Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of P-glycoprotein (P-gp) may decrease the oral bioavailability and plasma concentrations of tenofovir alafenamide (TAF), which is a substrate of the efflux transporter. In 26 healthy study subjects, administration of TAF (25 mg once daily) with the P-gp inducer carbamazepine (300 mg twice daily) decreased TAF plasma concentration (Cmax) and systemic exposure (AUC) by an average of 57% and 55%, respectively, compared to TAF administered alone. It is not known if, and to what extent, tenofovir disoproxil fumarate (TDF), another prodrug of tenofovir, may interact with P-gp inducers. The interaction has not been studied with TDF, and no information is found in the labeling of various products containing TDF, although it has been reported to be a P-gp substrate also.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of tenofovir alafenamide fumarate with P-gp inducers is not recommended. Whether this also applies to tenofovir disoproxil fumarate has not been established.

ADJUST DOSING INTERVAL: Food does not appear to substantially alter the pharmacokinetics of tipranavir. When tipranavir capsules or oral solution was coadministered with ritonavir capsules at steady-state, no clinically significant changes in tipranavir peak plasma concentration (Cmax) and systemic exposure (AUC) were observed under fed conditions (500 to 682 kcal, 23% to 25% calories from fat) relative to fasted conditions. The effect of food on tipranavir exposure during coadministration with ritonavir tablets has not been evaluated. High-fat foods may enhance the gastrointestinal absorption of tipranavir. In a multiple-dose study, administration of tipranavir capsules with a high-fat meal (868 kcal, 53% from fat, 31% from carbohydrates) increased the oral bioavailability of tipranavir by 31% compared to administration with toast and skimmed milk, but did not significantly affect tipranavir Cmax. Thus, tipranavir may be safely taken with standard or high-fat meals.

MANAGEMENT: Tipranavir coadministered with low-dose ritonavir should be taken with food to improve the gastrointestinal tolerability of ritonavir. According to the product labeling, tipranavir coadministered with ritonavir capsules or solution can be taken with or without meals, whereas tipranavir coadministered with ritonavir tablets must be taken with meals.

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.