Drug Interactions between mebendazole and nirmatrelvir / ritonavir

MONITOR: Coadministration with ritonavir may decrease the plasma concentrations of the benzimidazoles, albendazole and mebendazole, as well as the active metabolite of albendazole, albendazole sulfoxide. The precise mechanism has not been established, but may be related to the induction of CYP450 1A2, CYP450 2C9, and/or uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) by ritonavir following chronic administration. A pharmacokinetic study evaluating the effects of a single dose of either albendazole (400 mg) (n=8) or mebendazole (1000 mg) (n=8) administered with ritonavir (200 mg twice daily for 8 days) in healthy, nonsmoking male Caucasian subjects reported a significant reduction in the systemic exposure (AUC) and maximum plasma concentration (Cmax) of both albendazole and mebendazole. Specifically, mean AUC decreased to 27% and 43% of baseline for albendazole and mebendazole, respectively, and Cmax decreased to 26% and 41% of baseline, respectively. Albendazole sulfoxide AUC and Cmax were reduced to 41% and 52% of baseline, respectively. By contrast, pharmacokinetic parameters for albendazole, mebendazole, and albendazole sulfoxide were not significantly altered following administration of ritonavir for 2 doses only. The clinical relevance of the interaction observed following chronic ritonavir administration is unknown, since therapeutic ranges to optimize efficacy have not been established for either albendazole or mebendazole. Clinical impact is expected to be minimal in the treatment of intestinal infections, but may be increased when albendazole or mebendazole is used for systemic helminthic diseases.

MANAGEMENT: Caution and monitoring for altered clinical efficacy are recommended if albendazole or mebendazole is used in combination with ritonavir in patients being treated for systemic helminthic infections. Dose adjustments or alternative treatments may be required if an interaction is suspected.