Tolerability and safety of alosetron during long-term administration in female and male irritable bowel syndrome patients

OBJECTIVES: Alosetron (Lotronex is a new therapeutic agent for il irritable bowel syndrome (IBS) in women with diarrhea-predominant IBS. This multicen ter randomized, double-blind, placebo-controlled study assessed the safely and tolerability of alosetron during long-term (less than or equal to 12 mo nths) treatment. METHODS: A total of 859 subjects (637 female and 222 male) with IBS were en rolled from 130 sites in the United States and were randomized 3:1 to recei ve 1 mg alosetron or placebo b.i.d. for 48 wk; of the subjects, 649 (76%) w ere randomized to the alosetron group and 212 (24%) to the placebo group. O f the original group, 850 subjects received at least one dose of alosetron (n = 640) or placebo (n = 210). RESULTS: In all, 59% of the subjects completed the study. Safety data were similar in treatment groups and within age, sex, racial origin, and hormone use. Adverse events were reported by 83% (530/640) and 76% (159/210) of su bjects in the alosetron and placebo groups, respectively, (p < 0.05) and we re similar with the exception of constipation; 32% of subjects receiving al osetron reported constipation, compared to 5% in the placebo group (p < 0.0 01). Most reports (72%) of constipation were of mild or moderate severity, and 66% of subjects with constipation had single episode of 8 days median d uration. Constipation occurred a median of 13 days after initiating treatme nt and resolved spontaneously, with laxative, or after, a brief interruptio n of therapy. Of the subjects, 4% (11/210) ill the alosetron and 5% (28/640 ) in the placebo group experienced serious adverse events. Two deaths occur red in subjects with pre-existing cardiovascular risk factors; neither deat h was attributed to the study drug. CONCLUSIONS: Alosetron 1 mg b.i.d. for 12 months was well tolerated. Consti pation is the most frequent adverse event, with a higher incidence of trans ient constipation in alosetron-treated patients, typically occurring in the first month of treatment. (C) 2001 by Am. Cell. of Gastroenterology.