Drug Interaction Report

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp), uridine diphosphate glucuronosyltransferase (UGT) 1A1 or 2B7, and/or breast cancer resistance protein (BCRP) may increase the plasma levels and risk of adverse effects of binimetinib. The proposed mechanism involves the reduced metabolic clearance of binimetinib through inhibition of P-gp, UGT 1A1, UGT 2B7, and/or BCRP. The clinical significance of this interaction is unknown as no clinically relevant drug interactions have been demonstrated with binimetinib.

MANAGEMENT: Until further information is available, caution is recommended if binimetinib must be used concomitantly with P-gp, UGT 1A1, UGT 2B7, and/or BCRP inhibitors. Binimetinib should be monitored more closely whenever a P-gp, UGT 1A1, UGT 2B7, and/or BCRP inhibitor is added to or withdrawn from therapy, and the binimetinib dosage adjusted as necessary.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of afatinib. According to the product labeling, administration of afatinib with a high-fat meal decreased peak plasma concentration (Cmax) by 50% and systemic exposure (AUC) by 39% compared to administration in the fasted state.

MANAGEMENT: Afatinib should be taken at least 1 hour before or 2 hours after a meal.

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:

• afatinib
• binimetinib

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.