FDA Upgrades Rosiglitazone's Boxed Warning

FDA officials on Nov. 14 called for changes to the warning label for the oral antidiabetic drug rosiglitazone maleate, which is the sole active ingredient in the brand-name prescription medication Avandia (42-page PDF; About PDFs) and an ingredient in two other antidiabetic drugs, Avandamet (38-page PDF; About PDFs) and Avandaryl (36-page PDF; About PDFs). All three medications, which are used to treat type 2 diabetes, are manufactured by GlaxoSmithKline, or GSK.

At issue are research results that appear to demonstrate an increased risk of certain cardiovascular events associated with use of the drug. Specifically, the revision to rosiglitazone's existing boxed warning includes the following statement:

"A meta-analysis of 42 clinical studies (mean duration 6 months; 14,237 total patients), most of which compared Avandia to placebo, showed Avandia to be associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction. Three other studies (mean duration 41 months; 14,067 patients), comparing Avandia to some other approved oral antidiabetic agents or placebo, have not confirmed or excluded this risk. In their entirety, the available data on the risk of myocardial ischemia are inconclusive."

Given that remaining uncertainty, the FDA has asked GSK to conduct an additional long-term study comparing rosiglitazone to an active control medication. GSK has agreed to do so, and the company also is developing a medication guide for patients that provides additional information about the benefits and risks of rosiglitazone use.