PharmCAT Report
HG002.GRCh38.small_variants.phased.preprocessed.filtered
Date createdAugust 18, 2025
PharmCAT Version2.15.4
Data Version2024-08-27-21-12

Sections

  1. Genotype Summary
  2. Prescribing Recommendations
  3. Allele Matching Details
  4. 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 / 22

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 †
Reference/Reference Two Normal function alleles Uncertain Susceptibility
ivacaftor
CFTR †
Reference/Reference Two ivacaftor non-responsive alleles ivacaftor non-responsive in CF patients
efavirenz
sertraline
CYP2B6 †
*2/*5 Two Normal function alleles Normal Metabolizer
amitriptyline
citalopram
clomipramine
clopidogrel
dexlansoprazole
doxepin
escitalopram
fosphenytoin
imipramine
lansoprazole
omeprazole
pantoprazole
phenytoin
sertraline
trimipramine
voriconazole
CYP2C19 †
*1/*1 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
amoxapine
aripiprazole
atomoxetine
brexpiprazole
clomipramine
codeine
desipramine
doxepin
eliglustat
flecainide
fluvoxamine
haloperidol
hydrocodone
imipramine
meclizine
metoprolol
nortriptyline
ondansetron
paroxetine
pimozide
propafenone
risperidone
tamoxifen
tetrabenazine
thioridazine
tramadol
trimipramine
tropisetron
venlafaxine
vortioxetine
zuclopenthixol
CYP2D6 †
*2/*4 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 †
*3/*3 Two No function alleles Poor Metabolizer
warfarin
CYP4F2 †
*4/*5 N/A N/A
capecitabine
flucytosine
fluorouracil
tegafur
DPYD †
Reference/Reference Two 1.0 (Normal function) alleles See drug section
dapsone
methylene blue
nitrofurantoin
pegloticase
primaquine
rasburicase
tafenoquine
toluidine blue
G6PD †
B (reference)/B (reference) Two IV/Normal alleles Normal
carbamazepine
HLA-A †
*01:01/*26:01 N/A *31:01 negative
abacavir
allopurinol
carbamazepine
fosphenytoin
lamotrigine
oxcarbazepine
phenytoin
HLA-B †
*35:08/*38:01 N/A *15:02 negative; *57:01 negative; *58:01 negative
IFNL3/4 †
rs12979860 reference (C)/rs12979860 reference (C) Two Favorable response allele alleles n/a
amikacin
dibekacin
gentamicin
kanamycin
neomycin
netilmicin
paromomycin
plazomicin
ribostamycin
streptomycin
tobramycin
MT-RNR1 †
Reference Normal risk of aminoglycoside-induced hearing loss normal 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 †
Reference/Reference Two Normal function alleles See drug section
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 variant (T)/rs9923231 variant (T) N/A N/A
† Check Section III for more details about this call.
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

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

*57:01 negative

 HLA-B: Low or reduced risk of abacavir hypersensitivity Use abacavir per standard dosing guidelines Strong

DPWG Guideline Annotation 1

Genotype
HLA-B:*35:08/*38:01
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA Label Annotation 1

Genotype
HLA-B:*35:08/*38:01
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
HLA-B:*35:08/*38:01
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

acenocoumarol

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
  • VKORC1:
    rs9923231 variant (T)/
    rs9923231 variant (T)
Phenotype

-1639 AA

 An INR ≥ 6, resulting in an increased risk of bleeding, occurs in 8-12% of these patients during the first weeks of treatment with standard regulation by the Anticoagulation Clinic. The genetic variation increases the sensitivity to acenocoumarol. Monitoring by the ANTICOAGULATION CLINIC (National INR Monitoring Service):
  • recommend to use 50% of the standard initial dose
OTHERWISE:
  • recommend to use 50% of the standard initial dose
  • recommend more frequent monitoring of the INR
 Unspecified

Citations:

allopurinol

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

*58:01 negative

 HLA-B: Low or reduced risk of allopurinol-induced SCAR Use allopurinol per standard dosing guidelines Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
  • ABCG2:
    rs2231142 reference (G)/
    rs2231142 reference (G)
Phenotype

Normal Function

 The guideline does not provide a description of the impact of the ABCG2 rs2231142 GG genotype (c.421CC; p.141QQ) on allopurinol. The guideline does not provide a recommendation for allopurinol in patients with the the ABCG2 rs2231142 GG genotype (c.421CC; p.141QQ) No recommendation

FDA Label Annotation 1

Genotype
HLA-B:*35:08/*38:01
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
HLA-B:*35:08/*38:01
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

amikacin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

FDA Label Annotation 1

Genotype
MT-RNR1:Reference
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

amitriptyline

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotypes
CYP2C19:
Normal Metabolizer
CYP2D6:
Intermediate Metabolizer
Activity Scores
CYP2C19:
N/A
CYP2D6:
1.0
  • CYP2C19: Normal metabolism of tertiary amines
  • CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
 Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. 		Moderate

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The risk of side effects is increased, because the gene variation leads to higher plasma concentrations of the active metabolite nortriptyline and to a lesser extent of amitriptyline. Use 75% of the standard dose and monitor the efficacy and side effects or the plasma concentrations of amitriptyline and nortriptyline to adjust the maintenance dose Unspecified

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

amoxapine

Source Genes Implications Recommendation Classification

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

aripiprazole

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The genetic variation increases the plasma concentration of the sum of aripiprazole and the active metabolite dehydroaripiprazole to a limited degree. There is insufficient evidence that this increases the risk of side effects. NO action is needed for this gene-drug interaction. Unspecified

FDA Label Annotation 1

Genotype
CYP2D6:*2/*4
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

atazanavir

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

Normal Metabolizer

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

Other Considerations

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

Citations:

atomoxetine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
adults

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Possibly higher atomoxetine concentrations as compared to normal metabolizers but questionable clinical significance. Intermediate metabolizers with an activity score of 1 may be at an increased risk of discontinuation as compared to poor metabolizers. Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.

Other Considerations

Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated. 		Moderate

CPIC Guideline Annotation

Population:
pediatrics

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Possibly higher atomoxetine concentrations as compared to normal metabolizers but questionable clinical significance. Intermediate metabolizers with an activity score of 1 may be at an increased risk of discontinuation as compared to poor metabolizers. Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.

