Celecoxib is primarily metabolized by the CYP2C9 enyzme, with CYP3A4 playing a minor role. Individuals who carry CYP2C9 alleles leading to poor metabolization of CYP2C9 substrates (for example, CYP2C9*3 allele carriers) will have greatly increased exposure to celecoxib. Drugs that inhibit CYP2C9 (such as fluconazole) should also be used with caution in patients taking celecoxib since CYP2C9 is its major route of metabolism. Furthermore, celecoxib is a CYP2D6 inhibitor, so drugs that are metabolized by CYP2D6 (eg. Metoprolol) should be used with caution in patients also taking celecoxib.
Roughly 10% of the population carries a variant affecting celecoxib metabolism. Patients who are known or suspected to be CYP2C9 poor metabolizers should be administered celecoxib with caution as they may develop abnormally high plasma levels due to their reduced metabolic clearance.[PMID 26857349]
- rs1057910: PharmGKB level 2A annotation regarding toxicity & dosage; CPIC level B; FDA Actionable PGx labelling