New restrictions on the diabetes medication rosiglitazone(www.fda.gov) will require additional steps for physicians who continue to prescribe the drug, which is marketed as Avandia.
Acting in response to data that suggest an elevated risk of cardiovascular events in patients using rosiglitazone, the FDA announced Sept. 23 that it will restrict the use of the drug to patients with type 2 diabetes who cannot control their diabetes on other medications.
"The drug will be available to patients not already taking it only if they are unable to achieve glycemic control on other medications and (who), in consultation with their health care provider, decide not to use pioglitazone for medical reasons," said FDA Commissioner Margaret Hamburg, M.D., in a Sept. 23 news conference.
Pioglitazone, which is marketed as Actos, is the only other medication in the class of drugs known as thiazolidinediones.
Physicians will be required to attest to and document a patient's eligibility for rosiglitazone. Patients, meanwhile, will be required to review safety information describing the cardiovascular concerns associated with rosiglitazone.
Patients already using rosiglitazone may continue using the medication if they appear to be benefiting from it and they acknowledge that they understand the risks, said FDA Principal Deputy Commissioner Joshua Sharfstein, M.D.
According to Sharfstein, patients already taking rosiglitazone should continue taking their medication and consult their physician. However, he added, physicians may want to consider switching patients to a different medication because of the cardiovascular risks associated with rosiglitazone.
The FDA is requiring manufacturer GlaxoSmithKline, or GSK, to develop the restricted access program under a risk evaluation and mitigation strategy, or REMS. Physicians will have to enroll patients into the REMS so they can continue receiving rosiglitazone, according to Sharfstein.
But, he added, it will take several months to develop the REMS.
During a July 13-14 joint meeting of the FDA's Endocrinologic and Metabolic Drugs Advisory Committee and the agency's Drug Safety and Risk Management Advisory Committee, a plurality of the committees' members voted to recommend that the agency remove rosiglitazone from the market.
Janet Woodock, M.D., director of the FDA's Center for Drug Evaluation and Research, said the agency stopped short of removing the product from the market because there still is some uncertainty about the drug's link to cardiovascular risk. However, she said the FDA is acting prudently in restricting access to the drug because the link has not been refuted.
Meanwhile, the European Medicines Agency recommended suspension of the marketing authorizations(www.ema.europa.eu) for rosiglitazone-containing products.
Hamburg said the FDA expects the REMS to significantly limit use of rosiglitazone in the United States. The restrictions also will apply to the combination drugs marketed as Avandamet, which contains rosiglitazone and metformin, and Avandaryl, which contains rosiglitazone and glimepiride.
In addition to requiring GSK to develop the REMS, the FDA halted the manufacturer's Thiazolidinedione Intervention with Vitamin D Evaluation, or TIDE, trial, which compares rosiglitazone to pioglitazone.
Hamburg said the clinical trial did not meet Institute of Medicine requirements for safety evaluations.
The agency also ordered GSK to conduct an independent review of the company's Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes, or RECORD, trial because of potential bias. The RECORD trial studied the cardiovascular safety of rosiglitazone compared to other diabetes drugs.
Physicians and patients are encouraged to report adverse events or side effects related to the use of rosiglitazone to the FDA's MedWatch(www.accessdata.fda.gov) program.