Drug Interaction Report

MONITOR: Coadministration with isavuconazonium sulfate (prodrug of isavuconazole) may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp), such as dabigatran. The proposed mechanism is isavuconazole inhibition of P-gp-mediated efflux of these drugs.

MANAGEMENT: Caution is advised if isavuconazonium sulfate is used concomitantly with drugs that are substrates of P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever isavuconazonium sulfate is added to or withdrawn from therapy with these drugs. Patients receiving concomitant dabigatran should be monitored closely for the development of bleeding complications and the dosage of dabigatran adjusted as necessary.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.