antithrombin (human)

Absorption: IV administration results in complete bioavailability.

Distribution: 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:

Lactation: Use while breastfeeding only if clearly needed;
Pedi: Safety and effectiveness not established in children;
Geri: Use lower initial dose; consider age-related ↓ in hepatic, renal, or cardiac function, concurrent diseases or other drug therapy.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: flushing

GI: ↑liver enzymes

GU: hematuria

Hemat: hematoma, HEMORRHAGE

MS: hemarthosis

Misc: infusion site reactions, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), noncardiac 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

IV (Adults and Children ): Loading dose (units): [(100 – baseline antithrombin activity)/2.3] × weight (kg); Maintenance infusion (units/hr): [(100 – baseline antithrombin activity)/10.2] × body weight (kg). Goal is to restore/maintain functional antithrombin activity levels between 80–120% of normal antithrombin; antithrombin activity monitoring will determine changes in dosing/infusion rates.

Pregnant Women

IV (Adults and Children ): Loading dose (units): [(100 – baseline antithrombin activity)/1.3] × weight (kg); Maintenance infusion (units/hr): [(100 – baseline antithrombin activity)/5.4] × weight (kg). Goal is to restore/maintain functional antithrombin activity levels between 80–120% of normal; antithrombin activity monitoring will determine changes in dosing/infusion rates.

Availability ⬆ ⬇

Lyophilized powder for injection: 1750 units/vial

Assessment ⬆ ⬇

Monitor for signs/symptoms of bleeding or hemorrhage (weakness, tachycardia, dyspnea, dizziness, pallor, petechiae, fatigue, tarry stools, coffee ground emesis or obvious severe bleeding).
Monitor for signs/symptoms of venous thromboembolism such as pulmonary embolism (chest pain, dyspnea, tachycardia) or deep vein thrombosis (calf pain or tenderness, lower extremity edema, localized warmth or erythema).
Monitor for signs/symptoms of hypersensitivity reactions (rash, urticaria, pruritus, flushing, dizziness, vomiting, abdominal pain) and angioedema (swelling of throat, lips, tongue, or face; dyspnea; wheezing; hoarseness). If reaction occurs, discontinue immediately and provide supportive care.

Lab Test Considerations:

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

Implementation ⬆ ⬇

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

IV Administration:

Intermittent Infusion: Continuous Infusion: Bring vials to room temperature ≤3 hr prior to reconstitution. Reconstitute with 10 mL of 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 vials into syringe for IV administration or add solution to infusion bag containing 0.9% NaCl. Concentration: 100 units/mL. Administer within 8–12 hr of preparation when stored at room temperature.
Rate: Administer loading dose over 15 min; follow immediately with a continuous infusion for administration of maintenance dose. Administer using a 0.22-micron pore-size in-line filter.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of antithrombin human. Do not stop receiving drug without consulting health care provider. If an appointment is missed, reschedule as soon as possible. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
Advise patients and family to call 911 and seek urgent treatment for signs/symptoms of hypersensitivity reactions.
Tell patient to report and seek treatment for signs/symptoms of bleeding (weakness; fast heartbeat; trouble breathing; dizziness; pale skin; tiredness; obvious bleeding in urine, stool, mouth, or nose).
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