Drug Interactions between Akeega and mitotane

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of abiraterone, which is partially metabolized by the isoenzyme. In healthy subjects administered a single 1000 mg dose of abiraterone following pretreatment with the potent CYP450 3A4 inducer rifampin (600 mg daily for 6 days), mean abiraterone systemic exposure (AUC) decreased by 55%. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: Concomitant use of abiraterone acetate with potent CYP450 3A4 inducers should generally be avoided. Otherwise, an increase in dosing frequency for abiraterone acetate from once daily to twice daily during the coadministration period may be considered, although this dosage adjustment has not been studied clinically. The dosage should be adjusted back to the previous level when the CYP450 3A4 inducer is discontinued. If abiraterone acetate is part of a combination pill, the regimen may need to be split into its individual components to allow for changes in abiraterone acetate dosing without affecting the other component(s). If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath.

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.