PharmCAT Report [pharmcat.example]

Date created	September 22, 2023
PharmCAT Version	v2.7.1-19-g0d11f2b6
CPIC Version

Sections

Genotype Summary
Prescribing Recommendations
Allele Matching Details
Disclaimers

Disclaimer: PharmCAT is only able to generate recommendations based on the information provided to the software. The gene and variant information for all reported sections are interpreted directly from user-supplied data. The user recognizes they are using PharmCAT at their own risk. For a full list of disclaimers and limitations see Section IV.

Section I: Genotype Summary

Genotypes called: 22 / 23

Drugs

Gene

Genotypes

Genotype

Allele Functionality

Phenotype

allopurinol

rosuvastatin

ABCG2 ^‡

rs2231142 reference (G)/rs2231142 reference (G)

Two Normal function alleles

Normal Function

desflurane

enflurane

halothane

isoflurane

methoxyflurane

sevoflurane

succinylcholine

CACNA1S ^† ^‡

No CPIC variants found

Two Normal function alleles

Uncertain Susceptibility

ivacaftor

CFTR ^‡

No CPIC variants found

Two ivacaftor non-responsive alleles

ivacaftor non-responsive in CF patients

efavirenz

sertraline

CYP2B6 ^† ^‡

*1/*1

Two Normal function alleles

Normal Metabolizer

amitriptyline

citalopram

clomipramine

clopidogrel

dexlansoprazole

doxepin

escitalopram

imipramine

lansoprazole

omeprazole

pantoprazole

sertraline

trimipramine

voriconazole

CYP2C19 ^† ^‡

*38/*38

Two Normal function alleles

Normal Metabolizer

celecoxib

flurbiprofen

fluvastatin

fosphenytoin

ibuprofen

lornoxicam

meloxicam

phenytoin

piroxicam

siponimod

tenoxicam

warfarin

CYP2C9 ^† ^‡

*1/*1

Two 1.0 (Normal function) alleles

Normal Metabolizer

amitriptyline

aripiprazole

atomoxetine

brexpiprazole

clomipramine

codeine

desipramine

doxepin

eliglustat

flecainide

fluvoxamine

haloperidol

hydrocodone

imipramine

metoprolol

nortriptyline

ondansetron

paroxetine

pimozide

propafenone

risperidone

tamoxifen

tramadol

trimipramine

tropisetron

venlafaxine

vortioxetine

zuclopenthixol

CYP2D6 ^†

*1/*3

One 0.0 (No function) allele and one 1.0 (Normal function) allele

Intermediate Metabolizer

quetiapine

CYP3A4 ^† ^‡

*1/*1

Two Normal function alleles

Normal Metabolizer

tacrolimus

CYP3A5 ^† ^‡

*1/*1

Two Normal function alleles

Normal Metabolizer

warfarin

CYP4F2 ^† ^‡

*1/*1

N/A

capecitabine

flucytosine

fluorouracil

tegafur

DPYD ^†

Reference/Reference
Reference	1.0 (Normal function)	See drug section

hormonal contraceptives for systemic use

F5 ^‡

rs6025 C/rs6025 C

Two Factor V Leiden negative alleles

Factor V Leiden absent

dapsone

methylene blue

nitrofurantoin

pegloticase

primaquine

rasburicase

tafenoquine

toluidine blue

G6PD ^† ^‡

B (reference)/B (reference)

Two IV/Normal alleles

Normal

abacavir

allopurinol

carbamazepine

flucloxacillin

fosphenytoin

lamotrigine

oxcarbazepine

phenytoin

HLA-B ^†

*15:02/*57:01

N/A

*15:02 positive; *57:01 positive; *58:01 negative

peginterferon alfa-2a

peginterferon alfa-2b

ribavirin

IFNL3/4 ^‡

rs12979860 reference (C)/rs12979860 reference (C)

Two Favorable response allele alleles

n/a

amikacin

gentamicin

kanamycin

paromomycin

plazomicin

streptomycin

tobramycin

MT-RNR1 ^†

1555A>G

Increased risk of aminoglycoside-induced hearing loss

increased risk of aminoglycoside-induced hearing loss

azathioprine

mercaptopurine

thioguanine

NUDT15 ^† ^‡

*1/*1

Two Normal function alleles

Normal Metabolizer

desflurane

enflurane

halothane

isoflurane

methoxyflurane

sevoflurane

succinylcholine

RYR1 ^† ^‡

No CPIC variants found

Two Normal function alleles

Uncertain Susceptibility

atorvastatin

fluvastatin

lovastatin

pitavastatin

pravastatin

rosuvastatin

simvastatin

SLCO1B1 ^† ^‡

*1/*1

Two Normal function alleles

Normal Function

azathioprine

mercaptopurine

thioguanine

TPMT ^† ^‡

*1/*1

Two Normal function alleles

Normal Metabolizer

atazanavir

irinotecan

UGT1A1 ^† ^‡

*1/*1

Two Normal function alleles

Normal Metabolizer

acenocoumarol

phenprocoumon

warfarin

VKORC1 ^‡

rs9923231 reference (C)/rs9923231 reference (C)

N/A

^† Check Section III for more details about this call.

^‡ PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

CPIC terms for allele function and phenotype are used for all CPIC genes. For non-CPIC genes, DPWG terms are used.

For a full list of disclaimers and limitations see Section IV.

Section II: Prescribing Recommendations

abacavir

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Alternate Drug	Genotype HLA-B:15:02/57:01	HLA-B: Significantly increased risk of abacavir hypersensitivity	Abacavir is not recommended	Strong
PharmGKB-DPWG ¹ Population: Unspecified Alternate Drug	Genotype HLA-B:15:02/57:01	HLA-B57:01-positive patients have a strongly increased risk of a hypersensitivity reaction to abacavir. 48% of the HLA-B57:01-positive patients develop a severe and potentially life-threatening hypersensitivity reaction to abacavir	Abacavir is contra-indicated for HLA-B*57:01-positive patients. Avoid abacavir.	N/A

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

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

HLA-B: Significantly increased risk of abacavir hypersensitivity

Abacavir is not recommended

Strong

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Genotype

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

HLA-B*57:01-positive patients have a strongly increased risk of a hypersensitivity reaction to abacavir. 48% of the HLA-B*57:01-positive patients develop a severe and potentially life-threatening hypersensitivity reaction to abacavir

Abacavir is contra-indicated for HLA-B*57:01-positive patients.

Avoid abacavir.

N/A

Citations:

Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Clinical pharmacology and therapeutics. 2012. PMID:22378157
Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update. Clinical pharmacology and therapeutics. 2014. PMID:24561393
Pharmacogenetics: from bench to byte--an update of guidelines. Clinical pharmacology and therapeutics. 2011. PMID:21412232

acenocoumarol

Guideline	Genes	Implications	Recommendation	Classification
PharmGKB-DPWG ¹ Population: Unspecified No Action	Genotype VKORC1: rs9923231 reference (C)/ rs9923231 reference (C)	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

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

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

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

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general No Action	Genotype HLA-B:15:02/57:01	HLA-B: Low or reduced risk of allopurinol-induced SCAR	Use allopurinol per standard dosing guidelines	Strong
PharmGKB-DPWG ^{1, 2} Population: Unspecified No Action	Genotype ABCG2: rs2231142 reference (G)/ rs2231142 reference (G)	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

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

HLA-B: Low or reduced risk of allopurinol-induced SCAR

Use allopurinol per standard dosing guidelines

Strong

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

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

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

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

No recommendation

Citations:

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. 2022. PMID:36056234

amikacin

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Alternate Drug	Genotype MT-RNR1:1555A>G	MT-RNR1: Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.	Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. Other Considerations If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).	Strong

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

MT-RNR1:1555A>G

MT-RNR1: Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.

Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.

Other Considerations

If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical pharmacology and therapeutics. 2022. PMID:34032273

amitriptyline

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Dosing Info	Genotype CYP2C19:38/38; CYP2D6:1/3	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
PharmGKB-DPWG ¹ Population: Unspecified Dosing Info	Genotype CYP2D6:1/3	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	N/A

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

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

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

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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

N/A

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

aripiprazole

Guideline	Genes	Implications	Recommendation	Classification
PharmGKB-DPWG ¹ Population: Unspecified No Action	Genotype CYP2D6:1/3	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.	N/A

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

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.

N/A

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. 2023. PMID:37002327

atazanavir

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Other Guidance	Genotype UGT1A1:1/1	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Other Guidance

Genotype

UGT1A1:*1/*1

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

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: adults Dosing Info	Genotype CYP2D6:1/3	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 ¹ Population: pediatrics Dosing Info	Genotype CYP2D6:1/3	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
PharmGKB-DPWG ¹ Population: Unspecified Dosing Info	Genotype CYP2D6:1/3	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.	N/A

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
adults

Dosing Info

Genotype

CYP2D6:*1/*3

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 ¹

Population:
pediatrics

Dosing Info

Genotype

CYP2D6:*1/*3

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

Moderate

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

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. 2022. PMID:36509836

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.

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general No Action	Genotype SLCO1B1:1/1	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
PharmGKB-DPWG ¹ Population: Unspecified No Action	Genotype SLCO1B1:1/1	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

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

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

SLCO1B1:*1/*1

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

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

azathioprine

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general No Action	Genotype NUDT15:1/1; TPMT:1/1	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
PharmGKB-DPWG ^{1, 2} Population: Unspecified No Action	Genotype NUDT15:1/1	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
PharmGKB-DPWG ^{1, 2} Population: Unspecified No Action	Genotype TPMT:1/1	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

NUDT15:*1/*1;
TPMT:*1/*1

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

NUDT15:*1/*1

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

TPMT:*1/*1

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

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

brexpiprazole

Guideline	Genes	Implications	Recommendation	Classification
PharmGKB-DPWG ¹ Population: Unspecified No Action	Genotype CYP2D6:1/3	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.	N/A

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

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.

N/A

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. 2023. PMID:37002327

capecitabine

The two lowest activity values (variant activity scores, see CPIC guideline PMID:29152729) are used for unphased data and the lowest activity value per allele is used for phased data to determine the gene activity score and phenotype to retrieve prescribing recommendations.

