Drug Interactions between cobimetinib and niraparib

MONITOR: The concomitant use of myelosuppressive, immunosuppressive, or cytotoxic agents may potentiate and/or prolong the bone marrow toxicity associated with niraparib. Thrombocytopenia, anemia, neutropenia, and/or pancytopenia have all been observed with niraparib during clinical trials, especially during the initial phase of treatment. Additionally, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been reported in patients treated with niraparib. Some cases were fatal, and the duration of therapy with niraparib in patients who developed MDS/AML varied from less than 1 month to approximately 6 years. All patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

MANAGEMENT: Caution is advised if niraparib is prescribed with other myelosuppressive, immunosuppressive, or cytotoxic agents. Do not start niraparib until patients have recovered from hematological toxicity caused by previous chemotherapy (Grade 1 or less). Complete blood counts should be monitored as recommended in the product labeling and any relevant institutional protocols. Recommendations for dose adjustments as well as treatment interruption and discontinuation can also be found in the product labeling for serious hematologic adverse reactions. If hematological toxicities have not resolved within 4 weeks after interruption, discontinue niraparib and refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue niraparib. Patients should be advised to contact their physician if they experience pale skin, weakness, fatigue, fever, weight loss, infections, shortness of breath, unusual bleeding or bruising, or blood in urine or stool.