Pharmacological Class:
Clotting factor.

Active Ingredient(s):
Coagulation Factor XIII A-Subunit (recombinant) 2000–3125 IU; per vial; lyophilized pwd for IV inj after reconstitution; preservative-free.

Company
Novo Nordisk
Indication(s):
Routine prophylaxis of bleeding in patients with congenital factor XIII (FXIII) A-subunit deficiency. Limitations of use: not for use in patients with congenital factor XIII B-subunit deficiency.

Pharmacology:
FXIII is the terminal enzyme in the blood coagulation cascade. When activated by thrombin at the site of vessel wall injury, FXIII maintains hemostasis through cross-linking of fibrin and other proteins in the fibrin clot.

Activated recombinant FXIII has been shown to increase mechanical strength and resistance to fibrinolysis of the fibrin clot and contributes to enhance platelet and clot adhesion to injured tissue.

Clinical Trials:
The efficacy of Tretten for the prevention of bleeding in patients with congenital FXIII A-subunit deficiency was established in a multicenter, open-label, non-controlled trial over 52 weeks.

The study included 41 subjects ≥6 years old with congenital FXIII A-subunit deficiency confirmed by genotyping. All patients received monthly doses of Tretten at 35 IU/kg. Bleeding episodes that required treatment with a FXIII-containing product were observed to eva luate the efficacy of monthly replacement therapy with Tretten on prevention of bleeding episodes.

During the prophylaxis treatment period with Tretten for all 41 subjects, a mean annual rate of bleeding episodes that required treatment was determined to be 0.14 (95% CI: 0.058–0.332) per subject year. This was a statistically significant reduction from the historic bleeding rate of 1.68 per subject year for on-demand treatment. The age-adjusted rate of bleeding episodes that required treatment during the Tretten treatment period was 0.05 (95% CI: 0.0094–0.2501) per subject year with a model-based estimate corresponding to the mean age of 26.4 years. The mean annual bleeding rate was higher in patients <18 years of age compared to that in adults (0.362 vs. 0.040 bleeds/subject/year).

An ongoing second trial enrolled 34 of the original 41 subjects and an additional 21 new subjects. The mean annual rate of bleeding episodes requiring treatment was determined to be 0.056 per subject year. The age-adjusted rate of bleeding episodes that required treatment during the Tretten treatment period was 0.022 (95% CI: 0.0045, 0.1023) per subject year with a model-based estimate corresponding to a mean age of 29.5 years. The annual mean bleeding rate was higher in patients aged <18 years compared to that in adults (0.127 vs. 0.026 bleeds/subject/year) with some overlap of the respective 95% confidence intervals.

Legal Classification:
Rx
Adults & Children:
Give by IV inj at a rate of max 1–2mL/min. Initially 35 IU/kg once monthly to achieve a target trough FXIII activity level ≥10% using a validated assay. Consider dose adjustment if adequate coverage not achieved. Do not administer with other infusion solutions.

Warnings/Precautions:
Should be initiated under supervision of an experienced physician. Discontinue immediately and treat appropriately if anaphylaxis or hypersensitivity reactions occur. Conditions that predispose to thrombosis; monitor for signs/symptoms of thrombosis after administration. Measure FXIII inhibitory antibody concentrations if expected plasma FXIII activity levels not attained or if breakthrough bleeding occurs. Pregnancy (Category C). Nursing mothers.

Interaction(s)
Thrombosis risk with concomitant factor VIIa; avoid.

Adverse Reaction(s)
Headache, pain in the extremities, injection site pain, increase in fibrin D-dimer levels; hypersensitivity reactions.

How Supplied:
Single-use vials—1 (w. diluent, supplies)

LAST UPDATED:
4/4/2014
http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8664978e-1814-4930-aca5-97a24455f6df&type=display