Felbamate

FELBAMATE

Felbamate has been approved and marketed in the USA and in some European countries. Although it is effective in some patients with partial seizures, the drug causes aplastic anemia and severe hepatitis at unexpectedly high rates and has been relegated to the status of a third-line drug for refractory cases.Felbamate appears to have multiple mechanisms of action. It produces a use-dependent block of the NMDA receptor, with selectivity for the NR1-2B subtype. It also produces a barbitu-rate-like potentiation of GABA_A receptor responses. Felbamate has a half-life of 20 hours (somewhat shorter when administered with either phenytoin or carbamazepine) and is metabolized by hydroxylation and conjugation; a significant percentage of the drug is excreted unchanged in the urine. When added to treat-ment with other antiseizure drugs, felbamate increases plasma phenytoin and valproic acid levels but decreases levels of carbamazepine.

In spite of the seriousness of the adverse effects, thousands of patients worldwide utilize this medication. Usual dosages are 2000–4000 mg/d in adults, and effective plasma levels range from 30 mcg/mL to 100 mcg/mL. In addition to its usefulness in partial seizures, felbamate has proved effective against the seizures that occur in Lennox-Gastaut syndrome.