Abiraterone/niraparib Disease Interactions

Postmarketing studies have associated the use of abiraterone with severe hepatic toxicity, including fulminant hepatitis, acute liver failure and deaths. Serum transaminases and bilirubin levels should be measured before starting treatment and every 2 weeks for the first three months of treatment and then monthly thereafter. Any liver test elevations should prompt more frequently monitoring. Treatment should be discontinued permanently in patients with concurrent elevations of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN. In patients with baseline moderate hepatic impairment (Child-Pugh Class B), the recommended dose should be reduced to 250 mg once daily. Abiraterone should not be used in patients with severe hepatic impairment (Child-Pugh Class C).

Abiraterone may cause hypertension, hypokalemia and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Use caution when treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention such as patients with heart failure, recent myocardial infarction, ventricular arrhythmias. Use with caution in patients with cardiovascular disease and monitor regularly.

Niraparib has the potential to cause effects on pulse rate and blood pressure. Hypertension and hypertensive crisis have been reported in patients treated with niraparib. It is recommended to monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with niraparib. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Medically manage hypertension with antihypertensive medications and adjust the dose of niraparib as necessary.

No dose adjustment is needed in patients with mild hepatic impairment according to the National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG) criteria. Caution is recommended in patients with moderate to severe hepatic impairment as the safety of niraparib has not been established in these patients.

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including cases with fatal outcome, have been reported with the use of niraparib. It is recommended to use caution when using this agent in patients with MDS/AML, its use must be weighed against the risk. Discontinue the use of niraparib in patients who develop MDS/AML.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with niraparib. It is recommended to monitor complete blood counts weekly for the first month, monthly for the next eleven months of treatment, and periodically after this time. Do not start niraparib until patients have recovered from hematological toxicity caused by previous chemotherapy (less than equal to Grade 1). If hematological toxicities do not resolve within 28 days following interruption, discontinue niraparib, and refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics.

No dose adjustment is necessary for patients with mild to moderate renal impairment. Caution is recommended in patients with severe renal impairment or end stage renal disease undergoing hemodialysis as the safety of niraparib has not been established in these patients.