Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein may increase the blood concentrations of everolimus following oral administration. Everolimus is a substrate of both the CYP450 3A4 isoenzyme and P-glycoprotein drug efflux transporter, thus their inhibition in the intestine can enhance the absorption of everolimus.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of everolimus therapy should be considered during coadministration with CYP450 3A4 and/or P-glycoprotein inhibitors, including adverse effects such as pneumonitis, stomatitis, infection, dyspnea, diarrhea, anemia, leucopenia, thrombocytopenia, hyperglycemia, and hyperlipidemia. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy.

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered everolimus. The mechanism is inhibition of CYP450 3A4 and P-glycoprotein activity in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with everolimus should avoid consumption of grapefruit and grapefruit juice.

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.