Paracetamol: a haemorrhagic risk factor in patients on warfarin

Br J Clin Pharmacol. 2005 Mar;59(3):371-4. doi: 10.1111/j.1365-2125.2004.02199.x.


Aim: To quantify the effect of paracetamol on the anticoagulant effect of warfarin under normal clinical conditions.

Patients and 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).

Conclusion: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen*
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Non-Narcotic*
  • Anticoagulants / adverse effects*
  • Contraindications
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Synergism
  • Drug Therapy, Combination
  • Hemorrhage / chemically induced*
  • Humans
  • International Normalized Ratio
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Warfarin / adverse effects*


  • Analgesics, Non-Narcotic
  • Anticoagulants
  • Acetaminophen
  • Warfarin