PharmCAT Report [pharmcat.example2]

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Population:
Unspecified

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"In patients who are known or suspected to be CYP2C19 poor metabolizers, the recommended dosage of CIBINQO [abrocitinib] is 50 mg once daily. If an adequate response is not achieved with CIBINQO 50 mg orally daily after 12 weeks, consider increasing dosage to 100 mg orally once daily. Discontinue therapy if inadequate response is seen after dosage increase to 100 mg once daily." See label for more information. *

Unspecified

Affected subgroup: CYP2C19 poor metabolizers

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations and may result in higher adverse reaction risk. Dosage adjustment is recommended. Refer to FDA labeling for specific dosing recommendations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

acenocoumarol

Source	Genes	Implications	Recommendation	Classification
DPWG Guideline Annotation Population: Unspecified No Action	Genotype VKORC1: rs9923231 reference (C)/ rs9923231 reference (C) Phenotype -1639 GG	The guideline does not provide a description of the impact of the -1639 GG genotype on acenocoumarol.	The guideline does not provide a recommendation for acenocoumarol in patients with the VKORC1 rs9923231 CC genotype (-1639 GG genotype).	No recommendation

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

VKORC1:
rs9923231 reference (C)/
rs9923231 reference (C)

Phenotype

-1639 GG

The guideline does not provide a description of the impact of the -1639 GG genotype on acenocoumarol.

The guideline does not provide a recommendation for acenocoumarol in patients with the VKORC1 rs9923231 CC genotype (-1639 GG genotype).

No recommendation

Citations:

Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232

allopurinol

Source	Genes	Implications	Recommendation	Classification
DPWG Guideline Annotation Population: Unspecified No Action	Genotype ABCG2: rs2231142 reference (G)/ rs2231142 reference (G) Phenotype Normal Function	The guideline does not provide a description of the impact of the ABCG2 rs2231142 GG genotype (c.421CC; p.141QQ) on allopurinol.	The guideline does not provide a recommendation for allopurinol in patients with the the ABCG2 rs2231142 GG genotype (c.421CC; p.141QQ)	No recommendation

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

ABCG2:
rs2231142 reference (G)/
rs2231142 reference (G)

Phenotype

Normal Function

The guideline does not provide a description of the impact of the ABCG2 rs2231142 GG genotype (c.421CC; p.141QQ) on allopurinol.

The guideline does not provide a recommendation for allopurinol in patients with the the ABCG2 rs2231142 GG genotype (c.421CC; p.141QQ)

No recommendation

Citations:

Dutch pharmacogenetics working group guideline for the gene-drug interaction of ABCG2, HLA-B and Allopurinol, and MTHFR, folic acid and methotrexate. European journal of human genetics : EJHG. 2024. PMID:36056234

amitriptyline

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Alternate Drug Dosing Info	Genotype CYP2C19:2/2; CYP2D6:Not called - no variant data provided Phenotypes CYP2C19: Poor Metabolizer CYP2D6: No Result Activity Scores CYP2C19: N/A CYP2D6: No Result	CYP2C19: Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects CYP2D6: n/a	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Other Considerations Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose.	Moderate

Source

Genes

Implications

Recommendation

Classification

Population:
general

Alternate Drug

Dosing Info

Genotype

CYP2C19:*2/*2;
CYP2D6:Not called - no variant data provided

Phenotypes

CYP2C19:: Poor Metabolizer
CYP2D6:: No Result

Activity Scores

CYP2C19:: N/A
CYP2D6:: No Result

CYP2C19: Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects
CYP2D6: n/a

Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.

Other Considerations

Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose.

Moderate

Citations:

Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clinical pharmacology and therapeutics. 2013. PMID:23486447
Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical pharmacology and therapeutics. 2017. PMID:27997040

atazanavir

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Other Guidance	Genotype UGT1A1:1/1 Phenotype Normal Metabolizer	UGT1A1: Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir.	There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Inform the patient that some patients stop atazanavir because of jaundice (yellow eyes and skin), but that this patient’s genotype makes this unlikely (less than about a 1 in 20 chance of stopping atazanavir because of jaundice). Other Considerations All studies correlating UGT1A1 genotypes with atazanavir adverse events have involved ritonavir boosting. However, concentration-time profiles are equivalent when boosted with either cobicistat or ritonavir (PMID 23532097), and bilirubin-related adverse events including discontinuation of atazanavir occur in a similar percentage of patients prescribed atazanavir with cobicistat or ritonavir (PMID 23532097). Associations between UGT1A1 genotype, bilirubin elevations, and atazanavir/r discontinuation therefore almost certainly translate to atazanavir/cobicistat. "reference" function refers to the UGT1A1 allele to which other alleles are compared.	Strong

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

UGT1A1:*1/*1

Phenotype

Normal Metabolizer

UGT1A1: Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir.

There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Inform the patient that some patients stop atazanavir because of jaundice (yellow eyes and skin), but that this patient’s genotype makes this unlikely (less than about a 1 in 20 chance of stopping atazanavir because of jaundice).

Other Considerations

All studies correlating UGT1A1 genotypes with atazanavir adverse events have involved ritonavir boosting. However, concentration-time profiles are equivalent when boosted with either cobicistat or ritonavir (PMID 23532097), and bilirubin-related adverse events including discontinuation of atazanavir occur in a similar percentage of patients prescribed atazanavir with cobicistat or ritonavir (PMID 23532097). Associations between UGT1A1 genotype, bilirubin elevations, and atazanavir/r discontinuation therefore almost certainly translate to atazanavir/cobicistat. "reference" function refers to the UGT1A1 allele to which other alleles are compared.

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing. Clinical pharmacology and therapeutics. 2016. PMID:26417955

atorvastatin

The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype SLCO1B1:1/1 Phenotype Normal Function	SLCO1B1: Typical myopathy risk and statin exposure	Prescribe desired starting dose and adjust doses based on disease-specific guidelines. Other Considerations The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin.	Strong
DPWG Guideline Annotation Population: Unspecified No Action	Genotype SLCO1B1:1/1 Phenotype Normal Function	The guideline does not provide a description of the impact of the _SLCO1B1_ 521 TT genotype on atorvastatin.	The guideline does not provide a recommendation for atorvastatin in patients with the SLCO1B1 521 TT genotype	No recommendation
FDA PGx Association ¹	Genotype SLCO1B1:1/1	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

Phenotype

Normal Function

SLCO1B1: Typical myopathy risk and statin exposure

Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin.

Strong

Population:
Unspecified

No Action

Genotype

SLCO1B1:*1/*1

Phenotype

Normal Function

The guideline does not provide a description of the impact of the _SLCO1B1_ 521 TT genotype on atorvastatin.

