PharmCAT Report [pharmcat.example]

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
CPIC Guideline Annotation Population: general No Action	Genotype HLA-B:15:02/57:01 Phenotype *58:01 negative	HLA-B: Low or reduced risk of allopurinol-induced SCAR	Use allopurinol per standard dosing guidelines	Strong
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
FDA Label Annotation ¹	Genotype HLA-B:15:02/57:01	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype HLA-B:15:02/57:01	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clinical pharmacology and therapeutics. 2013. PMID:23232549
Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update. Clinical pharmacology and therapeutics. 2016. PMID:26094938
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
Drugs@FDA: Drug Product ALOPRIM (allopurinol), NDA020298, Mylan.
FDA Table of Pharmacogenetic Associations.

amitriptyline

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Dosing Info	Genotype CYP2C19:38/38; CYP2D6:1/3 Phenotypes CYP2C19: Normal Metabolizer CYP2D6: Intermediate Metabolizer Activity Scores CYP2C19: N/A CYP2D6: 1.0	CYP2C19: Normal metabolism of tertiary amines CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects	Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Other Considerations 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.	Moderate
DPWG Guideline Annotation Population: Unspecified Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	The risk of side effects is increased, because the gene variation leads to higher plasma concentrations of the active metabolite nortriptyline and to a lesser extent of amitriptyline.	Use 75% of the standard dose and monitor the efficacy and side effects or the plasma concentrations of amitriptyline and nortriptyline to adjust the maintenance dose	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0		"May alter systemic concentrations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38;
CYP2D6:*1/*3

Phenotypes

CYP2C19:: Normal Metabolizer
CYP2D6:: Intermediate Metabolizer

Activity Scores

CYP2C19:: N/A
CYP2D6:: 1.0

CYP2C19: Normal metabolism of tertiary amines
CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects

Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

Moderate

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

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The risk of side effects is increased, because the gene variation leads to higher plasma concentrations of the active metabolite nortriptyline and to a lesser extent of amitriptyline.

Use 75% of the standard dose and monitor the efficacy and side effects or the plasma concentrations of amitriptyline and nortriptyline to adjust the maintenance dose

Unspecified

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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 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
FDA Table of Pharmacogenetic Associations.

amoxapine

Source	Genes	Implications	Recommendation	Classification
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0		"May alter 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: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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:

FDA Table of Pharmacogenetic Associations.

aripiprazole

Source	Genes	Implications	Recommendation	Classification
DPWG Guideline Annotation Population: Unspecified No Action	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	The genetic variation increases the plasma concentration of the sum of aripiprazole and the active metabolite dehydroaripiprazole to a limited degree. There is insufficient evidence that this increases the risk of side effects.	NO action is needed for this gene-drug interaction.	Unspecified
FDA Label Annotation ¹	Genotype CYP2D6:1/3	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2D6:1/3	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The genetic variation increases the plasma concentration of the sum of aripiprazole and the active metabolite dehydroaripiprazole to a limited degree. There is insufficient evidence that this increases the risk of side effects.

NO action is needed for this gene-drug interaction.

Unspecified

FDA Label Annotation ¹

Genotype

CYP2D6:*1/*3

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

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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 CYP2D6, CYP3A4 and CYP1A2 and antipsychotics. European journal of human genetics : EJHG. 2024. PMID:37002327
Drugs@FDA: Drug Product ABILIFY (ARIPIPRAZOLE), NDA021436, Rebel Distributors Corp.
Drugs@FDA: Drug Product ABILIFY MAINTENA (aripiprazole), NDA202971, Otsuka America Pharmaceutical, Inc.
FDA Table of Pharmacogenetic Associations.

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

atomoxetine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: adults Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	CYP2D6: Possibly higher atomoxetine concentrations as compared to normal metabolizers but questionable clinical significance. Intermediate metabolizers with an activity score of 1 may be at an increased risk of discontinuation as compared to poor metabolizers.	Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations. Other Considerations Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated.	Moderate
CPIC Guideline Annotation Population: pediatrics Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	CYP2D6: Possibly higher atomoxetine concentrations as compared to normal metabolizers but questionable clinical significance. Intermediate metabolizers with an activity score of 1 may be at an increased risk of discontinuation as compared to poor metabolizers.	Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Other Considerations Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL.	Moderate
DPWG Guideline Annotation Population: Unspecified Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	The dose requirement can be reduced, because the genetic variation results in a higher atomoxetine plasma concentration.	In the event of side effects occurring and/or a response later than 9 weeks: reduce the dose and check whether the effect is conserved The plasma concentration of atomoxetine is a factor of 2-3 times higher for IM than for NM at the same dose.	Unspecified
FDA Label Annotation ¹	Genotype CYP2D6:1/3	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2D6:1/3	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for Cytochrome P450 (CYP)2D6 Genotype and Atomoxetine Therapy. Clinical pharmacology and therapeutics. 2019. PMID:30801677
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 CYP2D6 and COMT with atomoxetine and methylphenidate. European journal of human genetics : EJHG. 2023. PMID:36509836
Drugs@FDA: Drug Product Strattera (Atomoxetine hydrochloride), NDA021411, Eli Lilly and Company.
FDA Table of Pharmacogenetic Associations.

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.

brexpiprazole

Source	Genes	Implications	Recommendation	Classification
DPWG Guideline Annotation Population: Unspecified No Action	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	There are indications supporting an increase in the exposure to brexpiprazole, but no indications supporting an increase in side effects in patients with this gene variation.	NO action is required for this gene-drug interaction.	Unspecified
FDA Label Annotation ¹	Genotype CYP2D6:1/3	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2D6:1/3	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

There are indications supporting an increase in the exposure to brexpiprazole, but no indications supporting an increase in side effects in patients with this gene variation.

NO action is required for this gene-drug interaction.

Unspecified

FDA Label Annotation ¹

Genotype

CYP2D6:*1/*3

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

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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

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
Drugs@FDA: Drug Product REXULTI (brexpiprazole), NDA205422, Otsuka America Pharmaceutical, Inc.
FDA Table of Pharmacogenetic Associations.

