FDA officials announced this week(www.fda.gov) that restrictions the agency had placed on the diabetes medication rosiglitazone (Avandia) in September 2010 are being lifted based on recent research findings that failed to confirm a link between use of the drug and an increased risk for cardiovascular events.
Those restrictions, based on a signal of increased myocardial infarction risk that was found in a meta-analysis of clinical trials first reported in 2007, focused on limiting use of the drug only to patients whose diabetes could not be controlled with other medications. To that end, the agency directed Avandia's manufacturer, GlaxoSmithKline (GSK), to develop a restricted access program as part of a risk evaluation and mitigation strategy (REMS) for the drug.
In accordance with the REMS, physicians were required to attest to and document a patient's eligibility to receive the drug, and patients were required to review safety information describing the cardiovascular concerns associated with rosiglitazone. Additional restrictions were placed on how the drug was dispensed.
The same restrictions were applied to the combination drugs marketed as Avandamet, which contains rosiglitazone and metformin, and Avandaryl, which contains rosiglitazone and glimepiride.
At that time, the FDA also ordered GSK to conduct an independent review of the company's Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) clinical trial because of concerns about potential bias. The RECORD trial was designed to study the cardiovascular safety of rosiglitazone compared to that of other diabetes drugs.
In its recent announcement, the agency stated that the readjudicated RECORD trial results affirmed the trial's original findings and showed no elevated risk of heart attack or death in patients being treated with rosiglitazone versus standard-of-care diabetes medications. FDA officials also canceled their previous requirement that GSK conduct an additional clinical trial comparing rosiglitazone with pioglitazone (Actos), the only other approved drug in the thiazolidinedione class, and to standard diabetes drugs.
"Our actions today reflect the most current scientific knowledge about the risks and benefits of this drug," said Janet Woodcock, M.D., director of the FDA's Center for Drug Evaluation and Research, in a Nov. 25 FDA news release. "Given these new results, our level of concern is considerably reduced; thus, we are requiring the removal of certain prescribing restrictions."
Changes to the product labels for rosiglitazone-containing medications are yet to be finalized, according to the agency, but it anticipates that the new indication will state that the drug may be used along with diet and exercise to improve glycemic control in patients with type 2 diabetes, an indication that is similar to that for other diabetes drugs currently on the market.