Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing.

Authors

K E Caudle, Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital
A E Rettie, Department of Medicinal Chemistry, University of Washington, School of Pharmacy
M Whirl-Carrillo, Department of Genetics, Stanford University
L H Smith, Division of Pediatric Neurology, Department of Neurology, Indiana University
Scott Mintzer, Department of Neurology, Thomas Jefferson UniversityFollow
M T M Lee, Laboratory for International Alliance on Genomic Research, RIKEN Center for Integrative Medical Sciences; National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica; School of Chinese Medicine, China Medical University
T E Klein, Department of Genetics, Stanford University
J T Callaghan, Department of Medicines, Indiana University, School of Medicine and Pharmacology/Toxicology; Department of Veterans Affairs, RLR VA Medical Center

Document Type

Article

Publication Date

9-17-2014

Comments

This article has been peer reviewed. It was published in: Clinical Pharmacology and Therapeutics.

Volume 96, Issue 5, 17 September 2014, Pages 542-548.

The published version is available at DOI: 10.1038/clpt.2014.159

Copyright © 2014 The Authors

Abstract

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.

Recommended Citation

Caudle, K E; Rettie, A E; Whirl-Carrillo, M; Smith, L H; Mintzer, Scott; Lee, M T M; Klein, T E; and Callaghan, J T, "Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing." (2014). Department of Neurology Faculty Papers. Paper 83.
https://jdc.jefferson.edu/neurologyfp/83

PubMed ID

25099164