection for which ivermectin is indicated (strongylodiasis, onchocerciasis, lymphatic filariasis, cutaneous larva migrans, ascariasis, scabies and lice)
- Empiric treatment for Strongyloides stercolis in a hospitalized patient at epidemiologic risk (birth, long-term residence in or travel to endemic locations) who are being initiated on corticosteroids or other immunosuppressant medications
Additional Inclusion Criteria- For patients of child-bearing potential: pregnancy should be excluded prior to receiving ivermectin
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IXAZOMIB CAP,ORAL
NINLARO
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NINLARO |
2017-02-27 |
Disease Indication & Treatment Setting- Diagnosis of multiple myeloma with documented relapsed or progressive disease
- Use of ixazomib combination is for patient with newly diagnosed multiple myeloma
- Use of ixazomib combination is as maintenance myeloma therapy
Prior Therapy & Candidate Eligibility- Patient is not a candidate for lenalidomide or dexamethasone therapy
- Received at least one prior therapy (that did not include ixazomib)
Laboratory Parameters- Absolute neutrophil count (ANC) less than 1000/mm3 unless due to marrow involvement or associated with Duffy-null associated neutrophil count
- Platelet count less than 75,000/mm3 unless due to marrow involvement
Provider & Care Coordination- Care is provided by a VA/VA Community Care hematology or oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
Reproductive Health & Counseling- Pregnancy
- Lactating
- For patients who can become pregnant: Pregnancy must be excluded prior to receiving ixazomib
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for at least 90 days following treatment
- For patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for at least 90 days following treatment
Infection Prophylaxis- Assess need for antiviral prophylaxis to reduce risk of herpes zoster reactivation
Drug Interactions- Unmanageable drug-drug interaction
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IXEKIZUMAB INJ,SOLN
TALTZ AUTOINJECTOR, TALTZ AUTOINJECTOR (2 PACK), TALTZ AUTOINJECTOR (3 PACK), TALTZ SYRINGE
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TALTZ AUTOINJECTOR, TALTZ AUTOINJECTOR (2 PACK), TALTZ AUTOINJECTOR (3 PACK), TALTZ SYRINGE |
2017-02-27 |
Infection Screening & Management- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA].
- Completed hepatitis B screening (HBsAg, total anti-HBc and antibody to hepatitis B surface antigen [anti-HBs]).
- Current or past completion of hepatitis C screening.
- If HBsAg-negative but anti-HBc-positive: GI/liver or ID expert consult indicated for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation.
Contraindications & Exclusions- Uncontrolled, active, severe infection, including undrained abscess (may start/restart once treatment for the infection is initiated).
- Untreated latent or active tuberculosis infection.
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis with agents such as entecavir or tenofovir).
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated).
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation.
Diagnosis & Indication- Definite or provisional diagnosis of active ankylosing spondylitis (or radiographic axial spondyloarthritis).
Prescribing & Monitoring Requirements- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert.
- Prescribed at the FDA-approved dose for ankylosing spondylitis.
- Vaccinations should be updated before initiation; recombinant zoster vaccine should be completed or initiated by end of first year of treatment.
Prior Therapy Requirements- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated or not adequate (i.e., NO or partial response after 3 months or loss of initial response).
- Applies only to new starts; stable patients should not be switched to a criteria-required prior drug for nonmedical reasons.
Special Populations & Counseling- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
Infection Screening & Management- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA].
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs]).
- Current or past completion of hepatitis C screening.
- Antiviral prophylaxis for HBV must utilize agents with a high genetic barrier to resistance such as entecavir or tenofovir.
Contraindications & Exclusions- Uncontrolled, active, severe infection, including undrained abscess (may be started/restarted once treatment for the infection is initiated).
- Untreated latent or active tuberculosis infection.
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may be initiated after starting antiviral prophylaxis).
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated).
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation.
Diagnosis & Treatment Requirements- Definite or provisional diagnosis of active nonradiographic axial spondyloarthritis (nr-axSpA) made by a VA/VA Community Care rheumatologist.
- Prescribed at the FDA-approved dose for active nr-axSpA.
- Tumor necrosis factor inhibitor (TNFi) therapy is medically inadvisable, not tolerated, or not adequate (i.e., NO or partial response after 3 months or loss of initial response).
Specialist Oversight & Monitoring- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert.
Additional Patient-Specific Considerations- If HBsAg-negative but anti-HBc-positive and practitioner deems consult indicated: GI/liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation.
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
General Prescribing Notes- Criteria apply only to new starts; stable patients should not be switched to a criteria-required prior drug for nonmedical reasons.
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KETAMINE INJ,SOLN
KETALAR, KETAMINE HCL, KETAMINE HCL-0.9% NACL, KETAMINE HCL-NACL, KETAMINE HCL-WATER
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KETALAR, KETAMINE HCL, KETAMINE HCL-0.9% NACL, KETAMINE HCL-NACL, KETAMINE HCL-WATER |
2017-02-27 |
Indication & Patient Population- Veterans with intractable/treatment-resistant neuropathic pain or Complex Regional Pain Syndrome (CRPS), centralized pain disorder
- Must be under care of VHA Pain Specialists or Pain Management Teams (not VA Community Care)
- Must be part of a comprehensive, multi-modal pain care plan
Inclusion Criteria- Failed adequate trials (unless contraindicated) of TCAs (amitriptylline, desipramine, nortriptyline), SNRIs (venlafaxine, duloxetine), and alpha-2-delta calcium channel blockers (gabapentin, pregabalin)
- Evaluated and qualified by a pain management or interventional pain specialist with documented reasoning in the medical record
- Cleared of mental health contraindications by a Mental Health Pain Provider with documentation in the medical record
- Verbal informed consent provided by patient or legal representative
- Adult accompaniment for transportation arranged, or safe transport method documented
Exclusion Criteria- Current or past history of schizophrenia, schizoaffective disorder, bipolar disorder, or decompensated psychiatric disorder
- Dementia
- Current or recent (within 7 days) delirium
- Current uncontrolled hypertension (SBP >160 mm Hg or DBP >90 mm Hg)
- Conditions where increased blood pressure would be hazardous
- Severe cardiac decompensation
- Myocardial ischemia/angina, recent MI (within 3 months)
- Pregnant (positive test) or lack of birth control in women of childbearing potential
- Positive urine drug screen or current/previous abuse of ketamine (patients prescribed opioids/benzodiazepines/barbiturates by VHA are eligible; acute intoxication/detoxification requires exclusion until addressed)
- Allergy or previous serious adverse effects to ketamine
- Recent infection or illness
- Psychosis or decompensated psychiatric condition
- Ketamine-related cystitis
- Illicit drug use (cocaine, methamphetamine, marijuana)
- Morbid obesity with BMI > 40
- End-stage renal or hepatic disease
- DM2 with HbA1c > 9.0 (unless demonstrated improvement in diabetic control per recent 2-week glucose diary)
- Pulmonary HTN (mod-severe)
Screening & Pre-treatment Requirements- Screening completed no more than 30 days prior to first dose
- Includes verbal informed consent, inclusion/exclusion criteria review, physical exam with vitals (BP, HR, RR, SpO2, weight), relevant labs, urine toxicology, and pregnancy screen
- SBP >150 mm Hg or DBP >95 mm Hg at screening indicates higher risk; hypertension must be adequately treated prior to infusion
- Cardiopulmonary/cerebrovascular disease, recent MI, symptomatic ischemic heart disease, dyspnea/wheezing, poor exercise capacity (<6 METs), or conditions increasing risk of acute cardiac demand/BP/respiratory depression require individual case-by-case risk/benefit consideration
- Baseline HR <60 or >100 bpm requires case-by-case risk assessment
- SpO2 at screening must be >94% after mild exertion
- Other labs/screening determined per individual risk factors by prescribing psychiatrist
- Medical clearance from PCP or specialist consults based on risk factors (prescribing provider responsibility)
- History of substance abuse, alcohol use, smoking, medication misuse, positive UDS considered; length of sobriety factored in
- Concurrent barbiturates/opioids/Scheduled meds may delay recovery; wean opioids as much as possible prior due to respiratory depression risk with benzodiazepine coadministration
Administration & Monitoring Requirements- Facility identifies private/semi-private location large enough for patient and personnel
- Setting must provide immediate care capability with crash cart readily accessible
- Must monitor cardiovascular (ECG, BP) and respiratory (SpO2, end-tidal CO2) functions
- Capable of administering oxygen, medication, restraints for behavioral symptoms
- Plan for rapid response to sustained CV alterations (ACLS or transfer)
- High-risk patients treated at facilities equipped/staffed for CV/respiratory events
- Infusion ordered by pain management/interventional pain specialist
- Pre-medication/concurrent meds (e.g., IV lorazepam) ordered to prevent/manage adverse effects
- ACLS-certified pain physician or anesthesiologist present at initiation, intermittently during, and at end; ACLS-certified nurse present during infusion
- Ordering provider leaves after completion if stable; must return at end to evaluate and clear for discharge; ACLS provider remains until discharge
Dosing & Infusion Protocol- Dose: 0.5 mg/kg IV infusion over 4 hours using an infusion pump
- For BMI >30 kg/m2, calculate dose using ideal body weight (Men = 50 kg + [2.3 kg x each inch >5 feet]; Women = 45.5 kg + [2.3 kg x each inch >5 feet])
- T-2 days or sooner: UDS and pregnancy tests collected, meds reviewed, consent obtained
- T-60 min: IV line started, vitals (sitting/standing BP, sitting/standing pulse, RR, SpO2) taken, BPI baseline administered
- T-0 min: Administer ketamine if vitals acceptable and screens negative
- T+10, 20, 30, 40, 80, 110 min: Vitals and cognitive status check as indicated
- T+240 min: Vitals, Pain NRS (or other pain scale)
Parameters for Stopping Infusion- BP must remain <180 mm Hg systolic and <110 mm Hg diastolic at all times
- SBP drop >10 mm Hg accompanied by increased HR or distress requires stopping
- HR must remain below age-adjusted max: 20 yrs <140 bpm, 30 yrs <133, 40 yrs <126, 50 yrs <119, 60 yrs <112; for ≥65 yrs, individualize based on exercise capacity/risk factors
- Stop for: pallor/cyanosis/poor perfusion symptoms; respiratory symptoms (SOB, wheezing); chest/jaw/arm pain suggesting cardiac involvement; patient's desire to stop
Repeat Schedules & Discontinuation Criteria- May be repeated daily for up to 4 hours and up to 5 days (excluding weekends) per pain physician discretion based on response
- "Booster" sessions may be given no more frequently than every 3 months, individualized
- Alternative: Every other day x 3 days (M-W-F) for 1-2 weeks; failure to respond results in discontinuation
- Taper and discontinue in interest of safety; time frame undefined/individualized
- Discontinue if patient wishes for any reason
- Discontinue if infusion stopped >1 time due to exceeding BP or HR thresholds
- Discontinue after 4 to 6 infusions without adequate response (defined as ≥50% decline in NRS pain score from baseline)
- Discontinue when dosing cannot be spaced to minimum of 1 dose per week by second month of treatment
Outcomes Monitoring- Monitor at baseline, 1-2 weeks post-infusion, and monthly
- Track: Brief Pain Inventory (BPI), number/dosing regimens of opioid (MEDD) and non-opioid pain meds
Indication & Purpose- Treatment of acute behavioral agitation in VHA Emergency Departments (ED) and Urgent Care Centers (UCC).
- Indicated for non-procedural sedation.
Patient Selection (Inclusion Criteria)- Patients who are extremely combative and at immediate risk of causing physical harm to medical staff, the public, or themselves.
- Patients who have failed de-escalation techniques and one or more rapid tranquilization medications (e.g., benzodiazepines, droperidol, haloperidol, olanzapine, ziprasidone).
- Ketamine is determined to be a preferred first-line agent.
Contraindications- Hypersensitivity to ketamine or any excipient.
Precautions- Active psychosis.
- Pregnancy.
- Elevated intracranial or intraocular pressure.
- Severe cardiovascular disease: acute coronary syndrome, decompensated heart failure, severe valvular disease, active cardiac dysthymias.
- Pulmonary hypertension.
- Severe hepatic dysfunction.
Dosing & Pharmacokinetics- Intramuscular dosing: 1-3 mg/kg (Ideal Body Weight).
- If administered shortly after another sedating agent, dose at the lower end of the range.
- Onset: 5 minutes.
- Duration: Up to 60 minutes.
- Half-life: 2 to 3 hours.
- IM ketamine may have significant variation in clinical effect between individuals; caution advised.
Administration, Monitoring & Personnel Requirements- Facilities must develop and operationalize a procedure for administering IM ketamine in the ED/UCC.
- Facility is responsible for monitoring the patient during and after injection(s).
- Must be capable of administering oxygen, medication, and/or restraints to manage potentially dangerous behavioral symptoms.
- Bag Mask Valve (BVM) device and airway rescue equipment must be immediately available.
- Plan required to rapidly address sustained alterations in cardiovascular function, including advanced cardiac life support or transfer to a hospital capable of acute cardiovascular care.
- A Licensed Independent Practitioner (LIP) with at least Out of Operating Room Airway Management (OOORAM) Level 2 privileges must be immediately available at the bedside.
- Patient must be directly observed by clinical staff for at least 30 minutes after receiving IM ketamine.
- Non-invasive blood pressure monitoring, cardiac monitoring, continuous pulse oximetry, and respiratory rate monitoring recommended as practical.
- ED/UCC LIP responsible for ensuring patient appropriateness, documenting risk/benefits/alternatives in the medical record.
- ED/UCC RN may administer under an appropriate order from an ED/UCC LIP per state licensure requirements.
- Facilities must participate in ongoing VA MedSAFE Medication Use Evaluation (MUE).
Exclusions- Does not apply to deep sedation, acute pain management outside of sedation, securing an endotracheal airway (e.g., rapid sequence intubation), or care of mechanically ventilated patients.
Indication- Acute pain
- Intractable pain
- Clinically indicated when conventional modes of treatment have failed or ketamine is determined to be a more suitable agent
- Opioid-tolerant patients as an adjunct to opioid therapy for acute pain
- Patients on partial opioid or opioid antagonist therapy with acute tissue trauma related pain
Contraindications- Hypersensitivity to ketamine or any excipient
Precautions & Warnings- Active or history of psychosis
- Patients for whom significant elevations in blood pressure would constitute a serious hazard
- Myocardial ischemia
- Pregnancy or lactation
- Consider IVPB and lower dosing for older patients or patients with comorbidities to mitigate adverse effects
Dosing & Administration- Intravenous (IV)
- Initial dose: 0.1 to 0.3 mg/kg Ideal Body Weight (IBW)
- Administer via IVPB over 10-15 minutes (preferred) or slow IV push over 5 minutes
- Maximum single dose: 30 mg
- IV Compatibility: Dextrose 5% in Water (D5W), Normal Saline (NS), or Sterile Water for Injection
- Additional dosing: Repeat IV dose via IVPB/slow IV push OR start continuous infusion at 0.15 to 0.2 mg/kg/hr
- Titrate every 30 minutes until pain is relieved
- Total dose should not exceed 1 mg/kg IBW
- Intramuscular (IM) (when IV access not available)
- Initial dose: 0.35 to 0.7 mg/kg IM
- Additional dosing: Repeat IM dose OR, if IV access established, repeat via IV dosing OR start continuous infusion at 0.15 to 0.2 mg/kg/hr
- Titrate every 30 minutes until pain is relieved
- Total dose should not exceed 1 mg/kg IBW
Monitoring, Equipment, & Personnel Requirements- Bag Mask Valve (BVM) device must be available immediately at the bedside
- Licensed Independent Practitioner (LIP) with Out of Operating Room Airway Management (OOORAM) privileges must be available in ED/UC to immediately respond to the bedside
- Monitoring recommended during and for at least 15 minutes after administration: non-invasive blood pressure, cardiac monitoring, continuous pulse oximetry, respiratory rate
- LIP responsible for ensuring patient appropriateness, obtaining informed consent, and attending to patient in event of adverse effect
- RN responsible for patient monitoring activities and may administer medication under appropriate order from ED/UCC LIP consistent with applicable state licensure requirements
Adverse Effects (at Sub-Dissociative Doses)- Common: dizziness, sedation, sense of unreality, nausea
- Rare: excess sedation, respiratory compromise
- Adverse effects requiring additional management were rare in adults in ED SDK clinical trials; dizziness and perceptual changes attenuated with 15-minute infusion vs IV push
Scope & Exclusions- Does not apply to deep sedation, securing an endotracheal airway (e.g., rapid sequence intubation), or care of mechanically ventilated patients
- Facilities may exercise flexibility to modify protocol as necessary to operationalize parenteral (IV or IM) ketamine for treating acute pain
Indication & Patient Population- Management of treatment-refractory pain (nociceptive, neuropathic) when first-line therapies fail or are contraindicated.
- For non-sedation purposes in VHA Hospice or Palliative Care under the care or direction of a palliative care team (or locally identified expert).
- Applicable for inpatient or Community Living Center (CLC) settings.
Contraindications- Hypersensitivity to ketamine or any excipient.
Precautions- Active psychosis, delirium, or inability to report side effects.
- Patients for whom significant elevations in blood pressure would constitute a serious hazard.
- Patients with or at risk of increased intracranial pressure.
- Unstable cardiovascular disease.
- Consider lower dosing for older patients or patients with comorbidities to mitigate adverse effects.
Dosing & Administration- Continuous Infusion: Initial dose 0.1 to 0.2 mg/kg/hr of Ideal Body Weight (IBW) via continuous IV or SQ infusion. Titrate no sooner than every 12 hours; max titration increment 0.1 mg/kg/hr. Recommended maximum dose 0.5 mg/kg/hr IBW. Duration typically ranges from 1 to 5 days; consider titrating to effect/max tolerated dose and continuing for an additional 48 hours, then discontinue.
- IVPB or SQ Bolus: Initial dose 0.1 to 0.3 mg/kg (IVPB administered over 30 minutes). Additional doses may be repeated if effective or converted to alternate route; frequency not to exceed q8hr dosing. May increase dose up to 0.5 mg/kg; maximum total daily dose not to exceed 1 mg/kg IBW.
- Oral Administration: Test/initial dose 10 mg PO once, then 5-10 mg PO q8h based on response. Initial titration 5 to 10 mg per dose per 24 hours. Maximum dose 400 mg/day (e.g., 100 mg q6h). Parenteral to oral conversion: Calculate total 24-hour parenteral dose and replace at 2/3rds of that amount.
- Consider using actual body weight if less than IBW to calculate dose.
Monitoring Requirements- Check vital signs, pain, affect, and psychomimetic adverse effects at baseline, at 1 hour after infusion starts or first dose/dose increase, then with each shift change.
- Repeat initial monitoring process after each dose change.
- Palliative care team may adjust monitoring as needed if vital signs assessment is not consistent with patient goals.
- Alert provider if: Systolic BP change > 20 mmHg or HR change < or > 20 beats/min; Respiratory rate < 12 breaths/min or persistent shallow breathing/apnea; O2 saturation <90% or RASS score -2 or below.
Adverse Effects & Management- Common: Dizziness, sedation, sense of unreality, nausea. Manage with lower doses or slower routes; educate patient to report bothersome effects.
- Uncommon: Increase in blood pressure.
- Rare: Excess sedation, respiratory compromise.
- Psychomimetic side effects: Add benzodiazepine or haloperidol (lorazepam commonly used) and decrease ketamine dose to previously tolerated dose.
- Increased secretions/lacrimation/salivation: Manage with anticholinergic agent (glycopyrrolate, atropine ophthalmic drops, or scopolamine patch).
- Discontinuation/Withdrawal: Hyperalgesia and allodynia reported after abrupt discontinuation after 3 weeks. If used >10 days, safely taper over 48-72 hours. Monitor for withdrawal signs including nausea, dizziness, diarrhea, depression, anxiety, and schizophrenic-type behaviors.
Additional Clinical Considerations & Scope- Consider decreasing opioids by 15-50% at initiation due to opioid-sparing effect; may need to continue taper if excessive respiratory depression or hemodynamic instability occur.
- IV formulation may be drawn up directly for oral administration but is very bitter; administer with sweet liquid (e.g., fruit juice, cola).
- Does not apply to primary sedation, securing an endotracheal airway (e.g., rapid sequence intubation), mechanically ventilated patients, topical-oral ketamine for mucositis, or outpatient oral use.
- Dosing, duration, and route flexibility allowed per facility operational needs; must be individualized under guidance of providers experienced in palliative and hospice medicine.
Indications & Patient Selection- Treatment for treatment-resistant major depressive disorder (TRD) or severe suicidal ideation
- Meets one of the following:
- Remission not achieved from 2 antidepressant trials (including an augmentation strategy) in the current episode of depression AND 4 total adequate antidepressant trials in the patient’s lifetime
- Hospitalized with TRD with acute suicidal ideation/behavior
- Must meet ALL additional criteria:
- Moderate to severe depressive symptomatology (PHQ-9 > 15 within the last 30 days)
- Antidepressant trials considered unsuccessful if no response to at least 6 weeks of an antidepressant at half maximum dose or greater
- Evaluated and documented by a VA psychiatrist or VA licensed Mental Health care provider (CPP, NP, PA) as qualifying for ketamine treatment
- Signed informed consent from patient or legal representative
- Agreement to remain monitored post-administration, refrain from driving/operating machinery, and avoid making major financial/legal decisions for the remainder of the day
- Adult accompaniment for transportation OR documented safe transport method arranged
- For women of childbearing potential: Pregnancy excluded prior to administration; provided contraceptive counseling on risks vs. benefits
Exclusion Criteria- Current or history of schizophrenia, schizoaffective disorder, or bipolar disorder
- Dementia
- Current or recent (within 30 days) delirium
- Current uncontrolled hypertension (SBP >140 mm Hg or DBP >90 mm Hg)
- Severe cardiac decompensation (Class IV heart failure or unstable angina)
- Severe hepatic impairment (Child-Pugh class C)
- Uncontrolled seizures
- History of non-response to ketamine or esketamine
- Pregnant (positive pregnancy test) or lack of birth control method in women of childbearing potential
- Breastfeeding
- Current or previous abuse of ketamine or esketamine
- Clinical evidence for current substance misuse (except tobacco)
- Current moderate or severe substance use disorder (SUD)
- Allergy or previous serious adverse effects to ketamine or esketamine
Screening & Referral Requirements- Screening completed no more than 60 days prior to first dose acceptance/administration
- Required screening components: Signed informed consent, psychiatric examination (including inclusion/exclusion criteria assessment), PHQ-9 depression rating scale, cognitive status evaluation (e.g., M-ACE), suicide risk assessment (C-SSRS at intake/initial evaluation and within 24 hours of discharge/clinically indicated; CSRE if first ever or updated clinically indicated), physical examination with vitals (BP, HR), relevant laboratory measures, urine toxicology, pregnancy screens
- Medical clearance/consultation based on individual risk factors is the responsibility of the prescribing provider
- Concurrent psychoactive substance use/abuse history must be evaluated; patients in recovery warned of relapse risk; close monitoring/random monitored urine drug testing recommended if treatment is chosen
- CNS depressants (benzodiazepines, non-benzodiazepine hypnotics, naltrexone) may attenuate antidepressant effects; allow adequate washout time prior to administration
Administration & Monitoring Parameters- Facility must provide a private setting with crash cart access, capability for immediate care, monitoring of cardiovascular (ECG, BP) and respiratory function (O2 sat or end-tidal CO2), management of dangerous behavioral symptoms (oxygen, medications, restraints), and plan for sustained CV alterations/advanced cardiac life support
- High-risk patients must be treated at equipped/staffed facilities
- Ordering provider: VA psychiatrist or VA licensed Mental Health care provider (CPP, NP, PA)
- Required personnel during infusion: ACLS certified physician/nurse and ordering provider (ordering provider may leave once stable; must return 120 minutes after start to clear for discharge; ACLS provider remains until discharge)
- Dosing: 0.5 mg/kg IV infusion over 40 minutes (range 0.5–1 mg/kg). For BMI >30 kg/m2, calculate dose using ideal body weight
- Monitoring schedule during infusion: Vitals at T+10, 20, 30, 40 min; check for resolution of sedation/dissociation/adverse effects at T+80 and T+120 min
- Parameters to stop infusion: BP must remain <180 mm Hg systolic and <110 mm Hg diastolic. Stop if SBP drops >10 mm Hg with increased HR or distress. Heart rate must remain below age-adjusted maximum (e.g., 20 yrs <140, 30 yrs <133, 40 yrs <126, 50 yrs <119, 60 yrs <112; ≥65 yrs individualized). Stop for pallor/cyanosis/poor perfusion, respiratory symptoms (SOB/wheezing), chest/jaw/arm pain, or patient desire to stop
Infusion Schedule & Duration- Repeat no less than 2 days apart and not more frequently than twice a week for 4 weeks
- After 4 weeks: Once a week to once every 3 weeks, with goal of extending interval (usually monthly)
- Long-term maintenance may be used but requires regular clinical review/re-evaluation
Discontinuation Criteria- Discontinue if patient wishes for any reason
- Discontinue if infusion stopped >1 time due to exceeding BP or HR thresholds
- Discontinue if no response after 4 weeks (adequate response defined as ≥50% decline in PHQ-9 from baseline)
- Discontinue if pronounced or slow-to-correct cognitive impairment or repeated dissociative symptoms
- Discontinue when dosing cannot be spaced to a minimum of 1 dose per week by the second month
Longitudinal Monitoring- PHQ-9 completed prior to each IV ketamine dose
- PHQ-9 and cognitive evaluation (e.g., M-ACE) at end of induction phase, every 6 months, and at end of treatment course
- Suicide risk monitored via CSRE and C-SSRS Screener
- C-SSRS required at intake/initial evaluation and within 24 hours of discharge/discontinuation; CSRE at intake if first ever or updated clinically indicated
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KETOPROFEN CAP,ORAL
ORUDIS
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ORUDIS |
2017-02-27 |
Continuity of Care Inclusion Criteria- Veteran is transitioning care from the Department of Defense to VHA
- Must also meet one of the following Additional Inclusion Criteria:
- The medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making
- The medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making
Non-Continuity of Care Inclusion Criteria- All criteria must be met:
- Inadequate response or intolerance to two formulary NSAIDs (NSAIDs=Nonsteroidal anti-inflammatory drugs)
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KETOROLAC/ PHENYLEPHRINE OPH IRR
OMIDRIA
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OMIDRIA |
2017-02-27 |
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LEVOFLOXACIN TAB
LEVAQUIN, LEVAQUIN LEVA-PAK
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LEVAQUIN, LEVAQUIN LEVA-PAK |
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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LEVONORGESTREL INSERT,INTRAUTERINE
KYLEENA, LILETTA, MIRENA, SKYLA
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KYLEENA, LILETTA, MIRENA, SKYLA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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LEVONORGESTREL TAB
PLAN B ONE-STEP
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PLAN B ONE-STEP |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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LIFITEGRAST SOLN,OPH
XIIDRA
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XIIDRA |
2017-02-27 |
Exclusion Criteria- Active ophthalmic infections, including herpes keratitis
- Hypersensitivity to lifitegrast or any of its ingredients
Inclusion Criteria- Diagnosis of dry eye disease with lack of therapeutic response to at least two artificial tear agents from different categories and a trial of 0.05% cyclosporine eye drops
- Documented corneal surface damage despite frequent use of artificial tears and 0.05% cyclosporine eye drops
Provider Requirements- Provider must be a VA/VA Community Care ophthalmologist or optometrist
Clinical Considerations & Trial Data- Artificial tear categories include: Cellulose Derivatives, Liquid Polyols, Polyvinyl Alcohol, Oil containing, and High Viscosity (gel drops, gels, ointments)
- Cyclosporine typically requires 3 to 6 months for increased tear production or improved symptoms; lifitegrast symptom relief may begin as early as 2 weeks with general improvements at 6 and 12 weeks
- Co-administration with punctual occlusion should be reviewed on a patient-by-patient basis due to lack of subgroup efficacy and safety analysis
- Limited data exist for safety and efficacy in ocular graft vs. host disease and corneal transplant rejection
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LINACLOTIDE CAP,ORAL
LINZESS
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LINZESS |
2017-02-27 |
Exclusion Criteria- Mechanical gastrointestinal obstruction, known or suspected
- Age less than 18 years
- Presence of severe or frequent diarrhea
- Chronic idiopathic constipation (CIC) excludes drug-induced chronic constipation and chronic constipation due to neurogenic and non-neurogenic disorders
Inclusion Criteria- Men or women 18 years or older with a documented diagnosis of chronic idiopathic constipation (CIC)
- Intolerance or inadequate response to a 1-month trial of at least one bulk forming laxative (e.g., psyllium, oxidized cellulose, calcium polycarbophil) with fluids unless there is a contraindication or risk factor(s) for serious adverse event(s)
- Intolerance or inadequate response to a 1-month trial of either PEG-3350 powder for oral solution (17 g twice daily) or other osmotic laxative, unless there is a contraindication or risk factor(s) for serious adverse event(s)
- Intolerance or inadequate response to a 1-month trial of lubiprostone (24 mcg twice daily) unless there is a contraindication or risk factor(s) for serious adverse event(s)
Additional Recommendations & Notes- GI consultation (including e-consult) is highly recommended prior to using linaclotide for CIC
- Examples of osmotic laxatives include lactulose, sorbitol, magnesium citrate, magnesium hydroxide, and glycerin rectal suppositories
- During the 1-month trial, escalation/titration of therapy up to bowel-prep doses of PEG-3350 may be considered case by case to achieve the desired response
Exclusion Criteria- Mechanical gastrointestinal obstruction, known or suspected
- Age less than 18 years
- Presence of severe or frequent diarrhea
- IBS excludes drug-induced chronic constipation and chronic constipation due to neurogenic and non-neurogenic disorders
Inclusion Criteria (All must be met)- Men or women 18 years or older with irritable bowel syndrome with constipation (IBS-C)
- Intolerance or inadequate response to a 1-month trial of either PEG-3350 powder for oral solution or other osmotic laxative, unless there is a contraindication or risk factor(s) for serious adverse event(s)
- GI consultation (including e-consult) is highly recommended prior to using linaclotide for IBS-C
Additional Inclusion Criteria (One must be met)- For men: Intolerance or inadequate response to a 1-month trial of plecanatide (3 mg once daily), unless there is a contraindication or risk factor(s) for serious adverse event(s)
- For women: Intolerance or inadequate response to a 1-month trial of lubiprostone (8 mcg twice daily), unless there is a contraindication or risk factor(s) for serious adverse event(s). Use of lubiprostone is off-label for IBS-C in men.
