FDA Reduces Restrictions on Diabetes Medication Rosiglitazone

Following an extended review of safety data that showed no elevated risk of heart attack or death in patients taking rosiglitazone, the FDA announced it is lifting certain restrictions on the prescribing and dispensing of the drug.

Citing “new information regarding the cardiovascular risk of the medicine,” the FDA announced yesterday that it is “requiring the removal of certain restrictions on prescribing and use of the diabetes drug Avandia (rosiglitazone).”

According to a news release from the FDA, “Results from the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) clinical trial showed no elevated risk of heart attack or death in patients being treated with Avandia when compared to standard-of-care diabetes drugs. These data do not confirm the signal of increased risk of heart attacks that was found in a meta-analysis of clinical trials first reported in 2007.”

A “Drug Safety Communication” announcement from the FDA, also released yesterday, stated the agency “has determined that recent data for rosiglitazone-containing drugs, such as Avandia, Avandamet, Avandaryl, and generics, do not show an increased risk of heart attack compared to the standard type 2 diabetes medicines metformin and sulfonylurea." As a result, the agency said it is "requiring removal of the prescribing and dispensing restrictions for rosiglitazone medicines that were put in place in 2010.”

The FDA Drug Safety Communication explained that, because of these actions by the FDA, the following changes will occur:

  • Distribution of rosiglitazone-containing medications will no longer be restricted, meaning rosiglitazone “may be used along with diet and exercise to improve control of blood sugar in patients with type 2 diabetes mellitus”
  • Physicians and other prescribers, pharmacies, and patients “will no longer be required to enroll in the rosiglitazone REMS program to be able to prescribe, dispense, or receive rosiglitazone medicines”
  • As part of the REMS, “sponsors will ensure that health care professionals who are likely to prescribe rosiglitazone medicines are provided training based on the current state of knowledge concerning the cardiovascular risk of rosiglitazone medicines.” Manufacturers of the medications must also send “Dear Healthcare Provider and Dear Professional Society letters to educate prescribers about the new information”

The lifting of restrictions also means that patients will be able to obtain the medication through regular retail and mail-order pharmacies.

The FDA will require manufacturers to modify the information on the medication’s label regarding cardiovascular safety, and also require changes to the rosiglitazone Risk Evaluation and Mitigation Strategy (REMS) program. The FDA also announced that manufacturers will not be required to conduct a postmarket study.

In the news release announcing the change, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that the FDA’s actions “reflect the most current scientific knowledge about the risks and benefits of this drug,” and that given these new results, the FDA’s “level of concern is considerably reduced; thus, we are requiring the removal of certain prescribing restrictions.”

Interestingly, a Reuters report on these developments notes that they may not do much initially to change patients’ and providers’ views of the medication and its risk/benefit profile. In the report, Robert Tamler, MD, director of the Mount Sinai Diabetes Center in New York, said “The decision by the FDA is irrelevant in clinical practice… Patients have been reading about increased risk of cardiovascular events with rosiglitazone since 2007 and will not abandon their concerns overnight, despite the FDA decision.”

For its part, GlaxoSmithKline, said it “welcomes the decision of the FDA and appreciates the agency's robust review of the science with regard to Avandia” and maintains its view that “Avandia is a safe and effective treatment for Type 2 diabetes when used appropriately.” The company said it would work with the FDA to make the necessary labeling changes and implement the other requirements following the easing of restrictions.