Warfarin and celecoxib interaction in the setting of cytochrome P450 (CYP2C9) polymorphism with bleeding complication

Postgrad Med J. 2004 Feb;80(940):107-9. doi: 10.1136/pmj.2003.006478.

Abstract

Drug metabolism may be perturbed by genetically determined differences in the metabolic activity of cytochrome P450 enzymes. The authors encountered extensive bleeding in a patient receiving warfarin for anticoagulation after the introduction of celecoxib, an anti-inflammatory drug. As the CYP2C9 enzyme metabolises these drugs, it was determined whether variant alleles were responsible for altering warfarin handling. Genetic analysis established that the patient was a compound heterozygote with CYP2C9*2 and *3 variant alleles, which exhibit lower drug metabolising capacity and enhance susceptibility to drug toxicity.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anticoagulants / adverse effects*
  • Arthralgia / drug therapy
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Celecoxib
  • Cytochrome P-450 CYP2C9
  • Drug Interactions
  • Female
  • Hemorrhage / chemically induced*
  • Humans
  • International Normalized Ratio
  • Polymorphism, Genetic
  • Pyrazoles
  • Sulfonamides / adverse effects*
  • Warfarin / adverse effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticoagulants
  • Pyrazoles
  • Sulfonamides
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Celecoxib