The U.S. Food and Drug Administration on Thursday placed strict limits on the use of Avandia, three years after independent researchers said the diabetes drug increased the risk of heart attack and stroke.
"The FDA is taking this action today to protect patients, after a careful effort to weigh benefits and risks," said FDA Commissioner Margaret A. Hamburg, M.D. "We are seeking to strike the right balance to support clinical care."
In a separate but coordinated move, European regulators completely stopped the sale of Avandia. Hamburg said the FDA program to restrict access tightly rather than removing the drug is not an option available to European regulators.
That didn't satisfy FDA critics like Dr. Sidney Wolfe, director of watchdog group Public Citizen's Health Research, who said the agency was caving to pressure from the pharmaceutical industry. Avandia, once the top-selling diabetes drug in the world, is made by GlaxoSmithKline PLC, a British company.
"The FDA should have acted with its European counterpart and outright banned Avandia from the market," Wolfe said.
But restricting access through the FDA's Risk Evaluation and Mitigation Strategy program is expected to have much the same result. New patients will be allowed to receive Avandia only if they can prove they are unable to control their blood sugar on other drugs. People currently on Avandia will be able to remain on the therapy if they appear to be benefitting. But all Avandia patients and their doctors will have to sign documents showing that they have been informed about the drug's cardiovascular risks.
The same applies to AvandaMet and Avandaryl, which use Avandia.
The FDA's website shows more than 100 drugs are prescribed through a restricted access program, though the specific requirements can vary widely. Among them is thalidomide, known to cause severe birth defects but now used for certain kinds of cancer.
FDA officials said it will take several months to roll out the restricted access program for Avandia. In the meantime, they stressed that patients taking the drug should continue their medication and consult their physicians.
"It's very important that type 2 diabetics continue to control their blood sugar," said Dr. Joshua Sharfstein, the FDA's principal deputy commissioner. "Once the program is in place, health care professionals will need to enroll their patients in order to continue to receive rosiglitazone (Avandia)."
The agency estimates about 600,000 Americans take the medicine, which was approved in 1999. Last year, GlaxoSmithKline reported about $1.2 billion in worldwide sales of the drug. That's down from $3 billion in 2006, before the New England Journal of Medicine published a study that linked Avandia to a 43 percent increased risk of heart attack.
Tampa Bay area doctors said they started moving patients off Avandia after the first reports of cardiovascular problems appeared. Dr. Saji Koshy, associate director of the Diabetes and Endocrinology Institute at University Community Hospital in Tampa, said his patients responded well to Actos, a similar diabetes drug that doesn't have the same side effects as Avandia. Though the FDA said last week that it was investigating the possibility that Actos might increase the risk for bladder cancer, Koshy said he has seen no problems with patients who switched to the drug.
"We don't have anybody on Avandia now," Koshy said.
At USF Health, Dr. Hugo Narvarte, an internist and pediatrician, said his group did the same.
"I can't imagine going to the trouble of filling out paperwork and documenting that Avandia is a last resort when there's a widely available alternative out there," said Narvarte, who also has seen no problems with Actos.
In addition to restricting Avandia's use, a move recommended by an FDA advisory committee in July, the agency called a halt to an ongoing clinical trial comparing Avandia to Actos.
The FDA also ordered GlaxoSmithKline to commission an independent review of the company's study of Avandia's cardiovascular effects. That study, known as the Record trial, was criticized by an FDA medical officer who said errors in its design seriously biased the trial's conclusions.
GlaxoSmithKline said in a statement that it "continues to believe that Avandia is an important treatment for patients with type 2 diabetes." The company, whose share price closed Thursday at $39.43, down 72 cents, said it expects the regulators' decisions will reduce Avandia's global sales by half for the remainder of the year, "with minimal annual sales thereafter."
Dr. Steven Nissen, the cardiologist from the Cleveland Clinic who did the 2007 analysis linking Avandia to heart attacks, called the FDA's restrictions on the drug "a reasonable course of action." But he criticized delays by both regulators and the drugmaker, which he said endangered patients.
"The company first learned of these risks in 2005 and they informed the FDA but neither the company nor the FDA told doctors or patients," he said. "During those five years, many millions of patients took the drug and tens of thousands were harmed. We need to do better."
Kris Hundley can be reached at firstname.lastname@example.org or (727)892-2996.