CPIC Recommendations
amikacin
MT-RNR1: 1555A>G
increased risk of aminoglycoside-induced hearing loss
(from Outside Call)
| Type | Annotation |
|---|---|
| Population | general |
| Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
| Matched Diplotypes | MT-RNR1:1555A>G |
| Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
| Recommendation | Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. |
| Classification of Recommendation | Strong |
| Comments | If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring). |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of aminoglycosides based on MT-RNR1 genotype. [PMID:34032273] Clinical pharmacology and therapeutics. 2021.
amitriptyline
CYP2C19: *38/*38
Two normal function alleles
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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 |
| Implication for CYP2C19 | Normal metabolism of tertiary amines |
| Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
| Classification of Recommendation | Moderate |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update [PMID:27997040] Clinical pharmacology and therapeutics. 2016.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants [PMID:23486447] Clinical pharmacology and therapeutics. 2013.
atazanavir
UGT1A1: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for UGT1A1 | Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir. |
| Matched Diplotypes | UGT1A1:*1/*1 |
| Phenotype for UGT1A1 | Normal Metabolizer |
| Recommendation | 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). |
| Classification of Recommendation | Strong |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing [PMID:26417955] Clinical pharmacology and therapeutics. 2015.
atomoxetine
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | pediatrics |
| Implication for 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. |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | 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. |
| Classification of Recommendation | Moderate |
| Comments | 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. |
| Type | Annotation |
|---|---|
| Population | adults |
| Implication for 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. |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | 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. |
| Classification of Recommendation | Moderate |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Atomoxetine Therapy. [PMID:30801677] Clinical pharmacology and therapeutics. 2019.
azathioprine
NUDT15: *1/*1
Two normal function alleles
TPMT: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for TPMT | Lower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression. |
| Implication for NUDT15 | Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression |
| Matched Diplotypes | NUDT15:*1/*1, TPMT:*1/*1 |
| Phenotype for TPMT | Normal Metabolizer |
| Phenotype for NUDT15 | Normal Metabolizer |
| Recommendation | 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). |
| Classification of Recommendation | Strong |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing [PMID:21270794] Clinical pharmacology and therapeutics. 2011.
- Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update [PMID:23422873] Clinical pharmacology and therapeutics. 2013.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. [PMID:30447069] Clinical pharmacology and therapeutics. 2018.
capecitabine
DPYD: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for DPYD | Normal DPD activity and "normal" risk for fluoropyrimidine toxicity |
| Matched Diplotypes | DPYD:Reference/Reference |
| Phenotype for DPYD | Normal Metabolizer |
| Activity Score for DPYD | 2.0 |
| Recommendation | Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guidelines for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing [PMID:23988873] Clinical pharmacology and therapeutics. 2013.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update [PMID:29152729] Clinical pharmacology and therapeutics. 2017.
celecoxib
CYP2C9: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C9 | Normal metabolism |
| Matched Diplotypes | CYP2C9:*1/*1 |
| Phenotype for CYP2C9 | Normal Metabolizer |
| Activity Score for CYP2C9 | 2.0 |
| Recommendation | 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. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs. [PMID:32189324] Clinical pharmacology and therapeutics. 2020.
citalopram
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C19 | Normal metabolism |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | Initiate therapy with recommended starting dose |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors [PMID:25974703] Clinical pharmacology and therapeutics. 2015.
clomipramine
CYP2C19: *38/*38
Two normal function alleles
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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 |
| Implication for CYP2C19 | Normal metabolism of tertiary amines |
| Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
| Classification of Recommendation | Optional |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update [PMID:27997040] Clinical pharmacology and therapeutics. 2016.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants [PMID:23486447] Clinical pharmacology and therapeutics. 2013.
clopidogrel
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C19 | Normal platelet inhibition; normal residual platelet aggregation |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | Clopidogrel: label-recommended dosage and administration |
| Classification of Recommendation | Strong |
Antiplatelet therapy recommendations are based on CYP2C19 status when considering clopidogrel for acute coronary syndrome (ACS patients undergoing percutaneous coronary intervention (PCI)).
