Adjusting Sintrom (Acenocoumarol) Dose Based on INR Levels
For patients taking Sintrom (acenocoumarol), dose adjustments should follow a structured algorithm based on INR values, with a target therapeutic range of 2.0-3.0 for most indications. 1
INR-Based Dose Adjustment Algorithm
Subtherapeutic INR
Therapeutic INR
- INR 2.0-3.0: No change needed (maintain current dose) 1
Supratherapeutic INR
- INR 3.1-3.5: Decrease dose by 10% 1
- INR >3.5: Hold medication until INR <3.5, then restart at 20% lower dose 1
- INR >10: Hold medication and administer oral vitamin K 1
Management of Extreme INR Values
INR 4.5-10 without bleeding
- Suspend Sintrom for 1-2 doses
- Consider vitamin K 1-2.5 mg orally
- Resume at a lower dose when INR approaches therapeutic range 2
INR >10 without bleeding
- Suspend Sintrom immediately
- Administer vitamin K 2.5-5 mg orally
- Retest INR within 24 hours 2
Major bleeding with elevated INR
- Suspend Sintrom immediately
- Administer vitamin K 10 mg IV and prothrombin complex concentrate
- Monitor INR every 30-60 minutes after reversal agents 2
Practical Considerations
Single Out-of-Range INR
- For patients with previously stable INRs and a single reading 0.5 below or above therapeutic range, continue current dose and retest within 1-2 weeks rather than making immediate adjustments 2
- This approach has been shown to result in similar outcomes to dose adjustments 2
Monitoring Frequency
- After initiating therapy: Check INR frequently until stable (typically every 2-3 days)
- After dose changes: Monitor more frequently until stability is achieved
- Stable patients: Monitor every 4-6 weeks 1
Drug Interactions
- Be vigilant for medications that may interact with acenocoumarol:
Important Considerations
- Acenocoumarol has a shorter half-life than warfarin, potentially leading to more INR fluctuations 5
- For patients with unstable anticoagulation on acenocoumarol, switching to warfarin may improve control (transition factor approximately 1.8) 5
- Pharmacogenetic testing for CYP2C9 and VKORC1 variants has not shown significant improvement in time within therapeutic range over 12 weeks compared to clinical dosing algorithms 6
- Systematic and coordinated management of anticoagulation therapy, including patient education and systematic INR testing, is recommended 1
Pitfalls to Avoid
- Avoid large dose changes (most adjustments should alter weekly dose by 5-20%)
- Don't overlook dietary changes that affect vitamin K intake
- Don't make dose adjustments based on a single out-of-range INR if the patient was previously stable
- Avoid routine bridging with heparin for single subtherapeutic INR values in stable patients 2
- Don't forget to consider patient-specific factors like age, weight, comorbidities, and concomitant medications when adjusting doses