The guideline does not provide a recommendation for atorvastatin in patients with the SLCO1B1 521 TT genotype

No recommendation

FDA PGx Association ¹

Genotype

SLCO1B1:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clinical pharmacology and therapeutics. 2022. PMID:35152405
FDA Table of Pharmacogenetic Associations.

azathioprine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype NUDT15:1/1; TPMT:1/1 Phenotypes NUDT15: Normal Metabolizer TPMT: Normal Metabolizer	NUDT15: Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression TPMT: Lower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.	Start with normal starting dose (e.g., 2-3 mg/kg/day) and adjust doses of azathioprine based on disease-specific guidelines. Allow 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 11302950, 15606506). Other Considerations Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers.	Strong
DPWG Guideline Annotation Population: Unspecified No Action	Genotype NUDT15:1/1 Phenotype Normal Metabolizer	The guideline does not provide a description of the impact of a normal metabolizer phenotype on azathioprine.	The guideline does not provide a recommendation for azathioprine in normal metabolizers	No recommendation
DPWG Guideline Annotation Population: Unspecified No Action	Genotype TPMT:1/1 Phenotype Normal Metabolizer	The guideline does not provide a description of the impact of a normal metabolizer phenotype on azathioprine.	The guideline does not provide a recommendation for azathioprine in normal metabolizers.	No recommendation
FDA Label Annotation ¹	Genotypes NUDT15:1/1; TPMT:1/1	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotypes NUDT15:1/1; TPMT:1/1	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clinical pharmacology and therapeutics. 2011. PMID:21270794
Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clinical pharmacology and therapeutics. 2013. PMID:23422873
Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clinical pharmacology and therapeutics. 2019. PMID:30447069
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Drugs@FDA: Drug Product IMURAN (azathioprine), NDA016324, Sebela Pharmaceuticals Inc.
FDA Table of Pharmacogenetic Associations.

belzutifan

Source	Genes	Implications	Recommendation	Classification
FDA Label Annotation Population: Unspecified Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	"Patients who are dual UGT2B17 and CYP2C19 poor metabolizers have higher belzutifan exposures, which may increase the incidence and severity of adverse reactions of WELIREG [belzutifan]."	"Closely monitor for adverse reactions in patients who are dual UGT2B17 and CYP2C19 poor metabolizers." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Affected subgroup: CYP2C19 and/or UGT2B17 poor metabolizers Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic concentrations and may result in higher adverse reaction risk (anemia, hypoxia). Monitor patients who are poor metabolizers for both genes for adverse reactions." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Population:
Unspecified

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Patients who are dual UGT2B17 and CYP2C19 poor metabolizers have higher belzutifan exposures, which may increase the incidence and severity of adverse reactions of WELIREG [belzutifan]."

"Closely monitor for adverse reactions in patients who are dual UGT2B17 and CYP2C19 poor metabolizers." See label for more information. *

Unspecified

Affected subgroup: CYP2C19 and/or UGT2B17 poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations and may result in higher adverse reaction risk (anemia, hypoxia). Monitor patients who are poor metabolizers for both genes for adverse reactions." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

brivaracetam

Source	Genes	Implications	Recommendation	Classification
FDA Label Annotation Population: Unspecified Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		The brivaracetam (BRIVIACT) label states: "CYP2C19 poor metabolizers and patients using inhibitors of CYP2C19 may require dose reduction." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Affected subgroup: CYP2C19 intermediate or poor metabolizers Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic concentrations and higher adverse reaction risk. Consider dosage reductions in poor metabolizers." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Population:
Unspecified

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

The brivaracetam (BRIVIACT) label states: "CYP2C19 poor metabolizers and patients using inhibitors of CYP2C19 may require dose reduction." See label for more information. *

Unspecified

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations and higher adverse reaction risk. Consider dosage reductions in poor metabolizers." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

capecitabine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype DPYD:Reference/ Reference Phenotype Normal Metabolizer Activity Score 2.0	DPYD: Normal DPD activity and "normal" risk for fluoropyrimidine toxicity	Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration.	Strong
DPWG Guideline Annotation Population: Unspecified No Action	Genotype DPYD:Reference/ Reference Phenotype 2.0 (Normal Metabolizer)	The guideline does not provide a description of the impact of a DPYD activity score of 2 on capecitabine.	The guideline does not provide a recommendation for capecitabine in patients with a DPYD activity score of 2.	No recommendation
FDA Label Annotation ¹	Genotype DPYD:Reference/Reference	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype DPYD:Reference/Reference	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clinical pharmacology and therapeutics. 2013. PMID:23988873
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clinical pharmacology and therapeutics. 2018. PMID:29152729
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines. European journal of human genetics : EJHG. 2020. PMID:31745289
Drugs@FDA: Drug Product Xeloda (capecitabine), NDA020896, Genentech, Inc.
FDA Table of Pharmacogenetic Associations.

carisoprodol

Source	Genes	Implications	Recommendation	Classification
FDA Label Annotation Population: Unspecified Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Patients with Reduced CYP2C19 Activity: SOMA [carisoprodol] should be used with caution in patients with reduced CYP2C19 activity." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2C19 poor metabolizers Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic concentrations. Use with caution." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Population:
Unspecified

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Patients with Reduced CYP2C19 Activity: SOMA [carisoprodol] should be used with caution in patients with reduced CYP2C19 activity." See label for more information. *

Unspecified

Affected subgroup: CYP2C19 poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations. Use with caution." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

celecoxib

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype CYP2C9:1/1 Phenotype Normal Metabolizer Activity Score 2.0	CYP2C9: Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.	Strong
FDA Label Annotation ¹	Genotype CYP2C9:1/1	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2C9:1/1	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

Activity Score

2.0

CYP2C9: Normal metabolism

Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.

Strong

FDA Label Annotation ¹

Genotype

CYP2C9:*1/*1

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association ¹

Genotype

CYP2C9:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clinical pharmacology and therapeutics. 2020. PMID:32189324
Drugs@FDA: Drug Product CELEBREX (Celecoxib), NDA020998, Aphena Pharma Solutions - Tennessee, LLC.
FDA Table of Pharmacogenetic Associations.

citalopram

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Alternate Drug Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	CYP2C19: Reduced metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule and 50% reduction of the standard maintenance dose as compared to normal metabolizers. Other Considerations Per the FDA warning, citalopram 20 mg/day is the maximum recommended dose in CYP2C19 poor metabolizers due to the risk of QT prolongation. FDA product labeling additionally cautions that citalopram dose should be limited to 20 mg/day in patients with hepatic impairment, those taking a CYP2C19 inhibitor, and patients greater than 60 years of age.	Strong
DPWG Guideline Annotation Population: Unspecified Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	The risk of QT prolongation and therefore also the theoretical risk of torsades de pointes is increased as the gene variation leads to an increased citalopram plasma concentration. If you follow the dose recommendation below, the increased plasma concentration and the increased risk of QT prolongation will be offset.	Do not exceed the following daily doses (50% of the standard maximum dose): adults up to 65 years: 20mg as tablets or 16mg as drops, Adults 65 years or older: 10mg as tablets or 8mg as drops	Unspecified
FDA Label Annotation Population: Unspecified Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	CYP2C19 poor metabolizers have higher systemic concentration and adverse reaction risk (QT prolongation).	"Celexa [citalopram] 20 mg/day is the maximum recommended dose in CYP2C19 poor metabolizers due to the risk of QT prolongation." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Affected subgroup: CYP2C19 poor metabolizers Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic concentrations and adverse reaction risk (QT prolongation). The maximum recommended dose is 20 mg." *	Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clinical pharmacology and therapeutics. 2015. PMID:25974703
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clinical pharmacology and therapeutics. 2023. PMID:37032427
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs. European journal of human genetics : EJHG. 2022. PMID:34782755
Drugs@FDA: Drug Product Celexa (citalopram), NDA020822, Allergan, Inc.
FDA Table of Pharmacogenetic Associations.

clobazam

Source	Genes	Implications	Recommendation	Classification
FDA Label Annotation Population: Unspecified Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"In CYP2C19 poor metabolizers ... the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the dose presented in Table 1 [of the drug label], as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Affected subgroup: CYP2C9 intermediate or poor metabolizers Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic active metabolite concentrations. Poor metabolism results in higher adverse reaction risk. Dosage adjustment is recommended. Refer to FDA labeling for specific dosing recommendations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Population:
Unspecified

