Rosiglitazone

FDA News

FOR IMMEDIATE RELEASE
P07-88
May 21, 2007

Media Inquiries:Susan Cruzan, 301-827-6242
Consumer Inquiries:888-INFO-FDA

FDA Issues Safety Alert on Avandia

The U.S. Food and Drug Administration (FDA) is aware of a potentialsafety issue related to Avandia (rosiglitazone) , a drug approved totreat type 2 diabetes. Safety data from controlled clinical trialshave shown that there is a potentially significant increase in therisk of heart attack and heart-related deaths in patients takingAvandia. However, other published and unpublished data from long-termclinical trials of Avandia, including an interim analysis of data fromthe RECORD trial (a large, ongoing, randomized open label trial) andunpublished reanalyses of data from DREAM (a previously conductedplacebo-controlled, randomized trial) provide contradictory evidenceabout the risks in patients treated with Avandia.

Patients who are taking Avandia, especially those who are known tohave underlying heart disease or who are at high risk of heart attackshould talk to their doctor about this new information as theyevaluate the available treatment options for their type 2 diabetes.

FDA's analyses of all available data are ongoing. FDA has notconfirmed the clinical significance of the reported increased risk inthe context of other studies. Pending questions include whether theother approved treatment from the same class of drugs, pioglitazone,has less, the same or greater risks. Furthermore, there is inherentrisk associated with switching patients with diabetes from onetreatment to another even in the absence of specific risks associatedwith particular treatments. For these reasons, FDA is not askingGlaxoSmithKline, the drug's sponsor, to take any specific action atthis time. FDA is providing this emerging information to prescribersso that they, and their patients, can make individualized treatmentdecisions.

"FDA remains committed to assuring that doctors and patients have thelatest information available to make treatment and medication usedecisions. In this case, FDA is carefully weighing several complexsources of data, some of which show conflicting results, related tothe risk of heart attack and heart-related deaths in patients treatedwith Avandia," said Steven Galson, M.D., M.P.H., director of FDA'sCenter for Drug Evaluation and Research. "We will complete ouranalyses and make the results available as soon as possible. FDA willtake the issue of cardiovascular risk associated with Avandia andother drugs in this class to an Advisory Committee as soon as one canbe convened."

Avandia was approved in 1999 for treatment of type 2 diabetes, aserious and life threatening disease that affects about 18 to 20million Americans. Diabetes is a leading cause of coronary heartdisease, blindness, kidney failure and limb amputation. Since the drugwas approved, FDA has been monitoring several heart-related adverseevents (e.g., fluid retention, edema and congestive heart failure)based on signals seen in previous controlled clinical trials ofAvandia alone and in combination with other drugs, and frompostmarketing reports. FDA has updated the product's labeling onseveral occasions to reflect these new data, most recently in 2006.The most recent labeling change for Avandia also included a newwarning about a potential increase in heart attacks and heart-relatedchest pain in some individuals using Avandia. This new warning wasbased on the result of a controlled clinical trial in patients withexisting congestive heart failure.

Recently, the manufacturer of Avandia provided FDA with a pooledanalysis (meta analysis) of 42 randomized, controlled clinical trialsin which Avandia was compared to either placebo or other anti-diabetictherapies in patients with type 2 diabetes. The pooled analysissuggested that patients receiving short-term (most studies were6-months duration) treatment with Avandia may have a 30-40 percentgreater risk of heart attack and other heart-related adverse eventsthan patients treated with placebo or other anti-diabetic therapy.These data, if confirmed, would be of significant concern sincepatients with diabetes are already at an increased risk of heart disease.

Avandia is manufactured by GlaxoSmithKline, which is based in ResearchTriangle Park, N.C.

Source: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01636.html