“….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. Raczkowski denies that, calling the withdrawal of the drug Glaxo’s own decision.
Regardless, FDA should never have let Lotronex be sold, contends Dr. Sidney Wolfe of the consumer advocacy group Public Citizen, which had urged the drug’s ban for months. Lotronex is not very effective, and FDA ignored early warning signs of trouble, first in clinical trials and then when hospitalizations began last spring, he said…”
“Hopefully the FDA will learn something from this,” Wolfe said. “They’re saying, ‘Let’s bend over backwards and give the drug a chance.’ They wind up causing deaths and injuries that clearly would have been prevented” by stopping sales.”
In 2002 the FDA allowed GSK to re-introduced their Lotronex drug for limited use. It had previously been pulled by GSK because it was found to be dangerous. Considering GSK’s Seroxat (Paxil) has proven to be one of their most controversial and dangerous drugs of the passed 20 years, should it also be limited or restricted?
(see the BBC Seroxat Panorama E-mails for hundreds of Seroxat complaints)
Personally, I believe that Seroxat/Paxil should only be given to those who need to wean off it- those who are addicted/dependent on it etc. GSK should also help those who need to come off it with support mechanisms, guides, monitoring by an experienced doctor etc etc.
An outright ban should eventually happen in the future, however there are too many vested interests making too much money therefore GSK keep it on the market, and furthermore if they pulled it then they would effectively be admitting that there was severe problems with it all along (and I think this is the prime reason why it remains on sale).
It’s always GSK’s style to deny..
and deny and deny..
and as Glaxo deny .. patients die…
Lotronex is a prescription medicine used to treat women with irritable bowel syndrome (IBS) who have diarrhea as their main symptom (diarrhea-predominant IBS).
On November 28, 2000, GlaxoSmithKline, the manufacturer of Lotronex (alosetron) tablets withdrew Lotronex from the market.
This action was taken because the drug had been associated with reports of serious side effects such as intestinal damage as a result of reduced blood flow to the intestine (ischemic colitis), severely obstructed or ruptured bowels (complications of severe constipation), and death.
As of November 10, 2000, the FDA had reviewed a total of 70 cases of serious adverse events, including 49 cases of ischemic colitis and 21 cases of severe constipation. Of these 70 cases, 34 resulted in hospitalizations without surgery, 10 resulted in surgical procedures (some of which involved the removal of parts of patients’ intestines), and three resulted in death.
GSK gets OK to return Lotronex to US irritable bowel syndrome market
GlaxoSmithKline has been given the go-ahead by the US Food and DrugAdministration to re-introduce its irritable bowel syndrome drug Lotronex (alosetron), about 18 months after the company voluntarily withdrew the product due to the agency’s safety concerns.
Following a number of cases of serious gastrointestinal events in Lotronex-treated individuals, including ischemic colitis, GSK pulled the drug from the market after failing to agree on a risk-management plan that would support its safe use (Marketletter December 4, 2000). However, there is a desperate lack of effective therapies for IBS and patients who had been helped by the therapy have been lobbying for its re-introduction. Earlier this year, Lotronex received the backing of an FDA advisory panel which supported the use of measures to reduce risk, such as limiting supplies of the drug and strict oversight of its use (Marketletter April 29).
On June 7, the FDA approved GSK’s supplemental New Drug Application for Lotronex tablets, allowing it to be marketed specifically “for women with severe diarrhea-predominant IBS who have failed to respond to conventional therapy, whose IBS symptoms are chronic and that other gastrointestinal medical conditions that could explain their symptoms have been ruled out,” said the company in a statement.
By this definition, symptoms which would allow clinicians to diagnose their patients as having severe IBS would include frequent and severe abdominal pain, fecal incontinence or the uncontrolled urge to have a bowel movement, or curtailment of daily activities because of their condition.
This represents a significant narrowing of the indication over that originally approved by the agency, although off-label use of the drug, for example in men with severe IBS, cannot be ruled out. Lotronex will also carry a black box warning pointing to the risk of severe gastrointestinal side effects, such as ischemic colitis. Commenting on the reversal, Lester Crawford, the FDA’s Deputy Commissioner, said: “all drugs have risks. It is the FDA’s job to balance the need for access to effective medications with those risks.”
Lotronex had been tipped to become a major new product for GSK during its development, with some analysts suggesting that its sales could approach $1 billion a year, providing the firm was able to get the message across to doctors that IBS was amenable to treatment. However, the limitations on its use means that its re-introduction is expected to have only a minor impact on GSK’s finances. A return to market will also take several months, as the company relaunches manufacturing of the drug and gets its risk-management program up to speed.