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"In CYP2C19 poor metabolizers ... the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the dose presented in Table 1 [of the drug label], as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21." See label for more information. *

Unspecified

Affected subgroup: CYP2C9 intermediate or poor metabolizers

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic active metabolite concentrations. Poor metabolism results in higher adverse reaction risk. Dosage adjustment is recommended. Refer to FDA labeling for specific dosing recommendations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

clomipramine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Alternate Drug Dosing Info	Genotype CYP2C19:2/2; CYP2D6:Not called - no variant data provided Phenotypes CYP2C19: Poor Metabolizer CYP2D6: No Result Activity Scores CYP2C19: N/A CYP2D6: No Result	CYP2C19: Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects CYP2D6: n/a	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Other Considerations Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose.	Optional
DPWG Guideline Annotation Population: Unspecified No Action	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	The gene variation increases the plasma concentration of clomipramine. However, there is insufficient evidence to substantiate an increase of the plasma concentration of clomipramine+desmethylclomipramine to such an extent that it increases the risk of side effects. The increase in the plasma concentration of clomipramine is favourable for the efficacy in anxiety and obsessive compulsive disorder.	NO action is required for this gene-drug interaction.	Unspecified

Source

Genes

Implications

Recommendation

Classification

Population:
general

Alternate Drug

Dosing Info

Genotype

CYP2C19:*2/*2;
CYP2D6:Not called - no variant data provided

Phenotypes

CYP2C19:: Poor Metabolizer
CYP2D6:: No Result

Activity Scores

CYP2C19:: N/A
CYP2D6:: No Result

CYP2C19: Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects
CYP2D6: n/a

Other Considerations

Optional

Population:
Unspecified

No Action

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

The gene variation increases the plasma concentration of clomipramine. However, there is insufficient evidence to substantiate an increase of the plasma concentration of clomipramine+desmethylclomipramine to such an extent that it increases the risk of side effects. The increase in the plasma concentration of clomipramine is favourable for the efficacy in anxiety and obsessive compulsive disorder.

NO action is required for this gene-drug interaction.

Unspecified

Citations:

Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clinical pharmacology and therapeutics. 2013. PMID:23486447
Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical pharmacology and therapeutics. 2017. PMID:27997040
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232

clopidogrel

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: CVI ACS PCI Alternate Drug	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	CYP2C19: Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events	Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication. Other Considerations For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication.	Strong
CPIC Guideline Annotation Population: CVI non-ACS non-PCI Alternate Drug	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	CYP2C19: Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events	Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication. Other Considerations For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI.	Moderate
CPIC Guideline Annotation Population: NVI Alternate Drug	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	CYP2C19: Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events	Avoid clopidogrel if possible. Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication. Other Considerations For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms. Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. Given limited outcomes data for genotype-guided anti-platelet therapy for neurovascular indications, selection of therapy should depend on individual patient treatment goals and risks for adverse events.	Moderate
DPWG Guideline Annotation Population: Unspecified Alternate Drug	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	The risk of serious cardiovascular and cerebrovascular events is increased in patients undergoing balloon angioplasty or stent placement (percutaneous coronary intervention) and in patients with a stroke or TIA, because the genetic variation reduces the activation of clopidogrel. No negative clinical consequences have been proved in other patients.	PERCUTANEOUS CORONARY INTERVENTION, STROKE or TIA: avoid clopidogrel. Prasugrel, ticagrelor and acetylsalicylic acid/dipyridamole are not metabolised by CYP2C19 (or to a lesser extent). OTHER INDICATIONS: determine the level of inhibition of platelet aggregation by clopidogrel. Consider an alternative in poor responders. Prasugrel and ticagrelor are not metabolised by CYP2C19 (or to a lesser extent).	Unspecified
FDA Label Annotation Population: Unspecified Alternate Drug	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		The clopidogrel (Plavix) label states: "Consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Affected subgroup: CYP2C19 intermediate or poor metabolizers Alternate Drug	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in lower systemic active metabolite concentrations, lower antiplatelet response, and may result in higher cardiovascular risk. Consider use of another platelet P2Y12 inhibitor." *	Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clinical pharmacology and therapeutics. 2011. PMID:21716271
Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clinical pharmacology and therapeutics. 2013. PMID:23698643
Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update. Clinical pharmacology and therapeutics. 2022. PMID:35034351
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Drugs@FDA: Drug Product Plavix (clopidogrel bisulfate), NDA020839, Rebel Distributors Corp.
Drugs@FDA: Drug Product Plavix (clopidogrel), sanofi-aventis U.S. LLC - NDA020839/SUPPL-78, 09/16/2022.
FDA Table of Pharmacogenetic Associations.

dapsone

PharmCAT reports based on VCF file input and some VCF files do not specify hemizygous (one X chromosome) and instead represent samples as homozygous. See PharmCAT FAQs (https://pharmcat.org/faqs/).

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype G6PD:B (reference)/ B (reference) Phenotype Normal	G6PD: Low risk of acute hemolytic anemia	No reason to avoid based on G6PD status	Strong

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

Phenotype

Normal

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clinical pharmacology and therapeutics. 2014. PMID:24787449
Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2023. PMID:36049896

desflurane

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Other Guidance	Genotype CACNA1S:Reference/ Reference; RYR1:Reference/ Reference Phenotypes CACNA1S: Uncertain Susceptibility RYR1: Uncertain Susceptibility	These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).	Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.	Strong
FDA Label Annotation Population: Unspecified Alternate Drug	Genotype CACNA1S:Reference/ Reference; RYR1:Reference/ Reference Phenotypes CACNA1S: Uncertain Susceptibility RYR1: Uncertain Susceptibility		"The use of SUPRANE [desflurane] is contraindicated in...[cases of k]nown or suspected genetic susceptibility to malignant hyperthermia...SUPRANE [desflurane] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants. " See label for more information. *	Unspecified

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).

Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.

Strong

Population:
Unspecified

Alternate Drug

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

"The use of SUPRANE [desflurane] is contraindicated in...[cases of k]nown or suspected genetic susceptibility to malignant hyperthermia...SUPRANE [desflurane] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants. " See label for more information. *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clinical pharmacology and therapeutics. 2019. PMID:30499100
Drugs@FDA: Drug Product SUPRANE (desflurane), NDA020118, Baxter Healthcare Corporation.

dexlansoprazole

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2C19 intermediate or poor metabolizers Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic concentrations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Population:
general

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity

Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.

Optional

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clinical pharmacology and therapeutics. 2021. PMID:32770672
FDA Table of Pharmacogenetic Associations.

diazepam

Source	Genes	Implications	Recommendation	Classification
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2C19 poor metabolizers Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"May affect systemic concentrations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Affected subgroup: CYP2C19 poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"May affect systemic concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

FDA Table of Pharmacogenetic Associations.

doxepin

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Alternate Drug Dosing Info	Genotype CYP2C19:2/2; CYP2D6:Not called - no variant data provided Phenotypes CYP2C19: Poor Metabolizer CYP2D6: No Result Activity Scores CYP2C19: N/A CYP2D6: No Result	CYP2C19: Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects CYP2D6: n/a	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Other Considerations Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose.	Optional
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2C19 intermediate or poor metabolizers Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic concentrations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Population:
general

Alternate Drug

Dosing Info

Genotype

CYP2C19:*2/*2;
CYP2D6:Not called - no variant data provided

Phenotypes

CYP2C19:: Poor Metabolizer
CYP2D6:: No Result

Activity Scores

CYP2C19:: N/A
CYP2D6:: No Result

CYP2C19: Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects
CYP2D6: n/a

Other Considerations

Optional

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clinical pharmacology and therapeutics. 2013. PMID:23486447
Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical pharmacology and therapeutics. 2017. PMID:27997040
FDA Table of Pharmacogenetic Associations.

efavirenz

The assigned genotype is *1/*6; however, *4/*9 cannot be ruled out without phased data.

