Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of brexpiprazole. In vitro and in vivo data indicate that brexpiprazole is metabolized primarily by CYP450 3A4 and 2D6. When a single 4 mg oral dose of brexpiprazole was administered to healthy study subjects treated with the potent CYP450 3A4 inducer rifampin at 600 mg twice daily for 12 days, mean brexpiprazole peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 31% and 73%, respectively, compared to administration of brexpiprazole alone. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: Pharmacologic response to brexpiprazole should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the brexpiprazole dosage adjusted as necessary.

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.

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.