BACKGROUND: Ischemic colitis and serious complications of constipation have been reported in association with the use of alosetron, which is approved for women with severe diarrhea-predominant IBS who have failed conventional therapies. This systematic review calculated the incidence of these adverse events in alosetron-using patients in clinical trials and post-marketing surveillance. METHODS: A panel of experts in epidemiology and functional bowel disorders reviewed clinical trial report forms and FDA MedWatch forms of each reported case of ischemic colitis or serious complications of constipation. Experts were blinded about whether patients used alosetron or placebo. Using pre-specified criteria, experts rated the likelihood of an accurate diagnosis and an association between medication use and adverse events. Cases that were not consistent with the reported diagnosis or not possibly associated with medication use were eliminated from calculation of incidence rates of adverse events. RESULTS: Pooled data from clinical trials indicate an increased rate of ischemic colitis among alosetron-using patients compared to placebo-using patients (0.15%vs 0.0%, respectively, p= 0.03), but there was no significant difference in the rate of serious complications of constipation. All (19/19) alosetron-using patients with ischemic colitis had reversible colitis without long-term sequelae. Based on post-marketing surveillance data, the post-adjudication rate of ischemic colitis is 1.1 per 1,000 patient-years of alosetron use and the rate of serious complications of constipation is 0.66 per 1,000 patient-years of alosetron use. CONCLUSION: The incidence of ischemic colitis and serious complications of constipation is very low and is rarely associated with long-term sequelae or serious morbidity.
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