Clinical Decision Support

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Practical medication adjustment scenarios based on metabolizer phenotype. Select a gene-drug pair to see CPIC-aligned dosing recommendations.

Jump to Gene-Drug Scenarios

CYP2C19 CYP2D6 CYP2C9 CYP3A5 DPYD TPMT

CYP2C19 Scenarios

Clopidogrel, SSRIs, PPIs, Voriconazole

Clopidogrel (Plavix®) - Antiplatelet

Poor Metabolizer

CYP2C19 *2/*2, *2/*3, *3/*3

Clinical Problem

Cannot convert clopidogrel prodrug to active metabolite. Significantly reduced antiplatelet effect. High risk of stent thrombosis and cardiovascular events.

Recommended Action

  • AVOID clopidogrel
  • Use ticagrelor 90mg twice daily
  • Or prasugrel 10mg once daily

Normal Patient Dose

Clopidogrel 75mg daily

PM: Do NOT use

CPIC Level A | FDA Boxed Warning

Intermediate Metabolizer

CYP2C19 *1/*2, *1/*3, *2/*17

Clinical Problem

Reduced conversion to active metabolite. Diminished antiplatelet response, particularly in ACS/PCI patients.

Recommended Action

  • Consider ticagrelor 90mg twice daily
  • Or prasugrel 10mg once daily
  • If clopidogrel necessary: 150mg daily (double dose)

Normal Patient Dose

Clopidogrel 75mg daily

IM: 150mg daily or switch

CPIC Level A

Normal Metabolizer

CYP2C19 *1/*1

Clinical Expectation

Normal conversion to active metabolite. Expected antiplatelet response at standard doses.

Recommended Action

  • Loading dose: 300-600mg once
  • Maintenance: 75mg once daily

Standard Dosing

75mg once daily

Loading: 300-600mg

CPIC Level A

Ultrarapid Metabolizer

CYP2C19 *1/*17, *17/*17

Clinical Expectation

Increased conversion to active metabolite. Enhanced antiplatelet effect, potentially increased bleeding risk.

Recommended Action

  • Standard dosing: 75mg once daily
  • Monitor for bleeding signs

Standard Dosing

75mg once daily

No dose change needed

CPIC Level A

Escitalopram/Citalopram - SSRIs

Poor Metabolizer

CYP2C19 *2/*2, *2/*3, *3/*3

Clinical Problem

Decreased metabolism leads to ~2x higher drug concentrations. Increased risk of side effects including QT prolongation.

Recommended Action

  • Citalopram: Max 20mg/day (not 40mg)
  • Escitalopram: Max 10mg/day (not 20mg)
  • Consider ECG monitoring

Normal Patient Dose

Citalopram 20-40mg

Escitalopram 10-20mg

PM: 50% reduction

Ultrarapid Metabolizer

CYP2C19 *17/*17

Clinical Problem

Faster metabolism may result in reduced drug exposure and diminished therapeutic effect.

Recommended Action

  • Consider sertraline 50-200mg or fluoxetine 20-80mg instead
  • If using citalopram: may need 40-60mg/day
  • If using escitalopram: may need 20-30mg/day

Normal Patient Dose

Citalopram 20-40mg

Escitalopram 10-20mg

UM: May need 150%

CYP2D6 Scenarios

Codeine, Tramadol, Antidepressants, Tamoxifen

Codeine - Opioid Analgesic (Prodrug)

Ultrarapid Metabolizer

CYP2D6 *1/*1xN, *1/*2xN

Clinical Problem

Rapid conversion of codeine → morphine. Life-threatening toxicity risk: respiratory depression, sedation, especially in children and breastfeeding.

Recommended Action

  • AVOID codeine completely
  • AVOID tramadol
  • Use morphine 15-30mg q4h PRN
  • Or hydromorphone 2-4mg q4h PRN
  • Or NSAIDs/acetaminophen for mild pain

Normal Patient Dose

Codeine 30-60mg q4h

Tramadol 50-100mg q6h

UM: CONTRAINDICATED

FDA Warning

Poor Metabolizer

CYP2D6 *4/*4, *4/*5, *5/*5

Clinical Problem

Cannot convert codeine to morphine. No analgesic effect despite taking medication. Patient may appear to be "drug seeking."

