Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Intravenous [preservative free]:
Corifact: 1000 - 1600 units [contains albumin human]
Pharmacology
Mechanism of Action
Factor XIII (FXIII) is an endogenous plasma glycoprotein found in platelets, monocytes and macrophages that is converted to activated factor XIII (FXIIIa) in the presence of calcium ions. Once activated, FXIIIa cross-links fibrin and cross-links plasmin inhibitor to protect and strengthen the hemostatic platelet plug.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: 51.1 mL/kg
Metabolism
Factor XIII, a proenzyme, is converted to activated factor XIII
Excretion
Clearance:
Pediatric patients <16 years: 0.29 ± 0.12 mL/hour/kg
Adults: 0.22 ± 0.07 mL/hour/kg
Time to Peak
1.7 hours postinfusion
Duration of Action
Plasma levels of FXIII: ~28 days; FXIII activity maintained at ≥5% in ≥97% of patients and ≥10% in ≥85% of patients
Half-Life Elimination
Children (<16 years): 5.7 ± 1 days; Adults: 7.1 ± 2.7 days
Use: Labeled Indications
Prophylaxis against bleeding episodes and management of perioperative surgical bleeding in patients with congenital factor XIII deficiency
Contraindications
History of anaphylaxis or severe systemic reactions to human plasma-derived products or hypersensitivity to any component of the formulation
Dosage and Administration
Dosing: Adult
Congenital factor XIII deficiency: IV:
Prophylaxis:
Initial: 40 units/kg
Maintenance: Dose adjustment should be based on factor XIII activity trough levels (target level of 5% to 20% using Berichrom activity assay) and clinical response; repeat every 28 days
One trough level of <5%: Increase dosage by 5 units/kg
Trough level of 5% to 20%: No dosage change
Two trough levels of >20%: Decrease dosage by 5 units/kg
One trough level of >25%: Decrease dosage by 5 units/kg
Perioperative management of surgical bleeding: Individualize dosing based on factor XIII activity level, type of surgery, and clinical response; monitor factor XIII activity levels during and after surgery:
If time since last prophylactic dose ≤7 days: Additional dose may not be needed.
If time since last prophylactic dose 8 to 21 days: Additional partial or full dose may be necessary based on factor XIII activity level
If time since last prophylactic dose 21 to 28 days: Administer full prophylactic dose
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Congenital factor XIII deficiency: Infants, Children, and Adolescents: IV:
Prophylaxis:
Initial: 40 units/kg
Maintenance: Adjust dose in 5 units/kg increments based on factor XIII activity trough levels (target level of 5% to 20% using Berichrom activity assay) and clinical response; repeat every 28 days
Factor XIII Activity Trough Level (%):
One trough level <5%: Increase dosage by 5 units/kg
Trough level 5% to 20%: No dosage change
Two trough levels >20%: Decrease dosage by 5 units/kg
One trough level >25%: Decrease dosage by 5 units/kg
Treatment, perioperative management of surgical bleeding: Individualize dosing based on factor XIII activity level, type of surgery, and clinical response; monitor factor XIII activity levels during and after surgery:
If time since last prophylactic dose ≤7 days: Additional dose may not be needed.
If time since last prophylactic dose 8 to 21 days: Additional partial or full dose may be necessary based on factor XIII activity level.
If time since last prophylactic dose 21 to 28 days: Administer full prophylactic dose.
Reconstitution
Reconstitute with provided diluent (SWFI); gently swirl; do not shake. Product and diluent should be at room temperature prior to reconstitution. Reconstituted solution should be used within 4 hours (US labeling) or 3 hours (Canadian labeling); do not refrigerate or freeze.
Administration
IV: Administer by IV infusion at a rate not to exceed 4 mL/minute. Product should be brought to room temperature prior to infusing. Administer through a separate infusion line.
Storage
Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. May be stored at room temperature (≤25°C [≤77°F]) for up to 6 months; do not return to refrigerator if stored at room temperature.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
Frequency not defined.
>1%:
Central nervous system: Chills, headache
Dermatologic: Erythema, pruritus, skin rash
Endocrine & metabolic: Increased lactate dehydrogenase
Hematologic & oncologic: Hematoma
Hypersensitivity: Hypersensitivity reaction
Neuromuscular & skeletal: Arthralgia, arthritis
Miscellaneous: Fever
<1%, postmarketing, and/or case reports: Anaphylaxis, antibody development (factor XIII), infection, ischemia (acute), thromboembolism
Warnings/Precautions
Concerns related to adverse effects:
- Antibody formation: The development of factor XIII inhibitory antibodies has been reported. Factor XIII inhibitory antibodies should be measured when clinical response (breakthrough bleeding) and/or factor XIII trough levels are suboptimal after apparent adequate dosing.
- Hypersensitivity reactions: Hypersensitivity and anaphylactic reactions have been reported with use; discontinue immediately if develops and initiate appropriate management.
- Thrombotic events: Thromboembolic events have been reported; pregnant women may be at increased risk due to hypercoagulable state. Use with caution in patients with known risk factors for thrombosis.
Dosage form specific issues:
- Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer. Vaccination with hepatitis A and hepatitis B vaccines is recommended.
Monitoring Parameters
Factor XIII trough levels in conjunction with clinical response to assess efficacy (ie, approximately every 28 days for prophylaxis, during and after surgery for perioperative management of surgical bleeding). Factor XIII inhibitory antibodies if inadequate clinical response and/or factor XIII trough levels are suboptimal. Signs/symptoms of hypersensitivity reactions, thrombotic events, and infection.
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 concentrate (human) may be used in patients with a factor XIII 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, joint pain, or injection site irritation. Have patient report immediately to prescriber signs of infection, 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 DVT (edema, warmth, numbness, change in color, or pain in the extremities), shortness of breath, chest pain, coughing up blood, dizziness, passing out, chills, 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.
