Abstracts

Rationale: The majority of anticonvulsant drugs (ACDs) have multiple generic formulations currently available and patients are often transitioned between brand-name and generic formulations as cheaper options become available (Epilepsy Behav. 2004;5: 995-998; Neurology 2007;68:1245-1246). These substitutions often occur without physician or patient notification. For market approval, the FDA only requires that the generic compound show comparable bioequivalence to brand-name according to two bioavailability measures (the area under the drug concentration-time curve and maximum concentration) when tested on 24-36 healthy adults (Epilepsia. 2007;48 : 1825-1827). Different generic formulations are not required to fall within a comparable range from each other, inactive ingredients may differ, and the pharmacokinetics in medically complicated patients and children are not tested. Perhaps due to the narrow therapeutic range of many ACDs, many patients require switchback after generic substitution (Neurology 2008; 70: 2179-2186). We present a case series of pediatric and adult epilepsy patients followed at our institution who experienced significant adverse consequences temporally related to anticonvulsant formulation substitution requiring switchback to brand-name formulations. Methods: We performed a retrospective case series of patients with adverse events due to anticonvulsant formulation substitution and present brief vignettes on 3. Results: We identified 39 patients who reported 45 adverse events associated with formulation substitutions, as are shown in Table 1. Ages ranged from 3-31years (mean 13.4 years; SD 6.7 years). All patients returned to baseline after switching back to brand-name formulation with the exception of 9 patients who have not yet transitioned and 2 patients who developed a rash which did not resolve after switchback. Patient 1: A 14 year old girl with a baseline of 3-6 generalized tonic clonic (GTC) seizures per month on Keppra. Three days after transitioning to a generic formulation, her seizure frequency increased to 20-30 GTC seizures per night, which returned to baseline after switchback to brand-name. Patient 2: 10 year old girl with complex partial epilepsy and electrographic status epilepticus of sleep (ESES) who had been seizure free for 45 months on brand-name Keppra. Within 2 weeks after receiving a generic formulation of levetiracetam, she experienced cognitive decline and EEG revealed recurrent ESES. Cognition returned to baseline after switchback to brand-name. Patient 3: A 23 year old male with Angelman’s Syndrome and associated epilepsy who had been seizure free for over 14 years on Keppra. He developed an episode of status epilepticus 5 months after transition to generic levetiracetam. Conclusions: ACD formulation substitutions can be associated with significant morbidity in pediatric and adult epilepsy patients and should be elected with consent of the patient and treating physician. Prospective studies evaluating the indicidence of formulation change and adverse events are needed.