Impact of genetic variation on response to therapy
The SmPC for rabeprazole states that following a 20 mg daily dose of rabeprazole for 7 days, CYP2C19 slow (poor) metabolisers had AUC and t½ which were approximately 1.9 and 1.6 times the corresponding parameters in extensive (normal) metabolisers whilst Cmax had increased by 40%.
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 rabeprazole. CPIC® does not make any recommendations for adjustments to the dose of rabeprazole according to genotype.
For most therapeutic indications the SmPC for rabeprazole 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 rabeprazole 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 metabolisers
Some examples of CYP2C19 genotypes include: *1/*1
- Initiate standard starting dose.
- Monitor for efficacy and titrate according to response.
CYP1C19 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
Like other proton pump inhibitors, rabeprazole is metabolised by CYP450 isoenzymes CYP2C19 and CYP3A4. However, rabeprazole is less dependent on CYP2C19 metabolism and therefore may be less influenced by genetic variability in the CYP2C19 gene compared to first generation proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole.
References
Eisai Ltd (2022) Pariet 20mg gastro-resistant tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/7867/smpc (Accessed online 28 April 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 28 April 2025).
El Rouby, N., Lima, J.J. & Johnson, J.A. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin. Drug Metab. Toxicol. 14, 447–460 (2018).
