WASHINGTON, March 30 — The maker of Zelnorm, a medicine that treats constipation-related irritable bowel syndrome, stopped selling the drug Friday after federal drug officials concluded that it might cause heart attacks and strokes.
In 29 studies, 13 of 11,614 patients given Zelnorm had heart problems, including one who died. Just one of 7,031 patients given placebos had similar problems.
Officials at the Food and Drug Administration said the drug was not effective enough to merit such risks.
Executives at the drug’s maker, Novartis, the giant Swiss drug concern, said the studies’ findings could be a fluke and vowed to continue selling Zelnorm in Europe.
Driven by aggressive advertising, Zelnorm had $561 million in sales last year, up 34 percent from 2005. About 500,000 people are currently taking the medicine for the ailment, which is also known as I.B.S.
Patients criticized the food and drug agency’s decision.
“I can’t believe the F.D.A. would do such a thing. Why are they being so cruel?” asked Lori Egan, 39, of Fredericksburg, Va. “I would rather take my chances of having a heart attack than live in I.B.S. hell.”
When in 2000 the agency forced the withdrawal of Lotronex, another drug for irritable bowel syndrome, it was so inundated by complaints from sufferers that for the first time it allowed limited sales of a withdrawn drug to start again.
Officials promised to consider a similar program for Zelnorm.
Zelnorm seems to work by encouraging a wavelike movement in the gut that helps move stool through. Dr. John Jenkins, director of the Office of New Drugs at the agency, said he did not know why the drug might cause heart problems.
“There may be a hypothetical mechanism where Zelnorm will cause vasal spasms in the arteries,” Dr. Jenkins said. “That has not been proven.”
Agency observers said that the Zelnorm decision demonstrated that the F.D.A., which has been criticized by some lawmakers as too lenient, might be getting tougher.
But the Zelnorm case also shows how serendipity plays an important role in the agency’s safety decisions.
Congress is debating several bills that could sharply change the way the agency operates. The Zelnorm case could prove important in those debates.
The worries about Zelnorm began with a routine safety review last year by drug officials in Switzerland. To prepare, Novartis scientists gathered data from all 29 of their Zelnorm studies and looked for patterns. By January, they had found the difference in heart problems.
Thirteen cases of heart problems in more than 11,000 patients is about what one might find in a normal population, said Dr. Stephen Cunningham, head of clinical development and medical affairs in the United States at Novartis.
The company reported its finding to the drug agency on Feb. 22. The agency mobilized a team of reviewers.
The team met with Novartis officials on March 15 to ask questions. On Thursday, the F.D.A. notified the company that it had decided that Zelnorm should be withdrawn. On Friday the company complied.
In a news conference, Dr. Jenkins said the American agency was considering requiring drug makers to perform regularly the kind of analysis that Novartis undertook for the Swiss agency.
At present, the agency generally undertakes such analyses only when drug makers seek to win approval for a new use of a medicine, he said.
“We would have to rely on sponsors to do those and submit them,” Dr. Jenkins said.
Some on Capitol Hill have proposed legislation that would require regular safety reviews of approved medicines.
An important factor in the agency’s decision was that Zelnorm does not work very well.
Novartis’s own studies show that it is only 5 percent to 10 percent more effective than placebos at resolving the symptoms of constipation-related irritable bowel syndrome in women. Men were dropped from the initial studies because the drug did not appear to work in them at all.
The drug’s popularity has been driven by an eye-catching advertising campaign in which women pulled up their shirts to reveal writing on their bellies.
In a 2003 presentation, Thomas Ebeling, chief executive of Novartis’s drug division, said Zelnorm’s sales in the United States were closely tied to those commercials.
“The weeks we go off the air, the growth flattens,” Mr. Ebeling said. “When we restart, you see the growth accelerate again.”
Zelnorm’s withdrawal is likely to intensify a debate about whether widespread drug advertising is appropriate. Some on Capitol Hill have called for curbs on drug commercials, particularly in the year after a drug’s introduction.
