Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of elvitegravir, which is primarily metabolized by the isoenzyme. In a study of 12 healthy volunteers, coadministration of the potent CYP450 3A4 inducer carbamazepine (200 mg twice daily) with cobicistat-elvitegravir (150 mg-150 mg once a day) reduced the cobicistat systemic exposure (AUC) and peak plasma concentration (Cmax) by 84% and 72%, respectively, and the elvitegravir AUC and Cmax by 69% and 45%, respectively.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic drug levels, concomitant use of elvitegravir with potent CYP450 3A4 inducers is generally not recommended. In addition, other antiretroviral agents that are typically combined with elvitegravir may be contraindicated for use with potent CYP450 3A4 inducers. Please refer to the manufacturer's labeling for the specific elvitegravir-containing product for more information.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailabilities of both elvitegravir and tenofovir. When a single dose of cobicistat/elvitegravir/emtricitabine/tenofovir (trade name Stribild) was given with a light meal (approximately 373 kcal; 20% fat), mean elvitegravir and tenofovir systemic exposures (AUCs) increased by 34% and 24%, respectively, relative to fasting conditions. When administered with a high-fat meal (approximately 800 kcal; 50% fat), the mean AUC of elvitegravir and tenofovir increased by 87% and 23%, respectively, relative to fasting conditions. The alterations in mean AUCs of cobicistat and emtricitabine were not clinically significant with either the light or high-fat meal.

MANAGEMENT: Cobicistat/elvitegravir/emtricitabine/tenofovir as a fixed-dose preparation should be administered once daily with food. Elvitegravir as a single-ingredient preparation should also be administered once daily with food.