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Should newly diagnosed epilepsy be treated with generics?

Nature Clinical Practice Neurology volume 4, pages 176–177 (2008)Cite this article

In recent years, a fervent debate has been going on—at meetings more than in the literature—about possible risks related to the use of generic drugs in patients with epilepsy. This debate was summarized by Bialer,1 who underlined that the concern is not about the quality of the generic preparations. There is broad consensus that generics are prescribable if they are accepted as bioequivalent by the relevant national authority (in North America and the European Union, bioequivalence is achieved when the 90% CIs of the average ratio between the generic and brand product for key pharmacological parameters fall within the range of 80–125%). Rather, the concern is about the interchangeability of antiepileptic drug (AED) preparations—both branded products and generics.

Unlike most other medical conditions, in epilepsy therapeutic success is generally of the all-or-nothing type; either a patient becomes seizure-free, or he or she does not. Mere reduction of seizure frequency is unsatisfactory, because someone whose seizures are fully controlled can lead a more or less normal life, whereas ongoing seizures result in handicaps and risks of complications in the physical, social and psychological spheres. With the presently available AEDs, about 70% of all patients with epilepsy can be seizure-free.2 It was already discovered in the earliest period of therapeutic AED monitoring that, to maintain seizure control, the plasma level of a given AED needs to be kept above a threshold level, and that this level differs from person to person depending on the severity of the individual's epilepsy.3 Patients with a high seizure propensity have a higher therapeutic threshold than those with a low or moderate seizure propensity. In consequence, those with a high seizure propensity might display a narrow individual therapeutic index for a drug that in general has a wide therapeutic index. The doses and plasma levels of an AED that effectively control a patient's seizures might be so close to the therapeutic threshold that the shift to a preparation with a lower bioavailability, within the accepted range of bioequivalence, could produce a seizure relapse. Of the patients at a tertiary referral center who became seizure-free with lamotrigine (a drug with a wide therapeutic index), about 10% did indeed have a high therapeutic threshold.4

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References

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Author notes

  1. Danish Epilepsy Centre, Kolonivej 1, Dianalund, DK-4293, Denmark peterw@vestamt.dk

Authors and Affiliations

  1. P Wolf is Professor of Neurology/Epileptology at Copenhagen University Hospital, Copenhagen and at the Danish Epilepsy Centre, Dianalund, Denmark.,

    Peter Wolf

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Competing interests

The author has served as an advisor for Eisai, GlaxoSmithKline and UCB, and has been a speaker at conferences sponsored by these companies.

Supplementary information

Supplementary Figure 1

Drug plasma levels during dose titration with carbamazepine while switching between different drug preparations — a model case. (DOC 103 kb)

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Wolf, P. Should newly diagnosed epilepsy be treated with generics?. Nat Rev Neurol 4, 176–177 (2008). https://doi.org/10.1038/ncpneuro0753

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