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: child >40kg_adult Dosing Info	Genotype CYP2B6:1/6 Phenotype Intermediate Metabolizer	CYP2B6: Higher dose-adjusted trough concentrations of efavirenz compared with normal metabolizers; increased risk of CNS adverse events	Consider initiating efavirenz with decreased dose of 400 mg/day Other Considerations If therapeutic drug monitoring is available and a decreased efavirenz dose is prescribed, consider obtaining steady-state plasma efavirenz concentrations to ensure concentrations are in the suggested therapeutic range (~1 to 4 μg/mL). To prescribe efavirenz at a decreased dose of 400 mg/day or 200 mg/day in a multidrug regimen may require prescribing more than one pill once daily. If so, the provider should weigh the potential benefit of reduced dose against the potential detrimental impact of increased pill number.	Moderate
DPWG Guideline Annotation Population: Unspecified Dosing Info	Genotype CYP2B6:1/6 Phenotype Intermediate Metabolizer	Genetic variations increase the efavirenz plasma concentration and therefore the risk of side effects. However, the efavirenz plasma concentration remains within the therapeutic range for the majority of patients.	Determine the efavirenz plasma concentration if side effects occur and reduce the dose if needed. In 14 IM adults, a dose reduction to 400 mg/day (2/3rd of the standard dose) was sufficient to achieve therapeutic plasma concentrations and to reduce or resolve side effects. The therapeutic range established for efavirenz is 1000-4000 ng/ml.	Unspecified
FDA PGx Association ¹	Genotype CYP2B6:1/6	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Source

Genes

Implications

Recommendation

Classification

Population:
child >40kg_adult

Dosing Info

Genotype

CYP2B6:*1/*6

Phenotype

Intermediate Metabolizer

CYP2B6: Higher dose-adjusted trough concentrations of efavirenz compared with normal metabolizers; increased risk of CNS adverse events

Consider initiating efavirenz with decreased dose of 400 mg/day

Other Considerations

If therapeutic drug monitoring is available and a decreased efavirenz dose is prescribed, consider obtaining steady-state plasma efavirenz concentrations to ensure concentrations are in the suggested therapeutic range (~1 to 4 μg/mL). To prescribe efavirenz at a decreased dose of 400 mg/day or 200 mg/day in a multidrug regimen may require prescribing more than one pill once daily. If so, the provider should weigh the potential benefit of reduced dose against the potential detrimental impact of increased pill number.

Moderate

Population:
Unspecified

Dosing Info

Genotype

CYP2B6:*1/*6

Phenotype

Intermediate Metabolizer

Genetic variations increase the efavirenz plasma concentration and therefore the risk of side effects. However, the efavirenz plasma concentration remains within the therapeutic range for the majority of patients.

Determine the efavirenz plasma concentration if side effects occur and reduce the dose if needed. In 14 IM adults, a dose reduction to 400 mg/day (2/3rd of the standard dose) was sufficient to achieve therapeutic plasma concentrations and to reduce or resolve side effects. The therapeutic range established for efavirenz is 1000-4000 ng/ml.

Unspecified

FDA PGx Association ¹

Genotype

CYP2B6:*1/*6

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-Containing Antiretroviral Therapy. Clinical pharmacology and therapeutics. 2019. PMID:31006110
FDA Table of Pharmacogenetic Associations.

enflurane

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Other Guidance	Genotype CACNA1S:Reference/ Reference; RYR1:Reference/ Reference Phenotypes CACNA1S: Uncertain Susceptibility RYR1: Uncertain Susceptibility	These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).	Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.	Strong

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clinical pharmacology and therapeutics. 2019. PMID:30499100

escitalopram

Source

Genes

Implications

Recommendation

Classification

Population:
general

Alternate Drug

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

CYP2C19: Reduced metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects.

Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule and 50% reduction of the standard maintenance dose as compared to normal metabolizers.

Other Considerations

Per the FDA warning, citalopram 20 mg/day is the maximum recommended dose in CYP2C19 poor metabolizers due to the risk of QT prolongation. FDA product labeling additionally cautions that citalopram dose should be limited to 20 mg/day in patients with hepatic impairment, those taking a CYP2C19 inhibitor, and patients greater than 60 years of age.

Strong

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Population:
Unspecified

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

The risk of switching to another antidepressant is increased. In addition, the risk of QT prolongation and torsades de pointes is theoretically increased because the gene variation leads to an increased escitalopram plasma concentration. If you follow the dose recommendation below, the increased plasma concentration, the theoretically increased risk of QT prolongation and the increased risk of switching to another antidepressant will be offset.

Do not exceed the following doses (50% of the standard maximum dose): adults < 65 years 10 mg/day, =65 years 5 mg/day

Unspecified

Affected subgroup: CYP2C19 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"May alter systemic concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clinical pharmacology and therapeutics. 2015. PMID:25974703
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clinical pharmacology and therapeutics. 2023. PMID:37032427
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs. European journal of human genetics : EJHG. 2022. PMID:34782755
FDA Table of Pharmacogenetic Associations.

esomeprazole

Source	Genes	Implications	Recommendation	Classification
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2C19 poor metabolizers Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic concentrations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Affected subgroup: CYP2C19 poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

FDA Table of Pharmacogenetic Associations.

flibanserin

Source	Genes	Implications	Recommendation	Classification
FDA Label Annotation Population: Unspecified Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		The flibanserin (ADDYI) label states: "[...]increase monitoring for adverse reactions (e.g., hypotension) in patients who are CYP2C19 poor metabolizers." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Affected subgroup: CYP2C19 poor metabolizers Other Guidance	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"May result in higher systemic concentrations and higher adverse reaction risk. Monitor patients for adverse reactions." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Population:
Unspecified

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

The flibanserin (ADDYI) label states: "[...]increase monitoring for adverse reactions (e.g., hypotension) in patients who are CYP2C19 poor metabolizers." See label for more information. *

Unspecified

Affected subgroup: CYP2C19 poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"May result in higher systemic concentrations and higher adverse reaction risk. Monitor patients for adverse reactions." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

flucytosine

Source	Genes	Implications	Recommendation	Classification
DPWG Guideline Annotation Population: Unspecified No Action	Genotype DPYD:Reference/ Reference Phenotype 2.0 (Normal Metabolizer)	The guideline does not provide a description of the impact of a DPYD activity score of 2 on flucytosine.	The guideline does not provide a recommendation for flucytosine in patients with a DPYD activity score of 2.	No recommendation

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

DPYD:Reference/
Reference

Phenotype

2.0 (Normal Metabolizer)

The guideline does not provide a description of the impact of a DPYD activity score of 2 on flucytosine.

The guideline does not provide a recommendation for flucytosine in patients with a DPYD activity score of 2.

