Drug Interactions between famotidine / ibuprofen and niraparib

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.

H2 antagonists may alter the pharmacokinetic disposition of some nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data have been varied, even for the same NSAID. The mechanism may involve inhibition of metabolism, changes in gastric pH resulting in altered absorption, and/or reduced urinary elimination of the affected NSAIDs. Statistically significant changes have been small and of limited clinical significance when interactions have been observed.