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general No Action	Genotype DPYD:Reference/ Reference	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
PharmGKB-DPWG ¹ Population: Unspecified No Action	Genotype DPYD:Reference/ Reference	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

DPYD:Reference/
Reference

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

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

DPYD:Reference/
Reference

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

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. 2019. PMID:31745289

carbamazepine

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: CBZ naive Alternate Drug	Genotype HLA-A:Not called - no variant data provided; HLA-B:15:02/57:01	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 ¹ Population: CBZ use >3mos Other Guidance	Genotype HLA-A:Not called - no variant data provided; HLA-B:15:02/57:01	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 ¹ Population: CBZ-no alternatives Alternate Drug	Genotype HLA-A:Not called - no variant data provided; HLA-B:15:02/57:01	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
PharmGKB-DPWG ^{1, 2} Population: Unspecified Alternate Drug	Genotype HLA-B:15:02/57:01	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.	N/A

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

celecoxib

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general No Action	Genotype CYP2C9:1/1	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C9:*1/*1

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

Citations:

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

citalopram

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general No Action	Genotype CYP2C19:38/38	CYP2C19: Normal metabolism	Initiate therapy with recommended starting dose	Strong
PharmGKB-DPWG ¹	Genotype CYP2C19:38/38	PharmGKB-DPWG provides no genotype-based recommendations for the following genotype, after evaluating the evidence.

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C19:*38/*38

CYP2C19: Normal metabolism

Initiate therapy with recommended starting dose

Strong

PharmGKB-DPWG ¹

Genotype

CYP2C19:*38/*38

PharmGKB-DPWG provides no genotype-based recommendations for the following 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

clomipramine

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Dosing Info	Genotype CYP2C19:38/38; CYP2D6:1/3	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
PharmGKB-DPWG ^{1, 2} Population: Unspecified Dosing Info	Genotype CYP2D6:1/3	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.	N/A

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

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

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

Citations:

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

clopidogrel

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: CVI ACS PCI No Action	Genotype CYP2C19:38/38	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 ¹ Population: CVI non-ACS non-PCI No Action	Genotype CYP2C19:38/38	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 ¹ Population: NVI No Action	Genotype CYP2C19:38/38	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
PharmGKB-DPWG ¹	Genotype CYP2C19:38/38	PharmGKB-DPWG provides no genotype-based recommendations for the following 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

codeine

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Other Guidance	Genotype CYP2D6:1/3	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
PharmGKB-DPWG ¹ Population: Unspecified Alternate Drug Dosing Info Other Guidance	Genotype CYP2D6:1/3	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.	N/A

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Other Guidance

Genotype

CYP2D6:*1/*3

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

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Dosing Info

Other Guidance

Genotype

CYP2D6:*1/*3

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.

N/A

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

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/).

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general No Action	Genotype G6PD:B (reference)/ B (reference)	G6PD: Low risk of acute hemolytic anemia	No reason to avoid based on G6PD status	Strong

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

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 (CPIC) Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2022. PMID:36049896

desflurane

If the summary table (Section I) includes Malignant Hyperthermia Susceptibility as phenotype for either RYR1 or CACNA1S, please refer to the guideline publication PMID:30499100 since halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with Malignant Hyperthermia Susceptibility.

Guideline	Genes	Implications	Recommendation	Classification
CPIC ^{1, 2} Population: general Other Guidance	Genotype CACNA1S: No CPIC variants found	These results do not eliminate the chance that this patient is susceptible to Malignant Hyperthermia. 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
CPIC ^{1, 2} Population: general Other Guidance	Genotype RYR1: No CPIC variants found	These results do not eliminate the chance that this patient is susceptible to Malignant Hyperthermia. The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID: 28902675). A negative or inconclusive genetic test cannot be assumed to indicate normal RYR1-related phenotype and should be interpreted in context of clinical findings, family history and other laboratory data.	Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.	Strong

Guideline

Genes

Implications

Recommendation

Classification

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

CACNA1S:
No CPIC variants found

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

Strong

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

RYR1:
No CPIC variants found

These results do not eliminate the chance that this patient is susceptible to Malignant Hyperthermia. The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID: 28902675). A negative or inconclusive genetic test cannot be assumed to indicate normal RYR1-related phenotype and should be interpreted in context of clinical findings, family history and other laboratory data.

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

desipramine

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Dosing Info	Genotype CYP2D6:1/3	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

CYP2D6:*1/*3

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

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

dexlansoprazole

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Dosing Info	Genotype CYP2C19:38/38	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38

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

Citations:

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

doxepin

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: general Dosing Info	Genotype CYP2C19:38/38; CYP2D6:1/3	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
PharmGKB-DPWG ¹ Population: Unspecified Dosing Info	Genotype CYP2D6:1/3	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.	N/A

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

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

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

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

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

efavirenz

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: child >40kg_adult No Action	Genotype CYP2B6:1/1	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
PharmGKB-DPWG ¹ Population: Unspecified No Action	Genotype CYP2B6:1/1	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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
child >40kg_adult

No Action

Genotype

CYP2B6:*1/*1

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

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

CYP2B6:*1/*1

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

Citations:

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

eliglustat

Guideline	Genes	Implications	Recommendation	Classification
PharmGKB-DPWG ¹ Population: Unspecified Alternate Drug Dosing Info	Genotype CYP2D6:1/3	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.	N/A

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

enflurane

Guideline

Genes

Implications

Recommendation

Classification

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

CACNA1S:
No CPIC variants found

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

Strong

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

RYR1:
No CPIC variants found

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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C19:*38/*38

CYP2C19: Normal metabolism

Initiate therapy with recommended starting dose

Strong

PharmGKB-DPWG ¹

Genotype

CYP2C19:*38/*38

PharmGKB-DPWG provides no genotype-based recommendations for the following 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

flecainide

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

Citations:

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

flucloxacillin

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Other Guidance

Genotype

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

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

N/A

flucytosine

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

DPYD:Reference/
Reference

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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

DPYD:Reference/
Reference

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

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

DPYD:Reference/
Reference

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

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. 2019. PMID:31745289

flurbiprofen

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C9:*1/*1

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

fluvastatin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

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

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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2D6:*1/*3

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

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

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.

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
PHT naive

Alternate Drug

Genotype

CYP2C9:*1/*1;
HLA-B:*15:02/*57:01

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 ¹

Population:
PHT use >3mos

Other Guidance

Genotype

CYP2C9:*1/*1;
HLA-B:*15:02/*57:01

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

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

gentamicin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

MT-RNR1:1555A>G

MT-RNR1: Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.

Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.

Other Considerations

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical pharmacology and therapeutics. 2022. PMID:34032273

haloperidol

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

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.

N/A

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. 2023. PMID:37002327

halothane

Guideline

Genes

Implications

Recommendation

Classification

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

CACNA1S:
No CPIC variants found

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

Strong

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

RYR1:
No CPIC variants found

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

hormonal contraceptives for systemic use

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

F5:rs6025 C/
rs6025 C

The guideline does not provide a description of the impact of the absence of Factor V Leiden on estrogen-containing contraceptives.

The guideline does not provide a recommendation for estrogen-containing contraceptives in patients who do not have the Factor V Leiden variant.

No recommendation

Citations:

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

hydrocodone

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Other Guidance

Genotype

CYP2D6:*1/*3

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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C9:*1/*1

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

imipramine

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

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

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

Citations:

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

irinotecan

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

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

UGT1A1:*1/*1

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

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. 2022. PMID:36443464

isoflurane

Guideline

Genes

Implications

Recommendation

Classification

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

CACNA1S:
No CPIC variants found

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

Strong

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

RYR1:
No CPIC variants found

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

ivacaftor

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

CFTR:
No CPIC variants found

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

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clinical pharmacology and therapeutics. 2014. PMID:24598717

kanamycin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

MT-RNR1:1555A>G

MT-RNR1: Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.

Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.

Other Considerations

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical pharmacology and therapeutics. 2022. PMID:34032273

lamotrigine

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Other Guidance

Genotype

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

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.

N/A

lansoprazole

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38

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

Moderate

PharmGKB-DPWG ¹

Genotype

CYP2C19:*38/*38

PharmGKB-DPWG provides no genotype-based recommendations for the following 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

lornoxicam

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C9:*1/*1

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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

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

meloxicam

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C9:*1/*1

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

mercaptopurine

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

NUDT15:*1/*1;
TPMT:*1/*1

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

NUDT15:*1/*1

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

TPMT:*1/*1

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

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

methoxyflurane

Guideline

Genes

Implications

Recommendation

Classification

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

CACNA1S:
No CPIC variants found

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

Strong

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

RYR1:
No CPIC variants found

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/).

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

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 (CPIC) Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2022. PMID:36049896

metoprolol

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

Citations:

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

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/).

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Strong

nortriptyline

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

CYP2D6:*1/*3

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

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

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

omeprazole

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38

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

Moderate

PharmGKB-DPWG ¹

Genotype

CYP2C19:*38/*38

PharmGKB-DPWG provides no genotype-based recommendations for the following 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

ondansetron

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2D6:*1/*3

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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
OXC naive

Alternate Drug

Genotype

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

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 ¹

Population:
OXC use >3 mos

Other Guidance

Genotype

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

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

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Other Guidance

Genotype

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

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

N/A

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clinical pharmacology and therapeutics. 2018. PMID:29392710

pantoprazole

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

CYP2C19:*38/*38

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

Moderate

PharmGKB-DPWG ¹

Genotype

CYP2C19:*38/*38

PharmGKB-DPWG provides no genotype-based recommendations for the following 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

paromomycin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

MT-RNR1:1555A>G

MT-RNR1: Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.

Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.

Other Considerations

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical pharmacology and therapeutics. 2022. PMID:34032273

paroxetine

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

CYP2D6:*1/*3

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

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

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.

N/A

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

peginterferon alfa-2a

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹	Genotype IFNL3:rs12979860 reference (C)/rs12979860 reference (C)	CPIC provides no genotype-based recommendations for the following genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-alpha-based regimens. Clinical pharmacology and therapeutics. 2014. PMID:24096968

peginterferon alfa-2b

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹	Genotype IFNL3:rs12979860 reference (C)/rs12979860 reference (C)	CPIC provides no genotype-based recommendations for the following genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-alpha-based regimens. Clinical pharmacology and therapeutics. 2014. PMID:24096968

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/).

