CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. The levels (A,

B, C, and D)

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR OPIOIDS AND CYP2D6, OPRM1, AND COMT Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy (December 2020) Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of predicted CYP2D6 phenotypes based on diplotypes Table 2. Codeine therapy recommendations based on CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CLINICAL PHARMACOGENETICS IMPLEMENTATION CONSORTIUM (CPIC Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing KA Birdwell1,2, B Decker3, JM Barbarino4, JF Peterson2,5, CM Stein2,6, W Sadee7, D Wang7, AA Vinks8,9, YHe10, JJ Swen11, JS Leeder12, RHN van Schaik13, KE Thummel14, TE Klein4, KE Caudle15 and IAM MacPhee16 Tacrolimus is the mainstay immunosuppressant drug used after CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. The levels (A,

B, C, and D)

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR OPIOIDS AND CYP2D6, OPRM1, AND COMT Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy (December 2020) Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of predicted CYP2D6 phenotypes based on diplotypes Table 2. Codeine therapy recommendations based on CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CLINICAL PHARMACOGENETICS IMPLEMENTATION CONSORTIUM (CPIC Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing KA Birdwell1,2, B Decker3, JM Barbarino4, JF Peterson2,5, CM Stein2,6, W Sadee7, D Wang7, AA Vinks8,9, YHe10, JJ Swen11, JS Leeder12, RHN van Schaik13, KE Thummel14, TE Klein4, KE Caudle15 and IAM MacPhee16 Tacrolimus is the mainstay immunosuppressant drug used after

ABOUT US – CPIC

Kelly E. Caudle, PharmD, PhD, BCPS, FCCP CPIC Co-PI/Director, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN Dr. Caudle received her Pharm.D. and Ph.D. from The University of Tennessee Health Science Center and completed an ASHP-accredited PGY2 residency at Le Bonheur Children’s Hospital in Memphis, TN. She is also a LICENSING AND TERMS OF USE FOR CPIC CONTENT The information on this website is not intended for direct diagnostic use or medical decision-making without review by a health care

professional.

CPIC® GUIDELINE FOR NSAIDS BASED ON CYP2C9 GENOTYPE Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and NSAID Therapy (March 2020) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely CYP2C9 phenotypes based on genotypes Table 2. Therapeutic CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function 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 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 CPIC® GUIDELINE FOR SELECTIVE SEROTONIN REUPTAKE Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors (August 2015) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPIC® GUIDELINE FOR TRICYCLIC ANTIDEPRESSANTS AND CYP2D6 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update (December 2016) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPIC® GUIDELINE FOR HLA GENOTYPE AND USE OF CARBAMAZEPINE Most recent guideline publication Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update (December 2017) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of HLA-B and HLA-A CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. The levels (A,

B, C, and D)

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR OPIOIDS AND CYP2D6, OPRM1, AND COMT Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy (December 2020) Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of predicted CYP2D6 phenotypes based on diplotypes Table 2. Codeine therapy recommendations based on CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CLINICAL PHARMACOGENETICS IMPLEMENTATION CONSORTIUM (CPIC Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing KA Birdwell1,2, B Decker3, JM Barbarino4, JF Peterson2,5, CM Stein2,6, W Sadee7, D Wang7, AA Vinks8,9, YHe10, JJ Swen11, JS Leeder12, RHN van Schaik13, KE Thummel14, TE Klein4, KE Caudle15 and IAM MacPhee16 Tacrolimus is the mainstay immunosuppressant drug used after CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. The levels (A,

B, C, and D)

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR OPIOIDS AND CYP2D6, OPRM1, AND COMT Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy (December 2020) Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of predicted CYP2D6 phenotypes based on diplotypes Table 2. Codeine therapy recommendations based on CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CLINICAL PHARMACOGENETICS IMPLEMENTATION CONSORTIUM (CPIC Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing KA Birdwell1,2, B Decker3, JM Barbarino4, JF Peterson2,5, CM Stein2,6, W Sadee7, D Wang7, AA Vinks8,9, YHe10, JJ Swen11, JS Leeder12, RHN van Schaik13, KE Thummel14, TE Klein4, KE Caudle15 and IAM MacPhee16 Tacrolimus is the mainstay immunosuppressant drug used after

