Impact of genetic variation on response to therapy
Piroxicam 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 piroxicam compared to normal metabolisers. The SmPC for piroxicam 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 piroxicam with caution as they may have abnormally high plasma levels due to reduced metabolic clearance. Piroxicam adverse drug reactions include gastrointestinal bleeding, cardiotoxicity, hypertension, and nephrotoxicity.
Due to its long half-life compared to other commonly used NSAIDs such as ibuprofen, impaired piroxicam metabolism is expected to cause sustained increases in drug exposure. The Clinical Pharmacogenetics Implementation Consortium (CPIC®) reports the plasma half-life of piroxicam as ranging from 30-86 hours.
Testing recommendations
At the time of publication there are no UK recommendations for CYP2C9 genotype testing to guide the use of piroxicam.
Therapeutic recommendations
CYP2C9 metaboliser status unknown
- Initiate treatment with standard dose.
- 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 dose.
- 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.
- Increased plasma concentrations may increase risk of adverse drug reactions.
- Initiate treatment with standard dose.
- 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.
- Sustained increases in plasma concentrations may increase risk and severity of adverse drug reactions.
- Choose an alternative therapy without significant CYP2C9 metabolism or with a shorter half-life.
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.
- Sustained increases in plasma concentrations may increase risk and severity of adverse drug reactions.
- Choose an alternative therapy without significant CYP2C9 metabolism or with a shorter half-life.
Further information
Drug interactions
The impact of drug interactions with piroxicam may be more pronounced in people with reduced CYP2C9 activity. 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 additional risk factors.
Alternative NSAIDs in CYP2C9 intermediate or poor metabolisers
Alternative NSAIDs not known to be significantly impacted by CYP2C9 variation include naproxen, diclofenac and aspirin. NSAIDs metabolised by CYP2C9 but with a shorter half-life include ibuprofen, flurbiprofen and celecoxib. See individual drug monographs for further information.
References
Pfizer Limited (2025). Feldene Melt 20mg Tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/112/smpc Accessed online 16th 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 16th April 2026.