DAVID WILLMANTimes Staff Writer
Agency officials agreed in July 1999 to conduct a fast-track medical review of Lotronex, a pill from Glaxo Wellcome Inc. intended to treat irritable bowel syndrome in women. To justify such accelerated review, the FDA must find that the targeted disease is “serious.”
Irritable bowel syndrome can result in abdominal pain and frequent trips to the bathroom. But it neither maims nor kills people.
An FDA medical officer, Dr. John R. Senior, discovered during the review that four Lotronex patients in clinical studies suffered a potentially life-threatening complication called ischemic colitis, which results from inadequate blood flow to the colon.
Senior, a former pharmaceutical industry executive and a gastrointestinal specialist, knew the rarity of ischemic colitis: Some physicians can practice for decades without treating a single case.
While some cases would be mild and reversible, Senior wrote, ischemic colitis “can be catastrophic.”
Senior found other troubling results. He warned that 27% of the patients who took Lotronex in Glaxo’s studies experienced constipation. He noted that not a single patient who took a placebo pill developed ischemic colitis and that only 5% of the placebo patients got constipated.
Glaxo representatives denied that Lotronex had caused the cases of ischemic colitis and said any risks could be adequately managed. But Senior warned of the potential for Lotronex patients to suffer debilitating bowel injuries or death.
If these were the risks, what were the potential benefits?
FDA reviewers found that Lotronex improved symptoms in only 10% to 20% of the patients. Still, an FDA advisory committee, whose participants included a paid consultant to Glaxo, unanimously recommended approval. (The yes vote voiced by the Glaxo consultant, Dr. Arnold Wald of Pittsburgh, was invalid, agency officials say, because of his status as a temporary appointee.)
The FDA had a choice: Withhold approval of Lotronex until Glaxo undertook a major safety study to assess the drug’s link to ischemic colitis or approve the drug conditioned on a pledge by Glaxo to perform the study in the following year.
Top FDA officials chose not wait. They approved Lotronex on Feb. 9, 2000. The original labeling said that ischemic colitis had occurred “infrequently” in the clinical studies and that there was no way to predict which patient was at highest risk.
It was Lotronex’s first approval worldwide. Securities analysts estimated it would generate sales of up to $2 billion within five years.
A spate of bowel injuries emerged quickly–consistent with Senior’s fears.
In June, the FDA’s Woodcock embraced the crafting of a “medication guide” aimed at advising patients of Lotronex’s risks. But the leaflets were not delivered to pharmacies until late September. Meanwhile, Woodcock’s staff proposed a black box warning for Lotronex’s label but retreated when Glaxo publicly opposed the idea.
By October, 49 cases of ischemic colitis in Lotronex patients–including five deaths–had been reported to the FDA. Records show that no fewer than 91 patients were hospitalized, many with severe constipation. Several bowel surgeries, including the removal of a patient’s colon, were performed.
FDA officials who had backed the approval of Lotronex maintained their support for the drug into November, but staff epidemiologists pointed to the surgeries and deaths and the likelihood that those voluntarily reported events were a small fraction of the true scope of harm.
They urged withdrawal.
Glaxo and the FDA announced on Nov. 28 that Lotronex would be pulled from the U.S. market. At that point, Glaxo’s promised study of the drug’s link to ischemic colitis still had not enrolled a single patient.
Asked why the FDA approved Lotronex, given the ischemic colitis risk, Woodcock indicated that her aides had believed Glaxo’s view of the risk more than Senior’s.
“At the [November 1999] advisory committee, the company proposed that these were [unsurprising] incidences of ischemic colitis, not causally related to drug,” Woodcock said, adding: “We can’t not approve drugs because they have certain side effects; they’re all going to have side effects. We have to determine, are they going to be adequately managed?”
In subsequent written comments, Woodcock noted that some patients complain when a drug they believe helps them is withdrawn.
“People who suffer from serious, life-limiting, or life-threatening illnesses have repeatedly and forcefully told the FDA that they are willing to take greater risks because of the nature of their illnesses,” Woodcock told The Times.
A Glaxo executive, Dr. Richard S. Kent, said the company continued to believe that the risks could be satisfactorily managed through labeling and related measures.
During the nine months that Lotronex was on the U.S. market, sales exceeded $56 million through October, according to the research firm IMS Health. The drug was never sold in any other nation.