A boxed warning of increased risk of heart attack due to the diabetes drug rosiglitazone is inadequate and exposes patients to potentially unsafe medicine, according to a study published in the New England Journal of Medicine.

The Federal Drug Administration (FDA) should have either removed rosiglitazone from the shelves or provided better decision-making tools for clinicians and patients to evaluate their options, said senior author Cynthia Jackevicius, PharmD, Western University of Health Sciences College of Pharmacy Associate Professor for Pharmacy Practice and Administration. This is Jackevicius’ third publication in the New England Journal of Medicine in the past three years.

“When warnings come out, they are not very directive,” she said. “This may cause uncertainty to providers and patients, which leads to differences in care.”

The FDA issued a boxed warning on May 21, 2007, showing that rosiglitazone was associated with a 43 percent increase in the risk of myocardial infarction, according to the study. A consensus regarding the risk posed by rosiglitazone has emerged among experts, but data from some populations show some use persisted in certain areas despite an overall reduction in usage. On Sept. 23, 2010, the FDA decided to restrict access to rosiglitazone.

The use of rosiglitazone decreased 70 percent, but since the drug was not removed from the market an estimated 3.8 million rosiglitazone prescriptions were still being dispensed annually in the United States as of June 2009, according to the study. The absolute number of filled prescriptions for rosiglitazone decreased from 1.3 million monthly at the peak (in January 2007) to slightly more than 317,000 in June 2009, according to the study.

With other options on the market, there is no reason to keep rosiglitazone around, especially if it is not going to be used in an informed way, Jackevicius said.

Different regions of the country had a twofold variation in the use of the drug before the warning, and the variation increased to a three-fold variation after the warning.

“We need tools to reduce variation,” Jackevicius said.

The study concludes: “Variations in responsiveness to warnings within the United States should be of critical interest to the FDA, since patients may be exposed to risk differentially depending on where they live. Specifically, if the use of rosiglitazone varies widely throughout the country and thus can potentially cause differential harm, the best way for the FDA to protect the public’s health may be to remove the drug from the market. Alternatively, if the FDA values the practice of offering patients and clinicians as great a range of options as possible, it may need to provide decision-making tools for incorporating information about patients’ context and preferences to better align residual use with informed patient choice.”

The online version of the article was published on Nov. 17, 2010 and the print version was published on Thursday, Nov. 25, 2010.

Responding to an FDA Warning — Geographic Variation in the Use of Rosiglitazone

Authors: Nilay D. Shah, Ph.D., Victor M. Montori, M.D., Harlan M. Krumholz, M.D., Karen Tu, M.D., G. Caleb Alexander, M.D., and Cynthia A. Jackevicius, PharmD. New England Journal of Medicine. Nov. 17, 2010.