Alosetron tablets removed from market

Glaxo Wellcome is voluntarily withdrawing its alosetron (Lotronex) tablets from the market. The Food and Drug Administration (FDA) is telling patients taking alosetron to discuss other treatment options with their health care providers.

Alosetron received FDA approval in February for treating irritable bowel syndrome (IBS) in women whose predominant bowel symptom is diarrhea. In August, after approval and launch of the product, the FDA told Glaxo to provide a medication guide for alosetron patients to help ensure they understand the health risks associated with using the drug. (See Drug Utilization Review, October 2000 and August 2000.) Those risks included complications of constipation and ischemic colitis.

At the same time, information for prescribers included seven reports of serious complications from constipation (resulting in six hospitalizations and three surgeries) and eight reports of ischemic colitis (resulting in four hospitalizations, four endoscopies, and no surgeries).

Glaxo’s decision to pull the drug comes after further FDA analysis of post-marketing reports of patients taking alosetron, including 49 cases of ischemic colitis and 21 cases of severe constipation, resulting in 34 hospitalizations without surgery, 10 surgeries, and three deaths. The FDA also received reports of two additional deaths (not resulting from ischemic colitis or constipation). Following the analysis, Glaxo and the FDA met and discussed risk management options. Options included restriction of drug distribution and market withdrawal.

According to the FDA, goals of restricted drug distribution include:

• safer use of alosetron in appropriately informed patients;

• continued access to alosetron by severely debilitated IBS patients under closely monitored conditions;

• continued clinical studies into the benefits and risks and safe use of alosetron.

Volunteering to step aside

Glaxo Wellcome decided to voluntarily withdraw the drug and indicates its plan to recall the drug from pharmacies. In the mean time, alosetron will remain in pharmacies until supplies are returned to Glaxo or are depleted. Pharmacies may choose not to fill further prescriptions of alosetron.

The FDA has been aware of reports of adverse events since the drug’s approval in February and has been monitoring reports of adverse events. In June, the FDA held a public advisory committee meeting to discuss management strategies based on post-marketing reports of adverse events associated with ischemic colitis and complications of constipation. At that time, no deaths had been reported. Following this meeting, Glaxo was asked to provide a medication guide for alosetron so that both patients and providers could be advised of the serious adverse effects associated with use of the drug. Glaxo Wellcome also mailed "Dear Healthcare Professional" and "Dear Pharmacist" letters at that time.

Pharmacists aware of adverse events associated with the use of alosetron should report those events to the FDA using a MedWatch report by calling (800) FDA-1088 or visiting the FDA Web site at www.fda.gov/medwatch.

For more information, go to the Lotronex information Web page created by the FDA’s Center for Drug Evaluation and Research: www.fda.gov/cder/drug/infopage/lotronex/lotronex.htm.