Recommended Action

  • AVOID codeine (ineffective)
  • AVOID tramadol (ineffective)
  • Use morphine 15-30mg q4h PRN
  • Or hydromorphone 2-4mg q4h PRN
  • Or oxycodone 5-10mg q4h PRN

Normal Patient Dose

Codeine 30-60mg q4h

Tramadol 50-100mg q6h

PM: No effect - switch drug

Normal Metabolizer

CYP2D6 *1/*1, *1/*2

Clinical Expectation

Normal conversion to morphine. Expected analgesic response at standard doses.

Recommended Action

  • Codeine: 30-60mg every 4-6 hours PRN
  • Tramadol: 50-100mg every 4-6 hours PRN
  • Max codeine: 360mg/day

Standard Dosing

Codeine 30-60mg q4-6h

Tramadol 50-100mg q6h

CPIC Level A

Tamoxifen - Breast Cancer (Prodrug)

Poor Metabolizer

CYP2D6 *4/*4, *4/*5, *5/*5

Clinical Problem

Cannot convert tamoxifen → endoxifen (active metabolite). Significantly reduced efficacy for breast cancer prevention/treatment.

Recommended Action

  • AVOID tamoxifen if possible
  • Use anastrozole 1mg daily (postmenopausal)
  • Or letrozole 2.5mg daily (postmenopausal)
  • Or exemestane 25mg daily (postmenopausal)
  • Premenopausal: consult oncology

Normal Patient Dose

Tamoxifen 20mg daily

PM: Switch to aromatase inhibitor

CPIC Level B

Intermediate Metabolizer

CYP2D6 *1/*4, *1/*5, *4/*41

Clinical Problem

Reduced endoxifen formation. May have decreased efficacy compared to normal metabolizers.

Recommended Action

  • Consider aromatase inhibitor if postmenopausal
  • If tamoxifen: consider 40mg daily (double dose)
  • AVOID CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion)

Normal Patient Dose

Tamoxifen 20mg daily

IM: Consider 40mg daily

CPIC Level B

Normal Metabolizer

CYP2D6 *1/*1, *1/*2

Clinical Expectation

Normal endoxifen formation. Expected therapeutic response at standard doses.

Recommended Action

  • Tamoxifen 20mg once daily
  • Continue for 5-10 years per guidelines
  • Avoid CYP2D6 inhibitors if possible

Standard Dosing

20mg once daily

Duration: 5-10 years

CPIC Level A

CYP2C9 + VKORC1 Scenarios

Warfarin Dosing

Warfarin (Coumadin®) - Anticoagulant

Warfarin Dosing Requires Two Genes

CYP2C9 (metabolism) + VKORC1 (drug target sensitivity). Use validated algorithms combining both genes with clinical factors (age, weight, concomitant drugs). Visit warfarindosing.org

CYP2C9 Poor Metabolizer

CYP2C9 *3/*3, *2/*3

Clinical Problem

Significantly reduced warfarin clearance. High bleeding risk with standard doses. Prolonged time to stable INR.

Recommended Action

  • Start at 1-2mg daily (not 5mg)
  • Check INR in 3-4 days, then twice weekly
  • Expect 2-4 weeks to stable dose
  • Use warfarindosing.org calculator

Normal Patient Dose

Warfarin 5mg daily start

Maintenance 4-6mg/day

PM: Start 1-2mg/day

CPIC Level A

VKORC1 Low Expresser

VKORC1 -1639 AA

Clinical Problem

Reduced VKORC1 expression = increased warfarin sensitivity. Lower doses achieve therapeutic INR.

Recommended Action

  • Start at 2-3mg daily (not 5mg)
  • Expect maintenance 2-4mg/day
  • Common in Asian populations (80-90%)

Normal Patient Dose

Warfarin 5mg daily start

Maintenance 4-6mg/day

AA: Start 2-3mg, maint 2-4mg

Combined High Sensitivity

CYP2C9 *3/*3 + VKORC1 AA

Clinical Problem

Maximum sensitivity: reduced metabolism + increased target sensitivity. Extremely high bleeding risk.