No recommendation

fluorouracil

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype DPYD:Reference/ Reference Phenotype Normal Metabolizer Activity Score 2.0	DPYD: Normal DPD activity and "normal" risk for fluoropyrimidine toxicity	Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration.	Strong
DPWG Guideline Annotation Population: Unspecified No Action	Genotype DPYD:Reference/ Reference Phenotype 2.0 (Normal Metabolizer)	The guideline does not provide a description of the impact of a DPYD activity score of 2 on fluorouracil.	The guideline does not provide a recommendation for fluorouracil in patients with a DPYD activity score of 2.	No recommendation
FDA Label Annotation ¹	Genotype DPYD:Reference/Reference	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype DPYD:Reference/Reference	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clinical pharmacology and therapeutics. 2013. PMID:23988873
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clinical pharmacology and therapeutics. 2018. PMID:29152729
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines. European journal of human genetics : EJHG. 2020. PMID:31745289
Drugs@FDA: Drug Product Carac (fluorouracil), Bausch Health US, LLC - NDA020985/SUPPL-19, 05/26/2022.
Drugs@FDA: Drug Product FLUOROURACIL (FLUOROURACIL), Eugia US LLC - ANDA202669/SUPPL-9, 03/21/2024.
Drugs@FDA: Drug Product Fluorouracil (Fluorouracil), BluePoint Laboratories - ANDA210124/SUPPL-9, 03/21/2024.
FDA Table of Pharmacogenetic Associations.

flurbiprofen

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype CYP2C9:1/1 Phenotype Normal Metabolizer Activity Score 2.0	CYP2C9: Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.	Strong
FDA Label Annotation ¹	Genotype CYP2C9:1/1	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2C9:1/1	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

Activity Score

2.0

CYP2C9: Normal metabolism

Strong

FDA Label Annotation ¹

Genotype

CYP2C9:*1/*1

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association ¹

Genotype

CYP2C9:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clinical pharmacology and therapeutics. 2020. PMID:32189324
Drugs@FDA: Drug Product FLURBIPROFEN SODIUM (flurbiprofen sodium), NDA019404, Rebel Distributors Corp.
Drugs@FDA: Drug Product flurbiprofen (NDA018766)
FDA Table of Pharmacogenetic Associations.

fluvastatin

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2C9:*1/*1;
SLCO1B1:*1/*1

Phenotypes

CYP2C9:: Normal Metabolizer
SLCO1B1:: Normal Function

Activity Scores

CYP2C9:: 2.0
SLCO1B1:: N/A

CYP2C9: Normal exposure.
SLCO1B1: Typical myopathy risk and statin exposure.

Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin.

Strong

Citations:

The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clinical pharmacology and therapeutics. 2022. PMID:35152405

fosphenytoin

The displayed recommendation for CYP2C9 and phenytoin is ONLY valid for non-carriers of the HLA-B*15:02 high-risk allele. PharmCAT Named Allele Matcher does not determine HLA status. CPIC guidance: Fos-/Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of fos-/phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In HLA-B*15:02 carriers, carbamazepine should not be used as an alternative. Alternative medications such as oxcarbazepine, eslicarbazepine acetate, and lamotrigine have some evidence linking SJS/TEN with the HLA-B*15:02 allele, and thus caution should be used in choosing alternatives to phenytoin.

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: PHT naive No Action	Genotype CYP2C9:1/1; HLA-B:Unknown/Unknown Phenotype Normal Metabolizer Activity Scores CYP2C9: 2.0 HLA-B: N/A	CYP2C9: Normal phenytoin metabolism HLA-B: n/a	No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.	Strong
CPIC Guideline Annotation Population: PHT use >3mos No Action	Genotype CYP2C9:1/1; HLA-B:Unknown/Unknown Phenotype Normal Metabolizer Activity Scores CYP2C9: 2.0 HLA-B: N/A	CYP2C9: Normal phenytoin metabolism HLA-B: n/a	No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.	Strong
FDA Label Annotation ¹	Genotypes CYP2C19:2/2; CYP2C9:1/1; HLA-B:Unknown/Unknown	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ^{1, 2}	Genotypes CYP2C9:1/1; HLA-B:Unknown/Unknown	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clinical pharmacology and therapeutics. 2014. PMID:25099164
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update. Clinical pharmacology and therapeutics. 2021. PMID:32779747
Drugs@FDA: Drug Product CEREBYX (Fosphenytoin Sodium), NDA020450, Pfizer Laboratories Div Pfizer Inc.
FDA Table of Pharmacogenetic Associations.

halothane

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clinical pharmacology and therapeutics. 2019. PMID:30499100

ibuprofen

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

Activity Score

2.0

CYP2C9: Normal metabolism

Strong

FDA PGx Association ¹

Genotype

CYP2C9:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clinical pharmacology and therapeutics. 2020. PMID:32189324
FDA Table of Pharmacogenetic Associations.

imipramine

Source

Genes

Implications

Recommendation

Classification

Population:
general

Alternate Drug

Dosing Info

Genotype

CYP2C19:*2/*2;
CYP2D6:Not called - no variant data provided

Phenotypes

CYP2C19:: Poor Metabolizer
CYP2D6:: No Result

Activity Scores

CYP2C19:: N/A
CYP2D6:: No Result

CYP2C19: Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects
CYP2D6: n/a

Other Considerations

Optional

Population:
Unspecified

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

The risk of side effects is increased. The gene variation results in an increase in the plasma concentration of imipramine+desipramine.

Use 70% of the standard dose and monitor the effect and side effects or the imipramine and desipramine plasma concentrations to determine the maintenance dose, or, avoid imipramine. Antidepressants that are not or to a lesser extent metabolised by CYP2C19 include, for example, nortriptyline, fluvoxamine and mirtazapine.

Unspecified

Citations:

Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clinical pharmacology and therapeutics. 2013. PMID:23486447
Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical pharmacology and therapeutics. 2017. PMID:27997040
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232

irinotecan

Alleles determined based on the CPIC UGT1A1 allele definition file due to limited allele definition information in the DPWG UGT1A1 document

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

UGT1A1:*1/*1

Phenotype

Normal Metabolizer

The guideline does not provide a description of the impact of a normal metabolizer phenotype on irinotecan.

The guideline does not provide a recommendation for irinotecan in normal metabolizers

No recommendation

FDA Label Annotation ¹

Genotype

UGT1A1:*1/*1

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association ¹

Genotype

UGT1A1:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan. European journal of human genetics : EJHG. 2023. PMID:36443464
Drugs@FDA: Drug Product Camptosar (irinotecan hydrochloride), Pharmacia & Upjohn Company LLC - NDA020571/SUPPL-53, 01/27/2022.
Drugs@FDA: Drug Product Onivyde (IRINOTECAN HYDROCHLORIDE), Ipsen Biopharmaceuticals, Inc. - NDA207793/SUPPL-16, 02/13/2024.
FDA Table of Pharmacogenetic Associations.

isoflurane

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.

Strong

Population:
Unspecified

Alternate Drug

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

"CONTRAINDICATIONS...with known or suspected genetic susceptibility to malignant hyperthermia...FORANE [isoflurane] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants." See label for more information. *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clinical pharmacology and therapeutics. 2019. PMID:30499100
Drugs@FDA: Drug Product FORANE (isoflurane), NDA017624, Baxter Healthcare Corporation.

ivacaftor

Source

Genes

Implications

Recommendation

Classification

Population:
general

Alternate Drug

Genotype

CFTR:Reference/
Reference

Phenotype

ivacaftor non-responsive in CF patients

CFTR: An individual diagnosed with cystic fibrosis (CF) and negative for a CFTR variant listed in the FDA-approved drug label as being responsive to ivacaftor.

