Review Current approaches to the use of generic antiepileptic drugs G. Kra ¨mer a, * , A. Biraben b , M. Carreno c , A. Guekht d , G.J. de Haan e , J. Je ˛ drzejczak f , D. Josephs g , K. van Rijckevorsel h , G. Zaccara i a Swiss Epilepsy Center, Bleulerstrasse 60, CH-8008 Zu ¨ rich, Switzerland b Epileptology Unit, Department of Neurology, University Hospital of Pontchaillou, Rennes, France c Epilepsy Unit, Hospital Clı ´nic, Barcelona, Spain d Russian State Medical University, Moscow, Russia e Epilepsy Institute of The Netherlands SEIN, Heemstede, The Netherlands f Department of Neurology and Epileptology, Medical Centre for Postgraduate Education, Warsaw, Poland g Joint Epilepsy Council of the UK and Ireland, Leeds, UK h Cliniques Universitaire Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium i Neurology Unit, Santa Maria Nuova Hospital, Florence, Italy Received 24 January 2007; revised 20 March 2007; accepted 20 March 2007 Available online 29 May 2007 Abstract Generic substitution is encouraged as a cost containment strategy for the management of health care resources. However, in epilepsy, the consequences of loss of symptom control are important, and antiepileptic drugs have narrow therapeutic indices. For this reason, generic substitution may be problematic, and certain health authorities have excluded antiepileptic drugs from overall policy recommen- dations on generic prescribing. The absence of bioequivalence data among generic forms and the relatively broad criteria for bioequiv- alence with the branded drug allow differences in drug exposure to arise that may be clinically relevant and necessitate monitoring of plasma levels when switching formulations to avoid loss of seizure control or emergence of side effects. Management of these issues car- ries a significant cost, which should be weighed carefully against the cost savings acquired when purchasing the drug. Both physicians and patients have a right to be informed and approve before pharmacists make a generic substitution or switch between generics. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Epilepsy; Generic drugs; Bioequivalence; Adherence; Seizure control; Cost 1. Introduction Recent years have seen a growing perception by public health authorities throughout the world of the need to con- trol escalating health care costs and the subsequent imple- mentation of cost containment policies. Among these policies, encouragement of prescription of generic drugs is widely considered a simple and effective way of restrict- ing expenditure on medication. When the patent life of a drug comes to an end, manufacturers can introduce generic versions of the original brand into the marketplace at a considerably reduced cost, because the generic manufac- turer does not have to pay back the considerable research cost associated with the development and introduction of the original brand. Substitution of a cheaper generic alter- native can thus theoretically result in great cost savings. However, generic substitution does raise a number of med- ical issues, particularly for drugs with a narrow therapeutic window and for conditions where loss of optimal disease control may have serious consequences. Antiepileptic drugs (AEDs) represent a class of drugs for which these medical issues are potentially important [1,2]. Many, particularly some of the classic AEDs, have complicated pharmacokinetics and important dose-related side effects, resulting in narrow therapeutic windows and the need for careful dose titration in individual patients. Any loss of seizure control may carry a risk of injury and 1525-5050/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2007.03.014 * Corresponding author. Fax: +41 44 387 6396. E-mail address: G.Kraemer@swissepi.ch (G. Kra ¨mer). www.elsevier.com/locate/yebeh Epilepsy & Behavior 11 (2007) 46–52