Trial & Laxative Definitions- Examples of osmotic laxatives: lactulose, sorbitol, magnesium citrate, magnesium hydroxide, glycerin rectal suppositories
- During the 1-month trial, escalation/titration of therapy up to bowel-prep doses of PEG-3350 may be considered case by case to achieve the desired response.
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LUBRICANT,VAGINAL GEL
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|
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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MACITENTAN TAB,ORAL
OPSUMIT
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OPSUMIT |
2017-02-27 |
Inclusion Criteria- Care provided by a VA/VA Community Care provider experienced in the management of pulmonary arterial hypertension (PAH)
- World Health Organization (WHO) Group 1 PAH
- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis: mean pulmonary artery pressure (mPAP) >25 mmHg, pulmonary artery wedge pressure (PAWP) ≤15 mm Hg, and pulmonary vascular resistance (PVR) >3 Wood Units
- Baseline liver enzyme testing (with repeat testing as clinically indicated)
- Intolerance, inadequate response, or unable to use ambrisentan (ambrisentan is the preferred endothelin receptor antagonist in VA when clinically appropriate)
Reproductive & Pregnancy Management- For females who can become pregnant: Pregnancy must be excluded prior to receiving macitentan. Counseling provided on potential risk vs benefit of treatment and the use of effective contraception prior to, during, and one month after stopping treatment.
- For males of reproductive potential: Counseling provided on the potential risk of macitentan to adversely affect spermatogenesis and impair fertility.
→ Full criteria details
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MEDROXYPROGESTERONE INJ,SUSP
DEPO-PROVERA, DEPO-SUBQ PROVERA 104, MEDROXYPROGESTERONE ACETATE
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DEPO-PROVERA, DEPO-SUBQ PROVERA 104, MEDROXYPROGESTERONE ACETATE |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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MEDROXYPROGESTERONE TAB
MEDROXYPROGESTERONE ACETATE, PROVERA
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MEDROXYPROGESTERONE ACETATE, PROVERA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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MEPOLIZUMAB INJ,LYPHL
NUCALA
|
NUCALA |
2017-02-27 |
Indication & Patient Population- Add-on maintenance therapy in adults with inadequately controlled chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype.
- Patients must have an eosinophilic phenotype defined as EOS > 300 microL.
Prior Therapy & Treatment Requirements- Must be continuing to experience exacerbations despite adherence to maximal inhaled therapies (LAMA+LABA+ICS) with documented proper inhaler use technique.
- A trial of azithromycin and/or roflumilast should be considered prior to mepolizumab in certain patients with exacerbations of COPD.
Dosing & Administration- 100 mg subcutaneously (SQ) every 4 weeks.
- Available as 100 mg single dose vial, 100 mg single dose prefilled syringe, or prefilled autoinjector.
Contraindications & Precautions- Contraindicated in patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.
- Not indicated for treating acute symptoms or exacerbations of asthma or COPD.
- Pre-existing parasitic infection (Helminth) must be treated prior to initiating therapy.
- Monitor for risk of hypersensitivity reactions and opportunistic infections (e.g., herpes zoster).
Exclusion Criteria- Untreated acute bronchospasm or acute exacerbation of chronic obstructive pulmonary disease (COPD)
- Untreated parasitic (helminth) infection (infection must be treated prior to initiating mepolizumab)
- Concurrent use with therapeutic biologics unless potential benefit-risk favors use
- Inclusion Criteria (All criteria must be met)
- Provider is a VA or VA Community Care pulmonologist or designated expert
- Moderate to severe COPD (post-bronchodilator FEV1 30-70% predicted and FEV1/FVC <0.7, confirmed by pulmonary function testing)
- Blood eosinophils ≥300 cells/µL obtained prior to treatment (e.g., within the 3 months prior)
- Signs or symptoms of chronic bronchitis (chronic productive cough) for at least 3 months during the past year
- Receiving concurrent triple inhaled therapy with a long-acting beta-agonist (LABA), long-acting anticholinergic (LAMA), and inhaled corticosteroid (ICS) (unless ICS is contraindicated) for at least 3 months
- At least 2 moderate COPD exacerbations (requiring systemic steroids and/or antibiotics) or at least 1 severe COPD exacerbation (requiring hospitalization) in the previous 12 months
- Inadequate symptom control (e.g., mMRC dyspnea scale score > 2) or impaired health status (e.g., CAT score > 15)
- Unable to tolerate or had an inadequate response to a 6-month trial of roflumilast and a 6-month trial of azithromycin, unless not clinically appropriate for either agent
- Adherent to COPD medications as evidenced by prescription refill history review
- Demonstrated correct inhaler technique (documented in chart)
Additional Inclusion Criteria & Clinical Guidance- Patient is non-smoking or enrolled in a smoking cessation program/on cessation medications; current smokers may be considered if unable or refusing to quit
- Modifiable environmental triggers for Type 2 inflammation should be addressed, if not already done
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
Other Justification- Hypereosinophilic syndrome (HES) to reduce eosinophilia and minimize exposure to glucocorticoids, prescribed by a specialty provider experienced in managing HES
- Non-severe active eosinophilic granulomatosis with polyangiitis (EGPA) to induce remission, prevent relapse, and minimize exposure to glucocorticoids, prescribed by a specialty provider experienced in managing EGPA with an inadequate response to benralizumab
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METHYLNALTREXONE INJ
RELISTOR
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RELISTOR |
2017-02-27 |
Exclusion Criteria- Known or suspected mechanical gastrointestinal obstruction or other condition that may compromise drug action or cause bowel dysfunction (e.g., acute abdomen, ostomy, active diverticulitis, ischemic bowel, etc.)
- Placement of peritoneal catheter for chemotherapy or dialysis (not studied)
- End-stage renal impairment on dialysis (not studied)
- Use of methylnaltrexone solely for prevention of opioid-induced constipation or impaction (no supporting evidence)
- Use of methylnaltrexone for postoperative ileus (preliminary results showed inefficacy)
- Use of methylnaltrexone for constipation that is not opioid-related (not studied)
- Concomitant use of other opioid antagonists (potential for increased risks of additive effects and opioid withdrawal)
Inclusion Criteria: Opioid-Induced Constipation in Adults with Chronic Noncancer Pain- Patient has been taking opioids for chronic noncancer pain (including chronic pain related to prior cancer or its treatment) for at least 4 weeks and does not require frequent opioid dose escalation.
- A stimulant laxative (e.g., bisacodyl, sennosides; 1-month trial) is medically inadvisable, inadequate, or not tolerated.
- MIRALAX-equivalent (twice daily) or other osmotic laxative (e.g., sorbitol, magnesium citrate; 1-month trial) is medically inadvisable, inadequate, or not tolerated.
- Naloxegol at optimized, recommended oral dosage for renal function (at least a 1-week trial) is medically inadvisable, inadequate, or not tolerated.
- Naldemedine at optimized, recommended oral dosage (at least a 1-week trial) is medically inadvisable, inadequate, or not tolerated.
- Lubiprostone at optimized, recommended oral dosage for hepatic function (at least a 1-week trial) is medically inadvisable, inadequate, or not tolerated.
Inclusion Criteria: Opioid-Induced Constipation in Patients with Advanced Illness- Prescriber is a VA/VA Community Care palliative care specialist or provider locally designated to prescribe methylnaltrexone.
- Patient has advanced illness for which he/she is receiving palliative care in a monitored setting or at home with hospice care.
- Patient has opioid-induced constipation and requires PROMPT laxative effects.
- An oral and / or rectal stimulant laxative (e.g., bisacodyl, sennoside) in at least usual doses is medically inadvisable (e.g., dysphagia), inadequate, or not tolerated.
- An oral osmotic laxative (such as lactulose or PEG 3350 in low doses) in at least usual doses is medically inadvisable (e.g., dysphagia), inadequate, or not tolerated.
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METHYLNALTREXONE TAB
RELISTOR
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RELISTOR |
2017-02-27 |
Exclusion Criteria- Known or suspected mechanical gastrointestinal obstruction or other condition that may compromise drug action or cause bowel dysfunction (e.g., acute abdomen, ostomy, active diverticulitis, ischemic bowel, etc.)
- Placement of peritoneal catheter for chemotherapy or dialysis (not studied)
- End-stage renal impairment on dialysis (not studied)
- Use of methylnaltrexone solely for prevention of opioid-induced constipation or impaction (no supporting evidence)
- Use of methylnaltrexone for postoperative ileus (preliminary results showed inefficacy)
- Use of methylnaltrexone for constipation that is not opioid-related (not studied)
- Concomitant use of other opioid antagonists (potential for increased risks of additive effects and opioid withdrawal)
Inclusion Criteria: Opioid-Induced Constipation in Adults with Chronic Noncancer Pain- Patient has been taking opioids for chronic noncancer pain (including chronic pain related to prior cancer or its treatment) for at least 4 weeks and does not require frequent opioid dose escalation.
- A stimulant laxative (e.g., bisacodyl, sennosides; 1-month trial) is medically inadvisable, inadequate, or not tolerated.
- MIRALAX-equivalent (twice daily) or other osmotic laxative (e.g., sorbitol, magnesium citrate; 1-month trial) is medically inadvisable, inadequate, or not tolerated.
- Naloxegol at optimized, recommended oral dosage for renal function (at least a 1-week trial) is medically inadvisable, inadequate, or not tolerated.
- Naldemedine at optimized, recommended oral dosage (at least a 1-week trial) is medically inadvisable, inadequate, or not tolerated.
- Lubiprostone at optimized, recommended oral dosage for hepatic function (at least a 1-week trial) is medically inadvisable, inadequate, or not tolerated.
Inclusion Criteria: Opioid-Induced Constipation in Patients with Advanced Illness- Prescriber is a VA/VA Community Care palliative care specialist or provider locally designated to prescribe methylnaltrexone.
- Patient has advanced illness for which he/she is receiving palliative care in a monitored setting or at home with hospice care.
- Patient has opioid-induced constipation and requires PROMPT laxative effects.
- An oral and / or rectal stimulant laxative (e.g., bisacodyl, sennoside) in at least usual doses is medically inadvisable (e.g., dysphagia), inadequate, or not tolerated.
- An oral osmotic laxative (such as lactulose or PEG 3350 in low doses) in at least usual doses is medically inadvisable (e.g., dysphagia), inadequate, or not tolerated.
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METRONIDAZOLE TAB
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|
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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MIRTAZAPINE TAB,ORAL DISINTEGRATING
REMERON
|
REMERON |
2017-02-27 |
Continuity of Care- Veteran is transitioning care from the Department of Defense to VHA
- The medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making
- The medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making
Non-Continuity of Care- Difficulty swallowing oral tablet
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MOISTURIZER GEL,VAG
|
|
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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MOMETASONE INHL,ORAL
ASMANEX, ASMANEX HFA, ASMANEX TWISTHALER
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ASMANEX, ASMANEX HFA, ASMANEX TWISTHALER |
2017-02-27 |
Indications & Clinical Context- Recommended for conversion during mometasone inhaler (Asmanex) shortage due to favorable pricing.
- Dose comparison table explicitly provided for asthma.
- Clinically used as add-on therapy to bronchodilators for COPD, though not FDA-approved for COPD.
Dosing & Administration- Frequency of administration: Twice daily.
- Total daily dose categories (based on product labeling):
- Low: ≤160 mcg
- Medium: >160-320 mcg
- High: >320 mcg
Strengths & Formulation- Ciclesonide HFA MDI (Alvesco) available in 80 mcg and 160 mcg strengths.
Clinical Considerations & Monitoring- Consider disease control and severity when switching.
- Monitor patient response and adjust dose as appropriate.
- Refer to product package insert for further dosing information.
- Table provides suggested total daily doses based on product labeling, not equivalence or potency equivalence.
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NALOXEGOL TAB,ORAL
MOVANTIK
|
MOVANTIK |
2017-02-27 |
Exclusion Criteria- Age less than 18 years
- Known or suspected gastrointestinal obstruction or at risk of recurrent obstruction
- Concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole)
- Known serious or severe hypersensitivity to naloxegol or its excipients
- Presence of severe or frequent diarrhea
Inclusion Criteria- Patient is taking opioids for chronic, non-cancer pain (including chronic pain related to prior cancer or its treatment), does not require frequent opioid dose escalation, and is documented to have opioid induced constipation (OIC)
- Documentation of attempts to reduce constipation by change to less constipating analgesics or reduction of opioid dose, OR medical justification why changes are unable to be made in current regimen
- Documentation that benefits of opioid therapy exceed risks for the patient and all VA/DOD Directives/guidelines for prescribing and monitoring long-term opioids are being followed
- Intolerance or inadequate response to 1-month trials of: one stimulant laxative (e.g., bisacodyl, sennosides) AND a MIRALAX equivalent (twice daily) or other osmotic laxative (e.g., sorbitol, lactulose, magnesium citrate, magnesium hydroxide, glycerin rectal suppositories), unless contraindication or risk factor(s) for serious adverse event(s) exists
Laxative Management Prior to Initiation- Maintenance laxative therapy should be discontinued before starting naloxegol
- Laxatives may be resumed if OIC symptoms persist after taking naloxegol for 3 days
- Bulk forming laxatives are relatively contraindicated in OIC
- Stool softeners (e.g., docusate) are considered low benefit and low harm for OIC and may be used but are not required prior to use of naloxegol in OIC
Dosing & Administration- Recommended dose: 25 mg once daily in the morning
- If patient is unable to tolerate 25 mg, consider 12.5 mg daily
- If creatinine clearance is < 60 ml/min, 12.5 mg once daily is recommended with option to titrate to 25 mg daily if tolerated at the 12.5-mg dose
- Instruct patient to take on an empty stomach one hour prior to first meal of the day or two hours after a meal
- Consumption of grapefruit or grapefruit juice should be avoided
Monitoring & Safety Considerations- OIC defined as < 3 spontaneous bowel movements (SBMs) per week on average with at least 25% of SBMs associated with straining, hard/lumpy stools, or sensation of incomplete evacuation; SBMs defined as bowel movements without rescue laxatives taken within past 24 hours
- Clinical response defined as ≥ 3 SBMs per week and a change from baseline of ≥ 1 SBM per week for at least 9 of the 12 study weeks and 3 of the last 4 weeks
- Monitor for opioid withdrawal symptoms (e.g., hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, yawning); frequency of GI adverse reactions related to opioid withdrawal was higher in patients taking methadone
- Disruptions in blood-brain barrier may increase risk of opioid withdrawal or reduced analgesia
- Use with caution in patients at risk for gastrointestinal perforation (e.g., peptic ulcer disease, diverticular disease, infiltrative GI malignancy, peritoneal metastases, Crohn’s disease)
- Pregnancy Category C: May cross fetus's immature blood-brain barrier and precipitate opioid withdrawal; use only if potential benefit justifies potential risk to fetus
- Nursing Mothers: Potential for opioid withdrawal and other serious adverse reactions in nursing infants; discontinue nursing or using naloxegol considering risks and benefits to mother
Prescription Duration & Renewal Criteria- Initial prescription supply: Up to 2 weeks
- Renewal requires patient experiences clinically important benefit (improved constipation and abdominal pain) after an adequate therapeutic trial and tolerates treatment
- Adequate therapeutic trial is defined as 1 week
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NATALIZUMAB INJ,SOLN
TYSABRI
|
TYSABRI |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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NIVOLUMAB INJ,SOLN
OPDIVO
|
OPDIVO |
2017-02-27 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression requiring a corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Known pregnancy
- Breastfeeding
Inclusion Criteria (One must be fulfilled)- Indication is FDA-approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria (All must be fulfilled)- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (If applicable)- For females who can become pregnant: Pregnancy must be excluded prior to receiving either nivolumab product
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 5 months after stopping treatment
Product-Specific Administration Guidelines- Nivolumab IV has approval in classical Hodgkin Lymphoma; nivolumab/hyaluronidase SUBQ does not replace nivolumab IV in this setting
- Nivolumab/hyaluronidase-nvhy should not replace nivolumab when given in combination with ipilimumab
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NORETHINDRONE TAB
CAMILA, DEBLITANE, EMZAHH, ERRIN, GALLIFREY, HEATHER, INCASSIA, JENCYCLA, LYLEQ, LYZA, MELEYA, NORA-BE, NORETHINDRONE ACETATE, ORQUIDEA, ORTHO MICRONOR, SHAROBEL, TULANA
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CAMILA, DEBLITANE, EMZAHH, ERRIN, GALLIFREY, HEATHER, INCASSIA, JENCYCLA, LYLEQ, LYZA, MELEYA, NORA-BE, NORETHINDRONE ACETATE, ORQUIDEA, ORTHO MICRONOR, SHAROBEL, TULANA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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NORGESTREL TAB
|
|
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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NOVASOURCE LIQUID,NUTRITIONAL SUPPLEMENT
NOVASOURCE RENAL 2 CAL
|
NOVASOURCE RENAL 2 CAL |
2017-02-27 |
Inclusion Criteria- Provider is a VA / VA Community Care Nephrologist or Registered Dietitian
- Patient has renal impairment
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OFATUMUMAB INJ,SOLN
ARZERRA, KESIMPTA PEN
|
ARZERRA, KESIMPTA PEN |
2017-02-27 |
Exclusion Criteria- Diagnosis of primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis without activity (non-active SPMS)
- History of life-threatening infusion reaction to another anti-CD20 antibody (e.g., ublituximab, rituximab)
- Untreated active hepatitis B infection
- Untreated latent or active tuberculosis infection
- Concurrent use of another disease modifying therapy (DMT) to treat multiple sclerosis (MS) unless the previous agent will be discontinued when ofatumumab is initiated
- Active infection or receiving chemotherapy
- Pregnancy
Inclusion Criteria- Care provided by a VA/VA Community Care neurologist or locally designated MS expert (e.g., Spinal Cord Injury)
- Diagnosis of a relapsing form of multiple sclerosis (relapsing-remitting MS, active secondary progressive MS, or clinically isolated syndrome) has been established
- Intolerance or inadequate therapeutic response to ublituximab OR patient not a candidate for IV anti-CD20 antibody therapy due to inability to access an infusion center or poor venous access
- Patient screened for hepatitis B virus (HBV) including HBsAg, HBsAb and HBcAb. If HBsAb negative and HBcAb positive or HBsAg positive, a liver disease expert must be consulted first.
- Quantitative serum immunoglobulins tested. If low, neurologist has documented risk/benefit assessment and/or an immunology expert was consulted prior to start.
- All guideline recommended eligible immunizations administered at least 4 weeks prior to the start of treatment for live or live-attenuated vaccines, and whenever possible, at least 2 weeks prior to the start of treatment for inactivated vaccines.
Additional Inclusion Criteria (One of the following must be met)- Current treatment with natalizumab and patient has elevated risk factors for PML (anti-JC virus antibody positive, duration of therapy > 24 months or received immunosuppressant therapy prior to natalizumab)
- Ineffectiveness with at least one other MS DMT defined as: continued clinical relapses, central nervous system (CNS) lesion progression on MRI, or continued worsening of disability
- Highly active disease demonstrated by heavy burden of gadolinium enhancing and/or T2 lesions on MRI at onset of disease, high accumulation of CNS lesions on MRI, or rapid accrual of disability
Pregnancy and Counseling Requirements- For patients who can become pregnant: Pregnancy should be excluded prior to receiving ofatumumab
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 6 months after stopping treatment
Other Justification- Select for ARZERRA (oncologic indications, not multiple sclerosis)
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OLANZAPINE TAB,RAPID DISINTEGRATE
OLANZAPINE ODT, ZYPREXA ZYDIS
|
OLANZAPINE ODT, ZYPREXA ZYDIS |
2017-02-27 |
Continuity of Care Inclusion Criteria- Veteran is transitioning care from the Department of Defense to VHA
- Additional Inclusion Criteria (select one):
- The medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making.
- The medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making.
Non-Continuity of Care Inclusion Criteria- Difficulty swallowing oral tablet.
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OMALIZUMAB INJ,LYPHL
XOLAIR
|
XOLAIR |
2017-02-27 |
Exclusion Criteria- Prior severe hypersensitivity reaction to omalizumab or any of its ingredients
- Do not use to treat acute exacerbation of asthma or status asthmaticus
Inclusion Criteria- Care provided by a VA/VA Community Care pulmonologist, immunologist, allergist, or designated expert in the management of asthma
- Diagnosis of moderate to severe persistent asthma
- Pre-treatment serum IgE is 30 to 700 IU/mL
- Positive skin tests or in vitro reactivity to common aeroallergens (e.g., dust mites, pet dander, cockroach)
- Receiving medium to high dose inhaled corticosteroids and long-acting beta-agonist or other controller medication(s)
- Inadequate symptom control (e.g., short-acting beta-agonist use, nighttime awakening due to asthma more than once weekly, limitation with normal activity, Asthma Control Test less than 19) OR asthma exacerbation(s) requiring systemic corticosteroids in the last 12 months
- Adherent to asthma medications as evidenced by a review of prescription refill history during the last 12 months
- Should be nonsmoking or receiving smoking cessation treatment if smoking
- Has an epinephrine pen available at time of injection and for at least 24 hours after injection
- Therapy to be initiated in a healthcare setting
Additional Inclusion Criteria for Self-Administration- Provider has determined that self-administration with prefilled syringe by patient or caregiver is appropriate
- No previous history of anaphylaxis to omalizumab or other agents (e.g. food, drugs, biologics, etc.)
- At least 3 doses were administered in healthcare setting with no hypersensitivity reactions
- The patient and/or caregiver must be trained in and demonstrate the correct subcutaneous injection technique
- The patient and/or caregiver are taught to recognize signs and symptoms of anaphylaxis and is able to treat anaphylaxis appropriately
Other Justification- Patient has confirmed Ig-E mediated food allergy and a need for treatment with omalizumab to reduce the risk of type 1 allergic reactions, including anaphylaxis, and prescribed by a specialist in Allergy and Immunology.
Clinical Notes & Local Adjudication- Data for use in patients with baseline IgE serum levels up to 1500 IU/mL are available (considered off-label in the US). Use of omalizumab in such patients should be adjudicated locally.
- There is limited information on the efficacy and safety of omalizumab in patients who smoke. The decision to use omalizumab in patients who have had unsuccessful attempts at smoking cessation should be made on a case-by-case basis.
Exclusion Criteria- Prior severe hypersensitivity reaction to omalizumab or any of its ingredients
Inclusion Criteria (All must be fulfilled)- Diagnosis of severe chronic spontaneous urticaria (e.g., UAS7 >28 and/or UCT <12)
- Unacceptable symptoms despite a therapeutic trial of 1 non-sedating H antihistamine titrated up to 4 times the usual daily dose
- Has an epinephrine rescue device available at the time of injection and for at least 24 hours after the injection
- Omalizumab therapy is initiated in a healthcare setting
Provider Requirements- Provider is a VA or VA Community Care allergy specialist, dermatologist or designated expert in the management of allergic conditions
Additional Inclusion Criteria for Self-Administration- Provider has determined that self-administration with prefilled syringe by patient or caregiver is appropriate
- No previous history of anaphylaxis to omalizumab or other agents (e.g., food, drugs, biologics, etc.)
- At least 3 doses were administered in healthcare setting with no hypersensitivity reactions
- Patient and/or caregiver are taught to recognize signs and symptoms of anaphylaxis and able to treat anaphylaxis appropriately
Dosing/Pharmacology Notes- Dose is not dependent upon free or total serum IgE levels or body weight
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OMEGA-3 ACID CAP,ORAL
LOVAZA, OMEGA-3 ACID ETHYL ESTERS
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LOVAZA, OMEGA-3 ACID ETHYL ESTERS |
2017-02-27 |
Indication- Severe hypertriglyceridemia
Laboratory Criteria- Fasting triglyceride level of > 500 mg/dL on two occasions
Pre-treatment Considerations & Warnings- Secondary causes should be considered and addressed prior to initiation of therapy
- Effect of Lovaza and Lovaza generics on risk for pancreatitis in patients with severe hypertriglyceridemia has not been established
Therapeutic Efficacy & Alternatives- Evidence does not support a greater triglyceride lowering response between Lovaza, Lovaza generics and icosapent ethyl
- For patients who may be candidates for reducing cardiovascular (CV) risk with icosapent ethyl (established CV disease, on statins with LDL 41-100 mg/dL and fasting TG > 150 mg/dL), refer to CFU for Icosapent Ethyl
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OMEPRAZOLE CAP,EC
PRILOSEC
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PRILOSEC |
2017-02-27 |
Pharmacology & Drug Interaction- Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
- Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.
Gastrointestinal Risk Management- PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
- For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.
Cardiovascular Risk Management- Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
- No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.
Prescribing Criteria- Deprescribe PPIs as much as possible per established de-prescribing guidelines.
- Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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OMEPRAZOLE PWDR,RENST-ORAL
PRILOSEC
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PRILOSEC |
2017-02-27 |
Pharmacology & Drug Interaction- Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
- Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.
Gastrointestinal Risk Management- PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
- For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.
Cardiovascular Risk Management- Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
- No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.
Prescribing Criteria- Deprescribe PPIs as much as possible per established de-prescribing guidelines.
- Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.
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OMEPRAZOLE TAB,SA
|
|
2017-02-27 |
Pharmacology & Drug Interaction- Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
- Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.
Gastrointestinal Risk Management- PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
- For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.
Cardiovascular Risk Management- Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
- No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.
Prescribing Criteria- Deprescribe PPIs as much as possible per established de-prescribing guidelines.
- Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.
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OMEPRAZOLE/ SODIUM BICARBONATE CAP,ORAL
|
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2017-02-27 |
Pharmacology & Drug Interaction- Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
- Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.
Gastrointestinal Risk Management- PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
- For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.
Cardiovascular Risk Management- Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
- No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.
Prescribing Criteria- Deprescribe PPIs as much as possible per established de-prescribing guidelines.
- Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.
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OMEPRAZOLE/ SODIUM BICARBONATE PWDR,RENST-ORAL
|
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2017-02-27 |
Pharmacology & Drug Interaction- Clopidogrel is a prodrug requiring biotransformation to its active metabolite via the hepatic cytochrome P450 (CYP) 2C19 enzyme.
- Omeprazole and other proton pump inhibitors (PPIs) utilize the same CYP450 metabolic pathway, theoretically causing competitive inhibition and decreased concentration of the active clopidogrel moiety.
Gastrointestinal Risk Management- PPI therapy is indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.
- For patients with GERD on clopidogrel presenting with LA grade C or D esophagitis or uncontrolled GERD symptoms, established benefits of PPI treatment outweigh proposed cardiovascular risks.
Cardiovascular Risk Management- Concomitant use of omeprazole and clopidogrel does not demonstrate significant adverse cardiovascular effects; no significant differences in MACE, MI, or all-cause death are observed in randomized controlled trials and propensity score-matched studies.
- No interaction has been observed between PPIs and aspirin, prasugrel, or ticagrelor.
Prescribing Criteria- Deprescribe PPIs as much as possible per established de-prescribing guidelines.
- Do not limit omeprazole use in patients on clopidogrel due to the lack of demonstrated adverse cardiovascular effects.