Ivacaftor is not recommended

Moderate

FDA Label Annotation ¹

Genotype

CFTR:Reference/Reference

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clinical pharmacology and therapeutics. 2014. PMID:24598717
Drugs@FDA: Drug Product Kalydeco (ivacaftor), NDA203188, Vertex Pharmaceuticals Incorporated.

lansoprazole

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity

Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.

Moderate

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Population:
Unspecified

No Action

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

The higher plasma concentration of lansoprazole results in an increase in the therapeutic effectiveness, without an increase in the incidence of side effects.

NO action is needed for this gene-drug interaction.

Unspecified

Affected subgroup: CYP2C19 poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clinical pharmacology and therapeutics. 2021. PMID:32770672
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
FDA Table of Pharmacogenetic Associations.

lornoxicam

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

Activity Score

2.0

CYP2C9: Normal metabolism

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clinical pharmacology and therapeutics. 2020. PMID:32189324

lovastatin

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Indicate a Potential Impact on Safety or Response]

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

Phenotype

Normal Function

SLCO1B1: Typical myopathy risk and statin exposure

Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin.

Strong

Citations:

The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clinical pharmacology and therapeutics. 2022. PMID:35152405

mavacamten

Source

Genes

Implications

Recommendation

Classification

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations and may have higher adverse reaction risk (heart failure). Dosage is based on individual response. The dose titration and monitoring schedule accounts for differences due to CYP2C19 genetic variation, so adjustments based on CYP2C19 genotype are not necessary. Refer to FDA labeling for specific dosing recommendations and monitoring." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

FDA Table of Pharmacogenetic Associations.

meloxicam

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

Activity Score

2.0

CYP2C9: Normal metabolism

Strong

FDA Label Annotation ¹

Genotype

CYP2C9:*1/*1

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association ¹

Genotype

CYP2C9:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clinical pharmacology and therapeutics. 2020. PMID:32189324
Drugs@FDA: Drug Product Mobic (meloxicam), NDA020938, REMEDYREPACK INC.
Drugs@FDA: Drug Product QMIIZ ODT (meloxicam), NDA211210, TerSera Therapeutics LLC.
Drugs@FDA: Drug Product Vivlodex (meloxicam), NDA207233, Egalet US Inc.
FDA Table of Pharmacogenetic Associations.

mercaptopurine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype NUDT15:1/1; TPMT:1/1 Phenotypes NUDT15: Normal Metabolizer TPMT: Normal Metabolizer	NUDT15: Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression TPMT: Lower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.	Start with normal starting dose (e.g., 75 mg/m2/day or 1.5 mg/kg/day) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow at least 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 16401827, 11302950). Other Considerations Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers.	Strong
DPWG Guideline Annotation Population: Unspecified No Action	Genotype NUDT15:1/1 Phenotype Normal Metabolizer	The guideline does not provide a description of the impact of a normal metabolizer phenotype on mercaptopurine.	The guideline does not provide a recommendation for mercaptopurine in normal metabolizers	No recommendation
DPWG Guideline Annotation Population: Unspecified No Action	Genotype TPMT:1/1 Phenotype Normal Metabolizer	The guideline does not provide a description of the impact of a normal metabolizer phenotype on mercaptopurine.	The guideline does not provide a recommendation for mercaptopurine in normal metabolizers.	No recommendation
FDA Label Annotation ¹	Genotypes NUDT15:1/1; TPMT:1/1	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotypes NUDT15:1/1; TPMT:1/1	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clinical pharmacology and therapeutics. 2011. PMID:21270794
Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clinical pharmacology and therapeutics. 2013. PMID:23422873
Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clinical pharmacology and therapeutics. 2019. PMID:30447069
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Drugs@FDA: Drug Product PURINETHOL (Mercaptopurine), Quinn Pharmaceuticals - NDA009053/SUPPL-40, 12/29/2020.
Drugs@FDA: Drug Product PURIXAN (mercaptopurine), Nova Laboratories, Ltd - NDA205919/SUPPL-4, 04/07/2020.
FDA Table of Pharmacogenetic Associations.

methoxyflurane

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clinical pharmacology and therapeutics. 2019. PMID:30499100

methylene blue

PharmCAT reports based on VCF file input and some VCF files do not specify hemizygous (one X chromosome) and instead represent samples as homozygous. See PharmCAT FAQs (https://pharmcat.org/faqs/).

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

Phenotype

Normal

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Strong

FDA Label Annotation ¹

Genotype

G6PD:B (reference)/B (reference)

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clinical pharmacology and therapeutics. 2014. PMID:24787449
Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2023. PMID:36049896
Drugs@FDA: Drug Product PROVAYBLUE (methylene blue), NDA204630, American Regent, Inc.

nitrofurantoin

PharmCAT reports based on VCF file input and some VCF files do not specify hemizygous (one X chromosome) and instead represent samples as homozygous. See PharmCAT FAQs (https://pharmcat.org/faqs/).

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

Phenotype

Normal

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Strong

FDA Label Annotation ¹

Genotype

G6PD:B (reference)/B (reference)

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Drugs@FDA: Drug Product Furadantin (Nitrofurantoin), NDA009175, Casper Pharma LLC.

omeprazole

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity

Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.

Moderate

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Population:
Unspecified

No Action

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

The higher plasma concentration of omeprazole results in an increase in the therapeutic effectiveness, without an increase in the side effects.

NO action is required for this gene-drug interaction.

Unspecified

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clinical pharmacology and therapeutics. 2021. PMID:32770672
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
FDA Table of Pharmacogenetic Associations.

pantoprazole

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate
DPWG Guideline Annotation Population: Unspecified No Action	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer	The higher plasma concentration of pantoprazole results in an increase in the therapeutic effectiveness, without an increase in the side effects.	NO action is required for this gene-drug interaction.	Unspecified
FDA Label Annotation Population: Unspecified Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"For adult patients who are CYP2C19 poor metabolizers, no dosage adjustment is needed...For known pediatric poor metabolizers, a dose reduction should be considered." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Pediatrics; Affected subgroup: CYP2C19 intermediate or poor metabolizers Dosing Info	Genotype CYP2C19:2/2 Phenotype Poor Metabolizer		"Results in higher systemic concentrations. Consider dosage reduction in children who are poor metabolizers. No dosage adjustment is needed for adult patients who are intermediate or poor metabolizers." *	Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clinical pharmacology and therapeutics. 2021. PMID:32770672
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Drugs@FDA: Drug Product Protonix Delayed-Release (PANTOPRAZOLE SODIUM), NDA020987, Avera McKennan Hospital.
FDA Table of Pharmacogenetic Associations.

pegloticase

PharmCAT reports based on VCF file input and some VCF files do not specify hemizygous (one X chromosome) and instead represent samples as homozygous. See PharmCAT FAQs (https://pharmcat.org/faqs/).

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

Phenotype

Normal

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Strong

FDA Label Annotation ¹

Genotype

G6PD:B (reference)/B (reference)

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clinical pharmacology and therapeutics. 2014. PMID:24787449
Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2023. PMID:36049896
Drugs@FDA: Drug Product Krystexxa (pegloticase), BLA125293, Horizon Pharma Inc.

phenprocoumon

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

VKORC1:
rs9923231 reference (C)/
rs9923231 reference (C)

Phenotype

-1639 GG

The guideline does not provide a description of the impact of the VKORC1 rs9923231 CC genotype (-1639 GG genotype) on phenprocoumon.

