title: An observational study examining the impact of capecitabine on warfarin antithrombotic activity and bleeding complications.
abstract: OBJECTIVE
  The objectives of this study are to quantify the frequency of concomitant use of capecitabine and warfarin, and to quantify the rate of bleeding events and elevated international normalized ratio (INR) among concomitant users of warfarin and capecitabine.
  
  
  METHODS
  We conducted a retrospective population-based study within the Henry Ford Health System (Detroit, MI) and the Kaiser Permanente Medical Care Program of Northern California (Oakland, CA). The study population included patients prescribed concomitant capecitabine and warfarin from 1 April 1997 through 31 July 2002. Data from the medical records of concurrent users were extracted through 31 August 2002.
  
  
  METHODS
  Concomitant use of capecitabine and warfarin, bleeding events, and INR laboratory results, collected from computerized databases and medical record review.
  
  
  RESULTS
  Overall, 11% of capecitabine users also received warfarin (99 / 883). Among 17 patients who received warfarin for venous access device prophylaxis, one bleeding event occurred during concomitant capecitabine/warfarin use (rate = 35.7 bleeding events per 100 person-years, 95% confidence interval [CI] 0.9-198.9), and no events occurred during use of warfarin alone (95% CI 0.0-136.2) (p = 0.50). Among patients prescribed warfarin for indications other than port prophylaxis, no bleeding events occurred during concomitant use of capecitabine and warfarin (95% CI 0.0-34.6), and one event occurred during warfarin use alone (rate = 9.2 bleeding events per 100 person-years, 95% CI 0.2-51.3) (p = 0.54). We found one INR elevation > 3.0 among concomitant capecitabine/warfarin users receiving warfarin for port prophylaxis (rate = 35.7 per 100 person-years) and no INR elevations > 3.0 during use of warfarin alone (p = 0.46). Among patients using warfarin for indications other than port prophylaxis, the rates of INR > 3.0 were 309.7 per 100 person-years (95% CI 213.2-434.9) during concomitant capecitabine/warfarin use and 193.5 events per 100 person-years (95% CI 119.8-295.8) during use of warfarin alone (p = 0.09).
  
  
  CONCLUSIONS
  The results of our study show a low prevalence of capecitabine and warfarin concomitant use. We did not find large differences in the rates of bleeding events and elevated INR in patients receiving concomitant capecitabine and warfarin when compared with use of warfarin alone. While these results do not imply a lack of biologic interaction, our findings indicate that patients appear to be appropriately managed in clinical practice.
authors.affiliation: Josephine Ford Cancer Center, Henry Ford Health System, Detroit, MI, USA. muyood@muyood.com
authors.forename: Marianne Ulcickas
authors.initials: MU
authors.lastname: Yood
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.forename: Sharon Hensley
authors.initials: SH
authors.lastname: Alford
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Tsai
authors.forename: Karen E
authors.initials: KE
authors.lastname: Wells
authors.forename: Steven M
authors.initials: SM
authors.lastname: Yood
authors.forename: Susan P
authors.initials: SP
authors.lastname: Ackermann Shiff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D000069287:Capecitabine; D015331:Cohort Studies; D000075202:Contraindications; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008485:Medical Audit; D008824:Michigan; D008875:Middle Aged; D017060:Patient Satisfaction; D012189:Retrospective Studies; D014859:Warfarin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D003841:Deoxycytidine; D014859:Warfarin; D000069287:Capecitabine; D005472:Fluorouracil