ABOUT US – CPIC

Kelly E. Caudle, PharmD, PhD, BCPS, FCCP CPIC Co-PI/Director, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN Dr. Caudle received her Pharm.D. and Ph.D. from The University of Tennessee Health Science Center and completed an ASHP-accredited PGY2 residency at Le Bonheur Children’s Hospital in Memphis, TN. She is also a LICENSING AND TERMS OF USE FOR CPIC CONTENT The information on this website is not intended for direct diagnostic use or medical decision-making without review by a health care

professional.

CPIC® GUIDELINE FOR NSAIDS BASED ON CYP2C9 GENOTYPE Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and NSAID Therapy (March 2020) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely CYP2C9 phenotypes based on genotypes Table 2. Therapeutic CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function 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 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 CPIC® GUIDELINE FOR SELECTIVE SEROTONIN REUPTAKE Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors (August 2015) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPIC® GUIDELINE FOR TRICYCLIC ANTIDEPRESSANTS AND CYP2D6 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update (December 2016) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPIC® GUIDELINE FOR HLA GENOTYPE AND USE OF CARBAMAZEPINE Most recent guideline publication Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update (December 2017) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of HLA-B and HLA-A CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. LICENSING AND TERMS OF USE FOR CPIC CONTENT The information on this website is not intended for direct diagnostic use or medical decision-making without review by a health care

professional.

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR TRICYCLIC ANTIDEPRESSANTS AND CYP2D6 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update (December 2016) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. LICENSING AND TERMS OF USE FOR CPIC CONTENT The information on this website is not intended for direct diagnostic use or medical decision-making without review by a health care

professional.

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR TRICYCLIC ANTIDEPRESSANTS AND CYP2D6 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update (December 2016) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of

ABOUT US – CPIC

Kelly E. Caudle, PharmD, PhD, BCPS, FCCP CPIC Co-PI/Director, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN Dr. Caudle received her Pharm.D. and Ph.D. from The University of Tennessee Health Science Center and completed an ASHP-accredited PGY2 residency at Le Bonheur Children’s Hospital in Memphis, TN. She is also a

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR OPIOIDS AND CYP2D6, OPRM1, AND COMT Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy (December 2020) Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of predicted CYP2D6 phenotypes based on diplotypes Table 2. Codeine therapy recommendations based on 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

CONTACT (OLD)

CPIC Communication There are a few different ways to stay in touch with CPIC. I have a question or comment. Contact us with any questions or comments Contact CPIC I want to get announcements. CPIC has a public announcement list that anyone can join.The announcements include guideline updates, news, and solicitation of feedback. Sign Up CPIC® GUIDELINE FOR CLOPIDOGREL AND CYP2C19 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 update (September 2013) Updates since publication: March 2017: The FDA-approved label for clopidogrel (Plavix) was recently updated (September 2016) and warns that patients who are CYP2C19 poor metabolizers may have diminished DPYD CPIC GUIDELINES CPIC guideline for fluoropyrimidines based on DPYD genotype For gene-specific information tables (i.e. DPYD allele definition, allele functionality, and frequency tables) see CPIC® GUIDELINE FOR SELECTIVE SEROTONIN REUPTAKE Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors (August 2015) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPIC® GUIDELINE FOR SIMVASTATIN AND SLCO1B1 Most recent guideline publication: The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1 and Simvastatin-induced Myopathy: 2014 Update (October 2014) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely SLCO1B1 phenotype CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. LICENSING AND TERMS OF USE FOR CPIC CONTENT The information on this website is not intended for direct diagnostic use or medical decision-making without review by a health care

professional.

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR TRICYCLIC ANTIDEPRESSANTS AND CYP2D6 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update (December 2016) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. LICENSING AND TERMS OF USE FOR CPIC CONTENT The information on this website is not intended for direct diagnostic use or medical decision-making without review by a health care

professional.