Recommended Action

  • Start at 0.5-1mg daily
  • Check INR every 2-3 days initially
  • Consider apixaban 5mg BID or rivaroxaban 20mg daily
  • Expect maintenance 0.5-2mg/day

Normal Patient Dose

Warfarin 5mg start

Maint: 4-6mg/day

Combined: 0.5-1mg start

Maint: 0.5-2mg/day

Normal Genotype

CYP2C9 *1/*1 + VKORC1 GG

Clinical Expectation

Normal warfarin metabolism and sensitivity. Standard dosing approach appropriate.

Recommended Action

  • Start warfarin 5mg daily
  • Check INR in 3-5 days
  • Adjust to target INR 2-3 (or 2.5-3.5)
  • Typical maintenance: 4-6mg/day

Standard Dosing

Start: 5mg daily

Maint: 4-6mg/day

Target INR: 2-3

CPIC Level A

DPYD Scenarios

Fluoropyrimidines (5-FU, Capecitabine)

5-Fluorouracil / Capecitabine - Chemotherapy

Critical Safety Alert

DPYD deficiency can cause severe, life-threatening, or fatal toxicity including neutropenia, mucositis, diarrhea, and hand-foot syndrome. Pre-treatment testing is now mandated in Europe and strongly recommended by CPIC.

DPYD Deficient

*2A/*2A, *13/*13

Activity Score: 0

Clinical Problem

Complete DPD enzyme deficiency. Cannot metabolize fluoropyrimidines. Near-certain severe/fatal toxicity.

Recommended Action

  • CONTRAINDICATED - DO NOT USE
  • Use alternative regimen without 5-FU/capecitabine
  • Consult oncology for alternatives (e.g., oxaliplatin-based)

Normal Patient Dose

5-FU: 400-600 mg/m² bolus

Capecitabine: 1000-1250 mg/m² BID

Deficient: DO NOT USE

Partial Function

*1/*2A, *1/*13, c.2846A>T het

Activity Score: 1-1.5

Clinical Problem

Reduced DPD activity. Significantly increased risk of severe toxicity at standard doses.

Recommended Action

  • 5-FU: Start at 200-300 mg/m² (50% of standard)
  • Capecitabine: Start at 500-625 mg/m² BID (50%)
  • Close monitoring for toxicity
  • May titrate up cautiously based on tolerance

Normal Patient Dose

5-FU: 400-600 mg/m²

Cape: 1000-1250 mg/m² BID

Partial: 50% dose (200-300, 500-625)

Decreased Function

c.1236G>A het (HapB3)

Activity Score: 1.5

Clinical Problem

Mildly reduced DPD activity. Moderately increased toxicity risk.

Recommended Action

  • 5-FU: Start at 300-450 mg/m² (75% of standard)
  • Capecitabine: Start at 750-940 mg/m² BID (75%)
  • Titrate based on clinical tolerance

Normal Patient Dose

5-FU: 400-600 mg/m²

Cape: 1000-1250 mg/m² BID

Decreased: 75% dose

Normal Function

*1/*1 (no variants)

Activity Score: 2

Clinical Expectation

Normal DPD activity. Standard fluoropyrimidine dosing appropriate.

Recommended Action

  • 5-FU: 400-600 mg/m² IV bolus per protocol
  • Capecitabine: 1000-1250 mg/m² twice daily
  • Monitor per standard oncology protocols

Standard Dosing

5-FU: 400-600 mg/m²

Cape: 1000-1250 mg/m² BID

CPIC Level A

TPMT/NUDT15 Scenarios

Thiopurines (Azathioprine, 6-MP, Thioguanine)

Azathioprine / 6-Mercaptopurine - Immunosuppressants

Two Genes to Consider

Both TPMT and NUDT15 affect thiopurine toxicity. NUDT15 is especially important in Asian populations. Test both genes for comprehensive risk assessment.

