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) |
Please login or register first to view this content.