How do I adjust the Sintrom (Acenocoumarol) dose to achieve a therapeutic International Normalized Ratio (INR)?

Adjusting Sintrom (Acenocoumarol) Dose to Achieve Therapeutic INR

For patients on Sintrom (acenocoumarol) therapy, dose adjustments should follow a structured protocol with initial dosing of 0.06-0.20 mg/kg once daily (depending on age) and subsequent adjustments of 10-20% based on INR values to maintain the target therapeutic range. 1

Initial Dosing

Initial dosing of acenocoumarol should be based on age:

• 2 months to 1 year: 0.20 mg/kg once daily

• 1-5 years: 0.09 mg/kg once daily

• 6-10 years: 0.07 mg/kg once daily
• 11-18 years: 0.06 mg/kg once daily
• Adults: Typically start with 2-4 mg for patients at increased bleeding risk 1, 2

Note: Maximum starting dose should not exceed 10 mg.

Maintenance Dosing Algorithm for Target INR 2.0-3.0

INR Value	Recommended Adjustment
1.1-1.4	Increase dose by 20%
1.5-1.9	Increase dose by 10%
2.0-3.0	No change (therapeutic range)
3.1-3.5	Decrease dose by 10%
>3.5	Hold until INR <3.5, then restart at 20% decreased dose
>10	Hold and administer oral vitamin K

1

Monitoring Frequency

The monitoring frequency should be adjusted based on the stability of INR values:

1. Initial phase: Daily to weekly monitoring until stable
2. Transition phase: Weekly to biweekly monitoring
3. Maintenance phase:
   • Monthly for patients with stable INRs for at least 3 months
   • Up to 12 weeks for very stable patients (consistent INRs for >6 months) 1, 2

Management of Out-of-Range INR Values

For Single Out-of-Range INR

For patients with previously stable INRs who have a single out-of-range value:

• INR between 1.7 and 3.3: Evidence suggests no dose adjustment is needed; continue current dose and retest within 1-2 weeks 1
• INR slightly below therapeutic range (1.5-1.9): Consider increasing dose by 10% 1
• INR slightly above therapeutic range (3.1-3.5): Consider decreasing dose by 10% 1

For Severely Out-of-Range INR

• INR >3.5 but <5.0: Hold the next dose and resume at a lower dose (20% reduction) when INR <3.5 1, 2
• INR >10: Hold medication and administer oral vitamin K 1

Special Considerations

1. Drug Interactions: NSAIDs (diclofenac, naproxen, ibuprofen) can significantly increase INR in nearly half of patients on acenocoumarol, with average increases between 1-4 points. Monitor INR more frequently when starting or stopping these medications 3

2. Mechanical Heart Valves: Patients with mechanical heart valves may require higher target INR ranges (2.5-3.5). However, research shows that an INR of 2.0-3.0 combined with antiplatelet therapy may provide adequate protection with lower bleeding risk compared to higher INR targets 4

3. Bleeding Risk: Acenocoumarol has been associated with a higher risk of elevated INR values (≥6) compared to warfarin (0.3 vs 0.07 visits/patient/year) 5

4. Pharmacogenetic Testing: Genotype-guided dosing of acenocoumarol has not been shown to significantly improve the percentage of time in therapeutic INR range over 12 weeks, though it may improve control in the first 4 weeks 6

Common Pitfalls to Avoid

1. Making frequent dose changes for minor INR deviations: For stable patients with a single INR slightly outside the therapeutic range, continuing the current dose is often preferable to making adjustments 1, 2

2. Extending monitoring intervals too quickly: Ensure consistent stability before extending the interval between INR tests 2

3. Neglecting to increase monitoring frequency when introducing factors that may affect acenocoumarol metabolism (new medications, dietary changes) 2

4. Overlooking the impact of compliance issues: Poor adherence can significantly affect INR stability 2

By following this structured approach to Sintrom dose adjustment, you can optimize the time in therapeutic range while minimizing risks of thromboembolism and bleeding.