Drug Interaction Report

GENERALLY AVOID: Coadministration with dual potent inhibitors of CYP450 3A4 and P-glycoprotein (P-gp) may increase the plasma concentrations of tepotinib, which may increase the incidence and severity of adverse reactions such as interstitial lung disease/pneumonitis, hepatotoxicity, edema, nausea, vomiting, diarrhea, constipation, and musculoskeletal pain. Tepotinib is a substrate of both CYP450 3A4 isoenzyme and P-gp efflux transporter. However, the effect of strong CYP450 3A4 inhibitors or P-gp inhibitors on tepotinib has not been studied clinically.

MANAGEMENT: Concomitant use of tepotinib with potent CYP450 3A4 and P-gp inhibitors should generally be avoided.

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.