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Of the AEDs illustrated in Table 1, four (carbamazepine, phenytoin, primidone and
phenobarbital) are potent enzyme inducers. Valproate and stiripentol are potent inhibitors.
Phenytoin has some rather unique characteristics in that in addition to being an enzyme
inducer, it is only loosely bound to CYP isoenzymes. It also exhibits saturation metabolic
characteristics making it particularly susceptible to inhibitory interactions. Of the newly
licensed AEDs, gabapentin, lacosamide, levetiracetam, pregabalin and vigabatrin uniquely
do not appear to affect the concentrations of other AEDs. In contrast eslicarbazepine acetate,
lamotrigine, felbamate, oxcarbazepine, tiagabine, topiramate and zonisamide are associated
with numerous clinically significant interactions.

Finally, in the past few years, interactions relating to the selective inhibition of the
metabolism of carbamazepine to its epoxide metabolite, or subsequent metabolism of the
epoxide, have been described. These may have considerable clinical significance, particularly
since there is increasing evidence to suggest that the epoxide may contribute not only to the
efficacy of carbamazepine but also to its toxicity. Carbamazepine epoxide plasma
concentrations can be quadrupled in some patients by valproate, usually in the absence of
changes in carbamazepine, and precipitating toxicity. With the more widespread availability
of therapeutic monitoring of the epoxide, these interactions are increasingly being identified.

Further reading

JOHANNESSEN LANDMARK C, PATSALOS PN. Drug interactions involving the new second- and third-generation
antiepileptic drugs. Exp Rev Neurotherapeutics 2010; 10: 119-140.
PATSALOS PN. Anti-Epileptic Drug Interactions. A Clinical Guide. Springer, 2013.
PATSALOS PN, FROSCHER W, PISANI F, VAN RIJN CM. The importance of drug interactions in epilepsy therapy.
Epilepsia 2002; 43: 365-385.
PATSALOS PN. Drug interactions with the newer antiepileptic drugs (AEDs). Part 1: Pharmacokinetic and
pharmacodynamic interactions between AEDs. Clin Pharmacokinet 2013; 52: 927-966.
PATSALOS PN. Drug interactions with the newer antiepileptic drugs (AEDs). Part 2: Pharmacokinetic and
pharmacodynamic interactions between AEDs and drugs used to treat non-epilepsy disorders. Clin Pharmacokinet 2013;
52: 1045-1061.
PATSALOS PN, PERUCCA E. Clinically important interactions in epilepsy: General features and interactions between
antiepileptic drugs. Lancet Neurol 2003; 2: 347-356.
PATSALOS PN, PERUCCA E. Clinically important interactions in epilepsy: Interactions between antiepileptic drugs
and other drugs. Lancet Neurol 2003; 2: 473-481.