Drugs

, Volume 72, Issue 5, pp 643–669

Rasagiline

A Review of its Use in the Treatment of Idiopathic Parkinson’s Disease
Adis Drug Evaluation
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Abstract

Rasagiline (Azilect®), a selective, irreversible, monoamine oxidase-B inhibitor, is available in the EU, the US and in several other countries worldwide, including Canada and Israel. It is indicated for the treatment of idiopathic Parkinson’s disease as monotherapy or as adjunctive therapy to levodopa in patients with end-of-dose fluctuations in the EU and for the treatment of adult patients with the signs and symptoms of idiopathic Parkinson’s disease in the US. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of rasagiline as monotherapy or as adjunctive therapy to levodopa in patients with Parkinson’s disease.

Oral rasagiline as monotherapy or as adjunctive therapy to levodopa was effective in the symptomatic treatment of adult patients with Parkinson’s disease participating in double-blind, placebo-controlled, multinational studies. In patients with early Parkinson’s disease, monotherapy with rasagiline 1 mg/day (recommended dosage) significantly slowed the rate of worsening (i.e. an increase in the Unified Parkinson’s Disease Rating Scale [UPDRS] score) in the ADAGIO and TEMPO studies, with the results from the ADAGIO study for rasagiline 1 mg/day suggesting a slowing of clinical progression. However, at the higher dosage of 2 mg/day, rasagiline met the primary endpoint in the TEMPO study and the first, but not the second, of three hierarchical primary endpoints in the ADAGIO study. Compared with delayed-start rasagiline monotherapy, early initiation was associated with a slower long-term progression of the clinical signs and symptoms of Parkinson’s disease in the TEMPO study. As adjunctive therapy to levodopa in the LARGO and PRESTO studies, rasagiline 0.5 and/or 1 mg/day significantly reduced the total daily ‘off’ time (primary efficacy endpoint) and significantly improved the Clinical Global Impression score, the UPDRS activities of daily living subscale score during ‘off’ time and the UPDRS motor subscale score during ‘on’ time compared with placebo in patients with advanced Parkinson’s disease.

Although rasagiline showed neuroprotective properties both in vitro and in vivo, identifying its potential to slow clinical progression in the clinical setting has been elusive to date and was not definitively demonstrated in the studies discussed in this article. Additional rasagiline studies specifically designed to assess the clinical progression of Parkinson’s disease while addressing the potentially confounding factors of the delayed-start study design would therefore be of interest.

As monotherapy or as adjunctive therapy to levodopa, rasagiline was generally well tolerated, with the frequency and nature of treatment-emergent adverse events generally similar across clinical studies and between rasagiline and placebo groups. Therapy with rasagiline appears to be associated with a low incidence of cognitive and behavioural adverse events.

Thus, oral rasagiline as monotherapy or as adjunctive therapy to levodopa provides a useful option in the treatment of adult patients with Parkinson’s disease.

