P 1176. Unfamiliar Interactions of Antiepileptic Drugs

Background: About 20 to 30% of epilepsies in childhood and adolescents are therapy resistant and require antiepileptic polytherapy. Drug interactions constitute a relevant problem in this situation. However, the magnitude of drug level changes might be individually different and is often not predictable. Although most interactions are known, interactions of new or rarely used antiepileptic drugs might be unpredictable.

Methods: We report two unfamiliar interactions by means of two case reports.

Results: Patient 1: A 12-year-old boy presented with epilepsy (Lennox–Gastaut’s syndrome) due to a large focal cortical dysplasia, following incomplete resection, polytherapy with phenobarbital, ethosuximide, clobazam, felbamate, and pregabalin. Very complicated course of disease with frequent tonic and tonic-clonic seizures, absences, and obtundation status. As part of therapy adjustment reduction of felbamate. Concomitant drop of the nor-clobazam level with the clinical picture of benzodiazepine withdrawal and acute worsening of seizures.

Patient 2: An 18-year-old young woman presented with progressive myoclonic epilepsy (Lafora’s disease), frequent epileptic, and nonepileptic myoclonic seizures. Polytherapy with valproate, topiramate, clobazam, and perampanel was done. Due to worsening of seizures, stiripentol was added to increase nor-clobazam serum level and to avoid tachyphylaxia. During the next few weeks, the patient’s general condition became worse due to a massive increase of the perampanel blood level into the toxic range (> 2,000 ng/mL). She had mild proteinuria and hypoproteinemia with peripheral edema as a questionable consequence of the high serum level. As an immediate improvement of symptoms,the dose of stiripentol and perampanel has been reduced.

Conclusion: Interactions of antiepileptic drugs might be the cause of side effects or changes in seizure frequency. Not all potential drug interactions are well known. Especially when taking new and/or rarely used drugs, any unexplained deterioration of seizure frequency or general condition should prompt measurement of serum drug levels and adjustment of doses if necessary.