September 23rd, 2012

FDA Reviews Possible Mirapex Heart Risk

Epidemiological data suggest that pramipexole (Mirapex), used to treat Parkinson's disease and restless legs syndrome, is associated with an increased risk of heart failure, the FDA said.

Pooled data from randomized trials with the dopamine agonist, as well as two epidemiological studies involving some 1,300 patients with heart failure and more than 45,000 controls, showed that use of pramipexole was more common in the heart failure patients, the agency said.

But, the FDA emphasized, limitations to these studies precluded a firm conclusion that the drug itself was responsible for the increased risk.

The agency advised patients currently taking the drug to stay on it and to contact their healthcare providers with questions or concerns.

Prescribers should continue to follow pramipexole's label recommendations, which have not been changed, the FDA said.

Concern about a possible increase in heart failure risk with the drug first emerged in the pooled trial data, submitted by the drug's manufacturer, Boehringer Ingelheim, to the FDA in 2008 and updated in 2010.

Those data suggested that the risk of new-onset heart failure was approximately doubled with pramipexole -- but with only 16 cases seen among nearly 7,000 participants in the trials, the findings were not statistically significant.

Boehringer Ingelheim then sponsored a case-control study of patient records in the U.K.'s General Practice Research Database, in which 783 heart failure patients were matched to 7,454 controls.

It found that pramipexole use was associated with increased rates of heart failure at a relative risk of 1.86 (95% CI 1.21 to 2.85) compared with no use of the drug. A somewhat smaller but still significant increase in risk was seen with use of any dopamine agonist.

A similar study involving four European population-based databases, with a total of 518 new-onset heart failure cases and 38,641 controls, also found a similar risk with pramipexole compared with levodopa (OR 1.61, 95% CI 1.09 to 2.38).

But complicating the interpretation of this latter study was a finding that the risk appeared to be increased only during the first 3 months of pramipexole treatment. This result is "difficult to explain, since heart failure is generally considered to develop chronically," the FDA said.

The agency said it was continuing to work with Boehringer Ingelheim "to clarify further the risk of heart failure with Mirapex." It promised to provide an update when more information is available.