Dec 30, 2010 - ... Department, AP-HP, Louis-Mourier Hospital,. Colombes, France. Eur J Clin Pharmacol (2011) 67:309â314. DOI 10.1007/s00228-010-0975-2 ...
Eur J Clin Pharmacol (2011) 67:309–314 DOI 10.1007/s00228-010-0975-2
SHORT COMMUNICATION
Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a randomized controlled trial Qian Zhang & Claire Bal-dit-Sollier & Ludovic Drouet & Guy Simoneau & Jean-Claude Alvarez & Sandrine Pruvot & Romain Aubourg & Natacha Berge & Jean-Francois Bergmann & Stéphane Mouly & Isabelle Mahé
Received: 31 July 2010 / Accepted: 6 December 2010 / Published online: 30 December 2010 # Springer-Verlag 2010
Abstract Purpose We investigated whether acetaminophen, given at 2 g/day and 3 g/day might potentiate the anticoagulant effect of warfarin. Methods Forty-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. Results The 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 (R2 = 0.36, P 0.5 were significantly higher in either acetaminophen group than in the placebo, but there was no significant difference between the two acetaminophen dosing regimens (Table 1). The INR started to significantly increase after 3 days of treatment in patients treated with acetaminophen. Likewise, INRmax ranged from 2.53 with placebo to 3.17 with acetaminophen 2 g/day (Table 1). No relation was observed between age and the extent of INR increase (Spearman rank correlation coefficient, r s = 0.0002, P= 0.72). There was no significant changes in AT, R(−) and S(−) warfarin, and Gla-OC and Glu-OC plasma concentrations over the study period. The mean minimal total factor VII concentration was significantly lower, while no significant difference was observed in the mean minimal total factor II between groups (Table 1). Likewise, there was no significant decrease in factor V in each treatment group. Using stepwise forward and backward multiple regression analysis, INR increase was associated with a decrease in factor II (R2 = 0.36, P < 0.0001), factor VII (R2 = 0.46, P < 0.0001) activities and with an increase
Table 1 Demographic characteristics of the population as well as changes in the international normalized ratio (INR) and clotting factors in each treatment arm Parameters
Demographic characteristics Age (year) Gender (men/women) Body mass index (kg/m2) Baseline warfarin (mg/day) INR Baseline INR INR(max-D1) INR(max) INR D10 Patients with INR(max-D1)>0.5 Clotting factors Factor VII(min) Factor II (min) a
