FDA Approves Once-Daily Pramipexole for Early Parkinson's Disease
By Yael Waknine
Medscape Medical News
February 23, 2010 — The US Food and Drug Administration (FDA) has approved a new once-daily formulation of pramipexole dihydrochloride (Mirapex ER tablets, Boehringer Ingelheim Pharmaceuticals, Inc) for treating signs and symptoms of early idiopathic Parkinson's disease.
According to a company news release, use of the once-daily extended-release formulation rather than thrice-daily immediate-release pramipexole tablets may improve therapeutic compliance.
"Mirapex ER for early Parkinson's disease is a positive development in the treatment of this disease. This new, once-daily treatment has a more convenient dosing schedule, offering greater flexibility as someone with early Parkinson's disease plans his or her day," said Robert Hauser, MD, professor of neurology and director, Parkinson's Disease Movement Disorders Center, at the University of South Florida College of Medicine, Tampa. "In general, patients often prefer once-daily dosing to a more frequent regimen because of convenience."
FDA approval was based primarily on data from an 18-week, double-blind, multicenter clinical trial (n > 400) showing that extended-release pramipexole therapy significantly improved mean Unified Parkinson's Disease Rating Scale (UPDRS) II + III scores from baseline relative to placebo, with benefits comparable to that achieved with immediate-release tablets.
UPDRS scores are used to follow the longitudinal course of Parkinson's disease–related disability and impairment; the UPDRS parts II and III relate to activities of daily living and motor symptoms, respectively.
Findings from a second study (n = 104) demonstrated that 85% of patients with early Parkinson's disease were able to successfully switch overnight from thrice-daily pramipexole to the once-daily extended-release formulation. Success was defined as a 15% or less worsening of UPDRS II + III scores and a lack of adverse events leading to discontinuation of therapy. Dose adjustments were required in some cases.
A safety analysis of both studies revealed that the safety and tolerability profile of once-daily pramipexole was similar to that of the immediate-release formulation. Adverse events most commonly reported included nausea, dizziness, sleepiness, difficulty falling asleep, weakness, and constipation.
The FDA warns that somnolence is a common occurrence in patients receiving pramipexole therapy; patients should be advised regarding the risk of falling asleep while engaged in activities of daily living, including the operation of motor vehicles. Hallucinations may also occur, particularly in elderly patients.
Some patients receiving pramipexole have experienced intense gambling, sexual, and other urges, combined with an inability to control these urges. Although a causal role for the drug has not been established, dose reductions or discontinuation of therapy should be considered if such urges occur.
Patients may also develop orthostatic hypotension, potentially accompanied by symptoms such as dizziness, nausea, fainting/blackouts, and sweating. Because hypotension may occur more frequently during initial therapy, patients should be cautioned against rising rapidly after sitting or lying down during this period.
