Drug Interactions between Akeega and nilotinib

GENERALLY AVOID: Nilotinib can cause concentration-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Nilotinib treatment alone has been associated with reported cases of sudden death. The early occurrence of some of these deaths relative to the initiation of nilotinib suggests the possibility that ventricular repolarization abnormalities may have been involved. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of nilotinib with other drugs that can prolong the QT interval should generally be avoided. Should treatment with other QT-prolonging drugs be required, the manufacturer recommends that nilotinib therapy be withheld temporarily. Caution and clinical monitoring are recommended if concomitant use is unavoidable. Patients should have frequent ECGs and be monitored for arrhythmias when QT interval is prolonged. A QTc interval exceeding 480 msec will require suspension of nilotinib therapy and immediate action to correct any concomitant risk factors before resuming treatment. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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.