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

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 (CPIC) Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2022. PMID:36049896

phenprocoumon

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

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

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

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹ Population: PHT naive Alternate Drug	Genotype CYP2C9:1/1; HLA-B:15:02/57:01	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 ¹ Population: PHT use >3mos Other Guidance	Genotype CYP2C9:1/1; HLA-B:15:02/57:01	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
PharmGKB-DPWG ^{1, 2} Population: Unspecified No Action	Genotype CYP2C9:1/1	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
PharmGKB-DPWG ^{1, 2} Population: Unspecified Alternate Drug Other Guidance	Genotype HLA-B:15:02/57:01	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	N/A

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

pimozide

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

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

N/A

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. 2023. PMID:37002327

piroxicam

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C9:*1/*1

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

pitavastatin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

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

plazomicin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

MT-RNR1:1555A>G

MT-RNR1: Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.

Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.

Other Considerations

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical pharmacology and therapeutics. 2022. PMID:34032273

pravastatin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

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/).

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

G6PD: Low risk of acute hemolytic anemia

No reason to avoid based on G6PD status

Strong

Citations:

Expanded Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2022. PMID:36049896

propafenone

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Other Guidance

Genotype

CYP2D6:*1/*3

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.

N/A

Citations:

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

quetiapine

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

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

CYP3A4:*1/*1

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. 2023. 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/).

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

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 (CPIC) Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2022. PMID:36049896

ribavirin

Guideline	Genes	Implications	Recommendation	Classification
CPIC ¹	Genotype IFNL3:rs12979860 reference (C)/rs12979860 reference (C)	CPIC provides no genotype-based recommendations for the following genotype, after evaluating the evidence.

Citations:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-alpha-based regimens. Clinical pharmacology and therapeutics. 2014. PMID:24096968

risperidone

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

CYP2D6:*1/*3

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.

N/A

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. 2023. PMID:37002327

rosuvastatin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

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

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

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

sertraline

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

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

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

Initiate therapy with recommended starting dose.

Strong

PharmGKB-DPWG ¹

Genotype

CYP2C19:*38/*38

PharmGKB-DPWG provides no genotype-based recommendations for the following 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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

CACNA1S:
No CPIC variants found

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

Strong

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

RYR1:
No CPIC variants found

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

simvastatin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

SLCO1B1:*1/*1

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

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

SLCO1B1:*1/*1

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

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

siponimod

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

CYP2C9:*1/*1

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

streptomycin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

MT-RNR1:1555A>G

MT-RNR1: Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.

Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.

Other Considerations

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical pharmacology and therapeutics. 2022. PMID:34032273

succinylcholine

Guideline

Genes

Implications

Recommendation

Classification

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

CACNA1S:
No CPIC variants found

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

Strong

CPIC ^{1, 2}

Population:
general

Other Guidance

Genotype

RYR1:
No CPIC variants found

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

tacrolimus

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

CYP3A5:*1/*1

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

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP3A5:*1/*1

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.

N/A

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

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/).

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

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

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 (CPIC) Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2022. PMID:36049896

tamoxifen

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Dosing Info

Genotype

CYP2D6:*1/*3

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

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

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

tegafur

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

No Action

Genotype

DPYD:Reference/
Reference

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. 2019. PMID:31745289

tenoxicam

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2C9:*1/*1

CYP2C9: Normal metabolism

Strong

Citations:

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

thioguanine

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

NUDT15:*1/*1;
TPMT:*1/*1

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

NUDT15:*1/*1

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

TPMT:*1/*1

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

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

tobramycin

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Alternate Drug

Genotype

MT-RNR1:1555A>G

MT-RNR1: Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.

Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.

Other Considerations

Strong

Citations:

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical pharmacology and therapeutics. 2022. PMID:34032273

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/).

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

G6PD:B (reference)/
B (reference)

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 (CPIC) Guideline for Medication Use in the Context of G6PD Genotype. Clinical pharmacology and therapeutics. 2022. PMID:36049896

tramadol

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Other Guidance

Genotype

CYP2D6:*1/*3

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

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Dosing Info

Other Guidance

Genotype

CYP2D6:*1/*3

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.

N/A

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

trimipramine

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

Dosing Info

Genotype

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

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

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

tropisetron

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2D6:*1/*3

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

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2D6:*1/*3

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

PharmGKB-DPWG ¹

Population:
Unspecified

Alternate Drug

Dosing Info

Genotype

CYP2D6:*1/*3

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.

N/A

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

voriconazole

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
adults

No Action

Genotype

CYP2C19:*38/*38

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 ¹

Population:
pediatrics

No Action

Genotype

CYP2C19:*38/*38

CYP2C19: Normal voriconazole metabolism

Initiate therapy with recommended standard of care dosing

Other Considerations

Strong

PharmGKB-DPWG ¹

Genotype

CYP2C19:*38/*38

PharmGKB-DPWG provides no genotype-based recommendations for the following 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

vortioxetine

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
general

No Action

Genotype

CYP2D6:*1/*3

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

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

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).

Guideline

Genes

Implications

Recommendation

Classification

CPIC ¹

Population:
N/A

No Action

Genotype

CYP2C9:*1/*1;
CYP4F2:*1/*1;
VKORC1:
rs9923231 reference (C)/
rs9923231 reference (C);
rs12777823:G/G

Figure 2 from the CPIC guideline for warfarin

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

CYP2C9:*1/*1

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

PharmGKB-DPWG ^{1, 2}

Population:
Unspecified

No Action

Genotype

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

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

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

zuclopenthixol

Guideline

Genes

Implications

Recommendation

Classification

PharmGKB-DPWG ¹

Population:
Unspecified

Dosing Info

Genotype

CYP2D6:*1/*3

The risk of side effects may be elevated. The genetic variation leads to decreased conversion of zuclopentixol, which causes the plasma concentration to be approximately 1.35-fold higher.

Use 75% of the normal dose.

N/A

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. 2023. PMID:37002327

Section III: Allele Matching Details

ABCG2 allele match data
CACNA1S allele match data
CFTR allele match data
CYP2B6 allele match data
CYP2C19 allele match data
CYP2C9 allele match data
CYP2D6 allele match data
CYP3A4 allele match data
CYP3A5 allele match data
CYP4F2 allele match data
DPYD allele match data
F5 allele match data
G6PD allele match data
HLA-B allele match data
IFNL3/4 allele match data
MT-RNR1 allele match data
NUDT15 allele match data
RYR1 allele match data
SLCO1B1 allele match data
TPMT allele match data
UGT1A1 allele match data
VKORC1 allele match data

No data provided for HLA-A.

ABCG2 allele match data

Genotype Matched:

rs2231142 reference (G)/rs2231142 reference (G)

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function	Warnings
chr4:88131171	rs2231142	G/G	G	rs2231142 variant (T) - Decreased function

CACNA1S allele match data

Genotype Matched:

No CPIC variants found

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

The CACNA1S Reference allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function	Warnings
chr1:201060815	rs1800559	C/C	C	c.3257G>A - Malignant Hyperthermia associated
chr1:201091993	rs772226819	G/G	G	c.520C>T - Malignant Hyperthermia associated

CFTR allele match data

Genotype Matched:

No CPIC variants found

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr7:117509035	rs397508256	G/G	G	E56K - ivacaftor responsive
chr7:117509069	rs368505753	C/C	C	P67L - ivacaftor responsive
chr7:117509089	rs115545701	C/C	C	R74W - ivacaftor responsive
chr7:117530953	rs113993958	G/G	G	D110H - ivacaftor responsive
chr7:117530955	rs397508537	C/C	C	D110E - ivacaftor responsive
chr7:117530974	rs77834169	C/C	C	R117C - ivacaftor responsive
chr7:117530975	rs78655421	G/G	G	R117H - ivacaftor responsive
chr7:117534318	rs80282562	G/G	G	G178R - ivacaftor responsive
chr7:117534363	rs397508759	G/G	G	E193K - ivacaftor responsive
chr7:117534368	rs397508761	A/A	A	711+3A->G - ivacaftor responsive
chr7:117535285	rs121908752	T/T	T	L206W - ivacaftor responsive
chr7:117540270	rs77932196	G/G	G	R347H - ivacaftor responsive
chr7:117540285	rs121908753	G/G	G	R352Q - ivacaftor responsive
chr7:117548795	rs74551128	C/C	C	A455E - ivacaftor responsive
chr7:117587799	rs121908757	A/A	A	S549R(A>C) - ivacaftor responsive
chr7:117587800	rs121908755	G/G	G	S549N - ivacaftor responsive
chr7:117587801	rs121909005	T/T	T	S549R(T>G) - ivacaftor responsive
chr7:117587805	rs121909013	G/G	G	G551S - ivacaftor responsive
chr7:117587806	rs75527207	G/G	G	G551D - ivacaftor responsive
chr7:117590409	rs397508288	A/A	A	D579G - ivacaftor responsive
chr7:117594930	rs397508387	G/G	G	E831X - ivacaftor responsive
chr7:117602868	rs80224560	G/G	G	2789+5G->A - ivacaftor responsive
chr7:117603708	rs397508442	C/C	C	S945L - ivacaftor responsive
chr7:117606695	rs141033578	C/C	C	S977F - ivacaftor responsive
chr7:117611555	rs76151804	A/A	A	3272-26A->G - ivacaftor responsive
chr7:117611595	rs150212784	T/T	T	F1052V - ivacaftor responsive
chr7:117611620	rs397508513	A/A	A	K1060T - ivacaftor responsive
chr7:117611640	rs121909020	G/G	G	A1067T - ivacaftor responsive
chr7:117611646	rs200321110	G/G	G	G1069R - ivacaftor responsive
chr7:117611649	rs202179988	C/C	C	R1070W - ivacaftor responsive
chr7:117611650	rs78769542	G/G	G	R1070Q - ivacaftor responsive
chr7:117611663	rs186045772	T/T	T	F1074L - ivacaftor responsive
chr7:117614699	rs75541969	G/G	G	D1152H - ivacaftor responsive
chr7:117639961	rs75039782	C/C	C	3849+10kbC->T - ivacaftor responsive
chr7:117642451	rs267606723	G/G	G	G1244E - ivacaftor responsive
chr7:117642472	rs74503330	G/G	G	S1251N - ivacaftor responsive
chr7:117642483	rs121909041	T/T	T	S1255P - ivacaftor responsive
chr7:117642528	rs11971167	G/G	G	D1270N - ivacaftor responsive
chr7:117664770	rs193922525	G/G	G	G1349D - ivacaftor responsive

