Does acetaminophen (paracetamol) interact with warfarin and Trifolium pratense (purple clover) when taken in combination?

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Last updated: May 27, 2025View editorial policy

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From the Guidelines

Acetaminophen can interact with warfarin, potentially increasing the risk of bleeding, and purple clover may also interact with warfarin independently, thereby affecting morbidity, mortality, and quality of life. When considering the interaction between acetaminophen, warfarin, and purple clover, it is essential to prioritize the most recent and highest quality study. According to the study published in 2022 1, herbal supplements can affect oral anticoagulant use, and determining the risks of interactions with these supplements is challenging due to the lack of standardization and quality control. Some key points to consider:

  • Acetaminophen may increase warfarin's anticoagulant effect by inhibiting certain liver enzymes involved in warfarin metabolism, which can elevate INR values and require more frequent monitoring and possible warfarin dose adjustments 1.
  • Purple clover contains natural coumarins and has antiplatelet properties that could further enhance bleeding risk when combined with warfarin.
  • If acetaminophen needs to be taken while on warfarin, it is recommended to limit use to the lowest effective dose for the shortest duration possible, avoid exceeding 2 grams daily, and inform the healthcare provider.
  • It is advisable to avoid purple clover supplements entirely while taking warfarin due to the potential for additive anticoagulant effects.
  • Always consult the healthcare provider before taking any medications or supplements with warfarin, as this can significantly impact patient outcomes in terms of morbidity, mortality, and quality of life.

From the Research

Interaction between Acetaminophen, Warfarin, and Purple Clover

  • There is no direct evidence in the provided studies regarding the interaction between acetaminophen, warfarin, and purple clover.
  • However, it is known that warfarin can interact with various substances, including herbal supplements, and affect its efficacy and increase the risk of bleeding 2.
  • A study on red clover (Trifolium Pratense) reported a case of bleeding disorder in a patient taking red clover, which can cause an increase in international normalized ratio (INR) and bleeding due to its natural coumarin content 3.
  • There is no specific information on purple clover, but it is possible that it may have similar effects as red clover.
  • Warfarin interactions can be pharmacokinetic or pharmacodynamic, and monitoring International Normalised Ratio (INR) levels can help predict potential interactions 2.
  • Bleeding events can also lead to an increase in INR in patients on warfarin, and it is essential to identify the cause of the elevated INR to manage the patient's condition effectively 4, 5.
  • In cases of warfarin-induced hemorrhage, reversal therapies such as Four Factor Prothrombin Complex Concentrate (PCC) or fresh frozen plasma can be used to manage the condition 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Warfarin--indications, risks and drug interactions.

Australian family physician, 2010

Research

[Warfarin treatment and bleeding].

Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2003

Research

Reversal of warfarin-induced hemorrhage in the emergency department.

The western journal of emergency medicine, 2011

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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