Drug Interactions between alosetron and voriconazole

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of alosetron, which has been shown in vitro to be partially metabolized by the isoenzyme. In 38 healthy female subjects, pretreatment with ketoconazole (200 mg twice a day for 7 days) increased the area under the plasma concentration-time curve (AUC) of alosetron (1 mg single oral dose) by 29% compared to administration of alosetron alone. Concomitant administration of alosetron with other CYP450 3A4 inhibitors has not been evaluated.

MANAGEMENT: Because alosetron is associated with potentially serious and life-threatening, dose-related gastrointestinal adverse effects, caution is advised during concomitant use with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, nefazodone, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics. Patients should be advised to immediately discontinue alosetron and notify their physician if they experience constipation or signs and symptoms of ischemic colitis such as rectal bleeding, bloody diarrhea, and new or worsening abdominal pain. Alosetron should not be resumed if ischemic colitis is diagnosed. Ischemic colitis and other serious complications such as obstruction, perforation, impaction, and toxic megacolon have resulted in hospitalization, blood transfusion, surgery, and death.