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450-2C19 (CYP2C19) Genotype and Clopidogrel Therapy [PMID:21716271] Clinical pharmacology and therapeutics. 2011.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy: 2013 Update [PMID:23698643] Clinical pharmacology and therapeutics. 2013.
codeine
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2D6 | Reduced morphine formation |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1 |
| Recommendation | Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid. |
| Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype [PMID:22205192] Clinical pharmacology and therapeutics. 2011.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for cytochrome P450 2D6 (CYP2D6) genotype and codeine therapy: 2014 Update [PMID:24458010] Clinical pharmacology and therapeutics. 2014.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy. [PMID:33387367] Clinical pharmacology and therapeutics. 2021.
desflurane
CACNA1S: Reference/Reference
Two normal function alleles
RYR1: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for RYR1 | 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). |
| Implication for CACNA1S | 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). |
| Matched Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
| Phenotype for RYR1 | Uncertain Susceptibility |
| Phenotype for CACNA1S | Uncertain Susceptibility |
| Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes [PMID:30499100] Clinical pharmacology and therapeutics. 2018.
desipramine
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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. |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | 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. |
| Classification of Recommendation | Optional |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update [PMID:27997040] Clinical pharmacology and therapeutics. 2016.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants [PMID:23486447] Clinical pharmacology and therapeutics. 2013.
dexlansoprazole
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C19 | Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | 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. |
| Classification of Recommendation | Optional |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. [PMID:32770672] Clinical pharmacology and therapeutics. 2020.
doxepin
CYP2C19: *38/*38
Two normal function alleles
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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 |
| Implication for CYP2C19 | Normal metabolism of tertiary amines |
| Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
| Classification of Recommendation | Optional |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update [PMID:27997040] Clinical pharmacology and therapeutics. 2016.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants [PMID:23486447] Clinical pharmacology and therapeutics. 2013.
efavirenz
CYP2B6: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | child >40kg_adult |
| Implication for CYP2B6 | Normal efavirenz metabolism |
| Matched Diplotypes | CYP2B6:*1/*1 |
| Phenotype for CYP2B6 | Normal Metabolizer |
| Recommendation | Initiate efavirenz with standard dosing (600 mg/day) |
| Classification of Recommendation | Strong |
| Comments | 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). |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-containing Antiretroviral Therapy. [PMID:31006110] Clinical pharmacology and therapeutics. 2019.
enflurane
CACNA1S: Reference/Reference
Two normal function alleles
RYR1: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for RYR1 | 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). |
| Implication for CACNA1S | 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). |
| Matched Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
| Phenotype for RYR1 | Uncertain Susceptibility |
| Phenotype for CACNA1S | Uncertain Susceptibility |
| Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes [PMID:30499100] Clinical pharmacology and therapeutics. 2018.
escitalopram
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C19 | Normal metabolism |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | Initiate therapy with recommended starting dose |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors [PMID:25974703] Clinical pharmacology and therapeutics. 2015.
fluorouracil
DPYD: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for DPYD | Normal DPD activity and "normal" risk for fluoropyrimidine toxicity |
| Matched Diplotypes | DPYD:Reference/Reference |
| Phenotype for DPYD | Normal Metabolizer |
| Activity Score for DPYD | 2.0 |
| Recommendation | Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guidelines for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing [PMID:23988873] Clinical pharmacology and therapeutics. 2013.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update [PMID:29152729] Clinical pharmacology and therapeutics. 2017.
flurbiprofen
CYP2C9: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C9 | Normal metabolism |
| Matched Diplotypes | CYP2C9:*1/*1 |
| Phenotype for CYP2C9 | Normal Metabolizer |
| Activity Score for CYP2C9 | 2.0 |
| Recommendation | 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. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs. [PMID:32189324] Clinical pharmacology and therapeutics. 2020.
fluvoxamine
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2D6 | Reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects. |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Initiate therapy with recommended starting dose. |
| Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors [PMID:25974703] Clinical pharmacology and therapeutics. 2015.
gentamicin
MT-RNR1: 1555A>G
increased risk of aminoglycoside-induced hearing loss
(from Outside Call)
| Type | Annotation |
|---|---|
| Population | general |
| Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
| Matched Diplotypes | MT-RNR1:1555A>G |
| Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
| Recommendation | Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. |
| Classification of Recommendation | Strong |
| Comments | If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring). |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of aminoglycosides based on MT-RNR1 genotype. [PMID:34032273] Clinical pharmacology and therapeutics. 2021.
halothane
CACNA1S: Reference/Reference
Two normal function alleles
RYR1: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for RYR1 | 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). |
| Implication for CACNA1S | 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). |
| Matched Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
| Phenotype for RYR1 | Uncertain Susceptibility |
| Phenotype for CACNA1S | Uncertain Susceptibility |
| Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes [PMID:30499100] Clinical pharmacology and therapeutics. 2018.
