"The U.S. Food and Drug Administration is alerting hospitals, health care professionals, and patients of a voluntary recall of all non-expired drug products produced and distributed for sterile use by Abrams Royal Compounding Pharmacy in Dallas, T"...
THROMBATE (antithrombin) III is indicated for the treatment of patients with hereditary antithrombin III deficiency in connection with surgical or obstetrical procedures or when they suffer from thromboembolism.
The diagnosis of hereditary antithrombin III (AT-III) deficiency should be based on a clear family history of venous thrombosis as well as decreased plasma AT-III levels, and the exclusion of acquired deficiency. AT-III in plasma may be measured by amidolytic assays using synthetic chromogenic substrates, by clotting assays, or by immunoassays. The latter does not detect all hereditary AT-III deficiencies.16
The AT-III level in neonates of parents with hereditary AT-III deficiency should be measured immediately after birth. (Fatal neonatal thrombo-embolism, such as aortic thrombi in children of women with hereditary antithrombin III deficiency, has been reported.)17
Plasma levels of AT-III are lower in neonates than adults, averaging approximately 60% in normal term infants.18,19 AT-III levels in premature infants may be much lower.18,19 Low plasma AT-III levels, especially in a premature infant, therefore, do not necessarily indicate hereditary deficiency. It is recommended that testing and treatment with Antithrombin III (Human), THROMBATE III® (antithrombin) of neonates be discussed with an expert on coagulation.11
DOSAGE AND ADMINISTRATION
Each bottle of THROMBATE (antithrombin) 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 antithrombin III (AT-III) level, in order to increase plasma AT-III levels to the level found in normal human plasma (100%). Dosage of THROMBATE (antithrombin) III can be calculated from the following formula:
|units required (IU) =||[desired - baseline AT-III level*] x weight (kg)|
|*expressed as % normal level based on functional AT-III assay|
The above formula is based on an expected incremental in vivo recovery above baseline levels for Antithrombin III (Human), THROMBATE III® (antithrombin) of 1.4% per IU per kg administered.12 Thus, if a 70 kg individual has a baseline AT-III level of 57%, in order to increase plasma AT-III to 120%, the initial THROMBATE (antithrombin) 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 postinfusion. Subsequent doses can be calculated based on the recovery of 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 (antithrombin) III, plasma levels of AT-III be initially monitored at least every 12 hours and before the next infusion of THROMBATE (antithrombin) III to maintain plasma AT-III levels greater than 80%. In some situations, e.g., following surgery,20 hemorrhage or acute thrombosis, and during intravenous heparin administration,13,21–23 the half-life of Antithrombin III (Human) has been reported to be shortened. In such conditions, plasma AT-III levels should be monitored more frequently, and THROMBATE (antithrombin) III administered as necessary.
When an infusion of THROMBATE (antithrombin) III is indicated for a patient with hereditary deficiency to control an acute thrombotic episode or prevent thrombosis following surgical or obstetrical procedures, it is desirable to raise the AT-III 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 AT-III levels achieved:
a)An initial loading dose of THROMBATE (antithrombin) III calculated to elevate the plasma AT-III level to 120%, assuming an expected rise over the baseline plasma AT-III level of 1.4% (functional activity) per IU per kg of THROMBATE (antithrombin) III administered. Thus, if an individual has a baseline AT-III level of 57%, the initial THROMBATE (antithrombin) III dose would be (120–57)/1.4 = 45 IU/kg.
b)Measure preinfusion and 20 minutes postinfusion (peak) plasma antithrombin III levels following the initial loading dose, plasma antithrombin III level after 12 hours, then preceding the next infusion (trough level).
Subsequently measure antithrombin III 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 AT-III 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 AT-III levels achieved. In some situations, e.g., following surgery,20 with hemorrhage or acute thrombosis and during intravenous heparin administration,13,21–23 in vivo survival of infused THROMBATE (antithrombin) III has been reported to be shortened, resulting in the need to administer THROMBATE III more frequently.
Antithrombin III (Human), THROMBATE (antithrombin) III should be reconstituted with Sterile Water for Injection, USP and brought to room temperature prior to administration. THROMBATE (antithrombin) III should be filtered through a sterile filter needle as supplied in the package prior to use, and should be administered within 3hours following reconstitution. THROMBATE III® (antithrombin) may be infused over 10–20 minutes. THROMBATE (antithrombin) 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.
Note: Aseptic technique should be carefully followed. All needles and vial tops that will come into contact with the product to be administered via the intravenous route should not come in contact with any nonsterile surface. Any contaminated needles should be discarded by placing in a puncture-proof container and new equipment should be used.
- After removing all items from the box, warm the sterile water (diluent) to room temperature (25°C, 77°F).
