title: Simultaneous use of amiodarone influences warfarin maintenance dose but is not associated with adverse events.
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.
authors.affiliation: University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar - São Paulo - SP, Brazil, CEP 05403-000. alexandre.pereira@incor.usp.br; pacaleb@usp.br.
authors.forename: Paulo Caleb Junior Lima
authors.initials: PC
authors.lastname: Santos
authors.forename: Renata Alonso Gadi
authors.initials: RA
authors.lastname: Soares
authors.forename: Celia Maria Cassaro
authors.initials: CM
authors.lastname: Strunz
authors.forename: Max
authors.initials: M
authors.lastname: Grinberg
authors.forename: João Fernando M
authors.initials: JF
authors.lastname: Ferreira
authors.forename: Luiz Antônio Machado
authors.initials: LA
authors.lastname: Cesar
authors.forename: Maurício
authors.initials: M
authors.lastname: Scanavacca
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011517:Prothrombin Time; D012189:Retrospective Studies; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000638:Amiodarone