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.

carbamazepine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: CBZ naive Alternate Drug	Genotype HLA-A:Unknown/Unknown; HLA-B:15:02/57:01 Phenotype *15:02 positive	HLA-A: n/a HLA-B: Greater risk of carbamazepine-induced SJS/TEN	If patient is carbamazepine-naïve, do not use carbamazepine. Other Considerations Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B15:08, HLA-B15:11, and HLA-B15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B15:30 and HLA-B*15:31, should also be considered.	Strong
CPIC Guideline Annotation Population: CBZ use >3mos Other Guidance	Genotype HLA-A:Unknown/Unknown; HLA-B:15:02/57:01 Phenotype *15:02 positive	HLA-A: n/a HLA-B: Greater risk of carbamazepine-induced SJS/TEN	The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (~4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future. Other Considerations Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B15:08, HLA-B15:11, and HLA-B15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B15:30 and HLA-B15:31, should also be considered.	Optional
CPIC Guideline Annotation Population: CBZ-no alternatives Alternate Drug	Genotype HLA-A:Unknown/Unknown; HLA-B:15:02/57:01 Phenotype *15:02 positive	HLA-A: n/a HLA-B: Greater risk of carbamazepine-induced SJS/TEN	If patient is carbamazepine-naïve, do not use carbamazepine. Other Considerations Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B15:08, HLA-B15:11, and HLA-B15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B15:30 and HLA-B*15:31, should also be considered.	Strong
DPWG Guideline Annotation Population: Unspecified Alternate Drug	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive	Patients with this genetic variation have a severely increased risk of experiencing the life-threatening cutaneous adverse event Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The risk of carbamazepine-induced SJS/TEN in these patients is 1.8-3.4%.	Choose an alternative if possible. Phenytoin, lamotrigine and oxcarbazepine also pose an increased risk of SJS/TEN in these patients, but the final risk is 10-fold lower for these medicines than for carbamazepine. Furthermore, in the case of oxcarbazepine, the most severe forms (SJS/TEN overlap and TEN) have not been observed.	Unspecified
FDA Label Annotation Population: Unspecified Alternate Drug	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive		"Tegretol [carbamazepine] should not be used in patients positive for HLAB1502 unless the benefits clearly outweigh the risks." See label for more information.	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Affected subgroup: HLA-B*15:02 allele positive Alternate Drug	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive		"Results in higher adverse reaction risk (severe skin reactions). Avoid use unless potential benefits outweigh risks and consider risks of alternative therapies. Patients positive for HLA-B15:02 may be at increased risk of severe skin reactions with other drugs that are associated with a risk of Stevens Johnson Syndrome/Toxic Epidermal necrolysis (SJS/TEN). Genotyping is not a substitute for clinical vigilance."	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 HLA-B genotype and carbamazepine dosing. Clinical pharmacology and therapeutics. 2013. PMID:23695185
Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clinical pharmacology and therapeutics. 2018. PMID:29392710
Drugs@FDA: Drug Product Tegretol (carbamazepine), NDA016608, REMEDYREPACK INC.
FDA Table of Pharmacogenetic Associations.

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 No Action	Genotype CYP2C19:38/38 Phenotype Normal Metabolizer	CYP2C19: Normal metabolism	Initiate therapy with recommended starting dose	Strong
DPWG Guideline Annotation ¹	Genotype CYP2C19:38/38	DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA Label Annotation ¹	Genotype CYP2C19:38/38	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2C19:38/38	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

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.

clomipramine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Dosing Info	Genotype CYP2C19:38/38; CYP2D6:1/3 Phenotypes CYP2C19: Normal Metabolizer CYP2D6: Intermediate Metabolizer Activity Scores CYP2C19: N/A CYP2D6: 1.0	CYP2C19: Normal metabolism of tertiary amines CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects	Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Other Considerations 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.	Optional
DPWG Guideline Annotation Population: Unspecified Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	The risk of side effects may be increased, because the gene variation leads to increased plasma concentrations of clomipramine and the active metabolite desmethylclomipramine.	Use 70% of the standard dose and monitor the effect and side effects or the plasma concentrations of clomipramine and desmethylclomipramine. For depression, the therapeutic range is 200-400 ng/mL for the sum of the plasma concentrations of clomipramine and desmethylclomipramine. For anxiety disorders, the therapeutic plasma concentration of clomipramine is approximately 100 ng/mL, in combination with a plasma concentration of desmethylclomipramine lower than 200 ng/mL. For obsessive compulsive disorder, the therapeutic plasma concentration of clomipramine is higher than 200 ng/mL, in combination with a plasma concentration of desmethylclomipramine that is as low as possible. A sum of the plasma concentrations of clomipramine and desmethylclomipramine higher than 600 ng/mL is considered toxic.	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0		"May alter systemic concentrations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38;
CYP2D6:*1/*3

Phenotypes

CYP2C19:: Normal Metabolizer
CYP2D6:: Intermediate Metabolizer

Activity Scores

CYP2C19:: N/A
CYP2D6:: 1.0

CYP2C19: Normal metabolism of tertiary amines
CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects

Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Optional

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

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The risk of side effects may be increased, because the gene variation leads to increased plasma concentrations of clomipramine and the active metabolite desmethylclomipramine.

Use 70% of the standard dose and monitor the effect and side effects or the plasma concentrations of clomipramine and desmethylclomipramine. For depression, the therapeutic range is 200-400 ng/mL for the sum of the plasma concentrations of clomipramine and desmethylclomipramine. For anxiety disorders, the therapeutic plasma concentration of clomipramine is approximately 100 ng/mL, in combination with a plasma concentration of desmethylclomipramine lower than 200 ng/mL. For obsessive compulsive disorder, the therapeutic plasma concentration of clomipramine is higher than 200 ng/mL, in combination with a plasma concentration of desmethylclomipramine that is as low as possible. A sum of the plasma concentrations of clomipramine and desmethylclomipramine higher than 600 ng/mL is considered toxic.

Unspecified

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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 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
FDA Table of Pharmacogenetic Associations.

clopidogrel

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: CVI ACS PCI No Action	Genotype CYP2C19:38/38 Phenotype Normal Metabolizer	CYP2C19: Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity	If considering clopidogrel, use at standard dose (75 mg/day) 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 No Action	Genotype CYP2C19:38/38 Phenotype Normal Metabolizer	CYP2C19: Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity	If considering clopidogrel, use at standard dose (75 mg/day) 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.	Strong
CPIC Guideline Annotation Population: NVI No Action	Genotype CYP2C19:38/38 Phenotype Normal Metabolizer	CYP2C19: Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity	If considering clopidogrel, use at standard dose (75 mg/day) 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.	Strong
DPWG Guideline Annotation ¹	Genotype CYP2C19:38/38	DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA Label Annotation ¹	Genotype CYP2C19:38/38	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2C19:38/38	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

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.

