Activated prothrombin complex concentrates (factor VIII inhibitor bypassing activity)

Activated prothrombin complex concentrates (factor VIII inhibitor bypassing activity): Drug information
Copyright 1978-2011 Lexicomp, Inc. All rights reserved.
(For additional information see “Activated prothrombin complex concentrates (factor VIII inhibitor bypassing activity): Patient drug information” and see “Activated prothrombin complex concentrates (factor VIII inhibitor bypassing activity): Pediatric drug information”)

ALERT: U.S. Boxed Warning The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Brand Names: U.S. Feiba NF; Feiba VH [DSC]
Brand Names: Canada Feiba NF
Pharmacologic Category Activated Prothrombin Complex Concentrate (aPCC); Antihemophilic Agent; Blood Product Derivative
Dosing: Adult Control of bleeding: I.V.: 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 (maximum: 200 units/kg/day)

Joint hemorrhage: 50 units/kg every 12 hours; may increase to 100 units/kg every 12 hours; continue until signs of clinical improvement occur (maximum: 200 units/kg/day)

Mucous membrane bleeding: 50 units/kg every 6 hours; may increase to 100 units/kg every 6 hours up to 2 doses only (maximum: 200 units/kg/day)

Soft tissue hemorrhage (eg, retroperitoneal bleed): 100 units/kg every 12 hours (maximum: 200 units/kg/day)

Other severe hemorrhage (eg, intracranial hemorrhage): 100 units/kg every 12 hours; may be used every 6 hours if needed; continue until clinical improvement (maximum: 200 units/kg/day unless severity of hemorrhage justifies higher doses). Note: If total single dose exceeds 100 units/kg or total daily dose exceeds 200 units/kg/day, monitor closely for DIC and/or coronary ischemia.

Dosing: Pediatric
(For additional information see “Activated prothrombin complex concentrates (factor VIII inhibitor bypassing activity): Pediatric drug information”)

Refer to adult dosing.
Dosing: Geriatric Refer to adult dosing.
Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, powder for reconstitution:

Feiba NF: ~500 units, ~1000 units, ~2500 units [heparin free; contains natural rubber/natural latex in packaging; exact potency labeled on each vial]

Feiba VH: ~500 units, ~1000 units, ~2500 units [heparin free; contains natural rubber/natural latex in packaging; exact potency labeled on each vial] [DSC]

Generic Equivalent Available: U.S. No
Administration For I.V. injection or drip infusion only; maximum infusion rate: 2 units/kg/minute. Following reconstitution, complete infusion within 3 hours.
Use Hemophilia A & B patients with inhibitors who are to undergo surgery or those who are bleeding
Use – Unlabeled/Investigational Acquired hemophilia with factor VIII or factor IX inhibitor titers >5 Bethesda units (BU)
Adverse Reactions Significant Frequency not defined.
Cardiovascular: Blood pressure decreased, MI, thromboembolism

Central nervous system: Hypoesthesia (including facial)

Dermatologic: Rash, urticaria

Hematologic: DIC

Local: Injection site pain

Miscellaneous: Allergic reaction (including anaphylaxis), anamnestic response, hypersensitivity

Contraindications Hypersensitivity to anti-inhibitor coagulant complex or any component of the formulation; use in patients with normal coagulation mechanism; significant signs of disseminated intravascular coagulation (DIC); treatment of bleeding due to coagulation factor deficiencies in the absence of inhibitors to coagulation factors VIII or IX; acute thromboembolism (including myocardial infarction)
Warnings/Precautions
Boxed warnings:

• Thromboembolic events: See “Concerns related to adverse effects” below.

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: [U.S. 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. Administer to patients at risk of DIC or venous or arterial thrombosis only if alternative therapy is not available. Use with caution when administering to patients with liver disease, postoperative patients, neonates, elderly, or patients with signs of fibrinolysis due to the potential risk of thromboembolic complications. Observe closely for signs and symptoms of intravascular coagulation or thrombosis. Single doses should not exceed 100 units/kg and daily doses should not exceed 200 units/kg unless the severity of bleeding justifies use of larger doses. Large doses should be administered only as long as absolutely necessary to control bleeding.

Disease-related concerns:

• Hepatic impairment: Use with extreme caution in patients with hepatic impairment.

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.

• 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. Patients with signs/symptoms of infection (eg, fever, chills, drowsiness) should be encouraged to consult healthcare provider.

• Latex: Product packaging may contain natural rubber latex.

Other warnings/precautions:

• Appropriate use: Should only be used to control bleeding in patients with inhibitors resulting from coagulation factor deficiencies. Tests used to control improvement, such as aPTT, whole blood clotting time (WBCT), and thromboelastography (TEG), do not correlate with clinical efficacy. Dosing to normalize these values may result in DIC.

Drug Interactions
(For additional information: Launch Lexi-Interact™ Drug Interactions Program )
Antifibrinolytic Agents: May enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex. Risk X: Avoid combination

Pregnancy Risk Factor C (show table)
Pregnancy Implications Reproduction studies have not been conducted. Administer to pregnant women only if clearly indicated.
Dietary Considerations Some products may contain sodium.
Monitoring Parameters 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); hemoglobin and hematocrit; hypotension; have epinephrine ready to treat hypersensitivity reactions. Note: Tests used to control efficacy such as aPTT, WBCT, and TEG do not correlate with clinical improvement. Dosing to normalize these values may result in DIC.

 

REFERENCES
Huth-Kuhne A, Baudo F, Collins P, et al, “International Recommendations on the Diagnosis and Treatment of Patients With Acquired Hemophilia A,” Haematologica, 2009, 94(4):566-75. [PubMed 19336751]
Lloyd Jones M, Wight J, Paisley S, et al, “Control of Bleeding in Patients With Haemophilia A With Inhibitors: A Systematic Review,” Haemophilia, 2003, 9(4):464-520. [PubMed 12828680]
Ma AD and Carrizosa D, “Acquired Factor VIII Inhibitors: Pathophysiology and Treatment,” Hematology Am Soc Hematol Educ Program, 2006: 432-7. [PubMed 17124095]
Monahan PE and Aledort LM, “Factors Affecting Choice of Hemostatic Agent for the Hemophilia Patient With an Inhibitor Antibody,” Am J Hematol, 2004, 77(4):346-50. [PubMed 15558804]
Tjonnfjord GE, “Activated Prothrombin Complex Concentrate (Feiba®) Treatment During Surgery in Patients with Inhibitors to Factor VIII/IX: The Updated Norwegian Experience, Haemophilia, 2004, 10(Supp 2):41-5. [PubMed 15385045]