More than one dozen cases of liver failure and death were reported in
patients taking GlaxoSmithKline Plc's Avandia (rosiglitazone), advocacy
group Public Citizen said on Thursday in a petition calling for a ban of the
drug. But GlaxoSmithKline defended its drug, saying its own review by an
independent panel earlier this year said the liver risks were acceptable. "We do not believe there is a connection between liver toxicity and
this medicine," the company said in a statement, adding it had not yet read
the group's petition.
The safety of patients using our medicine is very important to us. On
a continual basis, an external Hepatic Safety Board reviews any adverse
event report received by GSK of liver failure, liver-related deaths and
liver transplants for possible relationship to AVANDIA. As recently as July
2008, this panel of experts continued to endorse a favorable hepatic safety
profile for AVANDIA. Patients being treated with AVANDIA or other medicines
to control blood sugar levels should remain on therapy, unless their doctor
advises a different course of action. AVANDIA has been shown to be a safe
and highly effective treatment for type 2 diabetes for the appropriate
patient. GSK strongly supports the safety and efficacy of AVANDIA based on
extensive clinical trial experience and widespread post-marketing use. The
record of safety and effectiveness of AVANDIA is backed by one of the
largest clinical trial programs (including 52,000 patients) ever undertaken
for any medicine.
Data from long-term clinical trials, which offer the most rigorous
scientific measurement of safety and efficacy, provide substantial evidence
to assess the benefit-risk of AVANDIA in treating patients with diabetes.
Importantly, the Public Citizen petition did not include data from the
current Prescribing Information for AVANDIA regarding ADOPT (A Diabetes
Outcomes Progression Trial). ADOPT, the largest head-to-head diabetes trial,
showed that AVANDIA sustained glycemic control longer than metformin or
sulfonylurea, for up to five years. Additionally, outcomes from five
long-term clinical studies did not demonstrate an increased risk of total
mortality for AVANDIA compared to other commonly used oral diabetes
medicines on the market. The current FDA-approved label for AVANDIA states
that the available data are inconclusive on the risk of myocardial ischemia.
Public Citizen said its review of U.S. Food and Drug Administration
data found 14 previously unpublished cases of severe drug-induced liver
failure, including 12 deaths.
That risk, coupled with other known complications that include heart
failure, fractures and vision loss, was too great to allow the drug to
continue to be sold in the United States, especially with other treatments
available, it said in a petition to the FDA. "The evidence for this unique combination of toxicities is compounded
by the accompanying lack of evidence of any clinical benefit, compared to
other approved drugs for diabetes," the petition said.
Sales of Avandia have plunged in the past year after the heart risk
surfaced in an analysis of available clinical studies.
Since then, experts at two major diabetes associations have withdrawn
their support of the drug, instead backing lifestyle changes such as diet
and exercise as well as other treatments.
Still, Public Citizen estimated about 10,000 prescriptions continue to
be filled each day. "Thus, it is urgent for the FDA to immediately ban
rosiglitazone," it said.
Please Click the links below to New York Times and NEJM for more info
Original Article: Rosiglitazone Evaluated for Cardiovascular Outcomes --
An Interim Analysis
P.D. Home and Others
Editorial: Rosiglitazone -- Continued Uncertainty about Safety
J.M. Drazen, S. Morrissey, and G.D. Curfman
Editorial: Rosiglitazone and Cardiotoxicity -- Weighing the Evidence D.M. Nathan
Editorial: The Record on Rosiglitazone and the Risk of Myocardial Infarction
B.M. Psaty and C.D. Furberg