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Timeline of Events
The L.A. Times reported on the Rezulin recall history, outlining
 notable
events in the development from the arrival of Rezulin onto
the market until reports of the federal investigation into
Rezulin’s approval.
6-11-96
The federal health agency, The National Institutes of Health,
chooses Rezulin to use in a $150 million diabetes study, run
by Richard Eastman, the government’s top diabetes doctor
and hired by Warner-Lambert, the diabetes drug developer,
as a consultant to launch Rezulin. After the study Warner-Lambert
issues a press release saying that Eastman found Rezulin to
correct underlying causes of diabetes.
7-31-96
Rezulin manufacturer, Warner-Lambert applies for the FDA
approval of the diabetes drug under the “fast-track”
procedures fairly recently enacted.
10-9-96
FDA scientists become concerned with the potential Rezulin
appears to have to harm the liver and heart in animal studies.
The first FDA doctor to look at Rezulin was Dr. John Gueriguian
who was opposed to the drug’s approval.
11-4-96
Warner-Lambert has Dr. Gueriguian removed from the Rezulin
evaluation after the manufacturer complains about his intemperate
language. His removal also dismisses his Rezulin review from
the FDA files.
12-11-96
Rezulin is presented by Warner-Lambert to an FDA advisory
committee in order to get approval and states that their diabetes
drug does not increase cardiac mass or impair cardiac function.
1-97
Rezulin received FDA approval through the “fast track”
approval procedure that cut the time it took to be approved
in half the normal time. There is no liver testing required.
2-24-97
The FDA states that Warner-Lambert made “false and misleading”
claims about Rezulin in a press release, recommending the
news release be immediately discontinued, as well as any other
piece of information containing similar claims.
5-1-97
Warner-Lambert’s clinical studies indicated that Rezulin
users were 3.6 times more likely to suffer liver injury than
patients taking placebos, but the company runs a full-page,
color magazine ad describing Rezulin as having side effect
comparable to placebo.
5-5-97
The CEO of Warner-Lambert tells investors that Rezulin holds
the potential to be a billion dollar blockbuster.
9-30-97
The FDA Diabetes Group Leader, Dr. Alexander Fleming, finds
it “hard to believe that patients with cardiac, liver,
or renal disease would not be adversely affected by the drug.”
10-10-97
The FDA receives two reports of Rezulin liver failure.
11-3-97
The
FDA requires the Rezulin label be changed to recommend
liver enzyme tests within the first one to two months and
then every three months during the first year of Rezulin therapy
and then periodically after that. Symptoms of Rezulin liver
dysfunction including, nausea, vomiting, abdominal pain, fatigue,
loss of appetite, or dark urine should get liver function
tests performed. Any Rezulin patient who develops a liver
injury should immediately discontinue the use of the drug.
Clinical trials showed approximately 2% of Rezulin patients
should be expected to stop taking the drug due to an elevated
level of liver enzymes.
11-12-97
Dr. Robert I. Misbin, an FDA diabetes specialist that supported
the Rezulin approval, sent an internal report to FDA supervisors
stating that 21 patients treated with Rezulin prior to FDA
approval had to discontinue the drug due to Rezulin liver
injury, 13 patients had markers of Rezulin liver injury 10
to 30 times above normal which can threaten the lives of patients,
and an estimated 2% or 12,350 of the 650,000 patients using
Rezulin would experience some degree of liver injury.
12-1-97
England prohibits sales of Rezulin due to concerns about
liver damage to patients in the U.S. The
FDA announces a label change to require more frequent
Rezulin liver testing. The new label recommends liver enzyme
tests before starting Rezulin, monthly for the first six months
of treatment, every other month for the next six months, and
periodically thereafter.
5-17-98
A 55 tear old woman in good health dies of Rezulin liver
failure while participating in the National Institutes of
Health diabetes study. The panel of specialists hired by NIH
concluded that her liver failure was probably due to the use
of Rezulin diabetes drug.
6-4-98
The NIH study drops Rezulin due to the risk of liver damage
in the remaining participants.
6-5-98
A press release by Warner-Lambert denies Rezulin killed the
woman and instead claimed her death was the result of complications
unrelated to the study or the diabetes medication. The FDA
had then received 21 reports of Rezulin liver failures resulting
in death and three Rezulin liver transplant patients.
7-27-98
The consumer group Public Citizen filed a petition for the
immediate ban of Rezulin. At this point the FDA had received
26 reports of Rezulin liver failure deaths.
7-28-98
The
FDA required another Rezulin label change to increase
the frequency of liver testing. The recommendation then stated
a Rezulin patient be tested before using Rezulin, monthly
for the following 8 months and every two months for the rest
of the year and periodically after that.
1-99
The FDA Commissioner orders a reevaluation of Rezulin after
the series of articles by the Los Angeles Times investigated
the “fast track” drug Rezulin tied to 33 Rezulin
liver failure deaths.
3-26-99
After two months of FDA research the findings are present
to an FDA advisory panel. The report found that an estimated
430 or more Rezulin patients have suffered a liver failure,
Rezulin patients incur 1,200 times more risk of liver failure,
one out of every 1,800 Rezulin patients can expect t suffer
a liver failure, and liver function tests do not provide enough
protection due to the rapid and unpredictable way Rezulin
can affect the liver. In addition, Rezulin patients did not
follow the recommended liver function tests after more than
4 months on the drug.
3-29-99
A Rezulin patient undergoing monthly monitoring in a Warner-Lambert
clinical trial dies of liver failure.
6-16-99
The
FDA requires the Rezulin label be changed for the
fourth time now, increasing the frequency once again for liver
tests. The new label recommended Rezulin patients get monthly
liver monitoring for the first year on the diabetes drug.
12-15-99
The Los Angeles Times reports 21 Rezulin patients have died
of liver failure since the March 26, 1999 report by Dr. Graham
to the FDA Advisory Panel. Graham begins a new analysis of
Rezulin despite his supervisors having no knowledge of his
actions.
3-3-00
Dr. Graham sends an email to 14 FDA officials with the opinion
that Rezulin is unsafe and should be stopped due to the liver
failure problems occurring. Graham stated there was no existing
data to support the idea that monitoring can prevent the Rezulin
liver failures from occurring.
3-00
The FDA diabetes specialist who had analyzed the first cases
of liver failure in October to November 1997 sends eight members
of Congress internal FDA emails discussing Rezulin liver toxicity.
Included in the email was the correspondence he had received
from Dr. Janet B. McGill who had conducted early research
on Rezulin for Warner-Lambert saying the company “deliberately
omitted reports of liver toxicity and misrepresented serious
adverse events experienced by Rezulin patients in their clinical
studies.” The FDA opens an internal-affairs investigation
after Warner-Lambert complains about the leaks.
3-21-00
The
FDA withdraws Rezulin from the U.S. market after finding
the benefits of other diabetes drugs offer the same benefits
Rezulin did without the same risks. Up to this point Warner-Lambert
had grossed $2.1 billion in Rezulin sales. The FDA had reports
of 63 Rezulin liver failure deaths.
8-16-00
The L.A. Times reports about the Federal prosecutors examining
the FDA’s quick approval method and the delayed withdrawal
of Rezulin. It was reported that both the FDA and Warner-Lambert’s
actions were being examined.
Serious, life-threatening Rezulin side effects have been
directly linked to the use of the diabetes drug. Warner-Lambert
has been blamed in dozens of deaths from life failure and
thousands of other liver damage cases from 1997-2000.
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