Other Considerations

Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. 		Moderate

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The dose requirement can be reduced, because the genetic variation results in a higher atomoxetine plasma concentration. In the event of side effects occurring and/or a response later than 9 weeks: reduce the dose and check whether the effect is conserved The plasma concentration of atomoxetine is a factor of 2-3 times higher for IM than for NM at the same dose. Unspecified

FDA Label Annotation 1

Genotype
CYP2D6:*2/*4
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

atorvastatin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

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

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Function

 The guideline does not provide a description of the impact of the _SLCO1B1_ 521 TT genotype on atorvastatin. The guideline does not provide a recommendation for atorvastatin in patients with the SLCO1B1 521 TT genotype No recommendation

FDA PGx Association 1

Genotype
SLCO1B1:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

azathioprine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotypes
NUDT15:
Normal Metabolizer
TPMT:
Normal Metabolizer
  • NUDT15: Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression
  • TPMT: Lower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.
 Start with normal starting dose (e.g., 2-3 mg/kg/day) and adjust doses of azathioprine based on disease-specific guidelines. Allow 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 11302950, 15606506).

Other Considerations

Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers. 		Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on azathioprine. The guideline does not provide a recommendation for azathioprine in normal metabolizers No recommendation

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on azathioprine. The guideline does not provide a recommendation for azathioprine in normal metabolizers. No recommendation

FDA Label Annotation 1

Genotypes
NUDT15:*1/*1;
TPMT:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotypes
NUDT15:*1/*1;
TPMT:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

brexpiprazole

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 There are indications supporting an increase in the exposure to brexpiprazole, but no indications supporting an increase in side effects in patients with this gene variation. NO action is required for this gene-drug interaction. Unspecified

FDA Label Annotation 1

Genotype
CYP2D6:*2/*4
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

capecitabine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • DPYD:Reference/
    Reference
Phenotype

Normal Metabolizer

Activity Score

2.0

 DPYD: Normal DPD activity and "normal" risk for fluoropyrimidine toxicity Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration. Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
  • DPYD:Reference/
    Reference
Phenotype

2.0 (Normal Metabolizer)

 The guideline does not provide a description of the impact of a DPYD activity score of 2 on capecitabine. The guideline does not provide a recommendation for capecitabine in patients with a DPYD activity score of 2. No recommendation

FDA Label Annotation 1

Genotype
DPYD:Reference/Reference
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
DPYD:Reference/Reference
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

carbamazepine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
CBZ naive

No Action
Genotype
Phenotypes
HLA-A:
*31:01 negative
HLA-B:
*15:02 negative
  • HLA-A: Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE
  • HLA-B: Normal risk of carbamazepine-induced SJS/TEN
 Use carbamazepine per standard dosing guidelines.

Other Considerations

HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835). 		Strong

CPIC Guideline Annotation

Population:
CBZ use >3mos

No Action
Genotype
Phenotypes
HLA-A:
*31:01 negative
HLA-B:
*15:02 negative
  • HLA-A: Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE
  • HLA-B: Normal risk of carbamazepine-induced SJS/TEN
 Use carbamazepine per standard dosing guidelines.

Other Considerations

HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835). 		Strong

CPIC Guideline Annotation

Population:
CBZ-no alternatives

No Action
Genotype
Phenotypes
HLA-A:
*31:01 negative
HLA-B:
*15:02 negative
  • HLA-A: Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE
  • HLA-B: Normal risk of carbamazepine-induced SJS/TEN
 Use carbamazepine per standard dosing guidelines.

Other Considerations

HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835). 		Strong

DPWG Guideline Annotation 1, 2

Genotypes
HLA-A:*01:01/*26:01;
HLA-B:*35:08/*38:01
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA Label Annotation 1, 2

Genotypes
HLA-A:*01:01/*26:01;
HLA-B:*35:08/*38:01
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1, 2

Genotypes
HLA-A:*01:01/*26:01;
HLA-B:*35:08/*38:01
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

celecoxib

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 CYP2C9: Normal metabolism Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Strong

FDA Label Annotation 1

Genotype
CYP2C9:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C9:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

citalopram

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal metabolism Initiate therapy with recommended starting dose Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on citalopram. The guideline does not provide a recommendation for citalopram in normal metabolizers. No recommendation

FDA Label Annotation 1

Genotype
CYP2C19:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C19:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

clomipramine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotypes
CYP2C19:
Normal Metabolizer
CYP2D6:
Intermediate Metabolizer
Activity Scores
CYP2C19:
N/A
CYP2D6:
1.0
  • CYP2C19: Normal metabolism of tertiary amines
  • CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
 Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. 		Optional

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on clomipramine. The guideline does not provide a recommendation for clomipramine in normal metabolizers. No recommendation

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

clopidogrel

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
CVI ACS PCI

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity If considering clopidogrel, use at standard dose (75 mg/day)

Other Considerations

For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication. 		Strong

CPIC Guideline Annotation

Population:
CVI non-ACS non-PCI

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity If considering clopidogrel, use at standard dose (75 mg/day)

Other Considerations

For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI. 		Strong

CPIC Guideline Annotation

Population:
NVI

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity If considering clopidogrel, use at standard dose (75 mg/day)

Other Considerations

For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms. 		Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on clopidogrel. The guideline does not provide a recommendation for clopidogrel in normal metabolizers. No recommendation

FDA Label Annotation 1

Genotype
CYP2C19:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C19:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

codeine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Reduced morphine formation Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid. Moderate

DPWG Guideline Annotation

Population:
Unspecified

Alternate Drug
Dosing Info
Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The genetic variation reduces the conversion of codeine to morphine. This can result in reduced analgesia. For PAIN: It is not possible to offer adequately substantiated advice for dose adjustment based on the limited available literature for this phenotype.
  1. Be alert to a reduced effectiveness.
  2. 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.
  3. If no alternative is selected: advise the patient to report inadequate analgesia.
For COUGH: No action required. 		Unspecified

FDA Label Annotation 1

Genotype
CYP2D6:*2/*4
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1, 2

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

dapsone

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • G6PD:B (reference)/
    B (reference)
Phenotype

Normal

 G6PD: Low risk of acute hemolytic anemia No reason to avoid based on G6PD status Strong

Citations:

desflurane

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

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

FDA Label Annotation

Population:
Unspecified

Alternate Drug
Genotype
Phenotypes
CACNA1S:
Uncertain Susceptibility
RYR1:
Uncertain Susceptibility
 "The use of SUPRANE [desflurane] is contraindicated in...[cases of k]nown or suspected genetic susceptibility to malignant hyperthermia...SUPRANE [desflurane] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants. " See label for more information. * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

desipramine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects. Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. 		Optional

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

dexlansoprazole

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy. Optional

FDA PGx Association 1

Genotype
CYP2C19:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

dibekacin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

Citations:

doxepin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotypes
CYP2C19:
Normal Metabolizer
CYP2D6:
Intermediate Metabolizer
Activity Scores
CYP2C19:
N/A
CYP2D6:
1.0
  • CYP2C19: Normal metabolism of tertiary amines
  • CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
 Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. 		Optional

