Avandia Stays On Market With Increased Boxed Warning While Safety Assessed

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Main Category: Diabetes
Also Included In: Regulatory Affairs / Drug Approvals;  Cardiovascular / Cardiology;  Pharma Industry / Biotech Industry
Article Date: 15 Nov 2007 - 3:00 PDT

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The US Food and Drug Administration (FDA) has asked the manufacturer of diabetes type 2 drug Avandia (rosiglitazone maleate) to carry out a new long term study to assess the cardiovascular risk of the drug. In the meantime it will stay on the market but carry a higher level of boxed warning about potential increased risk of heart attacks, said the agency in a statement on 14th November.

The FDA said doctors should monitor patients who take Avandia for any potential cardiovascular risks, and people with type 2 diabetes who are at higher risk of heart attack or who have underlying heart disease should make sure the new health warning is considered when they talk to their health care provider about available treatments.

Dr Janet Woodcock, deputy commissioner for scientific and medical programs, chief medical officer, and acting director of the Center for Drug Evaluation and Research at the FDA said the agency had:

"Moved expeditiously to review the cardiovascular risks of this drug so that we could inform patients and doctors at the earliest possible time of our findings."

"FDA remains committed to making sure that doctors and patients have the latest information about the risks and benefits of medicines," she added.

Avandia (rosiglitazone maleate) is made by global pharmaceutical giant GlaxoSmithKline (GSK), which in the US is headquartered in Philadelphia, Pennsylvania. The drug has been prescribed to more than 7 million people over the last 7 years to help them control blood sugar.

The FDA approved the drug in 1999 as an adjunct to diet and exercise, either on its own or in combination with other oral anti-diabetes drugs, metformin and sulfonylureas.

Over the last 12 months the FDA has been reviewing several studies showing conflicting results about the side effects of Avandia, such as the risk of chest pain, heart attacks, deaths related to heart problems and deaths from any cause.

The agency has concluded that the evidence is not sufficient to show conclusively that Avandia is any riskier than some other oral drugs for treating type 2 diabetes and has therefore asked GSK to set up a new long term study to assess the cardiovascular risks of Avandia. GSK has agreed to carry out such a study and said it will do so promptly.

In the meantime the drug company has agreed to add a new stronger boxed warning to the product, the strongest form suggested by the FDA. The new warning now includes the following statements:

• 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.

The warning had only been upgraded recently, in August this year, and had been applied to all the diabetes drugs in the class to which Avandia belongs (thiazolidinedione or TZD). This emphasized the higher risk of heart failure, which is when the heart can't pump enough blood.

The drug company is also issuing a new patient Medication Guide describing the benefits, risks and the safe use of Avandia.

According to the FDA, there is no oral anti-diabetes drug on the market that has conclusively shown it can reduce cardiovascular risk, so the agency said it will be asking all makers of such drugs to add information on their labels to this effect.

In July this year the agency's Endocrine and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees met and voted 22 to 1 to recommend Avandia stay on the market, pending review of new data. The meeting also recommended strengthening the label warning about the increased risk of heart attacks.

Rosiglitazone maleate is also marketed as Avandamet, and Avandaryl.

In October GSK announced that the European Medicine Agency (EMEA) had completed a benefit risk review of TZDs and concluded that the benefits of rosiglitazone continued to outweigh the risks.

Click here for more information on Avandia (FDA).

Written by: Catharine Paddock


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