hydrocodone
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2D6 | Minimal evidence for pharmacokinetic or clinical effect. |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1 |
| Recommendation | Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid. |
| Classification of Recommendation | Optional |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype [PMID:22205192] Clinical pharmacology and therapeutics. 2011.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for cytochrome P450 2D6 (CYP2D6) genotype and codeine therapy: 2014 Update [PMID:24458010] Clinical pharmacology and therapeutics. 2014.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy. [PMID:33387367] Clinical pharmacology and therapeutics. 2021.
ibuprofen
CYP2C9: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C9 | Normal metabolism |
| Matched Diplotypes | CYP2C9:*1/*1 |
| Phenotype for CYP2C9 | Normal Metabolizer |
| Activity Score for CYP2C9 | 2.0 |
| Recommendation | 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. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs. [PMID:32189324] Clinical pharmacology and therapeutics. 2020.
imipramine
CYP2C19: *38/*38
Two normal function alleles
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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 |
| Implication for CYP2C19 | Normal metabolism of tertiary amines |
| Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
| Classification of Recommendation | Optional |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update [PMID:27997040] Clinical pharmacology and therapeutics. 2016.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants [PMID:23486447] Clinical pharmacology and therapeutics. 2013.
isoflurane
CACNA1S: Reference/Reference
Two normal function alleles
RYR1: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for RYR1 | 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). |
| Implication for CACNA1S | 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). |
| Matched Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
| Phenotype for RYR1 | Uncertain Susceptibility |
| Phenotype for CACNA1S | Uncertain Susceptibility |
| Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes [PMID:30499100] Clinical pharmacology and therapeutics. 2018.
ivacaftor
CFTR: No CPIC variants found
Two ivacaftor non-responsive alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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. |
| Matched Diplotypes | CFTR:No CPIC variants found |
| Phenotype for CFTR | ivacaftor non-responsive in CF patients |
| Recommendation | Ivacaftor is not recommended |
| Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Ivacaftor Therapy in the Context of CFTR Genotype [PMID:24598717] Clinical pharmacology and therapeutics. 2014.
kanamycin
MT-RNR1: 1555A>G
increased risk of aminoglycoside-induced hearing loss
(from Outside Call)
| Type | Annotation |
|---|---|
| Population | general |
| Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
| Matched Diplotypes | MT-RNR1:1555A>G |
| Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
| Recommendation | Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. |
| Classification of Recommendation | Strong |
| Comments | If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring). |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of aminoglycosides based on MT-RNR1 genotype. [PMID:34032273] Clinical pharmacology and therapeutics. 2021.
lansoprazole
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C19 | Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | 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. |
| Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. [PMID:32770672] Clinical pharmacology and therapeutics. 2020.
lornoxicam
CYP2C9: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C9 | Normal metabolism |
| Matched Diplotypes | CYP2C9:*1/*1 |
| Phenotype for CYP2C9 | Normal Metabolizer |
| Activity Score for CYP2C9 | 2.0 |
| Recommendation | 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. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs. [PMID:32189324] Clinical pharmacology and therapeutics. 2020.
meloxicam
CYP2C9: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C9 | Normal metabolism |
| Matched Diplotypes | CYP2C9:*1/*1 |
| Phenotype for CYP2C9 | Normal Metabolizer |
| Activity Score for CYP2C9 | 2.0 |
| Recommendation | 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. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs. [PMID:32189324] Clinical pharmacology and therapeutics. 2020.
mercaptopurine
NUDT15: *1/*1
Two normal function alleles
TPMT: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for TPMT | Lower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression. |
| Implication for NUDT15 | Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression |
| Matched Diplotypes | NUDT15:*1/*1, TPMT:*1/*1 |
| Phenotype for TPMT | Normal Metabolizer |
| Phenotype for NUDT15 | Normal Metabolizer |
| Recommendation | 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). |
| Classification of Recommendation | Strong |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing [PMID:21270794] Clinical pharmacology and therapeutics. 2011.
- Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update [PMID:23422873] Clinical pharmacology and therapeutics. 2013.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. [PMID:30447069] Clinical pharmacology and therapeutics. 2018.
methoxyflurane
CACNA1S: Reference/Reference
Two normal function alleles
RYR1: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for RYR1 | 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). |
| Implication for CACNA1S | 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). |
| Matched Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
| Phenotype for RYR1 | Uncertain Susceptibility |
| Phenotype for CACNA1S | Uncertain Susceptibility |
| Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes [PMID:30499100] Clinical pharmacology and therapeutics. 2018.
nortriptyline
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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. |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | 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. |
| Classification of Recommendation | Optional |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update [PMID:27997040] Clinical pharmacology and therapeutics. 2016.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants [PMID:23486447] Clinical pharmacology and therapeutics. 2013.
omeprazole
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C19 | Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | 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. |
| Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. [PMID:32770672] Clinical pharmacology and therapeutics. 2020.
ondansetron
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2D6 | Very limited data available for CYP2D6 intermediate metabolizers |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. |
| Classification of Recommendation | No Recommendation |
| Comments | Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron [PMID:28002639] Clinical pharmacology and therapeutics. 2016.
pantoprazole
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C19 | Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | 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. |
| Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. [PMID:32770672] Clinical pharmacology and therapeutics. 2020.
paromomycin
MT-RNR1: 1555A>G
increased risk of aminoglycoside-induced hearing loss
(from Outside Call)
| Type | Annotation |
|---|---|
| Population | general |
| Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
| Matched Diplotypes | MT-RNR1:1555A>G |
| Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
| Recommendation | Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. |
| Classification of Recommendation | Strong |
| Comments | If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring). |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of aminoglycosides based on MT-RNR1 genotype. [PMID:34032273] Clinical pharmacology and therapeutics. 2021.
paroxetine
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2D6 | Reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects. |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Initiate therapy with recommended starting dose |
| Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors [PMID:25974703] Clinical pharmacology and therapeutics. 2015.
peginterferon alfa-2a
No CPIC recommendation for this allele combination.
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and peginterferon alpha based regimens [PMID:24096968] Clinical pharmacology and therapeutics. 2013.
peginterferon alfa-2b
No CPIC recommendation for this allele combination.
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and peginterferon alpha based regimens [PMID:24096968] Clinical pharmacology and therapeutics. 2013.
piroxicam
CYP2C9: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C9 | Normal metabolism |
| Matched Diplotypes | CYP2C9:*1/*1 |
| Phenotype for CYP2C9 | Normal Metabolizer |
| Activity Score for CYP2C9 | 2.0 |
| Recommendation | 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. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs. [PMID:32189324] Clinical pharmacology and therapeutics. 2020.
plazomicin
MT-RNR1: 1555A>G
increased risk of aminoglycoside-induced hearing loss
(from Outside Call)
| Type | Annotation |
|---|---|
| Population | general |
| Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
| Matched Diplotypes | MT-RNR1:1555A>G |
| Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
| Recommendation | Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. |
| Classification of Recommendation | Strong |
| Comments | If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring). |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of aminoglycosides based on MT-RNR1 genotype. [PMID:34032273] Clinical pharmacology and therapeutics. 2021.
rasburicase
G6PD: B (wildtype)/B (wildtype)
Two normal function alleles
(from Outside Call)
| Type | Annotation |
|---|---|
| Population | general |
| Implication for G6PD | Low or reduced risk of hemolytic anemia |
| Matched Diplotypes | G6PD:B (wildtype)/B (wildtype) |
| Phenotype for G6PD | Normal |
| Recommendation | No reason to withhold rasburicase based on G6PD status. |
| Classification of Recommendation | Strong |
| Comments | A negative or inconclusive genetic test cannot be assumed to indicate normal G6PD phenotype; an enzyme actiity test is needed to assign G6PD phenotype in such cases. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Rasburicase Therapy in the context of G6PD Deficiency Genotype [PMID:24787449] Clinical pharmacology and therapeutics. 2014.
sertraline
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C19 | Normal metabolism |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | Initiate therapy with recommended starting dose |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors [PMID:25974703] Clinical pharmacology and therapeutics. 2015.
sevoflurane
CACNA1S: Reference/Reference
Two normal function alleles
RYR1: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for RYR1 | 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). |
| Implication for CACNA1S | 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). |
| Matched Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
| Phenotype for RYR1 | Uncertain Susceptibility |
| Phenotype for CACNA1S | Uncertain Susceptibility |
| Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes [PMID:30499100] Clinical pharmacology and therapeutics. 2018.
simvastatin
SLCO1B1: *1A/*1A
Two normal function alleles
SLCO1B1 star allele nomenclature represents various SNPs alone or in combination. The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.