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The risk of side effects may be increased, because the gene variation leads to increased plasma concentrations of doxepin and the active metabolite nordoxepin. Use 80% of the standard dose and monitor the effect and side effects or the plasma concentrations of doxepin and nordoxepin in order to set the maintenance dose. The therapeutic range is 100-250 ng/mL for the sum of doxepin and nordoxepin plasma concentrations. Values higher than 400 ng/mL are considered toxic. Unspecified

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

efavirenz

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
child >40kg_adult

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2B6: Normal efavirenz metabolism Initiate efavirenz with standard dosing (600 mg/day)

Other Considerations

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

DPWG Guideline Annotation 1

Genotype
CYP2B6:*2/*5
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2B6:*2/*5
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

eliglustat

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 This gene variation reduces the conversion of eliglustat to inactive metabolites. However, in the absence of CYP2D6 and CYP3A inhibitors, this does not result in a clinically significant increased risk of side effects. Co-medication with BOTH a MODERATE to STRONG CYP2D6 INHIBITOR AND a MODERATE to STRONG CYP3A INHIBITOR:
  • Eliglustat is contra-indicated. Choose an alternative if possible.
Strong CYP2D6 inhibitor: for example paroxetine, fluoxetine, quinidine, bupropione. Moderate CYP2D6 inhibitor: for example duloxetine, terbinafine, moclobemide, mirabegron, cinacalcet, dronedarone. Strong CYP3A inhibitor: for example ketoconazole, clarithromycin, itraconazole, cobicistat, indinavir, lopinavir, ritonavir, saquinavir, telaprevir, tipranavir, posaconazole, voriconazole, telithromycin, conivaptan, boceprevir. Moderate CYP3A inhibitor: for example erythromycin, ciprofloxacin, fluconazole, diltiazem, verapamil, aprepitant, atazanavir, darunavir, fosamprenavir, imatinib, cimetidine. Co-medication with a STRONG CYP2D6 INHIBITOR (e.g. paroxetine, fluoxetine, quinidine, bupropione):
  • Use a dose of 84mg eliglustat 1x daily.
Co-medication with a MODERATE CYP2D6 INHIBITOR (for example duloxetine, terbinafine, moclobemide, mirabegron, cinacalcet, dronedarone):
  • Consider a dose of 84mg eliglustat 1x daily. Be alert to side effects.
Co-medication with a STRONG CYP3A INHIBITOR (for example ketoconazole, clarithromycin, itraconazole, cobicistat, indinavir, lopinavir, ritonavir, saquinavir, telaprevir, tipranavir, posaconazole, voriconazole, telithromycin, conivaptan, boceprevir):
  • Choose an alternative if possible.
  • If an alternative is not an option: consider a dose of 84 mg eliglustat 1x daily and be alert to side effects.
Co-medication with a MODERATE CYP3A INHIBITOR (for example erythromycin, ciprofloxacin, fluconazole, diltiazem, verapamil, aprepitant, atazanavir, darunavir, fosamprenavir, imatinib, cimetidine):
  • Choose an alternative.
  • If an alternative is not an option: consider a dose of 84mg eliglustat 1x daily and be alert to side effects.
Co-medication with a STRONG CYP3A INDUCER (for example rifampicin, carbamazepine, phenobarbital, phenytoin, rifabutine, hypericum): Eliglustat is not recommended. The plasma concentration may decrease so sharply that a therapeutic effect cannot be achieved.
  • Choose an alternative if possible.
NO co-medication with a moderate or strong CYP2D6 or CYP3A inhibitor or strong CYP3A inducer:
  • Use the standard dose of 84mg 2x daily.
 Unspecified

FDA Label Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

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

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

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Alters systemic concentrations, effectiveness, and adverse reaction risk (QT prolongation). Indicated for normal, intermediate, and poor metabolizer patients. Ultrarapid metabolizers may not achieve adequate concentrations to achieve a therapeutic effect. The recommended dosages are based on CYP2D6 metabolizer status. Coadministration with strong CYP3A inhibitors is contraindicated in intermediate and poor CYP2D6 metabolizers. Refer to FDA labeling for specific dosing recommendations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

enflurane

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

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

Citations:

escitalopram

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal metabolism Initiate therapy with recommended starting dose Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on escitalopram. The guideline does not provide a recommendation for escitalopram in normal metabolizers. No recommendation

FDA PGx Association 1

Genotype
CYP2C19:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

flecainide

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The genetic variation reduces conversion of flecainide to inactive metabolites. This may increase the risk of side effects. Indications other than diagnosis of Brugada syndrome:
  • Reduce the dose to 75% of the standard dose and record an ECG and monitor the plasma concentration.
Provocation test for diagnosis of Brugada syndrome:
  • No action required. At a dose of 2.0 mg/kg body weight to a maximum of 150 mg, the response is better for patients with alleles that result in reduced activity. All 5 patients with these alleles and 20% of the patients with two fully active alleles exhibited a response within 30 minutes.
 Unspecified

Citations:

flucytosine

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
  • DPYD:Reference/
    Reference
Phenotype

2.0 (Normal Metabolizer)

 The guideline does not provide a description of the impact of a DPYD activity score of 2 on flucytosine. The guideline does not provide a recommendation for flucytosine in patients with a DPYD activity score of 2. No recommendation

fluorouracil

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • DPYD:Reference/
    Reference
Phenotype

Normal Metabolizer

Activity Score

2.0

 DPYD: Normal DPD activity and "normal" risk for fluoropyrimidine toxicity Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration. Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
  • DPYD:Reference/
    Reference
Phenotype

2.0 (Normal Metabolizer)

 The guideline does not provide a description of the impact of a DPYD activity score of 2 on fluorouracil. The guideline does not provide a recommendation for fluorouracil in patients with a DPYD activity score of 2. No recommendation

FDA Label Annotation 1

Genotype
DPYD:Reference/Reference
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
DPYD:Reference/Reference
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

flurbiprofen

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 CYP2C9: Normal metabolism Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Strong

FDA Label Annotation 1

Genotype
CYP2C9:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C9:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

fluvastatin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotypes
CYP2C9:
Normal Metabolizer
SLCO1B1:
Normal Function
Activity Scores
CYP2C9:
2.0
SLCO1B1:
N/A
  • CYP2C9: Normal exposure.
  • SLCO1B1: Typical myopathy risk and statin exposure.
 Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.

