The drug's indication has been narrowed to be only for treatment of women with severe, diarrhea-predominant Irritable Bowel Syndrome (IBS), who have failed to respond to conventional IBS therapy.
Less than 5% of IBS is considered severe, and only a fraction of severe cases are diarrhea-predominant IBS.
Limiting the use of alosetron (Lotronex) to this severely affected population is intended to maximize the benefit to risk ratio.
The marketing of alosetron is being restricted because serious and unpredictable gastrointestinal adverse events, including some that resulted in death, were reported in association with its use when it was previously marketed.
The approved sNDA for alosetron includes a risk management program that the drug's manufacturer, GlaxoSmithKline (GSK), will implement.
| Alosetron approved for women with severe, diarrhea-predominant IBS.
"All drugs have risks. It's FDA's job to balance the need for access to effective medications with those risks," said Dr Lester M. Crawford, FDA Deputy Commissioner.
"Informed decision-making by physicians and patients is critically important in managing the risks of marketed medications. Everyone needs to take an active role," added Dr Janet Woodcock, Director of FDA's Center for Drug Evaluation and Research.
The action follows a recommendation on 23 April 2002, by FDA's Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Subcommittee of the Advisory Committee for Pharmaceutical Science, to restore access to alosetron through a restricted distribution and use program.
As of 8 March 2002, there had been 84 cases of ischemic colitis and 113 cases of serious complications of constipation reported to FDA through its Adverse Event Reporting System.
The 84 cases of ischemic colitis resulted in 54 patients requiring hospitalization, 2 receiving blood transfusions, 11 requiring surgery, and 2 deaths.
The 113 cases of serious complications of constipation resulted in 83 patients requiring hospitalization, 34 undergoing surgery, 2 receiving blood transfusions, and 2 deaths.
FDA first approved alosetron in February 2000.
GlaxoSmithKline voluntarily withdrew the drug from the market in November 2000, due to post-marketing reports of complications and deaths.