I read with interest the article by Camilleri et al1 on alosetron in women with diarrhea-predominant irritable bowel syndrome. However, the authors failed to address one important issue. While the side effects reported in this trial were relatively mild and were primarily limited to constipation, the manufacturer, Glaxo Wellcome, voluntarily withdrew the drug from the market in November 2000 following reports of more serious adverse events. The drug had been marketed as Lotronex and had been approved by the Food and Drug Administration (FDA) in February 2000. The action on the part of Glaxo Wellcome occurred subsequent to the FDA's analysis of postmarketing adverse reactions. As of November 2000, the FDA had received 70 reports of serious adverse effects, including 49 cases of ischemic colitis and 21 cases of severe constipation resulting in severely obstructed or ruptured bowels. Of these 70 cases, 34 required hospitalization, 10 required surgery, and 3 deaths were reported. Two additional deaths were reported in patients taking alosetron but they did not appear to be related to either ischemic colitis or bowel obstruction or rupture. At the time of Glaxo Wellcome's action, the FDA had been considering either restricting the drug's distribution or instituting a mandatory drug withdrawal. Prior to alosetron's approval, the FDA had been aware of the drug's potential to cause ischemic colitis but at that time no deaths had been reported and the reported adverse events were generally considered only mild to moderate.2 By August 2000, the FDA was working with Glaxo Wellcome in an attempt to avert further negative outcomes associated with alosetron use. Among the actions taken were (1) the development of a medication guide designed to inform and educate patients about the drug's potential side effects so that early intervention could occur to avert serious harm, (2) revision of the professional labeling to inform health care professionals about the risks associated with alosetron use and ways to avoid potential problems, and (3) the distribution of "Dear Health Care Practitioner" and "Dear Pharmacist" letters to convey important safety information.3-6 Lotronex is the first drug to have a medication guide utilized under regulations that became effective in 1999.6 These measures came from recommendations made by a FDA-convened public advisory committee that was held in June 2000 and had been charged with the task of developing risk management options for alosetron use. However, despite these measures, the FDA continued to receive reports of severe adverse events. Glaxo Wellcome's decision to withdraw Lotronex was announced on November 28, 2000.2
Lisi DM. Lotronex Withdrawal. Arch Intern Med. 2002;162(1):101. doi:
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