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR TRICYCLIC ANTIDEPRESSANTS AND CYP2D6 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update (December 2016) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of

ABOUT US – CPIC

Kelly E. Caudle, PharmD, PhD, BCPS, FCCP CPIC Co-PI/Director, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN Dr. Caudle received her Pharm.D. and Ph.D. from The University of Tennessee Health Science Center and completed an ASHP-accredited PGY2 residency at Le Bonheur Children’s Hospital in Memphis, TN. She is also a

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR OPIOIDS AND CYP2D6, OPRM1, AND COMT Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy (December 2020) Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of predicted CYP2D6 phenotypes based on diplotypes Table 2. Codeine therapy recommendations based on 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

CONTACT (OLD)

CPIC Communication There are a few different ways to stay in touch with CPIC. I have a question or comment. Contact us with any questions or comments Contact CPIC I want to get announcements. CPIC has a public announcement list that anyone can join.The announcements include guideline updates, news, and solicitation of feedback. Sign Up CPIC® GUIDELINE FOR CLOPIDOGREL AND CYP2C19 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 update (September 2013) Updates since publication: March 2017: The FDA-approved label for clopidogrel (Plavix) was recently updated (September 2016) and warns that patients who are CYP2C19 poor metabolizers may have diminished DPYD CPIC GUIDELINES CPIC guideline for fluoropyrimidines based on DPYD genotype For gene-specific information tables (i.e. DPYD allele definition, allele functionality, and frequency tables) see CPIC® GUIDELINE FOR SELECTIVE SEROTONIN REUPTAKE Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors (August 2015) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPIC® GUIDELINE FOR SIMVASTATIN AND SLCO1B1 Most recent guideline publication: The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1 and Simvastatin-induced Myopathy: 2014 Update (October 2014) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely SLCO1B1 phenotype CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. LICENSING AND TERMS OF USE FOR CPIC CONTENT The information on this website is not intended for direct diagnostic use or medical decision-making without review by a health care

professional.

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR TRICYCLIC ANTIDEPRESSANTS AND CYP2D6 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update (December 2016) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPICGUIDELINESGENES-DRUGSALLELESPUBLICATIONSMEETINGSRESOURCES The Clinical Pharmacogenetics Implementation Consortium (CPIC®) is an international consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for patient care.. One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable

prescribing

GUIDELINES – CPICLICENSINGCPIC GUIDELINE FOR FLUOROPYRIMIDINES AND DPYDMEMBERSPUBLICATIONSMEETINGSCONTACT CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered. A key assumption underlying the CPIC guidelines is that clinical high-throughput and pre-emptive (pre-prescription) genotyping will become more widespread, and that clinicians will be faced with having

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. LICENSING AND TERMS OF USE FOR CPIC CONTENT The information on this website is not intended for direct diagnostic use or medical decision-making without review by a health care

professional.

PRIORITIZATION

Prioritization. Assignment of CPIC Levels for Genes/Drugs. CPIC assigns CPIC levels to gene/drug pairs. The levels (A, B, C, and D) assigned are subject to change; only those gene/drug pairs that have been the subject of guidelines have had sufficient in-depth review of evidence to provide definitive CPIC level assignments. CPIC® GUIDELINE FOR THIOPURINES AND TPMT AND NUDT15 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update (November 2018) Updates since publication: April 2020: The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e. combination of uncertain and/or unknown function CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR FLUOROPYRIMIDINES AND DPYD The current DPYD guideline recommends to reduce the dose of fluoropyrimidines by 25-50% (from the full standard dose) in DPYD Intermediate Metabolizers with an activity score of 1.5. At the time of the guideline publication, this dose range was recommended due to limited evidence for genotype-guided dosing of decreased function

alleles/variants.

