The diabetes drug Avandia will now carry stronger warnings about heart failure risks, the Food & Drug Administration (FDA) said yesterday. Avandia, marketed by GlaxoSmithKline, is one of a class of diabetes drugs called thiazolidinediones that will carry the black box warning.
This class of drugs already had heart failure warnings on its labels, but they were buried deep within the label information. The FDA had asked all the manufacturers of thiazolidinediones to add the more prominent black box warnings in June, after the agency received reports that patients with heart failure had still taken the drugs and had died. In addition to Avandia, Glaxo manufactures two other thiazoldinediones, Avandaryl and Avandamet. Another company, Takeda, markets two thiazoldinediones under the names Actos and Duetact.
The new warnings will say that patients with the most severe forms of heart failure should not take the drugs, and that thiazoldinediones are not recommended for patients with heart failure that causes symptoms. The warnings also advise that doctors should reconsider the use of the drugs if a patient develops heart failure while taking thiazoldinediones.
The new warnings do not address a higher risk of heart attack that could be a side effect of thiazoldinediones. In May, the Cleveland Clinic had published a study showing that patients taking Avandia had a 43-percent higher risk of having a heart attack. After that study was published, Avandia became the subject of much controversy. In July, an FDA advisory panel voted to keep Avandia on the market despite the heart attack risk, but the panel also recommended that the drug bear the strongest possible FDA warnings about heart attacks. The FDA said that it is continuing to evaluate Avandia’s heart attack risks and the need for such a warning.
Over the summer both Glaxo and the FDA came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. Testimony at a congressional hearing in June revealed that the company and the FDA had known about a possible heart attack risk as far back as September 2005. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues. As a result, the cardiac problems were not made public until the Cleveland Clinic published its analysis in May.
That same congressional hearing also shed light on disturbing facts surrounding the FDA’s approval review of Avandia. At least one doctor testified that in 1999, he was pressured into downplaying his concerns with the medication’s cardiac side effects after Glaxo threatened him with legal action. It was also revealed that following its approval of the drug, the FDA had never required the manufacturer to conduct a post-market study of Avandia’s possible heart risks, even though an FDA reviewer had suggested such a study be done.