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ONABOTULINUMTOXINA INJ,PWDR
BOTOX, BOTOX COSMETIC
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BOTOX, BOTOX COSMETIC |
2017-02-27 |
Exclusion Criteria- Hypersensitivity to botulinum toxins or any components in the formulation (e.g., human serum albumin, lactose, sucrose, disodium succinate)
- Co-administration with neuromuscular blockade
- Neurologic condition where botulinum toxins pose risk for additive neuromuscular compromise (e.g., myasthenia gravis, amyotrophic lateral sclerosis), unless risks/benefits have been discussed with the patient and documented in the medical record
- Use for cosmetic purposes
Inclusion Criteria (Indications)- Cervical dystonia or focal dystonia
- Blepharospasm or hemifacial spasm
- Severe focal hyperhidrosis with inadequate response or unmanageable intolerance to prescription topical therapy (e.g., aluminum chloride hexahydrate 20% topical solution)
- Upper or lower limb spasticity
- Overactive bladder or neurogenic bladder dysfunction with contraindication, intolerance, or inefficacy to behavioral therapy and at least one pharmacotherapy (e.g., antimuscarinic agent, beta-3 adrenergic agonist)
- Chronic migraine prevention with contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 2 of the following: beta blocker, topiramate, divalproex, and ACE inhibitor or ARB
- Pharyngoesophageal segment spasm (PES)
- Sialorrhea with contraindication, intolerance, or lack of therapeutic response to anticholinergics and/or speech therapy
- Chronic anal fissure refractory to conservative treatment including supportive measures (e.g., dietary fiber, sitz bath) and topical vasodilator (e.g., topical nitrates)
- Esophageal achalasia if patient is not a candidate for surgery
- Idiopathic (primary or genetic) or symptomatic (acquired) torsion dystonia
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ORLISTAT CAP,ORAL
XENICAL
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XENICAL |
2017-02-27 |
Exclusion Criteria- Pregnancy
- Lactating
- Chronic malabsorption syndrome or chronic diarrhea
- History of cholestasis
Inclusion Criteria- Verifiable participation in a comprehensive lifestyle intervention (CLI) that targets all three aspects of weight management: diet, physical activity, behavioral changes
- BMI is greater than or equal to 30 kg/m2 OR BMI is greater than or equal to 27 kg/m2 with at least one weight-related comorbidity
- Demonstrated ability to comply with a low-fat diet
- Currently taking or receives a prescription for a multivitamin
Additional Inclusion Criteria- For patients who can become pregnant: Pregnancy should be excluded prior to receiving orlistat and the patient provided contraceptive counseling on potential risks vs. benefits of taking orlistat if the patient were to become pregnant
Indications & Eligibility- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance
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OSIMERTINIB TAB
TAGRISSO
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TAGRISSO |
2017-02-27 |
Exclusion Criteria- Baseline resting corrected QT interval (QTc) >470 msec obtained on more than one consecutive electrocardiogram (ECG) or risk factors (electrolyte abnormalities, heart failure, congenital long QT syndrome, family history of long QT syndrome, concomitant medications known to prolong QTc interval)
- Clinically important abnormalities in cardiac rhythm, conduction or morphology on ECG
- History of Interstitial Lung Disease or clinically active Interstitial Lung Disease
- Lactating status
- Pregnancy
Inclusion Criteria (Indications)- First-line treatment for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations
- In combination with pemetrexed and platinum-based chemotherapy for first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations
- Locally advanced or metastatic non-small cell lung cancer with a documented T790M mutation
- Adjuvant therapy after tumor resection for patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations
Additional Inclusion Criteria (Care Setting & Performance Status)- Care provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult discussed and documented
Additional Inclusion Criteria (Pregnancy & Contraception Counseling)- Patients who can become pregnant: counseling on potential risks vs benefits of treatment and use of effective contraception during therapy and for 6 weeks after stopping treatment
- Patients with partners who can become pregnant: counseling on potential risks vs benefits and use of effective contraception during therapy and for 4 months after stopping treatment
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OSPEMIFENE TAB,ORAL
OSPHENA
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OSPHENA |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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OXAPROZIN TAB,ORAL
DAYPRO
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DAYPRO |
2017-02-27 |
Continuity of Care Inclusion Criteria- Veteran is transitioning care from the Department of Defense to VHA (must be met along with one Additional Inclusion Criterion)
- Additional Inclusion Criteria (Select ONE if appropriate)
- The medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making
- The medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making
- Non-Continuity of Care Inclusion Criteria (All criteria must be met)
- Inadequate response or intolerance to two formulary NSAIDs
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OXYCODONE TAB,SA
OXYCODONE HCL ER, OXYCONTIN
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OXYCODONE HCL ER, OXYCONTIN |
2017-02-27 |
Transitioning Veteran Criteria- Veteran is transitioning care from the Department of Defense to VHA
- VA prescriber has assessed and consulted with the Veteran, determining that continuation of oxycodone SA tablets is safe and clinically appropriate
- If this criterion is met, the remainder of the criteria for use is not applicable
- Exclusion Criteria (Patient should NOT receive if ANY are met)
- Intended use is for treatment of mild pain
- Intended use is for treatment of acute pain
- Intended use is for postoperative pain (unless patient is already receiving the drug prior to surgery or postoperative pain is expected to be moderate to severe and persist for an extended period)
- Intended use is as an as-needed (prn) analgesic
- Patient has significant respiratory depression, condition predisposing to significant respiratory depression (e.g., acute or severe bronchial asthma), or known/suspected paralytic ileus
- Patient has hypersensitivity to oxycodone or other tablet contents
- Patient is unable to swallow whole tablets/requires tablets to be crushed before administration
- Inclusion Criteria (Must be fulfilled)
- Indication is management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period of time
- Patient has a documented contraindication to morphine, history of intolerable medication-related adverse effects to morphine, or documentation of inadequate analgesia despite appropriate upwards titration of morphine SA tablets
Therapeutic Alternatives- Methadone oral tablet is a long-acting opioid alternative; only clinicians familiar with its pharmacological characteristics, appropriate titration, risk profile, and prepared to educate/monitor patients should initiate or titrate
- Fentanyl TDS has safety concerns regarding dosing/absorption; only clinicians familiar with its properties and prepared to educate patients should initiate or titrate
Dosage and Administration- Available strengths: 10, 15, 20, 30, 40, 60, 80, 160 mg
- Opioid naïve patients: Use low-dose short-acting as-needed opioids to establish tolerance/efficacy and for dose finding prior to long-acting initiation
- Opioid tolerant definition: Receiving ≥1 week at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or equianalgesic dose of another opioid
- Conversion from other opioids: Use standard equianalgesic dosage estimates; new opioid typically dosed 33 to 50% less than calculated MME to avoid overdose due to incomplete cross-tolerance and individual variability
- Fentanyl TDS conversion: Initiate oxycodone SA 18 hours after patch removal; start with approximately 10 mg every 12 hours per 25 mcg/hr fentanyl TDS
- Methadone conversion: No widely accepted strategy; consult clinician with expertise in methadone dosing
- Titration/Conversion monitoring: Monitor and individualize to patient response; lower initial doses indicated for age >65, hepatic impairment, renal impairment, or concurrent CNS depressants; follow closely during conversion/titration
- Breakthrough pain: Rescue doses of oxycodone IR or other short-acting analgesic (alone or with acetaminophen/aspirin/NSAIDs) may be given as needed or ~1 h before anticipated incident pain; supplemental dose ~1/4 to 1/3 of the 12-h SA dose
- Co-therapy: Consider long-duration opioid + nonopioid analgesic (acetaminophen/NSAID) for opioid-sparing effects or additive analgesia
Safety and Monitoring- Adverse effect profile similar to morphine SA; no consistent safety/tolerability advantage over morphine SA
- Serious adverse reactions: Respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, shock
- Non-serious events (typically on initiation, decrease over time): Constipation, nausea, somnolence
- Monitor blood pressure during dose initiation/titration due to hypotensive potential
- Avoid in impaired consciousness/coma, head injury, or increased intracranial pressure (respiratory depressant effects may be magnified)
- Initiating/discontinuing CYP3A4 inducers may alter oxycodone plasma concentrations
- Pregnancy: Category B; use only if clearly indicated; may prolong labor and cause neonatal respiratory depression, physical dependence, and withdrawal syndrome
- Lactation: Excreted in breast milk; discontinue nursing or drug due to risk of infant sedation/respiratory depression/withdrawal
- Crushing tablets: Cannot be crushed; results in immediate release of full dose, risking fatal overdose
- Abuse hazard: Crushed tablet abuse increases overdose/death risk, especially with alcohol/substances; parenteral abuse risks local tissue necrosis, infection, pulmonary granulomas, endocarditis, and valvular heart injury
- CNS depressants: Concomitant use (other opioids, sedatives, hypnotics, tranquilizers/benzodiazepines, anesthetics, phenothiazines, muscle relaxants, alcohol) may cause respiratory depression, hypotension, profound sedation, or coma; concurrent opioids and benzodiazepines is recommended against
Provider-Related Guidance and Risk Mitigation- Implement risk mitigation strategies per VA/DOD Clinical Practice Guideline; include informed consent conversation covering risks/benefits of opioid therapy and alternatives
- Strategies and frequency should be commensurate with risk factors: ongoing random urine drug testing (with confirmatory testing), state PDMP checks, monitoring for overdose potential/suicidality, overdose education, naloxone rescue prescribing/education
- Initiation/Continuation: Guideline recommends against initiating long-term opioid therapy for chronic pain; for existing patients, continue risk mitigation, assess for OUD, consider tapering when risks exceed benefits
- Tapering: Screen/treat complicating conditions first (mental health disorders like PTSD/anxiety/depression, OUD/SUD, medical complications like lung/hepatic/renal disease, sleep disorders/apnea); typical taper involves 5% to 20% dose reductions every 4 weeks
- OUD Management: Aberrant behaviors may emerge during taper/discontinuation or as tolerance develops; DSM-5 criteria include craving, tolerance, withdrawal, using larger amounts/longer periods, spending excessive time obtaining/using/recovering, continued use despite problems; suspected OUD requires addiction-focused medical management in PACT, referral to Interdisciplinary Pain Management Team with Addiction Medicine/MAT expertise, or Primary Care Mental Health/specialty care; offer treatment in setting patient feels most comfortable if initial options are declined
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OXYMORPHONE TAB
OPANA, OXYMORPHONE HCL
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OPANA, OXYMORPHONE HCL |
2017-02-27 |
Indications & Inclusion Criteria- Intended use for treatment of moderate to severe acute pain where opioid use is appropriate
- Documented intolerance, contraindication, or lack of sufficient analgesic response to other formulary short-acting immediate-release opioids (tramadol, codeine, codeine/acetaminophen, hydrocodone/acetaminophen, oxycodone/acetaminophen, oxycodone, hydromorphone, and morphine)
- Patient approved for oxymorphone SA tabs requiring oxymorphone IR for breakthrough pain
- Transitioning Veteran care from Department of Defense to VHA, with VA prescriber determination that continuation is safe and clinically appropriate
Exclusion Criteria- Intended use for treatment of mild pain
- Opioid naïve patient with initial single dosage > 20mg
- Significant respiratory depression, condition predisposing to significant respiratory depression (acute or severe bronchial asthma), or known/suspected paralytic ileus
- Moderate or severe hepatic impairment
- Hypersensitivity to oxymorphone
Dosing & Administration- Available strengths: 5 and 10 mg
- Administer on empty stomach (at least 1 hour before or 2 hours after eating); high-fat meal increases CMAX
- Opioid naïve patients: Initiate at doses up to 10-20 mg every 4 to 6 hours; use higher starting doses cautiously due to risk of fatal respiratory depression
- Initiate with 5mg dose in opioid-naïve patients with mild hepatic impairment, impaired renal function (creatinine clearance < 50 ml/min), or age ≥ 65 years
- Opioid tolerant definition: Receiving for one week or longer at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or equianalgesic dose of another opioid
- Conversion: Use standard equianalgesic dosage estimates; new opioid typically dosed at 33 to 50% less than calculated MME dose to avoid accidental overdose due to incomplete cross-tolerance
Safety & Adverse Effects- Adverse effect profile includes nausea, somnolence, vomiting, pruritus, headache, dizziness, constipation, and confusion
- May cause severe hypotension in patients with compromised blood pressure maintenance (depleted blood volume or concurrent drugs compromising vasomotor tone)
- Avoid in patients with impaired consciousness/coma, head injury, or increased intracranial pressure (respiratory depressant effects may be magnified)
- Avoid co-administration with alcohol (significantly increases CMAX)
- Concomitant use with other CNS depressants (other opioids, sedative hypnotics, tranquilizers, general anesthetics, phenothiazines) increases risk of respiratory depression, profound sedation, coma, and death
- Concurrent use with benzodiazepines is not recommended; consider tapering if risks exceed benefits and obtain specialty consultation
Special Populations- Renal impairment: Effect on pharmacokinetics not studied for IR; SA formulation shows increased bioavailability in mild (26%), moderate (57%), and severe (65%) renal impairment
- Hepatic impairment: Contraindicated in moderate or severe hepatic impairment
- Pregnancy: Category C; use only if potential benefit justifies potential risk to fetus. Not recommended during/immediately prior to labor (may prolong labor, cause neonatal respiratory depression, physical dependence, and withdrawal syndrome)
- Lactation: Unknown if excreted in breast milk; monitor exposed infants for excess sedation and respiratory depression
Risk Mitigation & Provider Guidance- Implement risk mitigation strategies including informed consent conversation covering risks/benefits of opioid therapy and alternatives
- Ongoing, random urine drug testing (including appropriate confirmatory testing)
- Checking state prescription drug monitoring programs
- Monitoring for overdose potential and suicidality
- Providing overdose education
- Prescribing naloxone rescue kit with accompanying education
- Initiation/Continuation: Do not initiate long-term opioid therapy for chronic pain; for existing long-term therapy, conduct ongoing risk mitigation, assess for OUD, and consider tapering when risks exceed benefits
- Tapering: Screen/treat complicating conditions first (mental health disorders, OUD/SUD, medical complications, sleep disorders including sleep apnea); typical taper involves dose reductions of 5% to 20% every 4 weeks
- OUD Management: Suspected OUD requires addiction-focused medical management in PACT, referral to Interdisciplinary Pain Management Team with Addiction Medicine/MAT expertise, or Primary Care Mental Health/specialty care; DSM-5 criteria include craving, tolerance, withdrawal, using larger amounts/longer periods than intended, spending excessive time obtaining/using/recovering, and continued use despite physical/psychological problems
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OXYMORPHONE TAB,SA
OPANA ER, OXYMORPHONE HCL ER
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OPANA ER, OXYMORPHONE HCL ER |
2017-02-27 |
Transitioning Veteran Criteria- Veteran is transitioning care from the Department of Defense to VHA and has determined with a VHA health care prescriber to continue oxymorphone SA. If met, remainder of criteria for use is not applicable.
Exclusion Criteria- Intended use for treatment of mild pain, acute pain, or postoperative pain (unless patient is already receiving the drug prior to surgery or postoperative pain is expected to be moderate to severe and persist for an extended period).
- Intended use as an as-needed (prn) analgesic.
- Significant respiratory depression, condition predisposing to significant respiratory depression (e.g., acute or severe bronchial asthma), or known/suspected paralytic ileus.
- Moderate or severe hepatic impairment.
- Hypersensitivity to oxymorphone or other tablet contents.
- Inability to swallow whole tablets or requirement for tablets to be crushed before administration.
- Intent to consume or likelihood of consuming alcoholic beverages or prescription/non-prescription products containing alcohol during therapy.
Inclusion Criteria- Indication is management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period.
- Documented contraindication, history of intolerable medication-related adverse effects (to IR or SA forms), or inadequate analgesia despite appropriate upward titration in separate trials of morphine SA tabs and oxycodone SA tabs.
Therapeutic Alternatives- Methadone oral tablet is a long-acting opioid alternative; initiation/titration only for clinicians familiar with its pharmacological characteristics, appropriate titration, risk profile, and prepared to educate/monitor closely.
- Fentanyl TDS: Initiation/titration only for clinicians familiar with dosing/absorption properties and prepared to educate patients about use.
Practice Standards & Risk Mitigation- Utilize CDC and VA/DoD Clinical Practice Guidelines for prescribing opioids for chronic pain.
- Obtain informed consent explaining risks, benefits, and obligatory terms of long-term opioid treatment.
- Follow all federal and state guidelines on prescribing and dispensing opioids.
- Perform initial and periodic checks of State Prescription Drug Monitoring System (if available).
- Consider provision of naloxone rescue and other risk mitigation strategies commensurate with patient risk factors.
Dosage & Administration- Available strengths: 5, 7.5, 10, 15, 20, 30, 40 mg.
- Administer on empty stomach (1 hour before or 2 hours after eating); food increases CMAX.
- Tablets must not be wetted prior to placing in mouth.
- Opioid naïve: Initial dose 5 mg q 12 h; higher starting doses may cause fatal respiratory depression.
- Opioid tolerant definition: Receiving ≥60 mg oral morphine/day, ≥25 mcg transdermal fentanyl/hour, ≥30 mg oral oxycodone/day, ≥8 mg oral hydromorphone/day, ≥25 mg oral oxymorphone/day, or equianalgesic dose of another opioid for ≥1 week.
- Opioid-tolerant patients with mild hepatic impairment, impaired renal function (CrCl < 50 ml/min), or age ≥65 years: Initiate at 50% lower than usual doses and titrate slowly.
- Steady-state reached within 3 days; dosage adjustments preferably in increments of 5-10 mg every 12 hours, performed every 3 to 7 days.
- Conversion from fentanyl TDS: Initiate 18 hours after patch removal; conservative initial dose 5 or 7.5 mg q 12 h per 25 mcg fentanyl TDS, then titrate based on pain relief/tolerability.
- Conversion from methadone: Use 0.5 conversion factor (10 mg oral methadone/day ≈ 5 mg oral oxymorphone/day); consult clinician with methadone expertise.
- Rescue doses of oxymorphone IR or other short-acting analgesic may be administered for breakthrough pain as needed or ~1 hour before anticipated incident pain.
- Co-therapy with long-duration opioid and nonopioid analgesic (acetaminophen/NSAID) should be considered for opioid-sparing effects or additive analgesia.
Safety & Adverse Effects- Adverse effect profile similar to morphine SA; serious reactions include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, shock. Non-serious events typically occur on initiation and decrease over time (constipation, nausea, somnolence).
- Co-ingestion of alcohol may increase plasma levels and cause potentially fatal overdose; patients must not consume alcohol or alcohol-containing products.
- Concomitant use with other CNS depressants increases risk of respiratory depression, profound sedation, coma, and death; reduce dose of one or both agents.
- VA/DOD guideline recommends against concurrent use of opioids and benzodiazepines; consider tapering if risks exceed benefits and obtain specialty consultation.
- Bioavailability increased in renal impairment (mild 26%, moderate 57%, severe 65%); monitor blood pressure during initiation/titration due to hypotensive potential.
- Avoid in patients with impaired consciousness/coma, head injury, or increased intracranial pressure (respiratory depressant effects may be magnified).
- Pregnancy Category C; use only if maternal benefit justifies fetal risk. Not for use during/immediately prior to labor (may prolong labor and cause neonatal respiratory depression, physical dependence, and withdrawal syndrome).
- Unknown excretion in breast milk; monitor exposed infants for excess sedation and respiratory depression.
- Tablets cannot be crushed (causes immediate release of full dose, risking fatal overdose); do not pre-soak, lick, or wet tablets (swells/sticks, risk of GI obstruction/choking, particularly with prior GI surgery or structural abnormalities).
- Abuse of crushed tablets poses overdose/death hazard; parenteral abuse risks local tissue necrosis, infection, pulmonary granulomas, endocarditis, and valvular heart injury.
Provider Guidance & Opioid Use Disorder Management- Implement risk mitigation strategies: informed consent conversation, ongoing random urine drug testing (with confirmatory testing), PDMP checks, monitoring for overdose potential/suicidality, overdose education, and prescribing naloxone rescue with education.
- Initiation/Continuation: Recommend against initiating long-term opioid therapy for chronic pain; for existing patients, continue risk mitigation, assess for OUD, and consider tapering when risks exceed benefits.
- Tapering: Screen/treat complicating conditions first (mental health disorders, OUD/SUD, medical complications, sleep disorders). Typically involves dose reductions of 5% to 20% every 4 weeks.
- OUD Management: Aberrant behaviors may emerge during taper/discontinuation or as tolerance develops. DSM-5 criteria include craving/urge, tolerance, withdrawal, using larger amounts/longer periods than intended, spending excessive time obtaining/using/recovering, and continued use despite physical/psychological problems. Refer to addiction-focused medical management (PACT, Interdisciplinary Pain Management Team with Addiction Medicine/MAT, Primary Care Mental Health/specialty care).
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PALIPERIDONE INJ,SUSP,SA
ERZOFRI, INVEGA HAFYERA, INVEGA SUSTENNA, INVEGA TRINZA
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ERZOFRI, INVEGA HAFYERA, INVEGA SUSTENNA, INVEGA TRINZA |
2017-02-27 |
Transitioning Veteran- Veteran is transitioning care from the Department of Defense to VHA, and a VA prescriber has determined continuing the medication is safe and clinically appropriate (if met, remainder of criteria does not apply)
- Exclusion Criteria (Patient should NOT receive LAI if any criterion is met)
- Has never taken the ordered long-acting injectable antipsychotic in any formulation (e.g., oral), except prior exposure to risperidone is an acceptable substitute for paliperidone
- Hypersensitivity to the ordered antipsychotic (risperidone and paliperidone are cross-sensitive)
- Moderate to severe renal impairment (Creatinine Clearance < 50ml/min)
- Receiving a strong CYP3A4 and/or P-gp inducer during a dosing interval
- Inclusion Criteria (All must be met)
- Diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder
- Prescriber is a VA Mental Health Provider
- Patient has taken and tolerated the ordered antipsychotic prior to receiving it as a LAI for an adequate length of time (risperidone and paliperidone are cross-tolerant)
- Patient will be transitioned from monthly or every 3 month paliperidone extended release suspension to the long-acting injectable per guidelines/manufacturer recommendations
- Inclusion Criteria (Patient must meet ONE of the following)
- Relapsed or been hospitalized for the intended indication or complications of the intended indication because of nonadherence when treated with oral antipsychotics
- Care environment is such that a LAI is a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely)
Transitioning Veteran- Veteran is transitioning care from the Department of Defense to VHA
- VA prescriber has determined that continuing the medication is safe and clinically appropriate after assessment and consultation
Exclusion Criteria- Patient has never taken the ordered long-acting injectable antipsychotic in any formulation (e.g., oral), with prior exposure to risperidone being an acceptable substitute for paliperidone
- Hypersensitivity to the ordered antipsychotic (risperidone and paliperidone are cross-sensitive)
- Moderate to severe renal impairment (creatinine clearance < 50 ml/min)
Inclusion Criteria (All Required)- Diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder
- Prescriber is a VA/VA Community Care Mental Health Provider
- Patient has taken and tolerated the ordered antipsychotic prior to receiving it as a LAI for an adequate length of time (risperidone and paliperidone are cross-tolerant)
- Patient will be transitioned from oral medication to the long-acting injectable per guidelines/manufacturer recommendations
Inclusion Criteria (One Required)- Relapse or hospitalization for the intended indication or complications due to nonadherence when treated with oral antipsychotics
- Care environment makes a LAI a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely)
Transitioning Veteran- Veteran is transitioning care from the Department of Defense to VHA.
- A VA prescriber has determined, after assessing and consulting with the Veteran, that continuing the medication is safe and clinically appropriate.
- If met, the remainder of the criteria for use is not applicable.
- Exclusion Criteria (Patient should NOT receive a long-acting injectable antipsychotic if any are met)
- Patient has never taken the ordered long-acting injectable antipsychotic in any formulation (e.g., oral), with prior exposure to risperidone being an acceptable substitute for paliperidone.
- Patient has a hypersensitivity to the ordered antipsychotic (risperidone and paliperidone are considered cross-sensitive).
- For Paliperidone (Invega Trinza): Patient has moderate to severe renal impairment (creatinine clearance < 50 ml/min).
- Inclusion Criteria (ALL must be met)
- Diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder.
- Prescriber is a VA Mental Health Provider.
- Patient has taken and tolerated the ordered antipsychotic prior to receiving it as a long-acting injectable for an adequate length of time (risperidone and paliperidone are considered cross-tolerant).
- Patient will be transitioned from 1-month paliperidone extended-release suspension to the long-acting injectable per guidelines/manufacturer recommendations.
- Inclusion Criteria (ONE must be met)
- Patient has relapsed or been hospitalized for the intended indication or complications of the intended indication due to nonadherence when treated with oral antipsychotics.
- Patient’s care environment is such that a long-acting injectable is a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely).
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PANTOPRAZOLE TAB,EC
PANTOPRAZOLE SODIUM, PROTONIX
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PANTOPRAZOLE SODIUM, PROTONIX |
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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PAROXETINE TAB
PAROXETINE HCL, PAXIL
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PAROXETINE HCL, PAXIL |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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PEGINTERFERON BETA-1A PREFILLED SYRINGE
PLEGRIDY
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PLEGRIDY |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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PEGINTERFERON INJ,SOLN
PLEGRIDY PEN
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PLEGRIDY PEN |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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PEGINTERFERON INJ,SOLN
PLEGRIDY, PLEGRIDY PEN
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PLEGRIDY, PLEGRIDY PEN |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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PEGLOTICASE INJ,SOLN
KRYSTEXXA
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KRYSTEXXA |
2017-02-27 |
Indication & Patient Eligibility- Exclusion Criteria:
- G6PD deficiency (screen high-risk patients of African or Mediterranean descent)
- Concurrent use of other urate-lowering therapies (allopurinol, febuxostat, probenecid, etc.) due to risk of masking loss of efficacy/antibody development and increased infusion reaction/anaphylaxis risk
- Inclusion Criteria (New Patients):
- ≥3 gout flares in the past 18 months AND baseline serum uric acid concentration (SUAc) >8 mg/dl
- AND (≥1 tophi affecting physical function/QoL OR chronic gouty arthritis with documented joint damage)
- Failure to reduce SUAc <6 ml/dl despite adequate trial of maximally tolerated allopurinol (up to 800 mg/day) and febuxostat (up to 80 mg/day) for ≥3 months at highest tolerated dose, with >80% adherence confirmed; OR documented contraindication/inability to tolerate both agents
- Reversible causes of gout considered/treated (alcohol use, purine-rich foods, obesity, diuretics, niacin, low-dose salicylates, tacrolimus, cyclosporine)
- Prescribed by VA Rheumatologist or locally designated physician trained on infusion reactions and pegloticase-specific issues
Monitoring & Discontinuation Criteria- SUAc must be <6 mg/dl prior to each scheduled infusion
- Discontinue treatment if SUAc >6 mg/dl on more than one occasion during therapy
- Exercise caution for significant increases between infusions (e.g., 2.0 mg/dl to 5.5 mg/dl) as it may indicate antibody development
- Consider switching back to allopurinol or febuxostat maintenance therapy if individual treatment goals are met (improved QoL, reduced flares/mobility issues/tophi/pain, no longer need surgery for tophi) and no contraindications exist
Dosage, Administration & Preparation- Recommended dose: 8 mg IV infusion every 2 weeks
- Gout flare prophylaxis (colchicine or NSAIDs) initiated ≥1 week prior to first infusion and continued ≥6 months unless contraindicated/intolerant
- Preparation: Withdraw 1 ml into sterile syringe, inject into 250 ml bag of 0.9% sodium chloride injection, USP or 0.45% sodium chloride injection, USP. Do not mix with other drugs. Invert to mix; do not shake. Stable for 4 hours refrigerated or at room temperature (protect from light). Allow to reach room temperature prior to infusion; never use artificial heating
- Administration: Never administer as IV push or bolus. Infuse over ≥120 minutes via gravity feed, syringe-type pump, or infusion pump
Premedication & Infusion Protocol- Pre-treat with antihistamine and corticosteroid prior to each infusion to minimize anaphylaxis/infusion reaction risk (e.g., oral antihistamine evening prior & just before infusion; IV hydrocortisone 200 mg and acetaminophen 1000 mg immediately prior)
- Administer in a healthcare setting by providers prepared to manage anaphylaxis and infusion reactions
- Observe patients for an appropriate period post-infusion (≥1 hour recommended due to risk of delayed hypersensitivity)
- If infusion reaction occurs: slow/stop and restart at slower rate per physician discretion
Safety Considerations & Clinical Monitoring- Limited to FDA indication: adult patients with symptomatic gout refractory to conventional treatment; not indicated for rapid debulking in non-refractory patients or tumor lysis syndrome
- Monitor SUAc prior to each infusion; discontinue if >6 mg/dl, especially with two consecutive levels >6 mg/dl
- Re-treatment/restarting after >4 weeks off therapy lacks data and carries increased anaphylaxis/infusion reaction risk requiring closer monitoring
- Not recommended for nursing mothers due to unknown excretion in human milk and potential for serious adverse events in the infant
- Biweekly corticosteroid premedication may alter glucose control in diabetic patients; monitor closely
- Monitor cardiovascular safety post-marketing due to reported ischemic cardiovascular events, heart failure, cardiac arrhythmias, and death
Renewal Criteria- SUAc <6 mg/dl prior to each infusion
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PEMBROLIZUMAB INJ,SOLN
KEYTRUDA
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KEYTRUDA |
2017-02-27 |
Exclusion Criteria- Autoimmune disease
- Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
- Primary immunodeficiency
- History of allogeneic hematopoietic stem cell or solid organ transplant
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Indication is FDA approved
- Off-label use supported by high-level published data
Additional Inclusion Criteria- Care is provided by a VA/VA Community Care oncology or hematology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Female patients of child-bearing potential and male patients with female partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment. Use effective contraception during therapy and for 4 months after the last dose.
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PERTUZUMAB INJ,SOLN
PERJETA
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PERJETA |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity to pertuzumab or any of its excipients (L-histidine acetate, sucrose, polysorbate 20)
- Baseline Left Ventricular Ejection Fraction < 55% (< 50% if metastatic disease)
- Uncontrolled HTN
- Arrhythmia requiring treatment
- Myocardial infarction within prior 6 months
- History of Congestive Heart Failure (New York Heart Association Class 3 or 4)
- Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
- Tissue does not overexpress HER2 protein (defined as IHC 3+ or FISH amplification ratio > 2.0)
- Pregnancy
Inclusion Criteria (Indications & Treatment Regimens)- Metastatic breast cancer: In combination with trastuzumab and chemotherapy for patients not previously treated with HER2-directed therapy or chemotherapy
- Neoadjuvant therapy for breast cancer: In combination with trastuzumab and chemotherapy for HER2-positive, locally advanced, inflammatory, or early-stage breast cancer with primary tumor diameter > 2 cm or node positive
- Adjuvant therapy for breast cancer: In combination with trastuzumab and chemotherapy for HER2-positive, early breast cancer at high risk of recurrence
- Metastatic colorectal cancer: In combination with trastuzumab for HER2-positive, KRAS wild-type, chemotherapy-refractory metastatic colorectal cancer
Additional Inclusion Criteria (General Clinical Requirements)- Care provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 – 2
Additional Inclusion Criteria (Pregnancy & Contraception Management)- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment; use of effective contraception during therapy and for 7 months after last dose
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PIROXICAM CAP,ORAL
FELDENE
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FELDENE |
2017-02-27 |
Continuity of Care Inclusion Criteria- Veteran is transitioning care from the Department of Defense to VHA
- Must also meet one of the following Additional Inclusion Criteria:
- The medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making
- The medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making
Non-Continuity of Care Inclusion Criteria- Inadequate response or intolerance to two formulary NSAIDs (NSAIDs=Nonsteroidal anti-inflammatory drugs)
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PNEUMOCOCCAL VACCINE INJ
CAPVAXIVE, PNEUMOVAX 23, PREVNAR 20, VAXNEUVANCE
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CAPVAXIVE, PNEUMOVAX 23, PREVNAR 20, VAXNEUVANCE |
2017-02-27 |
Indication(s)- Prevention of invasive pneumococcal disease (IPD) and pneumonia caused by serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B.
Patient Population- Individuals 18 years of age and older.
- Specifically studied in adults ≥50 years, adults 18–49 years with underlying chronic conditions increasing IPD risk, adults living with HIV, vaccine-naïve individuals, and previously vaccinated individuals.
