Clinical and pharmacy utilization outcomes with brand to generic antiepileptic switches in patients with epilepsy *Sara C. Erickson, *Lisa Le, yScott D. Ramsey, *Brian K. Solow, *Armen Zakharyan, *Karen M. Stockl, *Ann S.M. Harada, and *Bradford Curtis *Prescription Solutions, Irvine, California, U.S.A.; and yFred Hutchinson Cancer Research Center, Seattle, Washington, U.S.A. SUMMARY Purpose: To determine if switching from select branded to generic equivalent antiepileptic drugs (AEDs) in patients with epilepsy is associated with adverse out- comes. Methods: A retrospective cohort study using a large health insurance plan claims database comparing patients with epilepsy who switched from brand to generic equiva- lent phenytoin, lamotrigine, or divalproex after 6 months (switch cohorts) to matched patients who remained on the brand (nonswitch cohorts). Primary outcomes measured include the incidence rate ratio (IRR) of discon- tinuation of the index AED; change in dose of index AED or addition of another AED; and the event rate ratio (ERR) of the composite of all-cause emergency depart- ment (ED) visits or hospitalizations. Key Findings: Lamotrigine and divalproex showed no dif- ferences in AED utilization changes between the switch- ers and nonswitchers [IRR for lamotrigine 1.00, 95% confidence interval (CI) 0.84–1.19; IRR for divalproex 1.02, 95% CI, 0.88–1.42]. Compared with nonswitchers, the phenytoin switch cohort had greater incidence of AED utilization changes (IRR 1.85, 95% CI 1.50–2.29). The switch versus nonswitch cohorts did not demonstrate dif- ferences in ED visits or hospitalizations for the studied AEDs (ERR for phenytoin 0.96, 95% CI 0.80–1.16; ERR for lamotrigine 0.97, 95% CI 0.80-1.17; ERR for divalproex 0.83, 95% CI 0.66–1.06). Significance: Brand to generic switching of phenytoin was not associated with more clinical events but was associ- ated with increased index drug discontinuations, dose changes, or therapy augmentations. Lamotrigine or divalproex brand to generic switching was not associated with increased incidence of events or utilization changes compared with patients remaining on the branded prod- uct. Changes in AED utilization may be more sensitive than ED visits and hospitalizations for detecting adverse outcomes. KEY WORDS: Antiepileptic drugs, Generic substitution. Adverse outcomes associated with the switching between A-rated (bioequivalent) brand name and generic antiepilep- tic drug (AED) products has been the subject of concern among patients with epilepsy and their clinicians. The U.S. Food and Drug Administration (FDA) Office of Generic Drugs affirms that A-rated generic drugs will perform the same as their brand counterparts (U.S. Food and Drug Administration, 2009a). The FDA requires that the 90% confidence interval (CI) surrounding the rate and extent of absorption (bioavailability) of the generic product must be within 80–125% of the log transformed data (Food and Drug Administration Center for Drug Evaluation and Research, 2010). This criterion has resulted in an observed average difference in bioavailability of 2–4% in surveys of generic drugs (U.S. Food and Drug Administration, 2009b; Food and Drug Administration Center for Drug Evaluation and Research, 2010). The American Academy of Neurology (AAN) issued a position statement in 2007 opposing generic AED substitu- tion without physician approval (Liow et al., 2007). The AAN asserts that AEDs differ from other classes of drugs in ways that make generic substitution problematic. The impact of clinically meaningful differences in bioavailabil- ity for this drug class is potentially significant due to the consequences of increased seizure activity resulting from subtherapeutic serum drug concentration. At the time of the publication of the AAN position statement regarding AEDs in the treatment of epilepsy, evidence of adverse outcomes associated with switching between bioequivalent brand and generic AEDs was limited to case reports and pharmaco- kinetic studies (MacDonald, 1987; Wyllie et al., 1987; Gilman et al., 1993; Burkhardt et al., 2004; Makus & McCormick, 2007). Since then, three case-control studies and one cohort study examining medical claims for adverse events have been published with conflicting results (Duh Accepted April 21, 2011; Early View publication June 22, 2011. Address correspondence to Sara C. Erickson, Clinical Analytics and Outcomes Research, Prescription Solutions, 2300 Main St. CA134-0404, Irvine, CA 92614, U.S.A. E-mail: sara_c_erickson@prescriptionsolutions. com Wiley Periodicals, Inc. ª 2011 International League Against Epilepsy Epilepsia, 52(7):1365–1371, 2011 doi: 10.1111/j.1528-1167.2011.03130.x FULL-LENGTH ORIGINAL RESEARCH 1365