FDA Offers Docs Guidance on Rosiglitazone as Safety Review Nears Completion

Senate Committee Critical of Agency, GSK

February 25, 2010 05:15 pm News Staff

The FDA is recommending that patients continue taking the diabetes medication rosiglitazone, unless told otherwise by their physicians, as the agency continues to look at the risks and benefits of using rosiglitazone to treat type 2 diabetes. Meanwhile, the Senate Committee on Finance and drug manufacturer GlaxoSmithKline, or GSK, are debating the safety of the drug.

[Avandia logo image]

The FDA said in Feb. 22 safety announcement(www.fda.gov) that it will present cardiovascular safety data regarding rosiglitazone, which is marketed as Avandia, during a public meeting in July. At that time, the agency also plans to provide an updated assessment of the risks and benefits of the medication.

In addition to its single ingredient formulation, rosiglitazone also is marketed in combination with other diabetes medications -- specifically, with metformin under the brand name Avandamet and with glimepiride under the brand name Avandaryl. All three medications are manufactured by GSK.

The FDA, which has been reviewing the safety of rosiglitazone since 2007, issued the following advice for physicians in its safety announcement:

  • Follow the recommendations in the drug label when prescribing rosiglitazone, including a boxed warning that states that use of the drug in patients with established New York Heart Association Class III or IV heart failure is contraindicated. Furthermore, rosiglitazone is not recommended in patients with symptomatic heart failure.
  • Rosiglitazone causes or exacerbates congestive heart failure in some patients. Physicians should monitor for signs and symptoms of heart failure (e.g., excessive, rapid weight gain; dyspnea; edema of feet or ankles) after starting treatment and after dose increases. If heart failure signs and symptoms occur, the condition should be managed appropriately, and discontinuation or dose reduction of rosiglitazone must be considered.
  • Discuss with patients the risks of treatment, taking into account the clinical utility of rosiglitazone, the risks and benefits of other diabetes medications, and the risks associated with poorly controlled blood glucose.
  • Discuss with patients the importance of adhering to their diabetes medication regimen.
  • Report any adverse events associated with the use of rosiglitazone to FDA's MedWatch(www.accessdata.fda.gov) program.

FDA officials also said that available data on rosiglitazone and risk of myocardial ischemia are inconclusive. A meta-analysis of 42 clinical studies -- most of which compared rosiglitazone to placebo -- found an association between use of the drug and an increased risk of myocardial ischemic events. Three other studies, which compared rosiglitazone to other oral diabetes medications or placebo, have not confirmed or excluded this risk, the agency said.

Meanwhile, Senate Committee on Finance chairman Max Baucus, D-Mont., and ranking member Chuck Grassley, R-Iowa, issued a news release(finance.senate.gov) Feb. 20 along with a committee report about rosiglitazone that criticizes not only manufacturer GSK but the FDA's handling of the drug.

According to the release, public safety has been put at risk because the FDA "has been too cozy with drug makers and has been regularly outmaneuvered by companies that have a financial interest in downplaying or underexploring potential safety risks."

The committee report(finance.senate.gov) itself says that the evidence reviewed suggests that GSK was aware of the cardiac risks associated with rosiglitazone years before that information became public and that the drug maker ignored its obligation to sufficiently warn patients and the FDA.

"Instead, GSK executives intimidated independent physicians, focused on strategies to minimize findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that the rival drug Actos (pioglitazone) might reduce cardiovascular risk," the report says.

GSK responded in a Feb. 23 news release(www.gsk.com) that said the senate report is misleading and contains errors of fact and omissions.

"A fair examination of the company's record will show that GSK has been diligent in its efforts to thoroughly study the safety and effectiveness of rosiglitazone and to widely communicate that information to governments, regulatory authorities, scientific peers, physicians and others in a variety of ways," said GSK in its release.