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Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a randomized controlled trial

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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 (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).

Conclusion

Acetaminophen, 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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Fig. 1

Abbreviations

INR:

International normalized ratio

CYP:

Cytochrome P450

AT:

Antithrombin

Gla:

γ-Carboxyglutamate

Gla-OC:

γ-Carboxyglutamate-containing osteocalcin

Glu-OC:

Undercarboxylated osteocalcin

CI:

Confidence interval

NAPQI:

N-acetyl-p-benzo-quinone imine

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Acknowledgements

The study was funded by a grant from Sanofi-Aventis France. The authors are grateful to the laboratory technicians for careful sample processing and analysis.

Conflict of Interest

Professor Jean-François Bergmann received an honorarium and consulting fees from GlaxoSmithKline, Sanofi-Aventis, AstraZeneca, and Novartis Pharmaceuticals. Professor Stéphane Mouly received an honorarium and consulting fees from Sanofi-Aventis, Génévrier, Bristol-Myers Squibb, Glaxo-Smithkline, Lilly Research Laboratories, Gilead, Pfizer, and Lundbeck. The honorarium and consulting fees received from Sanofi-Aventis France were not related to the current study. Although Sanofi-Aventis France funded the study, it was not involved in patient enrolment, data management, data analysis and manuscript writing and submission. The other authors had no conflict of interest to declare.

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Authors and Affiliations

  1. Unité de Recherches Thérapeutiques—Service de Médecine Interne A, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010, Paris, France

    Qian Zhang, Guy Simoneau, Romain Aubourg, Jean-Francois Bergmann & Stéphane Mouly

  2. Institut des Vaisseaux et du Sang, Experimental Thrombosis and Atherosclerosis Research Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Lariboisière Hospital, Paris, France

    Claire Bal-dit-Sollier, Ludovic Drouet, Sandrine Pruvot & Natacha Berge

  3. Laboratory of Pharmacology, AP-HP, Raymond Poincaré Hospital, Garches, France

    Jean-Claude Alvarez

  4. Internal Medicine Department, AP-HP, Louis-Mourier Hospital, Colombes, France

    Isabelle Mahé

Authors
  1. Qian Zhang
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  2. Claire Bal-dit-Sollier
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  3. Ludovic Drouet
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  4. Guy Simoneau
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  5. Jean-Claude Alvarez
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  6. Sandrine Pruvot
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  7. Romain Aubourg
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  8. Natacha Berge
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  9. Jean-Francois Bergmann
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  10. Stéphane Mouly
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  11. Isabelle Mahé
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Corresponding author

Correspondence to Stéphane Mouly.

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Zhang, Q., Bal-dit-Sollier, C., Drouet, L. et al. Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol 67, 309–314 (2011). https://doi.org/10.1007/s00228-010-0975-2

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  • DOI: https://doi.org/10.1007/s00228-010-0975-2

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