Epilepsy felbamate

Felbamate (Felbatol) was introduced with the expectation that it would become a major drug in the treatment of epilepsy. Felbamate exhibited few manifestations of serious toxicity in early clinical trials. Soon after its introduction, however, it became apparent that its use was associated with a high incidence of aplastic anemia. Consequently, felbamate is indicated only for patients whose epilepsy is so severe that the risk of aplastic anemia is considered acceptable. 

Excitatory neurotransmitters also may be involved in the appearance of epilepsy, since the bursting activity typically seen during epileptic discharges may be due in part to the action of glutamate acting on A-methyl-o-aspartate (NMDA) receptor channels to produce depolarization. It is likely that a major part of the anticonvulsant activity of felbamate involves blockade of the NMDA receptor. Table 32.2 summarizes the most likely mechanism of action associated with available anticonvulsant drugs. 

Sachdeo RC, Narang-Sachdeo S, Montgomery PA, Shumaker RC, Perhach JL, Lyness WH, Rosenberg A. Evaluation of the potential interaction between felbamate and erythromycin in patients with epilepsy. J Chn Pharmacol 1998 38(2) 184-90. 

Assessment of its benefit to harm balance does not support the use of felbamate in new-onset epilepsy in children and adults, in patients who have significant prior hematological adverse events, in patients in whom follow-up and comph-ance will not allow careful monitoring, and in patients who are unable to discuss risk/benefits and for whom no parent or legal guardian is available to provide consent... 

French J, Smith M, Faught E, Brown L. Practice advisory the use of felbamate in the treatment of patients with intractable epilepsy. Epilepsia 1999 40 803-8. 

Cilio MR, Kartashov AI, Vigevano F. The long-term use of felbamate in children with severe refractory epilepsy. Epilepsy Res 2001 47(l-2) l-7. 

Palmer KJ, McTavish D. Felbamate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in epilepsy. Drugs 1993 45(6) 1041-65. 

Ganger R, Vignoli A, Bonardi R, Guidolin L. Felbamate in refractory partial epilepsy. Epilepsy Res 1999 34(l) 43-8. 

Carmant L, Holmes GL, Sawyer S, Rifai N, Anderson J, Mikati MA. Efficacy of felbamate in therapy for partial epilepsy in children. J Pediatr 1994 125(3) 481-6. 

Felbamate. Felbamate is an adjuvant anticonvulsant, containing the warning that its use is associated with a marked increase in the incidence of aplastic anemia and that patients being started on the drug should have liver function tests performed before therapy is initiated. Animal studies have revealed a statistically significant increase in hepatic cell adenomas in high dose studies (18). It is postulated that this cancer was induced by toxic by-products urethane and methyl carbamate. Felbamate is not recommended as first-line therapy and is indicated for those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia or liver failure is deemed acceptable in light of the benefits provided by its use. 

Gidal BE, Kanner A Maly M, Rutecki P, Lensmeyer GL. Lamotr ine ikarmacokinetics in patients receiving felbamate. Epilepsy Res (1997)... 

Contin RivaR, Albani F, Baruzzi A. Effect of felbamate on clobazam and its metabolite kinetics in patients with epilepsy. Ther Drug Monit ( 999)2, 604-8. 

A method for the analysis of the basic antiepileptic compounds felbamate, lamotrigine, carbamazepine, carbamazepine-10,11-epoxide, gabapentin, pregabalin, levetiracetam, and oxcarbazepine monohydroxy derivative (oxcarb MHD) in human plasma is described. This protocol incorporates a simplified sample preparation step followed by quantitative high performance chromatography-tandem mass spectrometry detection of commonly prescribed and monitored anticonvulsant drugs. Since polytherapy is common in epilepsy patients, use of a multiconstituent assay can improve laboratory efficiency and reduce required analytical time. 

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