CYP2C9 and Celecoxib, Flurbiprofen, Ibuprofen

Normal Metabolizer

Clinical Implication

  • Normal CYP2C9 enzyme activity.
  • Normal response expected.

Therapeutic Recommendation

  • Initiate therapy with recommended starting dose.
  • In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.

Intermediate Metabolizer with an enzyme Activity Score of 1.5

Clinical Implication

  • Decreased CYP2C9 enzyme activity.
  • Slightly increased risk of adverse events (e.g., GI bleed, cardiovascular).

Therapeutic Recommendation

  • Initiate therapy with recommended starting dose. For ibuprofen, may consider initiating with a lower starting dose if CYP2C9 genotype includes *2.
  • In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.

Intermediate Metabolizer with an enzyme Activity Score of 1

Clinical Implication

  • Decreased CYP2C9 enzyme activity.
  • Increased risk of adverse events (e.g., GI bleed, cardiovascular).

Therapeutic Recommendation

  • Initiate therapy with lowest starting dose and titrate dose upward to clinical effect or maximum recommended dose with caution. Additional caution should be implemented with ibuprofen if CYP2C9 genotype includes *2.
  • In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.

Poor Metabolizer

Clinical Implication

  • Little to no CYP2C9 enzyme activity.
  • Increased risk of adverse events (e.g., GI bleed, cardiovascular).

Therapeutic Recommendation

  • Initiate therapy with a 25-50% initial dose reduction and titrate slowly, up to 50% of the maximum recommended dose. Allow at least one week between dose titrations.
  • Alternatively, consider an alternate NSAID not metabolized by CYP2C9 (e.g., aspirin, ketorolac, naproxen, and sulindac).
  • In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.

Unable to Genotype or Assay Failure

  • The analysis failed to yield an informative result and thus no genotype is reported.

Unknown Phenotype

  • This individual is carrying at least one allele with uncertain/unknown function and the predicted phenotype cannot be determined at this time.

Reference

  • Theken KN et al. Clin Pharmacol Ther. 2020 Aug;108(2):191-200. PMID: 32189324.

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