Thrombate III

Contraindications

None listed in the FDA approved manufacturing labeling

Cautions

Administer within 3 hr after reconstitution; do not refrigerate after reconstitution

Theoretical risk of blood-borne pathogens as it is a plasma product

Absorption

Plasma Concentrations

Therapeutic target plasma concentrations in patients with congenital antithrombin III deficiency range from 80–120% of values in healthy adults.1 18 23 (See Dosage under Dosage and Administration.) At plasma concentrations ≤70% of normal, increased thrombin generation.4 Supraphysiologic plasma concentrations (e.g., 150–200% of normal) have increased bleeding risk in patients with sepsis and disseminated intravascular coagulation†;11 not known whether supraphysiologic concentrations increase bleeding risk in patients with congenital antithrombin III deficiency.11 23

Distribution

Extent

Distributed into plasma (39%), extravascular space (49%), and vascular endothelial cells (11%).9 11 16

Elimination

Metabolism

<5% metabolized to low molecular weight breakdown products.16

Elimination Route

Complexes of antithrombin III with thrombin or other proteinases cleared principally by liver6 9 and excreted in urine.15 16

Half-life

Biphasic; terminal half-life is approximately 2.5–4.8 days.1 3 4 5 9 11 16 18

Special Populations

Decreased half-life associated with hemorrhage, acute thrombosis, pregnancy, surgery, or concurrent IV heparin therapy.1 4 5 9 16 18 (See Special Populations under Dosage and Administration.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• Tell all of your health care providers that you take Thrombate III. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine is made from human plasma (part of the blood) and may have viruses that may cause disease. This medicine is screened, tested, and treated to lower the chance that it carries an infection. Talk with the doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Thrombate III, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Thrombate III. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Thrombate III.

Review Date: October 4, 2017

Thrombate 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.

Subjects with AT-­III deficiency should be informed about the risk of thrombosis in connection with pregnancy and surgery and about the inheritance of the disease.

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 thromboembolism, 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 Thrombate III of neonates be discussed with an expert on coagulation.11

1. Cohn EJ, Strong LE, Hughes WL Jr, et al: Preparation and properties of serum and plasma proteins. IV. A system for the separation into fractions of the protein and lipoprotein components of biological tissues and fluids. J Am Chem Soc 68(3):459-­75, 1946.
2. Rosenberg RD, Bauer KA, Marcum JA: Antithrombin III “the heparin-­antithrombin system.” Rev Hematol 2:351­-416, 1986.
3. Murano G, Williams L, Miller-­Andersson M: Some properties of antithrombin-­III and its concentration in human plasma. Thromb Res 18(1­2):259­-62, 1980.
4. Rosenberg RD: Action and interactions of antithrombin and heparin. N Engl J Med 292(3):146­-51, 1975.
5. Winter JH, Fenech A, Ridley W, et al: Familial antithrombin III deficiency. Q J Med 51(204):373-­95, 1982.
6. Marciniak E, Farley CH, DeSimone PA: Familial thrombosis due to antithrombin III deficiency. Blood 43(2):219­31, 1974.
7. Thaler E, Lechner K: Antithrombin III deficiency and thromboembolism. Clin Haematol 10(2):369­-90, 1981.
8. Blauhut B, Necek S, Kramar H, et al: Activity of antithrombin III and effect of heparin on coagulation in shock. Thromb Res 19(6):775­-82, 1980.
9. Samson D, Stirling Y, Woolf L, et al: Management of planned pregnancy in a patient with congenital antithrombin III deficiency. Br J Haematol 56(2):243-­9, 1984.
10. Brandt P: Observations during the treatment of antithrombin-­III deficient women with heparin and antithrombin concentrate during pregnancy, parturition, and abortion. Thromb Res 22(1­-2):15­-24, 1981.
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.
12. Schwartz RS, Bauer KA, Rosenberg RD, et al: Clinical experience with antithrombin III concentrate in treatment of congenital and acquired deficiency of antithrombin. Am J Med 87 (Suppl 3B): 53S­-60S, 1989.
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.
14. Knot EAR, de Jong E, ten Cate JW, et al: Purified radiolabeled antithrombin III metabolism in three families with hereditary AT III deficiency: application of a three-­compartment model. Blood 67(1):93-­8, 1986.
15. Tengborn L, Frohm B, Nilsson LE, et al: Antithrombin III concentrate: its catabolism in health and in antithrombin III deficiency. Scand J Clin Lab Invest 41(5):469­-77, 1981.
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):531­5, 1982.
21. Marciniak E, Gockerman JP: Heparin­induced decrease in circulating antithrombin­III. Lancet 2(8038):581­4, 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.
24. Stenland CJ, Lee DC, Brown P, et al. Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma. Transfusion 2002. 42(11):1497­-500.
25. Lee DC, Stenland CJ, Miller JL, et al. A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins. Transfusion 2001. 41(4):449­-55.
26. Lee DC, Stenland CJ, Hartwell RC, et al. Monitoring plasma processing steps with a sensitive Western blot assay for the detection of the prion protein. J Virol Methods 2000. 84(1):77-­89.
27. Cai K, Miller JL, Stenland CJ, et al. Solvent­-dependent precipitation of prion protein. BiochimBiophys Acta 2002. 1597(1):28­-35.

08939599 (Rev. May 2009)

Talecris Biotherapeutics, Inc.
Research Triangle Park,  
NC 27709 USA U.S. License No. 1716

Applies to antithrombin iii: parenteral powder for injection

Side effects include:

Dizziness, chest tightness, nausea, foul taste, chills, cramps, shortness of breath, chest pain, film over eye, lightheadedness, bowel fullness, hives, fever, oozing, hematoma formation.

Antithrombin III (Human), THROMBATE III 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.

STORAGE

THROMBATE III should be stored under refrigeration (2-8°C; 36-46°F). Freezing should be avoided as breakage of the diluent bottle might occur.

CAUTION

Rx only

U.S. federal law prohibits dispensing without prescription.