Vigabatrin Felbamate

Anticonvulsants (barbiturates, including phenobar-bital and primidone carbamazepine felbamate phenytoin topiramate vigabatrin)... 

II.e. 5.2. Interactions between first and second generation AEDs. Felbamate raises plasma concentrations of phenytoin, valproic acid and carbamazepine. Clearance of tiagabine, topiramate and zon-isamide is increased in the presence of an enzyme inducer. Vigabatrin reduces phenytoin concentrations after 4-5 weeks of comedication (via an unknown mechanism). For tiagabine, the elimination half-life may be reduced by 2-3 hours in the presence of an enzyme-induction AED. Lamotrigine elimination is slower if given with valproic acid. Topiramate reduces elimination of phenytoin. 

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. 

Neither vigabatrin nor gabapentin caused porphyrin accumulation in chicken embryo cultured liver cells, whereas felbamate, lamotrigine, and tiagabine were por-phyrinogenic in this model (129). For gabapentin, safety in porphyrias has been confirmed in preliminary clinical observations (SEDA-19, 70) (SEDA-20, 62). 

A review of the second-generation anticonvulsants reveals that screening or serendipity led to the development of felbamate (10), 1am-otrigine (11), zonisamide (13), topiramate (15), and levetiracetam (16) on the other hand, clobazam (4d) and oxcarbazepine (12) were developed by structural variation of known agents (78). Only three, vigabatrin (8), gabapentin (9), and tiagabine (14), were developed by mechanism-based rational development (78). 

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]. 

Barbiturates phenobarbital 1 Benzodiazepines alprazolam, diazepam, i lorazepam, oxazepam Carbamazepine, ethosuximide, valproic acid, phenytoin, diazepam, lorazepam, gabapentin, lamotrigine, felbamate, topiramate, tiagabin, vigabatrin... 

Newer agents Felbamate, gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin ... 

Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of antiseizure drugs in pediatric patients. Part II. Phenytoin, carbamazepine, sulthiame, lamotrigine, vigabatrin, oxcarbazepine, and felbamate. Clin Pharmacokinet 1995 29 341-369. 

Battino, D., Estienne, M., and Avanzini, G., Chnical pharmacokinetics of antiepUeptic drugs in paediatric patients. Part II. Phenytoin, carhamazepine, sulthiame, lamotrig-ine, vigabatrin, oxcarbazepine and felbamate, Clin. Pharmacokinet., 29 341-369,... 

No clinically relevant pharmacokinetic interactions appear to occur between vigabatrin and felbamate. 

In a study of 16 subjects, felbamate 2.4 g daily inereased the AUC of vigabatrin 2 g daily by 13%, which is unlikely to be elinieally signifieant. In a seeond study in a further 18 subjects, vigabatrin did not ect felbamate pharmaeokineties. There would therefore seem to be no reason for avoiding eoneurrent use. 

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