Version May 2024
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 nonactivated therapeutic levels of factors II, IX, and X and mainly activated factor VII. Dosage is expressed in units of factor VIII inhibitor bypassing activity.
Control and prevention of bleeding episodes in patients with hemophilia: IV: Note: Considered a first-line treatment when factor VIII inhibitor titer is >5 Bethesda units (BU) (antihemophilic factor VIII concentrate may be preferred when titer <5 BU). Avoid use in patients with hemophilia A with inhibitors receiving concomitant emicizumab prophylaxis due to increased risk of thrombotic microangiopathy and for patients with hemophilia B with inhibitors due to risk for allergic reactions (Ref).
General dosing guidelines: 50 to 100 units/kg/dose. Dosage, dosing frequency, and duration of treatment depend on the location and extent of bleeding and clinical condition of the patient.
Joint hemorrhage: 50 to 100 units/kg every 12 hours until pain and acute disabilities are improved (maximum: 100 units/kg/dose; 200 units/kg/day).
Mucous membrane bleeding: 50 to 100 units/kg every 6 hours for at least 1 day or until bleeding is resolved (maximum: 100 units/kg/dose; 200 units/kg/day).
Soft tissue hemorrhage (eg, retroperitoneal bleed): 100 units/kg every 12 hours until resolution of bleed (maximum: 100 units/kg/dose; 200 units/kg/day).
Other severe hemorrhage (eg, intracranial hemorrhage): 100 units/kg every 6 to 12 hours; continue until resolution of bleed (maximum: 100 units/kg/dose; 200 units/kg/day).
Perioperative management:
Preoperative: 50 to 100 units/kg (single dose) administered immediately prior to surgery.
Postoperative: 50 to 100 units/kg every 6 to 12 hours until resolution of bleed and healing is achieved (maximum: 100 units/kg/dose; 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) (Ref).
Intracranial hemorrhage, pentasaccharide-mediated (eg, fondaparinux) (full-therapeutic dose) (off-label use): IV:
20 units/kg. Note: In patients receiving fondaparinux for venous thromboembolism prophylaxis (ie, not a full therapeutic dose), the Neurocritical Care Society and Society of Critical Care Medicine guidelines suggest against reversal unless there is evidence of bioaccumulation or impaired clearance (Ref).
Life-threatening bleeding associated with non-vitamin K antagonists (off-label use): Note: Generally used for life-threatening bleeding or bleeding into a critical organ that is not controlled with maximal supportive measures (Ref). The use of anti-inhibitor coagulant complex may be associated with a higher risk of thrombosis compared to nonactivated prothrombin complex concentrate, especially with higher doses; monitor closely for arterial and venous thrombosis.
Oral direct factor Xa inhibitor-mediated (apixaban, betrixaban, edoxaban, rivaroxaban [if andexanet alfa unavailable]): IV: 50 units/kg once, in addition to other supportive measures as clinically indicated (eg, activated charcoal [if ingestion is within 2 to 4 hours], antifibrinolytic agent) (Ref).
Direct thrombin inhibitor-mediated (argatroban, dabigatran, bivalirudin, desirudin [if idarucizumab unavailable]): IV: 50 units/kg once, in addition to other supportive measures as clinically indicated (eg, activated charcoal [if ingestion is within 2 to 4 hours], hemodialysis, antifibrinolytic agent) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥30 kg/m2): IV: For patients ≤100 kg, use actual body weight for weight-based dosing. For patients >100 kg, use a maximum 100 kg for dosing weight (Ref). Refer to adult dosing for indication-specific doses.
Rationale for recommendations: There is a lack of studies evaluating the influence of obesity on anti-inhibitor coagulant complex dosing or pharmacokinetics. The pharmacokinetics in healthy patients without obesity is complicated with different included clotting factors having vastly different half-lives. Further studies are required to evaluate weight metrics and clinical outcomes in patients with obesity.
Refer to adult dosing.