In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 is contained in SLCO1B1*5 (rs4149056 alone) as well as the *15 and *17 alleles, and is associated with lower plasma clearance of simvastatin. The magnitude of this effect is similar for *5, *15, and *17 alleles. A number of SLCO1B1 alleles (*2, *3, *6, *9, *10, *23, *31) are classified by CPIC as 'possible decreased function' alleles. These alleles are not accounted for in the recommendation based on the rs4149056 genotype. Carriage of additional variants is possible.
In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 is contained in SLCO1B1*5 (rs4149056 alone) as well as the *15 and *17 alleles, and is associated with lower plasma clearance of simvastatin. The magnitude of this effect is similar for *5, *15, and *17 alleles. A number of SLCO1B1 alleles (*2, *3, *6, *9, *10, *23, *31) are classified by CPIC as 'possible decreased function' alleles. These alleles are not accounted for in the recommendation based on the rs4149056 genotype. Carriage of additional variants is possible.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for SLCO1B1 | Normal myopathy risk |
| Matched Diplotypes | SLCO1B1:*1A/*1A |
| Phenotype for SLCO1B1 | Normal Function |
| Recommendation | Prescribe desired starting dose and adjust doses of simvastatin based on disease-specific guidelines |
| Classification of Recommendation | Strong |
| Comments | In all cases, the potential for drug-drug interactions should be evaluated before initiating a prescription. The US Food and Drug Administration recommends against 80 mg (unless already tolerated for 12 months). |
For more information read the guideline on cpicpgx.org.
Citations:
- The Clinical Pharmacogenomics Implementation Consortium: Guideline for SLCO1B1 and Simvastatin-Induced Myopathy [PMID:22617227] Clinical pharmacology and therapeutics. 2012.
- The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update [PMID:24918167] Clinical pharmacology and therapeutics. 2014.
streptomycin
MT-RNR1: 1555A>G
increased risk of aminoglycoside-induced hearing loss
(from Outside Call)
| Type | Annotation |
|---|---|
| Population | general |
| Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
| Matched Diplotypes | MT-RNR1:1555A>G |
| Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
| Recommendation | Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. |
| Classification of Recommendation | Strong |
| Comments | If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring). |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of aminoglycosides based on MT-RNR1 genotype. [PMID:34032273] Clinical pharmacology and therapeutics. 2021.
succinylcholine
CACNA1S: Reference/Reference
Two normal function alleles
RYR1: Reference/Reference
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | general |
| Implication for RYR1 | 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). |
| Implication for CACNA1S | 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). |
| Matched Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
| Phenotype for RYR1 | Uncertain Susceptibility |
| Phenotype for CACNA1S | Uncertain Susceptibility |
| Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes [PMID:30499100] Clinical pharmacology and therapeutics. 2018.
tacrolimus
CYP3A5: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP3A5 | Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations. |
| Matched Diplotypes | CYP3A5:*1/*1 |
| Phenotype for CYP3A5 | Normal Metabolizer |
| Recommendation | Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments. |
| Classification of Recommendation | Strong |
| Comments | This recommendation includes the use of tacrolimus in kidney, heart, lung and hematopoietic stem cell transplant patients, and liver transplant patients where the donor and recipient genotypes are identical. Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function). Typically with other CYP enzymes, a normal metabolizer would be classified as having normal metabolism, and therefore, the drug dose would not change based on the patient’s genotype. However, in the case of CYP3A5 and tacrolimus, a CYP3A5 expresser (i.e., CYP3A5 normal metabolizer or intermediate metabolizer) would require a higher recommended starting dose, and the CYP3A5 non-expresser (i.e., poor metabolizer) would require the standard recommended starting dose. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing [PMID:25801146] Clinical pharmacology and therapeutics. 2015.
tamoxifen
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2D6 | Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers. |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | 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. |
| Classification of Recommendation | Optional |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. [PMID:29385237] Clinical pharmacology and therapeutics. 2018.
tenoxicam
CYP2C9: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2C9 | Normal metabolism |
| Matched Diplotypes | CYP2C9:*1/*1 |
| Phenotype for CYP2C9 | Normal Metabolizer |
| Activity Score for CYP2C9 | 2.0 |
| Recommendation | 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. |
| Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs. [PMID:32189324] Clinical pharmacology and therapeutics. 2020.
thioguanine
NUDT15: *1/*1
Two normal function alleles
TPMT: *1/*1
Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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. |
| Implication for NUDT15 | Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression |
| Matched Diplotypes | NUDT15:*1/*1, TPMT:*1/*1 |
| Phenotype for TPMT | Normal Metabolizer |
| Phenotype for NUDT15 | Normal Metabolizer |
| Recommendation | 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). |
| Classification of Recommendation | Strong |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing [PMID:21270794] Clinical pharmacology and therapeutics. 2011.
- Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update [PMID:23422873] Clinical pharmacology and therapeutics. 2013.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. [PMID:30447069] Clinical pharmacology and therapeutics. 2018.
tobramycin
MT-RNR1: 1555A>G
increased risk of aminoglycoside-induced hearing loss
(from Outside Call)
| Type | Annotation |
|---|---|
| Population | general |
| Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
| Matched Diplotypes | MT-RNR1:1555A>G |
| Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
| Recommendation | Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. |
| Classification of Recommendation | Strong |
| Comments | If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring). |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of aminoglycosides based on MT-RNR1 genotype. [PMID:34032273] Clinical pharmacology and therapeutics. 2021.
tramadol
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2D6 | Reduced O-desmethyltramadol (active metabolite) formation |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1 |
| Recommendation | Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid. |
| Classification of Recommendation | Optional |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype [PMID:22205192] Clinical pharmacology and therapeutics. 2011.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for cytochrome P450 2D6 (CYP2D6) genotype and codeine therapy: 2014 Update [PMID:24458010] Clinical pharmacology and therapeutics. 2014.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy. [PMID:33387367] Clinical pharmacology and therapeutics. 2021.
trimipramine
CYP2C19: *38/*38
Two normal function alleles
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for 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 |
| Implication for CYP2C19 | Normal metabolism of tertiary amines |
| Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
| Classification of Recommendation | Optional |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update [PMID:27997040] Clinical pharmacology and therapeutics. 2016.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants [PMID:23486447] Clinical pharmacology and therapeutics. 2013.
tropisetron
CYP2D6: *1/*3
One no function allele and one normal function allele
(from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
| Type | Annotation |
|---|---|
| Population | general |
| Implication for CYP2D6 | Very limited data available for CYP2D6 intermediate metabolizers |
| Matched Diplotypes | CYP2D6:*1/*3 |
| Phenotype for CYP2D6 | Intermediate Metabolizer |
| Activity Score for CYP2D6 | 1.0 |
| Recommendation | Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. |
| Classification of Recommendation | No Recommendation |
| Comments | Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron [PMID:28002639] Clinical pharmacology and therapeutics. 2016.
voriconazole
CYP2C19: *38/*38
Two normal function alleles
| Type | Annotation |
|---|---|
| Population | pediatrics |
| Implication for CYP2C19 | Normal voriconazole metabolism |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | Initiate therapy with recommended standard of care dosing |
| Classification of Recommendation | Strong |
| Comments | 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. |
| Type | Annotation |
|---|---|
| Population | adults |
| Implication for CYP2C19 | Normal voriconazole metabolism |
| Matched Diplotypes | CYP2C19:*38/*38 |
| Phenotype for CYP2C19 | Normal Metabolizer |
| Recommendation | Initiate therapy with recommended standard of care dosing |
| Classification of Recommendation | Strong |
| Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium (CPIC®) Guideline for CYP2C19 and Voriconazole Therapy [PMID:27981572] Clinical pharmacology and therapeutics. 2016.
warfarin
CYP2C9: *1/*1
Two normal function alleles
CYP4F2: *1/*1
N/A
Please follow the flow chart in figure 2 of the CPIC warfarin guideline to determine the appropriate dosing recommendation.
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
The CPIC warfarin guideline only considers a single SNV in VKORC1 (rs9923231), which is found in the highest frequency in Caucasians and extremely low frequency in those of African descent. While other functional variants in VKORC1 have been observed in much higher frequencies in some populations, 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).
For more information read the guideline on cpicpgx.org.
Citations:
- Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing [PMID:21900891] Clinical pharmacology and therapeutics. 2011.
- Clinical pharmacogenetics implementation consortium (cpic) guideline for pharmacogenetics-guided warfarin dosing: 2017 update [PMID:28198005] Clinical pharmacology and therapeutics. 2017.