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.

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.