Simultaneous use of amiodarone influences warfarin maintenance dose but is not associated with adverse events

J Manag Care Spec Pharm. 2014 Apr;20(4):376-81. doi: 10.18553/jmcp.2014.20.4.376.

Abstract

Background: Drug interaction studies selecting patients in a real-life setting are scarce, and most studies to date are characterized by a small sample size.

Objective: To evaluate the effect of amiodarone on warfarin maintenance dose and adverse events in an anticoagulation cohort from a tertiary cardiovascular service.

Methods: This study recruited 866 patients, and oral anticoagulant therapy was monitored by the prothrombin time expressed as the international normalized ratio (INR). Genotyping of CYP2C9*2, CYP2C9*3, and VKORC1 3673 polymorphisms was performed.

Results: Of the 866 patients, 111 (12.8%) were taking amiodarone and warfarin simultaneously, and 514 (59.4%) reached the therapeutic target dose. The warfarin maintenance dose was significantly lower in patients simultaneously using amiodarone (23.8 ± 11.3 mg/wk) compared with other patients (29.5 ± 14.3 mg/wk; P < 0.001). Patients taking amiodarone had higher INR/current dose ratios (0.83 ± 0.04 per mg) compared with patients not using amiodarone (0.71 ± 0.02 per mg, P = 0.001). Adverse event frequency was not different between the groups (P = 0.40). No genotype effect was noted on the odds of bleeding associated with amiodarone use.

Conclusions: Simultaneous use of amiodarone influences warfarin maintenance dose, but is not associated with adverse events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amiodarone / administration & dosage
  • Amiodarone / adverse effects
  • Amiodarone / pharmacology*
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / pharmacology*
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / pharmacology*
  • Cohort Studies
  • Cytochrome P-450 CYP2C9 / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Prothrombin Time
  • Retrospective Studies
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin / administration & dosage
  • Warfarin / adverse effects
  • Warfarin / pharmacology*

Substances

  • Anti-Arrhythmia Agents
  • Anticoagulants
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases
  • Amiodarone