codeine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	CYP2D6: Reduced morphine formation	Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid.	Moderate
DPWG Guideline Annotation Population: Unspecified Alternate Drug Dosing Info Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	The genetic variation reduces the conversion of codeine to morphine. This can result in reduced analgesia.	For PAIN: It is not possible to offer adequately substantiated advice for dose adjustment based on the limited available literature for this phenotype. Be alert to a reduced effectiveness. In the case of inadequate effectiveness: 1. Try a dose increase. 2. If this does not work: choose an alternative. Do not select tramadol, as this is also metabolised by CYP2D6. Morphine is not metabolised by CYP2D6. Oxycodone is metabolised by CYP2D6 to a limited extent, but this does not result in differences in analgesia in patients. If no alternative is selected: advise the patient to report inadequate analgesia. For COUGH: No action required.	Unspecified
FDA Label Annotation ¹	Genotype CYP2D6:1/3	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ^{1, 2}	Genotype CYP2D6:1/3	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clinical pharmacology and therapeutics. 2012. PMID:22205192
Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clinical pharmacology and therapeutics. 2014. PMID:24458010
Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clinical pharmacology and therapeutics. 2021. PMID:33387367
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 CYP2D6 and opioids (codeine, tramadol and oxycodone). European journal of human genetics : EJHG. 2022. PMID:34267337
Drugs@FDA: Drug Product Codeine sulfate (codeine sulfate), NDA022402, West-Ward Pharmaceuticals Corp.
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.

desipramine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments. Other Considerations 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.	Optional
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0		"May alter 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

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.

Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Optional

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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 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.

dexlansoprazole

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Dosing Info	Genotype CYP2C19:38/38 Phenotype Normal Metabolizer	CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs	Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Optional
FDA PGx Association ¹	Genotype CYP2C19:38/38	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38

Phenotype

Normal Metabolizer

CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs

Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.

Optional

FDA PGx Association ¹

Genotype

CYP2C19:*38/*38

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

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.

doxepin

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Dosing Info	Genotype CYP2C19:38/38; CYP2D6:1/3 Phenotypes CYP2C19: Normal Metabolizer CYP2D6: Intermediate Metabolizer Activity Scores CYP2C19: N/A CYP2D6: 1.0	CYP2C19: Normal metabolism of tertiary amines CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects	Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Other Considerations 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.	Optional
DPWG Guideline Annotation Population: Unspecified Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	The risk of side effects may be increased, because the gene variation leads to increased plasma concentrations of doxepin and the active metabolite nordoxepin.	Use 80% of the standard dose and monitor the effect and side effects or the plasma concentrations of doxepin and nordoxepin in order to set the maintenance dose. The therapeutic range is 100-250 ng/mL for the sum of doxepin and nordoxepin plasma concentrations. Values higher than 400 ng/mL are considered toxic.	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only] Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0		"May alter systemic concentrations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38;
CYP2D6:*1/*3

Phenotypes

CYP2C19:: Normal Metabolizer
CYP2D6:: Intermediate Metabolizer

Activity Scores

CYP2C19:: N/A
CYP2D6:: 1.0

CYP2C19: Normal metabolism of tertiary amines
CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects

Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Optional

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

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The risk of side effects may be increased, because the gene variation leads to increased plasma concentrations of doxepin and the active metabolite nordoxepin.

Use 80% of the standard dose and monitor the effect and side effects or the plasma concentrations of doxepin and nordoxepin in order to set the maintenance dose. The therapeutic range is 100-250 ng/mL for the sum of doxepin and nordoxepin plasma concentrations. Values higher than 400 ng/mL are considered toxic.

Unspecified

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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 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
FDA Table of Pharmacogenetic Associations.

efavirenz

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: child >40kg_adult No Action	Genotype CYP2B6:1/1 Phenotype Normal Metabolizer	CYP2B6: Normal efavirenz metabolism	Initiate efavirenz with standard dosing (600 mg/day) Other Considerations The ENCORE study showed that in treatment-naïve patients randomized to initiate efavirenz-based regimens (combined with tenofovir and emtricitabine), 400 mg/day was non-inferior to 600 mg/day regardless of CYP2B6 genotype (PMID 24522178).	Strong
DPWG Guideline Annotation Population: Unspecified No Action	Genotype CYP2B6:1/1 Phenotype Normal Metabolizer	The guideline does not provide a description of the impact of a normal metabolizer phenotype on efavirenz.	The guideline does not provide a recommendation for efavirenz in normal metabolizers.	No recommendation
FDA PGx Association ¹	Genotype CYP2B6:1/1	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Source

Genes

Implications

Recommendation

Classification

Population:
child >40kg_adult

No Action

Genotype

CYP2B6:*1/*1

Phenotype

Normal Metabolizer

CYP2B6: Normal efavirenz metabolism

Initiate efavirenz with standard dosing (600 mg/day)

Other Considerations

The ENCORE study showed that in treatment-naïve patients randomized to initiate efavirenz-based regimens (combined with tenofovir and emtricitabine), 400 mg/day was non-inferior to 600 mg/day regardless of CYP2B6 genotype (PMID 24522178).

Strong

Population:
Unspecified

No Action

Genotype

CYP2B6:*1/*1

Phenotype

Normal Metabolizer

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

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

No recommendation

FDA PGx Association ¹

Genotype

CYP2B6:*1/*1

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.

eliglustat

Source	Genes	Implications	Recommendation	Classification
DPWG Guideline Annotation Population: Unspecified Alternate Drug Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	This gene variation reduces the conversion of eliglustat to inactive metabolites. However, in the absence of CYP2D6 and CYP3A inhibitors, this does not result in a clinically significant increased risk of side effects.	Co-medication with BOTH a MODERATE to STRONG CYP2D6 INHIBITOR AND a MODERATE to STRONG CYP3A INHIBITOR: Eliglustat is contra-indicated. Choose an alternative if possible. Strong CYP2D6 inhibitor: for example paroxetine, fluoxetine, quinidine, bupropione. Moderate CYP2D6 inhibitor: for example duloxetine, terbinafine, moclobemide, mirabegron, cinacalcet, dronedarone. Strong CYP3A inhibitor: for example ketoconazole, clarithromycin, itraconazole, cobicistat, indinavir, lopinavir, ritonavir, saquinavir, telaprevir, tipranavir, posaconazole, voriconazole, telithromycin, conivaptan, boceprevir. Moderate CYP3A inhibitor: for example erythromycin, ciprofloxacin, fluconazole, diltiazem, verapamil, aprepitant, atazanavir, darunavir, fosamprenavir, imatinib, cimetidine. Co-medication with a STRONG CYP2D6 INHIBITOR (e.g. paroxetine, fluoxetine, quinidine, bupropione): Use a dose of 84mg eliglustat 1x daily. Co-medication with a MODERATE CYP2D6 INHIBITOR (for example duloxetine, terbinafine, moclobemide, mirabegron, cinacalcet, dronedarone): Consider a dose of 84mg eliglustat 1x daily. Be alert to side effects. Co-medication with a STRONG CYP3A INHIBITOR (for example ketoconazole, clarithromycin, itraconazole, cobicistat, indinavir, lopinavir, ritonavir, saquinavir, telaprevir, tipranavir, posaconazole, voriconazole, telithromycin, conivaptan, boceprevir): Choose an alternative if possible. If an alternative is not an option: consider a dose of 84 mg eliglustat 1x daily and be alert to side effects. Co-medication with a MODERATE CYP3A INHIBITOR (for example erythromycin, ciprofloxacin, fluconazole, diltiazem, verapamil, aprepitant, atazanavir, darunavir, fosamprenavir, imatinib, cimetidine): Choose an alternative. If an alternative is not an option: consider a dose of 84mg eliglustat 1x daily and be alert to side effects. Co-medication with a STRONG CYP3A INDUCER (for example rifampicin, carbamazepine, phenobarbital, phenytoin, rifabutine, hypericum): Eliglustat is not recommended. The plasma concentration may decrease so sharply that a therapeutic effect cannot be achieved. Choose an alternative if possible. NO co-medication with a moderate or strong CYP2D6 or CYP3A inhibitor or strong CYP3A inducer: Use the standard dose of 84mg 2x daily.	Unspecified
FDA Label Annotation Population: Unspecified Dosing Info	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0		CYP2D6 IMs have a recommended dose of 84 mg orally twice daily. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] Affected subgroup: CYP2D6 ultrarapid, normal, intermediate, or poor metabolizers Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0		"Alters systemic concentrations, effectiveness, and adverse reaction risk (QT prolongation). Indicated for normal, intermediate, and poor metabolizer patients. Ultrarapid metabolizers may not achieve adequate concentrations to achieve a therapeutic effect. The recommended dosages are based on CYP2D6 metabolizer status. Coadministration with strong CYP3A inhibitors is contraindicated in intermediate and poor CYP2D6 metabolizers. Refer to FDA labeling for specific dosing recommendations." *	Unspecified

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

Alternate Drug

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

This gene variation reduces the conversion of eliglustat to inactive metabolites. However, in the absence of CYP2D6 and CYP3A inhibitors, this does not result in a clinically significant increased risk of side effects.

Co-medication with BOTH a MODERATE to STRONG CYP2D6 INHIBITOR AND a MODERATE to STRONG CYP3A INHIBITOR:

Eliglustat is contra-indicated. Choose an alternative if possible.

Strong CYP2D6 inhibitor: for example paroxetine, fluoxetine, quinidine, bupropione. Moderate CYP2D6 inhibitor: for example duloxetine, terbinafine, moclobemide, mirabegron, cinacalcet, dronedarone. Strong CYP3A inhibitor: for example ketoconazole, clarithromycin, itraconazole, cobicistat, indinavir, lopinavir, ritonavir, saquinavir, telaprevir, tipranavir, posaconazole, voriconazole, telithromycin, conivaptan, boceprevir. Moderate CYP3A inhibitor: for example erythromycin, ciprofloxacin, fluconazole, diltiazem, verapamil, aprepitant, atazanavir, darunavir, fosamprenavir, imatinib, cimetidine. Co-medication with a STRONG CYP2D6 INHIBITOR (e.g. paroxetine, fluoxetine, quinidine, bupropione):

Use a dose of 84mg eliglustat 1x daily.

Co-medication with a MODERATE CYP2D6 INHIBITOR (for example duloxetine, terbinafine, moclobemide, mirabegron, cinacalcet, dronedarone):

Consider a dose of 84mg eliglustat 1x daily. Be alert to side effects.

Co-medication with a STRONG CYP3A INHIBITOR (for example ketoconazole, clarithromycin, itraconazole, cobicistat, indinavir, lopinavir, ritonavir, saquinavir, telaprevir, tipranavir, posaconazole, voriconazole, telithromycin, conivaptan, boceprevir):

Choose an alternative if possible.
If an alternative is not an option: consider a dose of 84 mg eliglustat 1x daily and be alert to side effects.

Co-medication with a MODERATE CYP3A INHIBITOR (for example erythromycin, ciprofloxacin, fluconazole, diltiazem, verapamil, aprepitant, atazanavir, darunavir, fosamprenavir, imatinib, cimetidine):

Choose an alternative.
If an alternative is not an option: consider a dose of 84mg eliglustat 1x daily and be alert to side effects.

Co-medication with a STRONG CYP3A INDUCER (for example rifampicin, carbamazepine, phenobarbital, phenytoin, rifabutine, hypericum): Eliglustat is not recommended. The plasma concentration may decrease so sharply that a therapeutic effect cannot be achieved.

Choose an alternative if possible.

NO co-medication with a moderate or strong CYP2D6 or CYP3A inhibitor or strong CYP3A inducer:

Use the standard dose of 84mg 2x daily.

Unspecified

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

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6 IMs have a recommended dose of 84 mg orally twice daily. *

Unspecified

Affected subgroup: CYP2D6 ultrarapid, normal, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"Alters systemic concentrations, effectiveness, and adverse reaction risk (QT prolongation). Indicated for normal, intermediate, and poor metabolizer patients. Ultrarapid metabolizers may not achieve adequate concentrations to achieve a therapeutic effect. The recommended dosages are based on CYP2D6 metabolizer status. Coadministration with strong CYP3A inhibitors is contraindicated in intermediate and poor CYP2D6 metabolizers. 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:

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

No Action

Genotype

CYP2C19:*38/*38

Phenotype

Normal Metabolizer

CYP2C19: Normal metabolism

Initiate therapy with recommended starting dose

Strong

DPWG Guideline Annotation ¹

Genotype

CYP2C19:*38/*38

DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association ¹

Genotype

CYP2C19:*38/*38

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

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.

flecainide

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The genetic variation reduces conversion of flecainide to inactive metabolites. This may increase the risk of side effects.

Indications other than diagnosis of Brugada syndrome:

Reduce the dose to 75% of the standard dose and record an ECG and monitor the plasma concentration.

Provocation test for diagnosis of Brugada syndrome:

No action required. At a dose of 2.0 mg/kg body weight to a maximum of 150 mg, the response is better for patients with alleles that result in reduced activity. All 5 patients with these alleles and 20% of the patients with two fully active alleles exhibited a response within 30 minutes.