The guideline does not provide a recommendation for phenprocoumon in patients with the VKORC1 rs9923231 CC genotype (-1639 GG genotype).

No recommendation

Citations:

Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232

phenytoin

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: PHT naive No Action	Genotype CYP2C9:1/1; HLA-B:Unknown/Unknown Phenotype Normal Metabolizer Activity Scores CYP2C9: 2.0 HLA-B: N/A	CYP2C9: Normal phenytoin metabolism HLA-B: n/a	No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.	Strong
CPIC Guideline Annotation Population: PHT use >3mos No Action	Genotype CYP2C9:1/1; HLA-B:Unknown/Unknown Phenotype Normal Metabolizer Activity Scores CYP2C9: 2.0 HLA-B: N/A	CYP2C9: Normal phenytoin metabolism HLA-B: n/a	No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.	Strong
DPWG Guideline Annotation Population: Unspecified No Action	Genotype CYP2C9:1/1 Phenotype Normal Metabolizer	The guideline does not provide a description of the impact of a normal metabolizer phenotype on phenytoin.	The guideline does not provide a recommendation for phenytoin in normal metabolizers.	No recommendation
FDA Label Annotation ¹	Genotypes CYP2C9:1/1; HLA-B:Unknown/Unknown	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ^{1, 2}	Genotypes CYP2C9:1/1; HLA-B:Unknown/Unknown	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clinical pharmacology and therapeutics. 2014. PMID:25099164
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update. Clinical pharmacology and therapeutics. 2021. PMID:32779747
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Drugs@FDA Drug Product: DILANTIN (phenytoin), NDA008762, Upjohn.
FDA Table of Pharmacogenetic Associations.

piroxicam

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

Activity Score

2.0

CYP2C9: Normal metabolism

Strong

FDA Label Annotation ¹

Genotype

CYP2C9:*1/*1

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association ¹

Genotype

CYP2C9:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clinical pharmacology and therapeutics. 2020. PMID:32189324
Drugs@FDA: Drug Product Feldene (piroxicam), NDA018147, Pfizer Laboratories Div Pfizer Inc.
FDA Table of Pharmacogenetic Associations.

pitavastatin

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

Phenotype

Normal Function

SLCO1B1: Typical myopathy risk and statin exposure

Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin.

Strong

Citations:

The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clinical pharmacology and therapeutics. 2022. PMID:35152405

pravastatin

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

Phenotype

Normal Function

SLCO1B1: Typical myopathy risk and statin exposure

Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin.

Strong

Citations:

The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clinical pharmacology and therapeutics. 2022. PMID:35152405

primaquine

PharmCAT reports based on VCF file input and some VCF files do not specify hemizygous (one X chromosome) and instead represent samples as homozygous. See PharmCAT FAQs (https://pharmcat.org/faqs/).

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

Phenotype

Normal

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Strong

FDA Label Annotation ¹

Genotype

G6PD:B (reference)/B (reference)

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2023. PMID:36049896
Drugs@FDA: Drug Product Primaquine Phosphate (Primaquine Phosphate), NDA008316, PD-Rx Pharmaceuticals, Inc.

quetiapine

The CYP3A4 alleles are determined based on PharmVar CYP3A4 allele definitions. See PharmCAT disclaimer for further information.

Source

Genes

Implications

Recommendation

Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Population:
Unspecified

No Action

Genotype

CYP3A4:*1/*1

Phenotype

Normal Metabolizer

The guideline does not provide a description of the impact of a normal metabolizer phenotype on quetiapine.

The guideline does not provide a recommendation for quetiapine in normal metabolizers.

No recommendation

Citations:

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP3A4 and CYP1A2 and antipsychotics. European journal of human genetics : EJHG. 2024. PMID:37002327

rabeprazole

Source

Genes

Implications

Recommendation

Classification

Affected subgroup: CYP2C19 poor metabolizers

Other Guidance

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

"Results in higher systemic concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

FDA Table of Pharmacogenetic Associations.

rasburicase

PharmCAT reports based on VCF file input and some VCF files do not specify hemizygous (one X chromosome) and instead represent samples as homozygous. See PharmCAT FAQs (https://pharmcat.org/faqs/).

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

Phenotype

Normal

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Strong

FDA Label Annotation ¹

Genotype

G6PD:B (reference)/B (reference)

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clinical pharmacology and therapeutics. 2014. PMID:24787449
Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2023. PMID:36049896
Drugs@FDA: Drug Product Elitek (rasburicase), BLA103946, sanofi-aventis U.S. LLC.

rosuvastatin

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

ABCG2:
rs2231142 reference (G)/
rs2231142 reference (G);
SLCO1B1:*1/*1

Phenotypes

ABCG2:: Normal Function
SLCO1B1:: Normal Function

ABCG2: Typical myopathy risk and rosuvastatin exposure
SLCO1B1: Typical myopathy risk and statin exposure

Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin.

Strong

FDA PGx Association ¹

Genotype

SLCO1B1:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clinical pharmacology and therapeutics. 2022. PMID:35152405
FDA Table of Pharmacogenetic Associations.

sertraline

Source

Genes

Implications

Recommendation

Classification

Population:
general

Alternate Drug

Dosing Info

Genotype

CYP2B6:*1/*6;
CYP2C19:*2/*2

Phenotypes

CYP2B6:: Intermediate Metabolizer
CYP2C19:: Poor Metabolizer

CYP2B6: Reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.
CYP2C19: Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.

Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.

Moderate

Population:
Unspecified

Dosing Info

Genotype

CYP2C19:*2/*2

Phenotype

Poor Metabolizer

The risk of side effects is increased. The gene variation leads to increased plasma concentrations of sertraline.

Do not give doses exceeding 75 mg/day. Guide the dose by response and side effects and/or sertraline plasma concentration.

Unspecified

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clinical pharmacology and therapeutics. 2015. PMID:25974703
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clinical pharmacology and therapeutics. 2023. PMID:37032427
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs. European journal of human genetics : EJHG. 2022. PMID:34782755

sevoflurane

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.

Strong

Population:
Unspecified

Alternate Drug

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

"CONTRAINDICATIONS: Known or suspected genetic susceptibility to malignant hyperthermia...ULTANE [sevoflurane] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants." See label for more information. *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clinical pharmacology and therapeutics. 2019. PMID:30499100
Drugs@FDA: Drug Product Ultane (Sevoflurane), NDA020478, AbbVie Inc.

simvastatin

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

Phenotype

Normal Function

SLCO1B1: Typical myopathy risk and statin exposure

Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin.

Strong

Population:
Unspecified

No Action

Genotype

SLCO1B1:*1/*1

Phenotype

Normal Function

The guideline does not provide a description of the impact of the SLCO1B1 521 TT genotype on simvastatin.

The guideline does not provide a recommendation for atorvastatin in patients with the SLCO1B1 521 TT genotype.

No recommendation

FDA PGx Association ¹

Genotype

SLCO1B1:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clinical pharmacology and therapeutics. 2012. PMID:22617227
The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clinical pharmacology and therapeutics. 2014. PMID:24918167
The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clinical pharmacology and therapeutics. 2022. PMID:35152405
FDA Table of Pharmacogenetic Associations.

siponimod

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

The guideline does not provide a description of the impact of a normal metabolizer phenotype on siponimod.

The guideline does not provide a recommendation for siponimod in normal metabolizers.