- Comorbidities known to increase pneumococcal disease risk include diabetes, renal disorders, chronic heart disease, chronic lung disease, chronic liver disease, and alcoholism.
Dosing & Administration- Supplied as a single-dose prefilled syringe (refrigerated).
- Recommended as a single dose for adults ≥50 years.
Contraindications, Warnings & Precautions- Contraindicated in patients with a history of severe allergic reaction to any component of CAPVAXIVE or diphtheria toxoid.
- Warning regarding prevention and management of allergic reactions and syncope following administration.
- Precaution: Immunocompromised individuals may have a diminished immune response.
Safety & Adverse Reactions- Most commonly reported solicited adverse events: injection site pain, fatigue, and headache.
- Rates and severity of solicited adverse events are similar with or without concomitant influenza vaccine.
- No cases of Guillain-Barre syndrome reported in clinical trials.
Clinical Guidance & Place in Therapy- ACIP recommends a single dose of PCV20, PCV21, or PCV15 (the latter followed by a dose of PPSV23) for ALL adults ≥50 years, regardless of underlying conditions, with no preference among the three.
- PCV21 covers 85% of serotypes associated with adult IPD compared to 54% coverage for PCV20.
- PCV15 or PCV20 may be preferred in situations where high incidence of serotype 4 is suspected (>30% of IPD cases), as PCV21 lacks coverage for this serotype. High serotype 4 incidence has been noted in Alaska, Colorado, the Navajo Nation, New Mexico, and Oregon.
Limitations & Efficacy Data- Approval based on immunobridging data (OPA geometric mean antibody titers); no clinical efficacy data are available.
- An opsonophagocytic activity (OPA) titer predictive of protection has not been established for any pneumococcal conjugate vaccine.
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PRAZOSIN CAP,ORAL
PRAZOSIN HCL
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PRAZOSIN HCL |
2017-02-27 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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PROGESTERONE CAP,ORAL
PROMETRIUM
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PROMETRIUM |
2017-02-27 |
Systemic Hormonal Menopausal Therapy (Oral Estrogen Combinations)- Dosing Criteria: 0.45 mg conjugated equine estrogens/20 mg bazedoxifene daily
- Clinical Use Criteria: Bazedoxifene is an alternative to progestin for patients with a uterus
- Systemic Estrogen Formulary Requirements:
- Prescribe the lowest effective dose of estrogen
- Product selection should consider patient symptoms, risk-benefit profile, and patient preference
- A progestin (or bazedoxifene alternative) must be prescribed for all patients with an intact uterus receiving systemic estrogen to reduce endometrial hyperplasia and cancer risk
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PROTHROMBIN COMPLEX INJ,LYPHL
KCENTRA
|
KCENTRA |
2017-02-27 |
Exclusion Criteria- Patient with disseminated intravascular coagulation (DIC)
- History of heparin-induced thrombocytopenia (HIT)
- History of anaphylactic or severe systemic reaction to 4F-PCC or any components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin)
- Situation in which administration of intravenous vitamin K and withdrawal of warfarin therapy alone would adequately reverse anticoagulation within the required timeframe for an urgent invasive procedure or surgery
- Patients in whom complete correction of International Normalized Ratio (INR) is not clinically appropriate or necessary
Inclusion Criteria- Receiving treatment with a vitamin K antagonist (e.g., warfarin) therapy with INR ≥ 2 AND standard measures for bleeding cessation/reversal are contraindicated or insufficient
- Co-administration with vitamin K is required
- PLUS ONE of the following indications:
- Acute life-threatening major bleeding (including intracranial hemorrhage)
- Need for urgent life-saving surgery or invasive procedure
Dosage and Administration- Administered as a single dose IV infusion based on pre-treatment INR and actual body weight
- Dosing calculated based on the quantity of factor IX in the product (varies by vial potency)
- Pre-treatment dosing table:
- INR 2 to <4: 25 IU/kg (Maximum dose: 2500 IU)
- INR 4 to 6: 35 IU/kg (Maximum dose: 3500 IU)
- INR >6: 50 IU/kg (Maximum dose: 5000 IU)
- Dosing based on actual body weight up to 100 kg; do not exceed maximum doses for patients weighing >100 kg
- Do not mix with other products; administer through a separate infusion line
- Administer at a rate of 0.12 mL/kg/min, up to a maximum rate of 8.4 mL/min
- No blood should enter the syringe (risk of fibrin formation)
- Repeat dosing is not recommended as effectiveness and safety have not been established
Monitoring- Use a current, pre-treatment INR taken close to the time of 4F-PCC dosing due to potential fluctuations in acute bleeding or urgent settings
- Evaluate laboratory coagulation parameters alongside clinical signs of hemostasis and thromboembolism post-administration
Clinical Considerations & Risk Management- Thromboembolic Risk: Carries a Boxed Warning for arterial and venous thromboembolic complications. High-risk populations excluded from trials include patients with recent history (within last 3 months) of thrombotic event, myocardial infarction, cerebrovascular accident, transient ischemic attack, unstable angina pectoris, severe peripheral vascular disease, or DIC; known antiphospholipid syndrome; known inhibitors to coagulation factors II, VII, IX, or X; and known hereditary protein C or protein S deficiency.
- Non-warfarin Oral Anticoagulants: Insufficient clinical evidence for off-label use; not FDA approved. Consider only in severe, life-threatening situations where all other measures have failed or are not indicated. Weak preference noted for activated PCC (FEIBA) for dabigatran reversal and 4F-PCC for rivaroxaban/apixaban reversal.
- Fluid Status: Associated with a numerically lower rate of fluid overload or cardiac events compared to plasma. Mean infused volume <100 mL. May be preferred if patient cannot tolerate additional plasma volume.
- Timing of Reversal: Superior INR correction at 30 minutes to 12 hours post-infusion compared to plasma; difference not evident at 24 hours. Preferable for rapid reversal within 24 hours (e.g., intracranial hemorrhage, life-threatening bleeding, urgent surgery). No significant difference in effective hemostasis at 24 hours, mortality, or length of hospital stay.
- History of HIT: Contains heparin; history of HIT is a contraindication per FDA labeling. May be considered if patient has negative antibody testing for life-threatening bleeding requiring cardiac surgery (per ACCP guidelines), though evidence is limited.
- Infectious Disease Transmission: Blood-derived product carries infection risk despite two virus reduction steps.
- Pregnancy and Childbearing Potential: Reserve for life-threatening instances; weigh risks and benefits to mother and fetus. Category C; not studied in pregnancy.
General Principles & Supportive Care- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
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RAMUCIRUMAB INJ,SOLN
CYRAMZA
|
CYRAMZA |
2017-02-27 |
Exclusion Criteria- Non-healing wound or fracture
- Major surgery within prior 28 days
- Chronic anti-platelet therapy, NSAIDs (including aspirin > 325mg/day)
- Therapeutic anticoagulation, unless on stabilized outpatient doses
- Uncontrolled CNS metastases
- Pre-existing bleeding diathesis or coagulopathy
- History of GI perforation and/or fistulae within prior 6 months
- History of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months of therapy initiation
- Patients with tumor involving major blood vessels or intratumor cavitation
- Uncontrolled hypertension
- Severe renal impairment defined as CrCl < 15 ml/min
- Pre-existing proteinuria (> 2 g urine protein/24 hrs)
- Severe hepatic impairment defined as bilirubin > 3x Upper Limit of Normal
- Pregnancy
- Breastfeeding
Inclusion Criteria (Indications)- Diagnosis of advanced or metastatic gastric or gastro-esophageal Junction (GEJ) adenocarcinoma WITH disease progression on prior fluoropyrimidine- or platinum-containing chemotherapy
- Diagnosis of metastatic Non-Small Cell Lung Cancer (NSCLC) in combination with docetaxel in patients WITH disease progression on prior platinum-based chemotherapy; Patients with EGFR+ or ALK+ disease should have progressed on FDA-approved therapies for those aberrations
- Diagnosis of metastatic Non-Small Cell Lung Cancer (NSCLC) in combination with erlotinib for first-line treatment in patients whose tumors have an EGFR exon 19 deletion or exon 21 (L858R) substitution mutation
- Diagnosis of metastatic colorectal cancer in combination with FOLFIRI (fluorouracil, leucovorin, irinotecan) WITH disease progression on prior first-line therapy with bevacizumab, oxaliplatin and a fluoropyrimidine
- Diagnosis of hepatocellular carcinoma Barcelona Clinic Liver Cancer (BCLC) Stage C or B disease refractory or not amendable to locoregional therapy, Child-Pugh Class A and an alpha fetoprotein (AFP) > 400 ng/mL who have been previously treated with sorafenib
Additional Inclusion Criteria- Care for the condition provided by VA or VA Community Care oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 – 1
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 3 months after last dose
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REGORAFENIB TAB,ORAL
STIVARGA
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STIVARGA |
2017-02-27 |
Exclusion Criteria- Unmanageable drug-drug interaction
- Clinically significant cardiovascular disease (uncontrolled hypertension, unstable or new-onset angina, myocardial infarction within prior 6 months, history of congestive heart failure New York Heart Association Class 3 or 4)
- Pre-existing bleeding diathesis or coagulopathy
- Major surgical procedure within prior 28 days, non-healing wound, ulcer or bone fracture
- Hepatic impairment: Total bilirubin > 1.5 x Upper Limit of Normal (> 6 mg/dL if documented Gilbert’s syndrome); ALT and AST > 2 x ULN (> 5 x ULN if due to liver involvement); Alk phos > 2.5 x ULN (> 5 x ULN if due to liver involvement)
- Amylase and lipase > 1.5 x ULN
- GFR < 30 mL/min/1.73 m2
- Adequate hematologic parameters: platelet count < 100,000/mm3, hemoglobin < 9 mg/dL and ANC < 1500/mm3
- Known pregnancy
- Lactation
General Inclusion Criteria- Care provided by a VA/VA Community care oncology or hematology provider
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 or 1
Indication-Specific Inclusion Criteria (One must be met)- Metastatic colorectal cancer with prior treatment (or not a candidate) for fluoropyrimidine-, oxaliplatin-, irinotecan-based regimens, an anti-VEGF agent and if KRAS wild type, an anti-EGFR agent
- Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) with prior therapy with imatinib and sunitinib (unless contraindicated)
- Hepatocellular carcinoma (HCC) Child-Pugh A, previously treated with sorafenib
Pregnancy & Reproductive Requirements- For females who can become pregnant: Pregnancy must be excluded prior to receiving regorafenib
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during pregnancy and for 2 months after stopping treatment
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RIFABUTIN CAP,ORAL
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|
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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RIFAXIMIN TAB
XIFAXAN
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XIFAXAN |
2017-02-27 |
Exclusion Criteria- Known hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any other component of rifaximin
- Inclusion Criteria (Patient must meet one of the following sets; both endpoints in each set must be documented in the medical record)
- Refractory to lactulose: Recurrent or persistent hepatic encephalopathy despite receiving lactulose at a dose that obtains 2–3 loose stools per day
- Intolerance to lactulose: Treated with lactulose for recurrent or persistent hepatic encephalopathy and experiencing ≥4 loose stools per day despite lactulose dosage reductions
- Non-adherence to lactulose: Recurrent or persistent hepatic encephalopathy secondary to non-adherence of lactulose despite provision of patient education on more than one visit regarding the importance of adherence
Dosage and Administration- 550mg orally twice daily, with or without food
- Each prescription limited to no more than a 3-month supply
Monitoring and Clinical Considerations- May be used in combination with lactulose for hepatic encephalopathy
- Reassess medical treatment every 3 months after evaluating initial response and tolerability
- Monitor clinical signs and symptoms of hepatic encephalopathy, nutrition status, hydration status, and electrolytes
- Titrate lactulose dose to maintain two to three bowel movements per day; avoid overuse due to risks of aspiration, dehydration, hypernatremia, severe perianal skin irritation, and precipitation of hepatic encephalopathy
- Use with caution in patients with severe hepatic impairment (Child-Pugh C) due to increased systemic exposure; no dosage adjustment is recommended as rifaximin presumably acts locally
Indication & Patient Population- IBS-D (with or without SIBO)
- FDA-approved for treatment of IBS-D in adults; not FDA-approved for treatment of SIBO
- Restricted to patients with the IBS-D subtype who have not responded to effective and less costly symptom-based alternative therapies
Exclusion Criteria- Known hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any other component of rifaximin
- No documented benefit from prior rifaximin therapy for irritable bowel syndrome with diarrhea (IBS-D)
Inclusion Criteria (All must be met)- Patient is under the care of a VA or VA Community Care gastroenterologist or locally designated provider qualified to diagnose and treat both symptomatic small intestinal bacterial overgrowth (SIBO) and IBS-D
- Moderate to severe IBS-D (with or without SIBO)
- Moderate to severe symptoms (e.g., pain, bloating) continue or recur despite treatment
Prior Therapy Requirements- Trial of soluble fiber (e.g., psyllium) for 4 weeks unless medically inadvisable or not tolerated
- Trial of a tricyclic antidepressant (e.g., desipramine, nortriptyline) for 4 weeks unless medically inadvisable (e.g., elderly, suicidal ideation, QT prolongation, etc.) or not tolerated
- For females with severe, chronic IBS-D (generally ≥ 6 months): Trial of alosetron for 4 weeks unless medically inadvisable or not tolerated
Dosage & Administration- Approved dose for IBS-D: 550 mg 3 times a day for 14 days
Dispensing Limits- Authorize one course of rifaximin with a maximum dispensing limit of three 200-mg or 550-mg tablets per day for up to 14 days
Patient & Provider Eligibility- Patient must be under the care of a VA or VA Community Care gastroenterologist or locally designated provider qualified to diagnose and treat symptomatic SIBO.
Diagnosis & Clinical Presentation- Documented diagnosis or working diagnosis of SIBO without irritable bowel syndrome with diarrhea (IBS-D).
- Diagnosis based on typical clinical presentation and, if testing is feasible, positive carbohydrate breath test or jejunal aspirate culture.
Prior Therapy & Treatment History- Documented lack of benefit from prior metronidazole or other antibiotic therapy for SIBO.
- Documented benefit from prior rifaximin for SIBO.
- ≥ 4 distinct and well-documented SIBO episodes in one year.
- Presence of risk factors for recurrent SIBO (e.g., small intestinal strictures [Crohn’s disease, radiation, surgery]; surgically created blind loops [end-to-side anastomosis]).
Dosing & Administration- Prescription must be written for periodic administration (e.g., 5–10 days out of every month or every other week).
- For SIBO without IBS-D: 200 mg 3 times a day for 7 days to 550 mg 3 times a day for 10 days.
- Clinical study doses range from 200 to 550 mg 3 times a day, with durations often 7 to 10 days (range 5 to 28 days). Optimal dosage regimen has not been determined.
Dispensing & Retreatment Policies- Maximum dispensing limit of three 200-mg or 550-mg tablets per day for up to 14 days.
- Additional retreatments (renewals or refills) do not require re-evaluation of the patient if an initial course was previously approved.
Exclusion Criteria- Known hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any other component of rifaximin.
- No documented benefit from prior rifaximin therapy for SIBO.
- Reoccurrences of SIBO after durable response (≥ 3 months) to one antibiotic regimen for SIBO (these should be retreated rather than proceed to rifaximin).
Patient Eligibility & Provider Qualifications- Patient must be under the care of a VA or VA Community Care gastroenterologist or locally designated provider qualified to diagnose and treat symptomatic SIBO.
Diagnostic Criteria- Documented diagnosis or working diagnosis of SIBO without irritable bowel syndrome with diarrhea (IBS-D).
- Diagnosis based on typical clinical presentation and, if testing is feasible, positive carbohydrate breath test or jejunal aspirate culture.
Prior Therapy Requirements (Additional Inclusion Criteria)- Symptoms must not respond to a 7- to 10-day therapeutic trial of ONE of the following regimens (unless medically inadvisable or patient has history of intolerance):
- Metronidazole alone (250–500 mg 2–3 times a day; maximum two courses in a 6-month period)
- Metronidazole combined with cephalexin (500 mg 3–4 times a day) or sulfamethoxazole/trimethoprim double-strength (1 tab 2 times a day)
- Amoxicillin-clavulanate (500 mg 3 times a day or 875 mg 2 times a day)
- Neomycin (500 mg 2 times a day)
- Previous ciprofloxacin (250–500 mg twice a day) for SIBO (may count as required prior antibiotic; not recommended due to adverse effect profile)
- Ciprofloxacin-naïve patients with SIBO should first be tried on one of the other listed antibiotics.
Exclusion Criteria- Known hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any other component of rifaximin.
- No documented benefit from prior rifaximin therapy for SIBO.
- Reoccurrences of SIBO after a durable response (e.g., ≥ 3 months) to one of the listed antibiotic regimens (these reoccurrences should be retreated rather than proceed to rifaximin).
Dosage & Administration- For SIBO without IBS-D: 200 mg 3 times a day for 7 days to 550 mg 3 times a day for 10 days.
- Clinical study doses range from 200 to 550 mg 3 times a day, with duration often 7 to 10 days (range 5 to 28 days). Optimal dosage regimen has not been determined.
Dispensing Limits & Retreatment Guidelines- Authorize one course of rifaximin with a maximum dispensing limit of three 200-mg or 550-mg tablets per day for up to 14 days.
- Additional retreatments (renewals or refills) do not require re-evaluation of the patient if an initial course was previously approved.
- Prophylaxis for recurrent SIBO: If the patient benefited from metronidazole or other prior antibiotic therapy, has 4 or more distinct and well-documented SIBO episodes in one year, and has risk factors for recurrent SIBO, that antibiotic may be used for prophylaxis (per separate criteria).
- Rifaximin is not FDA-approved for the treatment of SIBO; it is FDA-approved for IBS-D.
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RIMABOTULINUMTOXINB INJ,SOLN
MYOBLOC
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MYOBLOC |
2017-02-27 |
Exclusion Criteria- Hypersensitivity to botulinum toxins or any components in the formulation (e.g., human serum albumin, lactose, sucrose, disodium succinate)
- Co-administration with neuromuscular blockade
- Neurologic condition where botulinum toxins pose risk for additive neuromuscular compromise (e.g., myasthenia gravis, amyotrophic lateral sclerosis), unless risks/benefits have been discussed with the patient and documented in the medical record
- Use for cosmetic purposes
Inclusion Criteria (Indications)- Cervical dystonia or focal dystonia
- Blepharospasm or hemifacial spasm
- Severe focal hyperhidrosis with inadequate response or unmanageable intolerance to prescription topical therapy (e.g., aluminum chloride hexahydrate 20% topical solution)
- Upper or lower limb spasticity
- Overactive bladder or neurogenic bladder dysfunction with contraindication, intolerance, or inefficacy to behavioral therapy and at least one pharmacotherapy (e.g., antimuscarinic agent, beta-3 adrenergic agonist)
- Chronic migraine prevention with contraindication, intolerance, or lack of therapeutic response after at least 12 weeks each of a therapeutic dose of at least 2 of the following: beta blocker, topiramate, divalproex, and ACE inhibitor or ARB
- Pharyngoesophageal segment spasm (PES)
- Sialorrhea with contraindication, intolerance, or lack of therapeutic response to anticholinergics and/or speech therapy
- Chronic anal fissure refractory to conservative treatment including supportive measures (e.g., dietary fiber, sitz bath) and topical vasodilator (e.g., topical nitrates)
- Esophageal achalasia if patient is not a candidate for surgery
- Idiopathic (primary or genetic) or symptomatic (acquired) torsion dystonia
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RITUXIMAB INJ,SOLN
RITUXAN
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RITUXAN |
2017-02-27 |
Administration & Dosing- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks
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ROMIPLOSTIM INJ,LYPHL
NPLATE
|
NPLATE |
2017-02-27 |
Exclusion Criteria- Anticipated antiviral treatment includes a direct-acting antiviral (DAA) for chronic HCV
- Currently receiving peginterferon and ribavirin with or without DAA for chronic HCV
- Any contraindications to peginterferon and ribavirin apply
- Active malignancy or stem cell disorder
- Prior history of arterial or venous thrombosis plus ≥2 risk factors (hereditary thrombophilic disorders, estrogen hormone replacement therapy, systemic contraception therapy containing estrogen, smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer)
- Serious cardiac, cerebrovascular, or pulmonary disease
- Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin
- Known hypersensitivity, intolerance, or allergy to peginterferon and ribavirin, eltrombopag tablets, or ingredients
- Evidence of decompensated liver disease (Child-Pugh score ≥7 and/or clinical manifestations)
- Patient infected with HIV
Inclusion Criteria- Under care of and/or in collaboration with an experienced VA HCV practitioner
- Provider has discussed risks/benefits with patient; shared decision made for use
- Diagnosis of chronic HCV infection
- Baseline platelet count <75,000/μL
- Appropriate candidates for peginterferon and ribavirin combination antiviral therapy
- Treatment with peginterferon and ribavirin (dual therapy) anticipated after reaching target platelet goal
- Abdominal imaging negative for portal vein thrombosis within past 3 months
Dosing & Administration- Initiate prior to peginterferon and ribavirin therapy to obtain target platelet count
- Initial dose: 25 mg once daily on empty stomach (1 hour before or 2 hours after meal)
- Adjust by 25 mg increments every 2 weeks to achieve target platelet count (≥90,000/μL for peginterferon alfa-2a; ≥100,000/μL for peginterferon alfa-2b)
- Use lowest dose to achieve/maintain necessary platelet count
- Maintain same pre-treatment dose when starting antiviral therapy; modify during therapy to maintain counts between 50,000-150,000/μL
- Dose reduction NOT needed solely based on East Asian ethnicity
- Maximum dose: 100 mg/day
- If platelets <50,000/μL after ≥2 weeks: increase by 25 mg; wait 2 weeks to assess
- If platelets ≥150,000-200,000/μL: decrease by 25 mg; wait 2 weeks
- If platelets >200,000/μL: stop eltrombopag; monitor twice weekly; reinitiate at dose reduced by 25 mg (or 12.5 mg if previously on 25 mg) when count <100,000/μL
Monitoring Requirements- Prior to initiation: CBC with differential (including platelet), ocular exam for cataracts, Liver Function Panel (Total/Direct bilirubin, AST, ALT, albumin, total protein)
- During therapy: CBC weekly until stable then monthly; Serum liver tests (ALT, AST, bilirubin) every 2 weeks during adjustment then monthly; fractionate bilirubin if elevated; repeat tests within 3-5 days if abnormal; monitor weekly until resolved/stabilized/baseline; regular ocular exams for cataracts
- Upon discontinuation: CBCs weekly for at least four weeks
Safety & Risk Considerations- Box warnings for hepatotoxicity and risk of hepatic decompensation (ascites, hepatic encephalopathy, variceal hemorrhage, spontaneous bacterial peritonitis, hepatocellular carcinoma, death)
- Patients with albumin <3.5g/dL or MELD scores ≥10 at baseline have greatest risk of hepatic decompensation
- High thromboembolism risk: may increase risk; consider risk vs benefit
- Cataracts developed/worsened in 8% of treated patients
Discontinuation Guidelines- Discontinue when antiviral therapy is discontinued
- Discontinue for hepatotoxicity if ALT increases to ≥3X ULN (normal liver) or ≥3X baseline (pre-treatment elevations) and is progressive, persistent ≥4 weeks, accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury/hepatic decompensation
- Non-response: Consider discontinuing after 9 weeks at maximum dose (100 mg/day) if platelet count not increased sufficiently to initiate antiviral therapy
Specific Populations & Interactions- HIV: No safety/efficacy data; limited drug-drug interaction studies
- Renal insufficiency (CrCl<50ml/min): Not studied; use with caution
- Hepatic insufficiency: Clearance reduced in moderate-severe impairment; initial dose 25 mg daily; monitor serum liver tests; AUC ~2-fold higher; half-life prolonged 2-fold
- Pregnancy: Category C; discuss risks/benefits; consider enrollment in Promacta Pregnancy Registry
- Interactions: Substrate of CYP1A2/CYP2C8; inhibitor of OATP1B1/UGTs; chelates polyvalent cations. Separate administration from iron, calcium, aluminum, magnesium, selenium, zinc-containing meds/supplements/food by at least 4 hours.
Exclusion Criteria- Stem cell disorder (i.e. myelodysplastic syndrome)
- Patient has not received prior therapy with steroids to increase platelet counts
- Thrombocytopenia secondary to bone marrow suppressive anti-cancer therapy, antibiotics, or other drugs
- Thromboembolic events within the past year (unless evaluated by a hematology provider and deemed an appropriate candidate)
- Pregnancy and/or breastfeeding
Inclusion Criteria- Diagnosis of chronic Immune Thrombocytopenia (ITP)
- Platelet count < 30,000 mm3 and/or persistent bleeding resistant/refractory to glucocorticoids
- Relapse after second-line therapies (unless contraindicated or patient is not a candidate):
- Splenectomy
- Rituximab
- For patients who can become pregnant: Counseling provided on potential risks vs. benefits of taking drug if patient were to become pregnancy; advise patients not to breastfeed during treatment
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RUXOLITINIB TAB,ORAL
JAKAFI
|
JAKAFI |
2017-02-27 |
Exclusion Criteria- Active or uncontrolled infection
- Unmanageable drug-drug interaction
- End stage renal disease (CrCl < 15ml/min) not on dialysis
- Absolute Neutrophil Count (ANC) < 1000/mm3 and/or platelet count < 50,000/mm3 unless due to marrow involvement or associated with Duffy-null Associated Neutrophil Count (DANC)
- Lactating
Inclusion Criteria (Provider, Monitoring, & Performance Status)- Care provided by a VA or VA Community Care hematology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group performance status 0 - 3
- Baseline Complete Blood Count (CBC) and documentation of spleen length or volume (by palpation OR imaging)
- Repeat CBC 1 week after initiation of treatment, then every 2-4 weeks until dose stabilizes, then as clinically necessary
Indication/Diagnosis Requirements- Diagnosis of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF, post-essential thrombocythemia MF
- Diagnosis of polycythemia vera with an inadequate response or intolerance to hydroxyurea
Special Population Considerations- For females who are breastfeeding: Manufacturer recommends discontinuing breastfeeding during treatment with ruxolitinib and for 2 weeks after stopping treatment.
Indication/Context- Graft Versus Host Disease (GVHD)
Exclusion Criteria- Active or uncontrolled infection
- Unmanageable drug-drug interaction
- End-Stage Renal Disease (CrCl < 15ml/min) not on dialysis
- Absolute Neutrophil Count (ANC)
- Lactating
Inclusion Criteria- Care provided by a VA or VA Community Care hematology provider
- Eastern Cooperative Oncology Group performance status 0-2
- Steroid-refractory (or dependent) acute Graft Versus Host Disease (GVHD) following allogeneic stem cell transplant
- Steroid-refractory chronic GVHD after >/= 1 line of therapy with progression, lack of response or steroid-intolerance
Additional Clinical Requirements- For females who are breastfeeding: Manufacturer recommends discontinuing breastfeeding during treatment with ruxolitinib and for 2 weeks after stopping treatment.
