The Food and Drug Administration announced yesterday that some patients suffering from irritable bowel syndrome could resume using the drug Lotronex, marking the first time the agency has allowed back on the market a prescription drug that was pulled for safety reasons.
The FDA announced that Lotronex could return under tight restrictions designed to limit the number of people using it and minimize the risk of serious side effects. The FDA withdrew the drug in 2000 after it was linked to complications that killed at least four people and sent 127 to the hospital.
The action came in response to heavy pressure from Lotronex users, who argued that the drug had allowed them for the first time to control debilitating chronic diarrhea and stomach pains caused by their illness.
The turnaround illustrates the increasingly fine line the agency is trying to navigate between making medicines available to desperate patients and protecting patients from potentially deadly side effects. As the FDA has speeded its drug review process in recent years, under pressure from Congress and drug companies, the agency has been criticized by some for giving too much attention to potential benefits and not enough to potential risks.
Under the FDA's new guidelines, Lotronex is supposed to be prescribed only by doctors especially familiar with the drug and only to a relatively small number of women with a particularly severe form of the disease who have not responded to other treatments. All patients will have to sign a form documenting that they are familiar with the drug's dangers.
Other drugs approved with similar restrictions include RU-486, the controversial "abortion pill," and thalidomide, the notorious medicine that can cause birth defects, which was recently approved to treat skin sores caused by leprosy.
"Informed decision-making by physicians and patients is critically important in managing the risks of marketed medications," said Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research. "Everyone needs to take an active role."
Sidney Wolfe of the Public Citizen Health Research Group, a consumer group that initially petitioned the FDA to have Lotronex withdrawn, said the agency had "abdicated its responsibilities" to protect public health with the Lotronex decision. He has argued the drug should be available but more tightly controlled.
"Woodcock and I both got lots of letters from groups of patients who thought they benefited from Lotronex," he said. "Her response was to put the drug back on the market . . . and I believe that is a decision that will come back to haunt her."
Despite the new, tighter restrictions, doctors legally could write prescriptions for the drug for more people than the narrow group officially approved to receive it. Although Lotronex was never approved for use by men, a number of those most active in pressing for its return were male patients.
Millions of Americans suffer from irritable bowel syndrome, most of them women. The disease is not life-threatening, but the symptoms can be so severe that people have difficulty leaving their homes.
An estimated 275,000 people had used Lotronex before it was taken off the market. GlaxoSmithKline, which makes the drug, estimates that 100,000 Americans now meet the criteria set by the FDA for Lotronex use, but the company had no projections of how many might use it under the restricted program. The company said it expected to have the drug available for patients by the end of the year.
The FDA reported yesterday that four people had died and 45 had required surgery because of complications from Lotronex, primarily severe (and sometimes fatal) constipation and ischemic colitis, which is the cutting off of blood flow to the colon. Wolfe said that adverse event reports monitored by his group showed a larger number of Lotronex deaths and injuries than the FDA reported.
Jeffrey Roberts of the IBS Self Help Group, which fought to have the drug restored, welcomed Lotronex's return. "A catastrophic mistake was averted and individuals can now breathe a sigh of relief," he said in a statement. "We are pleased with the initial method for access. However, we hope this onerous method of access will be loosened over time for patients continuing to show positive results" with Lotronex.
When problems with Lotronex first appeared, the FDA asked GlaxoSmithKline to develop a plan to make the drug available on a more restricted basis. But the FDA and the company could not reach an agreement, and the drug was taken off the market nine months after it was launched. Because of the pressure from former Lotronex users, however, the FDA and the company continued discussing how it might be brought back to the market.
An expert panel advising the FDA in April concluded that the drug should be restored with restrictions, and yesterday's decision generally followed those recommendations. The agency does, however, allow doctors to simply confirm they understand the potential problems with Lotronex use rather than follow a stricter protocol proposed by the advisory group.
"The patients who wrote letters and e-mails, made phone calls and especially those who came in person to provide compelling and impassioned testimony at the advisory committee meeting deserve a great deal of credit for getting [the company] and the FDA to resolve all of the issues leading to the reintroduction of this product," said Peter Traber, GlaxoSmithKline's chief medical officer.
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