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Paracetamol: a haemorrhagic risk factor in patients on warfarin
1Unité de Recherches Thérapeutiques, Hopital Lariboisiere, AP-HP, 2 Rue Ambroise Paré, 75010 Paris, France.
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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