Drug Interaction Report

MONITOR: Coadministration of niraparib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. In pooled safety population data of patients (n=1,314) with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with niraparib monotherapy, thrombocytopenia was reported in 60% of patients. Two niraparib clinical trials reported greater than or equal to Grade 3 thrombocytopenia in 29% to 39% of patients with niraparib discontinuation due to thrombocytopenia occurring in approximately 3% to 4% of patients. The MAGNITUDE study, which included an evaluation of niraparib in combination with abiraterone for breast cancer gene (BRCA)-mutated metastatic castration-resistant prostate cancer (mCRPC) reported Grade 3 or more thrombocytopenia in 8% of patients.

MANAGEMENT: Concomitant use of anticoagulants or other medications known to reduce platelet count should be approached with caution. Recommendations for holding, adjusting the dose of, or discontinuing niraparib can be found in the manufacturer's labeling. If the patient has additional risk factors for bleeding, such as coadministration with an anticoagulant or antiplatelet, it may be advisable to consider a platelet transfusion at a higher platelet count. For hematologic adverse reactions requiring transfusion, withhold niraparib and consider interrupting any drugs that interfere with platelet function or coagulation. Niraparib may be resumed at a reduced dose per manufacturer recommendations. If hematologic toxicity does not resolve within 28 days following interruption, discontinue niraparib and consider referral to a hematologist. Blood counts should be monitored as recommended by the manufacturer. Patients should be advised to promptly report any signs or symptoms of bleeding to their primary care provider.

ADJUST DOSING INTERVAL: Food reduces the oral bioavailability of betrixaban. When administered with a low-fat (900 calories; 20% fat) or high-fat (900 calories; 60% fat) meal, betrixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased relative to administration in the fasting state by an average of 70% and 61%, respectively, with the low-fat meal and 50% and 48%, respectively, with the high-fat meal. The effect of food on betrixaban pharmacokinetics could be observed for up to 6 hours after meal intake.

MANAGEMENT: The manufacturer recommends taking betrixaban at the same time each day with food.