References

  1. 1.
    Lees A. Alternatives to levodopa in the initial treatment of early Parkinson’s disease. Drugs Aging 2005; 22(9): 731–40PubMedCrossRefGoogle Scholar
  2. 2.
    Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill Medical, 2011Google Scholar
  3. 3.
    LeWitt PA. Levodopa for the treatment of Parkinson’s disease. N Engl J Med 2008 Dec; 359(23): 2468–76CrossRefGoogle Scholar
  4. 4.
    Clarke CE. Parkinson’s disease. BMJ 2007 Sep; 335(7617): 441–5PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Hauser RA, Zesiewicz TA. Advances in the pharmacologic management of early Parkinson disease. Neurologist 2007 May; 13(3): 126–32PubMedCrossRefGoogle Scholar
  6. 6.
    Elmer LW, Bertoni JM. The increasing role of monoamine oxidase type B inhibitors in Parkinson’s disease therapy. Expert Opin Pharmacother 2008 Nov; 9(16): 2759–72PubMedCrossRefGoogle Scholar
  7. 7.
    Jenner P, Langston JW. Explaining ADAGIO: a critical review of the biological basis for the clinical effects of rasagiline. Mov Disord 2011 Nov; 26(13): 2316–23PubMedCrossRefGoogle Scholar
  8. 8.
    Siddiqui MA, Plosker GL. Rasagiline. Drugs Aging 2005; 22(1): 83–91PubMedCrossRefGoogle Scholar
  9. 9.
    Oldfield V, Keating GM, Perry CM. Rasagiline: a review of its use in the management of Parkinson’s disease. Drugs 2007; 67(12): 1725–47PubMedCrossRefGoogle Scholar
  10. 10.
    Teva Pharma GmbH. Rasagiline (Azilect®): summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000574/WC500030048.pdf [Accessed 2011 Apr 12]
  11. 11.
    Teva Neuroscience Inc. Azilect® (rasagiline mesylate) tablets for oral use: prescribing information [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021641s002s003s004s005s007s008s010lbl.pdf [Accessed 2011 Apr 12]
  12. 12.
    Youdim MB, Gross A, Finberg JP. Rasagiline [N-propargyl-1 R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol 2001 Jan; 132(2): 500–6PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Thébault JJ, Guillaume M, Levy R. Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline: a potent, selective, and irreversible monoamine oxidase type B inhibitor. Pharmacotherapy 2004 Oct; 24(10): 1295–305PubMedCrossRefGoogle Scholar
  14. 14.
    Rabey JM, Sagi I, Huberman M, et al. Rasagiline mesylate, a new MAO-B inhibitor for the treatment of Parkinson’s disease: a double-blind study as adjunctive therapy to levodopa. Clin Neuropharmacol 2000 Nov-Dec; 23(6): 324–30PubMedCrossRefGoogle Scholar
  15. 15.
    Freedman NM, Mishani E, Krausz Y, et al. In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using 11C-L-deprenyl and PET. J Nucl Med 2005 Oct; 46(10): 1618–24PubMedGoogle Scholar
  16. 16.
    Goren T, Adar L, Sasson N, et al. Clinical pharmacology tyramine challenge study to determine the selectivity of the monoamine oxidase type B (MAO-B) inhibitor rasagiline. J Clin Pharmacol 2010 Dec; 50(12): 1420–8PubMedCrossRefGoogle Scholar
  17. 17.
    Naoi M, Maruyama W. Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson’s disease. Expert Rev Neurother 2009 Aug; 9(8): 1233–50PubMedCrossRefGoogle Scholar
  18. 18.
    Weinreb O, Bar-Am O, Amit T, et al. Neuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2 family members. FASEB J 2004 Sep; 18(12): 1471–3PubMedGoogle Scholar
  19. 19.
    Weinreb O, Bar-Am O, Prosolovich K, et al. Does 1-(R)-aminoindan possess neuroprotective properties against experimental Parkinson’s disease? Antioxid Redox Signal 2011 Mar; 14(5): 767–75PubMedCrossRefGoogle Scholar
  20. 20.
    Teva Pharmaceutical Industries Ltd. Data on file. 2011 DecGoogle Scholar
  21. 21.
    Perez-Lloret S, Rascol O. Safety of rasagiline for the treatment of Parkinson’s disease. Expert Opin Drug Saf 2011 Jul; 10(4): 633–43PubMedCrossRefGoogle Scholar
  22. 22.
    Chen JJ, Panisett M, Rhyee S. Rasagiline and antidepressant use in patients with Parkinson’s disease: assessing the occurrence of serotonin toxicity [abstract]. 2011 Annual Meeting of the American College of Clinical Pharmacy; 2011 Oct 16–19; Pittsburgh (PA)Google Scholar
  23. 23.
