Thiazolidinediones (Glitazones)

After a review of postmarketing adverse event reports, FDA determined that an updated label with a boxed warning on the risks of heart failure was needed for the entire thiazolidinedione class of antidiabetic drugs. These drugs are used in conjunction with diet and exercise to improve blood sugar control in adults with type 2 (non-insulin-dependent) diabetes. Manufacturers of certain drugs have agreed to the upgraded warning.

The strengthened warning advises healthcare professionals to observe patients carefully for the signs and symptoms of heart failure, including excessive, rapid weight gain, shortness of breath, and edema after starting drug therapy. Patients with these symptoms who then develop heart failure should receive appropriate management of the heart failure and use of the drug should be reconsidered. People who have questions should contact their healthcare providers to discuss alternative treatments.

Source: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01683.html

Avandia to stay on Market

A federal drug advisory committee voted overwhelmingly on Monday to recommend that the diabetes drug Avandia remain on the market, even after finding that it raised the risks of heart attacks.

Panel members said that studies concerning Avandia were too murky to merit drastic regulatory action and that other diabetes medicines might have similar risks.

Source: http://www.nytimes.com/2007/07/31/health/31drug.html?hp

Indian Drug Regulator to investigate Glitazones

The Indian drug regulator (Drug Controller General of India DCGI) will now investigate safety concerns on Avandia and Actos, two key diabetes medicines that could potentially be affecting 10 million diabetics in India.

The move follows the US Food and Drug Administration (FDA) directive putting both the drugs, Rosiglitazone and Pioglitazone, under the strictest drug safety warnings (Black Box) following the publication of recent studies linking them to an increased risk of heart failures.

Versions of Avandia are being sold by Indian companies such as Sun Pharmaceuticals Ltd, Cipla Ltd, Glenmark Pharmaceuticals Ltd and Torrent Pharmaceuticals Ltd, besides Glaxo’s GSK Pharmaceuticals Ltd unit.

Source: http://www.livemint.com/2007/06/08002046/DrugregulatorasksGSK-for-Av.html

FDA Asks for Black-Box Warning on Heart Failure Risk with Thiazolidinediones

The US FDA commissioner revealed that the agency has requested the manufacturers of rosiglitazone (Avandia) and pioglitazone (Actos) to add black-box warnings about the risk for heart failure with these drugs.

The FDA indicated that the request was made because although the drugs currently carry warnings about potential heart failure, they are still sometimes being prescribed to patients with this condition thus creating a need for stricter action.

Reference: New York Times dated 7th June 2007

http://www.nytimes.com/2007/06/07/health/07drug.html?_r=1&hp=&adxnnl=1&oref=slogin&adxnnlx=1181219366-DOm2snpHxZbSZJFCCGfiqw

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