Other Considerations

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

Citations:

fluvoxamine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Reduced metabolism of fluvoxamine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects. Initiate therapy with recommended starting dose. Moderate

FDA Label Annotation

Population:
Unspecified

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

fosphenytoin

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

CPIC Guideline Annotation

Population:
PHT naive

No Action
Genotype
Phenotypes
CYP2C9:
Normal Metabolizer
HLA-B:
*15:02 negative
Activity Scores
CYP2C9:
2.0
HLA-B:
N/A
  • CYP2C9: Normal phenytoin metabolism
  • HLA-B: n/a
 No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard. Strong

CPIC Guideline Annotation

Population:
PHT use >3mos

No Action
Genotype
Phenotypes
CYP2C9:
Normal Metabolizer
HLA-B:
*15:02 negative
Activity Scores
CYP2C9:
2.0
HLA-B:
N/A
  • CYP2C9: Normal phenytoin metabolism
  • HLA-B: n/a
 No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard. Strong

FDA Label Annotation 1

Genotypes
CYP2C19:*1/*1;
CYP2C9:*1/*1;
HLA-B:*35:08/*38:01
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1, 2

Genotypes
CYP2C9:*1/*1;
HLA-B:*35:08/*38:01
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

gentamicin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

FDA Label Annotation 1

Genotype
MT-RNR1:Reference
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

haloperidol

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The genetic variation results in a higher plasma concentration, but the effect is small and no clinically significant effects were found. NO action is required for this gene-drug interaction. Unspecified

Citations:

halothane

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

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

Citations:

hydrocodone

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Minimal evidence for pharmacokinetic or clinical effect. Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid. Optional

Citations:

ibuprofen

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 CYP2C9: Normal metabolism Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Strong

FDA PGx Association 1

Genotype
CYP2C9:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

imipramine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotypes
CYP2C19:
Normal Metabolizer
CYP2D6:
Intermediate Metabolizer
Activity Scores
CYP2C19:
N/A
CYP2D6:
1.0
  • CYP2C19: Normal metabolism of tertiary amines
  • CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
 Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. 		Optional

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on imipramine. The guideline does not provide a recommendation for imipramine in normal metabolizers. No recommendation

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

irinotecan

Alleles determined based on the CPIC UGT1A1 allele definition file due to limited allele definition information in the DPWG UGT1A1 document
Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on irinotecan. The guideline does not provide a recommendation for irinotecan in normal metabolizers No recommendation

FDA Label Annotation 1

Genotype
UGT1A1:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
UGT1A1:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

isoflurane

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

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

FDA Label Annotation

Population:
Unspecified

Alternate Drug
Genotype
Phenotypes
CACNA1S:
Uncertain Susceptibility
RYR1:
Uncertain Susceptibility
 "CONTRAINDICATIONS...with known or suspected genetic susceptibility to malignant hyperthermia...FORANE [isoflurane] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants." See label for more information. * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

ivacaftor

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Alternate Drug
Genotype
  • CFTR:Reference/
    Reference
Phenotype

ivacaftor non-responsive in CF patients

 CFTR: An individual diagnosed with cystic fibrosis (CF) and negative for a CFTR variant listed in the FDA-approved drug label as being responsive to ivacaftor. Ivacaftor is not recommended Moderate

FDA Label Annotation 1

Genotype
CFTR:Reference/Reference
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

kanamycin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

Citations:

lamotrigine

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

*15:02 negative

 The guideline does not provide a description of the impact of the absence of HLA-B*15:02 alleles on lamotrigine. The guideline does not provide a recommendation for lamotrigine in patients with no HLA-B*15:02 alleles or negative for the HLA-B*15:02 test. No recommendation

lansoprazole

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy. Moderate

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on lansoprazole. The guideline does not provide a recommendation for lansoprazole in normal metabolizers. No recommendation

FDA PGx Association 1

Genotype
CYP2C19:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

lornoxicam

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 CYP2C9: Normal metabolism Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Strong

Citations:

lovastatin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

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

Citations:

meclizine

Source Genes Implications Recommendation Classification

FDA Label Annotation

Population:
Unspecified

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "The genetic polymorphism of CYP2D6 that results in poor-, intermediate-, extensive-, and ultrarapid metabolizer phenotypes could contribute to large inter-individual variability in meclizine exposure." "... when ANTIVERT® [meclizine] is administered to patients with CYP2D6 polymorphism, monitor for adverse reactions and clinical effect accordingly." See label for more information. * Unspecified

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "May affect systemic concentrations. Monitor for adverse reactions and clinical effect." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

meloxicam

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 CYP2C9: Normal metabolism Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Strong

FDA Label Annotation 1

Genotype
CYP2C9:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C9:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

mercaptopurine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotypes
NUDT15:
Normal Metabolizer
TPMT:
Normal Metabolizer
  • NUDT15: Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression
  • TPMT: Lower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.
 Start with normal starting dose (e.g., 75 mg/m2/day or 1.5 mg/kg/day) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow at least 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 16401827, 11302950).

Other Considerations

Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers. 		Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on mercaptopurine. The guideline does not provide a recommendation for mercaptopurine in normal metabolizers No recommendation

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on mercaptopurine. The guideline does not provide a recommendation for mercaptopurine in normal metabolizers. No recommendation

FDA Label Annotation 1

Genotypes
NUDT15:*1/*1;
TPMT:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotypes
NUDT15:*1/*1;
TPMT:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

methoxyflurane

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

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

Citations:

methylene blue

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • G6PD:B (reference)/
    B (reference)
Phenotype

Normal

 G6PD: Low risk of acute hemolytic anemia No reason to avoid based on G6PD status Strong

FDA Label Annotation 1

Genotype
G6PD:B (reference)/B (reference)
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

metoprolol

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The gene variation reduces the conversion of metoprolol to inactive metabolites. However, the clinical consequences are limited mainly to the occurrence of asymptomatic bradycardia. If a GRADUAL REDUCTION in HEART RATE is desired, or in the event of SYMPTOMATIC BRADYCARDIA:
  • Use smaller steps in dose titration and/or prescribe no more than 50% of the standard dose.
OTHER CASES:
  • No action required.
 Unspecified

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

neomycin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

Citations:

netilmicin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

Citations:

nitrofurantoin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • G6PD:B (reference)/
    B (reference)
Phenotype

Normal

 G6PD: Low risk of acute hemolytic anemia No reason to avoid based on G6PD status Strong

FDA Label Annotation 1

Genotype
G6PD:B (reference)/B (reference)
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

nortriptyline

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The risk of side effects may be increased, because the gene variation leads to an increased plasma concentration of nortriptyline. Use 60% of the standard dose and monitor the effect and side effects or the plasma concentration of nortriptyline in order to set the maintenance dose. The therapeutic range of nortriptyline is 50-150 ng/mL. Values exceeding 250 ng/mL are considered toxic. Unspecified

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

omeprazole

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy. Moderate

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on omeprazole. The guideline does not provide a recommendation for omeprazole in normal metabolizers. No recommendation

FDA PGx Association 1

Genotype
CYP2C19:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

ondansetron

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Very limited data available for CYP2D6 intermediate metabolizers Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.

