FDA advisory panel hearing: managing risk of IBS drug Lotronex.(News)

ROCKVILLE, MD. -- Several members of a Food and Drug Administration advisory panel agreed that the risk management program in place for the irritable bowel syndrome drug alosetron should not be modified--despite some elements that the manufacturer says may deter physicians from prescribing the drug to appropriate patients.

At a meeting of the FDA's drug safety and risk management advisory committee, the drug's manufacturer GlaxoSmithKline (GSK) and the FDA provided an update on the risk management program for alosetron.

The program was instituted at the time of the drug's reintroduction in November 2002 for women with severe diarrhea-predominant irritable bowel syndrome who have failed to respond to conventional therapy. The program aims to make the drug available to appropriate patients and to ensure that alosetron is prescribed by physicians qualified to diagnose and manage not only IBS, but also ischemic colitis and severe complications of constipation--the serious adverse events that were reported in patients taking alosetron during the months following the drug's initial approval in February 2000. Some of these cases were fatal.

Alosetron, marketed as Lotronex, which blocks serotonin activity at 5-HT3 receptor sites in the enteric nervous system, was voluntarily withdrawn by GSK from the market in November 2000. But after the FDA and the manufacturer were contacted by desperate IBS patients who wanted the drug back--the FDA received approximately 5,000 e-mail messages--GSK submitted an approval application in December 2001. In June 2002, the FDA approved the drug's reintroduction with the following caveats: a narrower indication, a lower recommended starting dose, and the risk management program.

A main element of the program is that physicians who meet qualifications for diagnosing and managing IBS and potential side effects enroll in the program and sign a form attesting that they accept certain responsibilities, including educating patients about the risks of the drug and reporting serious adverse events. Other elements include a voluntary patient survey.

The purpose of the FDA meeting was to update the panel, not to seek specific recommendations. But after presentations by the FDA and manufacturer, panel members gave their opinions on the presentation.

Between Nov. 20, 2002, and Feb. 6, 2004, eight cases of ischemic colitis, which resolved without sequelae, and eight cases of constipation complications were reported: there were no reports of drug-associated deaths. The ischemic colitis and constipation cases were similar to those reported in trials, but resulted in less severe outcomes, suggesting that "prompt and appropriate action" is being taken by physicians and patients, said Craig Metz. Ph.D., GSK's vice president of U.S. regulatory affairs. Research Triangle Park, N.C.