CPIC® Guideline for Tamoxifen based on CYP2D6 genotype
Most recent guideline publication:
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy (January 2018)
Updates since publication:
October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CYP2D6 genotype to phenotype across guidelines (i.e. CPIC and DPWG) and between clinical genetic testing laboratories. CPIC recently conducted a modified-Delphi project to obtain consensus among a panel of international CYP2D6 experts for a uniform system for translating CYP2D6 genotype to phenotype (more information). Modifications to CPIC’s prior system include downgrading the value assigned to the CYP2D6*10 allele for activity score calculation from 0.5 to 0.25 and changing the phenotype assignment for an activity score of 1 from normal metabolizer to intermediate metabolizer (table of all previous and new phenotype groupings).
As a result, the following changes have been made in the CYP2D6 allele functionality table, CYP2D6 genotype to phenotype table, Tamoxifen pre- and post-test alerts and flow chart:
- Activity scores of 1 changed from CYP2D6 normal metabolizer to CYP2D6 intermediate metabolizer.
- Impact on the recommendations in this guideline: The current guideline has a specific recommendation for AS of 1 (no CYP2D6*10 allele present); thus, the current published recommendations for normal and intermediate metabolizers will remain unchanged.
- All activity scores for diplotypes containing a CYP2D6*10 allele have been updated accordingly (activity scores changed to reflect activity value of 0.25). See table of all previous and new phenotype groupings.
- Impact on the recommendations in this guideline: The recommendations for ultrarapid and normal metabolizers are the same so this change does not impact the recommended prescribing recommendations. The recommendations for the activity score of 1 (with a CYP2D6*10 allele present) and 0.5 are the same so the current published recommendations for CYP2D6*10/*10 will remain unchanged.
Tables provided in the main manuscript of the guideline:
|Table 1. Assignment of likely CYP2D6 phenotypes based on diplotypes|
|Table 2. Dosing Recommendations for tamoxifen based on CYP2D6 phenotype|
Supplement to: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy (January 2018)
Tables and figures provided in the guideline publication supplement or referenced in the guidelinea:
|Supplemental Table S1. Association between allelic variants and CYP2D6 enzyme activity|
|Supplemental Table S2. Evidence linking CYP2D6 to tamoxifen phenotype|
|CYP2D6 allele definition table|
|CYP2D6 allele functionality table|
|CYP2D6 frequency table|
|CYP2D6 diplotype-phenotype table|
|Gene Resource Mapping|
|Drug Resource Mapping|
|Clinical Decision Support: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).