Other Considerations

Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy. 		No recommendation

Citations:

oxcarbazepine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
OXC naive

No Action
Genotype
Phenotype

*15:02 negative

 HLA-B: Normal risk of oxcarbazepine-induced SJS/TEN Use oxcarbazepine per standard dosing guidelines. Strong

CPIC Guideline Annotation

Population:
OXC use >3 mos

No Action
Genotype
Phenotype

*15:02 negative

 HLA-B: Normal risk of oxcarbazepine-induced SJS/TEN Use oxcarbazepine per standard dosing guidelines. Strong

DPWG Guideline Annotation 1

Genotype
HLA-B:*35:08/*38:01
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA Label Annotation 1

Genotype
HLA-B:*35:08/*38:01
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
HLA-B:*35:08/*38:01
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

pantoprazole

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy. Moderate

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on pantoprazole. The guideline does not provide a recommendation for pantoprazole in normal metabolizers. No recommendation

FDA Label Annotation 1

Genotype
CYP2C19:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C19:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

paromomycin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

Citations:

paroxetine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Other Considerations

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

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The plasma concentration of paroxetine can increase as a result of the reduced activity of CYP2D6. However, studies did not find any clinical effects. NO action is needed for this gene-drug interaction. Unspecified

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

pegloticase

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • G6PD:B (reference)/
    B (reference)
Phenotype

Normal

 G6PD: Low risk of acute hemolytic anemia No reason to avoid based on G6PD status Strong

FDA Label Annotation 1

Genotype
G6PD:B (reference)/B (reference)
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

phenprocoumon

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
  • VKORC1:
    rs9923231 variant (T)/
    rs9923231 variant (T)
Phenotype

-1639 AA

 An INR ≥ 6, resulting in an increased risk of bleeding, occurs in 17% of these patients with standard regulation by the Anticoagulation Clinic. The genetic variation increases the sensitivity to phenprocoumon. Monitoring by a ANTICOAGULATION CLINIC:
  • recommend to use 50% of the standard initial dose
NO monitoring by a anticoagulation clinic:
  • recommend to use 50% of the standard initial dose
  • recommend more frequent monitoring of the INR
 Unspecified

Citations:

phenytoin

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

CPIC Guideline Annotation

Population:
PHT naive

No Action
Genotype
Phenotypes
CYP2C9:
Normal Metabolizer
HLA-B:
*15:02 negative
Activity Scores
CYP2C9:
2.0
HLA-B:
N/A
  • CYP2C9: Normal phenytoin metabolism
  • HLA-B: n/a
 No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard. Strong

CPIC Guideline Annotation

Population:
PHT use >3mos

No Action
Genotype
Phenotypes
CYP2C9:
Normal Metabolizer
HLA-B:
*15:02 negative
Activity Scores
CYP2C9:
2.0
HLA-B:
N/A
  • CYP2C9: Normal phenytoin metabolism
  • HLA-B: n/a
 No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard. Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on phenytoin. The guideline does not provide a recommendation for phenytoin in normal metabolizers. No recommendation

FDA Label Annotation 1

Genotypes
CYP2C19:*1/*1;
CYP2C9:*1/*1;
HLA-B:*35:08/*38:01
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1, 2

Genotypes
CYP2C9:*1/*1;
HLA-B:*35:08/*38:01
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

pimozide

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The risk of QT-prolongation – and thereby also the risk of torsade de points – is theoretically increased, because the genetic variation results in an increase in the plasma concentration of pimozide. The elevated plasma concentration and associated theoretical increased risk of QT elongation can be negated by following the dose recommendations provided below. Use no more than the following doses (80% of the normal maximum dose):
  • 12 years and older: 16 mg/day
  • younger than 12 years: 0.08 mg/kg per day to a maximum of 3 mg/day
 Unspecified

FDA Label Annotation 1

Genotype
CYP2D6:*2/*4
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

piroxicam

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 CYP2C9: Normal metabolism Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Strong

FDA Label Annotation 1

Genotype
CYP2C9:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C9:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

pitavastatin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

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

Citations:

plazomicin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

FDA Label Annotation 1

Genotype
MT-RNR1:Reference
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

pravastatin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

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

Citations:

primaquine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • G6PD:B (reference)/
    B (reference)
Phenotype

Normal

 G6PD: Low risk of acute hemolytic anemia No reason to avoid based on G6PD status Strong

FDA Label Annotation 1

Genotype
G6PD:B (reference)/B (reference)
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

propafenone

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

Alternate Drug
Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 Genetic variation increases the sum of the plasma concentrations of propafenone and the active metabolite 5-hydroxypropafenone. This may increase the risk of side effects. It is not possible to offer adequately substantiated recommendations for dose adjustment based on the literature.
  • Either guide the dose by therapeutic drug monitoring, perform an ECG and be alert to side effects.
  • Or choose an alternative. Antiarrhythmic drugs that are hardly if at all metabolised by CYP2D6 include, for example, sotalol, disopyramide, quinidine and amiodarone.
 Unspecified

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

quetiapine

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on quetiapine. The guideline does not provide a recommendation for quetiapine in normal metabolizers. No recommendation

Citations:

rasburicase

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • G6PD:B (reference)/
    B (reference)
Phenotype

Normal

 G6PD: Low risk of acute hemolytic anemia No reason to avoid based on G6PD status Strong

FDA Label Annotation 1

Genotype
G6PD:B (reference)/B (reference)
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

ribostamycin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

Citations:

risperidone

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 There is little evidence to support an increase in side effects caused by the gene variation. The gene variation may lead to a decrease in the required maintenance dose. However, as the effect on the dose is smaller than that of the normal biological variation, action is not useful. NO action is needed for this gene-drug interaction. Unspecified

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

rosuvastatin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • ABCG2:
    rs2231142 reference (G)/
    rs2231142 reference (G)    ;
    SLCO1B1:*1/*1
Phenotypes
ABCG2:
Normal Function
SLCO1B1:
Normal Function
  • ABCG2: Typical myopathy risk and rosuvastatin exposure
  • SLCO1B1: Typical myopathy risk and statin exposure
 Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines.

