lunes, 22 de septiembre de 2014

Clinical Pharmacology & Therapeutics - Abstract of article: Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing

Clinical Pharmacology & Therapeutics - Abstract of article: Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing



Pharmacogenomics

CPIC Guidelines

Clinical Pharmacology & Therapeutics advance online publication 17 September 2014; doi: 10.1038/clpt.2014.159

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

K E Caudle1, A E Rettie2, M Whirl-Carrillo3, L H Smith4, S Mintzer5, M T M Lee6,7,8, T E Klein3 and J T Callaghan9,10
  1. 1Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
  2. 2Department of Medicinal Chemistry, University of Washington School of Pharmacy, Seattle, Washington, USA
  3. 3Department of Genetics, Stanford University, Palo Alto, California, USA
  4. 4Division of Pediatric Neurology, Department of Neurology, Indiana University, Indianapolis, Indiana, USA
  5. 5Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  6. 6Laboratory for International Alliance on Genomic Research, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  7. 7National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
  8. 8School of Chinese Medicine, China Medical University, Taichung, Taiwan
  9. 9Division of Clinical Pharmacology, Department of Medicines, Indiana University School of Medicine and Pharmacology/Toxicology, Indianapolis, Indiana, USA
  10. 10Department of Veterans Affairs, RLR VA Medical Center, Indianapolis, Indiana, USA
Correspondence: K E Caudle, (Kelly.caudle@stjude.org or cpic@pharmgkb.org)
Received 10 June 2014; Accepted 31 July 2014
Accepted article preview online 6 August 2014; Advance online publication 17 September 2014
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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 CYP2C9and/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 athttp://www.pharmgkb.org.

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