    Teva Pharmaceutical Industries Ltd. Investigation of the occurrence of serotonin toxicity in Parkinson’s Disease (PD) patients treated concomitantly with rasagiline and antidepressants, using retrospective chart review [Clinical-Trials.gov identifier NCT00955604]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov/ [Accessed 2012 Jan 19]
  24. 24.
    Chen JJ, Swope DM, Dashtipour K. Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson’s disease. Clin Ther 2007 Sep; 29(9): 1825–49PubMedCrossRefGoogle Scholar
  25. 25.
    Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO study. Arch Neurol 2002 Dec; 59(12): 1937–43CrossRefGoogle Scholar
  26. 26.
    Parkinson Study Group. A controlled, randomized, delayedstart study of rasagiline in early Parkinson disease. Arch Neurol 2004 Apr; 61(4): 561–6CrossRefGoogle Scholar
  27. 27.
    Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 2005; 62(2): 241–8CrossRefGoogle Scholar
  28. 28.
    Olanow CW, Rascol O, Hauser R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med 2009 Sep; 361(13): 1268-PubMedCrossRefGoogle Scholar
  29. 78.
    Plus supplementary material available from URL: http://www.nejm.org/ [Accessed 2011 Mar 8]
  30. 29.
    Biglan KM, Schwid S, Eberly S, et al. Rasagiline improves quality of life in patients with early Parkinson’s disease. Mov Disord 2006 May; 21(5): 616–23PubMedCrossRefGoogle Scholar
  31. 30.
    Hauser RA, Lew MF, Hurtig HI, et al. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson’s disease. Mov Disord 2009 Mar; 24(4): 564–73PubMedCrossRefGoogle Scholar
  32. 31.
    Lew MF, Hauser RA, Hurtig HI, et al. Long-term efficacy of rasagiline in early Parkinson’s disease. Int J Neurosci 2010 Jun; 120(6): 404–8PubMedCrossRefGoogle Scholar
  33. 32.
    Rascol O, Fitzer-Attas CJ, Hauser R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes. Lancet Neurol 2011 May; 10(5): 415–23PubMedCrossRefGoogle Scholar
  34. 33.
    Brown RG, Dittner A, Findley L, et al. The Parkinson fatigue scale. Parkinsonism Relat Disord 2005 Jan; 11(1): 49–55PubMedCrossRefGoogle Scholar
  35. 34.
    Goetz CG, Tilley BC, Shaftman SR, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008 Nov; 23(15): 2129–70PubMedCrossRefGoogle Scholar
  36. 35.
    Rascol O, Brooks DJ, Melamed E, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005 Mar; 365(9463): 947–54PubMedCrossRefGoogle Scholar
  37. 36.
    Stocchi F, Rabey JM. Effect of rasagiline as adjunct therapy to levodopa on severity of OFF in Parkinson’s disease. Eur J Neurol 2011 Dec; 18(12): 1373–8PubMedCrossRefGoogle Scholar
  38. 37.
    Tolosa E, Stern MB. Efficacy, safety and tolerability of rasagiline as adjunctive therapy in elderly patients with Parkinson’s disease. Eur J Neurol 2012 Feb; 19(2): 258–64PubMedCrossRefGoogle Scholar
  39. 38.
    Reichmann H, Jost WH. Efficacy and tolerability of rasagiline in daily clinical use: a post-marketing observational study in patients with Parkinson’s disease. Eur J Neurol 2010 Sep; 17(9): 1164–71PubMedCrossRefGoogle Scholar
  40. 39.
    Goetz CG, Schwid SR, Eberly SW, et al. Safety of rasagiline in elderly patients with Parkinson disease. Neurology 2006 May; 66(9): 1427–9PubMedCrossRefGoogle Scholar
  41. 40.
    Elmer L, Schwid S, Eberly S, et al. Rasagiline-associated motor improvement in PD occurs without worsening of cognitive and behavioral symptoms. J Neurol Sci 2006 Oct; 248(1–2): 78–83PubMedCrossRefGoogle Scholar
  42. 41.
    Teva Pharmaceutical Industries Ltd. Teva announces Health Canada approves Azilect® (rasagiline) for Parkinson’s disease [online]. Available from URL: http://www.tevapharm.com/en-US/Media/News/Pages/2006/1557352. aspx [Accessed 2012 Jan 31]
  43. 42.
    Teva Pharmaceutical Industries Ltd. Teva announces that Azilect® (rasagiline) is approved for marketing in Israel [online]. Available from URL: http://www.tevapharm.com/en-US/Media/News/Pages/2005/1557104.aspx [Accessed 2012 Jan 31]
  44. 43.
    Henchcliffe C, Severt WL. Disease modification in Parkinson’s disease. Drugs Aging 2011; 28(8): 605–15PubMedCrossRefGoogle Scholar
  45. 44.
    Olanow CW, Kieburtz K. Defining disease-modifying therapies for PD: a road map for moving forward. Mov Disord 2010 Sep; 25(12): 1774–9PubMedCrossRefGoogle Scholar
  46. 45.
