Vonjo

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  • Leukemias, lymphomas, and other hematologic cancers
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Vonjo Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Pacritinib 100mg; caps.

    Pharmacological Class

    Kinase inhibitor.

    How Supplied

    Caps—120

    How Supplied

    100mg scarlet/gray oblong capsule printed with “Pacritinib 100 mg” on the cap and “C78837” on the body.

    Storage

    Store at room temperature, below 30°C (86°F).

    Keep the bottle tightly closed and protect from light.

    Store in original package.

    Dispense in original package or in a light-resistant container.

    Manufacturer

    CTI BioPharma Corp.

    Generic Availability

    NO

    Mechanism of Action

    Pacritinib is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function.

    Vonjo Indications

    Indications

    Treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50×109/L.

    Vonjo Dosage and Administration

    Prior to Treatment Evaluations

    Prior to initiating treatment with Vonjo:

    • Perform complete blood count (including white blood cell count differential and platelet count).
    • Coagulation testing (prothrombin time, partial
      thromboplastin time, thrombin time, and international normalized ratio).
    • Baseline electrocardiogram.

    Monitor as clinically indicated while patient is on treatment.

     

    Adult

    Swallow whole. 200mg twice daily. Dose modification for adverse reactions: see full labeling.

    Children

    Not established.

    Renal impairment

    Avoid use of Vonjo in patients with eGFR <30mL/min.

    Hepatic Impairment

    Avoid use of Vonjo in patients with moderate (Child-Pugh B) or severe hepatic impairment (Child-Pugh C).

    Other Modifications

    Planned surgical procedures or other interventions: Discontinue Vonjo 7 days before because of hemorrhage risk; restart only after hemostasis is assured.

    Dose Modifications for Adverse Reactions

    Dose Levels for Vonjo: 

    • 200mg twice daily (initial starting dose)
    • 100mg twice daily (first dose reduction)
    • 100mg once daily (second dose reduction)
    • Discontinue Vonjo if unable to tolerate 100mg daily

    Diarrhea

    New onset of diarrhea:

    • Initiate antidiarrheal.
    • Encourage adequate oral hydration.

    Grade 3 or 4:

    • Hold Vonjo until diarrhea resolves to grade 1 or lower or baseline; restart at the last given dose.
    • Intensify antidiarrheal; provide fluid replacement.
    • If diarrhea recurs, hold until diarrhea resolves to grade 1 or lower or baseline; restart at 50% of the last dose once toxicity resolved.
    • Concomitant antidiarrheal required for patients restarting Vonjo.

    Thrombocytopenia

    Clinically significant worsening of thrombocytopenia that lasts >7 days:

    • Hold Vonjo; restart at 50% of the last given dose once toxicity has resolved.
    • If toxicity recurs, hold Vonjo; restart at 50% of the last given dose once toxicity resolved.

    Hemorrhage

    Moderate bleeding; intervention indicated:

    • Hold Vonjo until hemorrhage resolves; restart at the last given dose.
    • If hemorrhage recurs, hold until resolution then restart at 50% of the last given dose.

    Severe bleeding; transfusion, invasive intervention, or hospitalization indicated:

    • Hold Vonjo until hemorrhage resolves.
    • Restart Vonjo at 50% of the last given dose.
    • If bleeding recurs, discontinue.

    Life-threatening bleeding; urgent intervention indicated:

    • Discontinue Vonjo.

    Prolonged QT interval

    QTc prolongation >500 msec or >60 msec from
    baseline:

    • Hold Vonjo.
    • If QTc prolongation resolves to ≤480 msec or baseline within 1 week, restart at the same dose.
    • If time to resolution is greater than 1 week, restart at a reduced dose.

     

     

     

    Administration

    Vonji may be taken with or without food.

    Swallow capsulrs whole; do not open, break, or chew capsules.

    Patients who are on treatment with other kinase inhibitors before the initiation of Vonjo must taper or discontinue according to the prescribing
    information for that drug.

    Missed Dose: Take the next prescribed dose at its scheduled time; extra capsules should not be taken to make up for the missed dose.

    Vonjo Contraindications

    Contraindications

    Concomitant with strong CYP3A4 inhibitors (eg, clarithromycin) or inducers (eg, rifampin).

    Vonjo Boxed Warnings

    Not Applicable

    Vonjo Warnings/Precautions

    Warnings/Precautions

    Risk for hemorrhage. Avoid use in those with active bleeding. Discontinue treatment 7 days prior to elective surgery or invasive procedures; restart only after hemostasis is assured. Control preexisting diarrhea prior to initiation. Interrupt or reduce dose if significant diarrhea occurs despite optimal supportive care. Preexisting moderate to severe thrombocytopenia. Interrupt treatment if clinically significant worsening of thrombocytopenia develops lasting for more than 7 days. Risk for prolonged QT interval; avoid use if baseline QTc >480msec. Correct hypokalemia prior to and during treatment. Perform CBCs (including WBC differential, platelets), coagulation testing, baseline ECG prior to initiation and monitor as indicated during therapy. Increased risk for MACE, thrombosis, lymphoma, and other malignancies; monitor. Consider the risks/benefits esp. in patients with known malignancy, cardiovascular risk factors, or current/past smokers. Increased risk of serious infections (eg, bacterial, mycobacterial, fungal, or viral); delay starting therapy until active serious infections have resolved. Monitor for infection during treatment. Renal impairment (eGFR <30mL/min), moderate or severe hepatic impairment: avoid. Pregnancy. Nursing mothers: not recommended (during and for 2 weeks after the last dose).

