FDA wants further warnings on Glaxo's Avandia.

FDA officials are pushing for a "black box" warning of the risk of heart attack on GlaxoSmithKline diabetes drug Avandia, the "Wall Street Journal" reported Oct. 24, citing unnamed sources.

The drug already carries one FDA black box warning for heart failure. A warning for the risk of heart attack would be more serious.

Another black box label warning--the strongest given by FDA--would be a further blow to the once-top-selling diabetes drug, which came under pressure last May when an analysis linked Avandia to a 43% higher risk of heart attack, Reuters reported.

Glaxo Chief Executive J.P. Garnier said the London-based company has not heard anything from FDA about further warnings. "In terms of further changes to the label, we will have to wait and see."

The European Medicines Agency last week recommended a tighter label for Avandia but said the benefits outweighed risks for the drug and for a similar one, Actos, sold by Takeda Pharmaceutical. Actos does not carry a warning for heart-attack risk.

If it goes into effect, the new warning would focus on Avandia's potential for increased ischemic risk. An FDA meta-analysis of multiple Avandia studies found that the drug appeared to be linked to a 38% higher risk of ischemic events. The company has said that such analyses aren't typically considered the strongest form of medical evidence, and that other data didn't show a similar risk.

The potential Avandia label-change has played out amid pressure from outside researchers and scrutiny from Capitol Hill. In June, there was a congressional hearing focused on the drug's safety, and the FDA's handling of it. The drug is the subject of continuing investigations by lawmakers, including the Senate Finance Committee, whose investigators announced Oct. 30 that an internal FDA drug-safety oversight board narrowly voted to keep Avandia on the market.

Sen. Charles Grassley (R-IA), the top Republican on the panel, who has been investigating the FDA's handling of drug-safety issues, said the drug-safety oversight board voted 8-7 earlier this month to keep Avandia on the U.S. market, "The Wall Street Journal" reported.

FDA officials have acknowledged there has been a split within the agency about whether to pull Avandia off the market or allow it to stay on the market with a tougher "black box" warning that the drug raises the risk of heart attacks. An outside panel of medical experts voted 22-1 on July 30 to keep Avandia on the market, but several panel members said the drug should have stricter warnings. FDA usually follows its panel's advice but isn't required to do so. A black-box warning is FDA's strongest drug warning.

FDA and GlaxoSmithKline have said they are working to finalize a new drug label for Avandia but won't discuss the specifics.

Sen. Grassley criticized FDA for not making details of the drug-safety oversight board's meeting on Avandia public. "The Avandia case continues to present new rounds of questions about the way the FDA monitors and assesses drug risks and decides whether to let the public know about emerging risks," he said.

An FDA spokeswoman declined to comment on the matter but said the agency would respond to Sen. Grassley shortly.