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Clinical Trial
. 2005 Mar;59(3):371-4.
doi: 10.1111/j.1365-2125.2004.02199.x.

Paracetamol: a haemorrhagic risk factor in patients on warfarin

I Mahé  1 , N Bertrand, L Drouet, G Simoneau, E Mazoyer, C Bal dit Sollier, C Caulin, J F Bergmann
Affiliations
Clinical Trial

Paracetamol: a haemorrhagic risk factor in patients on warfarin

I Mahé et al. Br J Clin Pharmacol. 2005 Mar.

Abstract

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.

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Figures

Figure 1
Figure 1
Changes in INR over time in patients receiving placebo or paracetamol (4 g per day). # paracetamol therapy was stopped in 3 patients because of 2 consecutive INR measurements above 3.5. There was no treatment interruption during the placebo period. Mean INR ± SD. *p < 0.05, INRji versus INRj0. Placebo n = 11 (○), paracétamol* (□)
Figure 2
Figure 2
Maximal INR variations observed in 11 patients on a stable regimen of warfarin receiving in random order placebo and paracetamol 4 g/d. Base: INR before study treatment; Max: maximal INR on study treatment
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