Paeds · clinical-pharmacology-and-therapeutics
Pharmacogenomics and precision therapeutics
Also known as Pharmacogenomics in children · Precision medicine and prescribing · TPMT and thiopurine testing · CYP2D6 and codeine · HLA-B and carbamazepine
A fellowship approach to pharmacogenomics and precision therapeutics in children covering how inherited gene variants change the way an individual child handles a drug, the Clinical Pharmacogenetics Implementation Consortium gene-drug pairs a general paediatrician must know, thiopurine methyltransferase and NUDT15 before azathioprine or 6-mercaptopurine, CYP2D6 and the codeine ultrarapid-metaboliser trap, HLA-B star 15 colon 02 screening before carbamazepine, HLA-B star 57 colon 01 before abacavir, CYP2C19 and clopidogrel, and how to order a genotype, read a report, and change the prescription.
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Target exams
Red flags
- Codeine or tramadol prescribed to a child under twelve years, or under eighteen after tonsillectomy or adenoidectomy
- Azathioprine or 6-mercaptopurine started without a documented thiopurine methyltransferase and NUDT15 result
- Carbamazepine or oxcarbazepine started in a child of Asian ancestry without a documented HLA-B star 15 colon 02 result
- Abacavir started without a documented HLA-B star 57 colon 01 result
- A pharmacogenomic result filed in the chart and the original prescription never adjusted
- Rasburicase, dapsone, primaquine or a sulphonamide given to a child with untested or known G6PD deficiency
Life stages
Care settings
Clinical exam formats
Board mappings
- General and Community Paediatrics
- Current 2026 PREP curriculum — Learning Objective 2.2.1: Recognise, prioritise and manage an acutely ill infant, child or young person
- Current 2026 PREP curriculum — Learning Objective: Safe prescribing and medication management in infants, children and young people
- Renewed curriculum for first-year trainees from 2027 — Learning goal 6: Clinical management – essential general paediatrics
- Renewed curriculum for first-year trainees from 2027 — Learning goal 9: Quality and safety, including medication safety
- Clinical Applications
- Medical Sciences
- Long Cases
- Short Cases
- 4. Professional skills and knowledge: Patient management
- 7. Patient safety, including safe prescribing
- 8. Quality improvement and patient safety
- General Paediatrics: Uses pharmacogenomic information to individualise prescribing and prevent avoidable adverse drug reactions
- Foundation of Practice (FOP)
- Theory and Science (TAS)
- Applied Knowledge in Practice (AKP)
- Clinical
- History
- Communication
- General Pediatrics Content Outline — Domain 10: Principles of Pharmacology and Medication Management
- General Pediatrics Content Outline — Universal Task 4: Management and Treatment
- General Pediatrics Content Outline — Universal Task 2: Health Maintenance
- Systems-Based Practice 2: Precision medicine and pharmacogenomic stewardship
- Patient Safety/Quality Improvement 1: Medication Safety
- Medical Knowledge 2: Diagnostic and Therapeutic Decision Making
- Medical Expert
- Scholar
- Pediatrics: Core EPA #5 — Recommending and Initiating Pharmacologic Interventions
Overview & Definition
Picture a six-year-old of Han Chinese background about to start carbamazepine for epilepsy, a ten-year-old with Crohn disease about to start azathioprine, and a four-year-old sent home with codeine after adenotonsillectomy. Each child is carrying a hidden inherited variant that will turn a standard prescription into a serious adverse drug reaction. Pharmacogenomics is the discipline that finds those variants first and changes the prescription before the harm arrives. [9] [10]
Two ideas carry the whole topic. The first is the gene-drug pair: pharmacogenomics is not a genome-wide screen, it is a small set of specific genes whose variants predict a specific drug's effect to a degree strong enough to change practice. The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes the gene-drug pairs that are ready for the clinic, and the fellowship candidate must know the four that meet children most often — TPMT and NUDT15 with the thiopurines, CYP2D6 with codeine, HLA-B star 15 colon 02 with carbamazepine, and HLA-B star 57 colon 01 with abacavir. The second is the actionable result: a pharmacogenomic test only helps if the result reaches the prescriber and the prescription changes, so the discipline closes on communication, not on the laboratory. [1] [9] [10]
From a planned prescription to a precision one
- 1
1 · Identify the gene-drug pair
Recognise the prescription that carries a CPIC-level pharmacogenomic risk — thiopurine, aromatic antiepileptic, codeine, abacavir.
- 2
2 · Order the genotype
Request TPMT and NUDT15, HLA-B star 15 colon 02, HLA-B star 57 colon 01, or CYP2D6 activity before the first dose when a result is available.
- 3
3 · Read the phenotype
Translate genotype into a metaboliser phenotype — poor, intermediate, normal, rapid, or ultrarapid — using the CPIC translation table.
- 4
4 · Change the prescription
Reduce the dose, choose an alternative drug, or avoid the drug entirely as the CPIC recommendation directs.
- 5
5 · Document and share
Record the result and the reason in the chart, flag it for future prescriptions, and tell the family in plain language.
References11ShowHide
- [1]Relling MV, Schwab M, Whirl-Carrillo M Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clinical pharmacology and therapeutics, 2019.PMID 30447069
- [2]Crews KR, Gaedigk A, Dunnenberger HM Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clinical pharmacology and therapeutics, 2014.PMID 24458010
- [3]Crews KR, Monte AA, Huddart R Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clinical pharmacology and therapeutics, 2021.PMID 33387367
- [4]Lee CR, Luzum JA, Sangkuhl K Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update. Clinical pharmacology and therapeutics, 2022.PMID 35034351
- [5]Phillips EJ, Sukasem C, Whirl-Carrillo M Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clinical pharmacology and therapeutics, 2018.PMID 29392710
- [6]Chung WH, Hung SI, Hong HS Medical genetics: a marker for Stevens-Johnson syndrome. Nature, 2004.PMID 15057820
- [7]Mallal S, Nolan D, Witt C Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet (London, England), 2002.PMID 11888582
- [8]Yang JJ, Landier W, Yang W Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. Journal of clinical oncology, 2015.PMID 25624441
- [9]Relling MV, Evans WE Pharmacogenomics in the clinic. Nature, 2015.PMID 26469045
- [10]Swen JJ, van der Wouden CH, Manson LE A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet (London, England), 2023.PMID 36739136
- [11]Maillard M, Nishii R, Yang W Additive effects of TPMT and NUDT15 on thiopurine toxicity in children with acute lymphoblastic leukemia across multiethnic populations. Journal of the National Cancer Institute, 2024.PMID 38230823