Drug Interaction Report

Coadministration with inducers of UGT1A and CYP450 3A4 isoenzymes may decrease the plasma concentrations of dolutegravir, which is primarily metabolized by UGT1A1 with some contribution from CYP450 3A4. Dolutegravir is also a substrate of UGT1A3, UGT1A9, and P-glycoprotein in vitro. In 9 study subjects, administration of dolutegravir 50 mg once daily with rifabutin 300 mg once daily decreased dolutegravir trough plasma concentration (Cmin; 24 hours postdose) by 30% compared to administration without rifabutin. The clinical significance is unknown. Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, caution may be advisable if dolutegravir is used in combination with mild or moderate UGT1A/CYP450 3A4 inducers.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.