FDA: Rosiglitazone Can Remain on the Market – With Big Restrictions

Researchers had hoped the RECORD study would set the rosiglitazone risk story straight. But in July, the FDA panel tasked with reviewing the drug’s safety questioned RECORD and its adjudication of cardiovascular events, Dr. Woodcock said. “RECORD was an open-label trial, and it was determined that we can’t rely on those results, even though they did not show a significantly increased risk of cardiac harm. Therefore, the questions raised by the meta-analysis have not really been answered. We still believe there is considerable uncertainty about the magnitude of the cardiovascular risk.”

The FDA will ask GlaxoSmithKline to conduct an independent review of RECORD’s adjudication at a patient record level in an effort, Dr. Sharfstein said, “to catch events that occurred but which might have not been properly referred to the adjudication committee.”

At the press briefing, Dr. Woodcock also announced the termination of the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) study, also sponsored by GlaxoSmithKline. TIDE was designed to determine any difference in cardiovascular safety between rosiglitazone and pioglitazone. In July, the FDA put TIDE on a partial hold, allowing patient enrollment, but not treatment. Today, Dr. Woodcock said the readjudication of RECORD should provide the answers needed to make the best decision about rosiglitazone’s future.

About 30 other drugs already carry REMS programs, including three formulations of pioglitazone. Pioglitazone tablets; pioglitazone/metformin tablets; and extended-release pioglitazone/metformin tablets all require the dispensing of a medical guide along with the medication – the most common REMS plan.

But other REMS programs – including the one that will be established for rosiglitazone – are much more restrictive, such as the one for the antiepileptic vigabatrin. That REMS requires not only a medication guide, but a communication plan to ensure reporting of adverse events, elements to assure safe use, and a system to ensure that physicians, pharmacies, and patients who do not comply with the rules lose access to the drug.