Manufacturer:

CSL Behring, LLC

Pharmacological Class:

Clotting factor.

Active Ingredient(s):

Factor XIII concentrate (human); 1000–1600 units; per vial; pwd for IV inj after reconstitution; preservative-free.

Indication(s):

Routine prophylactic treatment of congenital Factor XIII (FXIII) deficiency.

Pharmacology:

Corifact (FXIII) is an endogenous plasma glycoprotein consisting of two A-subunits and two B-subunits. FXIII circulates in blood and is present in platelets, monocytes, and macrophages. FXIII appears in two forms, a heterotetrameric (A₂B₂) plasma protein with a molecular weight of about 320 kilodaltons and a homodimeric (A₂) cellular form. FXIII is a proenzyme that is activated, in the presence of calcium ion, by thrombin cleavage of the A-subunit to become activated FXIII (FXIIIa). Intracellularly, the homodimeric form of only the A-subunits (A₂) is found. The B-subunits in plasma have no enzymatic activity, and function as carrier molecules for the A-subunits. They stabilize the structure of the A-subunits and protect them from proteolysis.

FXIIIa promotes cross-linking of fibrin during coagulation and is essential to the physiological protection of the clot against fibrinolysis. FXIIIa is a transglutaminase enzyme that catalyzes the cross-linking of the fibrin alpha- and gamma-chains for fibrin stabilization and renders the fibrin clot more elastic and resistant to fibrinolysis. FXIIIa also cross-links alpha2-plasmin inhibitor to the alpha-chain of fibrin, resulting in protection of the fibrin clot from degradation by plasmin. Cross-linked fibrin is the end result of the coagulation cascade, and provides tensile strength to a primary hemostatic platelet plug.

Clinical Trials:

The 12 week, prospective, open-label, multicenter, pharmacokinetic and safety study conducted in 7 females and 7 males with congenital FXIII deficiency (age 5–42 years) evaluated three doses at 40units/kg every 28 days for each subject. Blood sampling before and after infusion for the first two doses was to determine FXIII activity and a complete PK analysis was conducted after the third dose (steady state). FXIII activity levels were determined by the Berichrom activity assay.

Maintaining the FXIII activity trough level between 5% and 20% is predicted to provide a clinical benefit. The clinical benefit will be verified in a post-marketing study to measure the prevention of spontaneous bleeding episodes with routine prophylactic treatment for patients with congenital FXIII deficiency. Dosing will be individualized and adjusted with the objective to maintain FXIII activity trough levels of 5% to 20%.

Legal Classification:

Rx

Adults & Children:

Individualize. Give by slow IV inj at a rate of ≤4mL/min. Initially 40units/kg. Subsequent doses: give every 28 days; adjust ±5units/kg based on trough FXIII activity levels using Berichrom Activity Assay: One trough level of <5%: increase by 5units/kg; trough level of 5–20%: no change; two trough levels of >20%: decrease by 5units/kg; one trough level of >25%: decrease by 5units/kg. Maintain trough FXIII activity level between approximately 5–20%.

Warnings/Precautions:

Contains human plasma; monitor for possible infection transmission. Long-term therapy: consider appropriate vaccination (hepatitis A and B virus). Monitor for development of inhibitory antibodies. Pregnancy (Cat. C). Nursing mothers.

Adverse Reaction(s):

Hypersensitivity reactions (allergy, rash, pruritus, and erythema); discontinue if occurs, chills/rise in temperature, arthralgia, headache, elevated thrombin-antithrombin levels, increased LFTs; immunogenicity, thromboembolic complications.

How Supplied:

Single-use vial—1