Impact of genetic variation on response to therapy
The SmPC for pantoprazole states that after a single-dose administration of 40mg pantoprazole, the mean AUC was approximately 6 times higher in CYP2C19 poor metabolisers than in extensive (normal) metabolisers.
For most therapeutic indications the SmPC for pantoprazole provides a range of doses and recommends individual adjustment according to response or 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 pantoprazole 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.
CYP1C19 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 metabolism of pantoprazole is mainly catalysed by the enzyme CYP2C19. The enzyme CYP3A4 also contributes to the metabolism, and therefore there is potential for interactions with inhibitors or inducers of CYP2C19 and/or CYP3A4. Consult the SmPC for a full list of interactions.
References
Sandoz Ltd (2022) Pantoprazole 20mg gastro-resistant tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/450/smpc (Accessed online 2 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 19 March 2025)