    National Institute for Health and Clinical Excellence. Parkinson’s disease: diagnosis and management in primary and secondary care (NICE clinical guideline 35). London: NICE, 2006 [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/10984/30088/30088.pdf [Accessed 2011 Jul 27]
  47. 46.
    Oertel WH, Berardelli A, Bloem BR, et al. Early (uncomplicated) Parkinson’s disease. In: Gilhus NE, Barnes MP, Brainin M, editors. European handbook of neurological management. 2nd ed. Oxford: Wiley-Blackwell, 2011; 1: 217–36Google Scholar
  48. 47.
    Scottish Intercollegiate Guidelines Network. Diagnosis and pharmacological management of Parkinson’s disease: a national clinical guideline (SIGN publication no. 113). Edinburgh: SIGN, 2010 JanGoogle Scholar
  49. 48.
    Oertel WH, Berardelli A, Bloem BR, et al. Late (complicated) Parkinson’s disease. In: Gilhus NE, Barnes MP, Brainin M, editors. European handbook of neurological management. 2nd ed. Oxford: Wiley-Blackwell, 2011; 1: 237–67Google Scholar
  50. 49.
    Miyasaki JM, Martin W, Suchowersky O, et al. Practice parameter: initiation of treatment for Parkinson’s disease. An evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2002 Jan; 58(1): 11–7Google Scholar
  51. 50.
    Schapira AH. Treatment options in the modern management of Parkinson disease. Arch Neurol 2007 Aug; 64(8): 1083–8PubMedCrossRefGoogle Scholar
  52. 51.
    Zesiewicz TA, Sullivan KL, Arnulf I, et al. Practice parameter: treatment of nonmotor symptoms of Parkinson disease. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010 Mar; 74(11): 924–31PubMedCrossRefGoogle Scholar
  53. 52.
    Ahlskog JE, Uitti RJ. Rasagiline, Parkinson neuroprotection, and delayed-start trials: still no satisfaction? Neurology 2010 Apr; 74(14): 1143–8PubMedCentralPubMedCrossRefGoogle Scholar
  54. 53.
    Olanow CW, Rascol O. The delayed-start study in Parkinson disease: can’t satisfy everyone [letter]. Neurology 2010 Apr; 74(14): 1149–50PubMedCrossRefGoogle Scholar
  55. 54.
    Ahlskog JE, Uitti RJ. Reply to Drs. Olanow and Rascol [letter]. Neurology 2010 Apr; 74(14): 1151Google Scholar
  56. 55.
    Montgomery Jr EB. The delayed-start study in Parkinson disease: can’t satisfy everyone. Rasagiline, Parkinson neuroprotection, and delayed-start trials: still no satisfaction? [letter]. Neurology 2010 Nov; 75(21): 1943; author reply 1944-5Google Scholar
  57. 56.
    Schwarzschild MA. The delayed-start study in Parkinson disease: can’t satisfy everyone. Rasagiline, Parkinson neuroprotection, and delayed-start trials: still no satisfaction? [letter]. Neurology 2010 Nov; 75(21): 1943–4; author reply 1944-5Google Scholar
  58. 57.
    Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease. The Unified Parkinson’s Disease Rating Scale (UPDRS): status and recommendations. Mov Disord 2003; 18(7): 738–50CrossRefGoogle Scholar
  59. 58.
    Teva Pharmaceutical Industries Ltd. ADAGIO follow up study: evaluation of the long-term effects of rasagiline in Parkinson’s disease subjects [ClinicalTrials.gov identifier NCT00936676]. US National Institutes of Health. ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov/ [Accessed 2012 Jan 27]
  60. 59.
    Haycox A, Armand C, Murteira S, et al. Cost effectiveness of rasagiline and pramipexole as treatment strategies in early Parkinson’s disease in the UK setting: an economic Markov model evaluation. Drugs Aging 2009; 26(9): 791–801PubMedCrossRefGoogle Scholar
  61. 60.
    Groenendaal H, Tarrants ML, Armand C. Treatment of advanced Parkinson’s disease in the United States: a cost-utility model. Clin Drug Invest 2010; 30(11): 789–98CrossRefGoogle Scholar
  62. 61.
    Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: a randomized controlled trial. JAMA 2000 Oct 18; 284(15): 1931–8CrossRefGoogle Scholar
  63. 62.
    Hudry J, Rinne JO, Keränen T, et al. Cost-utility model of rasagiline in the treatment of advanced Parkinson’s disease in Finland. Ann Pharmacother 2006 Apr; 40(4): 651–7PubMedCrossRefGoogle Scholar
  64. 63.
    Liu R, Gao X, Lu Y, et al. Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology 2011 Jun; 76(23): 2002–9PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  1. 1.AdisMairangi Bay, North Shore 0754, AucklandNew Zealand

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