CPIC® GUIDELINE FOR TACROLIMUS AND CYP3A5 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. CPIC® GUIDELINE FOR TRICYCLIC ANTIDEPRESSANTS AND CYP2D6 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update (December 2016) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of

ABOUT US – CPIC

Kelly E. Caudle, PharmD, PhD, BCPS, FCCP CPIC Co-PI/Director, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN Dr. Caudle received her Pharm.D. and Ph.D. from The University of Tennessee Health Science Center and completed an ASHP-accredited PGY2 residency at Le Bonheur Children’s Hospital in Memphis, TN. She is also a

GENES-DRUGS

Genes-Drugs. CPIC assigns CPIC levels to genes/drugs with (1) PharmGKB Clinical Annotation Levels of Evidence of 1A, 1B, 2A and 2B, or (2) a PharmGKB PGx level for FDA-approved drug labels of “actionable pgx”, “genetic testing recommended”, or “genetic testing required”, or (3) based on nomination to CPIC for consideration. CPIC® GUIDELINE FOR RASBURICASE AND G6PD Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of likely G6PD phenotypes based on genotype/diplotype. Table 2. Recommended therapeutic use of rasburicase in relation to G6PD phenotype. Figure 1. Workflow for interpreting G6PD genotype and for assessing the need for an enzyme

activity test.

CPIC® GUIDELINE FOR OPIOIDS AND CYP2D6, OPRM1, AND COMT Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy (December 2020) Tables and figure provided in the main manuscript of the guideline: Table 1. Assignment of predicted CYP2D6 phenotypes based on diplotypes Table 2. Codeine therapy recommendations based on 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

CONTACT (OLD)

CPIC Communication There are a few different ways to stay in touch with CPIC. I have a question or comment. Contact us with any questions or comments Contact CPIC I want to get announcements. CPIC has a public announcement list that anyone can join.The announcements include guideline updates, news, and solicitation of feedback. Sign Up CPIC® GUIDELINE FOR CLOPIDOGREL AND CYP2C19 Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 update (September 2013) Updates since publication: March 2017: The FDA-approved label for clopidogrel (Plavix) was recently updated (September 2016) and warns that patients who are CYP2C19 poor metabolizers may have diminished DPYD CPIC GUIDELINES CPIC guideline for fluoropyrimidines based on DPYD genotype For gene-specific information tables (i.e. DPYD allele definition, allele functionality, and frequency tables) see CPIC® GUIDELINE FOR SELECTIVE SEROTONIN REUPTAKE Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors (August 2015) Updates since publication: October 2019: CYP2D6 genotype to phenotype translation changes: Up until August 2019, there were a few inconsistencies in the translation of CPIC® GUIDELINE FOR SIMVASTATIN AND SLCO1B1 Most recent guideline publication: The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1 and Simvastatin-induced Myopathy: 2014 Update (October 2014) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely SLCO1B1 phenotype

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* Alleles

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* Resources

* Working Groups

* Members

* Contact

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WHAT IS CPIC?

The Clinical Pharmacogenetics Implementation Consortium (CPIC®)

is an international

consortium of individual volunteers and a small dedicated staff who are interested in facilitating use of pharmacogenetic tests for

patient care.

One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable prescribing decisions for affected drugs. CPIC’s goal is to address this barrier to clinical implementation of pharmacogenetic tests by creating, curating, and posting freely available, peer-reviewed, evidence-based, updatable, and detailed gene/drug clinical practice guidelines (click here for all CPIC publications).  CPIC guidelines follow standardized formats, include systematic grading of evidence and clinical recommendations, use standardized terminology , are peer-reviewed, and are published in a leading journal (in partnership with Clinical Pharmacology and Therapeutics ) with simultaneous posting to cpicpgx.org, where they are regularly

updated.

CPIC started as a shared project between PharmGKB and the Pharmacogenomics Research Network (PGRN)  in 2009. CPIC guidelines are indexed in PubMed as clinical guidelines,

endorsed by ASHP

and ASCPT

,

and referenced in ClinGen and

PharmGKB .

Additionally, the College of American Pathologists (CAP)  has stated: “CAP applauds and supports the objectives, processes and work completed as of December 2018 by the Clinical Pharmacogenetics Implementation Consortium (CPIC®). These efforts will help clinicians, laboratories, health care providers and vendors.” CPIC RESOURCES ARE FREELY AVAILABLE under a Creative Commons public

domain license.

Read the license page for more details.

TEAM

LEADER

Mary V. Relling, Pharm.D. St. Jude Children’s Research Hospital, Memphis

LEADER

Teri E. Klein, Ph.D.

