Avandia: Do FDA Warnings Help Determine Whether a Medicine Should Be Prescribed?

Boston, MAIn September 2010, the US Food and Drug Administration (FDA) announced it was severely restricting the use of Avandia, GlaxoSmithKline's diabetes medication. The FDA concluded that in many patients, the risk of serious Avandia side effects outweighed the benefits of using the medication. Following the restrictions, doctors who wish to put their patients on Avandia must prove they have discussed Avandia risks with patients, including an increased risk of Avandia heart attack.

Despite the FDA severely restricting Avandia's use, there is evidence that doctors in various geographic locations in the US respond differently to FDA warnings, according to an article in The New England Journal of Medicine (11/17/10). The article suggests that following the May 21, 2007, FDA boxed warning about the increased risk of myocardial infarction, levels of use of the diabetes medication dropped, but that drop was not uniform across the country.

The article in The New England Journal of Medicine uses prescription information to determine how many prescriptions for Avandia were filled, as compared with other medications, following the FDA warning and following a consensus statement from the American Diabetes Association (issued in January 2009) advising against use of Avandia. Researchers found that following the FDA's 2007 warning, Avandia use dropped by approximately 70 percent, but that by June 2009, an estimated 3.8 million Avandia prescriptions were still being filled yearly. The consensus statement from the American Diabetes Association appears to have had virtually no effect on Avandia prescriptions.

As the article in The New England Journal of Medicine points out, "Research has shown, however, that the response by clinicians to boxed warnings is inadequate, which results in significant exposure of patients to potentially unsafe medications." Furthermore, response varies by geographical location.

Following the FDA's black box warning—the strongest warning the FDA can issue—Avandia use dropped to approximately 5.5 percent of total prescriptions filled in Oklahoma. In North Dakota, however, Avandia use dropped to 1.9 percent of total prescriptions filled. Possible explanations for the geographical differences in Avandia use include how doctors are made aware of FDA warnings, how doctors react to FDA warnings, how state health insurance plans cover drugs and how drug companies market to doctors.

According to researchers, doctors respond to FDA warnings in a variety of ways and the FDA does not provide guidance for doctors to determine what role the black box should play in determining whether or not to prescribe a medication.

The study's authors conclude that the addition of a black box warning does not guarantee that patients and doctors will have meaningful conversations about the risks of a drug versus its benefits. Furthermore, they argue that the same problem will continue with Avandia (known generically as rosiglitazone) because the FDA's Risk Evaluation and Mitigation Strategy (REMS) depends on the assumption that doctors and patients will have meaningful discussion about the medication. "But given the lack of tools available to clinicians for translating these additional warnings into practice, the warnings are likely to be translated inconsistently throughout the country," researchers note.