Unspecified

Citations:

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

flucloxacillin

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

Alternate Drug

Other Guidance

Genotype

HLA-B:*15:02/*57:01

Phenotype

*57:01 positive

HLA-B*57:01-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).

Regularly monitor the patient’s liver function
Choose an alternative if liver enzymes and/or bilirubin levels are elevated

Unspecified

flucytosine

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

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

fluvoxamine

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Reduced metabolism of fluvoxamine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.

Initiate therapy with recommended starting dose.

Moderate

Population:
Unspecified

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The fluvoxamine label states: "Caution is indicated in patients known to have reduced levels of cytochrome P450 2D6 activity[...]" See label for more information. *

Unspecified

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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:

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
Drugs@FDA: Drug Product fluvoxamine maleate (Fluvoxamine maleate), NDA021519, Bryant Ranch Prepack.
FDA Table of Pharmacogenetic Associations.

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 Alternate Drug	Genotype CYP2C9:1/1; HLA-B:15:02/57:01 Phenotypes CYP2C9: Normal Metabolizer HLA-B: *15:02 positive Activity Scores CYP2C9: 2.0 HLA-B: N/A	CYP2C9: Normal phenytoin metabolism HLA-B: Increased risk of phenytoin-induced SJS/TEN	If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine. Other Considerations Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent.	Strong
CPIC Guideline Annotation Population: PHT use >3mos Other Guidance	Genotype CYP2C9:1/1; HLA-B:15:02/57:01 Phenotypes CYP2C9: Normal Metabolizer HLA-B: *15:02 positive Activity Scores CYP2C9: 2.0 HLA-B: N/A	CYP2C9: Normal phenytoin metabolism HLA-B: Increased risk of phenytoin-induced SJS/TEN	If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing. Other Considerations Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants.	Optional
FDA Label Annotation Population: Unspecified Alternate Drug	Genotype CYP2C19:38/38; CYP2C9:1/1; HLA-B:15:02/57:01 Phenotypes CYP2C9: Normal Metabolizer HLA-B: *15:02 positive Activity Scores CYP2C9: 2.0 HLA-B: N/A		"Consider avoiding CEREBYX [fosphenytoin] as an alternative to carbamazepine in patients who are positive for HLA-B1502 or in CYP2C93 carriers." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] HLA-B*15:02 allele positive Alternate Drug	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive		"May result in higher adverse reaction risk (severe cutaneous reactions). Patients positive for HLA-B15:02 may be at increased risk of Stevens Johnson Syndrome/Toxic Epidermal necrolysis (SJS/TEN). Consider avoiding fosphenytoin as an alternative to carbamazepine in patients who are positive for HLA-B15:02. Genotyping is not a substitute for clinical vigilance and patient management." *	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 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.

haloperidol

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The genetic variation results in a higher plasma concentration, but the effect is small and no clinically significant effects were found.

NO action is required for this gene-drug interaction.

Unspecified

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 CYP2D6, CYP3A4 and CYP1A2 and antipsychotics. European journal of human genetics : EJHG. 2024. PMID:37002327

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

hydrocodone

Source

Genes

Implications

Recommendation

Classification

Population:
general

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Minimal evidence for pharmacokinetic or clinical effect.

Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid.

Optional

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clinical pharmacology and therapeutics. 2021. PMID:33387367

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

Dosing Info

Genotype

CYP2C19:*38/*38;
CYP2D6:*1/*3

Phenotypes

CYP2C19:: Normal Metabolizer
CYP2D6:: Intermediate Metabolizer

Activity Scores

CYP2C19:: N/A
CYP2D6:: 1.0

CYP2C19: Normal metabolism of tertiary amines
CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects

Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Optional

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

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The risk of side effects may be increased, because the gene variation leads to increased plasma concentrations of imipramine and desipramine.

Use 70% of the standard dose and monitor the effect and side effects or the plasma concentrations of imipramine and desipramine in order to set the maintenance dose. The therapeutic range is 150-300 ng/mL for the sum of the imipramine and desipramine plasma concentrations. Values exceeding 500 ng/mL are considered toxic.

Unspecified

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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 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
FDA Table of Pharmacogenetic Associations.

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.

lamotrigine

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

Alternate Drug

Other Guidance

Genotype

HLA-B:*15:02/*57:01

Phenotype

*15:02 positive

The life-threatening cutaneous side effect Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) occurs more often in patients with this genetic variation. Based on the estimated risk for all patients and the increase by a factor 3.6 for patients with this genetic variation, the risk of lamotrigine-induced SJS/TEN in patients with HLA-B*1502 is estimated at 0.4%.

Carefully weigh the risk of SJS/TEN against the benefits.
Avoid lamotrigine if an alternative is available.
- Carbamazepine carries a much higher risk of SJS/TEN in these patients and is therefore not an alternative.
- A similar risk has been reported for phenytoin as for lamotrigine.
- The same applies to oxcarbazepine, but the most severe forms (SJS/TEN overlap and TEN) have not been observed with oxcarbazepine.
If it is not possible to avoid these products, advise the patient to report any rash immediately.

Unspecified

lansoprazole

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38

Phenotype

Normal Metabolizer

CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs

Moderate

DPWG Guideline Annotation ¹

Genotype

CYP2C19:*38/*38

DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association ¹

Genotype

CYP2C19:*38/*38

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

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

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

meclizine

Source

Genes

Implications

Recommendation

Classification

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

Population:
Unspecified

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"The genetic polymorphism of CYP2D6 that results in poor-, intermediate-, extensive-, and ultrarapid metabolizer phenotypes could contribute to large inter-individual variability in meclizine exposure."

"... when ANTIVERT® [meclizine] is administered to patients with CYP2D6 polymorphism, monitor for adverse reactions and clinical effect accordingly." See label for more information. *

Unspecified

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"May affect systemic concentrations. Monitor for adverse reactions and clinical effect." *

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:

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.

metoprolol

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes

Initiate standard dosing

Moderate

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The gene variation reduces the conversion of metoprolol to inactive metabolites. However, the clinical consequences are limited mainly to the occurrence of asymptomatic bradycardia.

If a GRADUAL REDUCTION in HEART RATE is desired, or in the event of SYMPTOMATIC BRADYCARDIA:

Use smaller steps in dose titration and/or prescribe no more than 50% of the standard dose.

OTHER CASES:

No action required.

Unspecified

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy. Clinical pharmacology and therapeutics. 2024. PMID:38951961
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
FDA Table of Pharmacogenetic Associations.

