Background: Antiparkinsonian pharmacotherapy represents one of the most important
expenses related to Parkinson’s disease. The
application of generic drugs may help to reduce the economic burden of the
disease; however, efficacy and safety
of these products have been less studied. Objective: To
investigate the efficacy and safety of generic rasagiline (Ralago？) from a clinical perspective. Methods: The Clinical Global Impression of Severity scale was used to rate the
most important motor and non-motor symptoms at baseline and 12 weeks after the
initiation of Ralago？. Patients also identified
symptoms which were the main sources of their
disability and distress in everyday life. Results: A total of 499
patients were enrolled (231 females, mean age: 73.2 ± 9.1 years, mean duration
of disease: 3.6 ± 3.7 years). Of them,
486 patients completed the study protocol. Both motor and non-motor symptoms
showed improvement during 12-week Ralago？ treatment. Adverse events were rare, and the
majority of them were not considered
as serious. Conclusions: The generic rasagiline (Ralago？) is an effective and safe generic product.
References
[1]
Karlsen, K.H., Tandberg, E., Arsland, D. and Larsen, J.P. (2000) Health Related Quality of Life in Parkinson’s Disease: A Prospective Longitudinal Study. Journal of Neurology, Neurosurgery, and Psychiatry, 69, 584-589.
https://doi.org/10.1136/jnnp.69.5.584
[2]
Kadastik-Eerme, L., Rosenthal, M., Paju, T., Muldmaa, M. and Taba, P. (2015) Health-Related Quality of Life in Parkinson’s Disease: A Cross-Sectional Study Focusing on Non-Motor Symptoms. Health and Quality of Life Outcomes, 13, 83.
https://doi.org/10.1186/s12955-015-0281-x
[3]
Aquino, C.C. and Fox, S.H. (2015) Clinical Spectrum of Levodopa-Induced Complications. Movement Disorders: Official Journal of the Movement Disorder Society, 30, 80-89. https://doi.org/10.1002/mds.26125
[4]
Oertel, W.H., Berardelli, A., Bloem, B.R., et al. (2011) Late (Complicated) Parkinson’s Disease. In: Gilhus, N., Barnes, P.J. and Brainin, M., Eds., European Handbook of Neurological Management, Blackwell Publishing Ltd., Berlin, 237-267.
https://doi.org/10.1002/9781444328394.ch15
[5]
Aschermann, Z., Kovacs, N. and Komoly, S. (2013) Continuous Dopaminergic Stimulation in Parkinson Disease: Possibilities in 2013. Ideggyógyászati szemle, 66, 209-210.
[6]
Finberg, J.P. and Rabey, J.M. (2016) Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology. Frontiers in Pharmacology, 7, 340.
https://doi.org/10.3389/fphar.2016.00340
[7]
Parkinson Study Group (2002) A Controlled Trial of Rasagiline in Early Parkinson Disease: The TEMPO Study. Archives of Neurology, 59, 1937-1943.
https://doi.org/10.1001/archneur.59.12.1937
[8]
Parkinson Study Group (2005) A Randomized Placebo-Controlled Trial of Rasagiline in Levodopa-Treated Patients with Parkinson Disease and Motor Fluctuations: The PRESTO Study. Archives of Neurology, 62, 241-248.
https://doi.org/10.1001/archneur.62.2.241
[9]
Rascol, O., Brooks, D.J., Melamed, E., et al. (2005) 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. The Lancet, 365, 947-954.
https://doi.org/10.1016/S0140-6736(05)71083-7
[10]
Olanow, C.W., Rascol, O., Hauser, R., et al. (2009) A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson’s Disease. The New England Journal of Medicine, 361, 1268-1278. https://doi.org/10.1056/NEJMoa0809335
[11]
Hattori, N., Takeda, A., Takeda, S., et al. (2018) Rasagiline Monotherapy in Early Parkinson’s Disease: A Phase 3, Randomized Study in Japan. Parkinsonism & Related Disorders, 60, 146-152. https://doi.org/10.1016/j.parkreldis.2018.08.024
[12]
Sandoval-Rincon, M., Saenz-Farret, M., Miguel-Puga, A., Micheli, F. and Arias-Carrion, O. (2015) Rational Pharmacological Approaches for Cognitive Dysfunction and Depression in Parkinson’s Disease. Frontiers in Neurology, 6, 71.
https://doi.org/10.3389/fneur.2015.00071
[13]
Hanagasi, H.A., Gurvit, H., Unsalan, P., et al. (2011) The Effects of Rasagiline on Cognitive Deficits in Parkinson’s Disease Patients without Dementia: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study. Movement Disorders: Official Journal of the Movement Disorder Society, 26, 1851-1858.
https://doi.org/10.1002/mds.23738
[14]
Blandini, F., Armentero, M.T., Fancellu, R., Blaugrund, E. and Nappi, G. (2004) Neuroprotective Effect of Rasagiline in a Rodent Model of Parkinson’s Disease. Experimental Neurology, 187, 455-459.
https://doi.org/10.1016/j.expneurol.2004.03.005
[15]
Sagi, Y., Mandel, S., Amit, T. and Youdim, M.B. (2007) Activation of Tyrosine Kinase Receptor Signaling Pathway by Rasagiline Facilitates Neurorescue and Restoration of Nigrostriatal Dopamine Neurons in Post-MPTP-Induced Parkinsonism. Neurobiology of Disease, 25, 35-44. https://doi.org/10.1016/j.nbd.2006.07.020
[16]
Spottke, A.E., Reuter, M., Machat, O., et al. (2005) Cost of Illness and Its Predictors for Parkinson’s Disease in Germany. PharmacoEconomics, 23, 817-836.
