Drug Interaction Report

ADJUST DOSE: Coadministration with fostemsavir may increase the plasma concentrations of tenofovir alafenamide fumarate (TAF). The proposed mechanism is inhibition of organic anion transporting polypeptide (OATP) 1B1/1B3- mediated hepatic uptake by temsavir, the active moiety of fostemsavir. Inhibition of breast cancer resistance protein (BCRP)-mediated intestinal and hepatic transport of TAF may also contribute. However, clinical trial data are lacking. This interaction has not been observed with tenofovir disoproxil fumarate (TDF). Coadministration of TDF with fostemsavir increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of tenofovir by 18% and 19%, respectively, and is not considered clinically significant.

MANAGEMENT: Caution and clinical monitoring are recommended with concomitant use of fostemsavir and tenofovir alafenamide fumarate. Some authorities advise that the dose of TAF be reduced to 10 mg daily when coadministered with fostemsavir, although a 10 mg dose may not be commercially available for some TAF-containing products.

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.