CYP2B6 allele match data

Genotype Matched:

*1/*1

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

The CYP2B6 *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr19:40991224	rs34223104	T/T	T	22 - Increased function 34 - Decreased function 35 - No function 36 - Decreased function
chr19:40991367	rs34883432	A/A	A	*10 - Uncertain function
chr19:40991369	rs8192709	C/C	C	2 - Normal function 10 - Uncertain function
chr19:40991381	rs33973337	A/A	A	*17 - Normal function
chr19:40991388	rs33980385	A/A	A	*17 - Normal function
chr19:40991390	rs33926104	C/C	C	*17 - Normal function
chr19:40991391	rs34284776	G/G	G	*17 - Normal function
chr19:40991441	rs35303484	A/A	A	*11 - Uncertain function
chr19:41004015	rs281864907	T/T	T	*38 - No function
chr19:41004125	rs36060847	G/G	G	*12 - No function
chr19:41004133	rs148009906	G/G	G	*44 - Unassigned function
chr19:41004158	rs186335453	G/G	G	*35 - No function
chr19:41004303	rs139801276	T/T	T	*35 - No function
chr19:41004377	rs12721655	A/A	A	8 - No function 13 - No function
chr19:41004380	rs535039125	C/C	C	*39 - Unassigned function
chr19:41004381	rs35773040	G/G	G	*14 - Uncertain function
chr19:41004406	rs145884402	G/G	G	*35 - No function
chr19:41006919	rs3826711	C/C	C	*26 - Decreased function
chr19:41006923	rs36056539	C/C	C	*20 - Decreased function
chr19:41006936	rs3745274	G/G	G	6 - Decreased function 7 - Decreased function 9 - Decreased function 13 - No function 19 - Decreased function 20 - Decreased function 26 - Decreased function 34 - Decreased function 36 - Decreased function 37 - No function 38 - No function 39 - Unassigned function 40 - Unassigned function 41 - Unassigned function 42 - Unassigned function 43 - Unassigned function
chr19:41006967	rs58871670	G/G	G	*45 - Unassigned function
chr19:41006968	rs373489637	T/T	T	*37 - No function
chr19:41007013	rs36079186	T/T	T	27 - Uncertain function 35 - No function
chr19:41009313		A/A	A	*46 - Unassigned function
chr19:41009350	rs45482602	C/C	C	*3 - Uncertain function
chr19:41009358	rs2279343	A/A	A	4 - Increased function 6 - Decreased function 7 - Decreased function 13 - No function 18 - No function 19 - Decreased function 20 - Decreased function 26 - Decreased function 34 - Decreased function 36 - Decreased function 37 - No function 38 - No function 39 - Unassigned function 40 - Unassigned function 41 - Unassigned function 42 - Unassigned function *43 - Unassigned function
chr19:41010006	rs139029625	G/G	G	*35 - No function
chr19:41010088	rs34698757	C/C	C	*28 - No function
chr19:41010108	rs193922917	C/C	C	*31 - Normal function
chr19:41012316	rs28399499	T/T	T	*18 - No function
chr19:41012339	rs34826503	C/C	C	*19 - Decreased function
chr19:41012393	rs754621576	T/T	T	*47 - Unassigned function
chr19:41012394	rs780991919	A/A	A	*47 - Unassigned function
chr19:41012465	rs34097093	C/C	C	*28 - No function
chr19:41012466	rs200458614	G/G	G	*40 - Unassigned function
chr19:41012471	rs201500445	T/T	T	*41 - Unassigned function
chr19:41012478	rs200238771	T/T	T	*48 - Unassigned function
chr19:41012693	rs35979566	T/T	T	*15 - Uncertain function
chr19:41012740	rs193922918	G/G	G	*32 - Normal function
chr19:41012803	rs35010098	C/C	C	*21 - Uncertain function
chr19:41016652	rs764288403	G/G	G	*49 - Unassigned function
chr19:41016679	rs374099483	G/G	G	*42 - Unassigned function
chr19:41016726	rs3211369	A/A	A	*23 - Unknown function
chr19:41016741	rs117872433	G/G	G	*43 - Unassigned function
chr19:41016778	rs564083989	G/G	G	*24 - No function
chr19:41016805		A/A	A	*25 - Unknown function
chr19:41016810	rs3211371	C/C	C	5 - Normal function 7 - Decreased function 33 - Uncertain function 34 - Decreased function

CYP2C19 allele match data

Genotype Matched:

*38/*38

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

The CYP2C19 *38 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr10:94761900	rs12248560	C/C	C	4 - No function 17 - Increased function
chr10:94762706	rs28399504	A/A	A	*4 - No function
chr10:94762712	rs367543002	C/C	C	*34 - Uncertain function
chr10:94762715	rs367543003	T/T	T	*34 - Uncertain function
chr10:94762755	rs55752064	T/T	T	*14 - Uncertain function
chr10:94762760	rs17882687	A/A	A	15 - Normal function 28 - Normal function 35 - No function 39 - Uncertain function
chr10:94762788	rs1564656981	A/A	A	*29 - Uncertain function
chr10:94762856	rs1564657013	A/A	A	*19 - Decreased function
chr10:94775106	rs145328984	C/C	C	*30 - Uncertain function
chr10:94775121	rs1564660997	C/C	C	*31 - Uncertain function
chr10:94775160	rs118203756	G/G	G	*23 - Uncertain function
chr10:94775185	rs1288601658	A/A	A	*32 - Uncertain function
chr10:94775367	rs12769205	A/A	A	2 - No function 35 - No function
chr10:94775416	rs41291556	T/T	T	*8 - No function
chr10:94775423	rs17885179	A/A	A	*39 - Uncertain function
chr10:94775453	rs72552267	G/G	G	*6 - No function
chr10:94775489	rs17884712	G/G	G	*9 - Decreased function
chr10:94775507	rs58973490	G/G	G	2 - No function 11 - Normal function
chr10:94780574	rs140278421	G/G	G	*22 - No function
chr10:94780579	rs370803989	G/G	G	*33 - Uncertain function
chr10:94780653	rs4986893	G/G	G	*3 - No function
chr10:94781858	rs6413438	C/C	C	*10 - Decreased function
chr10:94781859	rs4244285	G/G	G	*2 - No function
chr10:94781944	rs375781227	G/G	G	*26 - Decreased function
chr10:94781999	rs72558186	T/T	T	*7 - No function
chr10:94842861	rs138142612	G/G	G	*18 - Normal function
chr10:94842866	rs3758581	A/A	A	1 - Normal function 2 - No function 3 - No function 4 - No function 5 - No function 6 - No function 7 - No function 8 - No function 9 - Decreased function 10 - Decreased function 11 - Normal function 12 - Uncertain function 13 - Normal function 14 - Uncertain function 15 - Normal function 17 - Increased function 18 - Normal function 19 - Decreased function 22 - No function 23 - Uncertain function 24 - No function 25 - Decreased function 26 - Decreased function 28 - Normal function 29 - Uncertain function 31 - Uncertain function 32 - Uncertain function 33 - Uncertain function 35 - No function 39 - Uncertain function
chr10:94842879	rs118203757	G/G	G	*24 - No function
chr10:94842995	rs113934938	G/G	G	*28 - Normal function
chr10:94849995	rs17879685	C/C	C	*13 - Normal function
chr10:94852738	rs56337013	C/C	C	*5 - No function
chr10:94852765	rs192154563	C/C	C	*16 - Decreased function
chr10:94852785	rs118203759	C/C	C	*25 - Decreased function
chr10:94852914	rs55640102	A/A	A	*12 - Uncertain function

CYP2C9 allele match data

Genotype Matched:

*1/*1

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

The CYP2C9 *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr10:94938683	rs114071557	A/A	A	*36 - n/a
chr10:94938719		T/T	T	*80 - Unassigned function
chr10:94938737	rs67807361	C/C	C	*7 - n/a
chr10:94938771	rs142240658	C/C	C	*21 - n/a
chr10:94938788		C/C	C	*83 - Unassigned function
chr10:94938800	rs1364419386	G/G	G	*76 - Unassigned function
chr10:94938803	rs2031308986	A/A	A	*22 - n/a
chr10:94938828	rs564813580	A/A	A	*37 - 0.5
chr10:94941897	rs371055887	G/G	G	*20 - n/a
chr10:94941915		G/G	G	*23 - 0.5
chr10:94941958	rs72558187	T/T	T	*13 - 0.0
chr10:94941975		G/G	G	*77 - Unassigned function
chr10:94941976		G/G	G	*38 - 0.5
chr10:94941982	rs762239445	G/G	G	*39 - 0.0
chr10:94942018		T/T	T	*40 - n/a
chr10:94942205	rs1304490498	CAATGGAAA GA/ CAATGGAAA GA	CAATGGAAA GA	*25 - 0.0
chr10:94942216	rs774607211	A/A	A	*41 - n/a
chr10:94942230	rs767576260	C/C	C	*43 - 0.0
chr10:94942231	rs12414460	G/G	G	*42 - 0.0
chr10:94942233	rs375805362	C/C	C	*62 - n/a
chr10:94942234	rs72558189	G/G	G	14 - 0.5 35 - 0.0
chr10:94942243	rs1375956433	T/T	T	*78 - Unassigned function
chr10:94942249	rs200965026	C/C	C	26 - 0.5 44 - 0.5
chr10:94942254	rs199523631	C/C	C	*45 - 0.0
chr10:94942255	rs200183364	G/G	G	*33 - 0.0
chr10:94942290	rs1799853	C/C	C	2 - 0.5 35 - 0.0 *61 - 0.5
chr10:94942291	rs141489852	G/G	G	*63 - n/a
chr10:94942305	rs754487195	G/G	G	*46 - 0.5
chr10:94942306	rs1289704600	C/C	C	*72 - n/a
chr10:94942308	rs17847037	C/C	C	*73 - n/a
chr10:94942309	rs7900194	G/G	G	8 - 0.5 27 - n/a
chr10:94947782	rs72558190	C/C	C	*15 - 0.0
chr10:94947785	rs774550549	C/C	C	*47 - n/a
chr10:94947869		A/A	A	*69 - n/a
chr10:94947907		A/A	A	*57 - n/a
chr10:94947917	rs1326630788	T/T	T	*48 - n/a
chr10:94947938	rs2031531005	A/A	A	*28 - 0.5
chr10:94947939	rs370100007	G/G	G	*74 - n/a
chr10:94949129		A/A	A	*49 - n/a
chr10:94949144		C/C	C	*50 - 0.5
chr10:94949145	rs772782449	C/C	C	*82 - Unassigned function
chr10:94949161		AT/AT	AT	*85 - Unassigned function
chr10:94949217	rs2256871	A/A	A	*9 - 1.0
chr10:94949280	rs9332130	A/A	A	10 - n/a 71 - n/a
chr10:94949281	rs9332131	GA/GA	GA	*6 - 0.0
chr10:94972119	rs182132442	C/C	C	*29 - 0.5
chr10:94972123		C/C	C	*64 - n/a
chr10:94972134		A/A	A	*51 - n/a
chr10:94972179	rs72558192	A/A	A	*16 - 0.5
chr10:94972180	rs988617574	C/C	C	*52 - 0.0
chr10:94972183		A/A	A	*81 - Unassigned function
chr10:94972233	rs1237225311	C/C	C	*53 - n/a
chr10:94981199		G/G	G	*65 - n/a
chr10:94981201	rs57505750	T/T	T	*31 - 0.5
chr10:94981224	rs28371685	C/C	C	*11 - 0.5
chr10:94981225	rs367826293	G/G	G	*34 - n/a
chr10:94981230	rs1274535931	C/C	C	*58 - n/a
chr10:94981250	rs750820937	C/C	C	*54 - n/a
chr10:94981258	rs1297714792	C/C	C	*79 - Unassigned function
chr10:94981281	rs749060448	G/G	G	*24 - 0.0
chr10:94981296	rs1057910	A/A	A	3 - 0.0 18 - n/a *68 - n/a
chr10:94981297	rs56165452	T/T	T	*4 - 0.5
chr10:94981301	rs28371686	C/C	C	*5 - 0.5
chr10:94981302	rs1250577724	C/C	C	*55 - 0.5
chr10:94981305	rs578144976	C/C	C	*66 - n/a
chr10:94981365		C/C	C	*17 - n/a
chr10:94981371	rs542577750	G/G	G	*68 - n/a
chr10:94986042	rs764211126	A/A	A	*56 - n/a
chr10:94986073	rs72558193	A/A	A	*18 - n/a
chr10:94986136	rs1254213342	A/A	A	*75 - n/a
chr10:94986174	rs1441296358	G/G	G	*84 - Unassigned function
chr10:94988852	rs776908257	C/C	C	*67 - n/a
chr10:94988855		A/A	A	*59 - n/a
chr10:94988880		G/G	G	*70 - n/a
chr10:94988917	rs769942899	G/G	G	*19 - n/a
chr10:94988925	rs202201137	A/A	A	*61 - 0.5
chr10:94988955	rs767284820	T/T	T	*60 - n/a
chr10:94988984	rs781583846	G/G	G	*30 - 0.5
chr10:94989020	rs9332239	C/C	C	12 - 0.5 71 - n/a
chr10:94989023	rs868182778	G/G	G	*32 - n/a

Other Positions of Interest

Position in VCF	RSID	Call in VCF
chr10:94645745	rs12777823	G/G

CYP2D6 allele match data

Genotype Reported:	1/3

This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.

CYP3A4 allele match data

Genotype Matched:

*1/*1

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

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

The CYP3A4 *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr7:99758183	rs67666821	G/G	G	*20 - No function
chr7:99758228		T/T	T	*46 - Unassigned function
chr7:99760836	rs4986913	G/G	G	*19 - Unassigned function
chr7:99760901	rs4986910	A/A	A	3 - Unassigned function 37 - Unassigned function *38 - Unassigned function
chr7:99760956	rs774109750	T/T	T	*34 - Unassigned function
chr7:99762047	rs4986909	G/G	G	*13 - Decreased function
chr7:99762054		A/A	A	*45 - Unassigned function
chr7:99762177	rs12721629	G/G	G	*12 - Decreased function
chr7:99762186	rs756833413	C/C	C	*33 - Unassigned function
chr7:99762206	rs67784355	G/G	G	11 - Decreased function 38 - Unassigned function
chr7:99763877	rs368296206	A/A	A	*32 - Unassigned function
chr7:99763909	rs1303250043	G/G	G	*31 - Unassigned function
chr7:99763925		T/T	T	*21 - Unassigned function
chr7:99764003	rs28371759	A/A	A	*18 - Decreased function
chr7:99766411	rs4646438	G/G	G	*6 - No function
chr7:99766424		T/T	T	*44 - Unassigned function
chr7:99766439		C/C	C	*43 - Unassigned function
chr7:99766440	rs138105638	G/G	G	*26 - No function
chr7:99768360	rs55785340	A/A	A	*2 - Unassigned function
chr7:99768371	rs55901263	G/G	G	*5 - Unassigned function
chr7:99768424	rs113667357	T/T	T	*24 - Unassigned function
chr7:99768447		T/T	T	*42 - Unassigned function
chr7:99768458	rs4987161	A/A	A	*17 - Decreased function
chr7:99768470	rs12721627	G/G	G	*16 - Decreased function
chr7:99768693	rs35599367	G/G	G	22 - Decreased function 37 - Unassigned function
chr7:99769769	rs4986908	C/C	C	*10 - Unassigned function
chr7:99769781	rs72552798	C/C	C	*9 - Unassigned function
chr7:99769804	rs4986907	C/C	C	*15 - Unassigned function
chr7:99769805	rs57409622	G/G	G	*23 - Unassigned function
chr7:99770165	rs72552799	C/C	C	*8 - Decreased function
chr7:99770166	rs778013004	G/G	G	*30 - Unassigned function
chr7:99770196		T/T	T	*41 - Unassigned function
chr7:99770202	rs55951658	T/T	T	*4 - Unassigned function
chr7:99770217	rs1449865051	A/A	A	*29 - Unassigned function
chr7:99778079	rs56324128	C/C	C	*7 - Unassigned function
chr7:99780036		G/G	G	*40 - Unassigned function
chr7:99784018	rs570051168	G/G	G	*28 - Unassigned function
chr7:99784038	rs12721634	A/A	A	*14 - Unassigned function
chr7:99784075	rs188389063	G/G	G	*35 - Unassigned function
chr7:99784078		C/C	C	*39 - Unassigned function

CYP3A5 allele match data

Genotype Matched:

*1/*1

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

The CYP3A5 *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr7:99652770	rs41303343	T/T	T	*7 - No function
chr7:99660516	rs28383479	C/C	C	*9 - Unknown function
chr7:99665212	rs10264272	C/C	C	*6 - No function
chr7:99672916	rs776746	T/T	T	*3 - No function
chr7:99676198	rs55817950	G/G	G	*8 - Unknown function

CYP4F2 allele match data

Genotype Matched:

*1/*1

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

The CYP4F2 *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr19:15878779	rs3093200	G/G	G	*5 - Unassigned function
chr19:15879412	rs138971789	C/C	C	*15 - Unassigned function
chr19:15879621	rs2108622	C/C	C	3 - Unassigned function 4 - Unassigned function
chr19:15886018	rs145174239	G/G	G	*14 - Unassigned function
chr19:15889671	rs144233412	C/C	C	*13 - Unassigned function
chr19:15890405	rs3093153	C/C	C	*6 - Unassigned function
chr19:15892541	rs145875499	C/C	C	*12 - Unassigned function
chr19:15895527	rs114396708	G/G	G	*11 - Unassigned function
chr19:15895560	rs144455532	G/G	G	*10 - Unassigned function
chr19:15897466	rs201380574	C/C	C	*9 - Unassigned function
chr19:15897473	rs115517770	G/G	G	*8 - Unassigned function
chr19:15897566	rs114099324	C/C	C	*7 - Unassigned function
chr19:15897578	rs3093105	A/A	A	2 - Unassigned function 4 - Unassigned function

