(an TEE in HI bi tor coe AG yoo lant KOM pleks HYU man)
Hemorrhage in patients with hemophilia: For use in patients with hemophilia A and B with inhibitors for control and prevention of bleeding episodes.
Perioperative bleeding management in patients with hemophilia: For use in patients with hemophilia A and B with inhibitors for perioperative management.
Routine prophylaxis of bleeding events in patients with hemophilia: For use in patients with hemophilia A and B for routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
Known anaphylactic or severe hypersensitivity to anti-inhibitor coagulant complex or any component of the formulation, including factors of the kinin generating system; disseminated intravascular coagulation (DIC); acute thrombosis or embolism (including myocardial infarction)
Thrombotic and thromboembolic events have been reported during postmarketing surveillance following infusion of anti-inhibitor coagulant complex, particularly following the administration of high doses and/or in patients with thrombotic risk factors. Monitor patients receiving anti-inhibitor coagulant complex for signs and symptoms of thromboembolic events.
Note: Anti-inhibitor coagulant complex (Human) contains mainly non-activated therapeutic levels of factors II, IX, and X and mainly activated factor VII
Control and prevention of bleeding episodes: IV: Note: Considered a first-line treatment when factor VIII inhibitor titer is >5 Bethesda units (BU) (antihemophilic factor may be preferred when titer <5 BU)
General dosing guidelines: 50-100 units/kg per dose (maximum: 100 units/kg [single dose], 200 units/kg/day [total daily dose]). Dosage and duration of treatment depend on the location and extent of bleeding and clinical condition of the patient. If total single dose exceeds 100 units/kg or total daily dose exceeds 200 units/kg/day, monitor closely for DIC, coronary ischemia, and signs/symptoms of other thromboembolic events.
Joint hemorrhage: 50-100 units/kg every 12 hours until pain and acute disabilities are improved (maximum: 200 units/kg/day)
Mucous membrane bleeding: 50-100 units/kg every 6 hours for at least 1 day or until bleeding is resolved (maximum: 200 units/kg/day)
Soft tissue hemorrhage (eg, retroperitoneal bleed): 100 units/kg every 12 hours until resolution of bleed (maximum: 200 units/kg/day)
Other severe hemorrhage (eg, intracranial hemorrhage): 100 units/kg every 6-12 hours; continue until resolution of bleed (maximum: 200 units/kg/day).
Perioperative management:
Preoperative: 50-100 units/kg (single dose) administered immediately prior to surgery.
Postoperative: 50-100 units/kg every 6-12 hours until resolution of bleed and healing is achieved (maximum: 200 units/kg/day)
Routine prophylaxis: 85 units/kg every other day.
Hemorrhage (moderate-to-severe) due to acquired hemophilia (off-label use): IV: Optimal dosing has not been established: 50 to 100 units/kg every 8 to 12 hours until bleeding controlled has been suggested; may continue for 24 to 72 hours based on site, type, and severity of bleeding (maximum: 200 units/kg/day) (Huth-Kuhne 2009; Sallah 2004).
Intracranial hemorrhage associated with non-vitamin K antagonist anticoagulants (off-label use): Adults: IV: According to the Neurocritical Care Society/Society of Critical Care Medicine (NCS/SCCM [Frontera 2016]):
Oral direct factor Xa inhibitor-mediated (apixaban, edoxaban, rivaroxaban): 50 units/kg if ICH occurred within 3 to 5 terminal half-lives of drug exposure or when liver failure co-exists.
Direct thrombin inhibitor-mediated (argatroban, dabigatran [if idarucizumab unavailable], bivalirudin, desirudin): 50 units/kg if direct thrombin inhibitor was administered within a period of 3 to 5 half-lives prior and there is no evidence of renal failure or there is renal impairment leading to drug exposure beyond 3 to 5 half-lives.
