In response to an FDA request, Novartis has suspended U.S. marketing and sales of Zelnorm, a treatment for irritable bowel syndrome (IBS) with constipation and chronic constipation. This action is the result of a retrospective analysis of data from more than 18,000 patients in the clinical trial database, as well as an ongoing review involving a number of health authorities including the FDA. A public discussion and an advisory committee meeting is expected to take place to determine the risks and benefits of this medicine.

The recent analysis revealed a statistically significant imbalance in the incidence of cardiovascular ischemic events in patients taking Zelnorm compared to those taking placebo. These events included myocardial infarction, stroke, and unstable angina pectoris. The data showed that events occurred in 13 out of 11,614 patients treated with Zelnorm (0.11%), compared to one case in 7,031 placebo-treated patients (0.01%). All patients affected had pre-existing cardiovascular disease and/or CV risk factors.

“My review of the data suggested that a causal relationship is unlikely between tegaserod [Zelnorm] and the rare cardiovascular ischemic events observed in clinical trials,” said Jeffrey L. Anderson, M.D., Professor of Internal Medicine at the University of Utah and Associate Chief, Cardiology Division, LDS Hospital in Salt Lake City, UT—an independent cardiologist. “Furthermore, the data did not show any consistent pattern of event type, time to event or dose relationship in tegaserod-treated patients.”

Novartis is in discussions with the FDA and other health authorities in other countries where Zelnorm is available to determine next steps.

Zelnorm received FDA approval for the short-term treatment of women with IBS with constipation on July 24, 2002. Zelnorm also received FDA approval for the treatment of men and women less than 65 years of age with chronic idiopathic constipation on August 20, 2004.