FDA Panel Recommends New Irritable Bowel Syndrome Drug for Women

Nov. 16, 1999 (Washington) -- An advisory committee to the FDA unanimously recommended a new treatment for women who suffer the pain and discomfort of irritable bowel syndrome (IBS). The Gastrointestinal Drugs Advisory Committee said Lotronex (alosetron) is appropriate to treat diarrhea in IBS patients, but not for those whose symptoms include constipation.

"I think the drug was found to be most effective in women who had diarrhea predominate irritable bowel syndrome. There are questions regarding other aspects of IBS that appear to be more difficult with this drug, particularly anyone who's had a history a history of constipation," Stephen Hanauer, MD, tells WebMD. Hanauer, a gastroenterologist at the University of Chicago, says he would use the drug in his practice.

Irritable bowel syndrome is a common disorder that effects the stomach and intestines. Symptoms include abdominal pain, bloating, and abnormal bowel movements -- both diarrhea and constipation -- often following meals. About half of those with IBS have predominately diarrhea, while others alternate between diarrhea and constipation, or are primarily constipated. It is believed to affect up to 20% of adults some time during their lives. Twice as many women as men are effected by IBS, and it is aggravated by stress or life changes.

Alosetron, manufactured by Glaxo Wellcome, is the first drug of its type to be developed for irritable bowel syndrome. It works against a special receptor called 5-HT₃, a key moderator of the nervous system. Widely diffused throughout the stomach and intestines, these receptors are responsible for many of the painful symptoms of IBS, including cramping and urgency.

While it's not clear exactly how alosetron works, it apparently blocks the action of the neurotransmitter serotonin at the 5-HT₃ receptor, so pain messages from the intestines aren't sent to the brain.

In two pivotal trials supported by the manufacturer, nearly 1,300 women with the non-constipating form of IBS were given either an alosetron tablet twice daily or placebo for a total of twelve weeks. Patients kept a record of their symptoms, with pain and discomfort relief being the primary goal.

According to Glaxo Wellcome, alosetron patients reported 10% to 15% fewer symptoms in two to four weeks compared to a placebo. The FDA has designated alosetron for priority review. If alosetron wins final approval, Glaxo Wellcome's Chief Medical Officer Richard Kent tells WebMD the drug could be on the market as early as February.

Currently, treatments for IBS are largely ineffective, limited to drugs that relieve constipation or diarrhea, says Lin Chang, MD, of the University of California, Los Angeles School of Medicine and principle investigator for alosetron.

The most commonly reported alosetron-associated side-effects were constipation as well as nausea and headache. FDA medical reviewer John Senior, MD said up to 30% of those in the studies experienced severe constipation, which he described as a "nuisance."