Impact of genetic variation on response to therapy
The SmPC for esomeprazole states that after repeated once-daily administration of 40mg esomeprazole, the mean AUC was approximately 100% higher and mean peak plasma concentrations were approximately 60% higher in CYP2C19 poor metabolisers than in subjects having a functional CYP2C19 enzyme.
A review of the evidence linking genetic variability to variability in drug-related phenotypes by the Clinical Pharmacogenetics Implementation Consortium (CPIC®) identified inconsistent findings regarding the effect of CYP2C19 genotype on the pharmacokinetics and therapeutic response to esomeprazole. CPIC® does not make any recommendations for adjustments to the dose of esomeprazole according to genotype.
For most therapeutic indications the SmPC for esomeprazole provides a range of doses and recommends individual adjustment according to response and indication. Knowledge of a patient’s CYP2C19 metaboliser phenotype may help guide this by identifying patients with genotypes predictive of higher plasma exposure.
Testing recommendations
At the time of publication, there are no UK recommendations for CYP2C19 genotype testing to guide esomeprazole dosing.
Therapeutic recommendations
CYP2C19 metaboliser status unknown
- Initiate standard starting dose.
- Monitor for efficacy and titrate according to response.
CYP2C19 Ultra-rapid metabolisers
Some examples of CYP2C19 genotypes include: *17/*17
- Initiate standard starting dose.
- Monitor for efficacy and titrate according to response.
CYP2C19 Rapid metabolisers
Some examples of CYP2C19 genotypes include: *1/*17
- Initiate standard starting dose.
- Monitor for efficacy and titrate according to response.
CYP2C19 Normal or unknown metaboliser status
Some examples of CYP2C19 genotypes include: *1/*1
- Initiate standard starting dose.
- Monitor for efficacy and titrate according to response.
CYP2C19 Intermediate metabolisers
Some examples of CYP2C19 genotypes include: *1/*2, *1/*3, *2/*17, *3/*17
- Initiate standard starting dose.
- Monitor for efficacy and titrate according to response.
CYP2C19 Poor metabolisers
Some examples of CYP2C19 genotypes include: *2/*2, *3/*3, *2/*3
- Predictive of higher plasma exposure than normal metabolisers.
- Initiate standard starting dose.
- Monitor for efficacy and titrate according to response.
Further information
The major part of esomeprazole metabolism is dependent on CYP2C19 with the remaining part dependent on CYP3A4. Esomeprazole is also a CYP2C19 inhibitor. Therefore, there is potential for interactions with inhibitors, inducers, or substrates of CYP2C19 and/or CYP3A4. Consult the SmPC for a full list of interactions.
References
AstraZeneca UK Ltd (2023) Nexium 20mg gastro-resistant tablets SmPC Capsules 10mg. Available at: https://www.medicines.org.uk/emc/product/4657/smpc (Accessed online 28 January 2025).
Clinical Pharmacogenetics Implementation Consortium CPIC® (2020) Guideline for Proton Pump Inhibitors and CYP2C19. Available at: https://cpicpgx.org/guidelines/cpic-guideline-for-proton-pump-inhibitors-and-cyp2c19/ (Accessed online 19 March 2025)
