# 2) Updated Report on Lotronex as of 11/1 Midnight



## JeanG (Oct 20, 1999)

This latest reports seems to be toning down the warnings, and says it's too early to predict whether or not Lotronex was involved in the deaths.The url for this article is: http://my.webmd.com/content/article/1728.62866 More Upsetting News About Irritable Bowel Treatment Death Reports Prompt FDA to Re-Evaluate the Benefits of Lotronex By Ori Twersky WebMD Washington Correspondent Reviewed by Dr. Dominique S. Walton Oct. 31, 2000 (Washington) -- Following 49 reports of a serious bowel condition called ischemic colitis and five reported deaths among people taking Lotronex (alosetron), a drug for irritable bowel syndrome (IBS), U.S. health officials are re-evaluating the risks and benefits of the drug. Though the FDA has yet to review the reports, and though a link with Lotronex has not been established, enough concern has been raised to warrant further investigation. FDA officials confirmed Monday that they are re-evaluating Lotronex after the prominent consumer watchdog group Public Citizen released a letter urging FDA Commissioner Jane Henney, MD, to withdraw the IBS drug from the U.S. market. In the letter, the group said that the drug was linked to 54 cases of ischemic colitis, making it "irresponsible for Glaxo Wellcome and for the FDA to allow this doomed drug to stay on the market any longer." IBS is a disorder of the large intestine that is characterized by abdominal pain and either constipation or diarrhea. It affects mostly women and occurs in about 15% of Americans, or five out of every 1,000 people. Ischemic colitis is a potentially life-threatening inflammation of the large intestine that is caused when blood flow to that area of the gastrointestinal tract is blocked. Lotronex, made by the U.K.'s Glaxo Wellcome, blocks certain receptors for serotonin, a chemical that relays sensations from the body to the brain. The blocked receptors, which are found throughout the gastrointestinal tract, are thought to play a large role in relaying the sensation of pain from the intestines to the brain. The receptors also are believed to help regulate certain bowel functions. This is not the first time the FDA has investigated a link between Lotronex and ischemic colitis, or that Public Citizen has called for the drug to be withdrawn. In late June, an expert panel of the FDA reviewed the link and concluded that a stricter warning label might be warranted -- even though the rate or cause of ischemic colitis was not fully understood. Then in August, Public Citizen called for the drug's withdrawal, citing the FDA's own publicly declared concerns as the basis of its complaint. Following the expert panel review, the FDA did require that an easy-to-read pamphlet explaining the risk of ischemic colitis, as well as the risk of severe constipation, be distributed to all patients taking the drug. The unprecedented move was ordered in August, when the FDA was aware of about 33 severe cases of both ischemic colitis and severe constipation. The FDA now has received 21 reports of severe constipation. While it is fair to say the additional reports have prompted the FDA to re-evaluate the drug's benefits and risks, it is still too early to say that Lotronex is responsible for the reported side effects or deaths or that the new reports really reflect any increased risk to patients, an agency spokesperson concedes. Speaking on condition of anonymity, he tells WebMD that the federal agency expected to receive additional reports of ischemic colitis after ordering the consumer pamphlet be distributed because of all the media hype surrounding the issue. "We are now trying to learn as much as we can about each of these events," he tells WebMD, adding that some of the recent reports refer to events that happened prior to September, when the consumer pamphlet was released. For its part, Glaxo Wellcome maintains that the risk of ischemic colitis is minimal and probably not associated with Lotronex. When asked whether there is a possible association, Eric Carter, MD, PhD, director of Glaxo Wellcome's U.S. gastrointestinal drug division, says that after extensive animal and human studies of the drug, the researchers there could not find a mechanism to explain the reports of ischemic colitis. The majority of events have been temporary and reversible, with less than half of the patients requiring hospitalization, Carter notes. This type of ischemic colitis also has been associated with a number of other medications, including oral contraceptives, he notes. The reports, Carter adds, may simply reflect the true incidence of ischemic colitis in the U.S. Currently, the estimated incidence is about three out of every 10,000 people, but the temporary ischemic colitis reported in association with Lotronex use "probably occurs more frequently [in the general public] than is recognized," he tells WebMD. Still, Carter cautions physicians and patients to take the time to determine whether Lotronex truly is the appropriate treatment. Clinical studies have shown Lotronex greatly benefits women, with about 75% reporting a significant improvement in their symptoms over 12 months, but the drug is not indicated for any men or for women whose predominate IBS symptom is constipation, he tells WebMD. "It is not the mandate of a pharmaceutical company to tell a physician how to practice medicine. Quite frankly, no one can do that," he says. But while the company is reluctant to question the clinical judgement of physicians, the recent reports do demonstrate that the drug is being prescribed inappropriately to some patients, including patients with a history of severe intestinal disease, he tells WebMD. To address this particular issue, the company is launching an advertising campaign aimed at consumers to help them determine whether Lotronex is appropriate for them. Despite Glaxo's actions, the controversy surrounding Lotronex is unlikely to die anytime soon. Because IBS is a difficult condition to diagnose, it is possible that a number of the patients prescribed Lotronex do not even have the condition, Public Citizen says. "We don't think it should have been approved in the first place," Larry Sasich, PharmD, MPH, the group's lead researcher, noted in a recent interview with WebMD. About 70-80% of patients prescribed Lotronex potentially are being exposed to the risk of ischemic colitis without enjoying any medical benefit, FDA officials also noted previously. This figure comes from clinical trials, which indicate that about 80% of the people who participated in the trials either failed to improve or improved due to other reasons, said Florence Houn, MD, director of the FDA's office responsible for intestinal drugs. But the argument goes both ways. Other experts say that drugs like Lotronex are needed desperately, even though IBS is not a life-threatening condition. Prior to the approval of Lotronex in February 1999, physicians recommended psychiatric treatment or a change in lifestyle as ways to treat IBS. But to assume that these treatments are sufficient is to ignore a major quality-of-life issue that can be debilitating, Harris Clearfield, MD, a professor of medicine at Hahnemann University Hospital in Philadelphia, recently told WebMD. "I would also take issue with the notion that IBS is often misdiagnosed," he said. Lotronex, which is approved for women whose predominate symptom is diarrhea, is the first drug to be approved for IBS in decades. The FDA is now expected to approve another IBS drug called Zelmac (tegaserod), which probably will be launched in the first half of 2001. But even then, Public Citizen is expected to protest that approval because the drug has been associated with ovarian cysts. "Right now, it looks like there is a lack of effectiveness and a real risk of side effects" associated with these drugs, Sasich told WebMD in an interview.


----------



## Mike NoLomotil (Jun 6, 2000)

"...could not find a mechanism..."Therefore, it does not exist. If I had a buck for every time I have heard this the last 30 years, I would be retired and living in Aruba. Unfortunately none of the deaths was ever reversible. No mechanism to do that has been found either.MNL


----------

