Rotigotine: Transdermal Dopamine Agonist Treatment of Parkinson's Disease and Restless Legs Syndrome

Abstract

Spanish

French

Objective:

To evaluate the pharmacology, pharmacokinetics, clinical efficacy, and tolerability of rotigotine, a nonergoline D₃/D₂/D₁ dopamine receptor agonist in the treatment of Parkinson's disease and restless legs syndrome (RLS).

Data Sources:

A literature search was conducted using MEDLINE (1996–December 2006) and International Pharmaceutical Abstracts, using the search terms rotigotine and dopamine agonist. References cited in the articles were reviewed for additional information. Information was also obtained from Schwarz Pharma. Abstracts for posters at scientific conferences were accessed from conference Web sites.

Study Selection and Data Extraction:

English-language literature reporting controlled animal and human clinical studies was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of rotigotine. Clinical trials selected for inclusion were limited to those with human subjects; data from animal studies were included if human data were not available.

Data Synthesis:

Rotigotine has been investigated in early Parkinson's disease, as adjuvant therapy to levodopa in advanced Parkinson's disease, and in RLS. It is administered transdermally, which provides the convenience of once-daily dosing, constant drug delivery, and sustained stable plasma concentrations. In clinical trials of patients with early Parkinson's disease, rotigotine has decreased combined scores on the motor and activities of daily living sections of the Unified Parkinson's Disease Rating Scale up to 85 weeks. In patients with advanced Parkinson's disease, rotigotine reduced mean off-time when used as an adjuvant to levodopa. Rotigotine has decreased the severity of RLS in Phase III trials. Acute adverse events are similar to those of other dopamine agonists and are most common during the titration phase. Mild-to-moderate application site reactions are common.

Conclusions:

Longer trials are required to determine whether transdermal rotigotine will reduce development of dyskinesias and motor fluctuations in Parkinson's disease and augmentation and rebound in RLS by preventing pulsatile dopamine stimulation associated with levodopa and other dopamine agonists.

Keywords

dopamine agonist rotigotine

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References

Rascol

. Transdermal delivery of dopaminergic agents. Neurology 2005;65(suppl 1):S1–2.

SchwarzPharma. Neupro approved in Europe for early Parkinson's disease. www.schwarzpharma.com/?node_id=2492 (accessed 2006 May 19).

SchwarzPharma. Neupro receives approvable letter from FDA for early Parkinson's disease in USA. www.schwarzpharma.com/?node_id=2494 (accessed 2006 May 19).

SchwarzPharma. Schwarz Pharma's Parkinson patch offers additional benefits. www.schwarzpharma.com/?action=show_content&print=1&node_id=2546 (accessed 2006 Sept 12).

Nugroho

Grossklaus

Danhof

Bouwstra

. Transdermal iontophoresis of rotigotine: influence of concentration, temperature and current density in human skin in vitro. J Control Release 2004;96:159–67.

Trenkwalder

Paulus

Walters

. The restless legs syndrome. Lancet Neurol 2005;4:465–75.

Chase

. The significance of continuous dopaminergic stimulation in the treatment of Parkinson's disease. Drugs 1998;55(suppl 1): 1–9.

Poewe

Luessi

. Clinical studies with transdermal rotigotine in early Parkinson's disease. Neurology 2005;65(suppl 1):S11–4.

Eisen

Miller

Woodward

Spitznagel

Przybeck

. The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med 1990;150:1881–4.

10.

Olanow

Watts

Koller

. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology 2001;56(suppl 5):S1–88.

11.

Rascol

Brooks

Korczyn

De Deyn

Clarke

Lang

. A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. 056 Study Group. N Engl J Med 2000;342:1484–91.

12.

Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: a randomized controlled trial. JAMA 2000;284:1931–8.

13.

Garcia Ruiz

Meseguer

Del Val

Vazquez

Sanchez Bernardos

Vazquez

. Motor complications in Parkinson disease: a prospective follow-up study. Clin Neuropharmacol 2004;27:49–52.

14.

Quinn

Parkes

Marsden

. Control of on/off phenomenon by continuous intravenous infusion of levodopa. Neurology 1984;34:1131–6.

15.

Baronti

Mouradian

Davis

. Continuous lisuride effects on central dopaminergic mechanisms in Parkinson's disease. Ann Neurol 1992;32:776–81.

16.

Colzi

Turner

Lees

. Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson's disease. J Neurol Neurosurg Psychiatry 1998;64:573–6.

17.

Happe

Trenkwalder

. Role of dopamine receptor agonists in the treatment of restless legs syndrome. CNS Drugs 2004;18:27–36.

18.

Allen

Earley

. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996;19:205–13.

19.

Mucke

. Rotigotine Schwarz Pharma. IDrugs 2003;6:894–9.

20.

Quinn

. For the European and South African Rotigotine CDS Study Group. A multicenter, double-blind, randomized, placebo-controlled safety and efficacy study of rotigotine constant delivery system (CDS) in patients with advanced Parkinson's disease (poster A223). Presented at: XIV International Congress on Parkinson's Disease, Helsinki, July 28–August 1, 2001.

21.

Jenner

. A novel dopamine agonist for the transdermal treatment of Parkinson's disease. Neurology 2005;65(suppl 1):S3–5.

22.

Standaert

Young

. Treatment of central nervous system degenerative disorders. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 11 th ed. New York: McGraw-Hill, 2006;527–45.

23.