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.

nortriptyline

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Reduced metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.

Other Considerations

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. Dosing recommendations only apply to higher initial doses of tricyclic antidepressants for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

Optional

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

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The risk of side effects may be increased, because the gene variation leads to an increased plasma concentration of nortriptyline.

Use 60% of the standard dose and monitor the effect and side effects or the plasma concentration of nortriptyline in order to set the maintenance dose. The therapeutic range of nortriptyline is 50-150 ng/mL. Values exceeding 250 ng/mL are considered toxic.

Unspecified

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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 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
FDA Table of Pharmacogenetic Associations.

omeprazole

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38

Phenotype

Normal Metabolizer

CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs

Moderate

DPWG Guideline Annotation ¹

Genotype

CYP2C19:*38/*38

DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association ¹

Genotype

CYP2C19:*38/*38

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

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.

ondansetron

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Very limited data available for CYP2D6 intermediate metabolizers

Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.

Other Considerations

Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy.

No recommendation

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and tropisetron. Clinical pharmacology and therapeutics. 2017. PMID:28002639

oxcarbazepine

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: OXC naive Alternate Drug	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive	HLA-B: Greater risk of oxcarbazepine-induced SJS/TEN	If patient is oxcarbazepine-naïve, do not use oxcarbazepine. Other Considerations Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital.	Strong
CPIC Guideline Annotation Population: OXC use >3 mos Other Guidance	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive	HLA-B: Greater risk of oxcarbazepine-induced SJS/TEN	The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (~4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used oxcarbazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of oxcarbazepine in the future. Other Considerations Previous tolerance of oxcarbazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital.	Optional
DPWG Guideline Annotation Population: Unspecified Alternate Drug Other Guidance	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive	Stevens-Johnson syndrome, the severe cutaneous side effect that can potentially result in permanent damage, occurs more often in patients with this genetic variation. The calculated risk of oxcarbazepine-induced SJS in patients with HLA-B*1502 is 0.73%.	Carefully weigh the risk of SJS against the benefits. Avoid oxcarbazepine if an alternative is available. Carbamazepine carries a 10-fold higher risk of SJS/TEN in these patients and is therefore not an alternative. In these patients, phenytoin and lamotrigine carry a similar risk of SJS/TEN as oxcarbazepine, but more severe forms of SJS/TEN (SJS/TEN overlap and TEN) are also observed with these medicines. Therefore, they are also not suitable as alternatives. If it is not possible to avoid oxcarbazepine, advise the patient to report any rash immediately	Unspecified
FDA Label Annotation Population: Unspecified Alternate Drug	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive		"The use of oxcarbazepine should be avoided in patients positive for HLA-B1502 unless the benefits clearly outweigh the risks." See label for more information.	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Indicate a Potential Impact on Safety or Response] Affected subgroup: HLA-B*15:02 allele positive Other Guidance	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive		"Results in higher adverse reaction risk (severe skin reactions). Patients positive for HLA-B15:02 may be at increased risk of severe skin reactions with other drugs that are associated with a risk of Stevens Johnson Syndrome/Toxic Epidermal necrolysis (SJS/TEN). Genotyping is not a substitute for clinical vigilance."	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 HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clinical pharmacology and therapeutics. 2018. PMID:29392710
Drugs@FDA: Drug Product OXTELLAR XR (OXCARBAZEPINE), NDA202810, Supernus Pharmaceuticals, Inc.
FDA Table of Pharmacogenetic Associations.

pantoprazole

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Dosing Info	Genotype CYP2C19:38/38 Phenotype Normal Metabolizer	CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs	Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
DPWG Guideline Annotation ¹	Genotype CYP2C19:38/38	DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA Label Annotation ¹	Genotype CYP2C19:38/38	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2C19:38/38	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

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.

paroxetine

Source

Genes

Implications

Recommendation

Classification

Population:
general

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Reduced metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers when starting treatment or at lower doses. Higher plasma concentrations may increase the probability of side effects. Paroxetine-associated phenoconversion of intermediate metabolizers to poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations.

Consider a lower starting dose and slower titration schedule as compared to normal metabolizers.

Other Considerations

Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy.

Optional

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

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The plasma concentration of paroxetine can increase as a result of the reduced activity of CYP2D6. However, studies did not find any clinical effects.

NO action is needed for this gene-drug interaction.

Unspecified

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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.

pazopanib

Source

Genes

Implications

Recommendation

Classification

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

Affected subgroup: HLA-B*57:01 allele positive

Other Guidance

Genotype

HLA-B:*15:02/*57:01

Phenotype

*57:01 positive

"May result in higher adverse reaction risk (liver enzyme elevations). Monitor liver function tests regardless of genotype." *

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.

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 Alternate Drug	Genotype CYP2C9:1/1; HLA-B:15:02/57:01 Phenotypes CYP2C9: Normal Metabolizer HLA-B: *15:02 positive Activity Scores CYP2C9: 2.0 HLA-B: N/A	CYP2C9: Normal phenytoin metabolism HLA-B: Increased risk of phenytoin-induced SJS/TEN	If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine. Other Considerations Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent.	Strong
CPIC Guideline Annotation Population: PHT use >3mos Other Guidance	Genotype CYP2C9:1/1; HLA-B:15:02/57:01 Phenotypes CYP2C9: Normal Metabolizer HLA-B: *15:02 positive Activity Scores CYP2C9: 2.0 HLA-B: N/A	CYP2C9: Normal phenytoin metabolism HLA-B: Increased risk of phenytoin-induced SJS/TEN	If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing. Other Considerations Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants.	Optional
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
DPWG Guideline Annotation Population: Unspecified Alternate Drug Other Guidance	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive	The life-threatening cutaneous side effect Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) occurs more frequently in patients with this genetic variation. The calculated risk of phenytoin-induced SJS/TEN in patients with HLA-B*1502 is 0.65%.	Carefully weigh the risk of SJS/TEN against the benefits Avoid phenytoin if an alternative is possible Carbamazepine carries a 10-fold higher risk of SJS/TEN for these patients and is therefore not an alternative. A comparable risk has been reported for lamotrigine as for phenytoin. The same applies for oxcarbazepine, but the most severe forms (SJS/TEN overlap and TEN) are not observed with oxcarbazepine. if it is not possible to avoid this medication, then advise the patient to report any skin rash immediately	Unspecified
FDA Label Annotation Population: Unspecified Alternate Drug	Genotype CYP2C9:1/1; HLA-B:15:02/57:01 Phenotypes CYP2C9: Normal Metabolizer HLA-B: *15:02 positive Activity Scores CYP2C9: 2.0 HLA-B: N/A		"Consider avoiding DILANTIN [phenytoin] as an alternative to carbamazepine in patients who are positive for HLA-B1502 or in CYP2C93 carriers." See label for more information. *	Unspecified
FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations] HLA-B*15:02 allele positive Alternate Drug	Genotype HLA-B:15:02/57:01 Phenotype *15:02 positive		"May result in higher adverse reaction risk (severe cutaneous reactions). Patients positive for HLA-B15:02 may be at increased risk of Stevens Johnson Syndrome/Toxic Epidermal necrolysis (SJS/TEN). Consider avoiding phenytoin as an alternative to carbamazepine in patients who are positive for HLA-B15:02. Genotyping is not a substitute for clinical vigilance and patient management." *	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 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.

