Rosiglitazone: FDA restricties, EMA opschorten
Rosiglitazone: FDA restricts, EMA suspends
Use of rosiglitazone has been placed under heavy restriction in the USA and has been suspended altogether in Europe, the respective regulatory agencies announced yesterday.
Rosiglitazone has been under review since 2007, when a meta-analysis found that patients given the drug had an increased risk for myocardial infarction (MI) and a trend toward more vascular mortality relative to those given placebo or other antidiabetic drugs.
At this time, the US Food and Drug Administration (FDA) ordered the initiation of the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) - a head-to-head cardiovascular safety trial of rosiglitazone versus pioglitazone, which it has now halted.
The FDA requires GlaxoSmithKline, the drug sponsor, to submit a Risk Evaluation and Mitigation Strategy (REMS), making the drug available only under certain circumstances.
It will be available to patients not already taking it only if they are unable to achieve glycemic control using other medications and have medical grounds for avoiding pioglitazone.
Current users of rosiglitazone can continue using it if they appear to be benefiting from it, but doctors will have to attest to their patients' eligibility and patients will have to review information on the cardiovascular risk associated with the drug.
"The agency anticipates that the REMS will limit use of rosiglitazone significantly," write FDA commissioner Margaret Hamburg and colleagues in the New England Journal of Medicine.
The advisory committee had split opinions regarding action over rosiglitazone, they note. Three of the 32 members wanted no action, seven voted to change the label, 10 voted for restrictions, and 12 wanted the drug removed from the market entirely.
Hamburg et al acknowledge that there is a strong argument for completely suspending access to the drug, as the European Medicines Agency (EMA) has done.
However, they argue that rosiglitazone does have proven benefits in glycemic control, and may therefore be of benefit for patients who do not tolerate pioglitazone, as long as the cardiovascular risks are carefully considered.
Also, they note that the FDA is investigating a possible increased risk for bladder cancer with long-term use of pioglitazone, a risk that may deter patients with a history of the condition from using the drug. "When there are just two drugs in a class, and many outstanding uncertainties, maintaining some flexibility may have value for patient care," say Hamburg and colleagues.
In Europe, the EMA has suspended the marketing authority for rosiglitazone, so that drugs containing the agent will no longer be available within Europe.
This will continue "unless the marketing authorization holder can provide convincing data to identify a group of patients in whom the benefits of the medicines outweigh their risks," said the agency.