DPYD allele match data

Genotype Matched:	Reference/Reference
Phasing Status:	Unphased

The DPYD Reference allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr1:97078987	rs114096998	G/G	G	c.3067C>A - 1.0
chr1:97078993	rs148799944	C/C	C	c.3061G>C - 1.0
chr1:97079005	rs140114515	C/C	C	c.3049G>A - 1.0
chr1:97079071	rs1801268	C/C	C	c.2983G>T (*10) - 0.0
chr1:97079076	rs139459586	A/A	A	c.2978T>G - 1.0
chr1:97079077	rs202144771	G/G	G	c.2977C>T - 1.0
chr1:97079121	rs72547601	T/T	T	c.2933A>G - 0.0
chr1:97079133	rs72547602	T/T	T	c.2921A>T - 1.0
chr1:97079139	rs145529148	T/T	T	c.2915A>G - 1.0
chr1:97082365	rs141044036	T/T	T	c.2872A>G - 0.0
chr1:97082391	rs67376798	T/T	T	c.2846A>T - 0.5
chr1:97098598	rs1801267	C/C	C	c.2657G>A (*9B) - 1.0
chr1:97098599	rs147545709	G/G	G	c.2656C>T - 1.0
chr1:97098616	rs55674432	C/C	C	c.2639G>T - 0.0
chr1:97098632	rs201035051	T/T	T	c.2623A>C - 1.0
chr1:97193109	rs60139309	T/T	T	c.2582A>G - 1.0
chr1:97193209	rs200687447	C/C	C	c.2482G>A - 1.0
chr1:97234958	rs199634007	G/G	G	c.2336C>A - 1.0
chr1:97234991	rs56005131	G/G	G	c.2303C>A - 1.0
chr1:97305279	rs112766203	G/G	G	c.2279C>T - 0.5
chr1:97305363	rs60511679	A/A	A	c.2195T>G - 1.0
chr1:97305364	rs1801160	C/C	C	c.2194G>A (*6) - 1.0
chr1:97305372	rs146529561	G/G	G	c.2186C>T - 1.0
chr1:97306195	rs145548112	C/C	C	c.2161G>A - 1.0
chr1:97373598	rs137999090	C/C	C	c.2021G>A - 0.0
chr1:97373629	rs138545885	C/C	C	c.1990G>T - 1.0
chr1:97382461	rs55971861	T/T	T	c.1906A>C - 1.0
chr1:97450058	rs3918290	C/C	C	c.1905+1G>A (*2A) - 0.0
chr1:97450059	rs3918289	G/G	G	c.1905C>G - 1.0
chr1:97450065	rs72549303	TG/TG	TG	c.1898delC (*3) - 0.0
chr1:97450068	rs17376848	A/A	A	c.1896T>C - 1.0
chr1:97450168	rs147601618	A/A	A	c.1796T>C - 1.0
chr1:97450187	rs145773863	C/C	C	c.1777G>A - 0.0
chr1:97450189	rs138616379	C/C	C	c.1775G>A - 0.0
chr1:97450190	rs59086055	G/G	G	c.1774C>T - 0.0
chr1:97515784	rs201615754	C/C	C	c.1682G>T - 1.0
chr1:97515787	rs55886062	A/A	A	c.1679T>G (*13) - 0.0
chr1:97515839	rs1801159	T/T	T	c.1627A>G (*5) - 1.0
chr1:97515851	rs142619737	C/C	C	c.1615G>A - 1.0
chr1:97515865	rs1801158	C/C	C	c.1601G>A (*4) - 1.0
chr1:97515889	rs190951787	G/G	G	c.1577C>G - 1.0
chr1:97515923	rs148994843	C/C	C	c.1543G>A - 1.0
chr1:97549565	rs138391898	C/C	C	c.1519G>A - 1.0
chr1:97549600	rs111858276	T/T	T	c.1484A>G - 0.0
chr1:97549609	rs72549304	G/G	G	c.1475C>T - 0.0
chr1:97549681	rs199549923	G/G	G	c.1403C>A - 1.0
chr1:97549713	rs57918000	G/G	G	c.1371C>T - 1.0
chr1:97549726	rs144395748	G/G	G	c.1358C>G - 1.0
chr1:97549735	rs72975710	G/G	G	c.1349C>T - 1.0
chr1:97573785	rs186169810	A/A	A	c.1314T>G - 0.5
chr1:97573805	rs142512579	C/C	C	c.1294G>A - 1.0
chr1:97573821	rs764666241	C/C	C	c.1278G>T - 1.0
chr1:97573839	rs200064537	A/A	A	c.1260T>A - 1.0
chr1:97573863	rs56038477	C/C	C	c.1129-5923C>G, c.1236G>A (HapB3) - 0.5
chr1:97573881	rs61622928	C/C	C	c.1218G>A - 1.0
chr1:97573918	rs143815742	C/C	C	c.1181G>T - 1.0
chr1:97573919	rs140602333	G/G	G	c.1180C>T - 1.0
chr1:97573943	rs78060119	C/C	C	c.1156G>T (*12) - 0.0
chr1:97579893	rs75017182	G/G	G	c.1129-5923C>G, c.1236G>A (HapB3) - 0.5
chr1:97593238	rs72549305	T/T	T	c.1108A>G - 1.0
chr1:97593289	rs143154602	G/G	G	c.1057C>T - 0.0
chr1:97593322	rs183385770	C/C	C	c.1024G>A - 0.0
chr1:97593343	rs72549306	C/C	C	c.1003G>T (*11) - 1.0
chr1:97593379	rs201018345	C/C	C	c.967G>A - 1.0
chr1:97595083	rs145112791	G/G	G	c.934C>T - 1.0
chr1:97595088	rs150437414	A/A	A	c.929T>C - 1.0
chr1:97595149	rs146356975	T/T	T	c.868A>G - 0.5
chr1:97679170	rs45589337	T/T	T	c.775A>G - 1.0
chr1:97691776	rs1801266	G/G	G	c.703C>T (*8) - 0.0
chr1:97699399	rs72549307	T/T	T	c.632A>G - 0.0
chr1:97699430	rs72549308	T/T	T	c.601A>C - 0.0
chr1:97699474	rs115232898	T/T	T	c.557A>G - 0.5
chr1:97699506	rs6670886	C/C	C	c.525G>A - 1.0
chr1:97699533	rs139834141	C/C	C	c.498G>A - 1.0
chr1:97699535	rs2297595	T/T	T	c.496A>G - 1.0
chr1:97721542	rs200562975	T/T	T	c.451A>G - 1.0
chr1:97721650	rs141462178	T/T	T	c.343A>G - 1.0
chr1:97740400	rs150385342	C/C	C	c.313G>A - 1.0
chr1:97740410	rs72549309	GATGA/ GATGA	GATGA	c.295_298delTCAT (*7) - 0.0
chr1:97883329	rs1801265	A/A	A	c.85T>C (*9A) - 1.0
chr1:97883352	rs80081766	C/C	C	c.62G>A - 1.0
chr1:97883353	rs72549310	G/G	G	c.61C>T - 0.0
chr1:97883368	rs150036960	G/G	G	c.46C>G - 1.0

F5 allele match data

Genotype Matched:

rs6025 C/rs6025 C

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function	Warnings
chr1:169549811	rs6025	C/C	C	rs6025 T (Factor V Leiden) - Factor V Leiden positive

G6PD allele match data

Genotype Matched:

B (reference)/B (reference)

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

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/).