pimozide

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

The risk of QT-prolongation – and thereby also the risk of torsade de points – is theoretically increased, because the genetic variation results in an increase in the plasma concentration of pimozide. The elevated plasma concentration and associated theoretical increased risk of QT elongation can be negated by following the dose recommendations provided below.

Use no more than the following doses (80% of the normal maximum dose):

12 years and older: 16 mg/day
younger than 12 years: 0.08 mg/kg per day to a maximum of 3 mg/day

Unspecified

FDA Label Annotation ¹

Genotype

CYP2D6:*1/*3

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

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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

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
Drugs@FDA: Drug Product ORAP (Pimozide), NDA017473, Teva Select Brands.
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.

propafenone

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

Alternate Drug

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

Genetic variation increases the sum of the plasma concentrations of propafenone and the active metabolite 5-hydroxypropafenone. This may increase the risk of side effects.

It is not possible to offer adequately substantiated recommendations for dose adjustment based on the literature.

Either guide the dose by therapeutic drug monitoring, perform an ECG and be alert to side effects.
Or choose an alternative. Antiarrhythmic drugs that are hardly if at all metabolised by CYP2D6 include, for example, sotalol, disopyramide, quinidine and amiodarone.

Unspecified

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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
FDA Table of Pharmacogenetic Associations.

quetiapine

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

Source

Genes

Implications

Recommendation

Classification

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

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.

risperidone

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

There is little evidence to support an increase in side effects caused by the gene variation. The gene variation may lead to a decrease in the required maintenance dose. However, as the effect on the dose is smaller than that of the normal biological variation, action is not useful.

NO action is needed for this gene-drug interaction.

Unspecified

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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 CYP2D6, CYP3A4 and CYP1A2 and antipsychotics. European journal of human genetics : EJHG. 2024. PMID:37002327
FDA Table of Pharmacogenetic Associations.

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

No Action

Genotype

CYP2B6:*1/*1;
CYP2C19:*38/*38

Phenotypes

CYP2B6:: Normal Metabolizer
CYP2C19:: Normal Metabolizer

CYP2B6: Normal metabolism of sertraline to less active compounds.
CYP2C19: Normal metabolism

Initiate therapy with recommended starting dose.

Strong

DPWG Guideline Annotation ¹

Genotype

CYP2C19:*38/*38

DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

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.

tamoxifen

Source

Genes

Implications

Recommendation

Classification

Population:
general

Alternate Drug

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers.

Consider hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women, given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype (PMID 26211827). If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day)(PMID 27226358). Avoid CYP2D6 strong to weak inhibitors.

Optional

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

Population:
Unspecified

Alternate Drug

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

This gene variation reduces the conversion of tamoxifen to the active metabolite endoxifen. This can result in reduced effectiveness.

Select an alternative or measure the endoxifen concentration and increase the dose if necessary, by a factor of 1.5-2. Aromatase inhibitors are a possible alternative for post-menopausal women.
If TAMOXIFEN is selected: avoid co-medication with CYP2D6 inhibitors such as paroxetine and fluoxetine.

Unspecified

Affected subgroup: CYP2D6 intermediate or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"Results in lower systemic active metabolite concentrations. The impact of CYP2D6 intermediate or poor metabolism on efficacy is not well established." *

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 Tamoxifen Therapy. Clinical pharmacology and therapeutics. 2018. PMID:29385237
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
FDA Table of Pharmacogenetic Associations.

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

tetrabenazine

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"Genotyped patients who are identified as extensive (EMs) or intermediate metabolizers (IMs) of CYP2D6, who need doses of XENAZINE [tetrabenazine] above 50 mg per day, should be titrated up slowly at weekly intervals by 12.5 mg daily, to allow the identification of a tolerated dose that reduces chorea. Doses above 50 mg per day should be given in a three times a day regimen. The maximum recommended daily dose is 100 mg and the maximum recommended single dose is 37.5 mg. If adverse reactions such as akathisia, parkinsonism, depression, insomnia, anxiety or sedation occur, titration should be stopped and the dose should be reduced. If the adverse reaction does not resolve, consideration should be given to withdrawing XENAZINE [tetrabenazine] treatment or initiating other specific treatment." See label for more information *

Unspecified

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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:

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.

thioridazine

Source

Genes

Implications

Recommendation

Classification

Population:
Unspecified

Alternate Drug

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"...thioridazine is contraindicated...in patients, comprising about 7% of the normal population, who are known to have a genetic defect leading to reduced levels of activity of P450 2D6." See label for more information. *

Unspecified

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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:

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

tramadol

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: general Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	CYP2D6: Reduced O-desmethyltramadol (active metabolite) formation	Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid.	Optional
DPWG Guideline Annotation Population: Unspecified Alternate Drug Dosing Info Other Guidance	Genotype CYP2D6:1/3 Phenotype Intermediate Metabolizer Activity Score 1.0	The genetic variation reduces the conversion of tramadol to a metabolite with a higher activity. This can result in reduced analgesia.	It is not possible to provide a recommendation for dose adjustment, because the total analgesic effect changes when the ratio between the mother compound and the active metabolite changes. Be alert to a reduced effectiveness. In the case of inadequate effectiveness: a. Try a dose increase. b. If this does not work: choose an alternative. Do not select codeine, as this is also metabolised by CYP2D6. Morphine is not metabolised by CYP2D6. Oxycodone is metabolised by CYP2D6 to a limited extent, but this does not result in differences in analgesia in patients. If no alternative is selected: advise the patient to report inadequate analgesia.	Unspecified
FDA Label Annotation ¹	Genotype CYP2D6:1/3	FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ^{1, 2}	Genotype CYP2D6:1/3	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clinical pharmacology and therapeutics. 2021. PMID:33387367
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 CYP2D6 and opioids (codeine, tramadol and oxycodone). European journal of human genetics : EJHG. 2022. PMID:34267337
Drugs@FDA: Drug Product ULTRAM (tramadol hydrochloride), NDA020281, Janssen Pharmaceuticals, Inc.
FDA Table of Pharmacogenetic Associations.

trimipramine

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:*38/*38;
CYP2D6:*1/*3

Phenotypes

CYP2C19:: Normal Metabolizer
CYP2D6:: Intermediate Metabolizer

Activity Scores

CYP2C19:: N/A
CYP2D6:: 1.0

CYP2C19: Normal metabolism of tertiary amines
CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects

Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Optional

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

"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 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.

tropisetron

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Very limited data available for CYP2D6 intermediate metabolizers

Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.

