Drug Interaction Report

Coadministration of fostemsavir with moderate or weak CYP450 3A4 inducers may decrease the plasma concentrations of temsavir, the active moiety of fostemsavir. According to the prescribing information, temsavir is a substrate of CYP450 3A4, esterases, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). When fostemsavir (600 mg twice daily) was coadministered with the moderate CYP450 3A4 inducer etravirine (200 mg twice daily) in 14 study subjects, mean temsavir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Ctau) decreased by 48%, 50% and 52%, respectively, compared to fostemsavir administered alone. When the same dosage of fostemsavir was given to 22 study subjects with another moderate CYP450 3A4 inducer, rifabutin (300 mg once daily), mean temsavir Cmax, AUC and Ctau decreased by 27%, 30% and 41%, respectively. These changes are not considered clinically relevant, and no dosage adjustment of fostemsavir is recommended when coadministered with moderate or weak CYP450 3A4 inducers.

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

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.