When to recheck International Normalized Ratio (INR) after starting paracetamol (acetaminophen) in patients taking warfarin?

INR Monitoring After Starting Paracetamol in Patients on Warfarin

Patients taking warfarin who start paracetamol (acetaminophen) should have their INR rechecked within 3 days of initiating paracetamol therapy, especially if the dose exceeds 2g/day, due to significant potential for increased anticoagulation effect.

Mechanism and Evidence of Interaction

• Paracetamol co-administration increases INR in a dose-dependent manner, with significant increases observed by day 3 of therapy 1
• In randomized controlled trials, paracetamol at doses of 2-4g/day significantly increased INR values within one week compared to placebo 2, 3
• The interaction appears to involve interference with vitamin K-dependent coagulation factor synthesis, with significant reductions in factors II, VII, IX, and X observed with paracetamol treatment 2
• The risk of developing an INR > 6 increases 10-fold once paracetamol intake exceeds 9.1 grams per week 1

Recommended Monitoring Protocol

For Standard Paracetamol Doses (≤2g/day):

• Check INR within 3-7 days of initiating paracetamol 1, 3
• Continue regular INR monitoring as clinically indicated based on results

For Higher Paracetamol Doses (>2g/day):

• Check INR within 3 days of initiating paracetamol 1, 3
• More frequent monitoring may be required if INR begins to rise
• Consider dose adjustment of warfarin if INR increases significantly

Clinical Considerations

• The magnitude of INR increase appears similar between 2g/day and 3g/day of paracetamol (mean maximal INR increase of 0.70 and 0.67, respectively) 3
• At 4g/day (higher than typically used in clinical practice), paracetamol can cause INR values to reach a mean maximum of 3.45 compared to 2.66 with placebo 2
• The interaction is often underestimated in clinical practice but is clinically significant 2

Management of Elevated INR

• For INR slightly above therapeutic range but <5, consider reducing the daily warfarin dose until the INR returns to therapeutic range 1
• For INR >5, defer any planned procedures and contact the anticoagulation clinic or medical practitioner for advice 1
• For a single out-of-range INR of 0.5 below or above therapeutic range in previously stable patients, consider continuing the current dose and retesting the INR within 1-2 weeks 1

Common Pitfalls and Caveats

• Failure to recognize the interaction between paracetamol and warfarin can lead to excessive anticoagulation and increased bleeding risk 1, 2
• The interaction may be more pronounced in elderly patients or those with hepatic impairment 1
• NSAIDs should be avoided in patients on warfarin due to even greater risk of bleeding compared to paracetamol 1
• Patients should be advised about this interaction and instructed to report any signs of bleeding promptly 1

Remember that close INR monitoring is essential when initiating any medication that may interact with warfarin, including paracetamol, to ensure patient safety and maintain therapeutic anticoagulation levels 1, 2, 3.