Impact of genetic variation on response to therapy
Celecoxib metabolism is primarily mediated via CYP2C9 enzymes. The activity of CYP2C9 enzymes is influenced by genetic variation in the CYP2C9 gene which can have an impact on drug exposure and the risk of adverse drug reactions.
CYP2C9 poor metabolisers are expected to have markedly reduced metabolism and an increase in plasma concentrations of celecoxib compared to normal metabolisers. The SmPC for celecoxib states that patients who are known or suspected to be CYP2C9 poor metabolisers based on genotyping or previous experience with other CYP2C9 substrates should be administered celecoxib with caution as the risk of dose-dependent adverse effects is increased. The SmPC advises considering reducing the dose to half the lowest recommended dose. Celecoxib adverse drug reactions include gastrointestinal bleeding, cardiotoxicity, hypertension, and nephrotoxicity.
Testing recommendations
At the time of publication there are no UK recommendations for CYP2C9 genotype testing to guide the use of celecoxib.
Therapeutic recommendations
CYP2C9 metaboliser status unknown
- Initiate treatment with standard starting dose and titrate according to response.
- Use the lowest effective dose for the shortest duration necessary to control symptoms.
CYP2C9 Normal metabolisers: Activity score 2.0
Some examples of CYP2C9 genotypes include: *1/*1
- Initiate treatment with standard starting dose and titrate according to response.
- Use the lowest effective dose for the shortest duration necessary to control symptoms.
CYP2C9 Intermediate metabolisers: Activity score 1.5
Some examples of CYP2C9 genotypes include: *1/*2
- Mildly reduced metabolism compared to normal metabolisers.
- Initiate treatment with standard starting dose and titrate according to response.
- Use the lowest effective dose for the shortest duration necessary to control symptoms.
CYP2C9 Intermediate metabolisers: Activity score 1.0
Some examples of CYP2C9 genotypes include: *1/*3, *2/*2
- Moderately reduced metabolism compared to normal metabolisers. Higher plasma concentrations may increase risk of adverse drug reactions.
- Initiate treatment with lowest recommended starting dose and titrate according to response.
- Use the lowest effective dose for the shortest duration necessary to control symptoms.
CYP2C9 Poor metabolisers: Activity score 0.5 or 0.0
Some examples of CYP2C9 genotypes include: *2/*3, *3/*3
- Greatly reduced metabolism compared to normal metabolisers. Higher plasma concentrations may increase risk and severity of adverse drug reactions.
- If treatment is still indicated, reduce the dose to 50% of therecommended dose, and use for the shortest duration possible to minimise the risk of cardiotoxicity.
- Alternatively, consider a therapy without significant CYP2C9 metabolism, especially if additional risk factors for toxicity are present (see Further information).
Further information
Drug interactions
The impact of drug interactions with celecoxib may be more pronounced in people with reduced CYP2C9 activity. Concomitant treatment with CYP2C9 inhibitors should be avoided in known CYP2C9 poor metabolisers. Consult the SmPC for more detailed information on drug interactions.
Additional risk factors for NSAID toxicity
The impact of genetic variation should be considered alongside additional individual risk factors for adverse drug reactions with NSAIDs, such as older age, drug interactions, and co-morbidities. Consult the SmPC for further details of drug interactions and additional risk factors.
Alternative NSAID in CYP2C9 poor metabolisers
Alternative NSAIDs not known to be significantly impacted by CYP2C9 variation include naproxen, diclofenac and aspirin.
References
Viatris (2026). Celebrex 2000mg capsule SmPC. Available at: https://www.medicines.org.uk/emc/product/2945/smpc Accessed online 14th April 2026.
Clinical Pharmacogenetics Implementation Consortium CPIC® (2020) Guideline for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Available at: https://www.clinpgx.org/guideline/PA166251464 Accessed online 14th April 2026.
