Generic Products of Antiepileptic Drugs (AEDs): Is It an Issue?

Abstract

Summary: The availability of generic products of antiepileptic drugs (AEDs) has raised the following concerns: (1) Do generic AEDs work as well as brand AEDs in terms of their efficacy, safety and quality? (2) Can generic AEDs be used as substitutions for brand AEDs? and (3) Can generic products of AEDs be used interchangeably? The traditional average bioequivalence analysis addresses concern 1 but does not provide a complete adequate response to concerns 2 and 3. Drug interchangeability can be classified as drug prescribability or drug switchability. Drug prescribability refers to the situation where a patient is treated for the first time so that either a brand or a bioequivalent generic AED can be chosen. Drug switchability refers to the situation in which a brand AED is switched to a bioequivalent generic product of the same AED. The traditional average bioequivalence approach is sufficient to evaluate the prescribability of generic products, but does not ensure the switchability between prescribable formulations. The necessity of assuring switchability of two formulations can be addressed by individual bioequivalence. While the switch to generic AEDs is well tolerated by many patients and in general cost‐effective, seizure control should not be sacrificed on the basis of cost alone, as the major end point in treating epilepsy with AEDs is seizure control without side effects. Until we have individual (within patient) bioequivalence data on generic AEDs and/or the tools to a priori identify the subset of patients susceptible to the generic switch, a switch of AED products in seizure‐free patients is not recommended.

Interchangeability among therapeutic equivalents of lamotrigine: evaluation of quality of life

“…Thus, the prescription of generic, similar or reference drug has been suggested only at the beginning of the epilepsy pharmacological treatment, where the physician is charged with choosing the most appropriate pharmaceutical equivalent (Krämer et al, 2007;Bialer, 2007). For patients who are free of seizures and side effects, interchangeability among AEDs is not recommended (Bialer, 2007).…”

“…For patients who are free of seizures and side effects, interchangeability among AEDs is not recommended (Bialer, 2007).…”

Considerações e recomendações para o uso de formulações de drogas antiepilépticas

“…5 Numa pesquisa com 6.420 neurologistas, dos 301 que responderam, 67% relataram recidiva das crises e 56% relataram aumento de efeitos adversos após a troca por medicamentos genéricos. 6 Em outra pesquisa foram questionados 2.285 pacientes.…”

Comparative Bioavailability of Two Extemporaneous Solid Formulations of Carbamazepine against the Innovator in Mexican Healthy Subjects

“…However, several reports have raised concerns about clinically meaningful differences in serum level, therapeutic effect, and adverse effects between generic and brand-name anticonvulsants, including carbamazepine [5][6][7][8]. Thus, extemporaneous products should be advised to demonstrate that are bioequivalent to the reference in order to guarantee efficacy and safety in patients treated with the drug in question.…”