The Food and Drug Administration (FDA) is investigating the risk of heart failure associated with the use of pramipexole (Mirapex), a drug used with or without levodopa in the treatment of Parkinson's disease. Originally approved for the treatment of restless legs syndrome, pramipexole works by stimulating dopamine receptors. Peripheral edema has always been listed as a possible adverse effect on the drug's label, although it isn't common. The FDA began its review of pramipexole after two epidemiologic studies suggested that the drug increased the risk of heart failure in patients with Parkinson's disease. The FDA notes various methodologic limitations of these studies that make it difficult for the agency to draw conclusions related to the drug's safety. One of the studies, for example, included patients with conditions other than Parkinson's disease; in both studies, review of some patients’ medical charts was insufficient to confirm the development of heart failure; in one, too, there were differences in the number of cardiovascular risk factors between patients in the experimental arm and patients in the control arm of the study. One of the studies showed an increased risk of heart failure but only in the first three months of treatment with pramipexole; because heart failure normally develops chronically, this finding is difficult to interpret.
The FDA also evaluated a pooled analysis of randomized clinical trials. Heart failure was more frequent with pramipexole use than with placebo use, but not to a statistically significant extent. As of this writing, the FDA is still investigating and hasn't concluded that pramipexole definitely increases the risk of heart failure. Patients don't need to be withdrawn from therapy at this time. The FDA encourages health care providers to be prudent, following labeling recommendations, educating patients on the risk of heart failure and its symptoms and instructing them to contact the prescriber if they develop any symptoms of fluid overload. Health care providers should contact the FDA MedWatch program at www.fda.gov/Safety/MedWatch if they believe a patient has experienced adverse effects of pramipexole.