Colorado Care Network

Pharmacogenomic profile

Patient cohortPopulation geneticsSeeking a lead#cohort-pharmacogenomicsPDF (members)

The anchor question: which of this patient's current and future prescriptions does the genotype change, and will the result be in front of whoever prescribes next? A germline result is good for life. CPIC guidelines tell us what to do once a genotype exists; they don't tell us when to test, and the societies that do address testing disagree with each other.1 2

Who this cohort covers

Adults on, or likely to start, a drug with a CPIC-actionable gene that primary care prescribes: clopidogrel, the SSRIs, codeine and tramadol, statins, allopurinol. It also covers the drugs specialists start that we should hand them a result for, fluoropyrimidines and thiopurines, and patients who arrive with a past adverse reaction, a nonresponse, or a panel or consumer result they want read.

Nearly everyone carries something. In the first 9,589 patients genotyped preemptively at Vanderbilt, 91% had at least one actionable variant across just five drug-gene pairs, 96% of African American patients, and a one-gene-per-prescription approach would have meant 14,656 tests.3 In a cluster-randomized trial across seven European countries, a 12-gene panel applied with the Dutch guidelines cut clinically relevant adverse drug reactions from 27.7% to 21.0% in patients with an actionable result (OR 0.70).4

Not every pair has outcome data to match. In TAILOR-PCI, genotype-guided P2Y12 selection after PCI missed significance on its primary endpoint (HR 0.66, P=.06).5 We use CPIC's strength ratings as written and tell patients which recommendations are strong and which are optional.

Care map

RoleYear 1, EstablishYear 2, TreatYear 3, Sustain
AnchorReconcile the medication list against CPIC-actionable pairs, current and likely. Prefer a preemptive panel when several actionable drugs are current or on the horizon; it puts the result at the point of care for every later prescription.3 4 Store results as phenotypes in CPIC standard terms where every prescriber will see them.6Apply the stored phenotype at every new prescription. Recheck for strong CYP2D6 inhibitors such as paroxetine and fluoxetine; CPIC's opioid guideline scores a patient on a strong inhibitor as a poor metabolizer.7 8Annual medication review against the stored phenotypes.
GeneticsOrder from a lab whose CYP2D6 assay calls copy number, the *5 deletion and duplications, which AMP lists as tier 1 and calls essential.11 Results reported per gene in CPIC phenotype terms, not star alleles alone.6Hand DPYD and TPMT/NUDT15 results to oncology, GI, rheumatology or dermatology before they prescribe.Re-read stored results when CPIC updates a guideline. The genotype doesn't change; the recommendation can, as it did for CYP2C19 intermediate metabolizers in 2022 and thiopurine dosing in 2025.9 10
SpecialistsCardiology: ACS or PCI in a CYP2C19 intermediate metabolizer, avoid standard-dose clopidogrel; in a poor metabolizer, avoid clopidogrel; both CPIC strong, with prasugrel or ticagrelor at standard dose if no contraindication. Neurology: stroke or TIA, consider an alternative such as ticagrelor; prasugrel is contraindicated after stroke or TIA.9Oncology before a fluoropyrimidine: DPYD activity score 1.5, reduce the dose 25 to 50%; 1, reduce 50%; 0 or 0.5, avoid.1 A 2026 ASCO review reports that FDA boxed warnings and NCCN and ASCO updates now support testing before treatment.12 GI, rheumatology or dermatology before azathioprine: TPMT or NUDT15 intermediate metabolizer, start at 30 to 80% of the standard dose; poor metabolizer, consider a nonthiopurine.10Each new specialist prescription checked against the stored results.
DiagnosticsA panel covering the genes on this map, with CYP2D6 copy number.11 HLA-B*58:01 before allopurinol in patients of Southeast Asian descent (Han Chinese, Korean, Thai) and African American patients, a conditional ACR recommendation; ACR recommends against universal testing in others.13None routinely.
TherapiesSSRIs: CYP2C19 poor metabolizer, citalopram or escitalopram at a lower start and 50% of the usual maintenance dose, or a non-CYP2C19 alternative; ultrarapid, choose an alternative. Sertraline in a poor metabolizer, lower start and 50% maintenance reduction. Paroxetine in a CYP2D6 poor metabolizer, halve the starting dose.8 Codeine and tramadol: avoid in CYP2D6 ultrarapid and poor metabolizers; CPIC makes no genotype recommendation for oxycodone or methadone.7 Simvastatin: SLCO1B1 decreased function, an alternative statin or under 20 mg/day; poor function, an alternative statin. Atorvastatin (SLCO1B1 poor function) and rosuvastatin (ABCG2 poor function) start at 20 mg or less.16 Allopurinol: not in HLA-B*58:01 carriers; the risk is severe cutaneous reactions, SJS, TEN and DRESS.14 15Same rules at every new start. The hard part is remembering, which is why storage matters.6As needed.
Behavioral health and nutritionFor antidepressants the result guides choice and dose. CPIC finds the evidence for SLC6A4 and HTR2A insufficient for prescribing, so we don't act on those genes.8Coordinate with the treating psychiatrist when a genotype changes the SSRI plan.
CommunityA patient copy of the phenotype list to show every prescriber and pharmacist.