The G6PD B (reference) allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chrX:154532046		A/A	A	Bangkok Noi - I/Deficient with CNSHA
chrX:154532055		CTCT/CTCT	CTCT	Brighton - I/Deficient with CNSHA
chrX:154532082		G/G	G	Arakawa - I/Deficient with CNSHA
chrX:154532083		G/G	G	Buenos Aires - I/Deficient with CNSHA
chrX:154532085		C/C	C	Campinas - I/Deficient with CNSHA
chrX:154532086		C/C	C	Fukaya - I/Deficient with CNSHA
chrX:154532203	rs137852348	G/G	G	Split - III/Deficient
chrX:154532231		T/T	T	Laibin - Uncertain function
chrX:154532245	rs137852344	G/G	G	Neapolis - III/Deficient
chrX:154532257	rs72554664	C/C	C	Kaiping, Anant, Dhon, Sapporo-like, Wosera - II/Deficient
chrX:154532258		G/G	G	Flores - II/Deficient Kamiube, Keelung - III/Deficient
chrX:154532264	rs782608284	C/C	C	Yunan - Uncertain function
chrX:154532265		C/C	C	Nice - III/Deficient
chrX:154532269	rs72554665	C/C	C	Bangkok Noi - I/Deficient with CNSHA Canton, Taiwan-Hakka, Gifu-like, Agrigento-like - II/Deficient Cosenza - II/Deficient
chrX:154532278		T/T	T	Amiens - I/Deficient with CNSHA
chrX:154532279		C/C	C	Figuera da Foz - I/Deficient with CNSHA
chrX:154532389	rs137852324	C/C	C	Andalus - II/Deficient
chrX:154532390	rs398123546	G/G	G	Hermoupolis - II/Deficient Honiara - I/Deficient with CNSHA Union,Maewo, Chinese-2, Kalo - II/Deficient
chrX:154532392		A/A	A	Harima - I/Deficient with CNSHA
chrX:154532403		C/C	C	Cassano - II/Deficient Hermoupolis - II/Deficient
chrX:154532408		T/T	T	S. Antioco - II/Deficient
chrX:154532411	rs137852317	C/C	C	Santiago de Cuba, Morioka - I/Deficient with CNSHA
chrX:154532432		G/G	G	Telti/Kobe - I/Deficient with CNSHA
chrX:154532434	rs137852337	C/C	C	Pawnee - II/Deficient
chrX:154532458		A/A	A	Sumare - I/Deficient with CNSHA
chrX:154532459	rs782098548	C/C	C	Surabaya - II/Deficient
chrX:154532570		G/G	G	Georgia - I/Deficient with CNSHA
chrX:154532590		G/G	G	202G>A_376A>G_1264C>G - I/Deficient with CNSHA
chrX:154532608		C/C	C	Tokyo, Fukushima - I/Deficient with CNSHA
chrX:154532623		T/T	T	Munich - I/Deficient with CNSHA
chrX:154532625	rs137852336	C/C	C	Japan, Shinagawa - I/Deficient with CNSHA Kawasaki - I/Deficient with CNSHA
chrX:154532626	rs137852323	C/C	C	Riverside - I/Deficient with CNSHA
chrX:154532628		G/G	G	Suwalki - I/Deficient with CNSHA
chrX:154532629		G/G	G	Utrecht - I/Deficient with CNSHA
chrX:154532634		T/T	T	Abeno - II/Deficient
chrX:154532639		C/C	C	Clinic - I/Deficient with CNSHA
chrX:154532649		G/G	G	Covao do Lobo - I/Deficient with CNSHA
chrX:154532661		T/T	T	Anadia - II/Deficient
chrX:154532662	rs137852325	C/C	C	Puerto Limon - I/Deficient with CNSHA
chrX:154532667		G/G	G	Bari - I/Deficient with CNSHA
chrX:154532674	rs137852335	C/C	C	Alhambra - I/Deficient with CNSHA
chrX:154532676	rs137852316	C/C	C	Nashville, Anaheim, Portici - I/Deficient with CNSHA
chrX:154532677		G/G	G	Wisconsin - I/Deficient with CNSHA
chrX:154532679		A/A	A	Krakow - I/Deficient with CNSHA
chrX:154532688		T/T	T	Praha - I/Deficient with CNSHA
chrX:154532692		T/T	T	Hartford - I/Deficient with CNSHA
chrX:154532694	rs137852321	C/C	C	Beverly Hills, Genova, Iwate, Niigata, Yamaguchi - I/Deficient with CNSHA
chrX:154532695	rs137852334	G/G	G	Guadalajara - I/Deficient with CNSHA Mt Sinai - I/Deficient with CNSHA
chrX:154532698	rs137852320	T/T	T	Iowa, Walter Reed, Springfield - I/Deficient with CNSHA
chrX:154532699		G/G	G	Madrid - I/Deficient with CNSHA
chrX:154532700		C/C	C	Lynwood - I/Deficient with CNSHA
chrX:154532701	rs137852322	A/A	A	Tomah - I/Deficient with CNSHA
chrX:154532713		A/A	A	Olomouc - I/Deficient with CNSHA
chrX:154532715		A/A	A	Riley - I/Deficient with CNSHA
chrX:154532716		T/T	T	Calvo Mackenna - I/Deficient with CNSHA
chrX:154532722	rs371489738	C/C	C	Montpellier - I/Deficient with CNSHA
chrX:154532752		CGGCCTTGC GCTCGTTCA G/ CGGCCTTGC GCTCGTTCA G	CGGCCTTGC GCTCGTTCA G	Tondela - I/Deficient with CNSHA
chrX:154532758		T/T	T	Tenri - I/Deficient with CNSHA
chrX:154532765	rs137852329	G/G	G	Aachen - I/Deficient with CNSHA Loma Linda - I/Deficient with CNSHA
chrX:154532772	rs137852345	G/G	G	Serres - I/Deficient with CNSHA
chrX:154532773		C/C	C	Iwatsuki - I/Deficient with CNSHA
chrX:154532797	rs137852333	G/G	G	Ierapetra - II/Deficient
chrX:154532802		C/C	C	Partenope - II/Deficient
chrX:154532945	rs34193178	C/C	C	Mira d'Aire - IV/Normal
chrX:154532956	rs398123544	T/T	T	Cincinnati - I/Deficient with CNSHA
chrX:154532969	rs137852342	G/G	G	Chinese-5 - III/Deficient
chrX:154532987		T/T	T	Torun - I/Deficient with CNSHA
chrX:154532989		G/G	G	Fushan - II/Deficient
chrX:154532990	rs5030869	C/C	C	Chatham - II/Deficient
chrX:154533004		C/C	C	Insuli - IV/Normal
chrX:154533012		CGTGGGGTC GTCCAGGTA CCCTTTG/ CGTGGGGTC GTCCAGGTA CCCTTTG	CGTGGGGTC GTCCAGGTA CCCTTTG	Nara - I/Deficient with CNSHA
chrX:154533016		G/G	G	Farroupilha - II/Deficient
chrX:154533025	rs76723693	A/A	A	A- 968C_376G - III/Deficient
chrX:154533029	rs137852347	A/A	A	Rehevot - I/Deficient with CNSHA
chrX:154533031		C/C	C	Manhattan - I/Deficient with CNSHA
chrX:154533044	rs137852339	C/C	C	Kalyan-Kerala, Jamnaga, Rohini - III/Deficient
chrX:154533064		C/C	C	Ludhiana - II/Deficient
chrX:154533072		C/C	C	Omiya - I/Deficient with CNSHA
chrX:154533077		C/C	C	Seoul - II/Deficient
chrX:154533083		C/C	C	West Virginia - I/Deficient with CNSHA
chrX:154533122	rs137852327	C/C	C	Ananindeua - II/Deficient Hechi - II/Deficient Viangchan, Jammu - II/Deficient
chrX:154533586	rs74575103	C/C	C	Montalbano - III/Deficient
chrX:154533587		G/G	G	Osaka - II/Deficient
chrX:154533589		A/A	A	Piotrkow - I/Deficient with CNSHA
chrX:154533591		G/G	G	Papua - Uncertain function
chrX:154533592		T/T	T	Mizushima - II/Deficient
chrX:154533596	rs137852318	C/C	C	Bajo Maumere - III/Deficient Seattle, Lodi, Modena, Ferrara II, Athens-like - III/Deficient
chrX:154533605		T/T	T	Chinese-1 - II/Deficient Haikou - II/Deficient
chrX:154533607		G/G	G	Wexham - I/Deficient with CNSHA
chrX:154533608		A/A	A	La Jolla - I/Deficient with CNSHA
chrX:154533614		G/G	G	Sugao - I/Deficient with CNSHA
chrX:154533615		C/C	C	Bangkok - I/Deficient with CNSHA
chrX:154533619		T/T	T	Lille - I/Deficient with CNSHA
chrX:154533620		C/C	C	Cleveland Corum - I/Deficient with CNSHA
chrX:154533629		C/C	C	Roubaix - II/Deficient
chrX:154533634	rs137852346	C/C	C	Aveiro - I/Deficient with CNSHA
chrX:154534036		G/G	G	Wayne - I/Deficient with CNSHA
chrX:154534074		TCAGTGC/ TCAGTGC	TCAGTGC	Stonybrook - I/Deficient with CNSHA
chrX:154534092		T/T	T	Durham - I/Deficient with CNSHA
chrX:154534102	rs782757170	G/G	G	Nanning - III/Deficient
chrX:154534110		C/C	C	Asahikawa - I/Deficient with CNSHA
chrX:154534116		ATGT/ATGT	ATGT	North Dallas - I/Deficient with CNSHA
chrX:154534125	rs137852328	C/C	C	A- 680T_376G - III/Deficient Mexico City - III/Deficient
chrX:154534126		G/G	G	Radlowo - II/Deficient
chrX:154534157	rs137852319	A/A	A	Harilaou - I/Deficient with CNSHA
chrX:154534345	rs137852326	C/C	C	Cincinnati - I/Deficient with CNSHA Minnesota, Marion, Gastonia, LeJeune - I/Deficient with CNSHA
chrX:154534348	rs782754619	T/T	T	Sibari - III/Deficient
chrX:154534387	rs781865768	T/T	T	Dagua - Uncertain function
chrX:154534389	rs137852332	C/C	C	Nilgiri - II/Deficient Santiago - I/Deficient with CNSHA
chrX:154534390	rs137852330	G/G	G	Coimbra Shunde - II/Deficient Vancouver - I/Deficient with CNSHA
chrX:154534409		G/G	G	Pedoplis-Ckaro - I/Deficient with CNSHA
chrX:154534414		GGGA/GGGA	GGGA	Tsukui - I/Deficient with CNSHA
chrX:154534419	rs5030868	G/G	G	Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham - II/Deficient
chrX:154534438	rs267606836	G/G	G	Vancouver - I/Deficient with CNSHA
chrX:154534440	rs5030872	T/T	T	Malaga - III/Deficient Santa Maria - II/Deficient
chrX:154534447		T/T	T	Chikugo - I/Deficient with CNSHA
chrX:154534455		T/T	T	Shinshu - I/Deficient with CNSHA
chrX:154534463		G/G	G	Miaoli - II/Deficient
chrX:154534465	rs137852343	A/A	A	Nankang - II/Deficient
chrX:154534468		G/G	G	Volendam - I/Deficient with CNSHA
chrX:154534485		C/C	C	Naone - II/Deficient
chrX:154534486		G/G	G	Toledo - II/Deficient
chrX:154534489	rs137852331	T/T	T	Taipei, Chinese-3 - II/Deficient
chrX:154534494		C/C	C	Plymouth - I/Deficient with CNSHA
chrX:154534495	rs137852314	C/C	C	Mahidol - III/Deficient
chrX:154535176	rs370918918	C/C	C	Gond - Uncertain function
chrX:154535180	rs782487723	C/C	C	Shenzen - II/Deficient
chrX:154535187	rs137852313	C/C	C	Ilesha - III/Deficient
chrX:154535190		G/G	G	Acrokorinthos - II/Deficient
chrX:154535211		C/C	C	Liuzhou - II/Deficient
chrX:154535244		G/G	G	Belem - II/Deficient
chrX:154535247		G/G	G	Valladolid - II/Deficient
chrX:154535249	rs782322505	T/T	T	Cairo - II/Deficient
chrX:154535261		C/C	C	Quing Yan - III/Deficient
chrX:154535269		G/G	G	Crispim - II/Deficient
chrX:154535270	rs78365220	A/A	A	Crispim - II/Deficient Salerno Pyrgos - III/Deficient Vanua Lava - II/Deficient
chrX:154535274		C/C	C	Crispim - II/Deficient
chrX:154535277	rs1050829	T/T	T	202G>A_376A>G_1264C>G - I/Deficient with CNSHA A - IV/Normal A- 202A_376G - III/Deficient A- 680T_376G - III/Deficient A- 968C_376G - III/Deficient Acrokorinthos - II/Deficient Ananindeua - II/Deficient Mt Sinai - I/Deficient with CNSHA Santa Maria - II/Deficient Sierra Leone - III/Deficient
chrX:154535278		C/C	C	Crispim - II/Deficient
chrX:154535301		A/A	A	Bao Loc - II/Deficient
chrX:154535316	rs5030870	C/C	C	Sao Borja - IV/Normal
chrX:154535330		A/A	A	Hammersmith - III/Deficient
chrX:154535336	rs267606835	G/G	G	Vancouver - I/Deficient with CNSHA
chrX:154535342	rs181277621	C/C	C	Sierra Leone - III/Deficient
chrX:154535367		GCTT/GCTT	GCTT	Urayasu - I/Deficient with CNSHA
chrX:154535379		G/G	G	Guangzhou - III/Deficient
chrX:154535962	rs782308266	C/C	C	Lagosanto - III/Deficient
chrX:154535963	rs138687036	G/G	G	Ube Konan - III/Deficient
chrX:154535980		A/A	A	Swansea - I/Deficient with CNSHA
chrX:154535995	rs782090947	T/T	T	Murcia Oristano - III/Deficient
chrX:154535996	rs137852349	A/A	A	Namouru - II/Deficient
chrX:154536002	rs1050828	C/C	C	202G>A_376A>G_1264C>G - I/Deficient with CNSHA A- 202A_376G - III/Deficient Asahi - III/Deficient Hechi - II/Deficient
chrX:154536008		A/A	A	Songklanagarind - II/Deficient
chrX:154536019		G/G	G	Amazonia - II/Deficient Musashino - III/Deficient
chrX:154536021		CAGA/CAGA	CAGA	Amsterdam - I/Deficient with CNSHA
chrX:154536025		A/A	A	Costanzo - II/Deficient
chrX:154536032	rs137852315	C/C	C	Metaponto - III/Deficient
chrX:154536034		C/C	C	Palestrina - III/Deficient
chrX:154536035		G/G	G	Kamogawa - II/Deficient
chrX:154536045		C/C	C	Kozukata - I/Deficient with CNSHA
chrX:154536151		G/G	G	Kambos - III/Deficient
chrX:154536156	rs76645461	A/A	A	Aures - III/Deficient
chrX:154536168	rs78478128	G/G	G	Orissa - III/Deficient
chrX:154536169		C/C	C	Rignano - III/Deficient
chrX:154546045	rs137852338	CATG/CATG	CATG	Sunderland - I/Deficient with CNSHA
chrX:154546046		A/A	A	Gidra - Uncertain function
chrX:154546057		T/T	T	Honiara - I/Deficient with CNSHA
chrX:154546061	rs137852340	T/T	T	Gaohe - III/Deficient
chrX:154546116		C/C	C	Lages - III/Deficient
chrX:154546122		C/C	C	Sinnai - III/Deficient
chrX:154546131		G/G	G	No name - I/Deficient with CNSHA

HLA-B allele match data

Genotype Reported:	15:02/57:01

This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.

