antithrombin (human)

Antithrombin inhibits thrombin and Factor Xa5, which play major roles in coagulation.
Recombinant antithrombin (AT) replaces antithrombin missing in deficient patients.

Therapeutic effects:

Prevention of clotting in deficient patients.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Enters breast milk; volume of distribution is greater in pregnant patients.

Metabolism/Excretion: Clearance is higher in pregnant patients.

Half-Life: 12–18 hr (dose related).

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	rapid	2 hr	end of infusion

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to goat/goat milk proteins.

Use Cautiously in:

Geri: Use lower initial dose, consider age-related decrease in hepatic, renal, or cardiac function, concurrent diseases or other drug therapy.;
OB: Has been used safely in pregnant women, use only if clearly needed;
Lactation: Use only if clearly needed, enters breast milk;
Pedi: Safety and effectiveness in children have not been established. .

Adv. Reactions/Side Effects ⬆ ⬇

Derm: flushing

GI: abnormal liver function

GU: hematuria

Hemat: hematoma, HEMORRHAGE

Local: infusion site reactions

MS: hemarthosis

Misc: allergic reactions including anaphylaxis, non-cardiac chest pain

Interactions ⬆ ⬇

Drug-drug:

↑anticoagulant effect of heparin and low molecular weight heparin.
Half-life may be altered by concurrent use of anticoagulants that use antithrombin to exert their effect.

Route/Dosage ⬆ ⬇

Surgical patients (dose expressed in International Units (IU)

IV (Adults and Children ): Loading dose as a 15 min infusion: [(100 - baseline AT activity)/ 2.3] x Body Wt (kg) followed by maintenance infusion: [(100 - baseline AT activity)/ 10.2] x Body Wt (kg) per hour. Goal is to restore/maintain functional antithrombin (AT) activity levels between 80% - 120% of normal AT activity monitoring will determine changes in dosing/infusion rates.

Pregnant women (dose expressed in International Units (IU)

IV (Adults and Children ): Loading dose as a 15 min infusion: [(100 – baseline AT activity)/ 1.3] x Body Wt (kg) followed by maintenance infusion: [(100 - baseline AT activity)/ 5.4] x Body Wt (kg) per hour. Goal is to restore/maintain functional antithrombin (AT) activity levels between 80% - 120% of normal. AT activity monitoring will determine changes in dosing/infusion rates.

Availability ⬆ ⬇

Sterile lyophilized powder for reconstitution. : 1750 IU/single dose vial. (

Assessment ⬆ ⬇

Assess for bleeding or thrombosis frequently during therapy.
Assess for signs and symptoms of anaphylaxis (hives, urticaria, chest tightness, wheezing, hypotension) during therapy. If symptoms occur, discontinue infusion and administer supportive treatment.

Lab Test Considerations:

Monitor AT activity once or twice daily, starting 2 hrs after initiation of treatment. If AT level is <80%,↑ dose by 30%. Recheck AT levels 2 hrs after each dose adjustment. If AT level is 80% to 120%, no dose adjustment is required. Recheck AT level 6 hrs after initiation of treatment or dose adjustment. If AT level is >120%, ↓ dose by 30%. Recheck AT levels 2 hrs after each dose adjustment.
- Surgery or delivery may rapidly ↓ AT levels; check AT level just after surgery or delivery. If AT level is <80%, an additional bolus dose may be administered to rapidly restore AT level.
- Monitor coagulation tests (aPTT, anti-Factor Xa activity) at close intervals for anticoagulants used concurrently, especially in first hrs following start or withdrawal of antithrombin human.

Implementation ⬆ ⬇

Initiate therapy prior to delivery or approximately 24 hrs before surgery to ensure plasma antithrombin level is in target range.
Dosing is different for pregnant women and surgical patients. Use dosing formula for pregnant patients for pregnant women who need surgical procedures other than Cesarean sections.

IV Administration:

Intermittent Infusion: Continuous Infusion: Bring vials to room temperature no more than 3 hrs prior to reconstitution. Reconstitute with 10 mL sterile water for injection immediately prior to use. Do not shake. Do not use solutions that are cloudy, discolored or contain particulate matter. Diluent: Draw solution from one or more vials into syringe for IV administration or add solution to infusion bag containing 0.9% NaCl. Concentration: 100 IU/mL.Administer within 8–12 hrs of preparation when stored at room temperature.
Rate: Administer using a 0.22 micron pore-size in-line filter. loading dose as a 15 min infusion. Follow immediately with a continuous infusion of maintenance dose.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