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SECUKINUMAB INJ,SOLN
COSENTYX, COSENTYX (2 SYRINGES), COSENTYX SENSOREADY (2 PENS), COSENTYX SENSOREADY PEN, COSENTYX SYRINGE, COSENTYX UNOREADY PEN
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COSENTYX, COSENTYX (2 SYRINGES), COSENTYX SENSOREADY (2 PENS), COSENTYX SENSOREADY PEN, COSENTYX SYRINGE, COSENTYX UNOREADY PEN |
2017-02-27 |
Exclusion Criteria- Uncontrolled active infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Inclusion Criteria- Chronic (≥ 6 months) moderate to severe plaque psoriasis (including involvement of nails only)
- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated psoriasis expert
- Secukinumab prescribed at the FDA-approved dose for plaque psoriasis
- Methotrexate monotherapy is medically inadvisable, not tolerated, or not adequate
- Phototherapy is medically inadvisable, inadequate, not available or not feasible
- Tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated or not adequate (i.e., NO or partial response after 3 months or loss of initial response)
Additional Inclusion Criteria- If HBsAg-negative but anti-HBc-positive: Consultation with a gastroenterologist/hepatologist or infectious diseases expert regarding antiviral prophylaxis or preemptive monitoring for HBV reactivation
- For new starts: Intolerance or inadequate response to ixekizumab (ixekizumab is the preferred interleukin-17A inhibitor in new starts)
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling on potential risks vs benefits of treatment and use of effective contraception
Screening, Monitoring, & Clinical Definitions- Tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA] must be completed; routine retesting not required for renewals, but should be considered in high-risk patients
- Hepatitis B screening (at minimum, HBsAg, total anti-HBc, and anti-HBs) must be completed; routine retesting not required for renewals, but should be considered in high-risk patients
- Hepatitis C screening must be current or past completed; may initiate while waiting for results; routine retesting not required for renewals, but should be considered in high-risk patients
- Methotrexate monotherapy is considered "not adequate" if there is NO treatment benefit after 3 months (with at least 2 months at standard target dose) or inadequate partial response after 6 months; target doses are 15–25 mg ONCE WEEKLY orally, subcutaneously, or intramuscularly
- Phototherapy is medically inadvisable for reasons including confirmed history of skin cancer, melanoma, or strong likelihood of developing them (e.g., Fitzpatrick skin type I or II)
- TNFi is medically inadvisable for reasons including heart failure, demyelinating disease, multiple sclerosis in first-degree relative, lupus, recurrent infections, or serious infections
- In HBsAg-negative but anti-HBc-positive patients, presence of anti-HBs does not guarantee protection against HBV reactivation; management depends on patient’s risk of HBV reactivation
Indication & Patient Population- Treatment of adults with moderate to severe hidradenitis suppurativa (HS)
- Adults ≥ 18 years of age
- Moderate to severe HS defined as total of ≥ 5 inflammatory lesions affecting at least two distinct anatomical areas for at least 1 year
Dosage & Administration- 300 mg subcutaneous injection at Weeks 0, 1, 2, 3, and 4, then every 4 weeks thereafter
- Dosage increase to 300 mg SC every 2 weeks may be considered if patient has an inadequate response
- Available as 300 mg/2 mL in a single-dose UnoReady pen or single-dose prefilled syringe
Contraindications & Warnings/Precautions- Hypersensitivity
- Infections
- Hypersensitivity reactions
- Tuberculosis (TB)
- Inflammatory bowel disease
- Eczematous eruptions
- Risk of hypersensitivity in latex-sensitive individuals
- Immunization: avoid live vaccines
VA Formulary Restrictions & Step Therapy Requirements- No CFU for other indications
- FDA approved for HS in 2023
- Potential Use in VHA: Treatment of moderate to severe HS after a trial of adalimumab / biosimilar (preferred) or infliximab / biosimilar (alternative)
Safety & Monitoring Considerations- Boxed Warnings: None
- Top Adverse Events: Nasopharyngitis, diarrhea, upper respiratory tract infection
- Drug Interactions: Certain CYP450 substrates, particularly those where minimal changes in concentration may affect efficacy or safety
Exclusion Criteria- Uncontrolled active infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Core Inclusion Criteria- Definite or provisional diagnosis of active ankylosing spondylitis (or radiographic axial spondyloarthritis)
- Prescribed and monitored by a VA / VA Community Care rheumatologist or locally designated expert
- FDA-approved dose for ankylosing spondylitis
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum: HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and anti-HBs)
- Current or past completion of hepatitis C screening (may initiate while waiting for results)
- Tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated, or not adequate (NO or partial response after 3 months or loss of initial response) [Applies only to new starts]
Additional Inclusion Criteria- If HBsAg-negative but anti-HBc-positive: Consultation with gastroenterologist/hepatologist or infectious diseases expert for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- For new starts: Intolerance or inadequate response to ixekizumab (preferred interleukin-17A inhibitor in new starts)
- For patients who can become pregnant and partners who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
Clinical Management & Monitoring Notes- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (entecavir or tenofovir)
- Vaccinations should be updated before initiation when possible; recombinant zoster vaccine should be completed or initiated by the end of the first year, preferably at low dosage, stable disease, or when robust immune response is expected
- Stable patients on secukinumab should not be switched to a criteria-required prior drug for nonmedical reasons
Diagnosis & Prescribing Requirements- Definite or provisional diagnosis of active nonradiographic axial spondyloarthritis (nr-axSpA) made by a VA/VA Community Care rheumatologist
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Prescribed at the FDA-approved dose for active nr-axSpA
Infectious Disease Screening & Management- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- If HBsAg-negative but anti-HBc-positive and practitioner deems consult indicated: GI/liver or ID expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
Exclusion Criteria- Uncontrolled active infection, including undrained abscess (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Prior Therapy Requirements- Tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated, or not adequate (NO or partial response after 3 months or loss of initial response) [Applies only to new starts]
- For new starts: Had intolerance or inadequate response to ixekizumab (Ixekizumab is the preferred interleukin-17A inhibitor in new starts)
Counseling & Special Populations- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception
Diagnosis & Disease Activity- Definite or provisional diagnosis of psoriatic arthritis
- Inflammatory articular disease (joint, spine, and/or entheseal)
Prior Therapy & Treatment History- Tumor necrosis factor inhibitor (TNFi) is medically inadvisable, not tolerated, or not adequate (i.e., NO or partial response after 3 months or loss of initial response)
- For new starts: Had intolerance or inadequate response to ixekizumab (ixekizumab is the preferred interleukin-17A inhibitor in new starts)
Infectious Disease Screening & Management- Exclusion: Uncontrolled active infection, including undrained abscess (may start/restart once the infection is controlled)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Inclusion: Completed hepatitis C screening (current or past completion; may initiate while waiting for test results)
- Additional: If HBsAg-negative but anti-HBc-positive, consultation with a gastroenterologist/hepatologist or infectious diseases expert is required to advise on starting antiviral prophylaxis versus preemptively monitoring for HBV reactivation
Vaccination Requirements- Exclusion: Concomitant live or live-attenuated vaccines, or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Supplemental: When possible, vaccinations should be updated before initiation; recombinant zoster (SHINGRIX) vaccine should be completed or at least initiated by the end of the first year of treatment, preferably when dosage is low, disease is stable, or at other times when a robust immune response can be expected
Pregnancy & Reproductive Counseling- For patients who can become pregnant and partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
Prescribing, Monitoring & Re-testing Guidelines- Prescribed and monitored by a VA / VA Community Care rheumatologist, dermatologist or locally designated expert
- Routine retesting for tuberculosis (TB), hepatitis B, and hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
- Exceptions to exclusion/inclusion criteria should be adjudicated at the local facility according to P&T committee and pharmacy services policy/procedures
Indication- Moderate to severe hidradenitis suppurativa (HS)
Provider Requirements- Prescribed and monitored by a VA / VA Community Care dermatologist or locally designated expert
Screening & Testing Requirements- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen (anti-HBc) and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening
Exclusion Criteria- Uncontrolled active infection, including furunculosis and carbuncles (may start/restart once controlled)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Prior Therapy Requirements- Adalimumab / biosimilar (preferred) or infliximab / biosimilar (alternative) is medically inadvisable, not tolerated, or not adequate (i.e., NO treatment benefit after 3 months or inadequate partial response after 4 months)
Additional Inclusion Criteria- If HBsAg-negative but anti-HBc-positive: A GI / liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
Adjudication & Monitoring Notes- Aversity to injections (adalimumab/biosimilar) or infusions/barriers to in-clinic administration (infliximab/biosimilar, e.g., travel) should be adjudicated case by case
- Routine retesting for TB, hepatitis B, and hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
- For HBsAg-negative/anti-HBc-positive patients, anti-HBs titers do not guarantee protection against HBV reactivation; management depends on the patient’s risk of HBV reactivation
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SELEXIPAG TAB
UPTRAVI
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UPTRAVI |
2017-02-27 |
Exclusion Criteria- Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil)
- Concomitant use with other prostacyclins such as epoprostenol, treprostinil, and iloprost
Inclusion Criteria- Definitive diagnosis of PAH confirmed by right-heart catheterization including hemodynamic diagnosis: mean pulmonary artery pressure [mPAP] >25 mmHg, pulmonary artery wedge pressure [PAWP] or left ventricular end diastolic pressure [LVEDP] ≤15 mm Hg, and pulmonary vascular resistance (PVR) >3 Wood units
- World Health Organization (WHO) Group 1 PAH
- Under the care of a VA authorized, experienced provider in the management of PAH
- Patient is treated with or has been assessed for adjunct therapies such as oxygen, diuretics, digoxin and oral anticoagulant
- If acute vasoreactivity test positive, calcium channel antagonist therapy has been tried unless right heart failure is present
- Inadequate response (e.g., progression, deterioration) or a documented contraindication or inability to tolerate a (phosphodiesterase type 5) PDE-5 inhibitor AND an endothelin receptior antagonist (ERA) prior to consideration of selexipag
Dosage and Administration- Initial dose: 200 mcg orally twice daily
- Titration: Increase dose by 200 mcg twice daily at weekly intervals to the highest tolerated dose, up to a maximum of 1600 mcg twice daily
- Interruptions/Discontinuations: If medication is missed for 3 days or longer, restart at a reduced dose and re-titrate
Efficacy and Patient Selection- Efficacy established in patients with WHO Group 1 PAH and functional class II or III symptoms
- Not established for patients with functional class IV symptoms; continuous infusion of a prostacyclin (e.g., intravenous epoprostenol) remains preferred therapy for severely ill patients
- Treatment of non-WHO Group 1 pulmonary hypertension is aimed at the underlying disease; current evidence does not support use in non-WHO Group 1 PAH
Safety and Tolerability- Safety profile consistent with other systemic vasodilators; primarily affects tolerability (e.g., headache, diarrhea, jaw pain, nausea, myalgia, vomiting, extremity pain, flushing, arthralgia, rash)
- Initiated at a low starting dose and titrated slowly as tolerated
Combination Therapy- Combination therapy with prostacyclins and selexipag has not been studied
- Appropriateness of combination PAH therapy should be assessed by a provider who specializes in PAH, considering potential drug interactions, potentially additive adverse effects, and current evidence
Renewal and Monitoring- Routine evaluation by the PAH provider to assess both effectiveness and tolerability is mandatory
- Patients with a poor response should be considered for continuous infusion of prostacyclin
- Provider must specify criteria (e.g., NYHA functional class assessment) and a timepoint (e.g., 1, 3, or 6 months) for evaluation and continuation of treatment prior to beginning therapy
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SILTUXIMAB INJ,LYPHL
SYLVANT
|
SYLVANT |
2017-02-27 |
Indication & Patient Selection- • Diagnosis of Multicentric Castleman’s Disease (MCD)
- • ECOG Performance Status 0–2
- • Goals of care and role of palliative care consult have been discussed and documented
Exclusion Criteria / Contraindications- • Care for the disease being treated not provided by VA or VA purchased care
- • HIV positive and/or HHV-8 positive
- • Chronic or unresolved infection
- • Hypersensitivity reaction to siltuximab or inactive ingredients (L-histidine, polysorbate 80, sucrose)
- • Severe hepatic impairment (Child-Pugh C)
- • Absolute Neutrophil Count (ANC) < 1.0 x 10^9/L prior to first dose
- • Platelet count < 75 x 10^9/L prior to first dose
- • Hemoglobin > 17 g/dL prior to first dose
Hematologic Treatment Criteria (Subsequent Doses)- • ANC > 1.0 x 10^9/L
- • Platelet count > 50 x 10^9/L
- • Hemoglobin < 17 g/dL
- • If criteria are not met, consider delaying treatment; do not reduce dose
Monitoring & Safety Requirements- • Perform hematologic lab tests prior to each siltuximab dose for the first 12 months and every 3 dosing cycles thereafter
- • Monitor therapeutic effect or drug concentration for concurrent CYP450 substrate therapies with narrow therapeutic indices (e.g., warfarin, cyclosporine, theophylline) upon initiation/discontinuation and as needed; adjust dose accordingly
- • Exercise caution when co-administered with CYP3A4 substrate drugs (e.g., oral contraceptives, lovastatin, atorvastatin) due to potential reduced efficacy
- • Inform patients to notify provider immediately if signs/symptoms suggestive of infection develop
- • Monitor for signs/symptoms of allergic reactions during infusion (difficulty breathing, chest tightness, wheezing, severe dizziness/light-headedness, swelling of lips or skin rash)
- • Monitor for signs/symptoms of infusion-related reactions (back pain, chest pain/discomfort, nausea/vomiting, flushing, erythema, palpitations)
- • Use cautiously in patients at risk of GI perforation; immediately evaluate if symptoms suggestive of GI perforation present
- • Assess disease response or progression via radiographic scan or symptomatology prior to each cycle and every 3 months
Discontinuation Recommendations- • Patient develops signs of anaphylaxis during the infusion
- • Persistent, severe infusion-related reactions despite adequate premedication (antihistamines, acetaminophen, corticosteroids)
- • Non-compliance with therapy, laboratory, or follow-up requests
- • Decline in ECOG performance status to level unacceptable for patient to maintain quality of life
- • Persistent or recurring toxicity despite a 3-week delay in dosing
- • Evidence of progressive disease
Special Populations & Precautions- • Women of childbearing potential: Exclude pregnancy prior to receiving siltuximab; provide contraceptive counseling on risks vs. benefits; utilize effective contraception during and for 3 months after treatment
- • Siltuximab may mask signs/symptoms of acute inflammation via suppression of fever and acute phase reactants (e.g., C-reactive protein); should not be given to patients with severe infections
- • Live vaccines should not be administered during therapy as IL-6 inhibition may interfere with normal immune response
- • Pharmacokinetic analysis shows no significant difference in clearance in mild-moderate hepatic impairment (Child-Pugh Classes A and B)
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SINECATECHINS OINT,TOP
VEREGEN
|
VEREGEN |
2017-02-27 |
Exclusion Criteria- Immunocompromised patient
- Treatment of urethral, intra-vaginal, cervical, rectal or intra-anal human papilloma viral disease
- Application to open wounds
Inclusion Criteria- Patient is under the care of a dermatologist, gynecologist, urologist, or Women’s Health provider and meets one of the following conditions:
- Extensive or severe external genital or perianal warts (Both must be selected to be eligible):
- Large number (≥ 10) of individual warts or warts involving large areas of skin in areas otherwise difficult to treat with typical destructive modalities such as cryotherapy, podophyllin or trichloroacetic acid
- Documented inadequate response or intolerance to other patient-administered agents (podofilox for at least 4 one-week cycles and imiquimod for at least 4 one-week cycles)
- Isolated external genital warts (<10) on penile shaft, glans or vulvar areas or isolated perianal warts (Both must be selected to be eligible):
- Documented inadequate response or intolerance to at least two of these treatment modalities: topical 0.5% podofilox (at least 4 one-week cycles), podophyllin 25% (at least 4 weekly applications), trichloroacetic acid (80% or higher strength for at least 4 weekly applications), and cryotherapy (at least 4 cycles)
- Documented inadequate response or intolerance to imiquimod (at least 4 one-week cycles)
Dosage and Administration- Topical administered three times per day until complete clearance of all warts (maximum of 16 weeks of therapy)
- Each wart should receive approximately 0.5cm strand of sinecatechins to ensure complete coverage
Recommended Monitoring- Tolerability of local adverse effects
- Patient adherence to dosage regimen
Issues for Consideration / FDA Approved Indication- Sinecatechins 15% ointment is indicated for the topical treatment of external genital and perianal warts (Condylomata acuminate) due to human papillomavirus infection (HPV) in immunocompetent patients 18 years and older.
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SIPULEUCEL-T INJ,SUSP
PROVENGE
|
PROVENGE |
2017-02-27 |
Exclusion Criteria- Unable to comply with a minimum of 3 leukapheresis appointments (scheduled every 2 weeks for 3 visits, may be more depending on cell collection)
- Contraindication to apheresis (e.g., active infection, unstable heart or lung condition)
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more
- Visceral metastases
- Pathologic bone fractures
- Spinal cord compression
- Previous treatment with chemotherapy or secondary hormonal therapy for prostate cancer within the past 90 days
- Requires opioid therapy for cancer-related pain due to lack of efficacy of prior non-opiate pain regimens (not intolerance)
- Requires concomitant immunosuppressive therapy (exception: replacement doses of steroids <30mg/day Hydrocortisone or <7.5mg/day Prednisone or equivalent)
- Average weekly prostate cancer-related pain score of 4 or more on a 10-point visual analog scale
Inclusion Criteria- Patient has been offered a referral for concurrent Palliative Care to assess goals of care
- Metastatic castrate resistant prostate cancer with progressive disease based on soft tissue and/or bony metastases on serial radiographs, or PSA progression (two consecutive PSA values at least 14 days apart, each ≥5.0 ng/mL and ≥50% above the minimum PSA obtained during castration therapy)
- Asymptomatic or minimally symptomatic metastatic disease
- Alternative therapies have been discussed with patient
- Concomitant medical or surgical castration (serum testosterone ≤ 50 ng/dL) started at least 3 months prior to sipuleucel-T
Dosage and Administration / Clinical Requirements- Recommended course consists of 3 complete doses given at approximately 2-week intervals
- Leukapheresis procedure required approximately 3 days prior to each dose to collect cells for incubation with an antigen
- Pre-medicate approximately 30 minutes prior to infusion with acetaminophen and diphenhydramine to minimize infusion reactions
- Infusion administered over 60 minutes; do not use a cell filter
- Observe patient for at least 30 minutes after each infusion
- If a scheduled dose is missed, another apheresis procedure is required if the treatment course is to be continued
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SUMATRIPTAN
IMITREX, SUMATRIPTAN SUCCINATE
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IMITREX, SUMATRIPTAN SUCCINATE |
2017-02-27 |
Indications for Treatment- Sumatriptan oral, nasal, and subcutaneous injection: FDA approved indication for acute treatment of migraine with or without aura.
- Subcutaneous injection only: FDA approved indication for acute treatment of cluster headache.
Cluster Headache- Clinical Presentation
- Rapid escalation to maximum intensity with typical durations of less than one hour; non-oral treatment recommended in most cases due to faster onset of action.
- Pharmacologic Options
- Sumatriptan nasal spray 20 mg once in the nostril contralateral to the side of headache. May repeat a single 20 mg dose after > 2 hours if needed. Maximum dose: 40 mg per 24 hours.
- Zolmitriptan nasal spray 5 to 10 mg once in the nostril contralateral to the side of headache. May repeat a single 5 mg dose after > 2 hours if needed. Maximum dose: 10 mg per 24 hours. (Note: 10 mg as a single dose is off-label for cluster headache; only available as 2.5 mg or 5 mg dose).
- Intranasal triptans do not have an FDA-approved indication for cluster headache but evidence supports their use and they are commonly used by clinicians.
- Non-Pharmacologic Options
- High-flow normobaric oxygen: 12 to 15 L/min for 20 minutes via non-rebreather mask.
- Non-invasive vagus nerve stimulator (gammaCoreTM): Two two-minute stimulations. Both stimulations may be performed on the same side of the neck or the patient can switch sides for the second stimulation. Requires training per product information.
Migraine Headache- Clinical Presentation
- Often associated with severe nausea with or without vomiting and/or rapid escalation to maximum intensity; non-oral, faster-onset dosage forms more desirable.
- Pharmacologic Options
- Rizatriptan ODT: 5 to 10 mg. May repeat a single dose after > 2 hours if needed. Maximum dose: 30 mg per 24 hours.
- Zolmitriptan ODT: 1.25 to 5 mg. May repeat a single dose after > 2 hours if needed. Maximum dose: 10 mg per 24 hours.
- Rimegepant ODT: 75 mg. Maximum dose: 75 mg per 24 hours.
- Sumatriptan nasal spray: 5 mg to 20 mg in one nostril. May repeat a single dose after > 2 hours if needed. Maximum dose: 40 mg per 24 hours.
- Zolmitriptan nasal spray: 2.5 to 5 mg in one nostril. May repeat a single dose after > 2 hours if needed. Maximum dose: 10 mg per 24 hours.
- Dihydroergotamine (DHE) nasal spray (MIGRANAL): 0.5 mg per spray; 1 spray into each nostril, repeat after 15 minutes. Maximum: 4 sprays (2 doses) per 24-hours. Similar contraindications as triptans in vascular disease. Cannot be given within 24 hours of a triptan or vice versa.
- Dihydroergotamine HFA nasal spray (TRUDHESA): 0.725 mg per spray; 1 spray into each nostril, may repeat after > 1 hour if needed. Maximum: 4 sprays (2 doses) per 24-hours.
- Zavegepant nasal spray: 10 mg per spray; 1 spray in one nostril as a single dose. Maximum: 10 mg per 24-hours.
- Non-Pharmacologic Options
- Neuromodulation devices: Multiple options including non-invasive vagus nerve stimulator (gammaCoreTM) and external trigeminal nerve stimulator (CefalyTM). Requires training per product information.
- Administration & Safety Considerations
- ODTs can be considered for patients with severe nausea without vomiting. Avoid in patients who experience vomiting as they require gastrointestinal absorption (not buccally or sublingually absorbed).
- Adding an antiemetic may benefit patients experiencing severe nausea and vomiting with migraines.
General Prescribing Considerations- Alternatives should be evaluated case-by-case with the patient’s headache provider based on clinical context.
- Drug interactions may exist for some pharmacologic options that are different from sumatriptan.
- Refer to PBM INTRAnet or VA Formulary Advisor for current formulary status, additional formulary information, and VA Criteria for Use.
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SUMATRIPTAN INJ
IMITREX, SUMATRIPTAN SUCCINATE, ZEMBRACE SYMTOUCH
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IMITREX, SUMATRIPTAN SUCCINATE, ZEMBRACE SYMTOUCH |
2017-02-27 |
Indications for Treatment- Sumatriptan oral, nasal, and subcutaneous injection: FDA approved indication for acute treatment of migraine with or without aura.
- Subcutaneous injection only: FDA approved indication for acute treatment of cluster headache.
Cluster Headache- Clinical Presentation
- Rapid escalation to maximum intensity with typical durations of less than one hour; non-oral treatment recommended in most cases due to faster onset of action.
- Pharmacologic Options
- Sumatriptan nasal spray 20 mg once in the nostril contralateral to the side of headache. May repeat a single 20 mg dose after > 2 hours if needed. Maximum dose: 40 mg per 24 hours.
- Zolmitriptan nasal spray 5 to 10 mg once in the nostril contralateral to the side of headache. May repeat a single 5 mg dose after > 2 hours if needed. Maximum dose: 10 mg per 24 hours. (Note: 10 mg as a single dose is off-label for cluster headache; only available as 2.5 mg or 5 mg dose).
- Intranasal triptans do not have an FDA-approved indication for cluster headache but evidence supports their use and they are commonly used by clinicians.
- Non-Pharmacologic Options
- High-flow normobaric oxygen: 12 to 15 L/min for 20 minutes via non-rebreather mask.
- Non-invasive vagus nerve stimulator (gammaCoreTM): Two two-minute stimulations. Both stimulations may be performed on the same side of the neck or the patient can switch sides for the second stimulation. Requires training per product information.
Migraine Headache- Clinical Presentation
- Often associated with severe nausea with or without vomiting and/or rapid escalation to maximum intensity; non-oral, faster-onset dosage forms more desirable.
- Pharmacologic Options
- Rizatriptan ODT: 5 to 10 mg. May repeat a single dose after > 2 hours if needed. Maximum dose: 30 mg per 24 hours.
- Zolmitriptan ODT: 1.25 to 5 mg. May repeat a single dose after > 2 hours if needed. Maximum dose: 10 mg per 24 hours.
- Rimegepant ODT: 75 mg. Maximum dose: 75 mg per 24 hours.
- Sumatriptan nasal spray: 5 mg to 20 mg in one nostril. May repeat a single dose after > 2 hours if needed. Maximum dose: 40 mg per 24 hours.
- Zolmitriptan nasal spray: 2.5 to 5 mg in one nostril. May repeat a single dose after > 2 hours if needed. Maximum dose: 10 mg per 24 hours.
- Dihydroergotamine (DHE) nasal spray (MIGRANAL): 0.5 mg per spray; 1 spray into each nostril, repeat after 15 minutes. Maximum: 4 sprays (2 doses) per 24-hours. Similar contraindications as triptans in vascular disease. Cannot be given within 24 hours of a triptan or vice versa.
- Dihydroergotamine HFA nasal spray (TRUDHESA): 0.725 mg per spray; 1 spray into each nostril, may repeat after > 1 hour if needed. Maximum: 4 sprays (2 doses) per 24-hours.
- Zavegepant nasal spray: 10 mg per spray; 1 spray in one nostril as a single dose. Maximum: 10 mg per 24-hours.
- Non-Pharmacologic Options
- Neuromodulation devices: Multiple options including non-invasive vagus nerve stimulator (gammaCoreTM) and external trigeminal nerve stimulator (CefalyTM). Requires training per product information.
- Administration & Safety Considerations
- ODTs can be considered for patients with severe nausea without vomiting. Avoid in patients who experience vomiting as they require gastrointestinal absorption (not buccally or sublingually absorbed).
- Adding an antiemetic may benefit patients experiencing severe nausea and vomiting with migraines.
General Prescribing Considerations- Alternatives should be evaluated case-by-case with the patient’s headache provider based on clinical context.
- Drug interactions may exist for some pharmacologic options that are different from sumatriptan.
- Refer to PBM INTRAnet or VA Formulary Advisor for current formulary status, additional formulary information, and VA Criteria for Use.
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SUVOREXANT TAB,ORAL
BELSOMRA
|
BELSOMRA |
2017-02-27 |
Exclusion Criteria- Narcolepsy and/or cataplexy (familial or idiopathic)
- Concomitant therapy with strong CYP3A4 inhibitors
- Circadian rhythm sleep disorders, restless legs syndrome, parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder, or REM behavior disorder
- Active substance use disorder
- Considered a high suicide risk
- Untreated sleep-related breathing disorder-obstructive or central sleep apnea syndrome or central alveolar hypoventilation syndrome
- Severe hepatic impairment (i.e., Child-Pugh C)
- Concurrent use with any other sedative hypnotics for the treatment of insomnia
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care sleep specialist or locally designated expert in sleep disorders
- Documented diagnosis of insomnia characterized by difficulties with sleep onset and/or sleep maintenance
- When available, cognitive behavioral therapy for insomnia (CBT-I) has been tried, via face to face, tele-mental health or non-VA care
- An adequate short-term trial of 2 formulary sedative hypnotics for the treatment of sleep onset and maintenance have been tried and failed to resolve symptoms or were not tolerated
- An adequate trial of daridorexant has been tried and failed or was not tolerated
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TAMSULOSIN CAP,ORAL
FLOMAX, TAMSULOSIN HCL
|
FLOMAX, TAMSULOSIN HCL |
2017-02-27 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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TERAZOSIN CAP,ORAL
TERAZOSIN HCL
|
TERAZOSIN HCL |
2017-02-27 |
Indication & Patient Population- Benign prostatic hypertrophy/hyperplasia (BPH) with moderate to severe symptoms
- Patients currently receiving alpha-blocker monotherapy at maintenance doses (e.g., alfuzosin 10 mg qd) or highest tolerated dose if maintenance dose was not achieved
- Alpha-blocker naive patients presenting with BPH symptoms
Clinical Criteria for Combination Therapy Initiation/Continuation- Large prostate volume (typically >40ml, approximately the size of a golf ball)
- Clinical progression of BPH symptoms evidenced by:
- Increase in AUA symptom score ≥4 points from baseline
- History of acute urinary retention
- Persistently bothersome symptoms despite adequate alpha-blocker therapy
- Baseline AUA symptom score ≥12 for patients not previously treated with alpha-blockers
- High risk for intervention or urinary retention due to large prostate volume (>40ml)
Safety, Monitoring & Precautions- Discuss risks and benefits of long-term finasteride therapy with the patient prior to initiation
- Finasteride is not recommended for prevention of prostate cancer based on the Prostate Cancer Prevention Trial
- Patients must be reevaluated on a regular basis
- Monitor PSA levels; double values after more than 6 months of finasteride therapy to approximate actual off-therapy levels
- Referral to a local expert is strongly advised for severe unrelenting symptoms, very large prostates, or smaller prostate mass with poor response to alpha-blockers
Adverse Event Profile- Alpha-blockers: dizziness, postural hypotension, asthenia
- Finasteride (monotherapy or combination): erectile dysfunction, decreased libido, abnormal ejaculation
- Combination therapy: increased frequency of abnormal ejaculation, peripheral edema, dyspnea; breast cancer diagnosed in a small number of patients
Drug Interactions (PDE5 Inhibitors)- Sildenafil: Do not administer within 4 hours of an alpha-blocker; 25mg dose may be taken at any time
- Tadalafil: Concomitant administration with alpha-blockers other than tamsulosin 0.4mg is not recommended
- Vardenafil: Concomitant administration with any alpha-blocker is contraindicated
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TESTOSTERONE GEL,TOP
ANDROGEL, TESTIM, VOGELXO
|
ANDROGEL, TESTIM, VOGELXO |
2017-02-27 |
Exclusion Criteria- Active prostate cancer
- Active breast cancer
- Uncontrolled or untreated erythrocytosis (e.g., Hematocrit >48%)
- Severe, untreated Obstructive Sleep Apnea (OSA)
- Unevaluated Prostate Specific Antigen (PSA) level greater than 4 ng/mL or PSA greater than 3 ng/mL in individuals with risk factors for prostate cancer
- Severe lower urinary tract symptoms (International Prostate Symptom Score [IPSS] >19)
- Inadequately controlled congestive heart failure
- Acute Coronary syndrome (ACS), stroke (CVA), or revascularization procedure in the last 4 months
- Thrombophilia or history of unprovoked venous thromboembolism
- Severe liver disease or renal failure
- Desire for future fertility
- Active, unaddressed anabolic steroid misuse
Inclusion Criteria- Hypogonadism diagnosed by at least one clinical sign or symptom consistent with androgen deficiency
- HIV infected men with low testosterone levels and weight loss
- Receiving high doses of glucocorticoids who have low testosterone levels (daily dose greater than 5mg of prednisone or equivalent for at least 6 months)
- Status post bilateral orchiectomy or unilateral orchiectomy (with documented atrophy of second testicle)
- Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism and signs/symptoms of hypogonadism
Additional Pre-Initiation Requirements- Document that other potential treatable causes of symptoms of low testosterone levels and their suspected etiologies have been addressed
- Two, unequivocally low baseline, fasting, total testosterone levels (determined based on local laboratory assay and patient specific factors), at least one week apart, between 8am - 10am
- Prior to initiation, potential risks and benefits discussed and documented in the medical record
- Baseline Hemoglobin and Hematocrit, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and prolactin levels assessed
- Discussion regarding prostate cancer screening and monitoring occurred; if shared decision-making results in screening, PSA is measured
Clinical & Laboratory Considerations- For patients with Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism, a single baseline testosterone level is sufficient
- Free testosterone assessment recommended if concern for Sex Hormone Binding Globulin (SHBG) alterations exists (e.g., elderly, obesity, diabetes, liver or HIV disease, medications such as anticonvulsants/anabolic steroids/progestins, thyroid disease); acceptable measurement methods include equilibrium dialysis or calculation using total testosterone, SHBG, and albumin levels
- For patients on long-standing TRT (>1 year) without documentation, the requirement for two low baseline serum total testosterone levels may be waived case-by-case
- Risk factors for prostate cancer include African-American background, first-degree relative with prostate cancer, and exposure to Agent Orange
Indication & Patient Population- Postmenopausal women (natural or surgically induced) with hypoactive sexual desire disorder (HSDD)
- Off-label use for other indications, including HSDD in premenopausal women, improvement in bone mineral density, or mood/cognition enhancement, is not recommended
Diagnosis & Clinical Criteria- Persistent or recurrent deficiency or absence of desire for sexual activity with marked personal distress
- Symptoms not otherwise accounted for by a general medical or psychiatric condition (per DSM IV-TR)
- HSDD may be primary or secondary; lifelong or acquired; or generalized or situational
Dosing & Administration- Starting dose: 1/10th of a 1% testosterone cream or gel approved for daily use in men (e.g., 5 mg [0.5 mL] from a 50 mg tube)
- Dose may be increased to 10 mg (1 mL) if needed
- Application sites: Back of the calf, upper outer thigh, or buttock
- Injections, pellets, and oral formulations are not recommended
Monitoring & Laboratory Requirements- Baseline labs: Total testosterone level, sex hormone binding globulin (SHBG) level, liver function tests, lipid panel (and other labs as indicated)
- Maintain total testosterone concentrations within the physiologic premenopausal range per local laboratory reference ranges
- Check total testosterone levels 3 to 6 weeks after starting treatment and after any dose adjustments; once stable, monitor every 4 to 6 months
- Monitor for signs and symptoms of androgen excess
- Additional periodic testing: Breast exam, mammography, and pelvic exams as clinically indicated
Treatment Duration & Response Assessment- Noticeable improvements are typically seen within 6 to 8 weeks of treatment
- Discontinue therapy after 6 months if there is no meaningful improvement
- Consider a drug holiday after 6 to 12 months to determine if treatment is still required
Contraindications & Exclusions- Premenopausal women (insufficient evidence of benefit)
- Patients at high cardiometabolic risk (excluded from most studies)
- Baseline total testosterone levels in the mid-range to high range (indicates symptoms are likely unrelated to testosterone; therapy should not be initiated)
- Supraphysiologic dosing is not recommended
VA Dispensing & Supply Limitations- Prefer unit dose tubes of 1% testosterone gel (50 mg testosterone per 5 grams of gel) over unit dose packets
- Federal law limits controlled substance dispensing to a maximum of 180 days’ supply
- VA pharmacies must fill prescriptions for partial boxes at the facility level to comply with the 180-day limit (e.g., 3 tubes for 30 days)
Exclusion Criteria- Patient is pregnant, lactating, or of childbearing potential
- Active breast cancer or other hormonally sensitive cancer
- Severe liver disease
- Baseline total testosterone level in the midrange or high range for premenopausal females (per local laboratory threshold)
- Uncontrolled severe cardiovascular or cerebrovascular disease
- Uncontrolled hyperlipidemia
- High risk of breast cancer
- Known thrombophilia or unprovoked venous thromboembolism
Inclusion Criteria- Provider initiating treatment is a VA or VA Community Care women’s health provider, urologist, or other locally designated provider experienced in the treatment of HSDD
- Patient is naturally or surgically postmenopausal (perimenopausal patients meeting other criteria may be considered on an individual basis)
- Documented diagnosis of hypoactive sexual desire disorder (HSDD)
- Any modifiable factors and comorbidities contributing to HSDD have been acknowledged and addressed (e.g., physical factors, psychosocial factors, relationship issues, medications)
- Any concurrent medical conditions and modifiable risk factors that can be exacerbated by hormone treatment have been considered and addressed (e.g., sleep apnea, hypertension, diabetes, dyslipidemia, diseases worsened by fluid retention such as heart failure, renal impairment, hepatic impairment, obesity, depression/mood disorders)
Baseline Assessment & Laboratory Requirements- Baseline total testosterone, sex hormone binding globulin (SHBG), and liver function tests obtained and evaluated
- Testosterone levels are not used to diagnose HSDD and do not predict treatment efficacy
- Elevated SHBG typically indicates nonresponders but may be elevated in patients on oral estrogens, thyroid replacement, or untreated hyperthyroidism; a trial of testosterone therapy may still be considered for patients with unmodifiable risk factors (e.g., thyroid replacement therapy)
Patient Education & Compliance Requirements- Patient informed of and expressed clear understanding of potential risks, benefits, side effects, and limitations of hormone treatment and that use is off-label; discussion and patient understanding documented
- Patient agrees to avoidance of additional testosterone hormonal treatments (including compounded products, pellets, etc.)
