title: Interaction between Warfarin and Linezolid in Patients with Left Ventricular Assist System in Japan.
abstract: OBJECTIVE
  The purpose of this study was to investigate the possible interaction between warfarin and linezolid in patients with a left ventricular assist system (LVAS) for the treatment of severe heart failure.
  
  
  METHODS
  Patients with LVAS who were treated with linezolid for the treatment of infections from January 2003 to March 2013 were identified from medical records. The impact of linezolid on the clotting function, as well as the dose of warfarin during the first 10 days of linezolid therapy, was investigated. The mean prothrombin time-international normalized ratio (PT-INR) and mean doses of warfarin during 7 days before and 10 days after the initiation of linezolid therapy were calculated for individual patients. The PT-INR per mg of WF dose on the previous day (X) was calculated. The warfarin dose, PT-INR, and warfarin sensitivity index (WSI) value before and after the initiation of linezolid were compared to evaluate the impact of linezolid on the effect of warfarin.
  
  
  RESULTS
  Sixteen patients were enrolled in the study. Although the mean PT-INR increased from 3.74 to 4.06, no significant difference was observed (p=0.05). A significant difference was observed in the mean dose of warfarin before and after the initiation of linezolid administration, with a decrease from 3.23 to 2.69 mg/day (p=0.001). In contrast, the mean WSI value significantly increased from 1.37 to 1.82 (p=0.014). After 10 days of linezolid administration, the mean X values increased over the baseline value by 31.7%.
  
  
  CONCLUSIONS
  These findings suggest that co-administration of linezolid results in increased PT-INR in patients with LVAS treated with warfarin.
authors.affiliation: Department of Pharmacy, National Cerebral and Cardiovascular Center, Japan.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Wada
authors.forename: Sachi
authors.initials: S
authors.lastname: Matsuda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuwahara
authors.forename: Haruki
authors.initials: H
authors.lastname: Sunami
authors.forename: Takuma
authors.initials: T
authors.lastname: Sato
authors.forename: Osamu
authors.initials: O
authors.lastname: Seguchi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yanase
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakatani
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Takada
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006353:Heart-Assist Devices; D006801:Humans; D019934:International Normalized Ratio; D007564:Japan; D000069349:Linezolid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011517:Prothrombin Time; D014859:Warfarin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D014859:Warfarin; D000069349:Linezolid