Impact of genetic variation on response to therapy
The SmPC for omeprazole states that the mean AUC was 5 to 10 times higher and the peak plasma concentrations were 3 to 5 times higher in CYP2C19 poor metabolisers than in subjects having a functional CYP2C19 enzyme.
For most therapeutic indications the SmPC for omeprazole 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 lower or higher plasma exposure.
Testing recommendations
At the time of publication, there are no UK recommendations for CYP2C19 genotype testing to guide omeprazole 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
- Predictive of lower plasma exposure than normal metabolisers.
- Increased risk of therapeutic failure.
- Initiate with maximum starting dose.
- Monitor for efficacy and titrate according to response with a low threshold for increasing the dose, particularly for eradication of Helicobacter pylori or severe oesophagitis.
CYP2C19 Rapid metabolisers
Some examples of CYP2C19 genotypes include: *1/*17
- Predictive of lower plasma exposure than normal metabolisers.
- Increased risk of therapeutic failure.
- Initiate standard starting dose.
- Monitor for efficacy and titrate according to response with a low threshold for increasing the dose, particularly for eradication of Helicobacter pylori or severe oesophagitis.
CYP2C19 Normal metabolisers
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
- Predictive of higher plasma exposure than normal metabolisers.
- Increased likelihood of efficacy and potentially toxicity.
- Initiate standard starting dose.
- Monitor efficacy and titrate dose according to response with a low threshold for decreasing the dose, particularly for long-term therapy.
CYP2C19 Poor metabolisers
Some examples of CYP2C19 genotypes include: *2/*2, *3/*3, *2/*3
- Predictive of higher plasma exposure than normal metabolisers.
- Increased likelihood of efficacy and potentially toxicity, particularly with long-term treatment.
- Initiate standard starting dose.
- Monitor efficacy and titrate dose according to response with a low threshold for decreasing the dose, particularly for long-term therapy.
Further information
The major part of omeprazole metabolism is dependent on the cytochrome P450 enzyme CYP2C19, with the remaining part dependent on CYP3A4. There is a potential for drug interactions with inhibitors or inducers of CYP2C19 and with other substrates for CYP2C19. In CYP2C19 poor metabolisers the metabolism of omeprazole is probably mainly catalysed by CYP3A4 and therefore there may be greater potential for interactions with inhibitors or inducers of CYP3A4 in CYP2C19 poor metabolisers. Consult the SmPC for a full list of interactions.
References
Neon Healthcare Ltd (2023) Losec Capsules 10mg SmPC. Available at: https://www.medicines.org.uk/emc/product/1495/smpc (Accessed online 10 September 2024).
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 10 September 2024).
