Introduction

Biosynthetic (recombinant DNA origin) preparation of human factor XIII A₂ homodimer consisting of 2 factor XIII A-subunits.

Uses for Factor XIII A-Subunit (Recombinant)

Congenital Factor XIII A-subunit Deficiency

Routine prophylaxis of bleeding in patients with congenital factor XIII A-subunit deficiency; designated an orphan drug by FDA for such use.

Prophylactic therapy with factor XIII concentrate is recommended in all patients with severe (<1% factor XIII activity) deficiency; considered current standard of care.

Factor XIII concentrate currently available in the US as a plasma-derived (Corifact) and a recombinant (Tretten) preparation. Some experts recommend preferential use of recombinant preparations because of potentially superior safety profile with respect to pathogen transmission. When selecting an appropriate factor XIII preparation, consider characteristics of each clotting factor concentrate in addition to individual patient variables.

Not effective and should not be used in patients with factor XIII B-subunit deficiency.

Factor XIII A-Subunit (Recombinant) Dosage and Administration

Administration

IV Administration

Administer by slow IV injection. (See Rate of Administration under Dosage and Administration.) Do not administer by continuous IV infusion.

Initiate therapy under supervision of a clinician experienced in the treatment of rare bleeding disorders. May be self-administered in the home setting after appropriate training provided.

Do not administer in the same IV line with other infusion solutions.

Reconstitution

Reconstitute lyophilized drug with sterile water for injection provided by manufacturer. Prior to reconstitution, allow drug vial and diluent to warm to (but not exceed) room temperature (25°C). To avoid foaming, do not inject diluent directly onto powder. Gently swirl vial; do not shake. Resulting solution should be clear and colorless; discard if particulate matter or discoloration observed.

May dilute solution with 0.9% sodium chloride injection to facilitate measurement of small doses (volumes) for administration.

Administer immediately after reconstitution or within 3 hours. If not used immediately, store in refrigerator or at room temperature (not to exceed 25°C). Discard unused portion.

Consult manufacturer's information for additional details on reconstitution and preparation of the drug.

Rate of Administration

Administer at a rate not exceeding 1–2 mL/minute.

Dosage

Dosage expressed in international units (IU, units). Each vial contains 2000–3125 units of factor XIII A-subunit (recombinant); actual number of units indicated on each vial and carton.

Individualize dosage based on factor XIII activity and clinical response. Dosage adjustments based on age not required.

Administer once a month to maintain trough factor XIII activity levels ≥10% (as measured by a validated assay). Pharmacokinetic studies indicate that a dose of 35 units/kg is sufficient to replace 100% of factor XIII activity; since factor XIII A₂B₂ tetramer levels increase proportionately with observed factor XIII activity up to 100%, higher doses may not result in further increases in factor XIII A₂B₂ tetramer levels.

Pediatric Patients

Congenital Factor XIII A-subunit Deficiency

IV

35 units/kg once monthly. Consider dosage adjustment if bleeding not adequately controlled.

Adults

Congenital Factor XIII A-subunit Deficiency

IV

35 units/kg once monthly. Consider dosage adjustment if bleeding not adequately controlled.

Contraindications

• Known hypersensitivity reactions to factor XIII A-subunit (recombinant) or any of its components.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Risk of hypersensitivity reactions (e.g., urticaria, rash, chest tightness, wheezing, hypotension).

If manifestations of anaphylaxis or hypersensitivity occur, immediately discontinue drug and initiate appropriate treatment.

Thromboembolic Complications

Risk of thromboembolic complications. Although not observed with factor XIII A-subunit (recombinant), has been reported with plasma-derived factor XIII concentrates.

In patients with an underlying risk of thrombosis, monitor for thromboembolic complications.

Immunogenicity

Neutralizing antibodies (inhibitors) to factor XIII may develop after treatment with factor XIII A-subunit (recombinant). May manifest as inadequate response to treatment.

Monitor for possible development of inhibitory antibodies. If expected plasma factor XIII activity levels not attained or bleeding occurs during factor XIII A-subunit (recombinant) prophylaxis, perform appropriate assay to detect presence of inhibitors.

Transient, low-titer non-neutralizing antibodies detected in pediatric patients receiving factor XIII A-subunit (recombinant); clinically important effects not observed.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether distributed into human milk. Use caution.

Pediatric Use

Pediatric patients 0–17 years of age have received factor XIII A-subunit (recombinant) in clinical studies. Adverse effects were reported more frequently in children 6 to <18 years of age than in adults. (See Immunogenicity under Cautions.)

Pharmacokinetic parameters are similar across different age groups, including in pediatric patients.

Geriatric Use

Safety and efficacy not established in geriatric patients.

Common Adverse Effects

Headache, extremity pain, injection site pain, increased fibrin D dimer levels.

Administration

IV Administration

Administer by slow IV injection. (See Rate of Administration under Dosage and Administration.) Do not administer by continuous IV infusion.

Initiate therapy under supervision of a clinician experienced in the treatment of rare bleeding disorders. May be self-administered in the home setting after appropriate training provided.

Do not administer in the same IV line with other infusion solutions.

Reconstitution

Reconstitute lyophilized drug with sterile water for injection provided by manufacturer. Prior to reconstitution, allow drug vial and diluent to warm to (but not exceed) room temperature (25°C). To avoid foaming, do not inject diluent directly onto powder. Gently swirl vial; do not shake. Resulting solution should be clear and colorless; discard if particulate matter or discoloration observed.

May dilute solution with 0.9% sodium chloride injection to facilitate measurement of small doses (volumes) for administration.

Administer immediately after reconstitution or within 3 hours. If not used immediately, store in refrigerator or at room temperature (not to exceed 25°C). Discard unused portion.

Consult manufacturer's information for additional details on reconstitution and preparation of the drug.

Rate of Administration

Administer at a rate not exceeding 1–2 mL/minute.

Dosage

Dosage expressed in international units (IU, units). Each vial contains 2000–3125 units of factor XIII A-subunit (recombinant); actual number of units indicated on each vial and carton.

Individualize dosage based on factor XIII activity and clinical response. Dosage adjustments based on age not required.

Administer once a month to maintain trough factor XIII activity levels ≥10% (as measured by a validated assay). Pharmacokinetic studies indicate that a dose of 35 units/kg is sufficient to replace 100% of factor XIII activity; since factor XIII A₂B₂ tetramer levels increase proportionately with observed factor XIII activity up to 100%, higher doses may not result in further increases in factor XIII A₂B₂ tetramer levels.

Pediatric Patients

Congenital Factor XIII A-subunit Deficiency

IV

35 units/kg once monthly. Consider dosage adjustment if bleeding not adequately controlled.

Adults

Congenital Factor XIII A-subunit Deficiency

IV

35 units/kg once monthly. Consider dosage adjustment if bleeding not adequately controlled.

Specific Drugs