IFNL3/4 allele match data

Genotype Matched:

rs12979860 reference (C)/rs12979860 reference (C)

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function	Warnings
chr19:39248147	rs12979860	C/C	C	rs12979860 variant (T) - Unassigned function

MT-RNR1 allele match data

Genotype Reported:	1555A>G

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function
chr2:233759924	rs887829	C/C	C	80 - Unknown function 80+28 - Decreased function 80+*37 - Decreased function
chr2:233760233	rs3064744	CAT/CAT	CAT	28 - Decreased function 36 - Increased function 37 - Decreased function 80+28 - Decreased function 80+*37 - Decreased function
chr2:233760498	rs4148323	G/G	G	*6 - Decreased function
chr2:233760973	rs35350960	C/C	C	*27 - Decreased function

VKORC1 allele match data

Genotype Matched:

rs9923231 reference (C)/rs9923231 reference (C)

Phasing Status:

Unphased

PharmCAT reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Calls at Positions

Position in VCF	RSID	Call in VCF	Reference	Related Alleles and Function	Warnings
chr16:31096368	rs9923231	C/C	C	rs9923231 variant (T) - Higher coumarin sensitivity

Disclaimers and Other Information

Liability: PharmCAT assumes no responsibility for any injury to person or damage to persons or property arising out of, or related to any use of PharmCAT, or for any errors or omissions. The user recognizes that PharmCAT is a research tool and that they are using PharmCAT at their own risk.

A. Allele and Genotype Determination

PharmCAT uses gene allele definitions included in the CPIC database, with exceptions as noted in Gene Definition Exceptions document. For allele definitions and the positions used in PharmCAT, see the gene definition tables.
Genes with DPWG recommendations that are not included in CPIC are discussed in Section C.
PharmCAT results are dependent on the supplied VCF calls for the queried positions (for technical information about PharmCAT input formatting and requirements, please go to pharmcat.org). PharmCAT does not assume any reference calls for positions missing from the submitted VCF file; all missing queried positions are not considered in the allele determination process. See the pharmcat_positions file for which positions are queried in the VCF file. Missing positions might alter the assigned genotype and subsequent phenotype prediction and CPIC recommendation. If the supplied VCF file has missing positions, those positions will be noted in Section III: Allele Matching Details for each gene of this report. For the most reliable allele determination, reference calls as well as variant calls in the VCF file for every queried position must be provided by the user. If an allele that includes a missing position is defined by an additional position(s) for which calls are provided, the allele will be considered in the matching process based on the available information. This might lead to the output of multiple possible genotypes that received the same highest matching score. In addition, alternate calls with a lower score is also possible. For instructions on getting PharmCAT to output all possible matching genotypes, consult the documentation.
For cytochrome P450 genes, TPMT, NUDT15, UGT1A1, and SLCO1B1, the *1 allele is defined by the absence of variation specified in the gene definition tables. This allele cannot be identified by variants; rather, *1 is assigned by default when no variation for the queried positions is reported in the submitted VCF file. The same is true for all other genes with multiple variant positions in the definition table (CACNA1S, CFTR, DPYD, RYR1): the reference sequence is the default result when variants are not reported in the VCF file. It is always possible un-interrogated variation can occur which could potentially affect allele function, but because it is undetected, the assignment would be defaulted to a *1 (or reference) allele and normal function.
For all genes, variation reported in the VCF file but NOT included in the gene definition table will not be considered during allele assignment. There is a possibility that any such variation results in a reduced or no activity allele which could lead to inaccurate phenotype and CPIC recommendation, similar to the situation in point 3, above.
Nucleotide base calls are displayed on the positive chromosomal strand regardless of the gene strand; further information is provided under Gene-specific warnings in Section III: Allele Matching Details.
Structural variation star alleles that cannot be detected using VCF file data:
- CYP2B7-CYP2B6 hybrids: CYP2B6*29, CYP2B6*30
- Partial and whole gene deletions: CYP2C19*36, CYP2C19*37, CYP4F2*16, SLCO1B1*48, SLCO1B1*49
PharmCAT matches variants to genotypes assuming unphased data (unless phased data is provided in the VCF file and noted as such, see pharmcat.org for details). The assumption is that defined alleles exist in trans configuration, i.e. on opposite chromosomes, with exceptions noted in Section III: Allele Matching Details under "Gene-specific warnings." However, in cases where an allele is defined by a combination of two or more variants, where each variant alone also defines an allele, the match is based on the longer allele. For example, TPMT*3B is defined by one SNP, *3C is defined by another SNP, and *3A is defined by the combination of those two SNPs. In the case of unphased data that is heterozygous for both SNPs, the *1/*3A genotype is returned though the possibility of *3B/*3C cannot be ruled out.

Below cases are summarized for which two calls with different scores are possible when provided unphased data and heterozygous calls for the variants that define the two alleles. The genotype with the higher score (longer allele) will be used to determine allele functionality, phenotype, and recommendation but the genotype with the lower score cannot be ruled out.

Table 1: Cases for which there is an overlap in the allele definitions.

Gene	Genotype (Higher Score)	Phenotype	Genotype (Lower Score)	Phenotype
UGT1A1	1/80+*28	Intermediate	28/80	Indeterminate
UGT1A1	1/80+*37	Intermediate	37/80	Indeterminate
TPMT	1/3A	Intermediate	3B/3C	Poor
NUDT15	1/2	Intermediate	3/6	Possible Intermediate
CYP2C9	1/71	N/A	10/22	Indeterminate
CYP2B6	1/36	Intermediate	6/22	Intermediate
CYP2B6	1/34	Intermediate	33/36	Indeterminate
CYP2B6	1/6	Intermediate	4/9	Intermediate
CYP2B6	1/7	Intermediate	5/6	Intermediate
CYP2B6	1/13	Intermediate	6/8	Intermediate
SLCO1B1	1/46	Decreased function	15/45	Possible Decreased Function
SLCO1B1	1/20	Normal Function	19/37	Indeterminate
SLCO1B1	1/12	Indeterminate	2/10	Indeterminate
SLCO1B1	1/13	Indeterminate	3/11	Indeterminate
SLCO1B1	1/14	Normal Function	4/37	Indeterminate
SLCO1B1	1/15	Decreased function	5/37	Decreased function
SLCO1B1	1/25	Indeterminate	4/28	Indeterminate
SLCO1B1	1/31	Decreased function	9/37	Decreased Function
SLCO1B1	1/32	Indeterminate	4/24	Indeterminate
SLCO1B1	1/40	Indeterminate	5/19	Possible Decreased Function
SLCO1B1	1/43	Indeterminate	4/44	Indeterminate
CYP4F2	1/4	N/A	2/3	N/A
CYP3A4	1/37	N/A	3/22	N/A
CYP3A4	1/38	N/A	3/11	N/A
G6PD	A- 202A_376G/B (reference)	Variable	A/Asahi	Variable
G6PD	B (reference)/Mt Sinai	Variable	A/Guadalajara	Variable
G6PD	B (reference)/Santa Maria	Variable	A/Malaga	Variable
G6PD	Ananindeua/B (reference)	Variable	A/Viangchan, Jammu	Variable
G6PD	B (reference)/Hechi	Variable	Asahi/Viangchan, Jammu	Deficient
G6PD	B (reference)/Hermoupolis	Variable	Cassano/Union,Maewo, Chinese-2, Kalo	Deficient

Table 2: Cases for which there is an overlap in the allele definitions because the definition of the non-*1 allele in the genotype with the higher score allows for reference or variant at the position that defines the first allele listed in the genotype with the lower score. Both genotypes cannot be ruled out with unphased data if the position that overlaps between the respective alleles is heterozygous (0/1) in addition to heterozygous calls for the other variants that define the non-*1 allele in the genotype with the higher score.

Gene	Genotype (Higher Score)	Phenotype	Genotype (Lower Score)	Phenotype
CYP2C19	1/4	Intermediate	17/4	Intermediate
CYP2C19	1/2	Intermediate	11/2	Intermediate
CYP2C19	1/35	Intermediate	15/35	Intermediate
CYP2B6	1/18	Intermediate	4/18	Indeterminate

B. CPIC Allele Function, Phenotype and Recommendation

All content is sourced from the CPIC database.

C. DPWG Allele Function, Phenotype and Recommendation

PharmGKB annotates PGx-based drug dosing guidelines published by the Royal Dutch Association for the Advancement of Pharmacy - Pharmacogenetics Working Group (DPWG). PharmGKB curates allele function assignments and phenotype mappings from the DPWG to provide genotype specific DPWG guideline recommendations. Where possible, PharmGKB maps DPWG terms to CPIC terms, as outlined on PharmGKB.
CYP3A4 is currently not part of a CPIC guideline. Since the DPWG CYP3A4 documentation includes limit variant notations for the included alleles (only *16, *20, and *22 are specified) PharmCAT relies on PharmVar CYP3A4 allele definitions. However, the CYP3A4*16, *20 and *22 definitions are the same in both sources.
The CPIC UGT1A1 allele definition file inc