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`June 23, 1998
`
`New Painkiller Is Withdrawn After 4 Deaths
`
`By SHERYL GAY STOLBERG
`
`WASHINGTON, June 22— For the second time in two weeks, the Food and Drug Administration has taken
`the rare step of pulling a prescription drug from pharmacy shelves, a move that is renewing questions about
`whether the agency's new emphasis on speeding up drug approvals is allowing unsafe medicines to reach
`patients.
`
`The drug, Duract, a painkiller manufactured by Wyeth-Ayerst Laboratories of St. Davids, Pa., has caused a dozen
`cases of serious liver failure since it went on the market last July; four patients died and eight required liver
`transplants. All the cases involved patients who took the drug for longer than the recommended 10 days.
`
`Both the agency and the company are advising patients who have been taking Duract for longer than 10 days to
`stop immediately; all patients who are using the medication should consult their doctors.
`
`Today's announcement is the third time in nine months that the food and drug agency has removed a new
`medicine for safety reasons. On June 8, Posicor, a medication for high blood pressure, was banned because it
`turned out to be potentially lethal when used with a long list of other drugs. Last September, the popular diet
`drug Redux was taken off the market along with its close cousin, fenfluoramine; both were implicated in heart-
`valve problems.
`
`''This is the worst record we have ever had; it's unprecedented,'' said Thomas J. Moore, a senior fellow in health
`policy at George Washington University Medical Center who studies drug safety. ''We are paying the wages of the
`one-sided debate that we have had in this country that the speed of F.D.A. approval is the only issue.''
`
`It is extremely unusual for the F.D.A., which is widely regarded as the most safety-conscious consumer
`protection agency in the world, to withdraw a drug once it has been approved. Including the most recent
`withdrawals, there have been only six in the past decade, said Dr. Murray M. Lumpkin, deputy director of the
`Center for Drug Evaluation and Research at the agency.
`
`In recent years, however, the agency has been under intense pressure from Congressional Republicans to speed
`its drug approval process; it has given its imprimatur to a record number of new drugs, 92, over the past two
`years. That fast-track approval process has been financed in large part by the pharmaceutical industry; between
`1992 and 1997 the industry paid the F.D.A. $327 million in user fees. The agency used the money to beef up its
`drug review division, buying new equipment and hiring 600 additional reviewers.
`
`Proponents of the fast-track system argue it is necessary to bring life-saving therapies to patients who
`desperately need them. But Dr. Lumpkin estimates that only 20 percent of the new medicines approved fall into
`the category of breakthrough drugs. The rest, including Duract and Posicor, are what is known as ''me-too
`drugs,'' medicines that treat disorders for which there are already plenty of approved therapies, leaving critics to
`wonder not only why they were approved in a hurry, but why they are let on the market at all when there is any
`hint of a safety problem.
`
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`''The agency has been put under too much pressure to approve more drugs faster, whether they are needed or
`not,'' said Larry D. Sasich, a pharmacist for Public Citizen's Health Research Group, an advocacy organization in
`Washington. ''This is the price that the American public is paying for believing that the F.D.A. was keeping
`lifesaving medicines out of the hands of the American public, which is simply not true.''
`
`Dr. Lumpkin defended the agency, saying the review of Duract took nearly three years and was extremely
`thorough. Although the agency was aware of the potential for liver problems with long-term use, he said, it made
`a calculated decision to approve the drug for short-term use, no more than 10 days, reasoning that the benefits
`outweighed the risks.
`
`''This was not a rushed decision by any means,'' Dr. Lumpkin said, adding that the agency still believes the drug
`is safe and effective when used for fewer than 10 days. ''There is nothing in our data that makes you think that if
`you used this product as labeled it would be unsafe.''
`
`But Dr. Sasich wondered why the agency approved Duract in the first place, when there are plenty of other drugs
`on the market to treat pain.
`
`''This was a drug that no one needed,'' he said. ''It's the same scenario as we went through with Posicor.''
`
`During the 11 months that Duract was on the market, it was prescribed to 2.5 million people, according to the
`manufacturer, Wyeth-Ayerst, a division of American Home Products Corporation. Dr. Philip deVane, the
`company's North American medical director, said 15 percent of the prescriptions were written for longer than 10
`days, despite clear warnings on the label.
`
`The drug, which goes by the generic name bromfenac, belongs to a class of medications known as nonsteroidal
`anti-inflammatory drugs. In addition to treating pain, these drugs, some of which are so safe they can be sold
`over the counter, are often used for chronic conditions like rheumatoid arthritis. Experts say patients typically
`take such drugs for weeks or months at a time, which may explain why doctors continued to prescribe Duract for
`long periods.
`
`Dr. Lumpkin said the long-term and short-term effectiveness of Duract was studied in 2,500 patients before it
`was approved. When patients in the long-term studies began showing evidence of dangerously elevated liver
`enzymes, he said, they were taken off the drug. After that, their liver functions returned to normal.
`
`Duract went on the market last July; by February of this year, Dr. deVane said, Wyeth-Ayerst had received three
`reports of liver injuries to patients who were taking the drug for longer than 10 days. At the F.D.A.'s request, the
`company then put a black box on Duract packages to highlight the warning against extended use. At the time, no
`patients had died; Dr. deVane estimated that only one of every 20,000 patients who took Duract suffered serious
`injury.
`
`But when the food and drug agency continued to receive reports of liver trouble, including the four deaths, Dr.
`Lumpkin said, officials decided that the risk was no longer worth the benefit.
`
`''When there are other alternatives that don't have this kind of serious reaction over long-term use, there is no
`reason to take the risk,'' he said.
`
`The agency asked the manufacturer to withdraw Duract, and Wyeth-Ayerst complied, describing the decision as
`voluntary.
`
`Page 2 of 3
`
`

`
`In both the case of Posicor and Duract, Dr. Lumpkin said, the agency's system for tracking adverse reactions to
`drugs once they are approved picked up problems that could not be detected in clinical trials, which involve
`much smaller numbers of people.
`
`''It's the system working; it's not the system not working,'' he said.
`
`But Mr. Moore, the health analyst at George Washington University, contends that the monitoring system is
`''extremely weak.''
`
`While the agency has 1,400 employees whose primary duties are to approve new drugs, he said, only 52 are
`assigned to monitor these drugs once they get into the medicine cabinets of consumers. That patients died even
`after doctors were warned about Duract, he said, is evidence of the system's flaws.
`
`''We have no system to know whether even the safety warning messages we are sending are even being received
`and heeded by doctors,'' Mr. Moore said. ''We don't even check.''
`
`Copyright 2015 The New York Times Company
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