Abstracts

Rationale: Generic substitution of anti-epileptic drugs (AED) is widely used after the expiration of the patent of the brand AED product. However, manufacturing of a bioequivalent product is difficult for many AEDs. There are numerous anecdotes and case reports of patients experiencing breakthrough seizures and or side effects when transitioned from brand to generic AED. The purpose of this study was to investigate variations in pharmacokinetics and impact on seizure frequency after brand to generic substitution of oxcarbazepine (OXC) in adults with epilepsy. Methods: The population studied resides and receives care in a community center where patients are closely monitored for seizure frequency, medication side effects and receipt of daily doses of medicines. Regular serum AEDs concentrations (trough levels) are obtained. Twenty two adult patients with epilepsy and receiving OXC were identified retrospectively. Of the 22 patients, 18 patients had complete and available medical records for review. The analysis was performed with comparison of pharmacokinetic parameters and clinical response before and after the transition from brand to generic OXC formulation. Approval was obtained through the Institutional Review Board at the University of Kentucky. Results: We identified 11 patients (7 men, age 35-66 years) who had at least one OXC level pre- and one level post-substitution from brand to generic formulation without undergoing any changes to the dosage of OXC. All patients were switched to a generic formulation provided by the same manufacturer. The OXC dose range was 1200-2100 mg total per day. On average, the OXC increased from 19.2mg/L to 23.2mg/L. Eight patients (72.7%) had a level that was higher after the substitution (by <7mg/L, except one patient who increased by 18mg/L). Two patients had no change in their OXC concentration after the substitution. One patient had a concentration that was lower (by 3mg/L) after the transition. One patient had worsening of seizures after the switch (from 1 seizure per year to 6) which coincided with an increase in OXC concentration by 1mg/L and worsening of pre-existing hyponatremia. A total of 4 patients (36.3%) exhibited hyponatremia after the switch to the generic product (average sodium of hyponatremic patients changed from 133mEq/L to 127mEq/L).