Avandia And Actos Add "Black Boxes" For Heart Failure
As an interim step in its ongoing review of thiazolidinedione cardiac safety, FDA has called for revised class labeling for the TZDs featuring strengthened warnings about the incidence of heart failure and contraindications for patients with existing heart failure.
The update to labeling for GlaxoSmithKline's Avandia (rosiglitazone) and Takeda's Actos (pioglitazone) includes the addition of a "black box" warning about the risk of heart failure with the type 2 diabetes drug, FDA announced Aug. 14.
Previously, TZD labeling contained information about congestive heart failure in the Warnings and Precautions sections, but FDA requested the strengthened warnings in May based on a review of postmarket adverse event reports (1"The Pink Sheet" June 11, 2007, p. 3).
Additional labeling changes are likely for Avandia and possibly for Actos as well, given the safety investigations underway. During a recent advisory committee review of Avandia, panel members suggested that rosiglitazone labeling should also carry a boxed warning about the risk of heart attacks (2"The Pink Sheet" Aug. 6, 2007, p. 3).
"This new boxed warning addresses FDA's concerns that despite the warnings and information already listed in the drug labels, these drugs are still being prescribed to patients without careful monitoring for signs of heart failure," CDER Director Steven Galson said in a press release.
The "black box" will contain the following two messages:
TZDs cause or exacerbate congestive heart failure in some patients. After initiation of TZD therapy, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to the current standards of care. Furthermore, discontinuation or dose reduction of the TZD must be considered.
TZDs are not recommended in patients with symptomatic heart failure. Initiation of TZD treatment in patients with established NYHA Class III or IV heart failure is contraindicated.
The new warnings also apply to the combination products that include the TZDs: Avandaryl (rosiglitazone and glimepiride), Avandamet (rosiglitazone and metformin), and Duetact (pioglitazone and glimepiride).
- Brian Marson
This article is reprinted from "The Pink Sheet" – August 20, 2007
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