Case report: dose adjustment of warfarin using genetic information and plasma concentration monitoring

J Clin Pharm Ther. 2014 Jun;39(3):319-21. doi: 10.1111/jcpt.12135. Epub 2014 Feb 25.

Abstract

What is known and objective: Carbamazepine is known to interact with warfarin. We report on a case of this interaction and on its management using the patient's genetic information.

Case summary: The case concerns a 74-year-old Japanese woman with a mood disorder and a central retinal vein occlusion. She was on therapy that included carbamazepine and had started to take warfarin. However, the patient's prothrombin time expressed as the international normalized ratio (PT-INR) was 1·40 despite taking a dose three times higher than the average. The patient's S-warfarin concentration was 0·15 μg/mL and R-warfarin was 0·52 μg/mL. Her cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex, subunit 1 (VKORC1), genotypes were *1/*1 and -1639GA, respectively. The VKORC1 genotype indicated that she would require an even higher dose. We proposed a further increase in dose and the patient's PT-INR rose to 1·99.

What is new and conclusion: The patient required a high warfarin dose because of the VKORC1 genotype, and induction of CYP2C9 by carbamazepine. We improved the patient's pharmacotherapy based on her genetic information.

Keywords: Japanese patient; carbamazepine; cytochrome P450 2C9; pharmacogenetics; pharmacy practice; therapeutic drug monitoring; vitamin K epoxide reductase complex, subunit 1; warfarin.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / pharmacokinetics*
  • Carbamazepine / pharmacology*
  • Cytochrome P-450 CYP2C9 Inducers / pharmacology*
  • Drug Antagonism
  • Female
  • Genotype
  • Humans
  • International Normalized Ratio
  • Pharmacogenetics
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin / administration & dosage*
  • Warfarin / pharmacokinetics*

Substances

  • Anticoagulants
  • Cytochrome P-450 CYP2C9 Inducers
  • Carbamazepine
  • Warfarin
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases