Usual Adult Dose for Antithrombin III Deficiency

The dosage of antithrombin recombinant is to be individualized based on the patient's pretreatment functional antithrombin (AT) activity level (expressed in percent of normal) and body weight (expressed in kilograms) and using therapeutic drug monitoring. The goal of treatment is to restore and maintain functional antithrombin (AT) activity levels between 80% - 120% of normal (0.8 - 1.2 International Unit /mL). Treatment should be initiated prior to delivery or approximately 24 hours prior to surgery to ensure that the plasma antithrombin level is in the target range at that time. Treatment should be initiated prior to delivery or approximately 24 hours prior to surgery to ensure that the plasma antithrombin level is in the target range at that time. Administer loading dose as a 15 minute intravenous infusion, immediately followed by a continuous infusion of the maintenance dose. Continue treatment until adequate follow on anticoagulation is established.

Surgical Patients:
loading dose (International Unit)=[(100 - baseline AT activity level)/2.3] x Body Weight (kg)
maintenance Dose (International Unit/hour)=[(100 - baseline AT activity level)/10.2] x Body Weight (kg)

Pregnant Women:
loading dose (International Unit)=[(100 - baseline AT activity level)/1.3] x Body Weight (kg)
maintenance Dose (International Unit/hour)=[(100 - baseline AT activity level)/5.4] x Body Weight (kg)

AT Activity Monitoring and Dose Adjustment
AT activity monitoring is required for proper treatment. Check AT activity once or twice per day

As surgery or delivery may rapidly decrease the AT activity levels, check the AT level just after surgery or delivery. If AT activity level is below 80%, an additional bolus dose may be administered to rapidly restore decreased AT activity level. In such instances, the loading dose formulae in Table 1 should be used, utilizing in the calculation the last available AT activity result. Thereafter, restart the maintenance dose at the same rate of infusion as before the bolus.

2 hours after initiation of treatment:
If the AT Level is less than 80% , increase dose by 30% and recheck AT level 2 hours after each dose adjustment.
If the AT Level is between 80% and 100%, maintain current dose and recheck AT level 6 hours after each dose adjustment.
If the AT Level is greater than 120% , decrease dose by 30% and recheck AT level 2 hours after each dose adjustment.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

Antithrombin recombinant is contraindicated in patients with known hypersensitivity to goat and goat milk proteins.

Allergic-type hypersensitivity reactions are possible. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. If these symptoms occur during administration, treatment must be discontinued immediately and emergency treatment should be administered.

The anticoagulant effect of drugs that use antithrombin to exert their anticoagulation may be altered when antithrombin recombinant is added or withdrawn. To avoid excessive or insufficient anticoagulation, coagulation tests suitable for the anticoagulant used (e.g., aPTT and antifactor Xa activity) are to be performed regularly, at close intervals, and in particular in the first hours following the start or withdrawal of antithrombin recombinant . Additionally, patients should be monitored for the occurrence of bleeding or thrombosis.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available