Is the FDA a watchdog or a dog?   (June 7, 2007)

The latest news about the diabetes drugs Avandia (rosiglitazone) and its close relative Actos (pioglitazone) is that the FDA had recently asked the manufacturers of these two “glitazones” to add “Black Box” warnings to their labels. Black Box warnings are the most severe warning that can be added to a label: see discussion elsewhere at Black box warning.

This request was disclosed by FDA Commissioner Andrew von Eschenbach in written testimony submitted to a congressional panel at a hearing yesterday. In his testimony, von Eschenbach apparently indicated that the FDA has asked GlaxoSmithKline, the maker of Avandia, and Takeda, the maker of Actos, to strengthen existing warnings about congestive heart failure (CHF). Both drugs have had warnings about the risk of heart failure for several years, but von Eschenbach said that these drugs were still being prescribed to patients with significant heart failure and implied that therefore stepped-up warnings were advisable. (As of this moment, I cannot locate a transcript of his exact words on-line.)

Amazingly, the FDA’s concern about CHF was not disclosed in an FDA “Safety Alert” published May 21st about the possibility of Avandia having an increased risk of myocardial infarction (MI, heart attack) and cardiovascular death. This Alert was rapidly published after the New England Journal of Medicine (NEJM) had posted a review article about Avandia the same day: “Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes.”

Unlike the “Safety Alert”, the latest FDA revelation now implicates Actos as well as Avandia in having worrisome heart problems: both drugs share a concern about increased risk of CHF, and Avandia also has a possible increased risk of MI and cardiovascular death.

My question: Why didn’t FDA announce its concern about CHF with both glitazones when it announced its official reaction to the Avandia article in the NEJM? Sheer sloppiness? Ignorance by the authors of the Safety Alert of the fact that their colleagues had already sent a request to add a Black Box warning? Was there some unknown ulterior motive to hide the request for a Black Box warning from the public - I doubt this explanation, although some paranoid folks will jump on it.

Whatever the reason, both “glitazones” are now under a very dark gray cloud, and the FDA comes off looking pretty silly (or more) to both physicians and patients.

As a final thought: do not stop these, or any other prescribed medications, without first discussing the issues and possible alternative therapies with your physician.