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CPIC® Guideline for Phenytoin and CYP2C9 and HLA-B

Most recent guideline publication:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C9 and HLA-B Genotype and Phenytoin Dosing (November 2014)

Updates since publication:

No updates on dosing recommendations since publication.

Tables and figure provided in the main manuscript of the guideline:

Table 1. Assignment of likely phenotype based on diplotypes
Table 2. Recommended dosing of phenytoin/fosphenytoin based on HLA-B*15:02 and CYP2C9 phenotype/genotype
Figure 1. Algorithm for suggested clinical actions based on HLA-B*15:02 and CYP2C9 genotypes

Supplement to: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C9 and HLA-B Genotype and Phenytoin Dosing (November 2014)

Tables and figures included in the supplementa or referenced in the guideline:

Supplemental Table S1. Genotypes that constitute the * alleles for CYP2C9 For an updated version of this table see the CYP2C9 allele definition table .
Supplemental Table S2. Association between CYP2C9 allelic variants and CYP2C9 function For an updated version of this table see the CYP2C9 allele functionality table .
Supplemental Table S3. Worldwide Allele Frequencies* of HLA-B*15:02 – Summary by Region
Supplemental Table S4. Worldwide Allele Frequencies of HLA-B*15:02 – Detailed by Sample
Supplemental Table S5. CYP2C9*2 (rs1799853) and *3 (rs1057910) allele frequencies (%) in A) 1000 Genomes populations and B) Populations from International Warfarin Pharmacogenetic Consortium For an updated version of this table see the CYP2C9 frequency table .
Supplemental Table S6. Diplotype frequencies (%) for CYP2C9 alleles in 1000 Genomes populations For an updated version of this table see the CYP2C9 frequency table .
Supplemental Table S7. Regional Diplotype frequencies (%) for CYP2C9 alleles in 1000 Genomes populations For an updated version of this table see the CYP2C9 frequency table .
Supplemental Table S8. Evidence linking HLA-B*15:02 genotype to phenytoin cutaneous adverse drug reaction phenotype
Supplemental Table S9. Evidence linking CYP2C9 genotype to phenytoin metabolism and/or toxicities
Supplementary Figure S1. Metabolism of phenytoin or see PharmGKB Phenytoin Pathway, Pharmacokinetics
Supplementary Figure S2. Metabolism of fosphenytion to phenytoin
Supplemental Figure S3a. HLA-B*15:02 Pharmacogenetic Test Result: Clinical Implementation Workflow for EHR
Supplemental Figure S3b. CYP2C9 Pharmacogenetic Test Result: Clinical Implementation Workflow for EHR For an updated version of this table see the CYP2C9 diplotype-phenotype tableb.
Supplemental Figure S4a. HLA-B*15:02 Genotype and Phenytoin: Point of Care Clinical Decision Support
Supplemental Figure S4b. CYP2C9 Genotype and Phenytoin: Point of Care Clinical Decision Support
Supplemental Figure S4c. HLA-B*15:02 and CYP2C9 Genotype and Phenytoin: Point of Care Clinical Decision Support
Supplemental Table S10. Drug(s) that pertain to this guideline
Supplemental Table S11. Genes that pertain to this guideline For an updated version of this table see the CYP2C9 gene resource mapping .
Supplemental Table S12a. Translation of HLA-B Genotype Test Results into Interpreted Phenotype
Supplemental Table S12b. Translation of CYP2C9 Genotype Test Results into Interpreted Phenotype For an updated version of this table see the CYP2C9 diplotype-phenotype tableb.
Supplemental Table S13a. Example Implementation of this Guideline for HLA-B: Pharmacogenetic Genotype/Phenotype Summary Entries
Supplemental Table S13b. Example Implementation of this Guideline for CYP2C9: Pharmacogenetic Genotype/Phenotype Summary Entries For an updated version of this table see the CYP2C9 diplotype-phenotype tableb.
Supplemental Table S14a. Example Implementation of this Guideline: Point of Care Clinical Decision Support (HLA-B)
Supplemental Table S14b. Example Implementation of this Guideline: Point of Care Clinical Decision Support (CYP2C9)
Supplemental Table S14c. Example Implementation of this Guideline: Point of Care Clinical Decision Support (CYP2C9 and HLA-B)

aSome of the tables included in the guideline may have been updated on-line, particularly to reflect newly described or newly characterized alleles. These include the gene-specific information tables (https://www.pharmgkb.org/page/pgxGeneRef) that support CPIC guidelines by providing information regarding star (*) allele definitions, allele function, allele frequency by major ethnic groups, translations of diplotype to phenotype, and gene resource mappings.

bThese resources support the adoption of CPIC guidelines into the electronic health record with clinical decision support and provide information that clinical implementers find helpful.

 

This guideline has been endorsed by the American Society of Health-System Pharmacists (ASHP).