FDA notice of black-box warnings for GlaxoSmithKline's Avandia, and drugs like it, for congestive heart failure came as a surprise to many.
Issued a mere two weeks after a federal advisory committee debated Avandia's heart attack risk, clinicians and others thought the warning may have had something to do with risk of ischemic events.
"[Physicians and patients] are confused about what this has to do with the recent news about…myocardial infarction. They think it's in relationship to that," said Bob Spanheimer, MD, senior medical director of diabetes for Takeda, which markets two of the drugs that will get the new boxed warning, Actos and Duetact. Spanheimer said that in the last 24 hours he has fielded queries from at least one physician concerned about the risk of heart attacks. He said some physicians are calling to say their patients are "slightly confused" about it, as well.
At the July 30 meeting, FDA advisors recommended that Avandia should stay on the market but get unspecified new warnings . The agency told manufacturers that the CHF warning was unrelated to that meeting, but its press release does not make the distinction clear.
The uncertainty was unfortunate, especially considering the long lead-up to yesterday's notice. For months the FDA had been working with manufacturers on the wording of the CHF warnings. During testimony before the House Committee on Oversight and Government Reform in June, FDA commissioner Andrew von Eschenbach told the committee the agency had requested black-box warnings on all thiazolidinediones (TZD) drugs in letters dated May 23.
The agency decided to strengthen the warnings because, while the labels of TZD drugs have mentioned CHF risk all along, clinicians still aren't monitoring for signs of heart failure after prescribing them, said Steven Galson, MD, director of FDA's Center for Drug Evaluation and Research, in the press release.
Drugs in the class include pioglitazone-containing drugs Actos and Duetact as well as rosiglitazone-containing products Avandia, Avandamet and Avandaryl.
"The discussion is still ongoing about myocardial ischemic events," explained Mary Anne Rhyne, GSK director, US media relations. Of yesterday's FDA notice, she said, "It's pretty much what we expected. This just gives us the go-ahead to implement the labeling we committed to before."
The stiffer warning "increases the prominence" of the preexisting warnings and will note that TZDs are not recommended in patients with symptomatic heart failure and are contraindicated in others, GSK said in its own statement.