Safinamide in the management of patients with Parkinson’s disease not stabilized on levodopa: A review of the current clinical evidence
TLDR
Evidence suggests that safinamide is a good option for add-on therapy to carbidopa/levodopa in patients with advanced Parkinson’s disease with motor complications, but there is still insufficient evidence to recommend it as monotherapy or add- on therapy in patientswith early PD.Abstract:
Safinamide (Xadago®) is a novel medication with both dopaminergic and non-dopaminergic effects, approved first by the European Commission and more recently by the US Food and Drug Administration (FDA) as an adjunctive treatment to carbidopa/levodopa in patients with mid- to late-stage Parkinson's disease (PD) and motor fluctuations. It works through multiple mechanisms, namely as a reversible selective monoamine oxidase-B inhibitor and through modulation of glutamate release. Safinamide is extensively metabolized via oxidation to several inactive metabolites that are excreted primarily through the urine. Several large Phase III clinical trials of patients with advanced PD with motor fluctuations have shown that safinamide, administered orally at doses of 50-100 mg daily, increased ON time with no or non-troublesome dyskinesia, decreased daily OFF time, improved overall motor function (as measured by Unified Parkinson's Disease Rating Scale [UPDRS] part III total score), and quality of life (as measured by Clinical Global Impression-Change and 39-item Parkinson's Disease Questionnaire). In large clinical trials of patients with early PD on a single dopamine agonist, safinamide administered orally at a dose of 100 mg daily improved overall motor function as measured by UPDRS part III total score; however, some of the results reported were exploratory. Safinamide is generally well-tolerated and safe, with few to no treatment-related adverse events. Safinamide does not cause new or worsening dyskinesia and may be able to reduce this symptom in patients reporting it at baseline. Evidence suggests that safinamide is a good option for add-on therapy to carbidopa/levodopa in patients with advanced PD with motor complications, but there is still insufficient evidence to recommend it as monotherapy or add-on therapy in patients with early PD.read more
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References
More filters
Journal ArticleDOI
Pharmacological Treatment of Parkinson Disease: A Review
TL;DR: Strong evidence supports using levodopa and dopamine agonists for motor symptoms at all stages of Parkinson disease, and other therapies for motor and nonmotor features is less well established.
Journal ArticleDOI
A review of Parkinson's disease
TL;DR: Although there is growing circumstantial evidence, it remains to be proven whether any of the current treatments for PD have a neuroprotective effect and how this research will benefit from further clinical research.
Journal ArticleDOI
Structures of Human Monoamine Oxidase B Complexes with Selective Noncovalent Inhibitors: Safinamide and Coumarin Analogs.
Claudia Binda,Jin Wang,Leonardo Pisani,C. Caccia,Angelo Carotti,Patricia Salvati,Dale E. Edmondson,Andrea Mattevi +7 more
TL;DR: Structures of human monoamine oxidase B in complex with safinamide and two coumarin derivatives, all sharing a common benzyloxy substituent, were determined by X-ray crystallography.
Journal ArticleDOI
Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations.
Rupam Borgohain,József Attila Szász,Paolo Stanzione,Chandrashekhar Meshram,Mohit Bhatt,D. Chirilineau,Fabrizio Stocchi,V. Lucini,R. Giuliani,Emma Forrest,P. Rice,R. Anand,M. Illiyas Sahadulla,U. Kardan,B. S. Keshava,A. Kishore,S. S. Kothari,J. M. Krishna Murthy,S. Kumar,P. Kumar Pal,N. Mehta,S. Prabhakar,S. Kr Prabhakar,S. Pradhan,A. K. Roy,C. Sankhla,P. K. Sethi,Amy Shah,N. Shankar,R. Shukla,A. Sowani,R. Srinivasa,M. Varma,D. Vasudevan,P. Vavilikolanu Sreenivas,C. U. Velmurugendran,K. Vijayan,Ovidiu Bajenaru,A. Bulboaca,A. Campeanu,D. Chirileanu,D. Muresanu,C. Panea,C. D. Popescu,Mihaela Simu,M. Ticmeanu,Tania P. Avarello,Ubaldo Bonuccelli,Roberto Eleopra,Marco Onofrj,Rocco Quatrale +50 more
TL;DR: The addition of safinamide 50 mg/day or 100mg/day to l‐dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating thatsafinamide improves motor symptoms and parkinsonistan without worsening dyskineia.
Journal ArticleDOI
Two-Year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease
Rupam Borgohain,József Attila Szász,Paolo Stanzione,Chandrashekhar Meshram,Mohit Bhatt,Dana Chirilineau,Fabrizio Stocchi,V. Lucini,R. Giuliani,Emma Forrest,Patricia Rice,R. Anand +11 more
TL;DR: This 2‐year, controlled study of add‐on safinamide in mid‐to‐late Parkinson's disease with motor fluctuations showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline, and demonstrated significant clinical benefits in ON‐time (without troublesome dysKinesia), OFF‐time, activities of daily living, motor symptoms, quality of life, and symptoms of depression.