Vigabatrin Phenobarbital

VIGABATRIN 1. BARBITURATES-phenobarbital, primidone 2. PHENYTOIN i levels of these antiepileptics Possibly induction of metabolism Watch for poor response to these antiepileptics... 

Bromide (1857) was the first drug to be used for the treatment of epilepsy, but it is now obsolete. Phenobarbital, introduced in 1912, controlled patients resistant to bromides. The next success was the discovery in 1938 of phenytoin (a hydantoin) which is structurally related to the barbiturates. Since then many other drugs have been discovered, but phenytoin still remains a drug of choice in the treatment of major epilepsy. Over the past ten years there has been a dramatic increase in the number of new anticonvulsant drugs (vigabatrin, gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam), but none has been shown to be superior to the major standard anticonvulsants (phenytoin, carbamazepine and sodium valproate). 

Clinically important, potentially hazardous interactions with carbamazepine, lamotrigine, phenobarbital, primidone, topiramate, valproic acid, vigabatrin... 

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... 

Vigabatrin causes a trivial decrease in phenobarbital and primidone levels. There is some evidence that phenobarbital may reduce the efficacy of vigabatrin in infantile spasms. 

In an early clinical study, vigabatrin 2 to 3 g daily did not change the serum levels of phenobarbital in 26 patients. Similarly, another study found that phenobarbital levels were not significantly altered by vigabatrin. Another study found that vigabatrin caused serum level reductions of 7% with phenobarbital and 11% with primidone. Alterations of this size would not be expected to be clinically significant. 

There is some evidence that the efficacy of vigabatrin for infantile seizures may be reduced in those taking phenobarbital. The median time to response after starting vigabatrin was 3 days in 3 infants not taking phenobarbital and 34 days in 6 patients taking phenobarbital. Three patients did not respond to vigabatrin until after phenobarbital was withdrawn. ... 

There appears to be no change in phenobarbital levels with vigabatrin, but some suggestion that vigabatrin may be less effective for infantile spasms in the presence of phenobarbital. Bear this possibility in mind. 

Spence SJ, Nakagawa J, Sankar R, Shields WD. Phenobarbital interferes with the efficacy of vigabatrin in treating infantile spaans in patients with tuberous sclerosis. Epilepsia (2000) 41 (Suppl 7), 189. 

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