As you may know, Avandia (rosiglitazone maleate) is an oral agent for the
treatment of type 2 diabetes. It is indicated for use as an adjunct to
diet and exercise as monotherapy or in combination with metformin or a sulfonylurea.
The labeling has been recently updated to reflect the extensive postmarketing
experience of the product since its launch in June 1999. The current labeling
changes also include safety information regarding the use of Avandia in
combination with insulin, an indication for which GlaxoSmithKline (GSK)
recently received an approvable letter from the Food and Drug Administration.
GSK will work with the FDA to address outstanding points that must be resolved before
approval for that use can be obtained. Avandia is not currently indicated
for use in combination with insulin.
As GSK wanted to ensure that you were aware of these changes, we have enclosed
a revised package insert for your review, and we have summarized the major
changes to the labeling, which are as follows:
First, the prior labeling addressed the issue of thiazolidinediones, including
Avandia, causing fluid retention and the potential for heart failure under
the Precautions, Edema subsection, and discussed the use of Avandia in patients
with New York Heart Association Class 3 and 4 status under Precautions,
Use in Patients with Heart Failure subsection. The language pertaining to heart
failure from these two sections has been revised and moved to a new section
called “Warnings: Cardiac Failure and Other Cardiac Effects.” Changes to
these sections include a new warning that Avandia should be discontinued
if any deterioration in cardiac status occurs, and a revised warning that
Avandia is not recommended in patients with New York Heart Association Class 3 or 4 cardiac status.
While Avandia is not currently indicated for use in combination with insulin,
the new section now also includes safety data from clinical trials evaluating
combination use of Avandia with insulin. In these clinical trials, which
included patients with long-standing diabetes (average 12 to 13 years) and
a high prevalence of pre-existing medical conditions (e.g., ischemic heart
disease 14%, vascular disease 9%, congestive heart failure 2.5%), an increased
incidence of cardiac failure and other cardiovascular adverse events was
seen in patients receiving Avandia and insulin compared to insulin alone.
Patients who experienced heart failure in these trials were on average older,
had a longer duration of diabetes and were mostly on the higher 8 mg dose
of Avandia.
Second, the Precautions section was modified in several ways. The Precaution
concerning edema was revised and a sentence added to the end of the third
paragraph regarding potential issues relating to combination use with insulin.
The Precaution regarding hepatic effects was revised to include postmarketing
reports of adverse events. Very rarely, these reports have involved hepatic
failure, with and without fatal outcome, although causality has not been established.
In addition, the labeling previously included information regarding weight
gain under the Clinical Pharmacology section. Information regarding weight
gain, including information from the Avandia and insulin combination clinical
trials, is now included as a separate Precaution
section.
Third, the Adverse Reactions section has also been updated regarding reports
of adverse events of edema and congestive heart failure seen in the insulin combination
studies. In
addition, that section has been updated to reflect postmarketing reports
of hepatic adverse events and events potentially related to volume expansion.
Finally, the Information for Patients subsection was also updated in accordance
with the other changes.
Please read the enclosed prescribing information for the full text describing
these labeling changes.
GSK is confident in the safety and efficacy profile of Avandia based upon
its extensive clinical trial experience and its widespread postmarketing
use. GSK is also committed to continuing to provide valued diabetes treatment
options to the millions of patients with type 2 diabetes. If you should
have any questions regarding the above information or any of our products,
please contact the GSK Medical Information Department at (800) 366-8900,
ext. 5231. In addition, should you need to report an adverse reaction, please
do so by contacting the GSK Medical Information Department at the above
number or by notifying the FDA MedWatch program by telephone at 1-800-332-1088,
by FAX at 1-800-332-0178, via www.fda.gov/medwatch, or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857.
Sincerely,
Martin I. Freed, M.D.
Vice President, Metabolic Therapeutic Area
North America Medical Affairs
SmithKline Beecham, a subsidiary of the GlaxoSmithKline Group of Companies
Rosiglitazone (avandia)
Fasting insulin levels
Dosage and administration
Supplied
Causes of insulin resistance
For prescriber
Rosiglitazone patient information sheet
Insulin resistance