Drug Interaction Report

ADJUST DOSE: Coadministration with inducers of P-glycoprotein (P-gp) may decrease the plasma concentrations of afatinib, which is a substrate of the efflux transporter. In study subjects, administration of afatinib in combination with the P-gp inducer rifampin (600 mg once daily for 7 days) resulted in a 34% decrease in afatinib systemic exposure.

MANAGEMENT: For patients who require chronic therapy with a P-gp inducer, it may be necessary to increase the daily dose of afatinib by 10 mg as tolerated. The previous dose may be resumed 2 to 3 days after discontinuation of the P-gp inducer.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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.