Pharmacogenetic Associations

PHARMACOGENETIC ASSOCIATIONS

This table is limited to pharmacogenetic associations that are related to drug metabolizing enzyme gene variants, drug transporter gene variants, and gene variants that have been related to a predisposition for certain adverse events.

Generic Brand Gene/ Enzyme Affected Subgroups Description and Dosing
abacavir Ziagen HLA-B *57:01 allele positive Increased risk of adverse reactions (hypersensitivity reactions) in HLA-B*57:01 allele carriers. Screen for presence of HLA-B*57:01 allele prior to initiation or reinitiation; if positive, use is contraindicated.
allopurinol Aloprim HLA-B *58:01 allele positive Increased risk of adverse reactions (severe skin reactions) in HLA-B*58:01 allele carriers. Genotype testing prior to initiation in genetically at-risk populations (eg, African, Asian, Native Hawaiian/Pacific Islander ancestry); avoid use if positive for HLA-B*58:01 unless benefits clearly outweigh the risks.
amifampridine Firdapse NAT2 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs. Initiate at 15mg/day in 3 divided doses.
Ruzurgi NAT2 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs. Initiate at 7.5mg/day (<45kg) or 15mg/day (≥45kg) in divided doses.
aripiprazole Abilify CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Reduce dose by 50%. For PMs on concomitant strong CYP3A4 inhibitors1, reduce dose by 75%.
Abilify Maintena CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Reduce dose to 300mg monthly. For PMs on concomitant strong CYP3A4 inhibitors1 for >14 days, reduce dose to 200mg monthly.
Aristada CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Avoid use due to inability to make dose adjustments with a single-dose syringe. For PMs on concomitant strong CYP3A4 inhibitors1 maintained on higher Aristada doses, reduce dose to 441mg monthly.
atomoxetine Strattera CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs. Initiate dose at 0.5mg/kg/day; only increase to usual target dose of 1.2mg/kg/day if no improvement after 4wks and if tolerated.
brexpiprazole Rexulti CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Reduce dose by 50%. For PMs on concomitant strong/moderate CYP3A4 inhibitors1, reduce dose by 75%.
brivaracetam Briviact CYP2C19 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs. Consider dose reductions.
carbamaze
pine
Equetro HLA-B *15:02 allele positive Strong association between the risk of developing severe skin reactions (SJS/TEN) and the presence of HLA-B*15:02 esp. in patients of Chinese ancestry. Test for HLA-B*15:02 prior to initiation; avoid use if positive for the HLA-B*15:02 allele unless benefits clearly outweigh the risks of serious skin reactions. Risk may be increased with concomitant drugs associated with a risk of SJS/TEN.
Tegretol
celecoxib Celebrex CYP2C9 Poor metabolizers Higher systemic concentrations in PMs. Reduce starting dose by 50%. Consider alternatives in patients with JRA.
citalopram Celexa CYP2C19 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions (QT prolongation) in PMs. Max 20mg/day.
clobazam Onfi CYP2C19 Poor metabolizers Higher systemic concentrations of the active metabolite and increased risk of adverse reactions in PMs. Initiate at 5mg/day and titrate slowly as tolerated to 50% of recommended dose. May further titrate to max 20mg/day (≤30kg) or 40mg/day (>30kg) starting on Day 21.
Sympazan
clopidogrel Plavix CYP2C19 Poor metabolizers Lower systemic concentrations of the active metabolite, lower antiplatelet response, and possibly higher cardiovascular risk in PMs. Consider alternative platelet P2Y12 inhibitor.
clozapine Clozaril CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. May need dose reductions.
Versacloz
codeine CYP2D6 Ultrarapid metabolizers Higher systemic concentrations of the active metabolite and increased risk of life-threatening respiratory depression and death in ultrarapid metabolizers. Avoid use. Do not breastfeed. Contraindicated in children <12yrs and in <18yrs following tonsillectomy and/or adenoidectomy.
deutetra
benazine
Austedo CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions (QT prolongation) in PMs. Max 18mg/dose and 36mg/day.
dextro
methorphan/ quinidine
Nuedexta CYP2D6 Poor metabolizers Quinidine component does not contribute to the effectiveness of Nuedexta in PMs but a possible risk of significant toxicity is present. Consider genotyping to determine PM status prior to initiation.
fluvoxamine CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Use with caution.
galantamine CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Titrate based on tolerability.
Razadyne ER
gefitinib Iressa CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs. Monitor closely.
iloperidone Fanapt CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions (QT prolongation) in PMs. Reduce dose by 50%.
irinotecan Camptosar UGT1A1 *28/*28 allele positive Higher systemic concentrations of the active metabolite and increased risk of adverse reactions (severe neutropenia) in UGT1A1*28/*28 allele carriers. Consider reducing starting dose by at least 1 level and individualize.
