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 for which data exists to support recommendations for therapeutic management.
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-B57:01 allele carriers. Screen for presence of HLA-B57:01 allele prior to initiation or reinitiation; if positive, use is contraindicated.
abrocitinib	Cibinqo	CYP2C19	Poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions in PMs. Initiate at 50mg/day; consider increasing to max 100mg/day if inadequate response after 12wks
allopurinol	Aloprim	HLA-B	*58:01 allele positive	Increased risk of adverse reactions (severe skin reactions) in HLA-B58:01 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-B58:01 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.
amphetamine	Adderall XR	CYP2D6	Poor metabolizers	Systemic concentrations may be affected, and increased risk of adverse reactions in PMs. Consider lower initial dose or use alternatives.
	Dyanavel XR
	Evekeo
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.
azathioprine	Imuran	TPMT and/or NUDT15	Intermediate or poor metabolizers	Systemic active metabolite concentrations and dosing requirements altered, and increased risk of adverse reactions (myelosuppression). Consider alternatives in PMs. IMs may require dose reductions.
belinostat	Beleodaq	UGT1A1	28/28 allele positive	Higher systemic concentrations and increased risk of adverse reactions in UGT1A128/28 allele carriers. Reduce starting dose to 750mg/m².
belzutifan	Welireg	CYP2C19 and/or UGT2B17	Poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions (anemia, hypoxia) in PMs. Monitor closely; may need dose reductions.
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.
capecitabine	Xeloda	DPYD	Intermediate or poor metabolizers	Increased risk of adverse reactions in IMs and PMs. Withhold or discontinue in the presence of early-onset or unusually severe toxicity.
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-B15:02 esp. in patients of Chinese ancestry. Test for HLA-B15:02 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.
carbamaze– pine	Tegretol	HLA-B	*15:02 allele positive
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.
clobazam	Sympazan	CYP2C19	Poor metabolizers
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.
clozapine	Versacloz	CYP2D6	Poor metabolizers
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.
dronabinol	Marinol	CYP2C9	Intermediate or poor metabolizers	May result in higher systemic concentrations and increased risk of adverse reactions in IMs and PMs. Monitor closely.
dronabinol	Syndros	CYP2C9	Intermediate or poor metabolizers
eliglustat	Cerdelga	CYP2D6	Ultrarapid, extensive, intermediate, or poor metabolizers	Systemic concentrations, efficacy, and risk of adverse reactions (QT prolongation) altered. Ultrarapid metabolizers may not achieve adequate concentrations to achieve a therapeutic effect. Contraindicated in IMs and PMs with concomitant strong CYP3A inhibitors¹. EMs and IMs: 84mg twice daily. PMs: 84mg/day; monitor.
erdafitinib	Balversa	CYP2C9	3/3 allele positive	May result in higher systemic concentrations and increased risk of adverse reactions in CYP2C9 3/3 allele carriers. Monitor closely.
flibanserin	Addyi	CYP2C19	Poor metabolizers	May result in higher systemic concentrations and increased risk of adverse reactions in PMs. Monitor closely.
fluorouracil	—	DPYD	Intermediate or poor metabolizers	Increased risk of adverse reactions in IMs and PMs. Withhold or discontinue in the presence of early-onset or unusually severe toxicity.
flurbiprofen	—	CYP2C9	Poor metabolizers or *3 allele carriers	Higher systemic concentrations in PMs; reduce dose.
fosphenytoin	Cerebyx	CYP2C9	Intermediate or poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions (CNS toxicity) in IMs and PMs. Consider initiating at lower end of dose range; monitor. CYP2C9*3 allele carriers may be at increased risk of severe skin reactions; consider avoiding as an alternative for carbamazepine.
fosphenytoin	Cerebyx	HLA-B	*15:02 allele positive	Increased risk of adverse reactions (severe skin reactions such as Stevens Johnson Syndrome, Toxic Epidermal Necrolysis) in HLA-B*15:02 allele carriers; consider avoiding as an alternative for carbamazepine.
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 UGT1A128/28 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.
meclizine	—	CYP2D6	Ultrarapid, intermediate, or poor metabolizers	Systemic concentrations may be affected. Monitor closely.
meloxicam	Anjeso	CYP2C9	Poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions in PMs. Consider dose reduction; monitor.
mercapto– purine	—	TPMT and/or NUDT15	Intermediate or poor metabolizers	Systemic active metabolite concentrations and dosing requirements altered, and increased risk of adverse reactions (myelosuppression). Reduce initial dose; PMs typically require 10% or less of recommended dose. IMs may require dose reductions based on tolerability; greater reductions may be needed in IMs for both genes.
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.
mivacurium	—	BCHE	Intermediate or poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions (prolonged neuromuscular blockade). Avoid use in PMs.
nateglinide	—	CYP2C9	Poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions (hypoglycemia) in PMs. Reduce dose and monitor.
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.
phenytoin	Dilantin	CYP2C9	Intermediate or poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions (CNS toxicity) in IMs and PMs. CYP2C9*3 allele carriers may be at increased risk of severe skin reactions; consider avoiding as an alternative for carbamazepine.
phenytoin	Dilantin	HLA-B	*15:02 allele positive	Increased risk of adverse reactions (severe skin reactions such as Stevens Johnson Syndrome, Toxic Epidermal Necrolysis) in HLA-B*15:02 allele carriers; consider avoiding as an alternative for carbamazepine.
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.
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.
propafenone	Rythmol SR	CYP2D6	Poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions (arrhythmia). Avoid use in PMs with concomitant CYP3A4 inhibitor.
sacituzumab govitecan	Trodelvy	UGT1A1	28/28 allele positive	Higher systemic concentrations and increased risk of adverse reactions (neutropenia) in UGT1A128/28 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. CYP2C91/3 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 CYP2C93/3: contraindicated.
succinylcholine	Quelicin	BCHE	Intermediate or poor metabolizers	Higher systemic concentrations and increased risk of adverse reactions (prolonged neuromuscular blockade). Avoid use in PMs. May give test dose to assess sensitivity and infuse slowly with caution.
tacrolimus	Envarsus XR	CYP3A5	Intermediate or normal metabolizers	Lower systemic concentrations, lower probability of achieving target concentrations and may increase rejection risk. Measure drug concentrations and adjust dose based on tacrolimus trough levels.
tacrolimus	Prograf	CYP3A5	Intermediate or normal metabolizers
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.
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.
venlafaxine	Effexor XR	CYP2D6	Poor metabolizers
vortioxetine	Trintellix	CYP2D6	Poor metabolizers	Higher systemic concentrations in PMs. Max 10mg/day.
warfarin	—	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.
warfarin	—	VKORC1	-1639G>A variant carriers
NOTES
Key: BCHE = butyrylcholinesterase; DPYD = dihydropyrimidine dehydrogenase; 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 October 26, 2022. Accessed December 29, 2022. (Rev. 1/2023)

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