- Patient expresses understanding on proper use of the product (e.g., transdermal use, correct dose, how to avoid transfer to others)
Clinical Considerations & Documentation- Insufficient evidence exists to guide therapy; recommend careful risk/benefit evaluation and shared decision-making approach with documentation in the Federal Electronic Health Record (EHR)
- Individual cases that are exceptions to exclusion and inclusion criteria should be adjudicated at the local facility according to P&T Committee and Pharmacy Services policy and procedures
Indications for Evaluation- • Men presenting with specific symptoms: erectile dysfunction, low libido, decreased frequency of morning erections, new unexplained gynecomastia, decreased body hair, eunuchoid features on exam, small testes, loss of male hair and gynecomastia
- • Men with findings associated with hypogonadism: infertility, unexplained anemia, fractures
- • Men with a history of conditions likely to cause hypogonadism: traumatic brain injury, orchiectomy, pituitary dysfunction, testicular trauma, chronic opioid use
Laboratory & Biochemical Assessment Criteria- • Serum total and/or free testosterone must be unequivocally and consistently low
- • Measurements must be obtained in the early morning (6–10 am), fasting state, and confirmed on at least two separate occasions
- • Total testosterone levels <150 ng/dL require evaluation for secondary/central hypogonadism
- • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must be measured to distinguish primary from secondary hypogonadism
- • Abnormal immunoassay results must be confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS)
- • Free testosterone should be measured when conditions affecting sex hormone-binding globulin (SHBG) are present: obesity, diabetes mellitus, glucocorticoid use, nephrotic syndrome, thyroid disease, acromegaly, androgen/estrogen use, liver disease
- • Harmonized lower limit of normal for total testosterone is 264 ng/dL for CDC-certified assays with normal SHBG
Contraindications to Testosterone Replacement Therapy (TRT)- • Active prostate or breast cancer
- • Uncontrolled/untreated erythrocytosis (initial hematocrit >48% or 54% on TRT)
- • Severe, untreated obstructive sleep apnea
- • Elevated prostate-specific antigen (PSA) (>4 ng/mL)
- • Severe lower urinary tract symptoms
- • Inadequately controlled congestive heart failure
- • Acute coronary syndrome, stroke, or revascularization procedure within 4 months
- • Thrombophilia or history of unprovoked venous thromboembolism
- • Severe liver disease or renal failure
- • Active, unaddressed anabolic steroid misuse
- • Desire for future fertility
Initiation, Monitoring, & Dosing Parameters- • Discontinue TRT if symptoms do not significantly and consistently improve after 6–12 months despite testosterone levels within the reference range
- • Monitor testosterone (including free/bioavailable), hemoglobin, hematocrit, and PSA at 3–6 months after initiation, again at 12 months
- • Dose adjustments indicated if testosterone falls outside laboratory limits or total testosterone exceeds 900 ng/dL
- • Discontinue testosterone if hematocrit exceeds 54%
- • Blood draw timing: midway between injections for injectable formulations; 2–8 hours after application for gel once steady-state is achieved (typically after ≥1 week)
- • PSA monitoring: baseline, repeated at 12 months, then annually (or sooner if clinically indicated)
Specialist Referral Criteria- • Endocrinology: Total testosterone <150 ng/dL with inappropriately normal or decreased LH/FSH; new/established contraindications to TRT; gynecomastia due to hypogonadism
- • Urology (for males receiving TRT): PSA rising >1.4 ng/mL from baseline or >4 ng/mL at any time; lack of improvement or intolerance of PDE-5 inhibitors
Alternative Therapies & Specific Clinical Scenarios- • Human chorionic gonadotropin (HCG) reserved for hypogonadotropic hypogonadism in men seeking to maintain fertility (restricted to endocrinology and infertility specialists)
- • Clomiphene may be considered on a case-by-case basis in males with hypogonadotropic hypogonadism desiring fertility prior to HCG use
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| ▸ |
TESTOSTERONE INJ,SOLN
AVEED
|
AVEED |
2017-02-27 |
Exclusion Criteria- Active prostate cancer
- Active breast cancer
- Uncontrolled or untreated erythrocytosis (e.g., Hematocrit >48%)
- Severe, untreated Obstructive Sleep Apnea (OSA)
- Unevaluated Prostate Specific Antigen (PSA) level greater than 4 ng/mL or PSA greater than 3 ng/mL in individuals with risk factors for prostate cancer
- Severe lower urinary tract symptoms (International Prostate Symptom Score [IPSS] >19)
- Inadequately controlled congestive heart failure
- Acute Coronary syndrome (ACS), stroke (CVA), or revascularization procedure in the last 4 months
- Thrombophilia or history of unprovoked venous thromboembolism
- Severe liver disease or renal failure
- Desire for future fertility
- Active, unaddressed anabolic steroid misuse
Inclusion Criteria- Hypogonadism diagnosed by at least one clinical sign or symptom consistent with androgen deficiency
- HIV infected men with low testosterone levels and weight loss
- Receiving high doses of glucocorticoids who have low testosterone levels (daily dose greater than 5mg of prednisone or equivalent for at least 6 months)
- Status post bilateral orchiectomy or unilateral orchiectomy (with documented atrophy of second testicle)
- Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism and signs/symptoms of hypogonadism
Additional Pre-Initiation Requirements- Document that other potential treatable causes of symptoms of low testosterone levels and their suspected etiologies have been addressed
- Two, unequivocally low baseline, fasting, total testosterone levels (determined based on local laboratory assay and patient specific factors), at least one week apart, between 8am - 10am
- Prior to initiation, potential risks and benefits discussed and documented in the medical record
- Baseline Hemoglobin and Hematocrit, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and prolactin levels assessed
- Discussion regarding prostate cancer screening and monitoring occurred; if shared decision-making results in screening, PSA is measured
Clinical & Laboratory Considerations- For patients with Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism, a single baseline testosterone level is sufficient
- Free testosterone assessment recommended if concern for Sex Hormone Binding Globulin (SHBG) alterations exists (e.g., elderly, obesity, diabetes, liver or HIV disease, medications such as anticonvulsants/anabolic steroids/progestins, thyroid disease); acceptable measurement methods include equilibrium dialysis or calculation using total testosterone, SHBG, and albumin levels
- For patients on long-standing TRT (>1 year) without documentation, the requirement for two low baseline serum total testosterone levels may be waived case-by-case
- Risk factors for prostate cancer include African-American background, first-degree relative with prostate cancer, and exposure to Agent Orange
Indications for Evaluation- • Men presenting with specific symptoms: erectile dysfunction, low libido, decreased frequency of morning erections, new unexplained gynecomastia, decreased body hair, eunuchoid features on exam, small testes, loss of male hair and gynecomastia
- • Men with findings associated with hypogonadism: infertility, unexplained anemia, fractures
- • Men with a history of conditions likely to cause hypogonadism: traumatic brain injury, orchiectomy, pituitary dysfunction, testicular trauma, chronic opioid use
Laboratory & Biochemical Assessment Criteria- • Serum total and/or free testosterone must be unequivocally and consistently low
- • Measurements must be obtained in the early morning (6–10 am), fasting state, and confirmed on at least two separate occasions
- • Total testosterone levels <150 ng/dL require evaluation for secondary/central hypogonadism
- • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must be measured to distinguish primary from secondary hypogonadism
- • Abnormal immunoassay results must be confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS)
- • Free testosterone should be measured when conditions affecting sex hormone-binding globulin (SHBG) are present: obesity, diabetes mellitus, glucocorticoid use, nephrotic syndrome, thyroid disease, acromegaly, androgen/estrogen use, liver disease
- • Harmonized lower limit of normal for total testosterone is 264 ng/dL for CDC-certified assays with normal SHBG
Contraindications to Testosterone Replacement Therapy (TRT)- • Active prostate or breast cancer
- • Uncontrolled/untreated erythrocytosis (initial hematocrit >48% or 54% on TRT)
- • Severe, untreated obstructive sleep apnea
- • Elevated prostate-specific antigen (PSA) (>4 ng/mL)
- • Severe lower urinary tract symptoms
- • Inadequately controlled congestive heart failure
- • Acute coronary syndrome, stroke, or revascularization procedure within 4 months
- • Thrombophilia or history of unprovoked venous thromboembolism
- • Severe liver disease or renal failure
- • Active, unaddressed anabolic steroid misuse
- • Desire for future fertility
Initiation, Monitoring, & Dosing Parameters- • Discontinue TRT if symptoms do not significantly and consistently improve after 6–12 months despite testosterone levels within the reference range
- • Monitor testosterone (including free/bioavailable), hemoglobin, hematocrit, and PSA at 3–6 months after initiation, again at 12 months
- • Dose adjustments indicated if testosterone falls outside laboratory limits or total testosterone exceeds 900 ng/dL
- • Discontinue testosterone if hematocrit exceeds 54%
- • Blood draw timing: midway between injections for injectable formulations; 2–8 hours after application for gel once steady-state is achieved (typically after ≥1 week)
- • PSA monitoring: baseline, repeated at 12 months, then annually (or sooner if clinically indicated)
Specialist Referral Criteria- • Endocrinology: Total testosterone <150 ng/dL with inappropriately normal or decreased LH/FSH; new/established contraindications to TRT; gynecomastia due to hypogonadism
- • Urology (for males receiving TRT): PSA rising >1.4 ng/mL from baseline or >4 ng/mL at any time; lack of improvement or intolerance of PDE-5 inhibitors
Alternative Therapies & Specific Clinical Scenarios- • Human chorionic gonadotropin (HCG) reserved for hypogonadotropic hypogonadism in men seeking to maintain fertility (restricted to endocrinology and infertility specialists)
- • Clomiphene may be considered on a case-by-case basis in males with hypogonadotropic hypogonadism desiring fertility prior to HCG use
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TESTOSTERONE INJ,SOLN
DELATESTRYL, DEPO-TESTOSTERONE, TESTOSTERONE CYPIONATE, TESTOSTERONE ENANTHATE
|
DELATESTRYL, DEPO-TESTOSTERONE, TESTOSTERONE CYPIONATE, TESTOSTERONE ENANTHATE |
2017-02-27 |
Exclusion Criteria- Active prostate cancer
- Active breast cancer
- Uncontrolled or untreated erythrocytosis (e.g., Hematocrit >48%)
- Severe, untreated Obstructive Sleep Apnea (OSA)
- Unevaluated Prostate Specific Antigen (PSA) level greater than 4 ng/mL or PSA greater than 3 ng/mL in individuals with risk factors for prostate cancer
- Severe lower urinary tract symptoms (International Prostate Symptom Score [IPSS] >19)
- Inadequately controlled congestive heart failure
- Acute Coronary syndrome (ACS), stroke (CVA), or revascularization procedure in the last 4 months
- Thrombophilia or history of unprovoked venous thromboembolism
- Severe liver disease or renal failure
- Desire for future fertility
- Active, unaddressed anabolic steroid misuse
Inclusion Criteria- Hypogonadism diagnosed by at least one clinical sign or symptom consistent with androgen deficiency
- HIV infected men with low testosterone levels and weight loss
- Receiving high doses of glucocorticoids who have low testosterone levels (daily dose greater than 5mg of prednisone or equivalent for at least 6 months)
- Status post bilateral orchiectomy or unilateral orchiectomy (with documented atrophy of second testicle)
- Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism and signs/symptoms of hypogonadism
Additional Pre-Initiation Requirements- Document that other potential treatable causes of symptoms of low testosterone levels and their suspected etiologies have been addressed
- Two, unequivocally low baseline, fasting, total testosterone levels (determined based on local laboratory assay and patient specific factors), at least one week apart, between 8am - 10am
- Prior to initiation, potential risks and benefits discussed and documented in the medical record
- Baseline Hemoglobin and Hematocrit, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and prolactin levels assessed
- Discussion regarding prostate cancer screening and monitoring occurred; if shared decision-making results in screening, PSA is measured
Clinical & Laboratory Considerations- For patients with Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism, a single baseline testosterone level is sufficient
- Free testosterone assessment recommended if concern for Sex Hormone Binding Globulin (SHBG) alterations exists (e.g., elderly, obesity, diabetes, liver or HIV disease, medications such as anticonvulsants/anabolic steroids/progestins, thyroid disease); acceptable measurement methods include equilibrium dialysis or calculation using total testosterone, SHBG, and albumin levels
- For patients on long-standing TRT (>1 year) without documentation, the requirement for two low baseline serum total testosterone levels may be waived case-by-case
- Risk factors for prostate cancer include African-American background, first-degree relative with prostate cancer, and exposure to Agent Orange
Indications for Evaluation- • Men presenting with specific symptoms: erectile dysfunction, low libido, decreased frequency of morning erections, new unexplained gynecomastia, decreased body hair, eunuchoid features on exam, small testes, loss of male hair and gynecomastia
- • Men with findings associated with hypogonadism: infertility, unexplained anemia, fractures
- • Men with a history of conditions likely to cause hypogonadism: traumatic brain injury, orchiectomy, pituitary dysfunction, testicular trauma, chronic opioid use
Laboratory & Biochemical Assessment Criteria- • Serum total and/or free testosterone must be unequivocally and consistently low
- • Measurements must be obtained in the early morning (6–10 am), fasting state, and confirmed on at least two separate occasions
- • Total testosterone levels <150 ng/dL require evaluation for secondary/central hypogonadism
- • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must be measured to distinguish primary from secondary hypogonadism
- • Abnormal immunoassay results must be confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS)
- • Free testosterone should be measured when conditions affecting sex hormone-binding globulin (SHBG) are present: obesity, diabetes mellitus, glucocorticoid use, nephrotic syndrome, thyroid disease, acromegaly, androgen/estrogen use, liver disease
- • Harmonized lower limit of normal for total testosterone is 264 ng/dL for CDC-certified assays with normal SHBG
Contraindications to Testosterone Replacement Therapy (TRT)- • Active prostate or breast cancer
- • Uncontrolled/untreated erythrocytosis (initial hematocrit >48% or 54% on TRT)
- • Severe, untreated obstructive sleep apnea
- • Elevated prostate-specific antigen (PSA) (>4 ng/mL)
- • Severe lower urinary tract symptoms
- • Inadequately controlled congestive heart failure
- • Acute coronary syndrome, stroke, or revascularization procedure within 4 months
- • Thrombophilia or history of unprovoked venous thromboembolism
- • Severe liver disease or renal failure
- • Active, unaddressed anabolic steroid misuse
- • Desire for future fertility
Initiation, Monitoring, & Dosing Parameters- • Discontinue TRT if symptoms do not significantly and consistently improve after 6–12 months despite testosterone levels within the reference range
- • Monitor testosterone (including free/bioavailable), hemoglobin, hematocrit, and PSA at 3–6 months after initiation, again at 12 months
- • Dose adjustments indicated if testosterone falls outside laboratory limits or total testosterone exceeds 900 ng/dL
- • Discontinue testosterone if hematocrit exceeds 54%
- • Blood draw timing: midway between injections for injectable formulations; 2–8 hours after application for gel once steady-state is achieved (typically after ≥1 week)
- • PSA monitoring: baseline, repeated at 12 months, then annually (or sooner if clinically indicated)
Specialist Referral Criteria- • Endocrinology: Total testosterone <150 ng/dL with inappropriately normal or decreased LH/FSH; new/established contraindications to TRT; gynecomastia due to hypogonadism
- • Urology (for males receiving TRT): PSA rising >1.4 ng/mL from baseline or >4 ng/mL at any time; lack of improvement or intolerance of PDE-5 inhibitors
Alternative Therapies & Specific Clinical Scenarios- • Human chorionic gonadotropin (HCG) reserved for hypogonadotropic hypogonadism in men seeking to maintain fertility (restricted to endocrinology and infertility specialists)
- • Clomiphene may be considered on a case-by-case basis in males with hypogonadotropic hypogonadism desiring fertility prior to HCG use
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| ▸ |
TESTOSTERONE INJECTION
DEPO-TESTOSTERONE, TESTOSTERONE CYPIONATE
|
DEPO-TESTOSTERONE, TESTOSTERONE CYPIONATE |
2017-02-27 |
Exclusion Criteria- Active prostate cancer
- Active breast cancer
- Uncontrolled or untreated erythrocytosis (e.g., Hematocrit >48%)
- Severe, untreated Obstructive Sleep Apnea (OSA)
- Unevaluated Prostate Specific Antigen (PSA) level greater than 4 ng/mL or PSA greater than 3 ng/mL in individuals with risk factors for prostate cancer
- Severe lower urinary tract symptoms (International Prostate Symptom Score [IPSS] >19)
- Inadequately controlled congestive heart failure
- Acute Coronary syndrome (ACS), stroke (CVA), or revascularization procedure in the last 4 months
- Thrombophilia or history of unprovoked venous thromboembolism
- Severe liver disease or renal failure
- Desire for future fertility
- Active, unaddressed anabolic steroid misuse
Inclusion Criteria- Hypogonadism diagnosed by at least one clinical sign or symptom consistent with androgen deficiency
- HIV infected men with low testosterone levels and weight loss
- Receiving high doses of glucocorticoids who have low testosterone levels (daily dose greater than 5mg of prednisone or equivalent for at least 6 months)
- Status post bilateral orchiectomy or unilateral orchiectomy (with documented atrophy of second testicle)
- Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism and signs/symptoms of hypogonadism
Additional Pre-Initiation Requirements- Document that other potential treatable causes of symptoms of low testosterone levels and their suspected etiologies have been addressed
- Two, unequivocally low baseline, fasting, total testosterone levels (determined based on local laboratory assay and patient specific factors), at least one week apart, between 8am - 10am
- Prior to initiation, potential risks and benefits discussed and documented in the medical record
- Baseline Hemoglobin and Hematocrit, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and prolactin levels assessed
- Discussion regarding prostate cancer screening and monitoring occurred; if shared decision-making results in screening, PSA is measured
Clinical & Laboratory Considerations- For patients with Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism, a single baseline testosterone level is sufficient
- Free testosterone assessment recommended if concern for Sex Hormone Binding Globulin (SHBG) alterations exists (e.g., elderly, obesity, diabetes, liver or HIV disease, medications such as anticonvulsants/anabolic steroids/progestins, thyroid disease); acceptable measurement methods include equilibrium dialysis or calculation using total testosterone, SHBG, and albumin levels
- For patients on long-standing TRT (>1 year) without documentation, the requirement for two low baseline serum total testosterone levels may be waived case-by-case
- Risk factors for prostate cancer include African-American background, first-degree relative with prostate cancer, and exposure to Agent Orange
Indications for Evaluation- • Men presenting with specific symptoms: erectile dysfunction, low libido, decreased frequency of morning erections, new unexplained gynecomastia, decreased body hair, eunuchoid features on exam, small testes, loss of male hair and gynecomastia
- • Men with findings associated with hypogonadism: infertility, unexplained anemia, fractures
- • Men with a history of conditions likely to cause hypogonadism: traumatic brain injury, orchiectomy, pituitary dysfunction, testicular trauma, chronic opioid use
Laboratory & Biochemical Assessment Criteria- • Serum total and/or free testosterone must be unequivocally and consistently low
- • Measurements must be obtained in the early morning (6–10 am), fasting state, and confirmed on at least two separate occasions
- • Total testosterone levels <150 ng/dL require evaluation for secondary/central hypogonadism
- • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must be measured to distinguish primary from secondary hypogonadism
- • Abnormal immunoassay results must be confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS)
- • Free testosterone should be measured when conditions affecting sex hormone-binding globulin (SHBG) are present: obesity, diabetes mellitus, glucocorticoid use, nephrotic syndrome, thyroid disease, acromegaly, androgen/estrogen use, liver disease
- • Harmonized lower limit of normal for total testosterone is 264 ng/dL for CDC-certified assays with normal SHBG
Contraindications to Testosterone Replacement Therapy (TRT)- • Active prostate or breast cancer
- • Uncontrolled/untreated erythrocytosis (initial hematocrit >48% or 54% on TRT)
- • Severe, untreated obstructive sleep apnea
- • Elevated prostate-specific antigen (PSA) (>4 ng/mL)
- • Severe lower urinary tract symptoms
- • Inadequately controlled congestive heart failure
- • Acute coronary syndrome, stroke, or revascularization procedure within 4 months
- • Thrombophilia or history of unprovoked venous thromboembolism
- • Severe liver disease or renal failure
- • Active, unaddressed anabolic steroid misuse
- • Desire for future fertility
Initiation, Monitoring, & Dosing Parameters- • Discontinue TRT if symptoms do not significantly and consistently improve after 6–12 months despite testosterone levels within the reference range
- • Monitor testosterone (including free/bioavailable), hemoglobin, hematocrit, and PSA at 3–6 months after initiation, again at 12 months
- • Dose adjustments indicated if testosterone falls outside laboratory limits or total testosterone exceeds 900 ng/dL
- • Discontinue testosterone if hematocrit exceeds 54%
- • Blood draw timing: midway between injections for injectable formulations; 2–8 hours after application for gel once steady-state is achieved (typically after ≥1 week)
- • PSA monitoring: baseline, repeated at 12 months, then annually (or sooner if clinically indicated)
Specialist Referral Criteria- • Endocrinology: Total testosterone <150 ng/dL with inappropriately normal or decreased LH/FSH; new/established contraindications to TRT; gynecomastia due to hypogonadism
- • Urology (for males receiving TRT): PSA rising >1.4 ng/mL from baseline or >4 ng/mL at any time; lack of improvement or intolerance of PDE-5 inhibitors
Alternative Therapies & Specific Clinical Scenarios- • Human chorionic gonadotropin (HCG) reserved for hypogonadotropic hypogonadism in men seeking to maintain fertility (restricted to endocrinology and infertility specialists)
- • Clomiphene may be considered on a case-by-case basis in males with hypogonadotropic hypogonadism desiring fertility prior to HCG use
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TETRABENAZINE TAB
XENAZINE
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XENAZINE |
2017-02-27 |
Exclusion Criteria- Patient is actively suicidal or with untreated or inadequately treated depression.
- Congenital long QT interval, or a QTc >450 ms for men or QTc >470 ms for women.
- History of cardiac arrhythmias (patients with a history of ventricular arrhythmias), cardiac conduction system disease (LBBB or RBBB) or cardiac device can be considered candidates with cardiology evaluation.
- Concurrent use of a monoamine oxidase inhibitor (MAOI).
- Current or use of reserpine within the past 20 days.
- Concurrent use of another VMAT2 inhibitor.
- A history of neuroleptic malignant syndrome (NMS).
- Current clinically significant hyperprolactinemia.
- Pregnant or breast feeding.
- Hepatic impairment.
- Patient is receiving a medication known to increase the QTc interval, e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone, antibiotics (e.g., moxifloxacin), Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic medications or any other medications known to prolong the QTc interval.
Inclusion Criteria: Treatment of Huntington Disease- When the initial prescriber is a resident, fellow or other trainee, an attending psychiatrist or neurologist has verified the diagnosis and need for tetrabenazine.
- The patient has a diagnosis of Huntington disease documented in his/her medical record.
- The chorea is disabling or painful and interferes with the patient’s functional status, including self-care and ambulation; quality of life; or creates a social stigma sufficient to cause social isolation or embarrassment.
- The prescriber has documented the specific movement(s) (e.g., facial, oral extremity, or trunk) in the patient’s medical record along with how the chorea is affecting the patient’s function, quality of life or socialization.
Inclusion Criteria: Treatment of Dystonia- When the initial prescriber is a resident, fellow or other trainee, an attending psychiatrist or neurologist has verified the diagnosis and need for tetrabenazine.
- No response or are intolerant to alternative agents (local botulinum toxin injections, anticholinergics, or benzodiazepines).
Inclusion Criteria: Treatment of Tardive Dyskinesia- The patient has a diagnosis of tardive dyskinesia (TD) secondary to a dopaminergic blocking agent, e.g. antipsychotic or metoclopramide.
- The patient’s TD interferes with the patient’s functional status, including self-care and ambulation; quality of life; or creates a social stigma sufficient to cause social isolation or embarrassment.
- The prescriber has documented the specific movement(s) (e.g., facial, oral extremity, or trunk) in the patient’s medical record along with how TD is affecting the patient’s function, quality of life or socialization.
- A recent Abnormal Involuntary Movement Scale (AIMS) score is recorded in the patient’s medical record.
- An ECG was performed to confirm a QTc <450 ms for men or QTc <470 ms for women.
- When the initial prescriber is a resident, fellow or other trainee, an attending psychiatrist or neurologist has verified the diagnosis and need for tetrabenazine.
Indications- Management of chorea associated with Huntington disease (HD)
- Management of tardive dyskinesia (TD)
Dosage & Administration- Dosage form: Oral tablets (6 mg, 9 mg, 12 mg); non-formulary status
- Administer with food; swallow tablets whole (do not crush, chew, or break)
- HD dosing: 6 mg once daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day. If total daily dose is ≥12 mg, administer in two divided doses. Maximum recommended dose: 48 mg/day.
- TD dosing: 6 mg twice daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day. If total daily dose is ≥12 mg, administer in two divided doses. Maximum recommended dose: 48 mg/day.
Contraindications- Suicidal/untreated depression
- Hepatic impairment
- Taking reserpine
- Taking MAOI (monoamine oxidase inhibitor)
- Taking another VMAT-2 inhibitor
Warnings & Precautions- Box warning for depression and suicidality
- Neuroleptic malignant syndrome
- Akathisia, restlessness, agitation
- Parkinsonism
- Sedation and somnolence
- QTc prolongation
Adverse Reactions- HD: Somnolence, diarrhea, dry mouth, fatigue, insomnia
- TD: Insomnia, nasopharyngitis, depression, akathisia
Drug Interactions- Strong CYP2D6 inhibitors
- Reserpine
- MAOIs
- Alcohol/Sedating drugs
- Drugs causing QTc prolongation
- Neuroleptic drugs
- Concomitant VMAT-2 inhibitors
Efficacy- HD: Demonstrated reduction in Total Chorea Score compared to placebo (p<0.0001) in a 12-week randomized, double-blind, placebo-controlled study.
- TD: Demonstrated reduction in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo at week 12 in the AIM-TD and ARM-TD trials.
Place in Therapy & Utilization- VMAT-2 inhibitor utilized for management of HD chorea and TD.
- Indirect evidence suggests better tolerability compared to tetrabenazine, though VA ADERS data does not fully support this finding.
- Sequencing of VMAT-2 inhibitors is not warranted based on current evidence and utilization data.
