Diabetes drugs to carry black-box warnings.

FDA announced Aug. 14 that GlaxoSmithKline and Takeda Pharmaceutical have agreed to add "black-box" warnings about the risk of heart failure to the labels for Avandia and Actos.

After a review of post-marketing adverse event reports, FDA determined that an updated label with a boxed warning on the risks of heart failure was needed for the entire thiazolidinedione class of anti-diabetic drugs, which includes Avandia (rosiglitazone), Actos (pioglitazone), Avandaryl (rosiglitazone and glimepiride), Avandamet (rosiglitazone and metformin) and Duetact (pioglitazone and glimepride).

"Under FDA's post-marketing surveillance program, we carefully monitor new safety information for marketed drugs and take appropriate action when necessary to inform patients and health care providers of new information," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drugs. "This new boxed warning addresses FDA's concerns that despite the warnings and information already listed in the drug labels, these drugs are still being prescribed to patients without careful monitoring for signs of heart failure."

FDA's review of adverse event reports found cases of significant weight gain and edema--warning signs of heart failure. In some reports, FDA noted, continuation of therapy has been associated with poor outcomes, including death.

The strengthened warning advises health care professionals to observe patients carefully for the signs and symptoms of heart failure, including excessive, rapid weight gain, shortness of breath and edema after starting drug therapy. Patients with these symptoms who then develop heart failure should receive appropriate management of the heart failure and use of the drug should be reconsidered. People who have questions should contact their health care providers to discuss alternative treatments.

The warning also states that these drugs should not be used by people with serious or severe heart failure who have marked limits on their activity and who are comfortable only at rest or who are confined to bed or a chair.

FDA's review of Avandia and possible increased risk of heart attacks is ongoing. On July 30, the agency's Endocrine and Metabolic Advisory Committee and the Drug Safety and Risk Management Advisory Committee recommended that Avandia continue to be marketed, and further recommended that information be added to the labeling for risk of heart attacks (ischemic risks).