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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 (August 2020)

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 HLA-B phenotypes based on genotypes
Table 2. Assignment of likely CYP2C9 phenotypes based on genotypes
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 genotype

Supplement to: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C9 and HLA-B Genotype and Phenytoin Dosing (August 2020)

Tables and figures included in the supplement or referenced in the guidelinea:

Supplemental Table S1. Evidence linking HLA allele to phenytoin cutaneous adverse drug reaction phenotype
Supplemental Table S2. 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
HLA-B frequency tables 
CYP2C9 allele definition table 
CYP2C9 allele functionality table 
CYP2C9 frequency table 
CYP2C9 diplotype-phenotype table 

Gene resource mappings

HLA-A and HLA-B gene reources mapping 

CYP2C9 gene resource mappings 

Drug resource mappings

Phenytoin

Fosphenytoin

Clinical decision supportb:

HLA-A and HLA-B consult text and implementation workflow 

Phenytoin pre- and post-test alerts and flow chart

Fosphenytoin pre- and post-test alerts and flow chart

aSome of the tables included in the guideline may have been updated online, 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.

Original guideline (November 2014) 

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