1 Dosing Considerations The dosage of ANTITHROMBIN III NF, Antithrombin III (human) depends on the cause and severity of AT III deficiency. Antithrombin III activity must be determined for accurate dosage calculation. The normal range of antithrombin III activity in human plasma is between 80% and 120%.
A decrease in activity to below 70% of normal is associated with an increased risk of thrombosis. Individual doses should therefore be large enough to assure that an antithrombin III plasma level of at least 70% of normal is maintained between infusions.
The amount to be administered and the frequency of administration should always be based on the clinical efficacy and laboratory assessment in the individual case. The initial target antithrombin activity depends on the clinical situation.
When the indication for antithrombin substitution is established, the dosage should be sufficient to reach the target antithrombin activity, and to maintain an effective level. Further monitoring of the antithrombin III plasma level at regular intervals may, however, be necessary for a prolonged period of time.
5 days. In congenital Antithrombin III deficiency, dosage should be individualized for each patient taking into account the family history with regard to the thromboembolic events, the actual clinical risk factors, and Antithrombin III plasma levels.
In cases of acute consumption of antithrombin III (DIC), the half life may be reduced to only a few hours. 2 Recommended Dose and Dosage Adjustment Dosage Guidelines For Disseminated Intravascular Coagulation Dosage of ANTITHROMBIN III NF should be based on a determination of the patient's antithrombin III activity prior to therapy and thereafter at intervals of approximately 4 -6 hours.
The initial dose should be large enough to raise the plasma level to normal (80-120%). Additional doses are required whenever the antithrombin III activity has dropped to less than 70%. In patients with an acute consumption of antithrombin III, the dosage calculations can be based on the formula: Dose (in IU1) = [desired ATIII activity (%) - baseline ATIII activity (%)] x body weight (in kg) divided by 1 % Maintenance dosage is also calculated using the formula stated above, except that the 1% is substituted instead, with the actual increase in ATIII activity (in %) produced by 1 IU per kg of body weight, as determined by the measurement of ATIII activity following the administration of the initial dose.
When using ANTITHROMBIN III NF in combination with heparin, it must be taken into account that the anticoagulant effect of heparin is accelerated by antithrombin III (see also 9 DRUG INTERACTIONS). For Other Antithrombin III Defects As a guideline, an initial dose of 1500 IU and a maintenance dose of one half the in itial dose given at 8 to 24 hour intervals is suggested for an average sized adult.
However, the dosage should be adjusted to individual needs, which can only be estimated by determination of the patient's antithrombin III activity at regular intervals. In the absence of acute consumption of AT III, dosage calculations can be based on the formula: Dose (in IU) = [desired ATIII activity (%) - baseline ATIII activity (%)] x body weight (in kg) divided by 2% Maintenance dosage is also calculated using the formula stated above, except that the 2% is substituted instead, with the actual increase in ATIII activity (in %) produced by 1 IU per kg of body weight, as determined by the measurement of ATIII activity following the administration of the initial dose.
3 Reconstitution: ANTITHROMBIN III NF is to be stored in its lyophilized condition and reconstituted immediately before application. Entered vials must not be reused. The product does not contain a preservative and must be handled with aseptic technique to prevent contamination.
P. U. antithrombin III is stated on the label of each vial. 1 IU antithrombin III (as determined w ith a standard calibrated against the 3rd International Standard for ATIII (Human) in Concentrates, Code 06/166) corresponds to the antithrombin III activity present in 1 mL of normal human plasma.
Antithrombin III NF (Antithrombin III (Human)) Page 6 of 19 For reconstitution, proceed as follows: 1. Remove the unopened bottle containing Sterile Water for Injection (diluent) from the refrigerator and allow it warm up to room temperature (not above 37°C, 98°F).
2. Remove caps from the concentrate and diluent bottles to expose central portions of the rubber stoppers (fig. A). 3. Cleanse exposed surface of the rubber stopper with germicidal solution and allow to dry. 4. Using aseptic technique, remove protective covering from one end of the double -ended needle and insert the exposed end through the diluent bottle stopper (fig.
B and C). 5. Remove protective covering from the other end of the double-ended needle, taking care not to touch the exposed end. Invert diluent bottle over the concentrate bottle, then rapidly insert free end of the needle through the concentrate bottle stopper (fig.
D). Diluent will be drawn into the concentrate bottle by vacuum. 6. Disconnect the two bottles by removing the needle from the concentrate bottle stopper (fig. E). Gently agitate or rotate the concentrate bottle until all material is dissolved.
7. Visually inspect the reconstituted product for particulate matter and discolouration prior to administration, whenever solution and container permit. Discard if particulate matter or discolouration exists. 8. Do not use solutions that are cloudy or have deposits.
Do not refrigerate after reconstitution. 4 Administration Administer ANTITHROMBIN III NF only by intravenous injection or infusion . The […]