Drug Interaction Report

GENERALLY AVOID: Coadministration with moderate to potent inhibitors of CYP450 3A4 and/or inhibitors of P-glycoprotein (P-gp) efflux transporter system may increase the plasma concentrations of ensartinib, which is a substrate of both the isoenzyme and efflux transporter in vitro. Concomitant use may increase the risk and/or severity of adverse events. Clinical data characterizing the extent of this interaction and data with less potent inhibitors are not available.

MANAGEMENT: Concomitant use of ensartinib with moderate to potent inhibitors of CYP450 3A4 and/or inhibitors of P-gp should generally be avoided. Consultation with package labeling and relevant institutional protocols may be advisable for further guidance.

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.

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

• ensartinib
• tepotinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.