Pubdate: Tue, 23 Jun 1998 Source: San Jose Mercury News (CA) Contact: Website: http://www.sjmercury.com/ Author: Sheryl Gay Stolberg, New York Times PAINKILLER TAKEN OFF THE MARKET Duract Linked To Major Liver Damage WASHINGTON -- For the second time in two weeks, the Food and Drug Administration has taken the rare step of pulling a prescription drug off 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 have died and eight required liver transplants. All cases involved patients who took the drug longer than the recommended 10 days. Both the agency and the company advised patients who have been taking Duract longer than 10 days to stop immediately; all patients who are using the medication should consult their doctors. The announcement Monday was the third time in nine months that the agency removed a new medicine for safety reasons. On June 8, the high blood pressure medication Posicor was banned because it was potentially lethal when used in combination with a long list of other drugs. In September, the popular diet drug Redux was taken off the market, along with its close cousin, fenfluoramine, when both were implicated in heart valve problems. ``This is the worst record we have ever had -- it's unprecedented,'' said Thomas Moore, a senior fellow in health policy at George Washington University Medical Center who studies drug safety. ``I believe we are paying the wages of the one-sided debate that we have had in this country that the speed of FDA approval is the only issue.'' It is extremely unusual for the FDA, which is widely regarded as the most safety-conscious consumer protection agency in the world, to have to withdraw a drug once it has been approved. Including the most recent withdrawals, there have been only six such withdrawals in the past decade, according to Dr. Murray Lumpkin, deputy director of the agency's Center for Drug Evaluation and Research. In recent years, however, the agency has been under intense pressure from congressional Republicans to speed up its drug approval process, and 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, which gave the FDA $327 million in user fees between 1992 and 1997. The money was used to hire 600 new employees to review drug applications. Proponents of the fast-track system say it is necessary to bring life-saving therapies to patients who desperately need them. However, Lumpkin estimated 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 why they are allowed on the market in the first place. ``The agency has been put under too much pressure to approve more drugs faster, whether they are needed or not,'' said Larry Sasich, a pharmacist for Public Citizen's Health Research Group, a Washington advocacy organization. Lumpkin, however, 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, because the benefits outweighed the risks. During the 11 months that Duract -- which goes by the generic name bromfenac - -- was on the market, it was prescribed to 2.5 million people, according to the manufacturer, Wyeth-Ayerst, a division of American Home Products Corp. 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.