Avandia label revised as per FDA directive

By Dr. Ananya Mandal, MDFeb 8 2011

Following the 2010 FDA directive, pharmaceutical manufacturer Glaxo-SmithKline announced this Monday that they have modified the label for diabetes drug rosiglitazone (Avandia). The new label restricts its use to patients already taking it or to those who have failed other antiglycemic drugs.

The label reads, rosiglitazone may be started only in patients who “are unable to achieve adequate glycemic control on other diabetes medications, and, in consultation with their healthcare provider, have decided not to take pioglitazone (Actos) for medical reasons.”

The directive came up when there was a evidence of heightened cardiovascular risks associated with rosiglitazone from a meta-analysis of 52 earlier studies as well as three stand-alone trials. The trials found higher rates of heart attacks in patients taking rosiglitazone versus placebo or another comparator drug.

The label warning also says rosiglitazone has not been compared with pioglitazone in a head-to-head study of cardiovascular risks. But a placebo-controlled trial of the latter drug did not indicate an increase in heart attacks or deaths. It warns that patients with NYHA Class III or IV heart failure should not receive rosiglitazone, and the drug may increase other cardiovascular risks in patients with milder forms of heart failure.

The directive from FDA came last September after an advisory committee vote that favoured keeping the drug on the market, but only if fewer and lower-risk patients were allowed to take it. The Food and Drug Administration announced the changes as the last in a series of safety actions against the former blockbuster drug, which has triggered thousands of lawsuits and a Department of Justice investigation. The European Union has banned the drug.

GSK in a statement said that it was continuing to work on another FDA request to re-analyze data from the so-called RECORD study with independent adjudication of cardiovascular outcomes. The team of researchers had faced criticism on the study for using questionable determinations of cardiovascular events that patients in the trial may have experienced. The FDA wants Glaxo to require patients to sign a statement indicating that they have reviewed the cardiovascular safety concerns about the drug. The company said it was “working closely with the FDA” to finalize the REMS.