Irritable Bowel Syndrome

FDA Consumer, July, 2001 by Carol Lewis

A Poorly Understood Disorder

It's the most common gastrointestinal disorder seen by doctors. Abdominal pain, cramps, gas, bloating, diarrhea and constipation are among the symptoms. For years, many thought it was a psychological condition, rather than a physical one. But the discomfort and inconvenience that result from the gut-wrenching pain of irritable bowel syndrome (IBS) are very real. "It feels like you're giving birth over and over again," says Hope Marcus of Miami, Fla.

Indeed, people with IBS can't stay out of the bathroom or their stomachs feel like they're tied in knots. Their bowel movements are either frequent and runny or sporadic and unusually hard. Mike Hoffman of West Palm Beach, Fla., says his intestines feel like they're constantly twisting and untwisting, "as though they're being wrung Out like a dishrag." Jeffrey Roberts of Hallandale, Fla., says the sudden recurring knifelike pain "doubles you over," while others claim it brings you to your knees. Some liken the pain to a charley horse, but in the gut--pain that is horrendous and then intensifies.

"And don't picture a diarrhea attack happening in the privacy of your own clean bathroom," says Cynthia Huschle of Tolland, Conn. "Picture it in the bathroom at work, the store, the movie theater, the park, the baseball stadium, or the port-o-potty at the fair."

IBS is a disorder of the intestine that shows no sign of disease that can be seen or measured. But doctors know that the intestine isn't functioning normally. Second only to the common cold in causing days missed from work, IBS may affect up to 20 percent of Americans--some 54 million people. IBS in women is not inherently different than in men, according to doctors at the American College of Gastroenterology (ACG), but the number of women with IBS is three times greater than the number of men. Researchers say that men are less likely to report the problem, and consequently, few studies on men with IBS have been done. Onset of IBS usually is in late adolescence or early adult life. It rarely appears for the first time after age 50.

"It's important that we allay those fears that IBS leads to more serious diseases," says William R. Stern, M.D., a Rockville, Md., gastroenterologist, "so that people can deal with the illness itself." Stern says that those he diagnoses with IBS seem more concerned about potential long-term implications of the illness than focusing on treating the symptoms they actually have. Although IBS is associated with severe pain and discomfort, he says, the illness does not lead to cancer or life-threatening conditions or surgery.

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Limits of Lotronex

Until last year, treatment for IBS relied in most cases on a diet high in fiber, use of antispasmodics and other medications, and recommended lifestyle changes. But many of those options generally treat only a single symptom of IBS. In February 2000, the Food and Drug Administration approved Lotronex (alosetron hydrochloride), the first of a new generation of agents developed specifically to treat the multiple symptoms of IBS in women whose main complaint was diarrhea. Two large clinical trials indicated that the drug was effective in relieving pain and discomfort, reducing the urgency to defecate, and decreasing stool frequency.

But as exciting as Lotronex was, its market life was short-lived. Just 10 months after hundreds of thousands of IBS sufferers began taking the drug, it was pulled off pharmacy shelves after several people died and many more suffered serious side effects associated with its use.

The FDA closely monitored Lotronex prior to, and after, its approval. Specifically, the agency was concerned about earlier reports of mild-to-moderate intestinal damage resulting from reduced blood flow to the intestine (ischemic colitis) and obstructed or ruptured bowels from complications of severe constipation. An FDA advisory committee--a panel of scientific and medical advisers outside the agency--recommended that both doctors and patients must be informed of the potentially serious adverse effects associated with Lotronex. The FDA updated the health-care professional labeling for the drug, and required the manufacturer, Glaxo Wellcome, now GlaxoSmithKline, to advise users of the risks in writing.

However, the FDA began receiving reports of deaths and more serious complications of ischemic colitis that required blood transfusions or surgery. The agency then met with the manufacturer to develop risk-management options that would ensure the drug's safe use. One option was to allow Lotronex to remain on the market under restricted conditions.

"This risk-benefit evaluation was difficult," says Janet Woodcock, M.D., director of the FDA's Center for Drug Evaluation and Research, "because we were aware that many users of Lotronex did not experience these adverse effects." But in November 2000, the manufacturer voluntarily withdrew Lotronex from the market.

The removal of Lotronex, however, has resulted in an odd turnabout. Despite the risks, some patients with IBS and their doctors want it back.