Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C9 and HLA-B Genotype and Phenytoin Dosing.

Caudle KE1, Rettie AE2, Whirl-Carrillo M3, Smith LH4, Mintzer SE5, Lee MT6, Klein TE3, Callaghan JT7.

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Abstract

Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large inter-patient variability partly due to genetic variations in CYP2C9. Furthermore, the variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotype (also available on PharmGKB: www.pharmgkb.org).Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 06 August 2014; doi:10.1038/clpt.2014.159.