antithrombin III (heparin cofactor I)
ATnativ, Thrombate III

Available forms
Available by prescription only
Injection: 500 IU, 1,000 IU

Indications and dosages
 Prophylaxis and adjunct treatment of thromboembolism related to hereditary antithrombin III deficiency. Adults, adolescents, and children: Initial dose is individualized to quantity required to increase antithrombin III activity to 120% of normal activity as determined 30 minutes after administration. Usual infusion rate is 50 to 100 IU/minute I.V., not to exceed 100 IU/minute. Dose is calculated based on anticipated 1% increase in plasma antithrombin III activity produced by 1 IU/kg of body weight using the formula:
  Dose = [(desired level - baseline level) × body weight (kg)] ÷ 1.4 kg

 Maintenance dose is individualized to quantity required to increase antithrombin III activity to 80% to 120%. This usually can be achieved with maintenance doses of 60% of the initial loading dose. Adjustments in maintenance dose or dosing interval should be based on actual plasma antithrombin III levels achieved.
 Treatment usually continues for 2 to 8 days except during pregnancy, surgery, or lengthy immobilization, when more prolonged administration may be needed.

Pharmacodynamics
Antithrombotic action: Administration of exogenous antithrombin III corrects hereditary antithrombin III deficiency, normalizing coagulation-inhibiting capability and inhibiting formation of thromboemboli. It also inactivates plasmin but to a lesser extent than the clotting factor.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Binding to epithelium and redistribution into the extravascular compartment removes antithrombin III from the blood. Special receptors on hepatocytes bind antithrombin III clotting factor complexes, rapidly removing them from circulation.
Metabolism: Unknown.
Excretion: Unknown.

Contraindications and precautions
No known contraindications. Use with extreme caution in children and neonates because safety hasn’t been established.

Interactions
Drug-drug. Heparin: Increases anticoagulant effect. Heparin dosage may need to be reduced.

Adverse reactions
CV: vasodilation, lowered blood pressure.
GU: diuresis.

Effects on lab test results
None reported.

Overdose and treatment
No information available. Patients with antithrombin III levels of 150% to 210% were asymptomatic.

Special considerations
 ALERT Prescribing, dispensing, and dosing errors have been reported using the abbreviation IU. Take care to write clearly or spell out if possible.
• Plasma levels of antithrombin III may be measured with clotting assays or amidolytic assays using synthetic chromogenic substrates. Immunoassays may not detect all congenital antithrombin III deficiencies.
• Transmission of viral disease by drug hasn’t been reported to date.
• 1 IU equals the amount of endogenous antithrombin III present in 1 ml of normal human plasma.
• Heparin binds to antithrombin III lysine-binding sites in a 1:1 molar ratio, which results in increased efficacy of heparin.
• Drug isn’t recommended for long-term prophylaxis of thrombotic episodes.
• Reconstitute using 10 ml sterile water (provided), normal saline solution, or D₅W. Don’t shake vial. Further dilution in same diluent solution is acceptable.
• Solutions should be at room temperature for administration and should be used within 3 hours of reconstitution.
• Monitor patient for dyspnea and increased blood pressure if drug is given too rapidly (1,500 IU in 5 minutes).
• Determinations of antithrombin III activity should be performed twice daily until the dosage requirement has stabilized, then performed daily, immediately before dose. Functional assays are preferable because quantitative immunologic test results may be normal despite decreased drug activity.
Breast-feeding patients
• Drug probably doesn’t appear in breast milk because of drug’s large molecular size. No problems have been reported in breast-fed infants.
Pediatric patients
• No specific problems have been reported.
Geriatric patients
• No specific problems have been reported.

Patient education
• Reassure patient that risk of HIV transmission is extremely low.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use