The FDA on Wednesday added a black box warning to GlaxoSmithKline's (GSK) Avandia (rosiglitazone), stating the diabetes treatment was linked to a potential increase in the risk of heart attacks.
The new warning was added to an existing black-box warning that says the Avandia increases the risk of heart failure.
The agency said the latest black box warning would also apply to GSK's diabetes drugs Avandamet and Avandaryl, since they both contain the same active ingredient found in Avandia.
Avandia is expected to remain on the market while a “safety assessment continues,” the FDA said.
Meanwhile GSK has been asked by the FDA to conduct an additional long-term safety study of Avandia comparing it to Takeda's diabetes drug Actos. The details of the study have not been yet been fully worked out between the FDA and Glaxo.
The safety of Avandia first came into question in May following publication of a New England Journal of Medicine (NEJM) analysis, conducted by prominent Cleveland Clinic cardiologist Steven Nissen. Nissen found that that rosiglitazone increased the risk of death from cardiovascular causes that had “borderline significance.”
Overall, the analysis concluded that patients receiving rosiglitazone had a 43% increase in the risk of having a heart attack, compared to patients not receiving the drug--a “significant increase” Nissen said.
The analyzed trials involved 15,560 patients who received drugs containing rosiglitazone and 12,283 who either received other drugs or a placebo.
Following Nissen's study, GSK said it strongly disagreed with the conclusions of the article, which it said were based on incomplete evidence and a methodology that has significant limitations.
Avandia was approved in 1999 for treatment of Type 2 diabetes, a disease that affects about 18 to 20 million Americans. Avandia had US sales of approximately $2.2 billion in 2006.
There has been a split within the FDA over whether to pull Avandia off the market or allow it to stay, with stronger warnings.
An outside panel of medical experts met in July to discuss the matter and voted 22-1 to keep Avandia on the market. However, several of those panel members also recommended that Avandia carry stricter warnings.