Visit one

The map above is the evidence. This is what to do with the patient in the room. Each line comes from the Year 1 column and carries the same citations.

AskEvery current drug and the ones on the horizon: planned PCI, chronic pain, depression or anxiety, gout, an upcoming chemotherapy or immunosuppressant. Past adverse reactions and nonresponse: codeine that did nothing, SSRI side effects, statin myalgia. Prior pharmacogenomic or consumer results, and the report. Ancestry, for HLA-B*58:01.13
ExamineReconcile the list against CPIC-actionable pairs, including strong CYP2D6 inhibitors such as paroxetine and fluoxetine, which make a normal metabolizer behave like a poor one.7 8
OrderA preemptive panel when several actionable drugs are current or likely,3 4 from a lab whose CYP2D6 assay calls copy number11 and that reports CPIC phenotype terms.6 A single-gene CYP2C19 test when the P2Y12 choice is imminent.9 HLA-B*58:01 before allopurinol where ACR's ancestry criteria apply.13
ReferCardiology, psychiatry, oncology, GI or rheumatology as the drugs call for, with the result in hand. Where: the esoteric assays, clinical expertise and specialist rosters.
Tell the patientThe result lasts a lifetime and changes the choice or dose of specific drugs. The serotonin-gene results some panels report aren't used for prescribing.8 Some drugs change how these genes behave.7 Show the result to every prescriber and pharmacist.
DocumentEach gene's phenotype in CPIC terms on the problem list or as a drug alert,6 the drugs it affects, the lab and assay, and the date. Give the patient a copy.

Roster for this cohort

Drawn from the esoteric assays roster (pharmacogenomic labs that publish a cash price and call CYP2D6 copy number), the clinical expertise roster (clinical pharmacists and pharmacogenomics consults), the specialist roster (cardiology, psychiatry, oncology, gastroenterology, rheumatology) and the primary care roster (anchors who hold the result for life). Forming; members propose and vet entries in the cohort's Slack channel.

Readings

References

  1. Amstutz U, Henricks LM, Offer SM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update. Clin Pharmacol Ther. 2018;103(2):210-216. doi:10.1002/cpt.911
  2. Hertz DL, Bousman CA, McLeod HL, et al. Recommendations for pharmacogenetic testing in clinical practice guidelines in the US. Am J Health Syst Pharm. 2024;81(16):672-683. doi:10.1093/ajhp/zxae110
  3. Van Driest SL, Shi Y, Bowton EA, et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin Pharmacol Ther. 2014;95(4):423-431. doi:10.1038/clpt.2013.229
  4. Swen JJ, van der Wouden CH, Manson LE, et al. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023;401(10374):347-356. doi:10.1016/S0140-6736(22)01841-4
  5. Pereira NL, Farkouh ME, So D, et al. Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA. 2020;324(8):761-771. doi:10.1001/jama.2020.12443
  6. Caudle KE, Dunnenberger HM, Freimuth RR, et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med. 2017;19(2):215-223. doi:10.1038/gim.2016.87
  7. Crews KR, Monte AA, Huddart R, et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6, OPRM1, and COMT genotypes and select opioid therapy. Clin Pharmacol Ther. 2021;110(4):888-896. doi:10.1002/cpt.2149
  8. Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes and serotonin reuptake inhibitor antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68. doi:10.1002/cpt.2903
  9. Lee CR, Luzum JA, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther. 2022;112(5):959-967. doi:10.1002/cpt.2526
  10. Maillard M, Schwab M, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2025 update. Clin Pharmacol Ther. 2026;119(4):916-927. doi:10.1002/cpt.70209
  11. Pratt VM, Cavallari LH, Del Tredici AL, et al. Recommendations for clinical CYP2D6 genotyping allele selection: a joint consensus recommendation of the Association for Molecular Pathology, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, and the European Society for Pharmacogenomics and Personalized Therapy. J Mol Diagn. 2021;23(9):1047-1064. doi:10.1016/j.jmoldx.2021.05.013
  12. Kratz J, Merritt K, Jorgensen J, et al. Importance of and strategies for implementing DPYD testing to prevent severe fluoropyrimidine chemotherapy toxicity in health care systems. Am Soc Clin Oncol Educ Book. 2026;46(3):e521184. doi:10.1200/EDBK-26-521184
  13. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180
  14. Hershfield MS, Callaghan JT, Tassaneeyakul W, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93(2):153-158. doi:10.1038/clpt.2012.209
  15. Saito Y, Stamp LK, Caudle KE, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update. Clin Pharmacol Ther. 2016;99(1):36-37. doi:10.1002/cpt.161
  16. Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin Pharmacol Ther. 2022;111(5):1007-1021. doi:10.1002/cpt.2557

References retrieved from PubMed on 2026-10-30. Care maps are peer-authored clinical frameworks for network members, not individualized medical advice, and are reviewed at each yearly cycle.

Discuss this cohort in Slack

Colorado Care Network. Pharmacogenomic profile. Version 2026-10-30.