Novartis Withdraws Constipation Drug in the U.S.

Novartis will stop selling its constipation drug Zelnorm because of an increased risk of serious adverse cardiovascular events, the FDA announced.

Results from an analysis of 29 short-term clinical trials showed that Zelnorm (tegaserod maleate) raised the risk of heart attack and stroke compared with placebo, the agency said. Zelnorm is approved to treat women with irritable bowel syndrome and chronic constipation in men and women under 65.

Novartis conducted the studies after Switzerland's medical regulatory agency requested more information on ischemic events related to Zelnorm, the director of CDER's Office of New Drugs, John Jenkins, said. The FDA received the results Feb. 28 and reviewed the data. Novartis agreed to withdraw the product from the market March 29.

The withdrawal comes five years too late, according to Public Citizen. In a March 2001 petition to the agency, the group noted that Zelnorm interacts with receptors in the intestinal tract and in the heart and warned the FDA not to approve it, Public Citizen said.

Another gastrointestinal drug, cisapride, affected the same receptors in the heart and was taken off the market because it caused cardiac arrhythmias, according to the group. Zelnorm's delayed withdrawal "raises questions about both the adequacy of the FDA's preapproval review and postmarketing surveillance," Public Citizen said.

The 29 studies included more than 11,600 patients treated with Zelnorm and more than 7,000 patients taking a placebo, Jenkins said. Among the patients taking Zelnorm, there were 13 confirmed cardiovascular events, including one death from a heart attack. One of the placebo patients had symptoms suggesting the beginning of stroke that went away without complication, according to the FDA.

While the actual number of reported events was small, the relative risk of the drug compared with the placebo was "significantly greater," prompting the withdrawal request, Jenkins noted.