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Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study
Isabelle Mahé1, Nathalie Bertrand, Ludovic Drouet
1Unité de Recherches Thérapeutiques, Hôpital Lariboisière, 2, rue Ambroise Paré, 75010 Paris, France. isabelle.mahe@lrb.aphp.fr
Haematologica
|December 6, 2006
Summary
Paracetamol (acetaminophen) significantly increases warfarin
Area of Science:
- Pharmacology
- Clinical Medicine
- Drug Interactions
Background:
- Paracetamol (acetaminophen) is a common analgesic.
- Potential interactions between paracetamol and warfarin have been anecdotally reported.
- The clinical significance of paracetamol's effect on warfarin anticoagulation requires elucidation.
Purpose of the Study:
- To investigate if paracetamol initiation potentiates the anticoagulant effect of warfarin.
- To explore the underlying mechanism of the paracetamol-warfarin interaction.
Main Methods:
- A double-blind, placebo-controlled, randomized cross-over study was conducted.
- Twenty patients on stable warfarin therapy received either placebo or paracetamol (1g four times daily) for 14 days.
- International Normalized Ratio (INR) and clotting factor activities were monitored throughout the study.
Main Results:
- Paracetamol significantly increased mean INR values compared to placebo within one week (p=0.0002).
- Mean maximum INR was 3.45 with paracetamol versus 2.66 with placebo (p=0.03).
- Paracetamol treatment led to significant reductions in vitamin K-dependent clotting factors II, VII, IX, and X.
Conclusions:
- Paracetamol (at 4g daily) potentiates warfarin's anticoagulant response.
- The interaction is likely due to paracetamol or its metabolites interfering with vitamin K-dependent coagulation factor synthesis.
- This clinically significant interaction between paracetamol and warfarin is underestimated and warrants clinical awareness.
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