Drug information of Factor XIII

Factor XIII

Drug group:

Brand drugs:Catridecacog . Corifact

Factor XIII (human) is a heat-treated, lyophilized concentrate of coagulation factor XIII, an endogenous enzyme responsible for the crosslinking of fibrin and an essential component of the coagulation cascade . For people with congenital deficiency or mutation of Factor XIII, a rare bleeding disorder, exogenous replacement of this key coagulation factor is essential for management and prevention of bleeding episodes.

Also known as Fibrin Stabilizing Factor (FSF), Factor XIII is an endogenously produced coagulation factor and the final enzyme within the blood coagulation cascade. Within the body, FXIII circulates as a heterotetramer composed of 2 A-subunits and 2 B-subunits (A2B2). When activated by thrombin at the site of injury, the FXIII pro-enzyme is cleaved resulting in activation of the catalytic A-subunit and dissociation from its carrier B-subunit. As a result, the active transglutaminase from subunit A cross-links fibrin and other proteins resulting in increased mechanical strength and resistance to fibrinolysis of the fibrin clot. This contributes to enhanced platelet and clot adhesion to injured tissue, thereby improving blood coagulation and maintenance of hemostasis 1.

Other drug products with similar structure and function to Factor XIII (human) include Catridecacog, which is a recombinant form of the A subunit of human coagulation factor XIII. Compared to Factor XIII (human), which is purified from pooled human plasma, Catridecacog is produced through recombinant DNA technology where the target protein is grown in yeast and then isolated .

Factor XIII (Human), available as the commercially available product Corifact, is approved by the Food and Drug Administration for routine prophylactic treatment and peri-operative management of surgical bleeding in adult and pediatric patients with congenital FXIII deficiency . As the half-life of endogenous Factor XIII is long (5-11 days), prophylactic therapy with the replacement of FXIII can be given every 4-6 to maintain hemostasis

Drug forms
  • Factor XIII A-subunit, recombinant 2000-3125 IU/vial
  • factor XIII concentrate, human 1000-1600 units/single-use vial

Mechanism of effect

Temporarily replaces missing clotting factor XIII which corrects and/or prevents bleeding

Factor XIII is a proenzyme activated by calcium ion, by thrombin cleavage of the A-subunit to become activated factor XIII (FXIIIa); promotes cross-linking of fibrin during coagulation and is essential to the physiological protection of the clot against fibrinolysis

Pharmacodynamic

Factor XIII A-Subunit (recombinant) is a protransglutaminase (rFXIII [rA2] homodimer) and binds to free human FXIII B-subunit resulting in a heterotetramer [rA2B2]. rFXIII has been shown to be activated by thrombin in the presence of Ca2+. Activated rFXIII has been shown in dose-dependent manner to increase mechanical strength of fibrin clots, retard fibrinolysis, and rFXIII has been shown to enhance platelet adhesion to the site of injury. After combining with available plasma B-subunits, factor XIII A-subunit (recombinant) has been shown to have the same pharmacodynamic properties in plasma as endogenous FXIII.

Pharmacokinetics

Half-Life: 6.6 ± 2.29 days

Vd: 51.1 ± 12.61 mL/kg

Peak Plasma Time: 1.7 ± 1.44 hr

Clearance: 0.25 mL/hr/kg

Dosage

CORTIFACT(R):
Initial dose: 40 international units/kg intravenously
Maximum rate: 4 mL/min
-Adjust dose up or down 5 international units/kg to maintain 5 to 20% trough factor XIII levels.

Routine prophylaxis: administer every 28 days

Perioperative management of surgical bleeding:
-Individualize dose based on factor XIII activity level, type of surgery, and clinical response.
-Monitor factor XIII levels during and after surgery.

TRETTEN(R):
Routine prophylaxis:
Initial dose: 35 international units/kg intravenously
Maximum rate: 1 to 2 mL/min
-Consider dose adjustment if adequate coverage is not achieved at the initial dose.
-Not for use in congenital factor XIII B-subunit deficiency.

Interactions

Factor VII , carfilzomib

Alerts

Contraindications

Contraindicated in patients with known anaphylactic or severe systemic reactions to human plasma-derived products or to any components in the formulation

Cautions

For IV use only

Hypersensitivity

Development of inhibitory antibodies against factor XIII has been detected; monitor for signs and symptoms of inadequate response to treatment (ie, inadequate factor XIII levels, breakthrough bleeding)

Increased risk of thromboembolic complications; assess benefits and risks of therapy in patients with hypercoagulable conditions (eg, pregnancy)

Made from human blood and may carry a risk of transmitting infectious agents (eg, viruses, and theoretically Creutzfeldt-Jakob disease [CJD] agent)

Points of recommendation

IV Preparation

IV infusion

Prior to reconstitution, allow Corifact and the supplied diluent to reach room temperature

Use the Mix2VialTM system as directed with provided diluent (ie, 20 mL of sterile water for injection)

Do not shake the vial to reconstitute – gently swirl until the powder is completely dissolved

IV Administration

Infuse through a separate infusion line; Y-site administration not advised

Infuse at a rate not to exceed 4 mL/min

Administer within 4 hr of reconstitution

Storage

Unreconstituted product

  • Store in a refrigerator at 2-8°C (36-46°F) – stable for up to 24 months within the expiration date
  • Can be stored at room temperature not to exceed 25°C (77°F) for up to 6 months within the expiration date; do not return product to refrigerator after stored at room temperature (clearly mark beginning date of room temperature storage)
  • Do not freeze
  • Protect from light

Reconstituted product

  • Contains no preservatives
  • Product must be used within 4 hr after reconstitution
  • Do not refrigerate or freeze the reconstituted solution
  • Discard partially used vials

Pregnancy level

C

Benefits and risks should be carefully assessed in pregnant women because of their hypercoagulable state and potential for increased risk of thromboembolic events

Breast feeding warning

Unknown if distributed in breast milk, caution advised

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