PACRITINIB CAP,ORAL
Clinical Criteria Summary
Document 441
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
Document 446
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.