Abstracts

Adjunctive-therapy anti-epileptic drugs (AEDs) such as levetiracetam and gabapentin are usually not indicated for monotherapy in patients with partial onset and secondarily generalized seizure disorders. However, little is known about combined therapy with levetiracetam and gabapentin in epileptic patients with phenytoin liver toxicity, who cannot tolerate AEDs with hepatic metabolism. In a prospective study, patients were selected if they had partial onset and secondarily generalized epilepsy demonstrated clinically and by electroencephalogram (EEG), were in monotherapy with phenytoin, and had developed elevated liver enzymes, which included alanine amino-transferase (ALT) and aspartate amino-transferase (AST). After seven days of combined therapy with levetiracetam and gabapentin, patients were tapered from phenytoin in three to five days. From January 2, 2003 to April 1, 2005, twelve patients fulfilled the selection criteria. There were eight men and four women, ages 31 to 91 years. All of them had partial onset and secondarily generalized epilepsy confirmed by EEG and had been taking phenytoin monotherapy at least for three months after which they developed increasing titers of ALT and AST. They had achieved good control of their seizures while taking phenytoin in doses from 300 to 500 mg/day. Levetiracetam was introduced in a dose of 500 mg PO bid for three days, followed by 1000 mg PO bid for another three days, reaching up to 1500 mg PO bid on day seven. Gabapentin was started simultaneously in a dose of 300 mg PO tid and, on day 7, increased up to 600 mg PO tid. Phenytoin was tapered in three to five days, after seven days of combined therapy with levetiracetam and gabapentin. All patients continued to achieve good control of their seizures and, within two to four weeks, developed nomal levels of ALT and AST. Adjunctive-therapy AEDs such as levetiracetam and gabapentin, which are known to have none or little hepatic metabolism, may be used safely as combined therapy AEDs in epileptic patients who, after receiving phenytoin monotherapy, have developed hepatic toxicity.