WASHINGTON — The Food and Drug Administration said Tuesday that the popular diabetes pill Rezulin--a drug that won "fast-track" government approval but was linked to scores of liver failures and deaths--will be withdrawn promptly from the U.S. market.
Compared to alternative diabetes treatments, "continued use of Rezulin now poses an unacceptable risk to patients," said Dr. Janet Woodcock, director of the FDA's drug evaluation center.
The end for Rezulin, a Wall Street blockbuster that generated more than $1.8 billion in sales and was promoted as free of serious side effects, came Tuesday evening when Woodcock telephoned representatives of the drug's manufacturer, New Jersey-based Warner-Lambert Co.
"FDA today asked the manufacturer of Rezulin . . . to remove the product from the market," the agency said in a prepared statement. "The drug's manufacturer . . . has agreed to FDA's request."
The action came 29 months after the first acknowledged death of a Rezulin patient in October 1997. The FDA has concluded that Rezulin use has "possibly or probably" resulted in 90 liver failures, including 63 deaths and seven nonfatal organ transplants.
About 300,000 Rezulin prescriptions are sold each month.
"Patients taking Rezulin should consult with their physicians as soon as possible to discuss alternative therapies," Warner-Lambert said late Tuesday. "Warner-Lambert will work closely with the Food and Drug Administration . . . to assure a safe and efficient transition for patients."
Rezulin becomes the eighth prescription drug to be withdrawn from the U.S. market in the last 2 1/2 years. Among the recent withdrawals were Pondimin and Redux, ingredients in the "fen-phen" weight-reduction cocktail, found to cause heart and lung maladies, and Duract, a nonaddictive painkiller that the FDA associated with four liver-failure deaths.
More Toxic Than Two Other Drugs
The FDA noted that Rezulin is more toxic to the liver than two other similar drugs, Avandia and Actos, that also lower blood-sugar levels for adult-onset diabetics.
The drugs, approved in the last year, "offer the same benefits as Rezulin without the same risk," the FDA said. Added Woodcock: "We are now confident that patients have safer alternatives."
The FDA sought the withdrawal of Rezulin within two hours of a meeting that included agency physicians, lawyers and other specialists. According to people familiar with the private session, Dr. David J. Graham, the FDA's senior epidemiologist, said he estimated that 20 Rezulin patients a month are suffering liver failure.
Graham compared Rezulin's tendency to cause fatal liver failure with the worst side effects associated with the other diabetes drugs. He concluded that Rezulin, by far, is the most dangerous. Graham was one of at least five FDA physicians who challenged top agency officials, beginning at a staff meeting on Jan. 6, by saying that Rezulin's risks outweighed its benefits and that it should be withdrawn.
The removal of Rezulin comes after Warner-Lambert and senior FDA officials had supported its continued use in the face of mounting deaths and recent repudiation of the pill by numerous health insurers and hospitals.
On four occasions after Rezulin was made available for sale in March 1997, the FDA and Warner-Lambert agreed to safety changes in the drug's labeling, instead of pulling the pill off the market.
The FDA's stance stood in stark contrast to that of its counterpart in Britain, the Medicines Control Agency, which oversaw another company's voluntary withdrawal of Rezulin in December 1997. Citing safety concerns, the British authority refused to allow the reintroduction of Rezulin in March 1999.
But within a week, officials at the FDA, on March 26, 1999, convened an advisory committee meeting, dominated by supporters of Rezulin, including paid consultants to Warner-Lambert. At the conclusion of the meeting, Woodcock indicated in an interview that she did not share the concern voiced by Graham, the senior agency epidemiologist, who presented a chilling picture of Rezulin's danger.
Graham told the committee that Rezulin was one of the most dangerous prescription drugs on the market, that every patient taking the pill was at risk of liver failure and that there was no reliable way to safeguard them. This flew in the face of repeated assurances from Warner-Lambert and others at the FDA, who said that patients would be adequately protected by monthly blood tests, intended to monitor their liver functions.
In June 1999, the FDA announced that it would follow the advisory committee's advice and keep Rezulin on the market. In fact, while the FDA said that Rezulin should no longer be used as a stand-alone diabetes treatment, the agency endorsed its expanded use, in "triple combination" with two other diabetes pills.