Version May 2024
Acquired hemophilia A: IV: Note: Dose, dosing frequency, and duration based on location and severity of bleeding, target factor VIII levels, and clinical condition of the patient. Plasma levels of factor VIII should not exceed 200% of normal or 200 units/dL. Patients with inhibitory antibodies to recombinant porcine factor VIII may require higher doses and/or more frequent administration than patients without inhibitory antibodies (Ref).
Minor to moderate hemorrhage: 200 units/kg initially to achieve factor VIII plasma level 50% to 100% of normal; titrate subsequent doses to maintain recommended factor VIII trough levels and individual clinical response; dose every 4 to 12 hours (frequency may be adjusted based on clinical response/factor VIII levels).
Major hemorrhage: 200 units/kg initially to achieve factor VIII plasma level 100% to 200% (for acute bleed) or 50% to 100% (after acute bleed is controlled, if required) of normal; titrate subsequent doses to maintain recommended factor VIII trough levels and individual clinical response; dose every 4 to 12 hours (frequency may be adjusted based on clinical response/factor VIII levels).
Off- label dosing: Based on limited data: 100 units/kg initially; titrate subsequent doses and dosing interval to maintain targeted peak and trough levels based on individual clinical response; refer to protocols for details (Ref).
Congenital hemophilia A (off-label use): Based on limited data: IV: Initial: 200 units/kg; titrate subsequent doses based on factor VIII activity levels and individual clinical response (Ref). Note: Loading doses used in this protocol varied based on the level of porcine factor VIII inhibitor levels (refer to protocol for further details); however, the authors concluded that a 200 units/kg loading dose is more clinically feasible (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
There are insufficient data to recommend the best dosing weight to use in patients with obesity. Dose adjustments should ultimately be made based on individual patient response to therapy. Due to the paucity of data, refer to institutional protocols. Refer to adult dosing for indication-specific dosing.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Hematologic & oncologic: Increased factor VIII inhibitors (anamnestic reaction)
Immunologic: Antibody development
Life-threatening hypersensitivity reactions to antihemophilic factor (recombinant [porcine sequence]) or any component of the formulation (including traces of hamster proteins); congenital hemophilia A with inhibitors due to high incidence of anamnestic reactions to human factor VIII and porcine factor VIII.
Concerns related to adverse effects:
• Antibody formation: Formation of antiporcine factor VIII antibodies has occurred; monitor patients for the development of antibodies. Suspect an antiporcine factor VIII antibody if the plasma factor VIII level does not increase as expected or if bleeding is not controlled after administration. Anamnestic reactions with rise in human factor VIII inhibitors and/or recombinant factor VIII, porcine sequence inhibitors have been reported and may result in a lack of response to antihemophilic factor. If inhibitory antibodies are suspected and there is a lack of clinical response, consider other therapy (eg, factor VIII bypassing agent).
• Hypersensitivity reactions: Hypersensitivity reactions may occur; discontinue immediately if allergic or anaphylactic-type reactions occur.
Dosage form specific issues:
• Hamster protein: May contain trace amounts of hamster proteins.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Sucrose: May contain sucrose.
Other warnings/precautions:
• Dose requirements: The dosage requirement will vary in patients with factor VIII inhibitors; optimal treatment should be determined by clinical response.
Strength expressed with approximate value. 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:
Obizur: 500 units (1 ea) [contains polysorbate 80]
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Generic: 500 units (1 ea)
IV: Administer IV at a rate of 1 to 2 mL/minute. Do not administer in the same tubing or container with other medications.
Acquired hemophilia A: On-demand treatment and control of bleeding episodes in adults with acquired hemophilia A.
Limitations of use: Not indicated for the treatment of von Willebrand disease; safety and efficacy have not been established in patients with baseline anti- porcine factor VIII inhibitor titer >20 BU.
Congenital hemophilia A
Factor VIII may be confused with Factor XIII
Confusion may occur due to the omitting of “Factor VIII” from some product labeling. Review product contents carefully prior to dispensing any antihemophilic factor.
None known.
There are no known significant interactions.
Pregnant carriers of hemophilia A may have an increased bleeding risk following invasive procedures, spontaneous miscarriage, termination of pregnancy, and delivery; close surveillance is recommended. Factor VIII levels should be monitored at the first antenatal visit, once or twice during the third trimester, prior to surgical or invasive procedures, and at delivery. Although factor VIII concentrations increase in pregnant patients, factor VIII replacement is recommended if concentrations are <50 units/dL and any of the following occur: need for invasive procedures (including delivery), spontaneous miscarriage, insertion and removal of epidural catheters, or active bleeding. Hemostatic factor VIII concentrations should be maintained for at least 3 to 5 days following invasive procedures or postpartum. If replacement with a factor VIII concentrate product is indicated, a recombinant product is preferred (NHF 2017; RCOG [Pavord 2017]; WFH [Srivastava 2020]).
It is not known if antihemophilic factor 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 benefits of treatment to the mother.
Heart rate and BP (before and during IV administration); plasma factor VIII activity prior to and during treatment (30 minutes and 3 hours after initial dose; 30 minutes after subsequent doses); development of factor VIII inhibitors or presence of cross-reacting antibodies prior to treatment if clinically indicated and during treatment if expected plasma factor VIII activity levels are not attained or if bleeding is not controlled as expected (manufacturer recommends using the Nijmegen Bethesda inhibitor assay with recombinant porcine factor VIII as substrate for recombinant porcine factor VIII antibodies); signs of bleeding; hemoglobin, hematocrit.
Classification of hemophilia; normal is defined as 100% factor VIII (WFH [Srivastava 2020]).
Severe: Factor level <1% of normal.
Moderate: Factor level 1% to 5% of normal.
Mild: Factor level >5% to <40% of normal.
Factor VIII replacement, necessary for clot formation and maintenance of hemostasis, activates factor X in conjunction with activated factor IX. Activated factor X converts prothrombin to thrombin, which converts fibrinogen to fibrin, and with factor XIII forms a stable clot.
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