https://doi.org/10.2165/00019053-200523080-00007
[17]
Winter, Y., von Campenhausen, S., Reese, J.P., et al. (2010) Costs of Parkinson’s Disease and Antiparkinsonian Pharmacotherapy: An Italian Cohort Study. Neuro-Degenerative Diseases, 7, 365-372. https://doi.org/10.1159/000302644
[18]
Hensler, K., Uhlmann, C., Porschen, T., Benecke, R. and Rosche, J. (2013) Generic Substitution of Antiepileptic Drugs—A Survey of Patients’ Perspectives in Germany and Other German-Speaking Countries. Epilepsy & Behavior, 27, 135-139.
https://doi.org/10.1016/j.yebeh.2012.12.029
[19]
European Medicines Agency (2010) Guideline on the Investigation of Bioequivalence. London.
https://www.ema.europa.eu/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf
[20]
US Food and Drug Administration (2003) Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Consideration. https://www.ipqpubs.com/wp-content/uploads/2014/04/BABEOld.pdf
[21]
Raw, A.S., Lionberger, R. and Yu, L.X. (2011) Pharmaceutical Equivalence by Design for Generic Drugs: Modified-Release Products. Pharmaceutical Research, 28, 1445-1453. https://doi.org/10.1007/s11095-011-0397-6
[22]
van der Meersch, A., Dechartres, A. and Ravaud, P. (2011) Quality of Reporting of Bioequivalence Trials Comparing Generic to Brand Name Drugs: A Methodological Systematic Review. PLoS ONE, 6, e23611.
https://doi.org/10.1371/journal.pone.0023611
[23]
Bosnyak, E., Herceg, M., Pal, E., et al. (2014) Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? A Rater-Blinded, Switch-Over, Multicenter Study. Parkinson’s Disease, 2014, Article ID: 158353.
https://doi.org/10.1155/2014/158353
[24]
Martinez-Martin, P., Rojo-Abuin, J.M., Rodriguez-Violante, M., et al. (2016) Analysis of Four Scales for Global Severity Evaluation in Parkinson’s Disease. NPJ Parkinson’s Disease, 2, Article ID: 16007. https://doi.org/10.1038/npjparkd.2016.7
[25]
Go, C.L., Rosales, R.L., Schmidt, P., Lyons, K.E., Pahwa, R. and Okun, M.S. (2011) Generic versus Branded Pharmacotherapy in Parkinson’s Disease: Does It Matter? A Review. Parkinsonism & Related Disorders, 17, 308-312.
https://doi.org/10.1016/j.parkreldis.2011.02.005
[26]
Pahwa, R.P.R., Lyons, K.E., Majama, J., McGuire, D., Koller, W., Silverstein, P., et al. (1994) Clinical Experience with Generic Carbidopa Levodopa (G-L) in Patients with Parkinson’s Disease (PD). Neurology, 44, A244.
[27]
Pahwa, R., Marjama, J., McGuire, D., et al. (1996) Pharmacokinetic Comparison of Sinemet and Atamet (Generic Carbidopa/Levodopa, a Single-Dose Study. Movement Disorders: Official Journal of the Movement Disorder Society, 11, 427-430.
https://doi.org/10.1002/mds.870110412
[28]
Hauser, R.A., Olanow, C.W. and Koller, W.C. (1994) Time Course of Washout of Symptomatic Medication in Parkinson’s Disease. Neurology, 44, A259.
[29]
Nutt, J.G., Carter, J.H. and Woodward, W.R. (1995) Long-Duration Response to Levodopa. Neurology, 45, 1613-1616. https://doi.org/10.1212/WNL.45.8.1613
[30]
Kasemsap, N., Onsanit, S., Chiewthanakul, P., et al. (2016) Efficacy and Motor Complications of Original and Generic Levodopa in Parkinson’s Disease Treatment. Neuropsychiatric Disease and Treatment, 12, 1185-1189.
https://doi.org/10.2147/NDT.S98597
[31]
Zhang, Z., Shao, M., Chen, S., et al. (2018) Adjunct Rasagiline to Treat Parkinson’s Disease with Motor Fluctuations: A Randomized, Double-Blind Study in China. Translational Neurodegeneration, 7, 14. https://doi.org/10.1186/s40035-018-0119-7
[32]
Martinez-Martin, P., Forjaz, M.J., Cubo, E., Frades, B., de Pedro Cuesta, J. and Members, E.P. (2006) Global versus Factor-Related Impression of Severity in Parkinson’s Disease: A New Clinimetric Index (CISI-PD). Movement Disorders, 21, 208-214. https://doi.org/10.1002/mds.20697
[33]
Arnold, G., Gasser, T., Storch, A., et al. (2005) High Doses of Pergolide Improve Clinical Global Impression in Advanced Parkinson’s Disease—A Preliminary Open Label Study. Archives of Gerontology and Geriatrics, 41, 239-253.
https://doi.org/10.1016/j.archger.2005.04.002
[34]
Takanashi, M., Shimo, Y., Hatano, T., Oyama, G. and Hattori, N. (2013) Efficacy and Safety of a Once-Daily Extended-Release Formulation of Pramipexole Switched from an Immediate-Release Formulation in Patients with Advanced Parkinson’s Disease: Results from an Open-Label Study. Drug Research, 63, 639-643.
https://doi.org/10.1055/s-0033-1351257
