• Qian Zhang, Claire Bal-dit-Sollier, Ludovic Drouet, Guy Simoneau, Jean-Claude Alvarez, Sandrine Pruvot, Romain Aubourg, Natacha Berge, Jean-Francois Bergmann, Stéphane Mouly, and Isabelle Mahé.
• Unité de Recherches Thérapeutiques-Service de Médecine Interne A, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010, Paris, France.
• Eur. J. Clin. Pharmacol. 2011 Mar 1;67(3):309-14.

PurposeWe investigated whether acetaminophen, given at 2 g/day and 3 g/day might potentiate the anticoagulant effect of warfarin.MethodsForty-five patients on stable warfarin therapy, enrolled in this prospective, randomized, parallel (three arms), placebo-controlled study, received a 10-day regimen of acetaminophen (2 g/day or 3 g/day) or placebo.ResultsThe mean maximal INR increase was 0.70 ± 0.49 and 0.67 ± 0.62 in patients receiving acetaminophen at 2 g/day and 3 g/day, respectively (P=0.01 for the respective comparisons versus placebo). The INR increase became significant on day 3 and was independently and significantly predicted by a maximal decrease in factor II (R(2)=0.36, P<0.0001), factor VII (R (2)=0.46, P<0.0001) and a maximal increase in acetaminophen plasma concentrations (R(2)=0.563, P<0.0001).ConclusionAcetaminophen, at 2 g/day or 3 g/day, enhanced the anticoagulant effect of warfarin in stable patients, thus requiring close INR monitoring in the clinical setting.

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