U.S.

Drugmaker Pulls Lotronex

By CBSNews.com staff CBSNews.com staff

November 28, 2000 / 6:38 PM EST / CBS

Anticipating a possible government recall order, the pharmaceutical giant Glaxo Wellcome Tuesday pulled its popular intestinal drug Lotronex off the market.

CBS News Correspondent Sharyl Attkisson reports most of the 300,000 women who've used the drug have done so without problems, but some have reported serious side effects.

The FDA approved Lotronex last February, hoping it could help hundreds of thousands of women suffering from painful diarrhea or constipation caused by a condition known as irritable bowel syndrome (IBS).

In just eight months on the market, Lotronex was linked to 54 cases of a severe and potentially fatal abdominal problem called ischemic colitis, and 20 more possible cases, including five deaths, listed in so-called "adverse event" reports submitted to the FDA.

Other reports said patients suffered constipation so severe that they needed parts of their intestines surgically removed.

A review of FDA records by The Associated Press indicates the agency knows of at least eight women who died with intestinal side effects while taking the prescription drug.

Consumer advocate Dr. Sid Wolfe twice petitioned the FDA to ban Lotronex.

"To take a disease that is not life-threatening and treat it with something that doesn't really work much better than a placebo and wind up killing people or hospitalizing large numbers of people doesn't seem like a good trade-off," Wolfe said.

IBS — a mysterious disorder that affects up to 15 percent of Americans, mostly women — is not life threatening but can cause misery. Also known as spastic colon, it involves chronic or recurrent abdominal pain, the sudden and urgent need to go to the bathroom and either frequent diarrhea, constipation or both.

In studies, Lotronex offered only modest relief to women whose main IBS symptom was diarrhea. It did not work for men, and was declared downright dangerous for anyone with constipation.

Even before Lotronex was approved, FDA scientists raised concerns about the very side effects that are now showing up.

One noted that Glaxo Wellcome found several cases of abdominal disorders in clinical trials, but "misleadlingly listed (all of them) as unrelated to the study…This…represents…a potentially serious problem."

"It is very disturbing that (Glaxo) has…totally ignored" it, warned the FDA medical officer.

Recent Recalls

Other drugs banned by the FDA in the past 30 months:

Lotronex, a drug for irritable bowel syndrome approved last February and pulled from the market Tuesday.

Rezulin, a diabetes drug approved in 1997 was banned last March.

Duract, an anti-inflammatory painkiller, was approved in 1997 and banned in 1998.

Posicor, a blood pressure medicine, was approved in 1997 and banned in 1998.

Redux, a diet drug and part of the fen-phen diet drug cocktail, was approved in 1996 and banned in 1997.

Rotashield, a vaccine for severe childhood diarrhea caused by rotavirus, was approved in 1998 and removed in 1999.

Propulsid, a chronic heartburn drug approved in 1993, was pulled from general pharmacies last summer but is being made available to a few severely ill patients.

Phenylpropanolamine or PPA, found in dozens of over-the-counter cold remedies and diet drugs, will be banned soon.

(Source: AP)

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Still, FDA officials decided Lotronex held promise as the first drug that could help so many people who suffer the misery of IBS. The FDA rushed through its approval and, under pressure from Glaxo Wellcome, dropped their proposal to put special "black box" warnings on the label.

However, the FDA warned the day it approved Lotronex that it might cause serious side effects because four women in clinical trials suffered ischemic colitis.

Within six months, there were so many reports of ischemic colitis that the company strengthened the warning label. Reports continued to pour in, doubling over the next two months.

By August, the FDA ordered Glaxo to attach special safety warnings to every bottle of Lotronex sold, urging doctors not to prescribe it to patients with constipation or other risk factors and telling women to stop using it at the first sign of trouble.

Still, however, the FDA was reluctant to ban Lotronex because some doctors and patients insisted the drug greatly helped them. And Glaxo argued Lotronex could be used safely by the right patient: Among the first five deaths, for instance, four were women over age 65, suggesting that it should not be prescribed to older women, said Dr. Richard Kent, Glaxo's chief medical officer.

Glaxo Wellcome Tuesday said it disagrees with the FDA's assessment of Lotronex, but still decided to address the agency's concerns by pulling the drug.

It's now the seventh prescription drug withdrawn from the market in the last two-and-a-half years.

Glaxo contends Lotronex is safe when ued by the right patient, and calls it no more risky than some other big-selling medicines. But, saying it was under orders from FDA, the company announced Tuesday that it would cease distribution of Lotronex immediately and recall the drug from pharmacies.

The FDA says it offered Glaxo an alternative to yanking the drug from the market, but the company rejected that proposal.

Tuesday morning, FDA told Glaxo the agency wanted to keep Lotronex on the market but restrict sales to just a few women with severe IBS who are treated by specialists, said FDA's Dr. Victor Raczkowski. Such restricted sales are used with the drugs thalidomide and Accutane, notorious for causing birth defects.

Kent called the option unworkable and said FDA's response was then was to order Lotronex banned. The FDA denied that, calling the withdrawal of the drug Glaxo's own decision.

Glaxo shares fell $2.31, or nearly 4 percent, to close at $56.56 Tuesday on the New York Stock Exchange.

About 150,000 people use Lotronex, and those who have supplies remaining can contact Glaxo about a refund at 1-888-825-5249.