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.