- Dosing Chart
- Once or Twice-Daily Dosing?
Protocol for dose titration of Acenocoumarol46
|INR||To current dose of acenocoumarol||INR monitoring|
|<1.3||Add 1 mg/day||Repeat INR after 1 week|
|1.4-2||Add 0.5 mg/day||Repeat INR after 1 week|
|2.1-3||Continue with current dose|
|3.1-3.5||Decrease by 0.5 mg/day||Repeat INR after 1 week|
|3.6-4||Repeat INR after 1 week|
|If INR remains >4||Discontinue therapy|
|If INR <4 on repeated measurement||Follow as above|
INR, international normalized ratio.
Precautions can be Taken in Case of Bleeding Due to High Dose or Adverse Effects
- The INR should be reduced to a safe level (<5) if excessive increase in prothrombin time and/or INR occur without bleeding or prospective surgery
- If serious bleeding is present, the INR should be reduced to 1 as soon as possible
- If elective surgery or urgent surgery is required, the INR can be reduced to 1 to 1.5 at the time of surgery
- INR can be reduced temporarily by withdrawing anticoagulant therapy and, if necessary, administering oral or parenteral vitamin K
- When immediate restoration of clotting factors is necessary for serious overdose or life-threatening bleeding, transfusion of fresh plasma or prothrombin (factor IX) complex concentrate along with vitamin K may be necessary
Owing to the short half-life of acenocoumarol, the reliability of its anticoagulant action following a once-daily administration is often questioned. Earlier studies carried out with acenocoumarol have established that the anticoagulant action of acenocoumarol does not show fluctuations when the drug is administered once-daily.
This debate, i.e., whether acenocoumarol has to be administered once or twice-daily has been put to rest by the study of Mismetti et al. documented that despite the short half-life, the anticoagulant activity of acenocoumarol does not show nycthemeral (day and night variations) when given once-daily.33
Pharmacokinetic and pharmacodynamic variations of acenocoumarol orally administrated either once or twice daily in patients with deep venous thrombosis
Mismetti P et al., Fundam Clin Pharmacol. 1998; 12(6):631-5.
The anticoagulant effects of acenocoumarol with INR, factors VII and X and protein C were assessed in 12 randomly selected hospitalized patients with deep-vein thrombosis, six of them receiving a daily dose of acenocoumarol, the other six receiving twice-daily doses. When the drug effect had been at a steady-state for at least 72 h, five blood samples were drawn per patient over a period of 24 h.
No nycthemeral significant variations were noted for INR, factor X and protein C in the two groups (P > 0.10). Nycthemeral significant variation in factor VII when acenocoumarol was administered once-daily was noted (P = 0.02), but the clinical relevance of factor VII variation at steady-state is uncertain.
In spite of the short pharmacokinetic half-life of acenocoumarol, a stable nycthemeral pharmacodynamic activity was observed after once-daily administration; twice-daily administration of acenocoumarol does not appear to be justified.