Drug Interaction Between Paracetamol and Warfarin

Last updated: April 13, 2010
Sponsor: Hopital Lariboisière
Overall Status: Completed

Phase

4

Condition

Pulmonary Embolism

Cardiac Disease

Deep Vein Thrombosis

Treatment

N/A

Clinical Study ID

NCT01104337
INPAWA2-URT
  • Ages > 18
  • All Genders

Study Summary

The objective of this study is to investigate whether paracetamol, given at therapeutic doses (2g/day and 3 g/day), may potentiate the anticoagulant effect of warfarin.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients treated with warfarin (target INR 2 to 3) stable anticoagulation at 2 to 9 mgfor more than 30 days

  • Aged 18 years or older

  • Laboratory values (hemoglobin, blood cell counts, albumin, blood ionogram,complementary hemostasis parameters and aspartate, alanine transaminases (AST andALT))remained within normal limits

Exclusion

Exclusion Criteria:

  • Any treatment change within 7 days before enrollment

  • Any paracetamol intake within the last 14 days

  • Drug allergy Concomitant drug ( 5-fluorouracile, acetylsalicylic acid, non steroidalanti-inflammatory drugs, chloramphenicol, diflunisal, miconazole)

  • St John's wort treatment

  • Pregnancy

Study Design

Total Participants: 45
Study Start date:
March 01, 2007
Estimated Completion Date:
February 28, 2010

Study Description

Paracetamol is recommended as a first-line analgesic and antipyretic therapy in patients receiving short- and long-term oral anticoagulation, especially elderly patient.However,Increased INR was previously observed in patients treated with warfarin and paracetamol given at the maximum recommended dose (4g/day).

To date, the mechanism of this interaction has not been determined.A recent in vitro study suggested that the toxic metabolite N-acetyl-para-benzoquinoneimine (NAPQI) appeared to interfere with vitamin K-dependent γ-carboxylase (VKD-carb) and vitamin K epoxide reductase (VKOR) activites12. The question remaining to be dealt with is whether this in vitro observation can explain the in vivo paracetamol-warfarin interaction. We aim to evaluate the effect of paracetamol at the most widely used doses 2 and 3g/day on INR in stable patients treated with warfarin in a double blind randomized placebo-controlled trial and to identify the mechanism involved in this interaction in vivo.

Connect with a study center

  • Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboière

    Paris, 75010
    France

    Site Not Available

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