Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Tretten: 2000 - 3125 units (1 ea)
Pharmacology
Mechanism of Action
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/Pharmacodynamics
Distribution
Vss: ~61–66 mL/kg
Half-Life Elimination
Children (<6 years): ~7 days; Children (≥7 years) and Adults ~ 5 days
Use: Labeled Indications
Factor XIII A-subunit deficiency: Routine prophylaxis of bleeding in patients with congenital factor XIII A-subunit deficiency
Contraindications
Hypersensitivity to coagulation factor XIII A-subunit (recombinant) or any component of the formulation.
Dosage and Administration
Dosing: Adult
Factor XIII A-subunit deficiency: IV: 35 units/kg once monthly to achieve a target trough level of factor XIII activity ≥10%; consider dose adjustment if adequate coverage is not achieved (higher doses may not increase the levels of tetrameric factor XIII).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Infants, Children, and Adolescents: Refer to adult dosing.
Reconstitution
Bring the vial of powder and diluent to room temperature, but not above 25°C (77°F). Reconstitute only with 3.2 mL sterile water (provided); do not inject the diluent directly on the powder to avoid foaming. Gently swirl; do not shake. After reconstitution, each vial contains 667-1042 units/mL recombinant coagulation factor XIII A-subunit. For smaller dose that requires less than the full volume in the vial, reconstituted solution may be diluted with sodium chloride 0.9% to facilitate measurement of small volumes; discard remaining product. Use immediately (or may store at room temperature not to exceed 25°C (77°F) for up to 3 hours).
Administration
IV: Administer IV at a rate not exceeding 1 to 2 mL/minute. Do not administer as a continuous infusion or with other infusion solutions.
Storage
Prior to reconstitution, store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze; protect from light. If the reconstituted solution is not used immediately, store refrigerated or at room temperature not to exceed 25°C (77°F) for up to 3 hours; discard after 3 hours.
Drug Interactions
Factor VIIa (Recombinant): Factor XIII A-Subunit (Recombinant) may enhance the thrombogenic effect of Factor VIIa (Recombinant). Monitor therapy
Adverse Reactions
1% to 10%:
Central nervous system: Headache (≥1%)
Hematologic & oncologic: Increased fibrinolysis (increase in fibrin D dimer levels; ≥1%)
Immunologic: Antibody development (non-neutralizing; 2% to 5%)
Local: Pain at injection site (≥1%)
Neuromuscular & skeletal: Limb pain (≥1%)
Warnings/Precautions
Concerns related to adverse effects:
- Antibody formation: Inhibitory antibodies may occur. Patients with inhibitory antibodies may manifest as an inadequate response to treatment. Factor XIII inhibitory antibodies should be measured when breakthrough bleeding or factor XIII activity levels are suboptimal after apparent adequate dosing.
- Hypersensitivity reactions: May cause allergic reactions; discontinue immediately if signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, hypotension) occur and institute appropriate management.
- Thrombotic events: Thromboembolic complications may occur; monitor patients with known risk factors for thrombosis.
Other Warnings/Precautions:
- Appropriate use: Not indicated for use in patients with congenital factor XIII B-subunit deficiency.
Monitoring Parameters
Factor XIII trough levels; development of factor XIII inhibitory antibodies; hypersensitivity reactions; thrombotic events.
Pregnancy
Pregnancy Considerations
Pregnant patients with factor XIII deficiency may have an increased risk of bleeding following abortion, antenatal procedures, and delivery. There is also a high rate of pregnancy loss without treatment; close surveillance is recommended. Maternal factor XIII concentrations decrease during pregnancy and dosing frequency should be increased. Additional treatment may be needed prior to delivery or procedures. Factor XIII A-Subunit (Recombinant) may be used in patients with a factor XIII A-subunit deficiency (RCOG [Pavord 2017]).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, painful extremities, or injection site pain. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood), dizziness, passing out, severe headache, bruising, or bleeding (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer:Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
