Two major prescription benefit managers (PBMs) announced Thursday that they were removing GlaxoSmithKline's Avandia (rosiglitazone) from their formularies due to potential heart risks.

The diabetes treatment has been the subject of controversy since meta-analysis in the 

 suggested Avandia increases the risk of heart attack by 40 percent compared with other oral diabetes therapies or placebo.

HealthTrans and Prime Therapeutics, which together account for more than 25 million covered lives, both cited safety as the reason for dropping the drug. They follow in the footsteps of the US Department of Veterans Affairs, which dropped Avandia from its formulary in October.

"It's based on the literature regarding evidence that Avandia is associated with primary myocardial risk and the meta-analysis of clinical trials, which was then replicated by the FDA and GlaxoSmithKline," Craig Mattson, Prime Therapeutics' senior director of drug technology assessment and formulary development, told 

 Friday. "Although their results were not the same, trends showed an increased risk."

The case against Avandia is far from universally accepted. FDA is keeping the drug on the market, with a black-box warning of increased risk of myocardial ischemic events, though FDA acknowledges that there is not enough evidence to prove conclusively that Avandia increases the risk of heart attack or cardiac ischemia more than other diabetes medications. A 

 on behalf of the American Diabetes Association urges caution, but states that the heart attack data against Avandia are inconclusive and that the increased risk of congestive heart failure with the drug is not great enough to remove it from treatment.

The PBM, in this case, is more cautious than the medical organization. "We always want to err on the side of safety," said HealthTrans Vice President of Clinical Services Lois Mastin.

"GSK has to make sure this doesn't become a trend," Mason Tenaglia, managing director at consulting firm The Amundsen Group, told 

 Monday. "But as long as doctors want to treat patients with Avandia, it will stay on the formularies."

GSK is designing a study that will test Avandia against other antidiabetic treatments, such as Actos (pioglitazone), its major competitor. The Takeda-manufactured drug is also being scrutinized for safety issues. GSK's study will be completed by 2014.

News Analysis

Avandia is not getting pulled from the market, but that doesn't mean prescription benefit managers are going to take any chances with the controversial diabetes med. Two PBMs have already stated that they will be dropping the drug from their formularies.

Pharmaceutical Executive-12-12-2007