indication

For use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use.

pharmacology

Felbamate is an antiepileptic indicated as monotherapy or as an adjunct to other anticonvulsants for the treatment of partial seizures resulting from epilepsy. Receptor-binding studies in vitro indicate that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding, and is devoid of activity at the MK-801 receptor binding site of the NMDA receptor-ionophore complex. However, felbamate does interact as an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex.

mechanism of action

The mechanism by which felbamate exerts its anticonvulsant activity is unknown, but in animal test systems designed to detect anticonvulsant activity, felbamate has properties in common with other marketed anticonvulsants. In vitro receptor binding studies suggest that felbamate may be an antagonist at the strychnine-insensitive glycine-recognition site of the N-methyl-D-aspartate (NMDA) receptor-ionophore complex. Antagonism of the NMDA receptor glycine binding site may block the effects of the excitatory amino acids and suppress seizure activity. Animal studies indicate that felbamate may increase the seizure threshold and may decrease seizure spread. It is also indicated that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding.

toxicity

LD₅₀=5000 mg/kg (Orally in rats)

biotransformation

Hepatic

absorption

>90%

half life

20-23 hours

drug interactions

Carbamazepine: Decreased effect of both products

Ethotoin: Increased phenytoin levels and decreased felbamate levels

Fosphenytoin: Increased phenytoin levels and decreased felbamate levels

Mephenytoin: Increased phenytoin levels and decreased felbamate levels

Phenobarbital: Felbamate increases the effect and toxicity of phenobarbital/primidone

Phenytoin: Increased phenytoin levels and decreased felbamate levels

Primidone: Felbamate may increase the effect and toxicity of primidone.

Quinupristin: This combination presents an increased risk of toxicity

Telithromycin: Telithromycin may reduce clearance of Felbamate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Felbamate if Telithromycin is initiated, discontinued or dose changed.

Triprolidine: The CNS depressants, Triprolidine and Felbamate, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Valproic Acid: Felbamate, a CYP2C19 inhibitor, may decrease the metabolism of Valproic acid, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Felbamate is initiated, discontinued or dose changed.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of felbamate by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of felbamate if voriconazole is initiated, discontinued or dose changed.