Actos Heart Failure Warning Strengthened in Canada

Health Canada has said that the warning label information about potential Actos heart failure side effects will be strengthened to indicate that the diabetes drug should not be used in patients with pre-existing heart failure or taken together with metformin and a sulfonylurea.

In the United States, the FDA required Takeda Pharmaceuticals North America, Inc, which manufactures Actos (pioglitazone), and GlaxoSmithKline PLA, which manufactures Avandia (rosiglitazone), to add “black box” warnings about the potential heart failure risk to the diabetes drugs in 2007.

Both Actos and Avandia are part of a class of medications known as thiazolidinedione (TZD) agents, which have been used by millions of diabetics to control blood sugar levels. However, the type 2 diabetes drugs have been associated with an increased risk of heart failure, which is a chronic condition that occurs when the heart can not effectively pump blood.

Although the previous labeling for Actos in Canada addressed the increased risk of heart failure, Health Canada indicates that they identified a need for new restrictions on use of the drug to better manage the risk. The new or updated information will indicate that Actos is contraindicated for individuals with any stage of heart failure and that Actos, metformin and a sulfonylurea drug should not be taken together.

In recent months, concerns about side effects of Avandia have over-shadowed the potential heart failure risks of Actos. In October, the American Diabetes Association and the European Association for the Study of Diabetes unanimously advised against the use of Avandia and the consumer advocacy group Public Citizen filed a petition with the FDA calling for an Avandia recall due to a number of different life-threatening side effects.

While both Actos and Avandia increase the risk of congestive heart failure, a study published last month in The Archives of Internal Medicine suggested that users of Avandia are more likely to experience heart failure or death than users of Actos. When comparing use of the two drugs among 28,000 diabetics over 65, researchers found that Avandia carried a 13% greater chance of heart failure and a 15% higher rate of death.

Last week, the FDA indicated that they will be increasing their scrutiny of new diabetes drugs in development by issuing revised guidance about additional studies that will be necessary to establish that the drugs do not increase the risk of heart attacks and cardiovascular events.

Although it is unclear what impact these new standards with have on drugs like Actos and Avandia, which are already approved despite their known heart risks, the agency has indicated that they are continuing to evaluate how their recommendations will be applied to diabetes drugs already on the market.