VONJO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VONJO (VONJO).
Pacritinib is a Janus kinase 2 (JAK2) and interleukin-1 receptor-associated kinase 1 (IRAK1) inhibitor. It inhibits JAK2 and mutant JAK2V617F, reducing cytokine signaling and proliferation of malignant cells.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C8; minor contributions from CYP1A2, CYP2C9, CYP2D6, and CYP3A5. |
| Excretion | Primarily metabolized by the liver via CYP3A4 and CYP2C8; ~90% eliminated in feces as metabolites, ~10% in urine as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life approximately 40–60 hours; allows once-daily dosing. Steady-state achieved in 8–14 days. |
| Protein binding | >99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution (Vd/F) approximately 400–600 L, indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral bioavailability is approximately 5–10% due to extensive first-pass metabolism; absorption is increased with a high-fat meal. |
| Onset of Action | Clinical effect (reduction in palpable spleen size and symptom improvement) observed within 4–8 weeks of oral administration. |
| Duration of Action | Duration of therapeutic effect persists with continued dosing; rebound of symptoms may occur within weeks of discontinuation. Continuous daily dosing is required for sustained response. |
| Molecular Weight | 382.5 |
400 mg orally once daily with food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 200 mg orally once daily. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 200 mg orally once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no recommended dose. |
| Geriatric use | No specific dose adjustment required based on age; monitor renal function and for increased risk of adverse effects. |
| 1st trimester | No adequate human data; animal studies show reproductive toxicity. Avoid use in first trimester. |
| 2nd trimester | No human data; potential fetal harm based on animal studies. Use only if potential benefit justifies risk. |
| 3rd trimester | No human data; potential fetal harm, including low birth weight and developmental delays. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for VONJO (VONJO).
| Placental transfer | Presumed to cross placenta based on molecular weight and animal studies; not quantified in humans. |
| Breastfeeding | No human data on presence in breast milk or effects on infant. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least 2 weeks after last dose. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to vonjo or any excipientsPregnancyBreastfeeding
| Precautions | Hemorrhage, Thrombocytopenia, QTc interval prolongation, Infections, Hepatotoxicity, Gastrointestinal toxicity, Fetal harm |
| Food/Dietary | Take with food to reduce gastrointestinal effects (e.g., nausea, diarrhea). Avoid grapefruit, grapefruit juice, and Seville oranges due to CYP3A4 inhibition, which can increase pacritinib levels and risk of toxicity. |
| Clinical Pearls | VONJO (pacritinib) is a JAK2/IRAK1 inhibitor for myelofibrosis. Monitor for hepatotoxicity: check LFTs before and during therapy. Avoid in severe hepatic impairment (Child-Pugh C). Dose reduction recommended for moderate hepatic impairment (Child-Pugh B). Administer with food to reduce GI adverse effects. CBC monitoring required monthly for first 2 months, then every 3 months for thrombo-cytopenia and neutropenia. Concomitant use with strong CYP3A4 inhibitors increases pacritinib exposure; avoid or reduce dose. No QTc prolongation noted, but monitor ECG if other QT-prolonging drugs used. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | VONJO (pacritinib) is contraindicated in pregnancy. Based on its mechanism of action (JAK2/IRAK1 inhibition) and animal studies, there is a potential for fetal harm. First trimester: High risk of teratogenicity; embryofetal toxicity observed in rats and rabbits. Second and third trimesters: Continued risk of fetal growth restriction and developmental abnormalities. Adequate contraception is required for females of reproductive potential during treatment and for at least 2 weeks after the last dose. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests, and serum creatinine at baseline and periodically during therapy. Assess pregnancy status in females of reproductive potential prior to initiation. Monitor for signs of infection, bleeding, and thrombosis. Fetal monitoring via ultrasound if pregnancy is suspected or confirmed. |
| Fertility Effects | Based on animal studies, pacritinib may impair fertility in females and males. In rats, decreased fertility and embryonic viability were observed at clinically relevant doses. Effects on human fertility are unknown; advise reproductive potential patients of potential risks. |
| Patient Advice | Take VONJO exactly as prescribed, usually twice daily with food to decrease stomach upset. · Do not crush, break, or chew capsules; swallow whole. · Avoid grapefruit, grapefruit juice, and Seville oranges during treatment as they can affect drug levels. · Report any signs of liver problems: yellowing of skin/eyes, dark urine, upper right stomach pain, or unusual bleeding/bruising. · Your doctor will perform blood tests regularly to monitor blood cell counts and liver function. · Tell your doctor about all medications you take, including over-the-counter, herbal supplements (especially St. John's wort), and other prescription drugs. · Use effective contraception during treatment and for at least 1 week after the last dose. Do not breastfeed during therapy. · Avoid live vaccines while taking VONJO. · If you miss a dose, take it as soon as you remember unless it is within 6 hours of the next dose. Do not double up. |