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TETRACYCLINE CAP,ORAL
TETRACYCLINE HCL
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TETRACYCLINE HCL |
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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TINIDAZOLE TAB
|
|
2017-02-27 |
Indication & Patient Population- Helicobacter pylori (H. pylori) infection
- Treatment-naïve patients
- Treatment-experienced patients with persistent H. pylori despite treatment with optimized bismuth quadruple therapy or vonoprazan dual therapy
Treatment Setting & Line of Therapy- Suggested as a first-line alternative treatment option for treatment-naïve patients when optimized bismuth quadruple therapy cannot be used
- Suggested as a salvage regimen for treatment-experienced patients with persistent H. pylori; supported by substantial data for rifabutin triple therapy given as individual components for salvage in patients with multiple treatment failures
- Can be administered without the need for susceptibility testing (the only other regimen besides optimized bismuth quadruple therapy that does not require susceptibility testing)
- Supported for use when optimized bismuth quadruple therapy and vonoprazan dual therapy cannot be used or have failed
- Note: The co-formulated combination product has not been studied in treatment-experienced patients; however, the 2024 ACG guidelines suggest it as an alternative to individual components to potentially maximize pharmacokinetics and lower the risk of myelotoxicity
Dosing & Administration- Co-formulated in a delayed release capsule containing omeprazole, rifabutin, and amoxicillin
- Administer 4 capsules TID with food
- Provides daily doses of 120 mg omeprazole, 150 mg rifabutin, and 2-3 g/day amoxicillin
Precautions & Drug Interactions- Rifabutin is a known CYP3A4 substrate and inducer; omeprazole inhibits CYP2C19
- Patients must be evaluated for drug-drug interactions prior to prescribing (e.g., azole antifungals, antiretrovirals, warfarin, methotrexate, cyclosporine, tacrolimus)
Formulary Status- Listed on the VA Formulary as PA-F
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TIPIRACIL/ TRIFLURIDINE TAB
LONSURF
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LONSURF |
2017-02-27 |
Exclusion Criteria- Inability to swallow/tolerate oral medications or known malabsorption condition
- Known pregnancy
- Lactating
Inclusion Criteria (All must be met)- Care provided by a VA/VA Community Care Hematology or Oncology provider
- Goals of care and role of palliative care consult has been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 or 1
- Adequate bone marrow function (hemoglobin ≥ 9 g/dL, Absolute Neutrophil Count ≥ 1500/mm3, platelet count ≥ 75,000/mm3)
- Adequate liver function (total bilirubin ≤ 1.5 X Upper Limit of Normal, ALT/AST ≤ 3 X ULN or ≤ 5 x ULN if liver metastases)
- Adequate renal function (CrCl > 30 mL/min)
Additional Inclusion Criteria (One must be met)- Metastatic colon cancer previously treated with all of the following, unless contraindicated: fluoropyrimidine-oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy and if RAS wild-type, an anti-EGFR therapy
- Metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with ≥ two prior regimens including a fluoropyrimidine, a platinum, either a taxane or irinotecan and a HER2/neu-targeted agent (if HER2+), unless contraindicated
Additional Inclusion Criteria if Applicable- For females who can become pregnant: Pregnancy must be excluded prior to receiving trifluridine-tipiracil
- For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for at least 3 months after stopping treatment
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TOCILIZUMAB INJ,SOLN
ACTEMRA, ACTEMRA ACTPEN
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ACTEMRA, ACTEMRA ACTPEN |
2017-02-27 |
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for the infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Congenital or acquired immunodeficiency
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 unless associated with Duffy-null Associated Neutrophil Count
- Baseline platelet count <100,000/mm3
- Baseline ALT and/or AST > 1.5x the upper limit of normal (ULN)
Inclusion Criteria- Diagnosis of moderate to severe rheumatoid arthritis
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally-designated expert
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- Tumor necrosis factor inhibitor (TNFI) therapy is medically inadvisable, not tolerated, or not adequate (i.e., NO response to ONE TNFI after 3 months, partial response to 3-month trials of TWO TNFIs = total 6 months), or lost response
Additional Inclusion Criteria- If HBsAg-negative but anti-HBc-positive and consult is deemed indicated: A GI/liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits of treatment
Laboratory, Screening, & Monitoring Requirements- Routine rescreening for hepatitis B or hepatitis C is not required for prescription renewals; retesting in high-risk patients should be considered
- Safety of using tocilizumab in patients positive for HBV or HCV is unknown as these patients were excluded from clinical trials
Concomitant Medication & Vaccination Guidelines- May be used in combination with methotrexate, other nonbiologic disease-modifying antirheumatic drugs (DMARDs), mycophenolate, hydroxychloroquine, or glucocorticoids
- Concomitant use of potent immunosuppressives should generally be avoided
- Vaccinations should be updated before initiation; recombinant zoster vaccine should be completed or at least initiated by the end of the first year of treatment, preferably when dosage is low, disease is stable, or at other times when a robust immune response to vaccination can be expected
Exclusion Criteria- Uncontrolled active infection (may start/restart once treatment for the infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Congenital or acquired immunodeficiency
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 unless associated with Duffy-null Associated Neutrophil Count
- Baseline platelet count <100,000/mm3
- Baseline ALT and/or AST > 1.5x the upper limit of normal (ULN)
Inclusion Criteria: Diagnosis & Disease Characteristics- Documented active systemic sclerosis (SSc) with laboratory, radiographic, histologic, or other clinical evidence of an inflammatory component
- Diagnosis of SSc-interstitial lung disease (ILD), preferably confirmed by multidisciplinary discussion
- Preferably without WHO functional class 2 to 4 pulmonary arterial hypertension (WHO functional class 1 preferred)
- SSc duration of not more than 5 years from onset of the first non-Raynaud phenomenon manifestation
- Active disease defined as at least one of: disease duration ≤18 months; worsening severity or extent of skin/body involvement; or ≥1 tendon friction rub
- Laboratory evidence of inflammation including elevated acute phase reactants (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], or platelet count above ULN)
Inclusion Criteria: Treatment History & Disease Progression- Must meet ONE of the following:
- Progression of clinically evident SSc-ILD during mycophenolate therapy, or mycophenolate is not tolerated/medically inadvisable
- Progression of clinically evident SSc-ILD during cyclophosphamide therapy, or cyclophosphamide is not tolerated/medically inadvisable
- Rapid clinical progression of SSc-ILD even without prior mycophenolate or cyclophosphamide therapy
- Subclinical SSc-ILD (no prior mycophenolate or cyclophosphamide required; objective is to slow/prevent ILD progression)
- Disease progression defined as: ≥10% absolute decrease from baseline in % predicted forced vital capacity (FVC) OR ≥15% absolute decrease from baseline in % predicted diffusing capacity of the lung for carbon monoxide (DLCO) OR progression on high-resolution computed tomography (HRCT)
Inclusion Criteria: Screening, Counseling & Monitoring- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
- If HBsAg-negative but anti-HBc-positive and consult indicated: GI/liver or infectious diseases expert consulted for advice on antiviral prophylaxis or preemptive monitoring for HBV reactivation
- Offered all age-appropriate vaccinations prior to initiating therapy
- For females who can become pregnant: Counseling provided on potential risks vs benefits and use of effective contraception
- For females who are breastfeeding/providing breastmilk: Counseling provided on potential risks vs benefits
Prescribing & Administration Requirements- Prescribed and monitored by a VA/VA Community Care rheumatologist, pulmonologist, or locally designated expert
- May be used in combination with methotrexate, other nonbiologic DMARDs, mycophenolate, hydroxychloroquine, or glucocorticoids
- Concomitant use of potent immunosuppressives should generally be avoided
General Principles & Substitution Guidelines- Every effort should be made to substitute tocilizumab SC with tocilizumab IV or an agent that has the same mechanism (e.g., sarilumab).
- If an in-class substitution is not feasible, every effort should be made to substitute the targeted therapy (tocilizumab or sarilumab) with other targeted therapies.
Rheumatoid Arthritis (Self-administered SC Alternatives)- Sarilumab SC, based on availability
- Abatacept SC
- Oral JAK inhibitor (tofacitinib preferred over baricitinib and upadacitinib) with shared decision making as related to recent FDA warnings (mortality, malignancy, MACE, thrombosis)
- Different SC TNFI if patient had a prior loss of initial response (secondary nonresponse) to a TNFI (not if there was primary nonresponse)
Rheumatoid Arthritis (IV Infusion Alternatives)- Tocilizumab IV, case by case based on site resources/availability of vials
- Abatacept IV
- Rituximab IV
- Infliximab-abda IV if patient had a prior loss of initial response (secondary nonresponse) to a different, non-infliximab TNFI product (not if there was primary nonresponse)
Giant Cell Arteritis (GCA)- Prioritize patients actively on tocilizumab for GCA for continuation of therapy and available vials as they are obtained.
- If a glucocorticoid-sparing, targeted agent is urgently needed and tocilizumab is not available, off-label use may be considered for:
- Sarilumab SC, based on availability
- Ustekinumab with maintenance of glucocorticoid therapy
- Abatacept
- Exclusion Criteria (Patient will not meet criteria if any are present)
- Uncontrolled, active, severe infection (including undrained abscess); may start/restart once treatment for the infection has been initiated
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis; may initiate after starting antiviral prophylaxis
- Untreated HIV infection; treated, well-controlled, asymptomatic HIV-positive patients are eligible
- Concomitant live or live-attenuated vaccines, or administration of inactivated/live/attenuated vaccines <2 weeks before initiation
- Concomitant immunosuppressive biologic, immunosuppressive targeted synthetic drug (e.g., tofacitinib or other JAK inhibitors), cyclophosphamide, or alkylating agents
- Active hepatic disease or hepatic impairment
- Baseline absolute neutrophil count (ANC) < 2000/mm3 (unless associated with Duffy-null Associated Neutrophil Count)
- Baseline platelet count <100,000/mm3
- Baseline ALT and/or AST > 1.5x the upper limit of normal (ULN)
- Inclusion Criteria (All must be met)
- Definite or provisional diagnosis of active giant cell arteritis
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening; may initiate while awaiting test results
- Initiated concurrently or after glucocorticoid therapy unless medically inadvisable
- Additional Inclusion Criteria (Select if applicable)
- For HBsAg-negative but anti-HBc-positive patients where practitioner deems consult indicated: GI/liver or infectious diseases expert consulted for advice on whether to start antiviral prophylaxis or preemptively monitor for HBV reactivation
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits
Indication & Patient Population- Hospitalized patients with severe COVID-19
- Positive SARS-CoV-2 direct viral test required
- Must be receiving systemic corticosteroids
- Must require supplemental oxygen, invasive or non-invasive mechanical ventilation, or ECMO
Dosing & Administration Requirements- Recommended dose: 8 mg/kg (max 800 mg) as a single intravenous infusion for patients weighing ≥30 kg
- One additional dose of 8 mg/kg may be administered at least 8 hours after the first dose if signs and symptoms worsen or do not improve
- Subcutaneous administration is NOT authorized
- Must be diluted in a 100 mL prefilled bag of 0.9% or 0.45% sodium chloride
- Infusion must be administered over 60 minutes
- Must be protected from light after dilution (stored up to 24 hours refrigerated or 4 hours at room temperature)
- Must not be infused concomitantly in the same intravenous line with other drugs
Contraindications- Known hypersensitivity to tocilizumab
- Active infection (including localized infection)
- ALT or AST greater than 10 times the upper limit of normal
- Absolute neutrophil count (ANC) < 1000/mm³
- Platelet count < 50,000/mm³
- Active hepatic disease or hepatic impairment
Warnings, Precautions & Monitoring- Serious infections: Do not administer if concurrent active infection exists. Prompt diagnostic workup and antimicrobial therapy required if new infection develops. Weigh risks/benefits in patients with chronic/recurrent infection or history of serious opportunistic infections.
- Gastrointestinal perforation: Use with caution in patients at increased risk; evaluate new abdominal symptoms early for perforation.
- Hepatotoxicity: Monitor AST and ALT per standard practice. Not recommended if transaminases >10x ULN.
- Hypersensitivity reactions: Infuse only by a healthcare professional with appropriate medical support to manage anaphylaxis. Stop and discontinue permanently if anaphylaxis occurs.
- Demyelinating disorders: Monitor for signs/symptoms; exercise caution in patients with pre-existing or recent history.
- Live vaccines: Safety of concurrent use not established.
- Immunomodulation: Avoid in significantly immunosuppressed patients, particularly those with recent or other biologic immunomodulating drugs.
- Laboratory monitoring: Monitor ALT/AST, neutrophils, and platelet counts according to standard practice.
Administrative & EUA Compliance Criteria- Patient-specific request on PBM EUA portal required (must include patient name, last four of SSN, date of birth, date of positive COVID-19 test)
- Documentation that patient meets all specified criteria is required
- Fact sheet for patients/parents/caregivers must be provided prior to administration (or as soon as practicable if delay endangers life)
- Patient or surrogate decision maker must have option to accept or refuse therapy
- Adverse drug events must be documented per local policy and reported to VA ADERS program
- FDA reporting required: patient-specific information, storage/cold-chain maintenance, lot numbers, administration timing, outcomes, and ADE documentation
Patient Eligibility & Clinical Status- Laboratory confirmed COVID-19 diagnosis
- Hospitalized for treatment of COVID-19
- Receiving systemic corticosteroids
- Requires supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
Laboratory Parameters- Most recent absolute neutrophil count (ANC) > 1000/mm3
- Most recent platelet count > 50,000/mm3
- Most recent AST and ALT < 10 x the upper limit of normal
- Without active hepatic disease or impairment
Contraindications & Precautions- No known hypersensitivity to tocilizumab (TOCI)
- No ongoing, active infection other than COVID-19
Dosing & Administration- Dose must be ≤ 800 mg (maximum dose per EUA)
- Recommended dose: 8 mg/kg as a single intravenous infusion over 60 minutes
- One additional dose may be administered at least 8 hours after the initial dose if symptoms worsen or do not improve with the first dose
Documentation & Monitoring Requirements- Information consistent with the TOCI fact sheet for patients, parents, and caregivers must be communicated prior to administration and documented in the medical record
- If communication delays administration to a degree that would endanger life, information must be provided to the caregiver as soon as feasible after administration (documented in the medical record)
- Patient-specific request on PBM EUA portal required prior to therapy initiation
- Post-administration tracking required: lot numbers administered, package arrival date, total doses given, start/completion dates and times of therapy, and any adverse events
- Any adverse drug events must be documented in accordance with local policy and placed in the VA ADERS program
Exclusion Criteria- Untreated active hepatitis B infection
- Untreated latent or active tuberculosis infection
- Active, clinically significant infection
- Active hepatic disease or hepatic impairment
- Baseline ALT and/or AST > 1.5 times the upper limit of normal (ULN)
- Baseline Absolute Neutrophil Count (ANC) < 2000/mm3
- Baseline platelet count <100,000/mm3
- Concomitant therapy with another biologic therapy for neuromyelitis optica spectrum disorder (NMOSD)
- Concomitant chronic therapy with intravenous immunoglobulin or plasma exchange (use of these treatments in exacerbations is reasonable)
- Pregnancy
Inclusion Criteria- Care provided by VA or VA Community Care neurology provider or locally designated expert
- Diagnosis of aquaporin-4 antibody positive NMOSD
- Completed hepatitis B screening (HBsAg, total anti-HBc and anti-HBs) and consult referral for hepatitis B management if either HBsAg or total anti-HBc positive
- All guideline recommended eligible immunizations administered at least 4 weeks prior to the start of treatment for live or live-attenuated vaccines, and whenever possible, at least 2 weeks prior to the start of treatment for inactivated vaccines
- Contraindication, intolerance, or lack of therapeutic response to rituximab
Additional Inclusion Criteria- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and to inform their provider of a known or suspected pregnancy
Formulation & Dosing Parameters- Evidenced formulation is the intravenous (IV) infusion; dosing 8mg/kg IV every 4 weeks
- Use in NMOSD is off-label
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TOFACITINIB TAB,ORAL
XELJANZ
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XELJANZ |
2017-02-27 |
Diagnosis & Monitoring- Definite or provisional diagnosis of active ankylosing spondylitis (or radiographic axial spondyloarthritis)
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Routine retesting for tuberculosis and hepatitis screening is not required for prescription renewals; consider retesting in high-risk patients
Active Infection & Immunodeficiency- Exclusion: Uncontrolled active infection (initiation/restart permitted once treatment for the infection is initiated)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (initiation permitted after starting prophylaxis)
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Exclusion: Congenital or acquired immunodeficiency
- Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Inclusion: Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Additional: If HBsAg-negative but anti-HBc-positive with consult deemed indicated, GI/liver or infectious diseases expert must advise on antiviral prophylaxis or preemptive monitoring for HBV reactivation
Malignancy- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless rheumatologist and oncologist agree that risk-benefits favor using the drug)
Hematologic & Hepatic Parameters- Exclusion: Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (initiation/restart permitted once lymphopenia, neutropenia, and/or anemia resolve)
- Exclusion: Severe hepatic impairment (Child-Pugh class C)
Cardiovascular Risk- Exclusion: At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh the anticipated benefits
Concomitant Medications & Vaccines- Exclusion: Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin) (except during treatment transition overlaps)
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Inclusion: Offered all age-appropriate vaccinations prior to initiating therapy
- Note: Recombinant zoster vaccine should be completed or at least initiated by the end of the first year, preferably when dosage is low, disease is stable, or at other times when a robust immune response to vaccination can be expected
Pregnancy, Lactation & Counseling- Exclusion: Pregnancy
- Exclusion: Breastfeeding
- Additional Inclusion (Females who can become pregnant): Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- Additional Inclusion (Females who are breastfeeding/providing breastmilk to an infant): Counseling provided on potential risks vs benefits of treatment
Prior Therapy Requirements- Inclusion: ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, not adequate after 3 months, or lost response
- Note: Criteria apply only to new starts; patients on tofacitinib who are stable (responded after 16 weeks and/or controlled on maintenance therapy) should not be switched to a criteria-required prior drug for nonmedical reasons
Dosing & Administration Considerations- Prescribed at the FDA-recommended dose for ankylosing spondylitis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Use with extreme caution in patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
Indication & Patient Population- Treatment of adult patients with active ankylosing spondylitis (AS)
- Patients must have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs)
- Active AS defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and BASDAI back pain score ≥ 4 despite ≥ 2 NSAIDs, or intolerance to NSAIDs
Dosing & Administration- Immediate-release: 5 mg twice daily
- Extended-release: 11 mg once daily
- Dose reduction required for patients receiving strong CYP3A4 inhibitors (e.g., ketoconazole) or moderate CYP3A4 inhibitors with a strong CYP2C19 inhibitor (e.g., fluconazole): immediate-release 5 mg once daily
- Dose reduction required for patients with moderate and severe renal impairment or moderate hepatic impairment: immediate-release 5 mg once daily
- Stable background therapies allowed: NSAIDs, methotrexate (≤ 25 mg/week), sulfasalazine (≤ 3 g/day), and oral glucocorticoids (≤ 10 mg/day prednisone equivalent)
Contraindications & Limitations of Use- Not recommended for use in combination with biologic disease modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine and cyclosporine
- Patients with current or prior treatment with targeted synthetic DMARDs (including JAK inhibitors) and current biologic DMARD therapy are excluded
Place in Therapy & Sequence of Use- Conditionally recommended as second-line therapy after TNFIs or IL-17AIs for active AS with inadequate response or intolerance to NSAID therapy
- Conditionally recommended as third-line therapy after IL-17AIs for active AS after primary nonresponse to TNFI
- Conditionally recommended against for active AS in secondary nonresponders to TNFI
Safety & Vaccination Requirements- Live vaccines should be administered at least 2 weeks prior to initiation of tofacitinib therapy
- All patients should complete the two-dose series of recombinant zoster vaccine (SHINGRIX) before becoming immunosuppressed
- If initiated before herpes zoster vaccination, vaccine series should preferably be given when immune response is likely strong and at least in process by the end of the first year of treatment
Infections- Exclusion: Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
Malignancy & Cardiovascular Risk- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- Exclusion: At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Laboratory & Hematologic Parameters- Exclusion: Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once resolved; requires confirmation by repeat testing)
Hepatic Screening & Management- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Exclusion: HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis; consultation with hepatologist or infectious diseases expert recommended)
- Inclusion: Current or past completion of hepatitis C screening (may initiate while waiting for results)
Concomitant Medications & Vaccines- Exclusion: Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin) [except overlaps during treatment transition]
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Pregnancy & Lactation- Exclusion: Pregnancy and females of reproductive potential not using adequate contraception
- Exclusion: Breastfeeding, unless breastfeeding occurs at least 18 hours after the most recent dose
Diagnosis, Monitoring & Prescribing Requirements- Inclusion: Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Inclusion: Tofacitinib prescribed at the FDA-recommended dose for psoriatic arthritis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Inclusion: Inflammatory articular disease (joint, spine, and/or entheseal) and a definite or provisional diagnosis of active psoriatic arthritis
- Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Inclusion: ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, or not adequate after 3 months
Exclusion Criteria- Uncontrolled active infection (initiation/restart permitted once treatment for the infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis (initiation permitted after starting prophylaxis)
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive without antiviral prophylaxis (initiation permitted after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are eligible)
- Congenital or acquired immunodeficiency
- Malignancy within the previous 5 years, excluding successfully treated nonmelanoma skin cancer or cervical cancer (unless treating rheumatologist and oncologist agree risk-benefits favor use)
- Increased risk of thrombosis or major adverse cardiovascular events where potential harms outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (initiation/restart permitted once cytopenias resolve)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin)
- Pregnancy
- Breastfeeding (unless occurring at least 18 hours after the most recent dose)
- Concomitant live or live-attenuated vaccines, or administration of inactivated/live/live-attenuated vaccines less than 2 weeks before initiation
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Moderate to severe active rheumatoid arthritis
- FDA-recommended dose for rheumatoid arthritis, with adjustments for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Tumor necrosis factor inhibitor (TNFi) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response
Clinical Precautions & Monitoring Guidelines- Extreme caution required for patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation when possible; recombinant zoster (SHINGRIX) vaccine should be completed or initiated by the end of the first year, preferably at low dosage, stable disease, or during periods expected to yield a robust immune response
Diagnosis & Indication- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging.
- Prescribed and monitored by a VA/VA Community Care gastroenterologist/hepatologist or locally-designated expert.
Screening & Laboratory Requirements- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA).
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs]).
- Current or past completion of hepatitis C screening.
- Routine retesting is not required for prescription renewals; retesting in high-risk patients should be considered.
Exclusion Criteria- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once infection treatment initiated).
- Untreated latent or active tuberculosis infection.
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis).
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated).
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer, unless treating gastroenterologist and oncologist agree risk-benefits favor use.
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits.
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once resolved).
- Severe hepatic impairment (Child-Pugh class C).
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin).
- Pregnancy and females of reproductive potential not using adequate contraception.
- Lactation/providing breastmilk to an infant unless it occurs at least 18 hours after the most recent dose.
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation.
Treatment History & Sequencing (Additional Inclusion Criteria)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar is the preferred TNFI in UC).
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in the presence of adequate TNFI levels (mechanistic failure).
- Loss of response to a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure.
Special Populations & Counseling- If HBsAg-negative but anti-HBc-positive: A GI/liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation.
- For women who can become pregnant: Pregnancy status verified. Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
Dosing & Monitoring- Prescribe at the FDA-recommended dose for UC, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias.
- Discontinue if no response after 16 weeks of induction with tofacitinib 10 mg twice daily (or extended-release tofacitinib 22 mg once daily).
- Patients achieving response or remission should have dose reduced to 5 mg twice daily (or 11 mg once daily of extended-release tofacitinib) and use the lowest effective dose needed to maintain response.
- Use of higher induction doses beyond induction should be limited to patients with loss of response for the shortest duration clinically feasible.
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| ▸ |
TOFACITINIB TAB,SA
XELJANZ XR
|
XELJANZ XR |
2017-02-27 |
Diagnosis & Monitoring- Definite or provisional diagnosis of active ankylosing spondylitis (or radiographic axial spondyloarthritis)
- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Routine retesting for tuberculosis and hepatitis screening is not required for prescription renewals; consider retesting in high-risk patients
Active Infection & Immunodeficiency- Exclusion: Uncontrolled active infection (initiation/restart permitted once treatment for the infection is initiated)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (initiation permitted after starting prophylaxis)
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
- Exclusion: Congenital or acquired immunodeficiency
- Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Inclusion: Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Additional: If HBsAg-negative but anti-HBc-positive with consult deemed indicated, GI/liver or infectious diseases expert must advise on antiviral prophylaxis or preemptive monitoring for HBV reactivation
Malignancy- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless rheumatologist and oncologist agree that risk-benefits favor using the drug)
Hematologic & Hepatic Parameters- Exclusion: Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (initiation/restart permitted once lymphopenia, neutropenia, and/or anemia resolve)
- Exclusion: Severe hepatic impairment (Child-Pugh class C)
Cardiovascular Risk- Exclusion: At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh the anticipated benefits
Concomitant Medications & Vaccines- Exclusion: Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin) (except during treatment transition overlaps)
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Inclusion: Offered all age-appropriate vaccinations prior to initiating therapy
- Note: Recombinant zoster vaccine should be completed or at least initiated by the end of the first year, preferably when dosage is low, disease is stable, or at other times when a robust immune response to vaccination can be expected
Pregnancy, Lactation & Counseling- Exclusion: Pregnancy
- Exclusion: Breastfeeding
- Additional Inclusion (Females who can become pregnant): Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
- Additional Inclusion (Females who are breastfeeding/providing breastmilk to an infant): Counseling provided on potential risks vs benefits of treatment
Prior Therapy Requirements- Inclusion: ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, not adequate after 3 months, or lost response
- Note: Criteria apply only to new starts; patients on tofacitinib who are stable (responded after 16 weeks and/or controlled on maintenance therapy) should not be switched to a criteria-required prior drug for nonmedical reasons
Dosing & Administration Considerations- Prescribed at the FDA-recommended dose for ankylosing spondylitis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Use with extreme caution in patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
Indication & Patient Population- Treatment of adult patients with active ankylosing spondylitis (AS)
- Patients must have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs)
- Active AS defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and BASDAI back pain score ≥ 4 despite ≥ 2 NSAIDs, or intolerance to NSAIDs
Dosing & Administration- Immediate-release: 5 mg twice daily
- Extended-release: 11 mg once daily
- Dose reduction required for patients receiving strong CYP3A4 inhibitors (e.g., ketoconazole) or moderate CYP3A4 inhibitors with a strong CYP2C19 inhibitor (e.g., fluconazole): immediate-release 5 mg once daily
- Dose reduction required for patients with moderate and severe renal impairment or moderate hepatic impairment: immediate-release 5 mg once daily
- Stable background therapies allowed: NSAIDs, methotrexate (≤ 25 mg/week), sulfasalazine (≤ 3 g/day), and oral glucocorticoids (≤ 10 mg/day prednisone equivalent)
Contraindications & Limitations of Use- Not recommended for use in combination with biologic disease modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine and cyclosporine
- Patients with current or prior treatment with targeted synthetic DMARDs (including JAK inhibitors) and current biologic DMARD therapy are excluded
Place in Therapy & Sequence of Use- Conditionally recommended as second-line therapy after TNFIs or IL-17AIs for active AS with inadequate response or intolerance to NSAID therapy
- Conditionally recommended as third-line therapy after IL-17AIs for active AS after primary nonresponse to TNFI
- Conditionally recommended against for active AS in secondary nonresponders to TNFI
Safety & Vaccination Requirements- Live vaccines should be administered at least 2 weeks prior to initiation of tofacitinib therapy
- All patients should complete the two-dose series of recombinant zoster vaccine (SHINGRIX) before becoming immunosuppressed
- If initiated before herpes zoster vaccination, vaccine series should preferably be given when immune response is likely strong and at least in process by the end of the first year of treatment
Infections- Exclusion: Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
Malignancy & Cardiovascular Risk- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- Exclusion: At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Laboratory & Hematologic Parameters- Exclusion: Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once resolved; requires confirmation by repeat testing)
Hepatic Screening & Management- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Exclusion: HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis; consultation with hepatologist or infectious diseases expert recommended)
- Inclusion: Current or past completion of hepatitis C screening (may initiate while waiting for results)
Concomitant Medications & Vaccines- Exclusion: Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin) [except overlaps during treatment transition]
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Pregnancy & Lactation- Exclusion: Pregnancy and females of reproductive potential not using adequate contraception
- Exclusion: Breastfeeding, unless breastfeeding occurs at least 18 hours after the most recent dose
Diagnosis, Monitoring & Prescribing Requirements- Inclusion: Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Inclusion: Tofacitinib prescribed at the FDA-recommended dose for psoriatic arthritis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Inclusion: Inflammatory articular disease (joint, spine, and/or entheseal) and a definite or provisional diagnosis of active psoriatic arthritis
- Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
- Inclusion: ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, or not adequate after 3 months
Exclusion Criteria- Uncontrolled active infection (initiation/restart permitted once treatment for the infection is initiated)
- Untreated latent or active tuberculosis infection
- Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis (initiation permitted after starting prophylaxis)
- HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive without antiviral prophylaxis (initiation permitted after starting prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are eligible)
- Congenital or acquired immunodeficiency
- Malignancy within the previous 5 years, excluding successfully treated nonmelanoma skin cancer or cervical cancer (unless treating rheumatologist and oncologist agree risk-benefits favor use)
- Increased risk of thrombosis or major adverse cardiovascular events where potential harms outweigh anticipated benefits
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (initiation/restart permitted once cytopenias resolve)
- Severe hepatic impairment (Child-Pugh class C)
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin)
- Pregnancy
- Breastfeeding (unless occurring at least 18 hours after the most recent dose)
- Concomitant live or live-attenuated vaccines, or administration of inactivated/live/live-attenuated vaccines less than 2 weeks before initiation
Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
- Moderate to severe active rheumatoid arthritis
- FDA-recommended dose for rheumatoid arthritis, with adjustments for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
- Offered all age-appropriate vaccinations prior to initiating therapy
- Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
- Tumor necrosis factor inhibitor (TNFi) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response
Clinical Precautions & Monitoring Guidelines- Extreme caution required for patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
- Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
- Vaccinations should be updated prior to initiation when possible; recombinant zoster (SHINGRIX) vaccine should be completed or initiated by the end of the first year, preferably at low dosage, stable disease, or during periods expected to yield a robust immune response
Diagnosis & Indication- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging.
