title: Paracetamol: a haemorrhagic risk factor in patients on warfarin.
abstract: OBJECTIVE
  To quantify the effect of paracetamol on the anticoagulant effect of warfarin under normal clinical conditions.
  
  
  METHODS
  In a prospective double-blind, cross-over, placebo-controlled study, 11 patients on stable warfarin therapy received in random order two 14-day regimens of paracetamol 4 g day(-1) or placebo, with a 14-day or more wash-out period in between, time necessary to fulfil the inclusion criteria.
  
  
  RESULTS
  In patients on paracetamol, the mean maximum increase in the International Normalized Ratio (INR) observed was 1.04 +/- 0.55 vs. 0.20 +/- 0.32 in those on placebo (P = 0.003). The mean maximum INR observed was significantly higher with paracetamol than with placebo (3.47 vs. 2.61, P = 0.01). In patients receiving paracetamol, the mean observed INR was significantly increased after 4 days (+ 0.6 +/- 0.6, P < 0.001).
  
  
  CONCLUSIONS
  Paracetamol at 4 g day(-1) induces a significant increase in INR in patients receiving a stable regimen of warfarin, increasing the risk of bleeding associated with warfarin.
authors.affiliation: Unité de Recherches Thérapeutiques, Hopital Lariboisiere, AP-HP, 2 Rue Ambroise Paré, 75010 Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Mahé
authors.forename: N
authors.initials: N
authors.lastname: Bertrand
authors.forename: L
authors.initials: L
authors.lastname: Drouet
authors.forename: G
authors.initials: G
authors.lastname: Simoneau
authors.forename: E
authors.initials: E
authors.lastname: Mazoyer
authors.forename: C
authors.initials: C
authors.lastname: Bal dit Sollier
authors.forename: C
authors.initials: C
authors.lastname: Caulin
authors.forename: J F
authors.initials: JF
authors.lastname: Bergmann
mesh_terms: D000082:Acetaminophen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic; D000925:Anticoagulants / Q000009:adverse effects*; D000075202:Contraindications; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D019934:International Normalized Ratio; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D018712:Analgesics, Non-Narcotic; D000925:Anticoagulants; D000082:Acetaminophen; D014859:Warfarin