ROMIPLOSTIM INJ,LYPHL

Clinical Criteria Summary

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

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

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

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

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

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

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.

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

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