Abstracts

Rationale: Controversy exists regarding the interchangeability of generic antiepileptic drugs (AEDs) with brand name medications in terms of efficacy and adverse events. Despite AAN’s opposition to unapproved by the physicians’ generic substitution of anticonvulsant drugs1, many states mandate this unapproved switch2. The goal of this study is to contribute to the growing evidence in the literature of adverse outcomes with the use generic AEDs, to increase awareness among neurologists of these outcomes and encourage reporting of these events to the FDA. Methods: We prospectively identified patients followed at the seizure clinic at Boston Medical Center, who reported adverse outcomes following state-mandated generic substitution of their AEDs during the period 01/05/2007-04/28/2009. Adverse outcomes were divided into breakthrough seizures, increased frequency of seizures and medication side effects. Seizure control was defined as >6 months of seizure freedom, in accordance with MA driving law. Increased seizure frequency was defined as at least >2 fold increase in seizure frequency from baseline. Serum levels of AEDs were collected and correlated with their previous levels prior to the substitution. Prior authorizations were submitted to insurance companies for the purpose of switchback to brand and medwatches to the FDA. We excluded cases without confirmation of compliance or with other recognized factors that may have contributed to the adverse outcome. Results: 99 seizure patients were identified (M: 56, F: 43). The mean age was 40 years old (range 20-84). Partial epilepsy was identified in 93 (94%) of the patients and generalized epilepsy in 6 (6%). 34, 44, 19 and 2 patients were on 1, 2, 3 and 4 AEDs respectively (mean 1.9). 29 (29%) of these patients experienced a breakthrough seizure after > 6 months seizure-free, while 44 (44%) of patients reported >2-fold increase in seizure frequency [Graph 1]. 26 patients (26%) reported a total of 37 medication side effects [Table 1]. Serum AED levels were available in 38 cases of generic exposure. Serum concentration of AEDs did not correlate consistently with adverse outcomes. Adverse outcomes resolved upon switchback to brand formulation. Conclusions: These results indicate that adverse outcomes can frequently occur with generic substitution of anti-epileptic medications, in the form of loss of seizure control, increased seizure frequency and medication side effects. Levels do not appear to be adequate predictors of outcome. Although proof of causality or an acceptable mechanism of generic failure in the treatment of epilepsy has not yet been identified, clinical observation reveals potential lack of therapeutic equivalence. Until a randomized, double-blind controlled study is conducted to resolve this issue, clinicians are urged to recognize, document and report these cases to the FDA.