Lotronex

A drug, banned two years ago because it caused death and severe injury, is about to make a comeback. A Food and Drug Administration advisory committee voted last April to allow the drug back on the market. I cast one of only two votes against the drug's return. If the FDA follows its Advisory Committees advice (and it usually does), this will be the first time that a drug withdrawn for safety reasons will be given a "second chance."

The drug, Lotronex, is a treatment for irritable bowel syndrome, or IBS, a non-life threatening condition that in its most severe form can seriously disrupt a person's life. First approved to treat IBS at the end of 1999, Lotronex was soon discovered to cause far more serious adverse reactions than had been evident during the required pre- approval clinical trials (see HealthFacts, 8/00) After several deaths, the drug was finally withdrawn from sale in November 2000.

Why did I vote against lifting the ban? Perhaps the most important reason was the alarming frequency of severe adverse reactions reported to the FDA. As of the April meeting, these included 7 deaths, 50 surgeries, 142 hospitalizations, and 4 transfusions resulting from drug-related ischemic colitis, small bowel ischemia or complications of constipation. These numbers are likely to be conservative given the undisputed underreporting of adverse drug reactions.

Lotronex has only been proven safe and beneficial to women whose IBS symptoms do not include constipation. The committee voted that the drug should be prescribed only to this group. However, I am concerned that such restrictions will be ignored by physicians who will, once again, prescribe this drug too broadly.

Based on the available evidence, there is no way to identify people in advance who are at risk for developing Lotronex-related ischemic colitis. The suggestion that restricting Lotronex to women who have diarrhea-predominant IBS would reduce the risk of serious complications of constipation is problematic because doctors frequently prescribe drugs for other than an approved indication. The pre-ban drug labeling which advised prescribing only to women (the Lotronex approval trials did not include men) have already failed. Several of the reported severe adverse reactions occurred in men and men were among those users who testified to the Committees in favor of ending the ban.

The committee also discussed other restrictions, including limiting Lotronex prescribing to doctors "certified" in the treatment of IBS and limiting dispensing to only prescriptions written by a certified doctor. But, there are serious problems in implementing these recommendations. Glaxo SmithKline, the drug's sponsor, made it clear that they do not want to maintain a directory of certified doctors. And the FDA hasn't the resources and may not have the authority to run such programs.

IBS patients came to the committee meeting after mounting a successful lobbying effort to get the FDA to lift the ban on this drug that many insist works where none have before. I consider it a bad precedent that the FDA relied on anecdotes, rather than science, to justify a reconsideration of the ban. The only new scientific evidence that was presented to the committee described Lotronex, as a drug that is even riskier than previously thought--a good reason for continuing the ban.

This experience demonstrates the critical importance of a sound FDA pre-approval process. Lotronex was "fast tracked"--that is, reviewed within six months. Given how quickly serious safety problems emerged after marketing (the drug was available only 11 months before it was withdrawn) a less rushed review process might have led FDA not to approve Lotronex.

In my view, the emotional appeals of patients for access are clearly hard for the agency to resist and it has even greater responsibility to "get it right" the first time around because withdrawing a drug with any patient support now becomes politically difficult. Finally, I worry that in the case of Lotronex emotion may have trumped evidence and reason in the advisory committee process.

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ArArthur A. Levin, MPH, is the director of the Center for Medical Consumers in New York City.

COPYRIGHT 2002 Center for Medical Consumers, Inc.
COPYRIGHT 2002 Gale Group