Drug Interaction Report

MONITOR: Coadministration with tepotinib may increase the plasma concentrations of drugs that are substrates of the breast cancer resistance protein (BCRP) transporter. The proposed mechanism is decreased clearance due to tepotinib-mediated inhibition of BCRP. In vitro studies have shown that tepotinib may inhibit intestinal BCRP at clinically relevant concentrations, but there are no clinical data regarding the use of tepotinib with BCRP substrates.

MANAGEMENT: Caution is advised when tepotinib is prescribed with drugs that are BCRP substrates, particularly those with a narrow therapeutic range. Clinical and laboratory monitoring may be appropriate for some drugs whenever tepotinib is added to or withdrawn from therapy.

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.

Food prolongs the gastrointestinal absorption of selexipag. When taken with food, the time to peak concentration (Tmax) was delayed and peak plasma concentration (Cmax) was approximately 30% lower. Selexipag systemic exposure (AUC) and that of its active metabolite did not significantly change, however. Selexipag may be taken with or without food. Tolerability may be improved when taken with food.