Antiepileptic drugs felbamate

I. M. Kapetanovic, C. D. Torchin, C. D. Thompson, T. A. Miller, P. J. McNeilly, M. L. Macdonald, H. J. Kupferberg, J. L. Perhach, R. D. Sofia, J. M. Strong, Potentially Reactive Cyclic Carbamate Metabolite of the Antiepileptic Drug Felbamate Produced by Human Liver Tissue in vitro, Drug Metab. Dispos. 1998, 26, 1089 -1095. 

The following method describes the analysis of the basic antiepileptic drugs felbamate, lamotrigine, carbamazepine, carbamazepine-10,11-epoxide, gabapentin, pregabalin, levetirac-etam, and oxcarbazepine monohydroxy derivative (oxcarb MHD) in human plasma using a combination of zinc sulfate and acetonitrile-induced protein precipitation followed by LC-MS/MS. 

Leone, A.M. et al. (2007) Evaluation of felbamate and other antiepileptic drug toxicity potential based on hepatic protein covalent binding and gene expression. Chemical Research in Toxicology, 20 (4), 600-608. 

Curry, W.J. and Kulling, D.L. (1998) Newer antiepileptic drugs ga-bapentin, lamotrigine, felbamate, topiramate and fosphenytoin. Am Fam Physician 57 513-520. 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

Felbamate is a broad-spectrum antiepileptic drug, whose use has been drastically curtailed owing to the risks of aplastic anemia and hepatotoxicity. 

Devinsky O, Vasquez B, Luciano D. New antiepileptic drugs for children Felbamate, gabapentin, lamotri-gine, and vigabatrine. J Child Neurol 1994 9(Suppl) S33-45. 

Importantly, Loscher et al. found that carbamazepine, felbamate, gabapentin, lamotrigine, phenobarbital, and topiramate are substrates of ABCBl (P-gp) [38]. Crowe et al. also studied the transport of a variety of antiepileptic drugs including vigabatrin, gabapentin, phenobarbitone, lamotrigine, phenytoin, carbamazepine, and acetazolamide in colorectal tumor-derived Caco-2 cell monolayers. They found that only one antiepileptic, acetazolamide, is a weak ABCBl substrate [39]. 

Of the newer antiepilepties, both felbamate and topiramate are weak inducers of CYP3A4. They may also inhibit CYP2C19. They are also partially metabolised by the cytochrome P450 isoenzyme system, so may have their metabolism altered by other drugs such as the older enzyme-inducing antiepileptics. 

None of the interactions between the benzodiazepines and antiepileptics described here appear to be of major clinical importance, with the possible exception of the interaction between clobazam and felbamate. If both drugs are given be aware that additive sedative or other adverse effects may occur. This may also be possible in some rare cases with chlordiazepoxide or clobazam and phenobarbital clonazepam and lamotrigine or primidone and clorazepate and primidone. 

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