Switching generic antiepileptic drug manufacturer not linked to seizures: A case-crossover study.
OBJECTIVE
With more antiepileptic drugs (AED) becoming available in generic form, we estimated the risk of seizure-related events associated with refilling generic AEDs and the effect of switching between different manufacturers of the same generic drug.


METHODS
We designed a population-based case-crossover study using the Medicaid Analytic eXtract and a US commercial health insurance database. We identified 83,001 generic AED users who experienced a seizure-related hospital admission or emergency room visit between 2000 and 2013 and assessed whether they received a refill of the same AED from the same manufacturer or a different manufacturer. Patients served as their own controls and conditional logistic regression was used to compare exposure to a refill during the hazard period, defined as days 2-36 preceding the seizure-related event, to exposure during the control period, defined as days 51-85 preceding the seizure-related event.


RESULTS
Generic AED refilling was associated with an 8% increase in the odds of seizure-related events (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.06-1.11). The OR following a switch to a different manufacturer of the same AED was 1.09 (95% CI 1.03-1.15); however, after adjusting for the process of refilling, there was no association between switching and seizure-related hospital visits (OR 1.00; 95% CI 0.94-1.07).


CONCLUSIONS
Among patients on a generic AED, refilling the same AED was associated with an elevated risk of seizure-related event; however, there was no additional risk from switching during that refill to a different manufacturer. Generic AEDs available to US patients, with Food and Drug Administration-validated bioequivalence, appear to be safe clinical choices.
From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. akesselheim@partners.org.
Aaron S
AS
Kesselheim
From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Katsiaryna
K
Bykov
From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Joshua J
JJ
Gagne
From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Shirley V
SV
Wang
From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Niteesh K
NK
Choudhry
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018672:Community Health Planning; D016208:Databases, Factual / Q000706:statistics & numerical data; D057915:Drug Substitution / Q000009:adverse effects* / Q000706:statistics & numerical data; D016568:Drugs, Generic / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007348:Insurance, Health / Q000706:statistics & numerical data; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012640:Seizures / Q000453:epidemiology* / Q000517:prevention & control*; D014481:United States; D055815:Young Adult
D000927:Anticonvulsants; D016568:Drugs, Generic
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