- Prescribed and monitored by a VA/VA Community Care gastroenterologist/hepatologist or locally-designated expert.
Screening & Laboratory Requirements- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA).
- Completed hepatitis B screening (at minimum, HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs]).
- Current or past completion of hepatitis C screening.
- Routine retesting is not required for prescription renewals; retesting in high-risk patients should be considered.
Exclusion Criteria- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once infection treatment initiated).
- Untreated latent or active tuberculosis infection.
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis).
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated).
- Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer, unless treating gastroenterologist and oncologist agree risk-benefits favor use.
- At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits.
- Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once resolved).
- Severe hepatic impairment (Child-Pugh class C).
- Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin).
- Pregnancy and females of reproductive potential not using adequate contraception.
- Lactation/providing breastmilk to an infant unless it occurs at least 18 hours after the most recent dose.
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation.
Treatment History & Sequencing (Additional Inclusion Criteria)- Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar is the preferred TNFI in UC).
- Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in the presence of adequate TNFI levels (mechanistic failure).
- Loss of response to a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure.
Special Populations & Counseling- If HBsAg-negative but anti-HBc-positive: A GI/liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation.
- For women who can become pregnant: Pregnancy status verified. Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
Dosing & Monitoring- Prescribe at the FDA-recommended dose for UC, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias.
- Discontinue if no response after 16 weeks of induction with tofacitinib 10 mg twice daily (or extended-release tofacitinib 22 mg once daily).
- Patients achieving response or remission should have dose reduced to 5 mg twice daily (or 11 mg once daily of extended-release tofacitinib) and use the lowest effective dose needed to maintain response.
- Use of higher induction doses beyond induction should be limited to patients with loss of response for the shortest duration clinically feasible.
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| ▸ |
TRAMADOL/ ACETAMINOPHEN TAB
TRAMADOL HCL-ACETAMINOPHEN, ULTRACET
|
TRAMADOL HCL-ACETAMINOPHEN, ULTRACET |
2017-02-27 |
Continuity of Care- Veteran is transitioning care from the Department of Defense to VHA
- Must also meet one of the following Additional Inclusion Criteria:
- The medication is safe and clinically appropriate as determined by a VA prescriber using shared decision making
- The medication is indicated for tapering the dose or slowly discontinuing therapy as determined by a VA prescriber using shared decision making
Non-Continuity of Care- Inadequate response to or unable to adhere to individual components
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| ▸ |
TRANEXAMIC ACID TAB
LYSTEDA
|
LYSTEDA |
2017-02-27 |
Exclusion Criteria- Hypersensitivity
- Concomitant use of combined hormonal contraceptives (contraindicated per U.S. product label due to increased risk of venous or arterial thromboembolism based on pharmacodynamics and postmarketing events, particularly in patients who are obese or cigarette smokers)
- History of or active thromboembolic disease or intrinsic risk of thrombosis or thromboembolism, including retinal vein or artery occlusion
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| ▸ |
TREPROSTINIL SOLN,INHL
TYVASO, TYVASO INSTITUTIONAL START KIT, TYVASO REFILL KIT, TYVASO STARTER KIT
|
TYVASO, TYVASO INSTITUTIONAL START KIT, TYVASO REFILL KIT, TYVASO STARTER KIT |
2017-02-27 |
Provider & Care Setting Requirements- Care provided by a VA or VA Community Care provider experienced in the management of PAH
Diagnostic & Hemodynamic Criteria- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis
- Mean pulmonary artery pressure greater than 20 mmHg
- Pulmonary capillary wedge pressure 15 mmHg or less
- Pulmonary vascular resistance greater than 2 Wood units
Classification & Clinical Status- World Health Organization (WHO) Group 1 PAH
- Unacceptable or deteriorating clinical status on PAH-directed therapy with, or not a candidate for, an endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5i)
- Efficacy established in patients with NYHA Functional Class III symptoms
Formulation & Dosing Preferences- Nebulized solution preferred if patient requires more than one cartridge or capsule per dose using the DPI (e.g., >64 mcg of TYVASO or >106 mcg of YUTREPIA)
- Dry powder inhalers (DPIs) reserved for patients with documented inability to use the nebulized product
Adjudication & Documentation- Individual cases that are exceptions to inclusion/exclusion criteria should be adjudicated at the local facility level per P&T committee and pharmacy services policy/procedures
- Product information should be consulted for detailed prescribing information
Provider & Care Setting Requirements- Care must be provided by a VA or VA Community Care provider experienced in the management of pulmonary hypertension (PH).
Diagnosis & Indication Criteria- Definitive, confirmed diagnosis of interstitial lung disease (ILD) (e.g., diffuse parenchymal lung disease on chest CT).
- Examples of ILD include idiopathic interstitial pneumonia, combined pulmonary fibrosis and emphysema, connective tissue disease, and chronic hypersensitivity pneumonitis.
- Definitive, confirmed diagnosis of WHO Group 3 PH associated with ILD.
Hemodynamic Criteria (via Right-Heart Catheterization)- Mean pulmonary artery pressure of at least 25 mmHg.
- Pulmonary capillary wedge pressure of 15 mmHg or less.
- Pulmonary vascular resistance greater than 3 Wood units.
Formulation & Dosing Preferences- Nebulized solution is preferred for patients requiring more than one cartridge per dose using the dry powder inhaler (DPI) (e.g., >64 mcg of TYVASO or >106 mcg of YUTREPIA).
- DPI should be reserved for patients with a documented inability to use the nebulized product.
Adjudication & Clinical Management- All inclusion criteria must be met.
- Individual cases that are exceptions to exclusion/inclusion criteria or require formulation preference adjustments should be adjudicated at the local facility level per P&T Committee and Pharmacy Services policies/procedures.
Indication & Patient Population- • Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability
- • Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability
- • PH-ILD patient criteria: ILD diagnosed by chest CT, Group 3 PH confirmed by right heart catheterization (RHC) with pulmonary vascular resistance (PVR) >3 Wood units, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, mean pulmonary arterial pressure (mPAP) ≥25 mm Hg, and baseline 6-minute walk distance (6MWD) ≥100 m
Dosing & Administration- • Dry powder inhaler (DPI) strengths: 16 mcg, 32 mcg, 48 mcg, and 64 mcg single-dose color-coded cartridges
- • Dosing frequency: 1 breath per cartridge, 4 times daily, administered about 4 hours apart
- • Titration regimen: Initial dose of 3 breaths (6 mcg per breath) 4 times daily; target dose of 9 breaths; maximum dose of 12 breaths
- • Cartridge-to-strength mapping: 6 to 7 breaths corresponds to 32 mcg, 8 to 10 breaths to 48 mcg, and 11 to 12 breaths to 64 mcg
Safety, Warnings & Monitoring- • Contraindications: None stated
- • Boxed Warnings: None stated for the drug itself
- • Warnings/Precautions: Risk of symptomatic hypotension, bleeding (due to platelet aggregation inhibition), and bronchospasm; drug interactions with CYP2C8 inhibitors (increased adverse effects) or CYP2C8 inducers (decreased effectiveness)
- • Adverse Reactions: Cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea
- • Excipient consideration: Contains fumaryl diketopiperazine (FDKP); while FDKP carries a boxed warning for acute bronchospasm risk in chronic lung disease per other products, no bronchospastic adverse events or safety signals were identified in clinical studies
Storage & Device Management- • Cartridges must be stored in a refrigerator; room temperature excursions are permitted but shorten shelf life
- • DPI should be at room temperature for 10 minutes prior to use
- • Inhaler device is reusable for 7 days, then must be replaced/discarded
Place in Therapy & Efficacy Considerations- • Indicated based on a placebo-controlled trial demonstrating improved 6MWD, NT-proBNP ratio, and reduced clinical worsening
- • May be considered as an alternative to the liquid inhalation nebulized formulation for patients with PAH or PH-ILD
- • Long-term data are lacking; European guidelines provide a weak recommendation for use in PH-ILD
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TRIMETHOBENZAMIDE CAP,ORAL
TRIMETHOBENZAMIDE HCL
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TRIMETHOBENZAMIDE HCL |
2017-02-27 |
Inclusion Criteria- Provider/Setting: Care provided by a VA or VA Community Care neurologist
- Concomitant Therapy: Prescribed in conjunction with apomorphine
- Indication: Recommended to control nausea and vomiting that can result from apomorphine treatment
- General Requirement: All of the following criteria must be met
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ULIPRISTAL TAB
ELLA
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ELLA |
2017-02-27 |
Indication & Efficacy- Highly effective in preventing pregnancy when used as directed
- Classified as a combination hormonal contraceptive agent
Regimen & Administration- Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills
Clinical Considerations & Management- Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
- Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)
Formulary & Substitution Criteria- Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
- Product availability varies and the listed products are not comprehensive
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URIDINE POWDER,ORAL
VISTOGARD, XURIDEN
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VISTOGARD, XURIDEN |
2017-02-27 |
Inclusion Criteria- Patient exhibits severe or life-threatening toxicity within 96 hours following the end of fluorouracil continuous IV infusion (CIVI) or capecitabine administration.
- An overdose of fluorouracil CIVI or capecitabine is suspected, regardless of the presence of symptoms.
Exclusion Criteria- Time from end of fluorouracil infusion or last capecitabine dose is greater than 4 days (96 hours).
Dosing & Administration- Premedication: Ondansetron 8 mg orally, given 20 minutes prior to each uridine dose.
- Dosage: 10 grams (1 packet) orally every 6 hours for 20 doses (full course), without regard to meals. Do not chew.
- Oral Administration: Mix each packet of granules with 3-4 ounces of soft foods (e.g., applesauce, pudding, yogurt) and ingest within 30 minutes. Drink at least 4 ounces of water. Do not chew the granules.
- Vomiting Management: If patient vomits within 2 hours of a dose, initiate another complete dose as soon as possible after vomiting episode. Administer next dose at regularly scheduled time.
- Missed Dose Management: Administer dose as soon as possible. Give next dose at regularly scheduled time.
- NG/G-Tube Administration: Prepare about 4 ounces (100 ml) of a food starch-based thickening product in water and stir until dissolved. Crush contents of a 10 gram packet to a fine powder. Add crushed granules to prepared thickening product and mix thoroughly. After administration, flush tube with water.
Supportive Care & Management- While awaiting antidote: Admit patient to inpatient unit and provide supportive care to reduce symptom severity (e.g., IV hydration, electrolyte replacement, treatment of diarrhea, mouth/skin care, granulocyte colony-stimulating factor administration, continuous cardiac monitoring).
- Avoid contraindicated medications that might interfere with clearance of fluorouracil or capecitabine (e.g., metronidazole, leucovorin, cimetidine, thiazide diuretics).
- Continue close monitoring post-hospitalization for possibly delayed adverse effects, particularly throughout the expected neutrophil nadir. Granulocyte colony-stimulating factors and antibiotics may need to be continued.
Clinical Considerations & Definitions- Uridine triacetate is NOT to be used to minimize non-emergent/non-life-threatening toxicity of fluorouracil or capecitabine, as use in this manner may diminish the efficacy of these drugs.
- Examples of early onset fluoropyrimidine toxicities include: Gastrointestinal (oral mucositis, diarrhea, anorexia), Cardiac (arrhythmia, chest pain, cardiac arrest), Hematologic (neutropenia, thrombocytopenia), Dermatologic (erythema, desquamation), and Neurologic/CNS (altered mental status, seizures, confusion).
- Overdose definition: Patient receives 10% more than intended dose (>110% of planned dose) or received full dose at an infusion rate 25% more than intended rate.
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URIDINE POWDER,ORAL
VISTOGARD, XURIDEN
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VISTOGARD, XURIDEN |
2017-02-27 |
Inclusion Criteria- Patient exhibits severe or life-threatening toxicity within 96 hours following the end of fluorouracil continuous IV infusion (CIVI) or capecitabine administration.
- An overdose of fluorouracil CIVI or capecitabine is suspected, regardless of the presence of symptoms.
Exclusion Criteria- Time from end of fluorouracil infusion or last capecitabine dose is greater than 4 days (96 hours).
Dosing & Administration- Premedication: Ondansetron 8 mg orally, given 20 minutes prior to each uridine dose.
- Dosage: 10 grams (1 packet) orally every 6 hours for 20 doses (full course), without regard to meals. Do not chew.
- Oral Administration: Mix each packet of granules with 3-4 ounces of soft foods (e.g., applesauce, pudding, yogurt) and ingest within 30 minutes. Drink at least 4 ounces of water. Do not chew the granules.
- Vomiting Management: If patient vomits within 2 hours of a dose, initiate another complete dose as soon as possible after vomiting episode. Administer next dose at regularly scheduled time.
- Missed Dose Management: Administer dose as soon as possible. Give next dose at regularly scheduled time.
- NG/G-Tube Administration: Prepare about 4 ounces (100 ml) of a food starch-based thickening product in water and stir until dissolved. Crush contents of a 10 gram packet to a fine powder. Add crushed granules to prepared thickening product and mix thoroughly. After administration, flush tube with water.
Supportive Care & Management- While awaiting antidote: Admit patient to inpatient unit and provide supportive care to reduce symptom severity (e.g., IV hydration, electrolyte replacement, treatment of diarrhea, mouth/skin care, granulocyte colony-stimulating factor administration, continuous cardiac monitoring).
- Avoid contraindicated medications that might interfere with clearance of fluorouracil or capecitabine (e.g., metronidazole, leucovorin, cimetidine, thiazide diuretics).
- Continue close monitoring post-hospitalization for possibly delayed adverse effects, particularly throughout the expected neutrophil nadir. Granulocyte colony-stimulating factors and antibiotics may need to be continued.
Clinical Considerations & Definitions- Uridine triacetate is NOT to be used to minimize non-emergent/non-life-threatening toxicity of fluorouracil or capecitabine, as use in this manner may diminish the efficacy of these drugs.
- Examples of early onset fluoropyrimidine toxicities include: Gastrointestinal (oral mucositis, diarrhea, anorexia), Cardiac (arrhythmia, chest pain, cardiac arrest), Hematologic (neutropenia, thrombocytopenia), Dermatologic (erythema, desquamation), and Neurologic/CNS (altered mental status, seizures, confusion).
- Overdose definition: Patient receives 10% more than intended dose (>110% of planned dose) or received full dose at an infusion rate 25% more than intended rate.
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VEDOLIZUMAB INJ,LYPHL
ENTYVIO
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ENTYVIO |
2017-02-27 |
Exclusion Criteria- Untreated latent or active tuberculosis infection
- Uncontrolled, active, severe infection (may start/restart once treatment for the infection is initiated)
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
- Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients can be treated)
- Congenital or acquired immunodeficiency
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
- Concomitant treatment with drugs that have a contraindicated drug interaction (e.g., Bacillus Calmette-Guerin [BCG] vaccine) unless risk-benefits favor use
- Primary nonresponse to natalizumab
Mandatory Inclusion Criteria- Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally designated expert
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
- Completed hepatitis B screening (HBsAg, total antibody to hepatitis B core antigen [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
- Current or past completion of hepatitis C screening (may initiate while waiting for test results)
Additional Clinical Indications & Scenarios- Current or prior overall physician assessment of “moderate to severe” CD or UC confirmed by endoscopy or imaging, and TNFI is medically inadvisable
- Current or prior overall physician assessment of “moderate to severe” CD or UC, and primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in the presence of adequate TNFI levels (mechanistic failure)
- Current or prior overall physician assessment of “moderate to severe” CD and loss of response to infliximab/biosimilar and another TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
- Current or prior overall physician assessment of “moderate to severe” UC and loss of response to a TNFI (infliximab/biosimilar preferred) despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure
- No prior TNFI was deemed required because of documented current or prior overall physician assessment of “moderate” CD or UC disease or documented absence of extraintestinal manifestations
- Underwent IPAA and has documented chronic antibiotic-refractory or -dependent CD or UC pouchitis with intolerance, loss of response, or medical inadvisability to long-term antibiotic therapy (no prior TNFI required)
- Maintenance of clinical response or remission achieved with cyclosporine rescue therapy when immunomodulator maintenance is medically inadvisable (used for acute, severe UC)
- Prevention of recurrence after surgery for CD if TNFI therapy is medically inadvisable
Patient-Specific Considerations- If HBsAg-negative but anti-HBc-positive: A GI/liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
Inclusion Criteria- Had a clinical response after Week 6 following vedolizumab intravenous induction doses at Weeks 0 and 2
- OR is receiving intravenous doses of vedolizumab to maintain clinical remission
Clinical Response Definitions- Ulcerative Colitis: Reduction in total Mayo score of ≥ 3 points and ≥ 30% from baseline with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1.
- Crohn's Disease: ≥ 70-point decrease in Crohn's Disease Activity Index (CDAI) score from baseline.
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VEMURAFENIB TAB
ZELBORAF
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ZELBORAF |
2017-02-27 |
Exclusion Criteria- Uncorrectable electrolyte abnormalities, QTc ≥500msec, or long QT syndrome
- Use of concomitant medications known to prolong QT interval
- Severe baseline hepatic impairment (Child-Pugh Class C) or severe renal impairment (creatinine clearance <30 mL/min)
- Active or symptomatic brain metastases
- Pregnancy (known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria- Care provided by a VA/VA purchased care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Female patients of child-bearing potential: counseling provided on contraception during treatment and for 2 weeks after completing treatment and risks vs. benefits of treatment
Indications / Additional Inclusion Criteria (One must be met)- Unresectable or metastatic melanoma with BRAF V600E mutation
- In combination with cobimetinib for unresectable or metastatic melanoma with BRAF V600E mutation if patient cannot tolerate dabrafenib plus trametinib
- Erdheim-Chester Disease (ECD) with BRAF V600 mutation
Treatment Preferences- Dabrafenib plus trametinib is the preferred BRAF + MEK inhibitor combination.
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VENETOCLAX TAB
VENCLEXTA, VENCLEXTA STARTING PACK
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VENCLEXTA, VENCLEXTA STARTING PACK |
2017-02-27 |
Exclusion Criteria- Patient is unable to comply with intense Tumor Lysis Syndrome (TLS) monitoring & hydration requirements that begin prior to first dose and continue during ramp-up phase
- Intolerance to BOTH xanthine oxidase inhibitors AND rasburicase
- Evidence of clinically significant conditions, including:
- • Uncontrolled systemic infection
- • Active and uncontrolled autoimmune cytopenias (AIHA, ITP)
- Richter’s transformation
- Severe hepatic dysfunction (Bilirubin > 3x ULN) – has not been studied
- Severe renal impairment (Clcr < 30 ml/min)
Inclusion Criteria: CLL/SLL- Diagnosis of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL) with/without deletion 17p
- ANC > 1000 cells/mm3 and/or platelet count > 30,000 cells/mm3 unless bone marrow involvement
- ECOG Performance Status 0-2
- Must be on tumor lysis prophylaxis
Inclusion Criteria: AML- Newly diagnosed Acute Myeloid Leukemia (AML)
- Age > 75 years OR not a candidate for intensive induction chemotherapy
- WBC < 25 x 109/L prior to start of therapy; cytoreduction prior to therapy may be required
- ECOG Performance Status 0-3
- Must be on tumor lysis prophylaxis
Additional/General Inclusion Criteria- Care provided by a VA or VA purchased care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- Mandatory identification of CYP3A4 inhibitors as they are contraindicated during ramp-up phase
- Mandatory assessment of tumor burden (outpatient vs. inpatient care)
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VISMODEGIB CAP,ORAL
ERIVEDGE
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ERIVEDGE |
2017-02-27 |
Exclusion Criteria- AST and ALT > 3 X the upper limit of normal or total bilirubin >1.5 X the upper limit of normal (or >3 X the upper limit of normal for patients with Gilbert disease)
- Creatinine clearance <30 mL/min
- Patient who is unable to swallow intact capsule
- Patients currently receiving systemic therapy for basal cell carcinoma
- Patient refuses transfer of care to VA Dermatologist or Oncologist
- Pregnancy or lactation
Inclusion Criteria- Goals of care and role of Palliative Care consult has been discussed and documented
- Diagnosis of metastatic basal cell carcinoma, or locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation or a diagnosis of basal-cell nevus (Gorlin) syndrome
- ECOG Performance Status 0-2
- Pregnancy must be excluded prior to receiving vismodegib and patient provided contraceptive counseling on potential risk vs benefit of taking vismodegib if patient were to become pregnant; female patients of childbearing potential and men with female partners of childbearing potential are required to use 2 methods of contraception
Dosage and Administration- Recommended dose is one 150mg capsule orally once daily until disease progression or unacceptable toxicity
- May be taken with or without food
- Capsules should remain whole and not opened or crushed
- Caution if given concomitantly with drugs that alter the pH of the upper GI tract
Monitoring- Metastatic disease: Assess radiographically at baseline and then every 2 months
- Locally advanced disease: If measurable disease assessed radiographically, assess at baseline and then every 2 months; if not measurable radiographically, assess by physical exam (digital photography) at baseline and every 2 months
- Assess renal and hepatic function periodically due to lack of data in safety and effectiveness in patients with either renal or hepatic impairment
Reproductive Safety and Counseling- Vismodegib may cause fetal death or severe birth defects; both female and male patients should be advised of the risk for fetal death or severe birth defects and the need for contraception during and after treatment
- Female patients should use a highly effective form of contraception starting before the first dose and continuing for 7 months after the last dose
- Male patients with female partners of childbearing potential should use condoms during vismodegib therapy and for 2 months after the last dose
- If pregnancy occurs or exposure occurs, inform of risk to fetus; exposure during pregnancy should be reported to the Genentech Adverse Event Line at 1-888-835-2555
- Women exposed to vismodegib during pregnancy can participate in a pharmacovigilance program by contacting Genentech at the same number
Blood Donation- Advise patients not to donate blood or blood components during vismodegib therapy and for at least 7 months after the last dose of vismodegib
Drug Interactions and Pharmacokinetics- Drugs that alter the pH of the upper GI tract (e.g., proton pump inhibitors, H2 antagonists, and antacids) may alter the solubility of vismodegib and reduce bioavailability
- No formal studies have been conducted to evaluate the effect of gastric pH on systemic exposure of vismodegib; increasing the dose is not likely to compensate for the loss of exposure
Discontinuation Criteria- Progressive disease (assess every 2 months): an increase in size of 20% or more in externally visible or radiographic dimension, new ulceration, or a new lesion; if multiple measurable lesions, the sum of the longest diameters should be used
- Unacceptable toxicity
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VORINOSTAT CAP,ORAL
ZOLINZA
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ZOLINZA |
2017-02-27 |
Indication- Cutaneous T-cell Lymphoma (CTCL)
Inclusion Criteria- Stage histological diagnosis of CTCL with advanced disease documented as Stage IIb or higher including Sézary syndrome
- Documented contraindication or treatment failure of radiotherapy, total skin electron beam therapy, no PUVA, or extracorporeal photopheresis
- Documented current or prior treatment or treatment failure of interferon-alpha and oral bexarotene
- Age > 18 years
- Ability to swallow capsules
- Adequate hepatic, renal, and hematological function at baseline
- Prior chemotherapy has been discontinued for at least 3 weeks and the patient has recovered from toxicities of prior therapy; exception in patients with rapidly progressing disease who should be considered for therapy on an individual basis
Exclusion Criteria- Hypersensitivity to vorinostat
- Pregnant women or women intending to become pregnant (Pregnancy Category D)
- Use for other indications (such as for colorectal cancer) or in combination with other chemotherapeutic agents is not recommended at this time due to insufficient evidence
Dosing- 400 mg orally once daily with food
- For those intolerant to therapy, dose can be reduced to 300 mg daily or further to 300 mg for 5 consecutive days each week
Monitoring- Severe thrombocytopenia and gastrointestinal bleeding (reported with concomitant use of vorinostat and other HDAC inhibitors like valproic acid): Monitor platelet count every 2 weeks during the first 2 months
- Thrombocytopenia and anemia: Doses should be modified or therapy discontinued according to any reductions in platelet counts and/or hemoglobin
- Discuss appropriate methods of contraception
- Pre-existing nausea, vomiting, and diarrhea should be adequately controlled before beginning therapy
- Hypokalemia or hypomagnesemia should be corrected prior to administration; potassium and magnesium should be considered in patients with nausea, vomiting, diarrhea, fluid imbalance or cardiac symptoms
- QTc prolongation has been reported; close monitoring should occur particularly among patients taking drugs known to prolong the QTc interval
- Pulmonary embolism and deep vein thrombosis have been reported; physicians should be alert to signs and symptoms, particularly in patients with a prior history of thromboembolic events
- Prolongation of prothrombin time and increased INR has occurred among some patients taking vorinostat and warfarin concomitantly
- Serum glucose should be monitored, especially in diabetic patients; adjustment of diet and/or therapy may be necessary
Discontinuation- Vorinostat is given until disease progression or intolerance to therapy occurs
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YELLOW FEVER VACCINE INJ
DILUENT FOR STAMARIL, STAMARIL, YF-VAX
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DILUENT FOR STAMARIL, STAMARIL, YF-VAX |
2017-02-27 |
Indications & Use- Recommended for travelers traveling to or living in areas at risk for yellow fever transmission in South America and Africa
- May be required for entry into certain countries
- Prevention is critical to lower disease risk and mortality due to the absence of specific antiviral treatment
Contraindications- Acute hypersensitivity to a prior dose of YF vaccine or any of its components
- Severely immunosuppressed individuals
- Thymic disorders with abnormal immune function (e.g., myasthenia gravis, thymoma)
- Women who are breastfeeding an infant younger than 9 months of age
Warnings & Precautions- Severe allergic reactions: Patients should be monitored for 15 minutes
- YF vaccine associated viscerotropic disease: Age greater than 60 years is a risk factor
- YF vaccine associated neurotropic disease: Age greater than 60 years and immunosuppression are risk factors
- Should not be administered intravascular, intramuscular or intradermal
- Syncope
- Testing for hypersensitivity can be considered for those with egg hypersensitivity
- Rate of seroconversion is reduced in those with HIV infection; documentation of protective antibody is recommended before travel
- Pregnancy
- Lactation: Vaccine-associated neurotropic disease has been reported in infants less than one month of age who were exclusively breastfed by vaccinated mothers
- Increased risk of severe adverse events in individuals 60 years of age or older
Adverse Reactions- Common: Fever, headache, backache, myalgias, injection site inflammation
- Severe/Uncommon: Hypersensitivity reactions (including anaphylaxis), YF vaccine associated neurologic disease (meningoencephalitis or Guillain-Barre), YF vaccine associated viscerotropic disease (mimics yellow fever, can result in multi-organ failure and death)
Dosage & Administration- Reconstitute freeze-dried, lyophilized live-attenuated strain (17D) with supplied sodium chloride diluent
- Allow mixture to sit for 1-2 minutes before swirling carefully until uniform
- Using aseptic technique and a separate needle and syringe, withdraw 0.5 mL
- Administer as a 0.5 mL subcutaneous injection to the upper-outer triceps
- Must be given within 60 minutes of reconstituting the vial
- Protective antibodies take 7-10 days to develop; international certificates are valid beginning 10 days after vaccination date
Storage & Handling- Store at 2-8°C (35-46°F)
- Do not freeze
Drug Interactions- Other live-attenuated viral vaccines: Should be given at the same time or at least 30 days apart
- Oral typhoid vaccine and inactivated vaccines: Can be administered at any time relative to YF vaccine
- PPD testing: Should be performed before or on the same day as YF vaccine, or 4 or more weeks after
Special Populations & Booster Recommendations- General protection is long-lasting; routine booster requirement was removed per 2014 WHO policy (travelers should verify specific entry requirements)
- ACIP recommends an additional dose(s) for:
- Women who were pregnant when first vaccinated (receive 1 additional dose)
- Hematopoietic stem cell transplant recipients vaccinated prior to transplantation (receive additional post-transplant dose before next travel; must be sufficiently immunocompetent)
- HIV+ patients (booster every 10 years if no contraindications or precautions exist)
- Travelers who received initial vaccination at least 10 years ago and are at higher risk (e.g., prolonged stay in an endemic area)
Monitoring & Documentation Requirements- Document date of vaccination, product name, lot number, expiration date, injection site, and name of person administering the vaccine
- Document any precautions or contraindications and planned travel destinations
- Report adverse events to VA ADERS as a MedWatch report
- Serious adverse events are defined as: death or life-threatening events; hospitalization or prolongation of an existing hospitalization; persistent or significant incapacity/substantial disruption of normal life functions; congenital anomaly/birth defect; or medical/surgical intervention needed to prevent death, life-threatening event, hospitalization, disability, or congenital anomaly
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ZIV-AFLIBERCEPT INJ
ZALTRAP
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ZALTRAP |
2017-02-27 |
Exclusion Criteria- Major surgery within prior 28 days
- Non-healing wound or fracture
- Recent venous or arterial thromboembolic event
- Nephrotic syndrome or thrombotic microangiopathy (TMA)
- Uncontrolled hypertension
- Chronic diarrhea and/or dehydration issues
- Bleeding issues or at high risk of bleed (i.e. GI bleed, hematuria, etc.)
- Pregnancy
- Lactating
Inclusion Criteria- Care provided by a VA/VA Community Care Hematology or Oncology provider
- Goals of care and role of palliative care consult has been discussed and documented
- Eastern Cooperative Oncology Group Performance Status 0 or 1
- Metastatic colorectal cancer with progressive disease on an oxaliplatin-based regimen
- Intended use of ziv-aflibercept is in combination with fluorouracil, leucovorin, irinotecan (i.e. FOLFIRI)
- Patient is irinotecan-naïve
- Adequate hematologic function defined as Absolute Neutrophil Count > 1500/mm3 and platelets > 100,000/mm3
Additional Inclusion Criteria (If Applicable)- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 3 months after stopping treatment
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