, Volume 72, Issue 5, pp 643-669
Date: 18 Nov 2012


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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.

Various sections of the manuscript reviewed by: K. Dashtipour, Faculty of Medical Offices, Loma Linda University, Loma Linda, CA, USA; P.J. Garcia Ruiz, Department of Neurology, Fundacion Jimenez Diaz, Madrid, Spain; E.B. Montgomery Jr, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA; J.C. Morgan, Movement Disorders Program, NPF Center of Excellence, Department of Neurology, Medical College of Georgia, Augusta, GA, USA; M. Naoi, Department of Neurosciences, Gifu International Institute of Biotechnology, Gifu, Japan; F. Stocchi, Institute of Neurology, IRCCS San Raffaele Pisana, Rome, Italy.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘rasagiline’ was identified by searching databases since 1996 (including MEDLINE and EMBASE), bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE and EMBASE search terms were ‘rasagiline’ and (‘Parkinson disease’ or ‘Parkinson’s disease’). Searches were last updated 12 March 2012.
Selection: Studies in patients with Parkinson’s disease who received rasagiline. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Rasagiline, Parkinson’s disease, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.