Translates CYP2C19 diplotype into actionable phenotype. Critical for clopidogrel (post-PCI), SSRIs, and PPIs. CPIC Level A recommendation for antiplatelet guidance.
Enter Diplotype from Report
— or select phenotype directly —
Guidelines & Evidence
Clinical Details
Section 1
When to Use
When to Use
Translating CYP2C19 diplotype results from pharmacogenomic testing panels into actionable phenotype categories.
CPIC (Clinical Pharmacogenomics Implementation Consortium) Level A recommendation for clopidogrel.
Section 2
Formula & Logic
CYP2C19 Phenotype Definitions
Phenotype
Activity Score
Common Diplotypes
Frequency (EUR)
Ultrarapid Metaboliser (UM)
> 2.0
*17/*17
~3%
Normal Metaboliser (NM / EM)
1.0–2.0
*1/*1, *1/*17
~35–38%
Intermediate Metaboliser (IM)
0.5–1.0
*1/*2, *1/*3, *2/*17
~26–30%
Poor Metaboliser (PM)
0
*2/*2, *2/*3, *3/*3
~2–5%
Activity Score System
*1 (reference) = 1.0 activity units
*17 (increased function) = 1.5 units
*2 (loss of function) = 0 units
*3 (loss of function) = 0 units
Diplotype activity score = sum of two allele scores
Clinical Implications by Drug Class
Drug
UM
NM
IM/PM
Clopidogrel
Consider dose increase or alternative
Standard dose
Use alternative (ticagrelor/prasugrel)
Citalopram / Escitalopram
Consider dose increase
Standard dose
Reduce dose (PM: lowest dose or alternative)
Amitriptyline / Nortriptyline
Alternative recommended
Standard dose
Reduce dose 25–50% (PM)
Omeprazole / Pantoprazole
May need higher PPI dose
Standard dose
Dose reduction may be warranted (PM)
Voriconazole
May need higher dose
Standard dose
High plasma levels — reduce dose or monitor TDM
Section 3
Pearls/Pitfalls
Key Pearls
IM/PM + clopidogrel post-PCI = significantly increased major adverse cardiovascular events (MACE) compared to NM (OR ~1.5–2.0) — MACE risk reduction with ticagrelor/prasugrel in these patients is guideline-endorsed (CPIC Level A).
CYP2C19 PM is especially prevalent in East Asian populations (~15%) and Oceanian populations (~70%) compared to Europeans (~2–5%).
CYP2C19 *17 (UM) is more prevalent in Ethiopians and Middle Eastern populations (~20%).
Proton pump inhibitors: PMs achieve higher plasma concentrations — may be beneficial for H. pylori eradication but risk of ADEs at standard doses.
Section 4
Next Steps
Clinical Actions by Phenotype
01
CYP2C19 PM or IM taking clopidogrel post-PCI: Switch to ticagrelor (90mg BD) or prasugrel (10mg OD) per CPIC/AHA/ESC guidance; document in pharmacy record.
02
CYP2C19 PM/IM on citalopram/escitalopram: Reduce dose by 50% (PM) or 25% (IM); consider fluvoxamine (not CYP2C19-dependent) as alternative.
03
CYP2C19 UM: Consider dose increases for clopidogrel or PPI therapy where clinical response is suboptimal; ECG monitoring for QTc if on serotonergic agents.
04
All results: Record CYP2C19 diplotype in medication record system; alert future prescribers to pharmacogenomic status.
Section 5
Evidence Appraisal
Primary Reference
Clinical pharmacogenomics implementation consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update
Scott SA et al. • Clinical Pharmacology & Therapeutics. 2013;94(3): 317–323
Section 6
Literature
CYP2C19 Discovery
CYP2C19 was identified as the gene responsible for mephenytoin S-hydroxylation polymorphism in the 1980s. The poor metaboliser phenotype was characterised as a clinically important pharmacogenomic variant before the gene was cloned. The *2 allele (c.681G>A splice variant) was sequenced in 1994.
CPIC Framework
The Clinical Pharmacogenomics Implementation Consortium (CPIC) was founded in 2009 to create standardised, peer-reviewed, expert-curated prescribing guidelines based on pharmacogenomic testing results. CPIC guidelines for CYP2C19 were first published in 2011 (clopidogrel) and have been progressively updated. The CPIC model pioneered the concept of returning pre-emptive pharmacogenomic results before prescribing, adopted by multiple health systems globally.
