Transdermal Rotigotine: A Clinically Innovative Dopamine‐Receptor Agonist for the Management of Parkinson's Disease

Abstract

Rotigotine is a highly lipophilic dopamine-receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce "off" hours in levodopa-treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D(2) and D(3) receptors. With once-daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine-receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2-3 weeks, and the once-daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24-hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine-receptor agonist class. This review summarizes the key pharmacologic and clinical data for rotigotine and provides a focused clinical context for its use in early-to-advanced Parkinson's disease, as well as a brief summary for its role in restless legs syndrome.