Strict Return of Bowel Drug Lotronex Approved by FDA

The Food and Drug Administration approved the limited return Friday of a bowel disorder drug that was pulled after evidence emerged that many people taking it developed serious and sometimes fatal ailments.

The drug, Lotronex, will be approved only for women with severe, diarrhea-predominant irritable bowel syndrome who have not responded to traditional therapy.

The drug was pulled by its manufacturer, GlaxoSmithKline, in November 2000, eight months after it was approved.

As of March, the FDA said, it had been told of 84 cases of ischemic colitis and 113 cases of serious complications of constipation in people taking Lotronex. Scores of people were hospitalized, and two cases of each kind of ailment were fatal, the FDA said.

“All drugs have risks,” said Lester M. Crawford, the FDA’s deputy commissioner. “It’s FDA’s job to balance the need for access to effective medications with those risks.”

The FDA brought back the pill after an outpouring of requests from patients who found relief from the symptoms of the common bowel problem, which causes pronounced abdominal bloating and pain and other vexing inconveniences, such as the need to go to the bathroom on a moment’s notice.

GlaxoSmithKline has developed a program to guide doctors and will ask pharmacists to fill only those prescriptions with stickers indicating a doctor has participated in the program. Patients will be asked to read and sign a document explaining the risks of the pill.

“Informed decision-making by physicians and patients is critically important in managing the risks of marketed medications,” said Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research.

Lotronex’s on-again, off-again history reflects the delicate balance the FDA must reach in handling drugs with demonstrated lethal risk and relatively modest proven benefits.

Lotronex was one of 11 prescription drugs withdrawn for safety reasons in the four years ending in May of last year. Eight of those drugs were approved from 1993 through 2000, an era when the FDA was under pressure from members of Congress and the White House to become more of a partner than an adversary of the $100-billion pharmaceutical industry. Aside from one antibiotic pill, none of the 11 withdrawn drugs was a proven lifesaver.

Opponents of Lotronex accused the FDA of making an irresponsible decision that will recklessly endanger patients.

“This drug is very, very dangerous,” said Dr. Sidney Wolfe of the consumer group Public Citizen. “I don’t know of any other drug put on the market with a more frequent risk of such a life-threatening illness.

Wolfe pointed to FDA data that showed the medicine at the dose suggested by the FDA does not have a statistically better result than placebos. The benefits of the treatment, he said, do not come close to justifying the risks of serious side effects, which could result in surgery, colectomy and death.

“If this were a drug to treat cancer or a life-threatening illness, it might be worth taking the risk,” Wolfe said.

FDA officials, however, said that they targeted the approval to those whose symptoms are most severe. The goal was “to steer the use of the drug to patients who are most likely to get the most benefit of the drug, patients who might be willing to accept more risk,” said Victor Raczkowski, acting director of FDA’s division of gastrointestinal and coagulation drug products.

Illness has severely disrupted the social and work lives of many of the patients who will qualify for the drug, Raczkowski added.

The drug company calculates that there are 185,000 women nationwide who could qualify for this drug.

About 15% to 20% of patients who try the drug find some relief, according to the FDA.