Anzeige
Erschienen in:
01.12.2007 | Adis Drug Evaluation
Rotigotine Transdermal Patch
A Review of its Use in the Management of Parkinson’s Disease
Erschienen in: CNS Drugs | Ausgabe 12/2007
Einloggen, um Zugang zu erhaltenSummary
Abstract
A transdermal patch formulation of the non-ergolinic dopamine agonist rotigotine (Neupro®) is indicated for use as monotherapy in the treatment of early-stage Parkinson’s disease or, in the EU, as an adjunct to levodopa across all disease stages. Transdermal rotigotine is an effective and generally well tolerated addition to the armamentarium for the control of Parkinson’s disease, with the once-daily transdermal patch system offering several practical advantages and the possible benefits of avoiding pulsatile dopaminergic stimulation. Transdermal rotigotine was superior to placebo in patients with early-stage and advanced Parkinson’s disease, although noninferiority to the oral dopamine agonists ropinirole or pramipexole was not consistently demonstrated. Additional active comparator trials would be of interest. In the meantime, transdermal rotigotine offers a convenient new treatment option for patients with Parkinson’s disease.
Pharmacological Properties
Rotigotine has agonist effects at all dopamine receptors in vitro, with the greatest affinity for, and activity at, the dopamine D3 receptor subtype. It also interacts to some extent with α2B- and α2C-adrenergic receptors, serotonin 5-HT1A and 5-HT7 receptors, and σ receptors, and to a minor extent with monoamine transporters. The beneficial effects of rotigotine in the treatment of Parkinson’s disease are thought to be mediated via activation of D1, D2 and D3 dopaminergic receptors within the caudate putamen. Rotigotine has demonstrated antiparkinsonian and potential neuroprotective effects in animal models of Parkinson’s disease.
A stable drug-release profile is maintained over 24 hours, with steady-state plasma concentrations of rotigotine reached after approximately 2–3 days in healthy volunteers. The pharmacokinetic profile of transdermal rotigotine does not differ according to patch application site, although there is wide interindividual variability in rotigotine exposure after patch application.
Therapeutic Efficacy
Transdermal rotigotine dose-dependently improved combined Unified Parkinson’s Disease Rating Scale (UPDRS) Activities of Daily Living (ADL) and motor subtotal scores in patients with early-stage Parkinson’s disease. The antiparkinsonian effects of transdermal rotigotine were significant when compared with placebo, although noninferiority to oral ropinirole in terms of response rates (proportion of patients with a ≥20% decrease from baseline in combined UPDRS ADL and motor subtotal scores) was not shown. The proportion of treatment responders was significantly higher in transdermal rotigotine than placebo recipients, as were Clinical Global Impression (CGI) scale scores. In longer-term trials, the benefits of transdermal rotigotine were maintained for periods of at least 12 months.
In patients with advanced Parkinson’s disease, transdermal rotigotine as adjunctive therapy to levodopa significantly reduced ‘off’ time (periods during which symptoms are not masked by medication) and increased response rates (the percentage of patients achieving a ≥30% reduction in ‘off’ time); transdermal rotigotine also had significant effects on the number of daily ‘off’ periods, ‘on’ time (periods when symptoms are well controlled) without troublesome dyskinesias, and combined UPDRS ADL and motor subtotal scores compared with placebo. Noninferiority of transdermal rotigotine to oral pramipexole was shown with respect to changes in absolute ‘off’ time but not with respect to responder rates.
Tolerability
Transdermal rotigotine is generally well tolerated and has a tolerability profile considered typical of a dopamine receptor agonist, with the exception of application-site reactions such as erythema, pruritus and dermatitis. Adverse events occurring in significantly more transdermal rotigotine than placebo recipients included nausea, vomiting, somnolence and fatigue. Across trials, other dopaminergic adverse events included hallucinations, peripheral oedema and orthostatic hypotension.