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The existing boxed warning has been revised to add the FDA's conclusionthat, while an FDA meta-analysis of short-term studies -- mostly againstplacebo -- showed an association between Avandia and an increase in myocardialischemic events, that risk was not confirmed or excluded in three long-termclinical trials comparing Avandia against both placebo and other oral anti-diabetes medicines. The box will state that the available data on the risk ofmyocardial ischemia are inconclusive.
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The FDA has also concluded there is insufficient information available todetermine whether any oral anti-diabetic medicine reduces cardiovascular risk.The FDA has directed that the sentence -- "There have been no clinical studiesestablishing conclusive evidence of macrovascular risk reduction with Avandiaor any other oral antidiabetic drugs" -- will be added as a warning on thelabels of all oral anti-diabetic medicines.
The Avandia label also has been updated to add that Avandia is notrecommended -- though not contraindicated -- for use with patients who aretaking insulin or nitrates. The label summarizes the data on myocardialischemia to help doctors continue to evaluate which patients could benefitfrom taking Avandia, and those for whom alternative treatment should beconsidered.
The changes are now included in labeling for Avandia, and will beincorporated into future revised labeling for all approvedrosiglitazone-containing products, including Avandamet (rosiglitazone maleateand metformin hydrochloride), and Avandaryl (rosiglitazone maleate andglimepiride). GSK is also preparing a Medication Guide to help educatepatients about potential benefits and risks and to provide other informationon Avandia.
"Avandia remains a safe and effective medicine for most patients with type2 diabetes when used appropriately," said Dr. Ronald Krall, GSK Chief MedicalOfficer. "Given the severity of this disease and the importance of Avandia inhelping patients manage their diabetes, we will continue to work with the FDAto conduct more studies about the safety and benefits of our medicine."
As previously stated by GSK, two long-term trials in diabetic patientscomparing Avandia to other oral anti-diabetic medicines show no increased riskfor cardiovascular events compared to other commonly used medications, otherthan the well-known risk of congestive heart failure with TZDs. One trial --ADOPT -- shows no increased myocardial ischemic risk compared to metformin orsulfonylurea. The interim results of a second long-term trial -- RECORD --also show no increased risk of major cardiovascular events (death, heartattack and stroke) between Avandia and other medications; however, firmconclusions cannot be drawn because the trial has not yet been completed. Theupdated label includes data from ADOPT and RECORD plus a third long-term trialin pre-diabetic patients (DREAM) which show there was no increased risk of
Avandia over comparators with regard to myocardial infarction, mortality, orother non-heart failure cardiovascular events.
GSK believes data from ongoing and future clinical trials will provideadditional scientific support for both the benefit and safety of Avandia. GSKhas agreed to work with the FDA to plan and carry out a clinical trial tofurther investigate the cardiovascular effects of Avandia.
Avandia has been prescribed to more than seven million people over thelast seven years to help them control their blood sugar levels. Importantly,Avandia has been shown to control blood sugar for longer than the mostcommonly used oral anti-
