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.
July 15, 2004 -- An expert panel has backed expanded use of the anticonstipation drug Zelnorm. But they're calling for far tighter restrictions than its manufacturer had requested.
Advisors also voted for stricter safety warnings for existing uses of Zelnorm amid concerns that it can lead to a dangerous form of intestinal disease called ischemic colitis.
Advisors voted 10 to 3 to approve Zelnorm for the treatment for chronic constipation with no identifiable cause -- fewer than three bowel movements per week. But every expert voted for approval on the stipulation that the drug be used only in women and not in men or people aged 65 and over.
That was a far more restrictive approval than Novartis, the drug's manufacturer had sought. The company was asking FDA to approve Zelnorm to treat chronic constipation in men and women of all ages.
"This shouldn't be used in the elderly and that needs to be made loud and clear," says Brian L. Stom, MD, an epidemiologist from the University of Pennsylvania School of Medicine and a member of FDA's Gastrointestinal Drugs Advisory Committee.
The FDA usually follows the recommendations of its expert panels.
The drug was approved in August 2002 to treat women with constipation caused by irritable bowel syndrome. Until April, FDA had received 20 reports linking it to development of ischemic colitis, a dangerous disorder in which blood supply to the intestine is cut off or severely restricted. Thirteen of those cases required hospitalization and there was one death, FDA officials say.
The FDA has not established that Zelnorm directly caused the ischemic colitis cases, but officials note that many of the patients showed no signs or risk factors for the disease before taking the drug.
"The role of [Zelnorm] cannot be ruled out," says Gary Della'Zanna, DO, a safety reviewer with FDA's division of drug risk evaluation.
Doctors have written more than 2 million Zelnorm prescriptions since its initial approval. But the cases prompted the FDA to send out millions of letters alerting of the risks of ischemic colitis and a side effect of severe diarrhea in some patients.
In a 12-week study of 1,265 patients submitted by Novartis, 43% of those taking 6 milligrams of Zelnorm per day experienced an improvement in constipation vs. 31% who experienced similar improvement with placebo. Another study showed similar responses.
Men and Elderly Understudied
Experts expressed concern, however, that both men and adults aged 65 and over were underrepresented in the studies.
Panelists were unanimous in rejecting a recommendation that Novartis had shown the drug to be safe or effective in elderly persons. They voted 8 to 5 to reject the drug's safety for men, citing insufficient data.
"This is not what we expected," one Novartis official said following the vote.
Bo Joelsson, MD, head of gastroenterology for Novartis, says that despite the panel's recommended restrictions, the company is still optimistic. "This is not really an elderly problem. This is a problem in all age groups. There's still a lot of patients that need this drug," he tells WebMD.