Medicamentos genéricos no tratamento das epilepsias: uma reflexão

Abstract

RESUMOObjetivos: Discutimos aspectos controversos para a prescrição de medicamentos genéricos no tratamento das epilepsias e problemas relacionados à biodisponilidade e bioequivalência. Algumas drogas antiepilépticas (DAE) apresentam baixa solubilidade em água, apresentam cinética não linear e faixa terapêutica estreita, dados sugestivos da ocorrência de problemas relacionados à bioequivalência. Métodos: Revisão da literatura. Resultados e conclusões: Há mais informações sobre as DAE tradicionais (fenitoína, carbamazepina e valproato) e apenas uma comunicação em congresso foi encontrada sobre a substituição de uma nova DAE, a lamotrigina. O nível de evidência é fraco, baseado em séries de casos e opinião de especialistas, com exceção talvez da fenitoína para a qual há alguns estudos analíticos. Podemos permitir o uso de genéricos para o tratamento das epilepsias, desde que tenhamos em mente que este abrirá a possibilidade de substituições sucessivas de formulações durante o tratamento, com conseqüências imprevisíveis como a recorrência de crises e suas conseqüências ou o aparecimento de efeitos adversos.Unitermos: medicamentos genéricos, bioquivalência, biodisponibilidade, intercambialidade. ABSTRACT Generics in the treatment of epilepsy. A reflectionObjective: We discuss some controversial aspects with prescription of generic drugs (GD) and the problems concerning bioequivalence in the treatment of epilepsy. Some antiepileptic drugs (AED) are poorly soluble in water, have nonlinear kinetics and a narrow therapeutic range, implying that problems with bioequivalence are likely to occur. There are clearly advantages (cost saving) and disadvantages (loss of seizure control or drug toxicity) in prescribing generics AED. Methods: Review of literature. Results and conclusion: The main information is about classical AED (phenytoin, carbamazepine and valproate). Regarding the new AED we found only one poster presentation related to lamotrigine substitution. The level of evidence is, generally, weak, based on case-series and expert opinion without explicit critical appraisal (except in phenytoin with level of evidence moderate, based on some analytical studies). We may allow the use of generics for epilepsy treatment. However, this opens the possibility of successive substitution of different formulations which may even be life threatening.Key words: generics, bioequivalence, bioavailability, interchangeability.Medicamento genérico é aquele similar a um produto de referência, inovador ou de marca, que pretende ser com este intercambiável, geralmente produzido após expiração ou renúncia da proteção patentária ou de outros direitos de exclusividade e designado pela denominação científica da droga. O medicamento de referência contém a entidade química (fármaco) desenvolvida e investigada originalmente pelo laboratório fabricante que é o responsável pelos ensaios pré-clínicos e clínicos nos quais foram demonstradas a eficácia e a segurança para as indicações clínicas e as condições de uso autorizadas. Para aceitação de um me...

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

“… 10 These results should raise attention for the possibility that therapeutic failures could be due to intrinsic properties of a specific generic preparation. 26 , 29 , 30…”

Determination of carbamazepine in pharmaceutical formulations

“…In Brazil, this role is performed by the National Health Surveillance Agency (ANVISA) (Storpirtis et al, 2004). The bioequivalence guarantees that two presentations will have the same drug absorption rate and quantity and hence bioavailability (Yacubian, 2007).…”

“…According to Brazilian law 9.787, published in February 10 th of 1999, reference medicines are those commercialized under registration in Brazil. Reference medicines contain the original drug, which was rigorously developed and investigated, and have been submitted to pre-clinical and clinical studies for evaluation of their safety and therapeutic efficacy (Yacubian, 2007).…”

“…According to Brazilian law 9.787, published in February 10 th of 1999, reference medicines are those commercialized under registration in Brazil. Reference medicines contain the original drug, which was rigorously developed and investigated, and have been submitted to pre-clinical and clinical studies for evaluation of their safety and therapeutic efficacy (Yacubian, 2007).Generic medicines have been in use in the United States and Europe since 1960. They can have a different formulation compared to the reference medicine, but must present the same dose, route of administration and presentation as the reference (Baracho, 2008).…”

“…In Brazil, this role is performed by the National Health Surveillance Agency (ANVISA) (Storpirtis et al, 2004). The bioequivalence guarantees that two presentations will have the same drug absorption rate and quantity and hence bioavailability (Yacubian, 2007).The similar medicine is the form having the same drug, dose, pharmaceutical form, route of administration, dosage and indication as the reference medicine, but which has not necessarily been submitted to equivalence and bioequivalence studies.The medicines acquired from compounding pharmacies are normally in capsule form. This pharmaceutical form permits a custom dosage of the drug, which reduces the cost compared to an industrialized medicine, and also facilitates acquisition of the medicine.…”