Avandia should stay on shelves, U.S. panel says

The widely used diabetes drug Avandia should stay on the market in the United States with a warning about increased risks of heart diseases, a panel of medical experts recommended to the U.S. Food and Drug Administration yesterday, in a decision that went against the urging of one federal scientist that the medicine be withdrawn.

The FDA is expected to follow the recommendation, although officials said it will need some time to make a final decision.

It was the latest development in the continuing saga of Avandia, a controversial drug manufactured by GlaxoSmithKline PLC that was the third most commonly prescribed oral pharmaceutical last year for the roughly 1.8 million Canadians with Type 2 diabetes.

The FDA was expected to follow the panel's recommendation, even though one of its own scientists testified earlier that the medicine should be pulled from the market because of increased heart risks.

Health Canada, which has confirmed that 19 Canadians have suffered fatal heart problems while using Avandia since its approval here in March, 2000, is conducting its own analysis of the drug.

The medicine's benefits are still deemed to outweigh its risks, an agency spokesman said.

Alastair Sinclair said a preliminary review of the 19 deaths suggests a possible link between the drug and six of the fatalities. In all, the agency has received 243 reports of adverse cardiovascular reactions to the drug, including 31 heart attacks, but said that they had not established a link between the cardiovascular problems and the drug.

"Medical and scientific information is continuously evolving, and the results of the advisory panel will be considered in Health Canada's assessment of Avandia, as will the findings of a number of scientific studies," Mr. Sinclair said.

The panel was convened by the FDA two months after a study published in The New England Journal of Medicine linked the drug to a 43 per cent higher chance of having a heart attack among sufferers of Type 2 diabetes.

Glaxo executives argued before the panel that there is no increased risk, citing its own studies of the drug.

"The number of heart attacks across all sources of data is small, the data are inconsistent, and the totality of evidence does not show a difference between Avandia and the most commonly prescribed anti-diabetic agents," read a summary of the company's defence to the committee.

According to IMS Health Canada, a private firm that collects information on the prescription drug market, nearly 1.2 million prescriptions for the drug were filled in Canada last year at a retail value of about $156 million.

Warnings of heart risks associated with Avandia have been around since it was authorized for mass distribution in Canada and the United States. Just four months after the drug was approved here, a group of physicians in British Columbia sounded the alarm about Avandia, citing side effects that included weight gain and a spike in so-called bad cholesterol.

"It was doing things that were known to be associated with adverse cardiovascular outcomes," said Jim Wright, a professor of pharmacology at the University of British Columbia and managing director of Therapeutics Initiative, the independent organization of physicians that raised the concern in a newsletter to doctors.

"There really is no evidence that the benefits outweigh the harm," Dr. Wright said in a telephone interview. "There was lots of time for [Health Canada] at that point to have done a trial and they didn't do it."

A year later, in July, 2001, Glaxo was reprimanded by the FDA about its promotion of Avandia and for playing down safety concerns. The company subsequently fired off letters to doctors warning them of risks of heart failure.

In a letter to Canadian doctors dated Nov. 13, 2001, Glaxo warned that Avandia could cause fluid retention, which, the company wrote, "can exacerbate or lead to congestive heart failure."

Canadian diabetes experts yesterday cautioned against reacting too hastily to the developments south of the border.

Lawrence Leiter, head of the division of endocrinology at St. Michael's Hospital in Toronto, said the drug is effective at lowering blood sugar and pointed to studies showing that half of all diabetics in Canada do not have their blood sugar under control.

"We don't want to unnecessarily lose a drug that can be very useful," Dr. Leiter said. "Right now, we have conflicting data."

Whitney Binns, spokeswoman for the Canadian Diabetes Association, recommended that diabetics on Avandia consult their doctors about the appropriate course of action and said the organization trusted that Health Canada would advise the diabetic community of its findings shortly.


Source:www.theglobeandmail.com