(For additional information see "Prothrombin complex concentrate, activated, from human plasma (factor eight inhibitor bypassing activity [FEIBA]): Pediatric drug information")
Note: Anti-inhibitor coagulant complex (Human) contains mainly nonactivated therapeutic levels of factors II, IX, and X and mainly activated factor VII. Dosage is expressed in units of factor VIII inhibitor bypassing activity and is dependent upon the severity and location of bleeding. Maximum dose should only be exceeded if bleeding severity warrants; monitor closely for disseminated intravascular coagulation, coronary ischemia and/or signs and symptoms of other thromboembolic events.
Control and prevention of bleeding episodes: Infants, Children, and Adolescents: Note: Dosage will vary with the bleeding site and severity.
Joint hemorrhage: IV: 50 to 100 units/kg/dose every 12 hours until pain and acute disabilities are improved; maximum daily dose: 200 units/kg/day.
Mucous membrane bleeding: IV: 50 to 100 units/kg/dose every 6 hours for at least one day or until bleeding is resolved; maximum daily dose: 200 units/kg/day.
Soft tissue hemorrhage (eg, retroperitoneal bleeding): IV: 100 units/kg/dose every 12 hours until resolution of bleed; maximum daily dose: 200 units/kg/day.
Other severe hemorrhages (eg, CNS bleeds): IV: 100 units/kg/dose every 6 to 12 hours until resolution of bleed; maximum daily dose: 200 units/kg/day.
Perioperative management: Infants, Children, and Adolescents:
Preoperative: IV: 50 to 100 units/kg (single dose) administered immediately prior to surgery.
Postoperative: IV: 50 to 100 units/kg/dose every 6 to 12 hours until resolution of bleed and healing is achieved; maximum daily dose: 200 units/kg/day.
Routine prophylaxis: Infants, Children, and Adolescents: IV: 85 units/kg/dose every other day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults.
1% to 10%:
Gastrointestinal: Diarrhea, nausea, vomiting
Hematologic & oncologic: Anemia
Hypersensitivity: Infusion-related reaction
Nervous system: Headache
Neuromuscular & skeletal: Hemarthrosis
Frequency not defined:
Cardiovascular: Chest discomfort, chest pain, thromboembolic complications (including cerebrovascular accident, deep vein thrombosis, pulmonary embolism)
Gastrointestinal: Dysgeusia
Hypersensitivity: Hypersensitivity reaction
Nervous system: Chills, dizziness, drowsiness, hypoesthesia
Respiratory: Dyspnea
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Flushing, tachycardia
Dermatologic: Pruritus
Gastrointestinal: Abdominal distress
Hematologic & oncologic: Disseminated intravascular coagulation
Local: Pain at injection site
Nervous system: Feeling hot, malaise
Respiratory: Bronchospasm, wheezing
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)
Concerns related to adverse effects:
• Hypersensitivity reactions: Hypersensitivity and allergic reactions (including severe and systemic reactions [eg, anaphylaxis with urticaria and angioedema, bronchospasm, circulatory shock]) have been observed following administration. Discontinue immediately with signs/symptoms of severe hypersensitivity reactions and provide appropriate supportive care.
• Infusion reactions: Infusion reactions (eg, chills, pyrexia, hypertension) have been reported.
• Thromboembolic events: [US Boxed Warning]: Thromboembolic events (including venous thrombosis, pulmonary embolism, MI, 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 200 units/kg/day is administered. Use with caution in patients with disseminated intravascular coagulation (DIC), advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with factor VIIa. Weigh the potential benefit of treatment against the potential risk of these thromboembolic events. Monitor patients receiving >100 units/kg for the development of DIC, acute coronary ischemia, and signs/symptoms of other thromboembolic events. If clinical signs/symptoms occur, discontinue use. In an emicizumab clinical trial where patients were also administered anti-inhibitor coagulant complex for breakthrough bleeding, there were reported cases of thrombotic microangiopathy (TMA). TMA has not been reported in clinical studies of anti-inhibitor coagulant complex. Use with caution and monitor closely if anti-inhibitor coagulant complex is used in patients receiving emicizumab.
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: Not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to factor VIII or factor IX. Use of antifibrinolytics within ~6 to 12 hours after the administration of anti-inhibitor coagulant complex is not recommended.
FEIBA strengths expressed in terms of Factor VIII inhibitor bypassing activity with nominal strength values. Consult individual vial labels for exact potency within each vial.
