Drug Interactions between conivaptan and fostemsavir

MONITOR: Coadministration with potent inhibitors of CYP450 3A4, P-glycoprotein (P-gp), and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of temsavir, the active moiety of fostemsavir. According to the prescribing information, temsavir is a substrate of CYP450 3A4, esterases, P-gp, and BCRP. In pharmacokinetic studies, mean temsavir peak plasma concentration (Cmax) increased by approximately 50% to 80% and systemic exposure (AUC) increased by approximately 35% to 100% when fostemsavir 600 mg twice daily was administered with various potent CYP450 3A4 inhibitors (atazanavir/ritonavir 300 mg/100 mg once daily; darunavir/ritonavir 600 mg/100 mg twice daily; darunavir/ritonavir/etravirine 600 mg/100 mg/200 mg twice daily; ritonavir 100 mg once daily; cobicistat 150 mg once daily; darunavir/cobicistat 800 mg/150 mg once daily). These changes are not considered clinically relevant. However, increased temsavir exposure may increase the risk of QT prolongation.

MANAGEMENT: No dosage adjustments are recommended for fostemsavir when used with potent CYP450 3A4, P-gp, and/or BCRP inhibitors. It may be advisable to monitor patients for increased adverse effects such as QT prolongation during coadministration, particularly in the elderly and patients with risk factors for torsade de pointes.