What dose of acenocoumarol should be restarted to achieve a target International Normalized Ratio (INR) of 3 in a patient who previously achieved an INR of 2.5 on 4mg and had an INR of 4.7 on 5mg, and is now at an INR of 0.7 after a 3-day hold?

Acenocoumarol Dosing After INR Overcorrection and Subsequent Hold

Restart acenocoumarol at 3.2 mg daily (20% reduction from the previous stable dose of 4 mg) to achieve a target INR of 3. 1

Understanding the Clinical Situation

This patient's anticoagulation history reveals a clear dose-response relationship:

• 4 mg daily → INR 2.5 (stable therapeutic level)
• 5 mg daily → INR 4.7 (supratherapeutic after one week)
• 3-day hold → INR 0.7 (subtherapeutic rebound)

The INR of 0.7 after a 3-day hold is unusually low and likely represents the nadir effect of acenocoumarol's short half-life (approximately 9 hours), which causes more dramatic fluctuations compared to warfarin 1. This rebound phenomenon is critical to recognize when restarting therapy.

Dosing Strategy to Achieve INR Target of 3

Starting dose calculation:

• The patient was stable at INR 2.5 on 4 mg daily
• Target INR is now 3.0 (20% higher than previous target)
• Apply a 10-20% dose increase from the previously stable dose 1
• Recommended starting dose: 4 mg × 1.2 = 4.8 mg daily, which can be practically administered as 5 mg on alternating days with 4 mg, or more conservatively as 4.4 mg daily (1 tablet + 1/10 tablet)

However, given the patient's demonstrated sensitivity to the 5 mg dose (which caused INR 4.7), a more cautious approach is warranted:

• Start with 4 mg daily initially (the previously stable dose)
• After achieving INR in the 2.0-3.0 range, increase by 10% to reach target of 3.0 2, 1

Critical Monitoring Protocol

Intensive monitoring phase (first 2 weeks):

• Check INR every 2-3 days until two consecutive readings are within target range 1
• Acenocoumarol's short half-life means INR values are heavily influenced by the dose administered 2 days prior to testing 3

Dose adjustment algorithm based on INR results:

• INR 1.1-1.4: Increase dose by 20% 2, 1
• INR 1.5-1.9: Increase dose by 10% 2, 1
• INR 2.0-2.9: Increase dose by 10% to reach target of 3.0 2, 1
• INR 3.0-3.5: Maintain current dose 2
• INR >3.5: Hold until INR <3.5, then restart at 20% lower dose 2, 1

Important Considerations for Acenocoumarol

Avoid uneven dosing patterns:

• Patients taking uneven doses of acenocoumarol (e.g., alternating 1/2 and 1/4 tablet) exhibit significantly greater INR fluctuations compared to uniform daily dosing 3
• If dose adjustments require splitting tablets, maintain the same daily dose rather than alternating between different amounts 3

Acenocoumarol-specific pharmacokinetics:

• The shorter half-life (9 hours vs. 42 hours for warfarin) means dose changes manifest more rapidly but also cause more variability 1
• INR values correlate most strongly with the dose administered 2 days before testing 3
• Interruption timing for acenocoumarol is shorter than warfarin (2-3 days vs. 5 days) due to rapid clearance 2

Transition to Maintenance Phase

Once stable at target INR:

• Reduce monitoring to weekly for 1-2 weeks 1
• If INR remains stable, extend to every 2-4 weeks 1
• Target time in therapeutic range (TTR) >65% for optimal efficacy and safety 1

Common pitfalls to avoid:

• Do not overreact to single INR deviations by making large dose adjustments 4
• Ensure consistent vitamin K intake in diet to minimize fluctuations 1
• Review all concomitant medications, as antibiotics, amiodarone, statins, and NSAIDs can increase INR 1