Drug information of Antithrombin alfa

Antithrombin alfa


Antithrombin Alfa is a recombinant antithrombin , an anticoagulant, that is used for the prevention of thromboembolic events in patients that have hereditary deficiency of antithrombin in high risk situations.

Mechanism of effect

Antithrombin is the main inhibitor of thrombin and Factor Xa , the serine proteases involved in blood coagulation. Antithrombin neutralizes the activity of thrombin and Factor Xa by forming a complex which is rapidly removed from the circulation.

Pharmacodynamic

Hereditary antithrombin deficiency causes an increased risk of venous thromboembolism (VTE). In high risk situations, such as surgery or trauma or for pregnant women during the peri-partum period, the risk of development of VTEs is 10-50 times greater than the general population. In hereditary antithrombin deficient patients antithrombin alfa normalizes plasma antthrombin activity levels during peri-operative and peri-partum periods.

Pharmacokinetics

  • Volume of distribution: Dose of: 50IU/kg: 126.2 ml/kg 100IU/kg: 156.1 ml/kg Vd in hereditary deficient pregnant women in high risk situations had increased Vd of 14.3L.
  • Route of elimination: Irreversible complexes formed between antithrombin III and its target protease are rapidly removed by the liver.
  • Half life: Dose of: 50IU/kg: 11.6 h 100IU/kg: 17.7 h
  • Clearance: Dose of: 50IU/kg: 9.6 ml/hr/kg 100IU/kg: 7.2 ml/hr/kg Cl in hereditary deficient pregnant women in high risk situations had increased Cl of 1.38L/h.
  • Toxicity:Highest dose tested was 360mg/kg/day in rats resulted in transient limb swelling.

Dosage

Pregnant Women

Initiate treatment prior to delivery or approximately 24 hours before surgery; 

Loading dose (units) = [ (100 − baseline antithrombin III activity level) / 1.3] × body weight in kg

Maintenance dose (units/hr) = [ (100 − baseline antithrombin III activity level) / 5.4] × body weight in kg

Nonpregnant Surgical Patients

Initiate treatment approximately 24 hours before surgery; continue until adequate follow-on anticoagulation is established.

Loading dose (units) = [ (100 − baseline antithrombin III activity level) / 2.3] × body weight in kg

Maintenance dose (units/hr) = [ (100 − baseline antithrombin III activity level) / 10.2] × body weight in kg

Drug contraindications

Known hypersensitivity to goat and goat milk proteins.

Side effects

Hemorrhage, infusion site reactions.

Alerts

  • Potential for enhanced anticoagulant effects if used concomitantly with unfractionated heparin, low molecular weight heparin, or other drugs that use antithrombin III to exert their anticoagulant effects.
  • Potential for allergic-type hypersensitivity reactions, including anaphylaxis.
  • Potential for antibody development to antithrombin alfa, goat antithrombin, or goat-milk proteins.

Points of recommendation

  • Risk of allergic-type hypersensitivity reactions; importance of recognizing early manifestations of hypersensitivity (e.g., hives, generalized urticaria, chest tightness, wheezing, hypotension, anaphylaxis) and immediately informing a clinician if any of these signs or symptoms occur.
  • Importance of reporting any previous or current known hypersensitivity to goat or goat milk proteins prior to receiving antithrombin alfa
  • Risk of bleeding with concurrent use of antithrombin alfa and other anticoagulants; importance of informing a clinician if any bleeding occurs during treatment.
  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
  • Importance of informing patients of other important precautionary information.

Pregnancy level

C

Does not appear to be associated with an increased risk of fetal abnormalities when administered during the third trimester. However, use during pregnancy only if clearly indicated.


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