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.

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.

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.