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TRETTEN- coagulation factor xiii a-subunit (recombinant)
Novo Nordisk
1 INDICATIONS AND USAGE
TRETTEN, Coagulation Factor XIII A-Subunit (Recombinant), is indicated for routine prophylaxis for bleeding in patients with congenital factor XIII A-subunit deficiency.
TRETTEN is not for use in patients with congenital factor XIII B‑subunit deficiency
2 DOSAGE AND ADMINISTRATION
For intravenous use only.
DOSAGE FORMS AND STRENGTHS
TRETTEN, Coagulation Factor XIII A-Subunit (Recombinant), is available as a white lyophilized powder in single-use vial containing nominally 2500 IU per vial (2000 � 3125 IU) of recombinant coagulation factor XIII A-subunit. The actual amount of TRETTEN in IU is stated on each carton and vial.
After reconstitution with the provided Sterile Water for Injection, each vial contains 667-1042 IU/mL recombinant coagulation factor XIII A-subunit.
DESCRIPTION
TRETTEN, Coagulation Factor XIII A-Subunit (Recombinant), is a recombinant human factor XIII-A2 homodimer composed of two factor XIII (FXIII) A-subunits. The FXIII A-subunit is a 731 amino acid chain with an acetylated N-terminal serine. When FXIII is activated by thrombin, a 37 amino acid peptide is cleaved from the N-terminus of the A‑subunit.
TRETTEN is manufactured as an intracellular, soluble protein in yeast (Saccharomyces cerevisiae) production strain containing the episomal expression vector, pD16. It is subsequently isolated by homogenization of cells and purification by several chromatography steps, including hydrophobic interaction and ion exchange chromatography. No human or animal derived products are used in the manufacturing process.
TRETTEN is supplied as a sterile, white lyophilized powder in a single use vial. Table 1 and Table 2 list the vial content of reconstituted TRETTEN and the diluent, respectively.
Table 1 Content of Reconstituted TRETTEN*
Content
Per Vial *
Function
Coagulation Factor XIII A-Subunit (Recombinant)
2000 - 3125 IU
Active substance
Sodium Chloride
8.70 mg
Stabilizer
Sucrose
174.0 mg
Stabilizer
Polysorbate 20
0.30 mg
Surfactant
L-Histidine
9.30 mg
Buffer
Mechanism of Action
FXIII is the terminal enzyme in the blood coagulation cascade. When activated by thrombin at the site of vessel wall injury, FXIII plays an important role in the maintenance of hemostasis through cross-linking of fibrin and other proteins in the fibrin clot.
In plasma, FXIII circulates as a heterotetramer [A2 B2 ] composed of two FXIII A-subunits and two FXIII B-subunits held together by strong non-covalent interactions. The FXIII A is the catalytic subunit and FXIII B-subunit acts as carrier molecule for the FXIII A-subunit in circulation, and is present in excess in plasma. When FXIII A-subunit is bound to FXIII B-subunit [A2 B2 ] the half-life of the FXIII A-subunit [A2 ] is prolonged. FXIII is a pro-enzyme (protransglutaminase), which is activated by thrombin in the presence of Ca2+. The enzymatic activity resides with the FXIII A-subunit. Upon activation, the FXIII A‑subunit dissociates from the FXIII B-subunit and thereby exposes the active site of the FXIII A-subunit. The active transglutaminase cross-links fibrin and other proteins resulting in increased mechanical strength and resistance to fibrinolysis of the fibrin clot and contributes to enhance platelet and clot adhesion to injured tissue.
Coagulation Factor XIII A-Subunit (Recombinant) is a protransglutaminase (rFXIII [rA2 ] homodimer) and binds to free human FXIII B-subunit resulting in a heterotetramer [rA2 B2 ] with a similar half-life to [A2 B2 ]. 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, Coagulation Factor XIII A-subunit (Recombinant) has been shown to have the same pharmacodynamic properties in plasma as endogenous FXIII.
