Irritable Bowel Syndrome and Ischemic Colitis: Evidence Supporting the Increased Use of Alosetron

Alosetron, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, was approved by the US Food and Drug Administration (FDA) for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in women in February 2000. Initial clinical trials demonstrated significant efficacy, particularly in improving fecal urgency, stool frequency and consistency [Camilleri et al. 2001]. In a recent review and systematic meta-analysis of eight alosetron clinical trials, the number needed to treat (NNT) was reported to be 7.5 [Shah et al. 2012]. Although its efficacy was never questioned, safety became a concern as cases of ischemic colitis (IC) were reported, leading to voluntary withdrawal of alosetron by GlaxoSmithKline in November 2000. Alosetron was reintroduced in 2002 as a result of patient advocacy, with a risk management plan (RMP) designed to limit availability to women with severe IBS-D [Chang et al. 2010; Lewis, 2011].