Rotigotine Transdermal Patch

Abstract

A transdermal patch formulation of the non-ergolinic dopamine agonist rotigotine (Neupro®) is indicated as monotherapy for the treatment of early Parkinson's disease and as combination therapy with levodopa throughout the course of the disease. Daily application of the rotigotine transdermal patch (referred to here as rotigotine) provided predictable release and absorption of rotigotine, with steady-state rotigotine concentrations reached within 1-2 days. In six large, well designed clinical trials, rotigotine was an efficacious treatment for Parkinson's disease. In early Parkinson's disease, rotigotine initiated without levodopa produced significantly greater improvements than placebo in the Unified Parkinson's Disease Rating Scale (UPDRS) summed motor and activities of daily living (ADL) scores, as well as significantly higher response rates. In a comparison with oral ropinirole, rotigotine did not meet a prespecified response-rate noninferiority criterion, although this may reflect the dosages used, which may not have been directly comparable. In advanced Parkinson's disease, rotigotine in combination with levodopa reduced 'off' time and improved motor functioning and ADL significantly more than levodopa plus placebo. Rotigotine was noninferior to oral pramipexole in reducing 'off' time, although it did not meet a response-rate noninferiority criterion. A recent trial focused on both motor and non-motor endpoints in patients with inadequate early morning motor control despite antiparkinsonian treatment (most received levodopa). Rotigotine improved morning motor functioning and reduced sleep disturbances, night-time motor symptoms, depressive symptoms, pain and functioning, and quality of life to a significantly greater extent than placebo. Rotigotine was generally well tolerated across the trials and in longer-term extension studies, with the most common treatment-emergent adverse events being application-site reactions, gastrointestinal disturbances, somnolence and headache. Application-site reactions were generally mild to moderate in severity; where reported, up to 3% of patients had severe skin reactions. Thus, rotigotine offers a novel approach to the treatment of Parkinson's disease and, given its ease of administration, efficacy in reducing disabling motor and non-motor symptoms, and acceptable tolerability profile, it has the potential to be an attractive treatment option for this highly debilitating disease.