Drug Interaction Report

MONITOR: Coadministration with gilteritinib may increase the plasma concentrations and the risk of adverse effects of orally administered drugs that are substrates of the intestinal P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and/or organic cation transporter 1 (OCT1) transporters, such as dabigatran, digoxin, rosuvastatin, methotrexate, and metformin. The proposed mechanism, based on in vitro data, is decreased clearance due to gilteritinib-mediated inhibition of intestinal P-gp, BCRP, and/or OCT1 efflux transport proteins.

MANAGEMENT: Until more information is available, caution is advised if gilteritinib is used concomitantly with drugs that are substrates of the intestinal P-gp, BCRP, and/or OCT1 transport proteins, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever gilteritinib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

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.