Technologies: Generic immediate release formulation of pramipexole.
Indication: Treatment of motor symptoms of Parkinson’s disease.
Technologies characterization: Pramipexole is a dopamine agonist that acts “replacing” dopamine, a neurotransmitter that is in decreased concentration in Parkinson’s disease.
Question: The generic drug pramipexole is safe and effective in the treatment of the motor symptoms of Parkinson’s disease in comparison to the reference medicine (Sifrol®) and the similar medicine (Stabil®)?
Search and analysis of scientific evidence: We performed a search for Brazilian official documents and reports that addressed the standards for registration of generic and similar medicines in the electronic sites of the National Health Surveillance Agency (from the Portuguese Agência Nacionald e Vigilância Sanitária – ANVISA) and international documents of the Food and Drug Administration (FDA), European Medicines Agency (EMA) sites and the World Health Organization (WHO). We conducted a searchfor scientific studies in Medline (via Pubmed), Centre for Reviews and Dissemination, The Cochrane Library, and LILACS.
Summary of results of the selected studies: According to Law and resolutions of ANVISA the interchangeability between reference and generic, or similar medicines, is expected as they have to demonstrate biequivalence for the registration of the medicine in the Ministry of Health. ANVISA Resolutions regulated waiver from traditional bioequivalence studies for drugs considered to present high solubility and high permeability according to the Biopharmaceutics Classification System. In August 2014 pramipexole was included in the list of drugs eligible for biowaiver as it is considered of high absorption (greater than or equal to 85%) and of broad therapeutic index, i.e., the therapeutic dose is distant to the toxic dose. Furthermore, this drug has no reports of human absence of bioequivalence. In the United States of America pramipexole is eligible for biowaiver since 2010. The European agency has not released the list of drugs eligible for biowaiver, but considers drugs with high solubility and high permeability eligible for biowaiver, as well as the World Health Organization. After applying the eligibility criteria a scientific study was included. It is a narrative review in which the authors indicate that patients with Parkinson’s disease should be treated with the brand name medicines. This study has important limitations regarding the method, as narrative reviews do not use a structured and reproducible search for studies, the authors can choose the ones that support their opinion. The peculiarities of patients with Parkinson’s disease presented as an argument, such as reduced gastric motility, affect the effectiveness of generic, similar and reference medicines the same way.
Recommendations: There is no legal and scientific support to justify the preference for brand name medicines with respect to pramipexole, since the Brazilian and foreign regulations point to the fact that there is no evidence of absence of bioequivalence between different formulations of immediate release pramipexole dichloridrate. In addition, we did not find high quality scientific evidence, according to the precepts of evidence-based medicine, which could point to differences in clinical outcomes between the formulations studied.
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