Coagulation factor xiii a-subunit

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 TRETTEN, Coagulation Factor XIII A-Subunit (Recombinant), is indicated for routine prophylaxis of bleeding in patients with congenital factor XIII A-subunit deficiency. TRETTEN is not for use in patients with congenital factor XIII B‑subunit deficiency.

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 [A 2 B 2 ] 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 [A 2 B 2 ] the half-life of the FXIII A-subunit [A 2 ] is prolonged. FXIII is a pro-enzyme (protransglutaminase), which is activated by thrombin in the presence of Ca 2+. The enzymatic activity resides with the FXIII A-subunit.

For intravenous use only. Dose: • 35 international units per kilogram body weight once monthly to achieve a target trough level of FXIII activity at or above 10% using a validated assay. • Consider dose adjustment if adequate coverage is not achieved with a 35 IU/kg dose. • Once reconstituted, TRETTEN may be diluted with 0.9% sodium chloride to facilitate measurement of small volumes. Rate: Do not exceed 1-2 mL per minute.

TRETTEN is contraindicated in patients who have known hypersensitivity to the active substance or to any of the excipients. Hypersensitivity to the active substance or to any of the excipients.

• Discontinue if allergic or hypersensitivity reactions occur. • Monitor patients for thrombosis. • Analyze for neutralizing antibodies if FXIII activity fails to reach expected levels or if reduced therapeutic effect is observed.

The most common adverse reactions reported in clinical trials (≥1%), were headache, pain in the extremities, injection site pain, and increase in fibrin D dimer levels. The most common adverse reactions reported in the clinical trials (≥1%) were headache, pain in the extremities, injection site pain, D dimer increase.

Thrombosis may occur if TRETTEN is administered concomitantly with factor VIIa. Do not administer TRETTEN with recombinant factor VIIa.

Do not freeze. • Store refrigerated at 2°C – 8°C (36°F – 46°F) prior to reconstitution. Store protected from light. • Use reconstituted TRETTEN within 3 hours. • If the reconstituted product is not used immediately, store the solution refrigerated or at room temperature not to exceed 25°C (77°F) for up to 3 hours following reconstitution.