January 23, 2002
Dear IBS Patient,

This letter is in response to recent requests from the Irritable Bowel Syndrome (IBS) patient community for information regarding the status of Lotronex (alosetron HCl) Tablets.

First, we value our ongoing dialogue with the IBS patient community about this product. Through this we have gained a much better understanding of how impairing IBS can be for patients and their families. We appreciate IBS patients’ willingness to participate in research programs to generate new information that might lead to ways to decrease the risks associated with the use of effective IBS treatments like Lotronex. In addition, it is important to develop measures that could ensure that Lotronex is used by patients in whom the benefits exceed the risks. Undoubtedly, we will keep these thoughts in mind with respect to Lotronex and other IBS treatments.

As you know, FDA approved Lotronex on February 9, 2000, for use in the treatment of IBS in women whose predominant bowel symptom is diarrhea. FDA subsequently received numerous reports of serious and fatal gastrointestinal adverse events in patients administered Lotronex, and we initiated efforts with the manufacturer, GlaxoWellcome, to address those concerns. As part of those ongoing activities, we met with company representatives on November 28, 2000, to discuss risk management options. GlaxoWellcome voluntarily withdrew Lotronex from the market later that day.

GlaxoWellcome merged with SmithKline Beecham on December 27, 2000, to form GlaxoSmithKline (GSK). Discussions between GSK representatives and FDA staff were initiated early in 2001, with the purpose of exploring ways to make Lotronex available to IBS patients while limiting risks of serious and fatal gastrointestinal adverse events. In these discussions, FDA proposed to GSK that they provide for interim patient access to Lotronex. The goals for a limited access program are to ensure that the drug is used as safely as currently possible, generate additional data to enable safer use of the drug, and ensure that the drug is used by patients in whom the benefits exceed the risks. At the present time, FDA and GSK continue to work together to find a way to make Lotronex available to people who need it, while assuring that the risks are managed as well as possible.

IBS patients have commented that FDA is applying a fundamentally different set of review standards in our consideration of risks and benefits in treatments for IBS. We have made every effort to apply the same standards in this case as in other diseases. FDA has received numerous adverse event reports associated with the use of Lotronex, including reports of death and surgery due to complications of constipation, as well as reports of ischemic colitis. In addition to the severity of these risks, we face considerable uncertainty regarding the nature of these risks and how to reduce them. There is little data currently available regarding specific risk factors, how patients can recognize emerging serious adverse events, or how Lotronex can be used to avoid or alleviate these risks. Under these circumstances, all IBS patients treated with Lotronex must be considered at risk for serious adverse events.

Nevertheless, we recognize that for some patients with debilitating IBS, Lotronex has a positive effect. However, we must address the unique circumstances of two distinct groups of IBS patients, former Lotronex users with severe disease that responded favorably to the drug, and IBS patients not previously treated with Lotronex. In those patients not previously treated, indiscriminant use of Lotronex can reasonably be expected to result in serious and fatal adverse events such as those previously reported. Many of these patients may have non-serious IBS and would be subjected to serious risks while realizing relatively modest benefit from treatment with Lotronex. In such cases, the risks of Lotronex appear substantially greater than its benefits. Our challenge is to learn more about these serious risks of Lotronex, and to develop measures that effectively limit these risks and ensure that the drug is used only by patients in whom the benefits exceed the risks. A carefully designed risk management program is essential for safe use of Lotronex for patients who need it, and to effectively discourage its use for patients where the risks are likely to exceed the benefits.

GSK continues to submit new Lotronex information. We anticipate that review of this new information will lead to a better understanding of the risks and benefits of this drug. FDA is committed to completing its review of this new information as soon as possible.

Given the importance of the risk/benefit issues that surround Lotronex, we will be seeking advice from a FDA Advisory Committee on those issues. The meeting has been tentatively scheduled for April 23, 2002. We are planning to have a Patient Representative, a person with IBS, serve on the committee. Through this process, the IBS patient community will have a direct voice in considering risks and benefits related to the use of Lotronex. The meeting will also include time for public input, whereby interested members of the public may voice their opinion. We look forward to public participation in this process. The discussions should help us reach a decision regarding if and under what terms Lotronex may again be available for use in the treatment of IBS patients. Additional information pertaining to the advisory committee meeting will be published in the Federal Register.

Again, thank you for your continued interest in the evaluation of drugs to treat IBS. We hope this information is helpful. If you have additional questions, please contact the staff in the Division of Drug Information at 888-INFO-FDA or e-mail us at druginfo@fda.hhs.gov.

Division of Drug Information
Office of Training and Communication
Center for Drug Evaluation and Research
U.S. Food and Drug Administration