Drug Interaction Report

CONTRAINDICATED: Coadministration of fostemsavir with potent CYP450 3A4 inducers may significantly 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 (1200 mg single dose) was coadministered with the potent CYP450 3A4 inducer rifampin (600 mg once daily) in 15 study subjects, mean temsavir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 76% and 82%, respectively, compared to fostemsavir administered alone. Induction of P-gp, an efflux transporter protein present in the apical membrane of enterocytes and kidney epithelium, may also contribute to the overall interaction.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of fostemsavir with potent CYP450 3A4 inducers is considered contraindicated.