avandia diabetic

The new heart-attack warning on the label of GlaxoSmithKline PLC's once-blockbuster diabetes drug Avandia will likely add to the company's challenge in marketing a product shadowed by a serious safety question.

Under pressure from the Food and Drug Administration, Glaxo agreed to a "black-box" warning that says an analysis showed Avandia "to be associated with an increased risk" of ischemic events such as heart attacks, in which blood is choked off from the heart. However, the new warning also says the overall data are "not conclusive."

The FDA said it doesn't have enough evidence to show that the risks of heart attacks or death for patients taking Avandia are different from those for people on other diabetes medications.

Despite the hedged language, Glaxo may have an uphill fight to convince doctors that Avandia is an attractive alternative to rival drugs that don't carry a similar warning, particularly Takeda Pharmaceutical Co.'s Actos, which is similar to Avandia. Sales of the Glaxo drug, which were £1.65 billion ($3.42 billion) world-wide last year, have plunged since the May publication of a medical journal article by Cleveland Clinic cardiologist Steven Nissen that raised concerns about its possible heart risk. Avandia sales in the first nine months of this year fell 14% globally, to £988 million, and 21% in the U.S., to £650 million, when compared with the same periods in 2006, Glaxo reported.

Both Actos and Avandia already have black-box warnings about a different side effect -- heart failure, a chronic condition in which the heart has trouble pumping blood. But heart attacks may be a bigger concern for doctors because, unlike heart failure, they can come without warning and be immediately fatal. In addition, diabetes patients in general tend to have a higher risk of cardiovascular problems.

The new warning will also apply to the Glaxo products that combine Avandia with other treatments, called Avandaryl and Avandamet. In a win for Glaxo, the FDA also said it would ask makers of other diabetes drugs to note in their labels that they hadn't been proven to reduce cardiovascular problems...

The new label has been changed to highlight the increased cardiovascular risks with the drug, noting in a boxed warning that in a meta-analysis of 52 studies, most of which compared rosiglitazone with placebo, the drug was associated with a significantly increased risk of MI. The new label highlights the lack of comparative clinical trials between rosiglitazone and pioglitazone but notes that pioglitazone, in a study compared with placebo, was not associated with an increased risk of death..