GlaxoSmithKline and Takeda’s type 2 diabetes treatments, respectively Avandia and Actos, will now have to carry boxed warnings stating that they may "cause or worsen heart failure in certain patients", US regulators have declared.
Following its review, the US Food and Drug Administration said the new warnings will apply to the entire thiazolidinedione class of drugs and as well as Avandia (rosiglitazone) and Actos (pioglitazone) includes Avandaryl (rosiglitazone and glimepiride), Avandamet (rosiglitazone and metformin) and Duetact (pioglitazone and glimepride).
"This new boxed warning addresses FDA's concerns that despite the warnings and information already listed on the drug labels, these drugs are still being prescribed to patients without careful monitoring for signs of heart failure," noted Steven Galson, director of the Center for Drug Evaluation and Research.
The agency noted that its review of adverse event reports found cases of significant weight gain and oedema – warnings signs of heart failure and in some of these reports, continuation of therapy had been associated with poor outcomes, including death.
The strengthened warning advises healthcare professionals to look carefully for the signs and symptoms of heart failure in their patients, including excessive, rapid weight gain, shortness of breath, and oedema after starting drug therapy. Patients with these symptoms who then develop heart failure should receive appropriate management of the heart failure and use of the drug should be reconsidered.
The boxed warning, the strongest there is, also states that these drugs should not be used by people with serious or severe heart failure who have marked limits on their activity and who are comfortable only at rest or who are confined to bed or a chair.
GSK noted that since 2001, US prescribing information for Avandia has included a warning for cardiac failure and other cardiac effects with a recommendation that use of the drug be discontinued in patients if their cardiac status worsened. Increasing the prominence of the warning comes as no surprise especially given the prominence that the thiazolidinedione class has had of late, and Avandia in particular, but Chris Viehbacher, president of US pharmaceuticals at GSK, said on a conference call that
"I don't, at this stage, think we're going to see a significant impact on prescribing in terms of dollar value".
The announcement comes after the recent decision by FDA advisory committees to allow Avandia to stay on the market as long as its label is tightened concerning ischaemic risk and the agency noted that its review of Avandia and possible increased risk of heart attacks is ongoing.