AimTo quantify the effect of paracetamol on the anticoagulant effect of war farin under normal clinical conditions.
Patients and methodsIn 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.
ResultsIn 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).
ConclusionParacetamol 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.