Fondaparinux-mediated (full therapeutic dose): 20 units/kg
Life-threatening bleeding associated with non-vitamin K antagonist anticoagulation (off-label use): IV: Optimal dosing has not been established. Based on multiple case reports with various types of hemorrhage due to either dabigatran or rivaroxaban, a dosage range of 25 to 100 units/kg has been used (Dager 2013; Faust 2014; Kiraly 2013; Maurice-Szamburski 2014; Neyens 2014; Schulman 2014). In 1 case study, after administration of 26 units/kg, an additional dose of 16 units/kg was administered for a concern of rebleeding (Dager 2013). Note: The use of anti-inhibitor coagulant complex (FEIBA, activated 4-factor PCC) may be associated with a higher risk of thrombosis compared to nonactivated PCCs especially with higher doses; monitor closely for arterial and venous thrombosis.
Refer to adult dosing.
Note: Anti-inhibitor coagulant complex (Human) contains mainly non-activated therapeutic levels of factors II, IX, and X and mainly activated factor VII
Control and prevention of bleeding episodes: Children and Adolescents: IV: Note: Considered a first-line treatment when factor VIII inhibitor titer is >5 Bethesda units (BU) (antihemophilic factor may be preferred when titer <5 BU)
General dosing guidelines: 50-100 units/kg per dose (maximum: 100 units/kg [single dose], 200 units/kg/day [total daily dose]). Dosage and duration of treatment depend on the location and extent of bleeding and clinical condition of the patient. If total single dose exceeds 100 units/kg or total daily dose exceeds 200 units/kg/day, monitor closely for DIC, coronary ischemia, and signs/symptoms of other thromboembolic events.
Joint hemorrhage: 50-100 units/kg every 12 hours until pain and acute disabilities are improved (maximum: 200 units/kg/day)
Mucous membrane bleeding: 50-100 units/kg every 6 hours for at least 1 day or until bleeding is resolved (maximum: 200 units/kg/day)
Soft tissue hemorrhage (eg, retroperitoneal bleed): 100 units/kg every 12 hours until resolution of bleed (maximum: 200 units/kg/day)
Other severe hemorrhage (eg, intracranial hemorrhage): 100 units/kg every 6-12 hours; continue until resolution of bleed (maximum: 200 units/kg/day).
Perioperative management:
Preoperative: 50-100 units/kg (single dose) administered immediately prior to surgery.
Postoperative: 50-100 units/kg every 6-12 hours until resolution of bleed and healing is achieved (maximum: 200 units/kg/day)
Routine prophylaxis: 85 units/kg every other day.
No dosage adjustment provided in manufacturer 's labeling.
No dosage adjustment provided in manufacturer 's labeling.
If refrigerated, allow the vials of anti-inhibitor coagulant complex (concentrate) and SWFI (diluent) to reach room temperature. Reconstitute with provided SWFI. Swirl to gently dissolve powder; do not shake. Do not refrigerate after reconstitution.
For IV injection or drip infusion only; maximum infusion rate: 2 units/kg/minute. Following reconstitution, complete infusion within 3 hours.
Some products may contain sodium.
Prior to reconstitution, store at room temperature (maximum of 25 ‹ šC [77 ‹ šF]); store in the original package to protect from light. Do not freeze. Following reconstitution, infusion must be completed within 3 hours.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
FEIBA: 500 units (1 ea); 1000 units (1 ea); 2500 units (1 ea)
Antifibrinolytic Agents: May enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human). Avoid combination
Monitor for control of bleeding, signs and symptoms of DIC (blood pressure changes, pulse rate changes, chest pain/cough, fibrinogen decreased, platelet count decreased, fibrin-fibrinogen degradation products, significantly-prolonged thrombin time, PT, or partial thromboplastin time), thrombotic and thromboembolic events; hemoglobin and hematocrit; hypotension; have epinephrine ready to treat hypersensitivity reactions. Note: Tests used to monitor hemostatic efficacy, such as aPTT and TEG, are not useful for monitoring responses with anti-inhibitor coagulant complex (Hoffman, 2012). Dosing to normalize these values may result in DIC.
Frequency not defined.
