http://www.latimes.com/news/nation/reports/fda/lat_duract001220.htm
Wednesday, December 20, 2000 |
DURACT:
Painkiller Posed Risk of Damage to Liver
Drugmaker's lobbying won fine print instead of prominent warning.
By DAVID WILLMAN, Times Staff Writer
The FDA medical officers who reviewed a proposed painkiller
called Duract saw the problem from the outset: Too many patients who
took the pill in clinical trials suffered liver injury.
"It seems imprudent to open the doors to extensive use when
there have been early warning signs," an FDA medical officer, Dr.
John E. Hyde, wrote on July 31, 1996. He said the specialists
reviewing Duract "were concerned about the frequency and severity" of
the injuries reflected in patients' blood tests.
Hyde and a colleague, Dr. Rudolph M. Widmark, concluded in
another report: "The [liver] toxicity is a significant concern with
this drug."
Believing that the risk increased the longer a patient remained
on Duract, they sought to rid the label of any reference to long-term
use. They also proposed a prominent black box warning regarding
Duract's liver toxicity.
This was not what the manufacturer, Wyeth-Ayerst Laboratories,
had in mind.
"They were unhappy with my review," Widmark said in an interview.
In a market already stocked with more than 20 prescription and
over-the-counter painkillers, a black box warning could turn off
doctors and cripple sales.
Wyeth-Ayerst took its case to Widmark's superiors. Widmark
responded, in a memo dated Nov. 14, 1996, to the FDA drug center's
No. 2 administrator, Dr. Murray M. "Mac" Lumpkin:
"The company would like a label that actually puts the onus on
the prescribing physician because if severe and maybe fatal liver
toxicity [occurs], the physician will be sued and will be found
liable if he/she did not 'monitor' for liver damage. Wyeth-Ayerst
will be in the clear, because 'it is in the label.' "
Widmark added, "I hope that this short memo will help you to
make the right decision in this dispute."
When the company rolled out Duract following the FDA's approval
on July 15, 1997, there was no black box on the label. Securities
analysts predicted that in four years Duract could yield annual sales
topping $500 million.
Beginning on the 135th line, the label's fine print informed
doctors that Duract was recommended for "generally less than 10
days." The label also advised that, "if a physician chooses to
administer Duract for a longer duration," patients' liver functions
should be checked after a month.
Seven months after Duract's market launch, the FDA and
Wyeth-Ayerst responded to reports of severe liver damage: A black box
was added.
The revised labeling also flatly warned doctors for the first
time "not" to prescribe the drug for longer than 10 days.
"Patients using Duract for more than 10 days have developed
jaundice, fulminant hepatitis and liver failure requiring
transplants," the FDA said, announcing the label change.
By the time Wyeth-Ayerst announced Duract's withdrawal on June
22, 1998, the FDA had received 13 voluntarily filed reports of liver
failure. The agency said that "almost all" of the cases occurred
among patients who took the drug longer than 10 days.
Widmark, an Austrian immigrant, said he believes that lives
would have been saved if FDA administrators had stood behind his
original recommendation for a black box warning.
"I personally think yes," Widmark said. "They were more
impressed with the company's consultants than they had confidence in
their own reviewers. . . .
"Something is wrong and something should be done to avoid this
in the future."
Now 75, Widmark retired in December 1997 after spending 11 years
with the FDA. He still works as a consultant to the pharmaceutical
industry.
The spokesman for Wyeth-Ayerst, Petkus, said the company's
consultants "made a case that there was no need for a black box,"
believing the recommendation to use Duract generally less than 10
days was sufficient. The FDA's management, he said, agreed.
In their May 1999 medical journal article, Woodcock and Lumpkin
said the problems that emerged with Duract were "unexpected," adding:
"Given the availability of other analgesics with a wider margin of
safety than [Duract], the FDA believed that the risk from this
product outweighed its benefits."
In a written response to questions, Woodcock said, that if used
short term, "it was felt that Duract would not cause liver damage
more often than" certain other painkillers. She said the findings of
potential danger, identified in advance by the agency's two medical
officers, involved tests that "do not always signal clinically
important [liver] toxicity."
By late 1998, the FDA had received voluntary reports citing
Duract as a suspect in 68 deaths, including 17 that involved liver
failure. During its one year on the market, Duract generated sales
totaling $89.7 million for Wyeth-Ayerst.
_______________________________________________
Biofuel mailing list
Biofuel@sustainablelists.org
http://sustainablelists.org/mailman/listinfo/biofuel_sustainablelists.org
Biofuel at Journey to Forever:
http://journeytoforever.org/biofuel.html
Search the combined Biofuel and Biofuels-biz list archives (50,000 messages):
http://www.mail-archive.com/biofuel@sustainablelists.org/
