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Clin Pharmacol Ther. 2014 Aug 6. doi: 10.1038/clpt.2014.159. [Epub ahead of print]

Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing.

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  • 1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • 2Department of Medicinal Chemistry, University of Washington School of Pharmacy, Seattle, Washington, USA.
  • 3Department of Genetics, Stanford University, Palo Alto, California, USA.
  • 4Division of Pediatric Neurology, Department of Neurology, Indiana University, Indianapolis, Indiana, USA.
  • 5Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
  • 61] Laboratory for International Alliance on Genomic Research, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan [2] National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan [3] School of Chinese Medicine, China Medical University, Taichung, Taiwan.
  • 71] Division of Clinical Pharmacology, Department of Medicines, Indiana University School of Medicine and Pharmacology/Toxicology, Indianapolis, Indiana, USA [2] Department of Veterans Affairs, RLR VA Medical Center, Indianapolis, Indiana, USA.


Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large interpatient variability, partly due to genetic variations in the gene encoding cytochrome P450 (CYP)2C9 (CYP2C9). Furthermore, the variant allele HLA-B*15:02, encoding human leukocyte antigen, 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: http://www.pharmgkb.org). The purpose of this guideline is to provide information for the interpretation of HLA-B and/or CYP2C9 genotype tests so that the results can guide dosing and/or use of phenytoin. Detailed guidelines for the use of phenytoin as well as analyses of cost-effectiveness are out of scope. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are periodically updated at http://www.pharmgkb.org.Clinical Pharmacology & Therapeutics (2014); advance online publication 17 September 2014. doi:10.1038/clpt.2014.159.

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