Stanford University

DIRECTOR

Kelly Caudle, Pharm.D., Ph.D. St. Jude Children’s Research Hospital, Memphis CPIC INFORMATICS CO-DIRECTORS Michelle Whirl-Carrillo, Ph.D.

Stanford University

James M. Hoffman, Pharm.D. St. Jude Children’s Research Hospital, Memphis STANFORD CPIC COORDINATOR Michelle Whirl-Carrillo, Ph.D.

Stanford University

STEERING COMMITTEE

Mary V. Relling, Pharm.D. St. Jude Children’s Research Hospital, Memphis Teri E. Klein, Ph.D.

Stanford University

Julie A. Johnson, Pharm.D. University of Florida

Dan M. Roden, M.D.

Vanderbilt University Rachel F. Tyndale, Ph.D. University of Toronto and CAMH Larissa Cavallari, Pharm.D. University of Florida

Stuart Scott, Ph.D.

Icahn School of Medicine at Mount Sinai SCIENTIFIC ADVISORY BOARD Gwendolyn A. McMillin, Ph.D.

ARUP Laboratories

Robert Nussbaum, M.D. University of California, San Francisco

Heidi Rehm, Ph.D.

Partners Healthcare

Marc S. Williams, M.D.

Geisinger

Sandy Aronson

Partners Personalized Medicine Justin B. Starren, M.D., Ph.D. Northwestern University

NEWS

& ANNOUNCEMENTS

* CPIC to issue guidance on non-actionable pharmacogenes

July 2, 2019

The Clinical Pharmacogenetics Implementation Consortium (CPIC) hopes to provide more guidance in the future about gene-drug pairs which have a weak evidence base and are not clinically actionable, despite being heavily marketed to healthcare providers and the public. Many of these gene-drug pairs have already been curated by CPIC staff and assigned a CPIC level of C * PharmVar core alleles to be used by PharmGKB and CPIC

May 21, 2019

PharmVar has released core alleles - single, rule-based definitions per star allele distilled from the respective suballeles - for the cytochrome P450 genes CYP2C9, CYP2C19, and CYP2D6. Only sequence variations that change an amino acid or impact function by changing expression levels or interfere with splicing and are present in ALL suballeles within a star allele, * New CPIC Guideline: CYP2B6 and efavirenz

May 1, 2019

The CPIC Guideline for CYP2B6 and efavirenz is now published in Clinical Pharmacology and Therapeutics. The accepted article can be viewed on the PharmGKB pages for efavirenz, CYP2B6, and on the CPIC website.Efavirenz is a non-nucleoside reverse transcriptase inhibitor widely used worldwide to treat HIV-1 infection. It is predominantly metabolized into inactive metabolites by cytochrome P450-2B6 (CYP2B6). Genetic variants * CYP2C19 testing may assist with prescribing sertraline and

escitalopram

April 16, 2019

Mary Relling (St. Jude Children's Research Hospital) and I (Teri Klein) as Co-Principal Investigators of the Clinical Pharmacogenetics Implementation Consortium (CPIC) have been discussing the letter that the FDA recently sent to a genomics laboratory expressing concern that “providers may make inappropriate treatment decisions based” on pharmacogenetic testing offered by that lab. The FDA specifically * New CPIC Guideline: CYP2D6 and atomoxetine

March 5, 2019

The CPIC Guideline for atomoxetine and CYP2D6 is now published in Clinical Pharmacology and Therapeutics. The accepted article can be viewed on the PharmGKB page for atomoxetine, and the CPIC website.Atomoxetine is a non-stimulant medication used in the treatment of attention-deficit/hyperactivity disorder. Atomoxetine is metabolized by CYP2D6 and  genetic variation effects atomoxetine pharmacokinetics. Atomoxetine exposure is __ __ Follow @cpicpgx on Twitter

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This page last modified: Aug 21, 2019 @ 8:37 am CPIC® is a partnership between PharmGKB

and PGRN .

CPIC® is managed at Stanford University & St. Jude Children’s Research Hospital

(U24HG010135)

Contact CPIC® – Licensing CPIC® is a registered service mark of the US Department of Health & Human Services (HHS) .

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