Zelnorm is taken off the market
Irritable bowel syndrome can cause constipation, which the widely prescribed drug treats. The FDA cited heart risks in requesting its withdrawalMar 31, 2007 | Los Angeles Times A widely prescribed drug for severe constipation is being taken off the market after it was linked to a higher risk of heart attacks and strokes, federal regulators said.
Doctors said the voluntary withdrawal of Zelnorm by its manufacturer would leave few options for patients who suffer from a type of irritable bowel syndrome that affects about 12 million Americans, mostly women.
"This is really a sort of one-of-a-kind drug," said Dr. Bennett Roth, chief of gastroenterology at UCLA Medical Center. "It doesn't work for everybody, but in those for whom it works, it gets pretty good results. There are going to be a lot of unhappy patients."
The Food and Drug Administration said it asked for the withdrawal of Zelnorm after an analysis of 29 studies involving more than 18,000 patients found that those who took the medication had significantly higher rates of cardiac problems than those who were given a sugar pill.
Patients taking Zelnorm should call their doctors to discuss alternative treatments, the agency said. Options include laxatives. Any patients who experience chest pain, sudden weakness or other symptoms of heart attack or stroke should immediately go to the emergency room.
The drug's maker, Novartis, said it was complying with the FDA request but did not believe the drug was to blame.
A consultant who reviewed the data for the company said the rates of heart problems in patients taking Zelnorm roughly corresponded with the expected rates in the population.
But Dr. John Jenkins, head of the FDA's Office of New Drugs, said the differences between patients on Zelnorm and those given a sugar pill were significant.
Jenkins said 13 patients taking Zelnorm suffered heart attacks, chest pain or strokes, and one died. Of those taking a sugar pill, one had symptoms of a stroke that went away without further problems. None died.
Although the overall rates of problems were low 0.1% for those taking Zelnorm, compared with 0.01% for those on the sugar pill, the disparity between the two groups got the FDA's attention.
"We found the signal worrisome enough that we thought the benefit of the drug no longer outweighed the risk," Jenkins said.
Zelnorm ranked among the top 200 brand-name prescriptions last year, according to the Internet site drugtopics.com, which monitors the drug industry.
More than 2.6 million prescriptions were written for the medication in 2006, a 25% increase from the previous year.
Novartis said its sales of the drug approached $490 million in 2006. "The product was growing quickly," said spokeswoman Sherry Pudloski. It was approved in the United States in 2002.
Novartis, headquartered in Switzerland, said it would continue talking with the FDA to see whether the medication could remain available to a limited number of patients under tightly controlled conditions. The FDA followed a similar approach a few years ago with another drug for irritable bowel problems, Lotronex.
The discovery of possible heart risks followed a 2004 request from Swiss regulators for a closer look at the data. Novartis submitted the findings to the FDA beginning in February.
Swiss regulators have decided to keep Zelnorm on the market in that country with stronger warnings, Pudloski said. And Novartis is discussing the drug's future in Canada with regulators there.
Peter Lurie, deputy director of Public Citizen's Health Research Group, said his calculations indicated that those taking Zelnorm would face a seven- to eight-fold increase in risk of cardiac problems.
"When you remember that a number of patients taking this drug are younger, otherwise healthy people, the tolerance for serious side effects should be very low, even if they are rare," Lurie said.
Irritable bowel syndrome is estimated to affect up to 20% of Americans, most of whom do not seek treatment. But some patients suffer from continuing bouts of sharp abdominal pains and bloating. About a third have constipation, another third have diarrhea and the remainder alternate between the conditions.
The causes of the syndrome are not fully understood.