Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or uridine diphosphate glucuronosyltransferase (UGT) 1A1 may increase the plasma concentrations of bictegravir. According to the product labeling, bictegravir is a substrate of both CYP450 3A4 and UGT1A1; however, the extent to which each enzymatic pathway contributes to the metabolic clearance of bictegravir has not been reported. In healthy volunteers studied under fasted conditions, administration of a single 75 mg dose of bictegravir during treatment with the potent CYP450 3A4 inhibitor voriconazole (300 mg twice daily) increased mean bictegravir peak plasma concentration (Cmax) and systemic exposure (AUC) by 9% and 61%, respectively, compared to administration of bictegravir alone. In addition, in healthy volunteers studied under fed conditions, administration of a single 75 mg dose of bictegravir during treatment with the potent CYP450 3A4 and UGT1A1 inhibitor atazanavir (400 mg once daily) increased mean bictegravir AUC by 315%, compared to administration of bictegravir alone.

MANAGEMENT: Caution is advised when bictegravir is used with CYP450 3A4 and UGT1A1 inhibitors. Patients should be monitored for increased adverse effects such as diarrhea, nausea, and vomiting.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

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.