title: Effect of oseltamivir treatment on anticoagulation: a cross-over study in warfarinized patients.
abstract: OBJECTIVE
  To investigate whether oseltamivir enhances the anticoagulant effect of warfarin and to evaluate any pharmacokinetic (PK) interaction between the agents.
  
  
  METHODS
  Twenty volunteers (mean age 62 years) receiving daily warfarin and with INR values of 2.0-3.5 during the previous 2 weeks were randomized to concomitant oseltamivir 75 mg twice daily for 4.5 days or warfarin alone in a two-way cross-over design with a 4-8 day wash-out. Anticoagulant effects were assessed by calculating overall [AUEC(0,96 h)] and observed maximum effect (E(max) ) increase from baseline in INR, decrease from baseline in factor VIIa, and change in vitamin K₁ concentrations. Plasma pharmacokinetics of (R)- and (S)-warfarin and oseltamivir were also assessed.
  
  
  RESULTS
  For both treatments, changes in INR and factor VIIa during treatment were small; for net AUEC(0,96 h), least square mean values were -9.53 (oseltamivir + warfarin) and -1.69 h (warfarin alone) for INR (difference -7.84 h, 90% CI -18.86, 3.17 h), and 1.56 and 0.54 kIU l⁻¹ h, respectively, for factor VIIa (difference, 1.01 kIU l⁻¹ h; 90% CI -1.18, 3.21). Differences between the treatments in E(max) increase from baseline for INR, decrease from baseline for factor VIIa and change from baseline in vitamin K₁ concentration were not statistically significant. Oseltamivir did not alter warfarin pharmacokinetics. Oseltamivir was well tolerated in this study with no clinically significant adverse safety findings.
  
  
  CONCLUSIONS
  Concomitant administration of oseltamivir for 4.5 days to volunteers on daily warfarin had little or no effect on warfarin pharmacokinetics and no effect on pharmacodynamics.
authors.affiliation: Hoffmann-La Roche Inc., Nutley, NJ, USA. brian.davies@roche.com
authors.forename: Brian E
authors.initials: BE
authors.lastname: Davies
authors.forename: Pau
authors.initials: P
authors.lastname: Aceves Baldó
authors.forename: Sian
authors.initials: S
authors.lastname: Lennon-Chrimes
authors.forename: Mike
authors.initials: M
authors.lastname: Brewster
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000097:blood / Q000494:pharmacology*; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004347:Drug Interactions; D015942:Factor VIIa / Q000378:metabolism; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D010837:Vitamin K 1 / Q000097:blood; D014859:Warfarin / Q000097:blood / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D000998:Antiviral Agents; D053139:Oseltamivir; D014859:Warfarin; D010837:Vitamin K 1; D015942:Factor VIIa