Bioequivalence of antiepileptic drugs: How close is close enough?

Abstract

During the past few years, the use and substitution of generic antiepileptic drug products has been increasing both in the United States as well as globally. Although these less expensive products may represent an important alternative for many patients, there may be reasons for concern. Despite well-controlled regulatory studies, concerns persist regarding potential therapeutic inequivalence in some patients with epilepsy. These concerns have prompted some in the US neurology community as well as patient advocacy groups to question the current regulatory requirements for both establishing bioequivalence as well as product substitution. In addition, recent data have questioned the actual cost savings associated with generic substitution in this unique patient population. This article reviews current regulatory requirements and pharmacokinetic, biopharmaceutical, and clinical outcome issues that clinicians, pharmacists, and policymakers should consider regarding generic substitution of these complicated agents.

Possible Genetic Determinants of Response to Phenytoin in a Group of Colombian Patients With Epilepsy

“…The availability of this information for all patients would have allowed an accurate correlation between CYP2C9 genotypes, plasmatic levels of phenytoin and therapeutic response, as well as a more precise attribution of causal relationship in ADRs according to the Naranjo algorithm, which includes supratherapeutic plasma levels of the suspect drug as one of the items to be evaluated. While phenytoin has a narrow therapeutic range, there is evidence to suggest that this drug should not be freely interchangeable (Gidal, 2009;Rediguieri and Zeredo, 2014). Therefore, the lack of control over which specific…”

Generic Substitution of Antiepileptics: Need for a Balanced View

“…As a result, there is still significant uncertainty and ongoing debate about the role of generic brands of drugs for treating epilepsy. [1][2][3][4][11][12][13][14][15] The FDA includes phenytoin, carbamazepine, and valproate as narrow therapeutic index medicines, although the argument that AEDs have a narrow therapeutic index is not widely accepted, except in the case of phenytoin. 12,13…”

“…People with well-controlled epilepsy may be most vulnerable, because a single seizure could jeopardise driving privileges or work. 1,11,[14][15][16][17][18] Much more is at stake than with the generic brand substitution of antibiotics.…”

“…"Few medical issues in recent history have resulted in as much controversy, confusion, and angst as the issue of generic drug substitution." 1 There is considerable interest and debate concerning the place of generic substitution, especially relating to antiepileptic drugs (AEDs). 2,3 One of the causes of the ongoing debate is, sadly, confusion, often fueled intentionally by the pharmaceutical industry, amongst health professionals and patients regarding the regulatory definition of bioequivalence.…”

The Problems Associated With Switching Brand-Name Antiepileptic Drugs to Generics: A Focus on Topamax: A Review of Literature and a Case Report

“…Переход с оригинального препарата на более де-шевый генерический может снизить стоимость лече-ния (что возможно и допустимо во многих сферах ме-дицины), однако в отношении АЭП следует соблюдать особую осторожность [10,14,21]. Это связано с опре-деленными особенностями течения эпилепсии и ее лечения, которые осложняют переход с оригинальных препаратов на генерические [9,17,24], включая сле-дующие.…”