TPMT Deficient

*3A/*3A, *2/*3A, *3C/*3C

Clinical Problem

No TPMT activity. Massive accumulation of toxic thioguanine nucleotides. Life-threatening myelosuppression at standard doses.

Recommended Action

  • Azathioprine: Start 0.5 mg/kg 3x weekly (not 2-3 mg/kg daily)
  • 6-MP: Start 10 mg/m² 3x weekly (not 75 mg/m² daily)
  • CBC weekly for first 2 months
  • Consider alternative if available

Normal Patient Dose

Aza: 2-3 mg/kg/day

6-MP: 75 mg/m²/day

Deficient: 10% dose, 3x/week

TPMT Intermediate

*1/*3A, *1/*3C, *1/*2

Clinical Problem

Reduced TPMT activity. Increased risk of myelosuppression with standard doses.

Recommended Action

  • Azathioprine: Start 1-1.5 mg/kg/day (50% reduction)
  • 6-MP: Start 40-50 mg/m²/day (50-70%)
  • Titrate based on CBC and response
  • Monitor CBC every 1-2 weeks initially

Normal Patient Dose

Aza: 2-3 mg/kg/day

6-MP: 75 mg/m²/day

IM: 30-70% of standard

Normal Function

*1/*1

Clinical Expectation

Normal TPMT activity. Standard thiopurine dosing appropriate.

Recommended Action

  • Azathioprine: 2-3 mg/kg/day (IBD, transplant)
  • 6-MP: 75 mg/m²/day (ALL maintenance)
  • Standard CBC monitoring

Standard Dosing

Aza: 2-3 mg/kg/day

6-MP: 75 mg/m²/day

CPIC Level A

NUDT15 Poor Function

*3/*3, *2/*3

Common in East Asians

Clinical Problem

Absent NUDT15 function leads to thioguanine accumulation. Severe leukopenia risk even with normal TPMT.

Recommended Action

  • Azathioprine: Start 0.5 mg/kg 3x weekly
  • 6-MP: Start 10 mg/m² 3x weekly
  • Intensive CBC monitoring
  • NUDT15*3: ~10% in East Asians, rare in Europeans

Normal Patient Dose

Aza: 2-3 mg/kg/day

6-MP: 75 mg/m²/day

NUDT15 Poor: 10% dose, 3x/week

CYP3A5 Scenarios

Tacrolimus Dosing in Transplant

Tacrolimus (Prograf®) - Immunosuppressant

CYP3A5 Expresser

*1/*1 or *1/*3

Extensive Metabolizer

Clinical Problem

Active CYP3A5 expression increases tacrolimus clearance. Standard doses may be subtherapeutic, risking organ rejection.

Recommended Action

  • Increase starting dose by 1.5-2x
  • Start at 0.3 mg/kg/day (vs 0.15-0.2 mg/kg/day)
  • Monitor trough levels closely, titrate to target

Starting Dose

0.3 mg/kg/day

CPIC Level A

CYP3A5 Non-Expresser

*3/*3

Poor Metabolizer

Clinical Expectation

No functional CYP3A5. Tacrolimus metabolism relies on CYP3A4 alone. Standard dosing typically appropriate.

Recommended Action

  • Standard starting dose: 0.15-0.2 mg/kg/day
  • Titrate to target trough concentration

Starting Dose

0.15-0.2 mg/kg/day

CPIC Level A

Population Considerations

Caucasians

~85-90% non-expressers (*3/*3)

African Americans

~45-70% expressers (*1 carriers)

Asians

~60-75% non-expressers

Quick Reference: Key Dose Adjustments

Gene Drug Poor/Deficient Ultrarapid/Expresser
CYP2C19 Clopidogrel Avoid → Ticagrelor Standard dose
CYP2D6 Codeine Avoid (no effect) Avoid (toxicity)
CYP2C9+VKORC1 Warfarin ↓50-70% May need ↑dose
DPYD 5-FU/Capecitabine Avoid or ↓50-90% Standard dose
TPMT Azathioprine/6-MP ↓90% (10% dose) Standard dose
CYP3A5 Tacrolimus Standard dose ↑1.5-2x starting

Always refer to current CPIC guidelines for complete recommendations