Antithrombin III dosage and administration
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2]
Dosage and Administration
Eavv ch bottle of THROMBATE III has the functional activity, in international units (IU), stated on the label of the bottle. The potency assignment has been determined with a standard calibrated against a World Health Organization antithrombin III reference preparation.
Dosage should be determined on an individual basis based on the pre-therapy plasma ATIII level, in order to increase plasma ATIII levels to the level found in normal human plasma (80-120%). Dosage of THROMBATE III can be calculated from the following formula:
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The above formula is based on an expected incremental in vivo recovery above baseline levels for Antithrombin III (Human), THROMBATE III® of 1.4% per IU per kg administered.(14) Thus, if a 70 kg individual has a baseline ATIII level of 57%, in order to increase plasma ATIII to 120%, the initial THROMBATE III dose would be [(120–57) × 70]/1.4 = 3150 IU total.
However, recovery may vary, and initially levels should be drawn at baseline and 20 minutes post infusion. Subsequent doses can be calculated based on the level achieved with the first dose. These recommendations are intended only as a guide for therapy. The exact loading dose and maintenance intervals should be individualized for each patient.
It is recommended that following an initial dose of THROMBATE III, plasma levels of ATIII be initially monitored at least every 12 hours and before the next infusion of THROMBATE III to maintain plasma ATIII levels greater than 80%. In some situations, e.g., following surgery,(26) hemorrhage or acute thrombosis, and during intravenous heparin administration,(19,27–29) the half-life of Antithrombin III (Human) has been reported to be shortened. In such conditions, plasma ATIII levels should be monitored more frequently, and THROMBATE III administered as necessary.
When an infusion of THROMBATE III is indicated for a patient with hereditary deficiency to control an acute thrombotic episode or prevent thrombosis during or following surgical or obstetrical procedures, it is desirable to raise the ATIII level to normal and maintain this level for 2 to 8 days, depending on the indication for treatment, type and extent of surgery, patient’s medical condition, past history and physician’s judgment. Concomitant administration of heparin in each of these situations should be based on the medical judgment of the physician.
As a general recommendation, the following therapeutic program may be utilized as a starting program for treatment, modifying the program based on the actual plasma ATIII levels achieved:
- a) An initial loading dose of THROMBATE III calculated to elevate the plasma ATIII level to 120%, assuming an expected rise over the baseline plasma ATIII level of 1.4% (functional activity) per IU per kg of THROMBATE III administered. Thus, for an individual with a body weight of 70 kg and a baseline ATIII level of 57%, the initial THROMBATE III dose would be 3150 IU:
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- b) Measure preinfusion and 20 minutes postinfusion (peak) plasma ATIII levels following the initial loading dose, plasma ATIII level after 12 hours, then preceding the next infusion (trough level). Subsequently measure ATIII levels preceding and 20 minutes after each infusion until predictable peak and trough levels have been achieved, generally between 80%–120%. Plasma levels between 80%–120% may be maintained by administration of maintenance doses of 60% of the initial loading dose, administered every 24 hours. Adjustments in the maintenance dose and/or interval between doses should be made based on actual plasma ATIII levels achieved.
The above recommendations for dosing are provided as a general guideline for therapy only. The exact loading and maintenance dosages and dosing intervals should be individualized for each subject, based on the individual clinical conditions, response to therapy, and actual plasma ATIII levels achieved. In some situations, e.g., following surgery,(26) with hemorrhage or acute thrombosis and during intravenous heparin administration,(19,27–29) in vivo survival of infused THROMBATE III has been reported to be shortened, resulting in the need to administer THROMBATE III more frequently.
Antithrombin III (Human), THROMBATE III is reconstituted with Sterile Water for Injection, USP at room temperature. THROMBATE III should be filtered through a sterile filter needle as supplied in the package prior to use, and should be administered within 3 hours following reconstitution. THROMBATE III may be infused over 10–20 minutes. THROMBATE III must be administered intravenously.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.[1]
References
- ↑ "THROMBATE III (ANTITHROMBIN III) KIT [GRIFOLS USA, LLC]". Retrieved 7 March 2014.
Adapted from the FDA Package Insert.