- Remove the plastic flip tops from each vial (Fig. A). Cleanse vial tops (grey stoppers) with alcohol swab and allow surface to dry. After cleaning, do not allow anything to touch the stopper.
- Carefully remove the plastic sheath from the short end of the transfer needle. Insert the exposed needle into the diluent vial to the hub (Fig.B).
- Carefully grip the sheath of the other end of the transfer needle and twist to remove it.
- Invert the diluent vial and insert the attached needle into the concentrate vial at a 45°angle (Fig. C). This will direct the stream of diluent against the wall of the concentrate vial and minimize foaming. The vacuum will draw the diluent into the concentrate vial.*
- When diluent transfer is complete, remove the diluent vial and transfer needle (Fig. D).
- Immediately after adding the diluent, swirl continuously until completely dissolved (Fig. E). Some foaming may occur, but attempt to avoid excessive foaming. The vial should then be visually inspected for particulate matter and discoloration prior to administration.
- Clean the top of the vial of reconstituted THROMBATE (antithrombin) III again with alcohol swab and let surface dry.
- Attach the filter needle (from the package) to sterile syringe. Withdraw the THROMBATE (antithrombin) III solution into the syringe through the filter needle (Fig. F).
- Remove the filter needle from the syringe and replace with an appropriate injection or butterfly needle for administration. Discard filter needle into a puncture-proof container.
- If the same patient is using more than one vial of THROMBATE (antithrombin) III, the contents of multiple vials may be drawn into the same syringe through the filter needles provided.
*If vacuum is lost in the concentrate vial, use a sterile syringe to remove the sterile water from the diluent vial and inject it into the concentrate vial, directing the stream of fluid against the wall of the vial.
A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product is stored properly, that the directions are followed carefully during use, and that the risk of transmitting viruses is carefully weighed before the product is prescribed.
Rate of Administration
The rate of administration should be adapted to the response of the individual patient, but administration of the entire dose in 10 to 20 minutes is generally well tolerated.
Antithrombin III (Human), THROMBATE III® (antithrombin) is supplied in the following single use vials with the potency in international units stated on the label of each vial. A suitable volume of Sterile Water for Injection, USP, a sterile double-ended transfer needle, and a sterile filter needle are provided.
|NDC Number||Approximate Antithrombin III Potency||Diluent|
|13533-603-20||500 IU||10 mL|
|13533-603-30||1000 IU||20 mL|
THROMBATE (antithrombin) III should be stored under refrigeration (2–8°C; 36–46°F). Freezing should be avoided as breakage of the diluent bottle might occur.
11. Hellgren M, Tengborn L, Abildgaard U: Pregnancy in women with congenital antithrombin III deficiency: experience of treatment with heparin and antithrombin. Gynecol Obstet Invest 14(2):127-41, 1982.
13. Collen D, Schetz J, de Cock F, et al: Metabolism of antithrombin III (heparin cofactor) in man: effects of venous thrombosis and of heparin administration. Eur J Clin Invest 7(1):27-35, 1977.
16. Sas G, Blasko G, Banhegyi D, et al: Abnormal antithrombin III (antithrombin III "Budapest") as a cause of familial thrombophilia. Thromb Diath Haemorrh 32(1):105-15, 1974.
17. Bjarke B, Herin P, Blomback M: Neonatal aortic thrombosis. A possible clinical manifestation of congenital antithrombin III deficiency. Acta Paediatr Scand 63:297-301, 1974.
18. Hathaway WE, Bonnar J: Perinatal coagulation. New York, Grune & Stratton, 1978, p.68.
19. Peters M, Jansen E, ten Cate JW, et al: Neonatal antithrombin III. Br J Haematol 58(4):579-87, 1984.
20. Mannucci PM, Boyer C, Wolf M, et al: Treatment of congenital antithrombin III deficiency with concentrates. Br J Haematol 50(3):531-5, 1982.
21. Marciniak E, Gockerman JP: Heparin-induced decrease in circulating antithrombin-III. Lancet2(8038):581-4, 1977.
22. O'Brien JR, Etherington MD: Effect of heparin and warfarin on antithrombin III. Lancet 2(8050):1232, 1977.
23. Kakkar VV, Bentley PG, Scully MF, et al: Antithrombin III and heparin. Lancet 1(8159):103-4, 1980.
Talecris Biotherapeutics, Inc. Research Triangle Park, NC 27709, USA. FDA Rev date: n/a
Last reviewed on RxList: 10/21/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Thrombate Information
- Thrombate Drug Interactions Center: antithrombin iii (human) iv
- Thrombate Side Effects Center
- Thrombate FDA Approved Prescribing Information including Dosage
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.