Other Considerations

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

FDA PGx Association 1

Genotype
SLCO1B1:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

sertraline

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotypes
CYP2B6:
Normal Metabolizer
CYP2C19:
Normal Metabolizer
  • CYP2B6: Normal metabolism of sertraline to less active compounds.
  • CYP2C19: Normal metabolism
 Initiate therapy with recommended starting dose. Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on sertraline. The guideline does not provide a recommendation for sertraline in normal metabolizers. No recommendation

Citations:

sevoflurane

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

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

FDA Label Annotation

Population:
Unspecified

Alternate Drug
Genotype
Phenotypes
CACNA1S:
Uncertain Susceptibility
RYR1:
Uncertain Susceptibility
 "CONTRAINDICATIONS: Known or suspected genetic susceptibility to malignant hyperthermia...ULTANE [sevoflurane] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants." See label for more information. * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

simvastatin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

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

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Function

 The guideline does not provide a description of the impact of the SLCO1B1 521 TT genotype on simvastatin. The guideline does not provide a recommendation for atorvastatin in patients with the SLCO1B1 521 TT genotype. No recommendation

FDA PGx Association 1

Genotype
SLCO1B1:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

siponimod

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on siponimod. The guideline does not provide a recommendation for siponimod in normal metabolizers. No recommendation

FDA Label Annotation 1

Genotype
CYP2C9:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C9:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

streptomycin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

FDA Label Annotation 1

Genotype
MT-RNR1:Reference
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

succinylcholine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

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

FDA Label Annotation

Population:
Unspecified

Alternate Drug
Other Guidance
Genotype
Phenotypes
CACNA1S:
Uncertain Susceptibility
RYR1:
Uncertain Susceptibility
 "ANECTINE [succinylcholine] is contraindicated in patients with...[k]nown or suspected genetic susceptibility to malignant hyperthermia...Anectine [succinylcholine] can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants...Succinylcholine is metabolized by plasma cholinesterase and should be used with caution, if at all, in patients known to be or suspected of being homozygous for the atypical plasma cholinesterase gene [BCHE] ." See label for more information. * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

tacrolimus

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Poor Metabolizer

 CYP3A5: Higher ("normal") dose-adjusted trough concentrations of tacrolimus and increased chance of achieving target tacrolimus concentrations. Initiate therapy with standard recommended dose. 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. 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

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Poor Metabolizer

 The guideline does not provide a description of the impact of a non-expressor phenotype on tacrolimus. The guideline does not provide a recommendation for tacrolimus in CYP3A5 non-expressers. No recommendation

FDA PGx Association 1

Genotype
CYP3A5:*3/*3
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

tafenoquine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • G6PD:B (reference)/
    B (reference)
Phenotype

Normal

 G6PD: Low risk of acute hemolytic anemia No reason to avoid based on G6PD status

Other Considerations

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

FDA Label Annotation 1

Genotype
G6PD:B (reference)/B (reference)
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

tamoxifen

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers. Consider hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women, given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype (PMID 26211827). If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day)(PMID 27226358). Avoid CYP2D6 strong to weak inhibitors. Optional

DPWG Guideline Annotation

Population:
Unspecified

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 This gene variation reduces the conversion of tamoxifen to the active metabolite endoxifen. This can result in reduced effectiveness.
  • Select an alternative or measure the endoxifen concentration and increase the dose if necessary, by a factor of 1.5-2. Aromatase inhibitors are a possible alternative for post-menopausal women.
  • If TAMOXIFEN is selected: avoid co-medication with CYP2D6 inhibitors such as paroxetine and fluoxetine.
 Unspecified

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

Affected subgroup: CYP2D6 intermediate or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Results in lower systemic active metabolite concentrations. The impact of CYP2D6 intermediate or poor metabolism on efficacy is not well established." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

tegafur

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
  • DPYD:Reference/
    Reference
Phenotype

2.0 (Normal Metabolizer)

 The guideline does not provide a description of the impact of a DPYD activity score of 2 on tegafur. The guideline does not provide a recommendation for tegafur in patients with a DPYD activity score of 2. No recommendation

Citations:

tenoxicam

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 CYP2C9: Normal metabolism Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Strong

Citations:

tetrabenazine

Source Genes Implications Recommendation Classification

FDA Label Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

thioguanine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotypes
NUDT15:
Normal Metabolizer
TPMT:
Normal Metabolizer
  • NUDT15: Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression
  • TPMT: Lower concentrations of TGN metabolites, but note that TGN after thioguanine are 5-10X higher than TGN after mercaptopurine or azathioprine. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.
 Start with normal starting dose (e.g., 40-60 mg/m2/day) and adjust doses of thioguanine and of other myelosuppressive therapy without any special emphasis on thioguanine. Allow 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 11037857).

Other Considerations

Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers. 		Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on thioguanine. The guideline does not provide a recommendation for thioguanine in normal metabolizers No recommendation

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on thioguanine. The guideline does not provide a recommendation for thioguanine in normal metabolizers. No recommendation

FDA Label Annotation 1

Genotypes
NUDT15:*1/*1;
TPMT:*1/*1
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotypes
NUDT15:*1/*1;
TPMT:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

thioridazine

Source Genes Implications Recommendation Classification

FDA Label Annotation

Population:
Unspecified

Alternate Drug
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

tobramycin

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

normal risk of aminoglycoside-induced hearing loss

 MT-RNR1: Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance.

Other Considerations

Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. 		Strong

FDA Label Annotation 1

Genotype
MT-RNR1:Reference
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

toluidine blue

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • G6PD:B (reference)/
    B (reference)
Phenotype

Normal

 G6PD: Low risk of acute hemolytic anemia No reason to avoid based on G6PD status

Other Considerations

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

Citations:

tramadol

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Reduced O-desmethyltramadol (active metabolite) formation Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid. Optional

DPWG Guideline Annotation

Population:
Unspecified

Alternate Drug
Dosing Info
Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The genetic variation reduces the conversion of tramadol to a metabolite with a higher activity. This can result in reduced analgesia. It is not possible to provide a recommendation for dose adjustment, because the total analgesic effect changes when the ratio between the mother compound and the active metabolite changes.
  1. Be alert to a reduced effectiveness.
  2. 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.
  1. If no alternative is selected: advise the patient to report inadequate analgesia.
 Unspecified

FDA Label Annotation 1

Genotype
CYP2D6:*2/*4
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1, 2

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

trimipramine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotypes
CYP2C19:
Normal Metabolizer
CYP2D6:
Intermediate Metabolizer
Activity Scores
CYP2C19:
N/A
CYP2D6:
1.0
  • CYP2C19: Normal metabolism of tertiary amines
  • CYP2D6: Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
 Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. 		Optional

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

Affected subgroup: CYP2D6 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

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

Citations:

tropisetron

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Very limited data available for CYP2D6 intermediate metabolizers Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.

