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.

MONITOR: Isolated case reports have suggested that the ingestion of alcohol during griseofulvin therapy may rarely cause disulfiram-like reactions, flushing, tachycardia, or increased effects of alcohol. The mechanism is unknown.

MANAGEMENT: Patients should be advised of the possibility of increased adverse effects or a disulfiram-like reaction.

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.