Pacritinib (Vonjo) is a kinase inhibitor indicated for the treatment of intermediate- or high-risk primary or secondary myelofibrosis in patients with a platelet count below 50×10⁹/L. Although it demonstrates good efficacy, the drug may cause a range of side effects, some of which can even be life-threatening.

What Are the Side Effects of Pacritinib (Vonjo)?

Common Side Effects

(1) Gastrointestinal System: Diarrhea (48%), nausea (32%), vomiting (19%).

(2) Hematological System: Thrombocytopenia (34%), anemia (24%).

(3) Others: Peripheral edema (22%), dizziness (15%), fever (15%), pruritus (10%).

Severe Side Effects of Pacritinib (Vonjo) Requiring Vigilance

1. Bleeding

(1) Risk: Severe bleeding occurs in 11% of patients, and 2% of cases may be fatal (the risk is higher when platelets < 100×10⁹/L).

(2) Manifestations: Intracranial hemorrhage, gastrointestinal bleeding, etc.

(3) Management: Discontinue the drug 7 days before surgery; in cases of active bleeding, the drug must be discontinued and intervention initiated.

2. Diarrhea

(1) Risk: Occurs in 48% of patients; 3% require treatment interruption, and severe cases may lead to acute kidney injury.

(2) Management: Prepare antidiarrheal medications (e.g., loperamide) at the start of treatment; for severe diarrhea, discontinue the drug and administer fluid replacement.

3. Cardiotoxicity

(1) QT Interval Prolongation: 1.4% of patients develop a QTc interval > 500 ms; concurrent use of other drugs that prolong the QT interval should be avoided.

(2) Major Adverse Cardiovascular Events (MACE): Patients with a smoking history or high cardiovascular risk require close monitoring for signs of myocardial infarction/stroke.

4. Thrombosis and Malignant Tumors

(1) Thrombosis Risk: Deep vein thrombosis, pulmonary embolism, etc.

(2) Secondary Malignant Tumors: Lymphoma, etc. (the risk is higher in smokers).

5. Infection Risk

(1) Common Pathogens: Bacteria, fungi, herpes viruses, etc.

(2) Management: Delay drug administration during active infection and monitor for signs of infection.

Precautions for Pacritinib (Vonjo) Use

Pre-Treatment Assessment

(1) Contraindications: Avoid concurrent use with strong CYP3A4 inhibitors/inducers (e.g., clarithromycin, rifampicin).

(2) Baseline Examinations: Complete blood count, coagulation function, electrocardiogram (ECG), thyroid function.

Dosage Adjustment

(1) Hepatic Impairment: For patients with Child-Pugh Class C hepatic impairment, reduce the dose to 100 mg twice daily.

(2) Renal Impairment: Avoid use in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min.

Special Populations

(1) Pregnant Women: Animal studies have shown embryotoxicity; contraceptive measures must be used during treatment.

(2) Lactating Women: Breastfeeding is prohibited within 2 weeks after discontinuing the drug.

(3) Male Fertility: May reduce fertility.

Drug Interactions

(1) CYP3A4 Substrates: Pacritinib may reduce the efficacy of these drugs (e.g., hormonal contraceptives should be replaced with non-hormonal alternatives).

(2) P-gp Substrates: Increases the concentration of digoxin; blood drug levels need to be monitored.