Other Considerations

Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy. 		No recommendation

Citations:

venlafaxine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Decreased metabolism of venlafaxine to active metabolite O-desmethylvenlafaxine (desvenlafaxine) and decreased O-desmethylvenlafaxine:venlafaxine ratio as compared to normal metabolizers. There is insufficient evidence supporting the clinical impact of the decreased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 intermediate metabolizers. No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects. No recommendation

DPWG Guideline Annotation

Population:
Unspecified

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 There are indications of an increased risk of side effects and a reduced chance of efficacy. The gene variation reduces the conversion of venlafaxine to the active metabolite O-desmethylvenlafaxine, whilst an association between high O-desmethylvenlafaxine/venlafaxine ratios and response without side effects was found. It is not possible to offer adequately substantiated advice for dose reduction based on the literature.
  • Avoid venlafaxine. Antidepressants that are not metabolised by CYP2D6 - or to a lesser extent - include, for example, duloxetine, mirtazapine, citalopram and sertraline.
  • If it is not possible to avoid venlafaxine and side effects occur:
  1. Reduce the dose
  2. Monitor the effect and side effects or check the plasma concentrations of venlafaxine and O-desmethylvenlafaxine. It is not known whether it is possible to reduce the dose to such an extent that the side effects disappear, while the effectiveness is maintained. In general, it is assumed that the effectiveness is determined by the sum of the plasma concentrations of venlafaxine and O-desmethylvenlafaxine. However, the side effects do not appear to be related to this sum.
 Unspecified

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

voriconazole

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
adults

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal voriconazole metabolism Initiate therapy with recommended standard of care dosing

Other Considerations

Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities. 		Strong

CPIC Guideline Annotation

Population:
pediatrics

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2C19: Normal voriconazole metabolism Initiate therapy with recommended standard of care dosing

Other Considerations

Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities. 		Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on voriconazole. The guideline does not provide a recommendation for voriconazole in normal metabolizers. No recommendation

FDA PGx Association 1

Genotype
CYP2C19:*1/*1
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

vortioxetine

Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2D6: Reduced metabolism of vortioxetine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects. Initiate therapy with recommended starting dose. Moderate

FDA Label Annotation 1

Genotype
CYP2D6:*2/*4
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2D6:*2/*4
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

warfarin

Please follow the flow chart in figure 2 of the CPIC warfarin guideline to determine the appropriate dosing recommendation.
The CPIC warfarin guideline only considers a single SNV in VKORC1 (rs9923231), which has varying frequency among different ancestral populations, and largely explains the differences in average dose requirements between people of European, African, and Asian descents. While other functional variants in VKORC1 have been associated with warfarin resistance (high dose requirements), there are currently no CPIC recommendations for how to use these other variants in warfarin dosing. An alternate name for rs9923231 is -1639G>A (note that VKORC1 is on the negative chromosomal strand, so displayed alleles are complemented).
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
N/A
Genotype
  • CYP2C9:*1/*1;
    CYP4F2:*4/*5;
    VKORC1:
    rs9923231 variant (T)/
    rs9923231 variant (T)    ;
    rs12777823:Unknown
Figure 2 from the CPIC guideline for warfarin

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on warfarin. The guideline does not provide a recommendation for warfarin in normal metabolizers. No recommendation

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
  • VKORC1:
    rs9923231 variant (T)/
    rs9923231 variant (T)
Phenotype

-1639 AA

 The genetic variation results in increased sensitivity to warfarin. This results in an increase in the risk of excessively severe inhibition of blood clotting (INR > 4) during the first month of the treatment. Use 60% of the standard initial dose. The genotype-specific initial dose and maintenance dose can be calculated using an algorithm, as used in EU-PACT: see https://www.knmp.nl/patientenzorg/medicatiebewaking/farmacogenetica. From day 6 on the standard algorithm without genotype information can be used to calculate the dose. Unspecified

FDA Label Annotation 1

Genotypes
CYP2C9:*1/*1;
VKORC1:rs9923231 variant (T)/rs9923231 variant (T)
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1, 2

Genotypes
CYP2C9:*1/*1;
VKORC1:rs9923231 variant (T)/rs9923231 variant (T)
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

zuclopenthixol

Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 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. Unspecified

Citations:

Drugs With No Guidance

The following drugs are known to be associated with the given genes but have no guidance for their genotypes.

  • Ascorbic acid (vitamin C), combinations
  • Ascorbic acid (vitamin C), plain
  • abrocitinib
  • acetaminophen / caffeine / dihydrocodeine
  • amphetamine
  • aripiprazole lauroxil
  • articaine / epinephrine
  • avatrombopag
  • belinostat
  • belzutifan
  • brivaracetam
  • bupivacaine
  • carisoprodol
  • carvedilol
  • ceftriaxone
  • cevimeline
  • chloroquine
  • chlorpropamide
  • clobazam
  • clozapine
  • dabrafenib
  • darifenacin
  • deutetrabenazine
  • dextromethorphan / quinidine
  • dextromethorphan hydrobromide / bupropion hydrochloride
  • diazepam
  • dolutegravir
  • donepezil
  • dronabinol
  • elagolix
  • erdafitinib
  • esomeprazole
  • fesoterodine
  • flibanserin
  • flucloxacillin
  • fluoxetine
  • flutamide
  • galantamine
  • gefitinib
  • glimepiride
  • glipizide
  • glyburide
  • hydroxychloroquine
  • iloperidone
  • lesinurad
  • lidocaine / prilocaine
  • lidocaine and tetracaine
  • lofexidine
  • mavacamten
  • mepivacaine
  • metoclopramide
  • mirabegron
  • moviprep
  • nalidixic acid
  • nateglinide
  • nebivolol
  • nilotinib
  • oliceridine
  • oxymetazoline and tetracaine
  • pazopanib
  • peginterferon alfa-2a
  • peginterferon alfa-2b
  • perphenazine
  • pitolisant
  • propranolol
  • protriptyline
  • rabeprazole
  • raltegravir
  • ribavirin
  • sacituzumab govitecan
  • sodium ascorbate
  • sodium nitrite
  • sulfasalazine
  • tamsulosin
  • tolazamide
  • tolbutamide
  • tolterodine
  • valbenazine
  • viloxazine

Section III: Allele Matching Details

  1. ABCG2 allele match data
  2. CACNA1S allele match data
  3. CFTR allele match data
  4. CYP2B6 allele match data
  5. CYP2C19 allele match data
  6. CYP2C9 allele match data
  7. CYP2D6 allele match data
  8. CYP3A4 allele match data
  9. CYP3A5 allele match data
  10. CYP4F2 allele match data
  11. DPYD allele match data
  12. G6PD allele match data
  13. HLA-A allele match data
  14. HLA-B allele match data
  15. IFNL3/4 allele match data
  16. MT-RNR1 allele match data
  17. NUDT15 allele match data
  18. RYR1 allele match data
  19. SLCO1B1 allele match data
  20. TPMT allele match data
  21. UGT1A1 allele match data
  22. VKORC1 allele match data

ABCG2 allele match data

Variant Reported: rs2231142 reference (G)/rs2231142 reference (G)
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called rs2231142 reference (G)/rs2231142 reference (G) based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

CACNA1S allele match data

Variant Reported: Reference/Reference
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called Reference/Reference based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

CFTR allele match data

Variant Reported: Reference/Reference
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called Reference/Reference based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

CYP2B6 allele match data

Allele Reported: *2/*5
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *2/*5 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

CYP2C19 allele match data

Allele Reported: *1/*1
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *1/*1 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

CYP2C9 allele match data

Allele Reported: *1/*1
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *1/*1 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

CYP2D6 allele match data

Allele Reported: *2/*4
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

Allele Reported: *1/*1
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *1/*1 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

CYP3A5 allele match data

Allele Reported: *3/*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.
PharmCAT would have called *3/*3 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

CYP4F2 allele match data

Allele Reported: *4/*5
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *4/*5 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

DPYD allele match data

Variant Reported: Reference/Reference
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called Reference/Reference based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

G6PD allele match data

Variant Reported: B (reference)/B (reference)
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called B (reference)/B (reference) based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

HLA-A allele match data

Allele Reported: *01:01/*26:01
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.

