Interactions between alosetron and Fluvoxamine (fluvoxamine)
fluvoxamine and alosetron (Major Drug-Drug)
CONTRAINDICATED: Coadministration with fluvoxamine may significantly increase the plasma concentrations of alosetron. The proposed mechanism is fluvoxamine inhibition of alosetron metabolism via CYP450 1A2. In 40 healthy female subjects, pretreatment with fluvoxamine (in escalating doses from 50 to 200 mg/day for 16 days) increased the area under the plasma concentration-time curve (AUC) and half-life of alosetron (1 mg single oral dose) by approximately 6-fold and 3-fold, respectively. Fluvoxamine is known to also inhibit CYP450 2C9 and 3A4, both of which have been shown in vitro to be involved in the metabolism of alosetron. However, it is uncertain to what extent inhibition of these isoenzymes actually contribute to the interaction.
MANAGEMENT: Because alosetron is associated with potentially serious and life-threatening, dose-related gastrointestinal adverse effects (e.g., ischemic colitis; intestinal obstruction, perforation, and impaction; toxic megacolon), concomitant use with fluvoxamine is considered contraindicated.
