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Severe (11%) and fatal (2%) bleeding events occurred in patients treated with pacritinib who had a platelet count < 100 × 10⁹/L. Among patients treated with pacritinib who had a platelet count < 50 × 10⁹/L, severe (13%) and fatal (2%) bleeding events were reported. Grade ≥ 3 bleeding events (defined as those requiring blood transfusion or invasive intervention) occurred in 15% of patients in the pacritinib group, compared with 7% in the control group. Due to bleeding, 3%, 3%, and 5% of pacritinib-treated patients required dose reduction, treatment interruption, and permanent discontinuation, respectively.
Avoid the use of pacritinib in patients with active bleeding. Discontinue pacritinib 7 days prior to any planned surgery or invasive procedure.
Monitor platelet counts periodically based on clinical indications. Manage bleeding with treatment interruption and medical interventions.
In a clinical trial, diarrhea occurred in approximately 48% of pacritinib-treated patients, compared with 15% in the control group. The median time to resolution of diarrhea was 2 weeks in pacritinib-treated patients. The reported incidence of diarrhea decreased over time: 41% of patients reported diarrhea in the first 8 weeks of treatment, 15% between Weeks 8 and 16, and 8% between Weeks 16 and 24. Diarrhea led to treatment discontinuation in 3% of pacritinib-treated patients. Severe diarrhea adverse reactions occurred in 2% of patients in the pacritinib group, with no such reactions reported in the control group. Post-marketing reports have documented cases of severe diarrhea induced by pacritinib, which resulted in acute kidney injury and treatment discontinuation.
Control pre-existing diarrhea before initiating pacritinib treatment. Manage diarrhea with antidiarrheal medications, fluid replacement, and dose adjustment. At the start of treatment, prescribe an antidiarrheal agent (e.g., loperamide) and instruct patients to treat diarrhea immediately upon the first appearance of symptoms (changes in stool frequency or consistency) after starting pacritinib. For patients who develop severe diarrhea despite optimal supportive care, interrupt or reduce the dose of pacritinib.
Pacritinib may exacerbate thrombocytopenia. Among patients with pre-existing moderate to severe thrombocytopenia (platelet count < 100 × 10⁹/L), 2% required a dose reduction of pacritinib due to worsening thrombocytopenia. In patients with pre-existing severe thrombocytopenia (platelet count < 50 × 10⁹/L), 2% also required a dose reduction of pacritinib due to exacerbation of thrombocytopenia.
Monitor platelet counts before and during pacritinib treatment based on clinical indications. For clinically significant worsening of thrombocytopenia that persists for more than 7 days, interrupt pacritinib treatment. After resolution of toxicity, resume pacritinib at 50% of the last administered dose. If toxicity recurs, suspend pacritinib again and resume at 50% of the last administered dose after the toxicity resolves.
Pacritinib can cause QTc interval prolongation. The proportion of patients with QTc prolongation > 500 ms was higher in the pacritinib group than in the control group (1.4% vs. 1%). The proportion of patients with a QTc increase ≥ 60 ms from baseline was also higher in the pacritinib group compared to the control group (1.9% vs. 1%). QTc prolongation as an adverse reaction was reported in 3.8% of patients in the pacritinib group and 2% in the control group. No cases of torsades de pointes were reported.
Avoid the use of pacritinib in patients with a baseline QTc > 480 ms. Avoid concomitant use of pacritinib with drugs that have a potential to significantly prolong QTc interval. Correct hypokalemia before and during pacritinib treatment.
Manage QTc prolongation with pacritinib interruption and electrolyte management.
Another Janus-associated kinase (JAK) inhibitor has been shown to increase the risk of MACE (including cardiovascular death, myocardial infarction, and stroke) in patients with rheumatoid arthritis (an indication for which pacritinib is not approved), compared with patients receiving tumor necrosis factor (TNF) blockers.
Before initiating or continuing pacritinib treatment, consider the benefits and risks for individual patients, especially current or former smokers and those with other cardiovascular risk factors. Inform patients of the symptoms of serious cardiovascular events and the measures to take if such events occur.
Another JAK inhibitor has been demonstrated to increase the risk of thrombosis (including deep vein thrombosis, pulmonary embolism, and arterial thrombosis) in patients with rheumatoid arthritis (an indication for which pacritinib is not approved), compared with patients receiving TNF blockers.
Promptly evaluate and appropriately treat patients who present with symptoms of thrombosis.
Another JAK inhibitor has been found to increase the risk of malignancies other than lymphoma and non-melanoma skin cancer in patients with rheumatoid arthritis (an indication for which pacritinib is not approved), compared with patients receiving TNF blockers. The risk is further increased in current or former smokers.
Before initiating or continuing pacritinib treatment, weigh the benefits and risks for individual patients, particularly those with a known history of malignancy (except for successfully treated non-melanoma skin cancer), patients who develop a malignancy, and current or former smokers.
Another JAK inhibitor has been shown to increase the risk of serious infections in patients with myeloproliferative neoplasms, compared with best available therapy. Patients receiving pacritinib may develop severe bacterial, mycobacterial, fungal, and viral infections. Delay the initiation of pacritinib until active severe infections have resolved. Monitor patients receiving pacritinib for signs and symptoms of infection and manage promptly. Conduct active monitoring and prophylactic antibiotic use in accordance with clinical guidelines.
Concomitant use of pacritinib with strong CYP3A4 inhibitors or inducers is prohibited. When co-administering pacritinib with moderate CYP3A4 inhibitors, monitor patients for an increase in pacritinib-related adverse reactions.
FDA，2025.10
