Drug Interaction Report

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.

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.