No recommendation

Population:
Unspecified

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

Activity Score

2.0

The MAYZENT (siponimod) label states: "Recommended Dosage in Patients With CYP2C9 Genotypes *1/*1, *1/*2, or *2/*2" "Initiate MAYZENT with a 5-day titration, as shown in Table 1... A starter pack should be used for patients who will be titrated to the 2-mg maintenance dosage" "After treatment titration (see Treatment Initiation), the recommended maintenance dosage of MAYZENT is 2 mg taken orally once daily starting on Day 6." See label for more information. *

Unspecified

FDA PGx Association ¹

Genotype

CYP2C9:*1/*1

FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

succinylcholine

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.

Strong

Population:
Unspecified

Alternate Drug

Other Guidance

Genotype

CACNA1S:Reference/
Reference;
RYR1:Reference/
Reference

Phenotypes

CACNA1S:: Uncertain Susceptibility
RYR1:: Uncertain Susceptibility

"ANECTINE [succinylcholine] is contraindicated in patients with...[k]nown or suspected genetic susceptibility to malignant hyperthermia...Anectine [succinylcholine] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants...Succinylcholine is metabolized by plasma cholinesterase and should be used with caution, if at all, in patients known to be or suspected of being homozygous for the atypical plasma cholinesterase gene [BCHE] ." See label for more information. *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clinical pharmacology and therapeutics. 2019. PMID:30499100
Drugs@FDA: Drug Product Anectine (Succinylcholine Chloride), NDA008453, Sandoz Inc.

tacrolimus

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP3A5:*1/*1

Phenotype

Normal Metabolizer

CYP3A5: Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations.

Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.

Other Considerations

This recommendation includes the use of tacrolimus in kidney, heart, lung and hematopoietic stem cell transplant patients, and liver transplant patients where the donor and recipient genotypes are identical. Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function). Typically with other CYP enzymes, a normal metabolizer would be classified as having normal metabolism, and therefore, the drug dose would not change based on the patient’s genotype. However, in the case of CYP3A5 and tacrolimus, a CYP3A5 expresser (i.e., CYP3A5 normal metabolizer or intermediate metabolizer) would require a higher recommended starting dose, and the CYP3A5 non-expresser (i.e., poor metabolizer) would require the standard recommended starting dose.

Strong

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Population:
Unspecified

Dosing Info

Genotype

CYP3A5:*1/*1

Phenotype

Normal Metabolizer

An increase of the initial dose can result in an increased chance of reaching a tacrolimus concentration within the target range before the start of therapeutic drug monitoring. However, there is no direct evidence that this results in improved clinical results. The genetic variation results in an increased conversion of tacrolimus to inactive metabolites and therefore a higher required dose.

LIVER TRANSPLANTATION In addition to the patient’s genotype, the metabolism of tacrolimus is also determined by the genotype of the transplanted liver. LIVER is also of the genotype HOMOZYGOUS EXPRESSOR: Use 2.5 times the normal initial dose. Adjustment of the dose should then be based on therapeutic drug monitoring. LIVER has a DIFFERENT genotype: There is insufficient evidence in the literature to support a dose recommendation. OTHER TRANSPLANTATION Use 2.5 times the initial dose that would yield the desired result in non-expressers. Adjustment of the dose should then be based on therapeutic drug monitoring. For example: One Dutch study found a median trough concentration for tacrolimus after three days of 9.4 ng/mL at an initial dose of 0.15 mg/kg twice daily for 5 homozygous kidney transplant patients. Their target value was 10 - 15 ng/mL.

Unspecified

Affected subgroup: CYP3A5 intermediate or normal metabolizers

Dosing Info

Genotype

CYP3A5:*1/*1

Phenotype

Normal Metabolizer

"Results in lower systemic concentrations, lower probability of achieving target concentrations and may result in higher rejection risk. Measure drug concentrations and adjust dosage based on trough whole blood tacrolimus concentrations." *

Unspecified

^* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clinical pharmacology and therapeutics. 2015. PMID:25801146
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
FDA Table of Pharmacogenetic Associations.

tafenoquine

PharmCAT reports based on VCF file input and some VCF files do not specify hemizygous (one X chromosome) and instead represent samples as homozygous. See PharmCAT FAQs (https://pharmcat.org/faqs/).

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

Phenotype

Normal

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Other Considerations

Tafenoquine’s safety has been established for a G6PD enzyme activity ≥70% of normal. (Inclusion criteria for clinical trials involving tafenoquine included G6PD activity ≥70%.)

Strong

FDA Label Annotation ¹

Genotype

G6PD:B (reference)/B (reference)

FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clinical pharmacology and therapeutics. 2014. PMID:24787449
Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2023. PMID:36049896
Drugs@FDA: Drug Product Arakoda (Tafenoquine), NDA210607, 60 Degrees Pharmaceuticals, LLC.

tegafur

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

DPYD:Reference/
Reference

Phenotype

2.0 (Normal Metabolizer)

The guideline does not provide a description of the impact of a DPYD activity score of 2 on tegafur.

The guideline does not provide a recommendation for tegafur in patients with a DPYD activity score of 2.

No recommendation

Citations:

Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines. European journal of human genetics : EJHG. 2020. PMID:31745289

tenoxicam

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2C9:*1/*1

Phenotype

Normal Metabolizer

Activity Score

2.0

CYP2C9: Normal metabolism

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clinical pharmacology and therapeutics. 2020. PMID:32189324

thioguanine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general No Action	Genotype NUDT15:1/1; TPMT:1/1 Phenotypes NUDT15: Normal Metabolizer TPMT: Normal Metabolizer	NUDT15: Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression TPMT: Lower concentrations of TGN metabolites, but note that TGN after thioguanine are 5-10X higher than TGN after mercaptopurine or azathioprine. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.	Start with normal starting dose (e.g., 40-60 mg/m2/day) and adjust doses of thioguanine and of other myelosuppressive therapy without any special emphasis on thioguanine. Allow 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 11037857). Other Considerations Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers.	Strong
DPWG Guideline Annotation Population: Unspecified No Action	Genotype NUDT15:1/1 Phenotype Normal Metabolizer	The guideline does not provide a description of the impact of a normal metabolizer phenotype on thioguanine.	The guideline does not provide a recommendation for thioguanine in normal metabolizers	No recommendation
DPWG Guideline Annotation Population: Unspecified No Action	Genotype TPMT:1/1 Phenotype Normal Metabolizer	The guideline does not provide a description of the impact of a normal metabolizer phenotype on thioguanine.	The guideline does not provide a recommendation for thioguanine in normal metabolizers.	No recommendation
FDA Label Annotation ¹	Genotypes NUDT15:1/1; TPMT:1/1	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotypes NUDT15:1/1; TPMT:1/1	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clinical pharmacology and therapeutics. 2011. PMID:21270794
Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clinical pharmacology and therapeutics. 2013. PMID:23422873
Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clinical pharmacology and therapeutics. 2019. PMID:30447069
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
Drugs@FDA: Drug Product TABLOID (thioguanine), NDA012429, Aspen Global Inc.
FDA Table of Pharmacogenetic Associations.

toluidine blue

PharmCAT reports based on VCF file input and some VCF files do not specify hemizygous (one X chromosome) and instead represent samples as homozygous. See PharmCAT FAQs (https://pharmcat.org/faqs/).

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

Phenotype

Normal

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Other Considerations

Toluidine blue classification strength is based on extrapolation from methylene blue data

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clinical pharmacology and therapeutics. 2014. PMID:24787449
Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2023. PMID:36049896

trimipramine

Source

Genes

Implications

Recommendation

Classification