Sept. 23, 2010 -- The FDA will not ban Avandia -- but stringent restrictions will make it far harder for doctors to prescribe the safety-troubled diabetes drug.

The European Medicines Agency took harsher action. European sales of Avandia-containing drugs will be suspended over the next few months, although the agency did not formally withdraw approval.

The 600,000 U.S. patients currently taking Avandia can continue to take the drug only if their doctors officially attest that their patients understand the risks, that the drug is helping them, and that no other diabetes drug can keep their blood sugar under control.

New Avandia prescriptions can only be written for patients who, for medical reasons, cannot take Actos. Actos, a diabetes medication in the same class as Avandia, does not cause the heart problems linked to Avandia.

"Avandia will be available to new patients only if they cannot achieve [blood sugar] control on other agents and cannot take Actos," FDA commissioner Margaret A. Hamburg, MD, said at a news conference. "Current patients can continue taking Avandia only if they benefit and understand the risks."

Avandia maker GlaxoSmithKline will be required to establish a Risk Evaluation and Mitigation Strategy (REMS) program. Patients, their doctors, and their pharmacists will have to enroll in the program in order to receive, prescribe, or sell Avandia.
Avandia Heart Risks Clouded by Uncertainty

Hamburg admitted that FDA experts are split over how to interpret the scientific evidence suggesting that Avandia damages the heart. Both Avandia and Actos increase the risk of heart failure. But evidence suggests that only Avandia increases risk of heart attack.

Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, noted that an FDA advisory panel last July split over the issue of whether the evidence proved Avandia unsafe.

"In and outside the agency there is mostly agreement on the facts, but not on the weight of the safety analysis," Woodcock said at the news conference. "This has resulted in different conclusions, not only inside FDA but among outside experts. This reflects uncertainty in the science that tells us whether or not Avandia causes these problems."

Questions about Avandia heart safety should have been answered by the RECORD study, which Avandia maker GlaxoSmithKline conducted at the behest of the European drug agency. This study found Avandia to be safe, but critics have lambasted the study's poor design. Moreover, an FDA analysis suggests that the study failed to investigate all possible heart attacks in study patients.

Today's FDA action will require GlaxoSmithKline to convene a panel of independent scientists to review the RECORD data. That review may cause the FDA to lift the new Avandia restrictions -- or to ban the drug.

The FDA today also officially ended a study called TIDE, which was directly comparing Avandia and Actos. The FDA decided that the study, which already had been suspended, posed too much risk to participants.

In a statement, GlaxoSmithKline says it "continues to believe that Avandia is an important treatment for patients with type 2 diabetes," but that it will work with the FDA and the European Medicines Agency to implement their decisions.