Introduction
Phenytoin is a frequently used drug treatment for
epilepsy. Genetic polymorphisms in the metabolism of
phenytoin, particularly
CYP2C9, are strongly associated with increased plasma concentrations and can result in toxicity.
Human leukocyte antigen (HLA) alleles are well-known genetic predictors of certain
antiepileptic drug-associated severe cutaneous adverse reactions (
SCAR), including
Stevens-Johnson syndrome (SJS) and
toxic epidermal necrolysis (TEN). Recent pharmacogenomic studies show genetic polymorphisms in
CYP2C9, as well as HLA alleles, are significantly associated with
phenytoin-related
SCAR. Areas covered Updated pharmacogenomic information of
CYP2C9 variants and HLA alleles involved in
phenytoin-associated cutaneous
adverse drug reactions (cADRs) are discussed in this article. Expert opinion
CYP2C9*3 has been identified as the most significant genetic variant associated with increased
phenytoin concentrations and adverse events. Recent pharmacogenomic findings reveal that
CYP2C9*3 and HLA alleles, i.e.
HLA-B*15:02,
HLA-B*13:01, and
HLA-B*51:01, are important genetic variants in the occurrence of
phenytoin-induced cADRs or
SCAR. A phenotype- and population-specific multigene panel can be used before prescribing to predict
phenytoin-induced cADRs and further guide optimal dose selection.