CPIC Quick Reference Card — Actionable Gene-Drug Pairs

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Oncology

Gene	Drug(s)	Actionability	Key Guidance
DPYD	5-FU, Capecitabine, Tegafur	Contraindication	Poor metabolizer (AS 0): contraindicated. AS 1.0: ↓50%. AS 1.5: ↓25–50%. EU mandate since 2020.
UGT1A1	Irinotecan	Dose Reduce	28/28 (poor metabolizer): ↓30% starting dose. Risk of severe neutropenia and diarrhea.
TPMT / NUDT15	Mercaptopurine, Thioguanine, Azathioprine	Contraindication	Poor metabolizer (both genes): contraindicated. Intermediate: start at 30–80% dose. Risk of fatal myelosuppression.
CYP2D6	Tamoxifen	Alternative	Poor metabolizer: consider aromatase inhibitor (postmenopausal) or alternative endocrine therapy. Reduced endoxifen activation.

Note: DPYD testing is mandatory in the EU before fluoropyrimidine therapy. TPMT/NUDT15 testing is standard of care before thiopurine initiation in oncology and autoimmune settings.

Cardiology

Gene	Drug(s)	Actionability	Key Guidance
CYP2C19	Clopidogrel	Alternative	Poor/intermediate metabolizer: use prasugrel or ticagrelor. Reduced active metabolite → increased MACE risk.
CYP2C9 + VKORC1	Warfarin	Dose Adjust	CYP2C9 2/3 + VKORC1 -1639 G>A: lower starting dose. Use validated dosing algorithms (e.g., warfarindosing.org).
SLCO1B1	Simvastatin	Dose Limit	*5 carriers (poor function): avoid simvastatin 80 mg. Consider rosuvastatin or pravastatin. Risk of myopathy/rhabdomyolysis.
CYP2C19	Voriconazole	Dose Adjust	Ultrarapid: may need higher dose. Poor metabolizer: ↓dose or use alternative antifungal. Monitor trough levels.

Psychiatry & Neurology

Gene	Drug(s)	Actionability	Key Guidance
CYP2D6	Codeine, Tramadol	Contraindication	Ultrarapid metabolizer: avoid (fatal respiratory depression, esp. pediatric). Poor metabolizer: no efficacy — use alternative analgesic.
CYP2D6	Amitriptyline, Nortriptyline	Dose Adjust	Poor metabolizer: ↓50% dose or use alternative. Ultrarapid: may need higher dose or switch. Monitor plasma levels.
CYP2C19	Escitalopram, Citalopram, Sertraline	Dose Adjust	Poor metabolizer: ↓50% citalopram/escitalopram. Ultrarapid: consider alternative SSRI. Sertraline: select alternative if PM.
HLA-A / HLA-B	Carbamazepine, Oxcarbazepine, Phenytoin	Contraindication	HLA-B15:02 (SE Asian): contraindicated — risk of SJS/TEN. HLA-A31:01 (European): increased hypersensitivity risk.

Pain & Anesthesia

Gene	Drug(s)	Actionability	Key Guidance
CYP2D6	Hydrocodone, Oxycodone	Dose Adjust	Poor metabolizer: reduced efficacy for both. Ultrarapid: increased toxicity risk for hydrocodone. Use morphine or non-opioid alternative.
CYP2B6	Efavirenz, Methadone	Dose Adjust	Poor metabolizer (6/6): ↓efavirenz dose to 400 mg or use alternative ARV. Methadone: risk of QTc prolongation.
RYR1 / CACNA1S	Volatile anesthetics, Succinylcholine	Contraindication	Malignant hyperthermia susceptibility: avoid triggering agents. Use total IV anesthesia (TIVA). Family screening recommended.

Immunology & Infectious Disease

Gene	Drug(s)	Actionability	Key Guidance
HLA-B*57:01	Abacavir	Contraindication	Positive: do not prescribe. Risk of fatal hypersensitivity reaction. Testing mandatory before initiation per FDA/EMA.
HLA-B*58:01	Allopurinol	Contraindication	Positive: contraindicated — risk of SJS/TEN. Use febuxostat as alternative. Higher prevalence in SE Asian, African American, and Korean populations.
G6PD	Rasburicase, Dapsone, Primaquine	Contraindication	Deficient: contraindicated. Risk of acute hemolytic anemia. Screen before prescribing. Higher prevalence in Mediterranean, African, and SE Asian descent.
IFNL3 (IL28B)	PEG-IFN / Ribavirin (HCV)	Informative	CC genotype: higher SVR to IFN-based therapy. Less relevant in DAA era but useful for resource-limited settings.

Contraindication Avoid or use alternative

Dose Adjust Modify dose per genotype

Informative Guides decision-making

Sources: CPIC Guidelines (cpicpgx.org), PharmGKB, FDA Table of Pharmacogenomic Biomarkers, EMA SmPC updates. All recommendations reflect Level A evidence (strong, based on consistent published literature). This reference does not replace clinical judgment or comprehensive pharmacogenomic consultation. Updated March 2026.

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