Restrictions on use of diabetes drug rosiglitazone lifted after FDA re-examines cardiovascular risk data

ST LOUIS - On November 25, 2013, the US Food and Drug Administration (FDA) issued a safety alert stating that it is requiring the removal of certain restrictions on prescribing and use of Avandia (rosiglitazone), a drug used in the treatment of diabetes. This new label information concerns cardiovascular risk. The FDA is also requiring the same modifications be made to the labels for any other drugs that contain rosiglitazone. The decision to remove the previous prescribing and dispensing restrictions for rosiglitazone-containing medicines was made on the basis of results from the FDA's review of data of a large, long-term clinical trial. Moreover, the decision to change the restrictions was supported by a comprehensive, outside, expert re-evaluation of the data conducted by the Duke Clinical Research Institute. In 2010, in response to data from a meta-analysis of placebo-controlled randomized trials that suggested an elevated risk of cardiovascular events in association with rosiglitazone use, the FDA announced it would restrict the drug to use in patients with type 2 diabetes who could not manage their disease with other medications. The FDA also required GlaxoSmithKline, the manufacturer of Avandia, to convene an independent group of scientists to readjudicate key aspects of the trial known as Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD). This trial evaluated the cardiovascular safety of Avandia compared with standard diabetes drugs. The original evaluation of data from RECORD suggested an increase in myocardial infarctions (MIs) and decreases in the rates of death and stroke in patients treated with rosiglitazone. These results were not statistically significant. During the course of the FDA's original 2010 review of the RECORD trial, important questions had arisen about potential bias in the identification of cardiovascular events. The readjudicated results could not dismiss an increased risk of MI with rosiglitazone versus placebo, because the trial did not use a placebo. However, the readjudicated results did assess rosiglitazone versus the standard-of-care diabetes drugs metformin and sulfonylurea and confirmed the original RECORD finding that did not show an increased risk of MI associated with the use of rosiglitazone. In the trial, patients treated with rosiglitazone experienced fewer deaths from a cardiovascular cause, from a stroke, and from an MI; fewer nonfatal strokes; and fewer deaths from any cause compared with patients treated with metformin and sulfonylurea. Patients treated with metformin and sulfonylurea experienced fewer nonfatal MIs compared with patients treated with rosiglitazone. However, none of these results were statistically significant. On the basis of the results from the readjudicated RECORD trial, the FDA is requiring modifications to the rosiglitazone Risk Evaluation and Mitigation Strategy (REMS) program to remove the requirements for restricted distribution. After the changes to the REMS are finalized, health care professionals, pharmacists, and patients will no longer be required to enroll in the rosiglitazone REMS program to prescribe, dispense, or receive rosiglitazone medicines. Patients will also be able to receive rosiglitazone through regular retail pharmacies and mail order pharmacies.