Drug Interactions between encorafenib and tacrine

GENERALLY AVOID: Encorafenib may cause dose-related 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. A dedicated study to evaluate the QT prolongation potential of encorafenib has not been conducted. Based on a central tendency analysis of QTc in a study of adult patients with melanoma, the largest mean QTcF change from baseline was 18 msec following administration of the recommended dose of encorafenib in combination with binimetinib. In the COLUMBUS trial, an increase in QTcF to >500 msec was measured in 0.5% (1/192) of patients who received encorafenib with binimetinib. 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 encorafenib with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. Hypokalemia and hypomagnesemia should be corrected prior to initiation of encorafenib treatment, and electrolytes periodically monitored during 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. Withhold, reduce dose, or permanently discontinue encorafenib in accordance with the product labeling for QTc exceeding 500 msec.