lofexidine Lucemyra CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs. Monitor for orthostatic hypotension and bradycardia.
meloxicam Anjeso CYP2C9 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs. Consider dose reduction; monitor.
metoclo
pramide
Reglan CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs.
GERD: 5mg 4 times daily or 10mg 3 times daily; max 30mg/day.
Gastroparesis: 5mg 4 times daily; max 20mg/day.
oliceridine Olinvyk CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions (respiratory depression and sedation) in PMs. May require less frequent dosing; monitor closely.
pantoprazole Protonix CYP2C19 Poor metabolizers Higher systemic concentrations in PMs. Consider dose reduction in children.
pitolisant Wakix CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Initiate at 8.9mg daily and titrate to max 17.8mg daily after 7 days.
perphenazine CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions in PMs.
pimozide CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Max 0.05mg/kg/day in children or 4mg/day in adults; do not increase dose earlier than 14 days.
piroxicam Feldene CYP2C9 Poor metabolizers Higher systemic concentrations in PMs. Consider dose reduction.
protriptyline CYP2D6 Poor metabolizers Higher systemic concentrations in PMs.
risperidone Perseris CYP2D6 Extensive and poor metabolizers Systemic parent drug and metabolite concentrations altered.
Half-life (EMs): 3hrs
Half-life (PMs): 20hrs
Mean half-life (overall): 20hrs
Risperdal
sacituzumab govitecan Trodelvy UGT1A1 *28/*28 allele positive Higher systemic concentrations and increased risk of adverse reactions (neutropenia) in UGT1A1*28/*28 allele carriers. Monitor closely.
siponimod Mayzent CYP2C9 *1/*3, *2/*3, *3/*3 allele positive Higher systemic concentrations in CYP2C9 variants. Genotype testing prior to initiation.
CYP2C9*1/*3 or *2/*3: initiate 4-day titration (0.25mg on Days 1-2, 0.5mg on Day 3, 0.75mg on Day 4); reduce maintenance dose to 1mg daily starting on Day 5
CYP2C9*3/*3: contraindicated.
tetrabenazine Xenazine CYP2D6 Extensive, intermediate, or poor metabolizers Higher systemic concentrations of active metabolites in PMs. Perform genotyping prior to initiation to determine status for doses >50mg/day.
EMs or IMs: max 37.5mg/dose and 100mg/day.
PMs: max 25mg/dose and 50mg/day.
thioguanine TPMT and/or NUDT15 Intermediate and poor metabolizers Systemic active metabolite concentrations and dosing requirements altered, and increased risk of adverse reactions (myelosuppression) in PMs. Reduce initial dose; PMs typically require 10% or less of recommended dose. IMs may require dose reductions based on tolerability.
thioridazine CYP2D6 Poor metabolizers Higher systemic concentrations and increased risk of adverse reactions (QT prolongation) in PMs. Contraindicated.
tramadol Ultram CYP2D6 Ultrarapid metabolizers Higher systemic and breast milk concentrations of the active metabolite and increased risk of life-threatening respiratory depression and death in ultrarapid metabolizers. Avoid use. Do not breastfeed. Contraindicated in children <12yrs and in <18yrs following tonsillectomy and/or adenoidectomy.
tricyclic anti
depressants (TCAs)2
CYP2D6 Ultrarapid, intermediate, or poor metabolizers May alter systemic concentrations.
valbenazine Ingrezza CYP2D6 Poor metabolizers Higher systemic concentrations of the active metabolite and increased risk of adverse reactions (QT prolongation) in PMs. Max 40mg/day.
venlafaxine CYP2D6 Poor metabolizers Systemic parent drug and metabolite concentrations altered in PMs. Consider dose reductions.
Effexor XR
vortioxetine Trintellix CYP2D6 Poor metabolizers Higher systemic concentrations in PMs. Max 10mg/day.
warfarin Coumadin CYP2C9 Intermediate or poor metabolizers Variability in dose requirements. Select initial dosing based on clinical and genetic factors. Monitor and adjust doses based on INR.
VKORC1 -1639G>A variant carriers
NOTES

Key: EM = extensive metabolizer; HLA = human leukocyte antigen; IM = intermediate metabolizer; JRA = juvenile rheumatoid arthritis; NAT2 = N-acetyltransferase 2; NUDT15 = nudix hydrolase 15; PM = poor metabolizer; SJS = Stevens Johnson syndrome; TEN = toxic epidermal necrolysis; TPMT = thiopurine methyltransferase; UGT = uridine diphosphate-glucuronosyl transferase; VKORC = vitamin K epoxide reductase complex

1 Strong CYP3A4 inhibitors include itraconazole, ketoconazole, clarithromycin.

2 Include amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, trimipramine.

Not an inclusive list of medications and/or official indications. Please see drug monograph at www.eMPR.com and/or contact company for full drug labeling.

REFERENCES

Table of Pharmacogenetic Associations. Food and Drug Administration Web site. https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations. Published February 25, 2020. Updated May 24, 2021. Accessed June 14, 2021.

(Rev. 6/2021)