title: Generic products of antiepileptic drugs: a perspective on bioequivalence and interchangeability.
abstract: Most antiepileptic drugs (AEDs) are currently available as generic products, yet neurologists and patients are reluctant to switch to generics. Generic AEDs are regarded as bioequivalent to brand AEDs after meeting the average bioequivalence criteria; consequently, they are considered to be interchangeable with their respective brands without loss of efficacy and safety. According to the U.S. Food and Drug Administration (FDA) the present bioequivalence requirements are already so rigorous and constrained that there is little possibility that generics that meet regulatory bioequivalence criteria could lead to therapeutic problems. So is there a scientific rationale for the concerns about switching patients with epilepsy to bioequivalent generics? Herein we discuss the assessment of bioequivalence and propose a scaled-average bioequivalence approach where scaling of bioequivalence is carried out based on brand lot-to-lot variance as an alternative to the conventional bioequivalence test as a means to determine whether switching patients to generic formulations, or vice versa, is a safe and effective therapeutic option. Meeting the proposed scaled-average bioequivalence requirements will ensure that when an individual patient is switched, he or she has fluctuations in plasma levels similar to those from lot-to-lot of the brand reference levels and thus should make these generic products safely switchable without change in efficacy and safety outcomes.
authors.affiliation: Faculty of Medicine, Institute of Drug Research, School of Pharmacy and David R Bloom Center for Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel. bialer@md.huji.ac.il
authors.forename: Meir
authors.initials: M
authors.lastname: Bialer
authors.forename: Kamal K
authors.initials: KK
authors.lastname: Midha
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016568:Drugs, Generic / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration / Q000639:trends
chemical_list: D000927:Anticonvulsants; D016568:Drugs, Generic