    Pregnancy Considerations

    There are no available data on Vonjo use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse
    maternal or fetal outcomes.

    Consider the benefits and risks for the mother and possible risks to the fetus when prescribing Vonjo to a pregnant woman.

    Nursing Mother Considerations

    There are no data on the presence of pacritinib in human milk, the effects on the breastfed child, or the effects on milk production.

    Breastfeeding not recommended during treatment with Vonjo, and for 2 weeks after the last dose.

    Pediatric Considerations

    Safety and effectiveness in pediatric patients have not been established.

    Geriatric Considerations

    Clinical studies did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from
    younger subjects.

    Renal Impairment Considerations

    Avoid use of Vonjo in patients with eGFR <30mL/min.

    Hepatic Impairment Considerations

    Avoid use of Vonjo in patients with moderate (Child-Pugh B) or severe hepatic impairment (Child-Pugh C).

    Vonjo Pharmacokinetics

    Absorption

    Pacritinib achieves Cmax within approximately 4 to 5 hours post-dose.

    Distribution

    ~98.8% plasma protein bound.

    Metabolism

    Predominantly metabolized by the CYP3A4 isozyme.

    Elimination

    Fecal (87%), renal (6%). Half-life: 27.7 hours.

    Vonjo Interactions

    Interactions

    See Contraindications. Avoid concomitant drugs with significant potential for QTc prolongation. Potentiated by moderate CYP3A4 inhibitors; avoid. Antagonized by moderate CYP3A4 inducers; avoid. Potentiates sensitive substrates of CYP1A2, CYP3A4, P-gp, BCRP, or OCTI; avoid.

    Vonjo Adverse Reactions

    Adverse Reactions

    Diarrhea, thrombocytopenia, nausea, anemia, peripheral anemia, vomiting, dizziness, pyrexia, epistaxis, dyspnea, pruritus, upper RTI, cough; serious cardiovascular events.

    Vonjo Clinical Trials

    Clinical Trials

    The approval of Vonjo was based on data from the randomized, controlled, phase 3 PERSIST-2 trial (ClinicalTrials.gov Identifier: NCT02055781), which evaluated the efficacy and safety of pacritinib in adults with thrombocytopenia and primary or secondary myelofibrosis. Patients were randomly assigned to receive 1:1:1 to receive pacritinib 400mg orally once daily (n=104), 200mg twice daily (n=107), or best available therapy (BAT; n=100). 

    Among 31 evaluable patients who received pacritinib 200mg twice daily and had a platelet count less than 50×109/L, findings showed that 29% (95% CI, 14.2-48.0) of patients achieved a reduction in spleen volume of at least 35% at week 24 (as measured by magnetic resonance imaging or computed tomography) vs 3.1% (95% CI, 0.1-16.2) of those treated with BAT (most common agents included ruxolitinib, watchful waiting, and hydroxyurea).

    The median reduction in spleen volume for patients with a platelet count less than 50×109/L was 27.3% for patients treated with pacritinib 200mg twice daily compared with 0.9% for those treated with BAT.

    Vonjo Note

    Not Applicable

    Vonjo Patient Counseling

    Patient Counseling

    Patients who are currently taking a kinase inhibitor must taper or discontinue their current kinase inhibitor therapy according to the
    package insert for that drug prior to starting Vonjo.

    Vonjo can cause hemorrhage; report bleeding immediately. Seek emergency care for any bleeding that cannot be stopped.

    Vonjo can cause diarrhea; patients should stay hydrated and report diarrhea. An antidiarrheal can be started if diarrhea occurs. Seek emergency care if diarrhea is severe.

    CBCs should be monitored before and during treatment; thrombocytopenia is possible with Vonjo.

    Feeling faint, loss of concsiousness, signs/symptoms suggestive of arrhythmia: Seek immediate care.

    Electrolyte monitoring important for patients with a history of hypokalemia.

    Current or past smokers, patients with other cardiovascular risk factors: Be alert for developments of signs/symptoms of cardiovascular events.

    Monitor for signs/symptoms of DVT/PE.

    Monitor for signs/symptoms of infection.

    Nausea and vomiting may occur during treatment; seek immediate care if it becomes severe.

    Avoid breastfeeing while on Vonjo and for 2 weeks after final dose.

    Follow dosing and administration instructions; do not change or stop taking Vonjo without consulting a physician first.

    Cost Savings Program

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