Editor's Note: In March 2007 the FDA asked Novartis -- the maker of Zelnorm -- to pull the drug from the market because of evidence that it raises the risk of heart attacks and stroke. But in July 2007 the FDA ruled that Zelnorm may be used by some patients in critical need of the drug who do not have heart problems.
Oct. 29, 2002 -- Zelnorm is safe for at least 12 months of use, say doctors who tested the newly approved drug for the constipating form of irritable bowel syndrome (IBS). But not everyone agrees.
Zelnorm -- known as Zelmac in Europe -- traveled a rocky road on its way to U.S. approval. Concerns that the drug might cause gallbladder problems held up approval for a year. Those fears proved groundless, experts tell WebMD.
However, the consumer watchdog group Public Citizen unsuccessfully petitioned the FDA to deny approval. It says the drug's small benefit in clinical trials doesn't justify the risk of possible side effects. And the group points to evidence that ovarian cysts -- sometimes requiring surgery -- could be a rare but serious Zelnorm side effect.
One reason for concern is recent history. Zelnorm affects the serotonin system, a complex series of chemical signals that keep the body in synch. Two other digestive system drugs that affect this same pathway system recently ran into problems. Propulsid was taken off the market when it turned out to harm the heart. And Lotronex, a drug for IBS diarrhea, can cause life-threatening constipation.
So there's lots of interest in a new study that followed 579 patients who were supposed to take Zelnorm for one year. About half of them stopped taking it, but only a few stopped because of side effects. Those who kept taking the drug had very few problems. One patient did develop an ovarian cyst, but lead researcher Gervais Tougas, MD, says it appeared unrelated to the medication. Tougas is director of the gastrointestinal motility laboratory and chief of gastrointestinal Services at St. Joseph's Hospital in Hamilton, Ontario. His study appears in the current issue of Alimentary Pharmacology and Therapeutics.
"There is nothing in these data to support the idea that this [ovarian cyst] is a signal that such problems happen with increased frequency in [people who take] Zelnorm," Tougas tells WebMD.
The data show nothing because the study was poorly designed, counters pharmacologist Elizabeth Barbehenn, PhD. Barbehenn is a former FDA scientist who now serves as a research analyst for Public Citizen.
"It's a big joke," Barbehenn tells WebMD. "There was no control group, so you could say anything you want. Half the people dropped out before the study ended. And there was no protocol for whether the drug caused problems. They let the investigators just decide whether they thought adverse events were related to the drug."
Private practice gastroenterologist and Johns Hopkins clinical instructor James Novick, MD, headed a major clinical trial of Zelnorm. He says ovarian cysts simply aren't a real problem for people taking Zelnorm.
"As far as I understand, the ovarian cyst concern holds no water whatsoever," Novick tells WebMD. "The most common side effect was headache -- 3% more in [Zelnorm] patients than in placebo patients. Then 5% of patients get what they consider to be diarrhea, mostly in the first couple of weeks of treatment. Best of all, there is no interaction with other drugs, not even SSRI antidepressants. That doesn't seem to happen, which is a real godsend."
Novick notes that the only other concern with Zelnorm was that several patients taking the drug needed gallbladder surgery.
Initially there was a scare the drug might be causing gallstones symptoms -- that was the data that led the FDA to slow approval, he says. "That was far more troubling than the ovarian cyst worry. But now it appears the drug has no effect on the gallbladder. The FDA had a look at the data before approving the drug, and they were happy enough."
Doctors who treat IBS patients are optimistic but cautious about using Zelnorm, says gastroenterologist Eri Ehrenpreis, MD, director of the gastroenterology fellowship training program at the University of Chicago.
"For the GI doc on the street, the impression has been positive," Ehrenpreis tells WebMD. "Everybody is a bit gun-shy about using serotonin-manipulating drugs. Remember, with Lotronex we learned of the danger only six months after approval. But I think this is a safe drug. If you look at these studies on IBS patients, these are really very intensively conducted trials. There are hundreds and hundreds and hundreds of patients who were treated."
"These organizations that want to put brakes on finding new treatments -- I'm not sure they appreciate the cost," he says. "We could keep on having no treatments if we keep raising and raising the bar for saying when the safety data looks good enough."
Novick says he thinks IBS constipation is only the tip of the iceberg for Zelnorm. He says he thinks the drug will be an extremely useful drug for other kinds of constipation -- and for other digestive system diseases, too.