Cardiovascular: Cerebrovascular accident (embolic/thrombotic stroke), chest discomfort, chest pain, decreased blood pressure, flushing, hypertension, hypotension, myocardial infarction, pulmonary embolism, tachycardia, thromboembolism, thrombosis (arterial thrombosis, venous thrombosis)
Central nervous system: Chills, dizziness, drowsiness, headache, hypoesthesia (including facial), malaise, paresthesia
Dermatologic: Pruritus, skin rash, urticaria
Gastrointestinal: Abdominal distress, diarrhea, dysgeusia, nausea, vomiting
Hematologic & oncologic: Disseminated intravascular coagulation
Hypersensitivity: Angioedema, hypersensitivity reaction (including anaphylaxis)
Immunologic: Anamnestic response
Local: Pain at injection site
Miscellaneous: Fever
Respiratory: Bronchospasm, cough, dyspnea, wheezing
Concerns related to adverse effects:
- Allergic reactions: Allergic reactions (including severe anaphylactoid reactions) have been observed following administration. Discontinue immediately with signs/symptoms of hypersensitivity. Appropriate medication including epinephrine should be readily available.
- Thromboembolic events: [US Boxed Warning]: Thrombotic and thromboembolic events (including venous thrombosis, pulmonary embolism, disseminated intravascular coagulation [DIC], myocardial infarction and stroke) have been reported following administration of anti-inhibitor coagulant complex, particularly with administration of high doses and/or in patients with thrombotic risk factors. Monitor patients receiving anti-inhibitor coagulant complex for signs and symptoms of thromboembolic events, especially if more than 100 units/kg is administered. Use with caution when administering to patients with advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with factor VIIa due to increased risk of developing thrombotic events due to circulating tissue factor or predisposing coagulopathy. Weigh the potential benefit of treatment against the potential risk of these thromboembolic events.
Concurrent drug therapy issues:
- Antifibrinolytic agents: Thromboembolic events may be increased with concurrent use of an antifibrinolytic (tranexamic acid, aminocaproic acid); avoid or delay use of antifibrinolytic for at least 12 hours.
Dosage form specific issues:
- Factor VIII: Product contains minute amounts of factor VIII which may cause an anamnestic response; anamnestic rises were not associated with reduced efficacy.
- Human plasma: Product of human plasma; may potentially contain infectious agents that could transmit disease. During the manufacturing process, 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 and/or to FDA MedWatch. Patients with signs/symptoms of infection (eg, fever, chills, drowsiness) should be encouraged to consult health care provider.
Other warnings/precautions:
- Appropriate use: The manufacturer recommends that anti-inhibitor coagulant complex should only be used to control bleeding resulting from coagulation factor deficiencies in patients with inhibitors to coagulation factor VIII or coagulation factor IX.
- Monitoring: Tests used to monitor hemostatic activity, such as aPTT and thromboelastography (TEG), are not useful for monitoring responses with anti-inhibitor coagulant complex (Hoffman 2012). Dosing to normalize these values may result in DIC.
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Animal reproduction studies have not been conducted.
Multiple interactions of the components in anti-inhibitor coagulant complex restore the impaired thrombin generation of hemophilia patients with inhibitors. In vitro, anti-inhibitor coagulant complex shortens the activated partial thromboplastin time of plasma containing factor VIII inhibitor.
Peak thrombin generation: Within 15-30 minutes (Varadi, 2003)
8-12 hours (based on thrombin generation) (Varadi, 2003)
4-7 hours (based on thrombin generation) (Varadi, 2003)
- 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 fatigue or change in taste. Have patient report immediately to prescriber signs of blood clots (numbness or weakness on one side of your body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; fast heartbeat; or coughing up blood), signs of infection, signs of breathing problems (shortness of breath, wheezing, coughing, or breathing gets worse), severe dizziness, passing out, severe nausea, vomiting, severe headache, chills, tachycardia, mouth discoloration, difficulty speaking or thinking, change in balance, or blurred vision (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 healthcare 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.