HLA-B allele match data

Allele Reported: *35:08/*38:01
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

Allele Reported: rs12979860 reference (C)/rs12979860 reference (C)
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called rs12979860 reference (C)/rs12979860 reference (C) based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

MT-RNR1 allele match data

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

NUDT15 allele match data

Allele Reported: *1/*1
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *1/*1 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

RYR1 allele match data

Variant Reported: Reference/Reference
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called Reference/Reference based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

SLCO1B1 allele match data

Allele Reported: *1/*1
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *1/*1 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

TPMT allele match data

Allele Reported: *1/*1
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *1/*1 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

UGT1A1 allele match data

Allele Reported: *1/*1
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called *1/*1 based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

VKORC1 allele match data

Variant Reported: rs9923231 variant (T)/rs9923231 variant (T)
This comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
PharmCAT would have called rs9923231 variant (T)/rs9923231 variant (T) based on the VCF but it has been ignored in favor of the outside call. If you want to use the PharmCAT call for this gene then remove the gene from the outside call data.

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

  1. 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.

  2. Genes with DPWG recommendations that are not included in CPIC are discussed in Section C.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  1. 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.

  2. 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.

  3. The CPIC UGT1A1 allele definition file includes *6, *27, *28, *36, *37, and *80. Since the DPWG UGT1A1 document does not include allele definitions besides for the UGT1A1 TA box promoter polymorphism, PharmCAT only includes the UGT1A1 positions from the CPIC UGT1A1 allele definition file. Other UGT1A1 alleles can be supplied as outside calls but not be determined from the VCF file by the Named Allele Matcher.

D. FDA drug-label and Table of Pharmacogenetic Associations recommendations

PharmCAT includes recommendations from PharmGKB-annotated FDA drug labels and the FDA Table of Pharmacogenetic Associations. It only contains FDA information for genes with CPIC or DPWG guidelines because the FDA does not offer any genotype-to-phenotype mapping information. PharmCAT uses CPIC genotype-to-phenotype mappings when they exist, and DPWG genotype-to-phenotype mappings when no CPIC mappings exist, to determine the phenotypes to use with FDA label annotations and Table of Pharmacogenetic Associations entries. Results presented for FDA Table of Pharmacogenetic Associations use wording and “Affected Subgroups” taken directly from the Table. Results presented from PharmGKB-annotated drug labels present wording from the specific label that was curated. In many cases, multiple FDA labels may exist for a particular medication. Typically, PharmGKB annotates the label linked to from the FDA Table of Pharmacogenomic Biomarkers in Drug Labeling but in some cases a different label may be annotated. Follow the “FDA Label Annotation” link in section II of the report to access the annotated label and more information.

E. Source Tags in Section II

Part of PharmGKB’s annotations of guidelines, drug labels and Table of Pharmacogenetic Associations is the assignment of labels that are meant to provide a high-level indication of the provided action. If recommendations or FDA Table wording exists, yellow boxes display if the guidance/wording is regarding (1) a dosing change, (2) recommending an alternate drug be used, or (3) other guidance. These boxes are included in the Source column in Section II of the PharmCAT report. More detailed information about what the yellow boxes mean is available on PharmGKB.

F. PharmCAT Exceptions to the CPIC Guideline Gene List

  1. PharmCAT does not determine CYP2D6, MT-RNR1, HLA-A, or HLA-B genotypes from the VCF file, but genotypes for CYP2D6, MT-RNR1, HLA-A, or HLA-B can be provided to PharmCAT from an outside source and the corresponding phenotype prescribing recommendations will be included in the generated report. For the required format of the outside calls refer to the PharmCAT outside calls documentation.

  2. CPIC has assigned function to the following CYP2D6 CNV alleles: *1x2, *1x≥3, *2x2, *2x≥3, *3x2, *4x2, *4x≥3, *6x2, *9x2, *10x2, *17x2, *29x2, *35x2, *36x2, *41x2, *41x3, *43x2, *45x2, *146x2. These alleles are part of the CPIC diplotype to phenotype translation and can be connected to recommendations. Other CNV notations from outside calls need to be mapped accordingly.

G. CPIC Guideline Disclaimers and Caveats

  1. A version of the following quoted disclaimer is part of each CPIC guideline and applies to the CPIC recommendations as used in PharmCAT. For the full description of potential benefits and risks, additional considerations (general and specific to gene-drug pairs), limitations, information about respective gene nomenclature systems, potential drug-drug interactions and clinical factors to consider, please see individual CPIC guidelines at (cpicpgx.org).

    1. "CPIC guidelines reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time a guideline was submitted for publication. Guidelines are limited in scope and are not applicable to interventions or diseases not specifically identified. Guidelines do not account for all individual variations among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guidelines is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. CPIC assumes no responsibility for any injury to persons or damage to persons or property arising out of or related to any use of CPIC's guidelines, or for any errors or omissions." (PMID: 27997040)

    2. "Caveats: appropriate use and/or potential misuse of genetic tests. The application of genotype-based dosing is most appropriate when initiating therapy with a tricyclic. Obtaining a pharmacogenetic test after months of drug therapy may be less helpful in some instances, as the drug dose may have already been adjusted based on plasma concentrations, response, or side effects. Similar to all diagnostic tests, genetic tests are one of several pieces of clinical information that should be considered before initiating drug therapy." (PMID: 27997040)

  2. CPIC guidelines reflect the alleles/genotypes known and considered by the guideline authors for inclusion by the time of publication, however they may be updated online at cpicpgx.org and in the CPIC database in between publications. Additional alleles and/or more extensive allele definitions might exist by the representative gene nomenclatures for various genes.

  3. CPIC is a registered service mark of the U.S. Department of Health & Human Services (HHS).

H. PharmGKB Disclaimers and Caveats

PharmGKB is a registered service mark of the U.S. Department of Health & Human Services (HHS).