Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inducers and/or P-glycoprotein (P-gp) inducers may decrease the plasma concentrations of tepotinib. The proposed mechanism involves induction of CYP450 3A4, which is one of the primary enzymes responsible for the metabolic clearance of tepotinib, and induction of the efflux transporter P-gp, of which tepotinib is also a substrate. However, the effect of CYP450 3A4 inducers and/or P-gp inducers on tepotinib has not been studied clinically.

MANAGEMENT: The potential for diminished pharmacologic effects of tepotinib should be considered during coadministration with CYP450 3A4 inducers and/or P-gp inducers. Alternative treatments may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of tepotinib. When tepotinib was administered after a high-fat, high-calorie meal (approximately 800 to 1000 calories; 150 calories from protein, 250 calories from carbohydrate, 500 to 600 calories from fat), tepotinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2-fold and 1.6-fold, respectively, compared to administration under fasted conditions.

MANAGEMENT: Tepotinib should be administered with food at approximately the same time each day.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.