Bezard

Ferry

Mach

. Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function. Nat Med 2003;9:762–7.

24.

Sanders-Bush

Mayer

. 5-Hydroxytryptamine (serotonin): receptor agonists and antagonists. In: Brunton

Lazo

Parker

, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006;297–315.

25.

Westfall

. Neurotransmission. The autonomic and somatic motor nervous systems. In: Brunton

Lazo

Parker

, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006;137–81.

26.

The Parkinson Study Group. A controlled trial of rotigotine monotherapy in early Parkinson's disease. Arch Neurol 2003;60:1721–8.

27.

Braun

Cawello

Poole

Hortsmann

. Steady-state pharmacokinetics of rotigotine in patients with early-stage Parkinson's disease (poster P1245). Presented at: 9th Congress of the European Federation of Neurological Societies, Athens, September 17-20, 2005.

28.

Metman

Gillespie

Farmer

. Continuous transdermal dopaminergic stimulation in advanced Parkinson's disease. Clin Neuropharmacol 2001;24:163–9.

29.

Watts

Wendt

Nausieda

Poole

Sommerville

Boroojerdi

. Efficacy, safety, and tolerability of the rotigotine transdermal patch in patients with early-stage, idiopathic Parkinson's disease. A multicenter, multinational, randomized, double-blind, placebo-controlled trial (abstract P737 and poster). Mov Disord 2004;19(suppl 9):S258. Presented at: 8th International Congress of Parkinson's Disease and Movement Disorders, Rome, June 14-17, 2004.

30.

Cawello

Braun

Horstmann

. Pharmacokinetics of transdermal rotigotine in subjects with impaired renal function (abstract). J Clin Pharmacol 2005;45:1091.

31.

Güldenpfennig

Poole

Sommerville

Boroojerdi

. Safety, tolerability, and efficacy of continuous transdermal dopaminergic stimulation with rotigotine patch in early-stage idiopathic Parkinson disease. Clin Neuropharmacol 2005;28:106–10.

32.

Hansen

Braun

Horstmann

. Low drug–drug interaction potential of rotigotine (abstract 101). J Clin Pharmacol 2005;45:1091.

33.

Watts

LeWitt

Giladi

Sommerville

Boroojerdi

. Treatment with rotigotine transdermal system may attenuate progression of disability in patients with early-stage Parkinson's disease (abstract P02.103). Neurology 2005;64(suppl 1):A107.

34.

Watts

Pahwa

Lyons

Boroojerdi

Wallen

. Long-term safety and efficacy of the rotigotine transdermal patch in early-stage Parkinson's disease (poster P05.136). Presented at: 58th Annual Meeting of the American Academy of Neurology, San Diego, CA, April 6, 2006.

35.

Hutton

Metman

Chase

. Transdermal dopaminergic D₂ receptor agonist therapy in Parkinson's disease with N-0923 TDS: a double-blind, placebo-controlled study. Mov Disord 2001;16:459–63.

36.

LeWitt

Chang

F-L

Fazzini

Nausieda

Daniel

Boroojerdi

. Rotigotine transdermal system in treatment of patients with advanced-stage Parkinson's disease (abstract no. SC115). Presented at: 9th Congress of the European Federation of Neurological Societies, Athens, September 17-20, 2005.

37.

Giladi

Tolosa

Boothman

. Rotigotine transdermal system in patients with idiopathic Parkinson's disease: results of two placebo- and comparator-controlled trials (poster). Presented at: First World Parkinson's Congress, Washington, DC, February 21-26, 2006.

38.

Poewe

Giladi

Boothman

Maguire

Boroojerdi

. For SP515 Study Group. Rotigotine transdermal system in patients with advanced-stage Parkinson's disease as adjunctive therapy to levodopa: results of a placebo- and pramipexole-controlled trial. Presented at: First World Parkinson's Congress, Washington, DC, February 21-26, 2006.

39.

Widnell

Cornelia

. Role of COMT inhibitors and dopamine agonists in the treatment of motor fluctuations. Mov Disord 2005;20(suppl 11):S30–7.

40.

Shetty

Friedman

Kieburtz

Marshall

Oakes

. The placebo response in Parkinson's disease. Parkinson Study Group. Clin Neuropharmacol 1999;22:207–12.

41.

Patton

Neilson

Boroojerdi

. Tolerability of switching from an oral dopamine agonist to transdermal rotigotine in Parkinson's disease (poster). Presented at: First World Parkinson's Congress, Washington, DC, February 21-26, 2006.

42.

Stiasny-Kolster

Kohnen

Schollmayer

Moller

Oertel

; Rotigotine Sp 666 Study Group. Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-controlled pilot study. Mov Disord 2004;19:1432–8.

43.

Stiasny-Kolster

Garcia-Borreguero

Saletu

Schollmayer

Kohnen

Oertel

; SP709 Study Group. Rotigotine in the treatment of moderate to severe idiopathic restless legs syndrome—a double-blind placebo-controlled multi-center dose-finding study (poster). Presented at: 9th Congress of the European Federation of Neurological Societies, Athens, September 17-20, 2005.

44.

Babic

Boroojerdi

Randerath

Poole

Sommerville

. Rotigotine CDS patch in advanced-stage, idiopathic Parkinson's disease: a parallel group, open-label, dose-escalation trial (poster). Presented at: 56th Annual Meeting of the American Academy of Neurology, San Francisco, April 27–May 1, 2004.