Limitations on prescribing the drug rosiglitazone to a small group of people with type 2 diabetes, and other restrictions that have been in place since 2010, are being removed, the Food and Drug Administration announced on Nov. 25.
Concurring with the recommendations of two expert advisory panels in June, the FDA is modifying the cardiovascular safety statement in the labels of rosiglitazone products, changing the rosiglitazone Risk Evaluation and Mitigation Strategy (REMS), and releasing the manufacturer from a requirement to conduct a postmarketing safety study, according to the announcement.
The FDA is also lifting the requirement that physicians, pharmacies, and patients enroll in the REMS program, to prescribe, dispense, or receive any of the available rosiglitazone products.
Rosiglitazone, a thiazolidinedione, is marketed as Avandia, and as Avandamet (combined with metformin), and Avandaryl (combined with glimepiride); generic formulations are also available.
"Although some scientific uncertainty about the cardiovascular safety of rosiglitazone medicines still remains, in light of the new reevaluation of the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, FDA’s concern is substantially reduced and the rosiglitazone REMS program requirements will be modified," the statement said.
The drug was restricted in 2010, based on a recommendations of FDA advisory panels. The panel members reviewed data that included a meta-analysis suggesting rosiglitazone was associated with an increased cardiovascular risk (N. Engl. J. Med. 2007;356:2457-71). Under the REMS, rosiglitazone products can be prescribed only to patients after the prescriber has discussed the potential increased risk of MI associated with the drug – and only in patients who are already taking rosiglitazone or are unable to achieve glycemic control on other medications.
But at the joint meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee in June, 20 of the 26 panel members voted to modify (13) or remove (6) the required REMS, based on the readjudicated results of the RECORD trial, conducted independently by the Duke Clinical Research Institute in Durham, N.C. The reanalysis found no significant differences in the composite of CV death, MI, or stroke; numerically fewer CV deaths and numerically fewer strokes in the rosiglitazone arm; and a lower risk of all-cause death. There were more MIs in the rosiglitazone arm, but the difference was not significant.
In the Nov. 25 statement, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said the FDA’s actions "reflect the most current scientific knowledge about the risks and benefits" of rosiglitazone. "Given these new results, our level of concern is considerably reduced; thus, we are requiring the removal of certain prescribing restrictions."
The remaining requirement under the REMS is that manufacturers of rosiglitazone products need to ensure that health care professionals "who are likely to prescribe rosiglitazone medicines" receive training "based on the current state of knowledge concerning the cardiovascular risk of rosiglitazone medicines."