Dangerous Drug for Irritable Bowel Syndrome: Constipation-Predominant Tegaserod (ZELNORM)

Tegaserod has been approved by the FDA for the treatment of women with IBS in whom constipation is the predominant symptom. The drug is not approved for men. The drug stimulates the 5-HT4 receptor, one of a family of serotonin receptors. Public Citizen opposed the approval of the drug based on its marginal efficacy and concerns about the induction of cysts in the ovaries.

IBS itself is not a life-threatening condition, although it can be debilitating. If the major symptom is diarrhea, the condition is known as diarrhea-predominant IBS; if it is characterized by constipation, it is called constipation-predominant IBS. The diagnosis of IBS should be based on a set of internationally recognized symptoms known as the Rome II Criteria which include, for constipation-predominant irritable bowel syndrome, having fewer than three bowel movements a week and requiring exclusion of treatable causes of the patient’s symptoms, such as ulcerative colitis. This is especially important if the following signs of ulcerative colitis are present: onset after age 50, rectal bleeding, fever, weight loss or anemia. There are no abnormal laboratory tests or changes in the cells of the GI tract on biopsy that can objectively establish the diagnosis of IBS. In fact, the diagnosis of IBS can only be made if all tests for other diseases that might explain the patient’s symptoms are negative and the patient continues to have recurrent abdominal discomfort or pain associated with diarrhea, constipation, or both.

There were eight cases of ovarian cysts in women taking tegaserod during the clinical trials, compared to one in the placebo groups. Although the company ultimately convinced the FDA that these were not related to the drug, we remain concerned because tegaserod induced ovarian cysts in rats and because there are 5-HT4 receptors in human ovaries. In addition, there was an increase in abdominal surgeries in patients taking tegaserod during clinical trials compared to placebo-treated patients. The increase was attributed primarily to an increase in gall bladder removals.

After marketing, new safety concerns with tegaserod arose. In April 2004, the FDA announced that the drug would be relabeled because of 21 cases of serious diarrhea and 23 cases of ischemic colitis or closely related diseases.

In addition to the ovarian cysts, the diarrhea, the ischemic colitis and the non-life threatening nature of IBS, tegaserod also has questionable efficacy: none of the three pivotal clinical trials demonstrated effectiveness, as judged by the original, predetermined primary clinical outcome measures. When it was seen, after the fact, that there was no significant improvement for either of the two original outcome measures in the first completed trial, Novartis cunningly altered the endpoints for the other two ongoing (but still blinded) trials, eliminating one measure and redefining the other in a manner that created a lower threshold for declaring improvement. However, even this manipulation produced only one pivotal trial with a statistically significant result, and that result was only half of what Novartis had expected.

In sum, tegaserod is a potentially dangerous drug of minimal efficacy used in the treatment of a non-life threatening condition. We recommend that you not use it and try the measures suggested below instead. If you are using the drug, the following precautions were issued with the above warning:

If you get new or worse abdominal pain with or without blood in your stools, stop taking Zelnorm right away and tell your doctor. Your doctor may need to do tests to find out if you have a serious problem. Sometimes Zelnorm causes diarrhea. Stop taking Zelnorm and call your doctor right away if you get so much diarrhea that you get light-headed, dizzy, or faint.

What You Can Do:

Alternative treatments for Irritable Bowel Syndrome

General measures include reducing intake of caffeine, alcohol and fried foods. Because intolerance to lactose (milk sugar) can mimic some symptoms of irritable bowel syndrome , a test to determine if you are lactose intolerant should be done. Sorbitol, the sugar in sugarless gum or candy, should be avoided. Minimization of stress and the use of relaxation techniques have helped many people. For constipation-predominant IBS, increased dietary fiber and/or the use of psyllium (METAMUCIL) and increased fluid intake may be helpful.