Drug Interaction Report

MONITOR: Coadministration with tepotinib may increase the plasma concentrations and risk of adverse effects of drugs that are substrates of P-glycoprotein (P-gp). The proposed mechanism is decreased clearance due to tepotinib-mediated inhibition of P-gp efflux transport protein. Coadministration with tepotinib increased the peak plasma concentration (Cmax) and systemic exposure (AUC0-INF) of dabigatran (a P-gp substrate) by 40% and 50%, respectively.

MANAGEMENT: Caution is advised when tepotinib is used concomitantly with drugs that are substrates of P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever tepotinib is added to or withdrawn from therapy. Patients should be monitored for the development of adverse effects. The prescribing information recommends avoiding concomitant use of tepotinib with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. When concomitant use is unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

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 enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.