Other Considerations

Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy.

No recommendation

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and tropisetron. Clinical pharmacology and therapeutics. 2017. PMID:28002639

venlafaxine

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Decreased metabolism of venlafaxine to active metabolite O-desmethylvenlafaxine (desvenlafaxine) and decreased O-desmethylvenlafaxine:venlafaxine ratio as compared to normal metabolizers. There is insufficient evidence supporting the clinical impact of the decreased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 intermediate metabolizers.

No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.

No recommendation

Population:
Unspecified

Alternate Drug

Dosing Info

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

There are indications of an increased risk of side effects and a reduced chance of efficacy. The gene variation reduces the conversion of venlafaxine to the active metabolite O-desmethylvenlafaxine, whilst an association between high O-desmethylvenlafaxine/venlafaxine ratios and response without side effects was found.

It is not possible to offer adequately substantiated advice for dose reduction based on the literature.

Avoid venlafaxine. Antidepressants that are not metabolised by CYP2D6 - or to a lesser extent - include, for example, duloxetine, mirtazapine, citalopram and sertraline.
If it is not possible to avoid venlafaxine and side effects occur:

Reduce the dose
Monitor the effect and side effects or check the plasma concentrations of venlafaxine and O-desmethylvenlafaxine. It is not known whether it is possible to reduce the dose to such an extent that the side effects disappear, while the effectiveness is maintained. In general, it is assumed that the effectiveness is determined by the sum of the plasma concentrations of venlafaxine and O-desmethylvenlafaxine. However, the side effects do not appear to be related to this sum.

Unspecified

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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

Citations:

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 CYP2D6, CYP2C19 and non-SSRI/non-TCA antidepressants. European journal of human genetics : EJHG. 2024. PMID:38956296
FDA Table of Pharmacogenetic Associations.

voriconazole

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: adults No Action	Genotype CYP2C19:38/38 Phenotype Normal Metabolizer	CYP2C19: Normal voriconazole metabolism	Initiate therapy with recommended standard of care dosing Other Considerations Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities.	Strong
CPIC Guideline Annotation Population: pediatrics No Action	Genotype CYP2C19:38/38 Phenotype Normal Metabolizer	CYP2C19: Normal voriconazole metabolism	Initiate therapy with recommended standard of care dosing Other Considerations Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities.	Strong
DPWG Guideline Annotation ¹	Genotype CYP2C19:38/38	DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.
FDA PGx Association ¹	Genotype CYP2C19:38/38	FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy. Clinical pharmacology and therapeutics. 2017. PMID:27981572
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232
FDA Table of Pharmacogenetic Associations.

vortioxetine

Source

Genes

Implications

Recommendation

Classification

Population:
general

No Action

Genotype

CYP2D6:*1/*3

Phenotype

Intermediate Metabolizer

Activity Score

1.0

CYP2D6: Reduced metabolism of vortioxetine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.

Initiate therapy with recommended starting dose.

Moderate

FDA Label Annotation ¹

Genotype

CYP2D6:*1/*3

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

FDA PGx Association ¹

Genotype

CYP2D6:*1/*3

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

Citations:

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
Drugs@FDA: Drug Product Trintellix (vortioxetine), NDA204447, Cardinal Health.
FDA Table of Pharmacogenetic Associations.

warfarin

Please follow the flow chart in figure 2 of the CPIC warfarin guideline to determine the appropriate dosing recommendation.

The CPIC warfarin guideline only considers a single SNV in VKORC1 (rs9923231), which has varying frequency among different ancestral populations, and largely explains the differences in average dose requirements between people of European, African, and Asian descents. While other functional variants in VKORC1 have been associated with warfarin resistance (high dose requirements), there are currently no CPIC recommendations for how to use these other variants in warfarin dosing. An alternate name for rs9923231 is -1639G>A (note that VKORC1 is on the negative chromosomal strand, so displayed alleles are complemented).

Source	Genes	Implications	Recommendation	Classification
CPIC Guideline Annotation Population: N/A	Genotype CYP2C9:1/1; CYP4F2:1/1; VKORC1: rs9923231 reference (C)/ rs9923231 reference (C); rs12777823:G/G
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 warfarin.	The guideline does not provide a recommendation for warfarin in normal metabolizers.	No recommendation
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 VKORC1 rs9923231 CC genotype (-1639 GG genotype) on warfarin.	The guideline does not provide a recommendation for warfarin in patients with the VKORC1 rs9923231 CC genotype (-1639 GG genotype).	No recommendation
FDA Label Annotation Population: Unspecified Dosing Info	Genotype CYP2C9:1/1; VKORC1: rs9923231 reference (C)/ rs9923231 reference (C) Phenotype Normal Metabolizer Activity Scores CYP2C9: 2.0 VKORC1: N/A		Table 1 in the drug label provides ranges of expected maintenance daily doses of warfarin (COUMADIN) based on CYP2C92, CYP2C93 and VKORC1−1639G>A (rs9923231) genotypes. For CYP2C91/1, VKORC1 GG (rs9923231CC), the range of expected maintenance daily dose is 5-7 mg. *	Unspecified
FDA PGx Association ^{1, 2}	Genotypes CYP2C9:1/1; VKORC1:rs9923231 reference (C)/rs9923231 reference (C)	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:

Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clinical pharmacology and therapeutics. 2011. PMID:21900891
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clinical pharmacology and therapeutics. 2017. PMID:28198005
Drugs@FDA: Drug Product COUMADIN (warfarin sodium), NDA009218, Bristol-Myers Squibb Pharma Company.
FDA Table of Pharmacogenetic Associations.

zuclopenthixol

Source

Genes

Implications

Recommendation

Classification