Antiepileptics 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. 

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. 

It would seem therefore that no dosage adjustments are normally needed if gabapentin is added to treatment with most of these antiepileptics. However, if gabapentin is added to pbenytoin it may be wise to bear the possibility of raised pbenytoin levels in mind. For mention that gabapentin may prolong the half-life of felbamate, see Felbamate + Gabapentin , p.540. For mention of the lack of interaction between levetiracetam and gabapentin, see Levetiracetam + Other antiepileptics , p.543. 

The activity of mesuximide is thought to be due to its active metabolite, A-desmethylmesuximide. Therefore, it has been suggested that levels of this metabolite should also be monitored. Anticipate the need to reduce the dose of mesuximide if felbamate is added. Other antiepileptics such as phenobarbital and phenytoin may also increase levels of A-desmethylm-esuximide. ... 

Any changes in the pharmacokinetics of oxcarbazepine brought about by other antiepileptics seem to be of minimal clinical relevance. However, the clinical relevance of the increase in the active metabolite monohydroxyoxcarbazepine with lamotrigine requires further study. In addition, there is the theoretical risk that monohydroxyoxcarbazepine levels might rise to toxic levels if carbamazepine or phenytoin were withdrawn. For mention that there may be an increase in adverse effects if oxcarbazepine is used with felbamate, see Oxcarbazepine +Felbamate , p.545. 

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. 

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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