The Food and Drug Administration said Thursday that it would sharply limit access to the diabetes drug Avandia because of concerns that it increases the risk of heart attacks and other cardiovascular problems.
Patients who are now taking the drug will have to sign an informed consent statement acknowledging that they understand all the risks before they will be allowed to refill their prescriptions. New patients will not be able to receive the drug unless their doctors certify that they are unable to control their blood sugar levels with other therapies and that medical problems preclude them from taking Avandia’s primary competitor, Actos.
At the same time, the European Medicines Agency said that it would suspend marketing of Avandia throughout the European Union. Regulators there don’t have the option of requiring patients to acknowledge a drug’s risk, so the suspension was necessary.
Dr. Margaret A. Hamburg, the FDA commissioner, said the two agencies had been in close consultation regarding the drug, which is also known by the generic name rosiglitazone.
“In our view, there is substantial alignment between the agencies on the interpretation and the risk to health,” Hamburg said at a news conference.
In both cases, the new rules will not take effect for several months.
In the United States, about 600,000 diabetes patients are receiving Avandia. “We think the number will go down very, very significantly with these new requirements,” Hamburg said.
Dr. Ellen Strahlman, chief medical officer for GlaxoSmithKline, which makes the drug, said in a statement that the company believes Avandia “is a safe and effective treatment when used appropriately,” but it will stop promotion of the drug in all the countries in which it operates.
Dr. Joshua Sharfstein, the FDA’s principal deputy commissioner, said that “patients should continue taking the medication and consult their healthcare provider. It’s very important that patients continue to control their blood sugar.”
The new rules will also apply to combination drugs made with rosiglitazone, including Avandamet, which contains metformin, and Avandaryl, which contains glimepiride.
Concerns about Avandia’s safety also led the FDA to suspend a major clinical study, called TIDE, that directly compares the efficacy of Avandia and Actos in controlling blood sugar.
Patients with Type 2 diabetes lose their ability to respond to insulin, which prevents them from converting glucose into energy. As a result, it builds up in their blood, putting them at risk for heart disease, vision problems and damage to nerves and blood vessels. The National Institutes of Health estimates that 23.6 million Americans have Type 2 diabetes.
Avandia was hailed as a major improvement in diabetes control when it was introduced in 1999. In 2006, at least 1 million Americans with Type 2 diabetes were taking it.
But Avandia became the subject of fierce debate when Cleveland Clinic cardiologist Steven Nissen published a study in 2007 suggesting that there was as much as a 40% increase in risk of cardiovascular disease, heart attack, stroke and death among users.
Subsequent studies generally supported his findings, and the drug came to be seen as a test of how an Obama administration FDA weighed risks and benefits in determining the fate of high-profile pharmaceuticals and the billions of dollars in revenue that comes with them.
In 2007, the FDA put a so-called black box warning on the drug’s label alerting consumers to the risk, and sales began falling. An FDA advisory committee revisited the issue in a heated meeting in July, where some experts argued for stronger warning labels on Avandia and others called for its immediate withdrawal.
Thursday’s rulings by the FDA and its European counterpart mean “the drug is effectively gone from use,” Nissen said in an interview Thursday.
The restriction “is not going to be a problem for us as practitioners” because of the availability of Actos and other treatment options, said Dr. Mark Molitch, an endocrinologist at Chicago’s Northwestern Memorial Hospital.
Molitch said he grew wary of Avandia as the debate over it progressed. “I’ve never taken people off of it, but I have to confess I haven’t been putting new patients on it,” he said.
Nissen lauded the curbing of Avandia, but he complained that “this took far too long” because within the FDA, “the promotion of drugs gets much more consideration than the restriction of drugs. That’s got to change.”
Actos, made by Japan-based Takeda Pharmaceuticals, has not been associated with cardiovascular problems, but last week the FDA announced it was studying whether there is an increased risk of bladder cancer from taking the drug.
Shares of Britain-based GlaxoSmithKline fell 72 cents, to $39.43, Tuesday on the New York Stock Exchange.
Maugh reported from Los Angeles and Zajac reported from Washington