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)
No
Solution (reconstituted) (Feiba Intravenous)
500 unit (Price provided is per AHF Unit): $3.14
1000 unit (Price provided is per AHF Unit): $3.14
2500 unit (Price provided is per AHF Unit): $3.14
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Feiba NF: 1000 units (1 ea); 2500 units (1 ea)
IV: For IV injection or infusion only; maximum infusion rate: 10 units/kg/minute. A syringe pump may be used to control the rate of administration. Use plastic luer lock syringes (anti-inhibitor coagulant complex may stick to the surface of all-glass syringes); do not administer in the same tubing or container with other medications. Following reconstitution, administer immediately and complete infusion within 3 hours.
IV: For IV injection or infusion only. Flush line with NS prior to and following administration; do not administer in the same tubing or container with other medications. Use plastic luer lock syringes; anti-inhibitor coagulant complex may stick to the surface of all-glass syringes. Maximum infusion rate: 2 units/kg/minute. A syringe pump may be used to control the rate of administration. Complete infusion within 3 hours of reconstitution.
Hemorrhage in patients with hemophilia: Control and prevention of bleeding episodes in patients with hemophilia A and B with inhibitors.
Perioperative bleeding management in patients with hemophilia: Perioperative bleeding management in patients with hemophilia A and B with inhibitors.
Routine prophylaxis of bleeding events in patients with hemophilia: Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A and B with inhibitors.
Acquired hemophilia with factor VIII or factor IX inhibitor titers >5 Bethesda units; Intracranial hemorrhage, pentasaccharide-mediated (eg, fondaparinux) (full-therapeutic dose); Life-threatening bleeding associated with non-vitamin K antagonists; Reversal of dabigatran in patients who require urgent procedure (if idarucizumab unavailable)
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antifibrinolytic Agents: May enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human). Risk X: Avoid combination
Concizumab: Anti-inhibitor Coagulant Complex (Human) may enhance the thrombogenic effect of Concizumab. Management: Discontinue anti-inhibitor coagulant complex (aPCC) at least 48 hours before starting concizumab. If aPCC is required during concizumab prophylaxis, use the lowest possible effective aPCC dose. Risk D: Consider therapy modification
Emicizumab: May enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human). Risk C: Monitor therapy
Factor VIIa (Recombinant): Anti-inhibitor Coagulant Complex (Human) may enhance the thrombogenic effect of Factor VIIa (Recombinant). Management: Consider avoiding concomitant use of factor VIIa (recombinant) and activated prothrombin concentrates, such as anti-inhibitor coagulant complex (human), due to an increased risk of developing thrombotic events. Risk D: Consider therapy modification
Limited outcome information is available from a pregnancy registry following use of anti-inhibitor coagulant complex (human) in pregnant patients with acquired hemophilia A (Tengborn 2012). Other products are preferred for the routine prophylaxis of bleeding events in pregnant patients with known hemophilia (NHF 2017; RCOG [Pavord 2017]; WFH [Srivastava 2020]). However, the use of anti-inhibitor coagulant complex (human) may be considered in select patients with bleeding associated with postpartum acquired hemophilia A (a recombinant product may be preferred) (Huth-Kuhne 2009; Kruse-Jarres 2017; Windyga 2019).
It is not known if anti-inhibitor coagulant complex is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Some products may contain sodium.
There are no reliable laboratory tests to measure activated prothrombin complex concentrate efficacy. Monitor for clinical response and evidence of hemostasis; signs/symptoms of disseminated intravascular coagulation (DIC) and thrombosis; hemoglobin and hematocrit; blood loss; hypotension; signs/symptoms of hypersensitivity reactions. Note: Tests used to monitor hemostatic efficacy, such as PT/INR, aPTT, factor activity assays, and TEG, are not useful for monitoring responses with anti-inhibitor coagulant complex (Hoffman 2012). Dosing to normalize these values may result in DIC.
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.
Onset: Peak thrombin generation: Within 15 to 30 minutes (Varadi 2003)
Duration: 8 to 12 hours (based on thrombin generation) (Varadi 2003)
Half-life elimination: 4 to 7 hours (based on thrombin generation) (Varadi 2003)
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