title: Brand name to generic substitution of antiepileptic drugs does not lead to seizure-related hospitalization: a population-based case-crossover study.
abstract: OBJECTIVE
  There is still controversy on brand-to-generic (B-G) antiepileptic drugs (AEDs) substitution.
  
  
  METHODS
  To assess association between B-G AED substitution and seizure-related hospitalization, we designed a case crossover using the French National Health Insurance Database. We identified a cohort of adult patients who filled a prescription in 2009-2011 for AEDs with at least one brand name and one generic form. The outcome date was defined as the date of hospitalization, coded G40.x or G41.x, with a G40/G41 hospitalization-free period of at least 1 year. Patients with a medical history of cancer and women who gave birth in 2009-2011 were excluded. We required individuals to have regular dispensations of AEDs within the year preceding the outcome date. Free patients were defined as patients who had only brand name dispensations before the control period.
  
  
  RESULTS
  Eight thousand three hundred seventy nine patients (mean age ± standard deviation, 52.7 ± 18.8 years; sex ratio male/female, 1.27) were analyzed. Discordant pairs were 491 with B-G substitution in the control period only and 478 with B-G substitution in the case period only; odds ratio (95% confidence interval) 0.97 (0.86-1.10). No statistically significant interaction was detected among the four prespecified subgroup analyses (gender, age strata, free or non-free, and strict AED monotherapy or not). Controlling for non-seizure-related hospitalizations made no material difference. Sensitivity analyses yielded similar results.
  
  
  CONCLUSIONS
  Brand-to-generic AED substitution was not associated with an elevated risk of seizure-related hospitalization.
authors.affiliation: Department of Pharmacology, Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France.|Pharmacoepidemiology team (CTAD-PEPI), Rennes University Hospital, Rennes, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Polard
authors.affiliation: Pharmacoepidemiology team (CTAD-PEPI), Rennes University Hospital, Rennes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nowak
authors.affiliation: Pharmacoepidemiology team (CTAD-PEPI), Rennes University Hospital, Rennes, France.
authors.forename: André
authors.initials: A
authors.lastname: Happe
authors.affiliation: Department of Neurology, Rennes University Hospital, Rennes, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Biraben
authors.affiliation: Department of Pharmacology, Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France.|Pharmacoepidemiology team (CTAD-PEPI), Rennes University Hospital, Rennes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Oger
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000627:therapeutic use; D018592:Cross-Over Studies; D016208:Databases, Factual; D057915:Drug Substitution; D016568:Drugs, Generic / Q000008:administration & dosage* / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005602:France / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000927:Anticonvulsants; D016568:Drugs, Generic
keywords: crossover studies; drugs; epilepsy/*drug therapy; generic/adverse effects/pharmacokinetics/*therapeutic use; pharmacoepidemiology; seizures/*prevention & control; therapeutic equivalency