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 use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

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.