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 guideline^a:

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: Implementation workflow CYP2C9 consult HLA-B consult 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)

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

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