Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Obizur: 500 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]
Pharmacology
Mechanism of Action
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.
Use: Labeled Indications
Acquired hemophilia A: Treatment of bleeding episodes in adults with acquired hemophilia A
Limitations of use: Not indicated for the treatment of congenital hemophilia A or von Willebrand disease; safety and efficacy of has not been established in patients with baseline anti- porcine factor VIII inhibitor titer >20 BU.
Use: Off Label
Congenital hemophilia Ac
Data from a small prospective, multicenter, open-label, phase 2 trial suggests that antihemophilic factor (recombinant [porcine sequence]) replacement therapy may be efficacious as an alternative to bypassing agents for the treatment of bleeding episodes in patients with congenital hemophilia A and factor VIII inhibitors Mahlangu 2017.
Contraindications
Life-threatening hypersensitivity reactions to antihemophilic factor (recombinant [porcine sequence]) or any component of the formulation (including traces of hamster proteins).
Dosage and Administration
Dosing: Adult
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 (Kruse-Jarres 2015).
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 (Martin 2016; Stemberger 2016; Tarantino 2017).
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 (Mahlangu 2017). 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 (Mahlangu 2017).
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Allow vial and diluent to warm to room temperature before reconstitution. Gently swirl vial in a circular motion after adding diluent until dissolved.
Administration
IV: Administer IV at a rate of 1 to 2 mL/minute. Do not administer in the same tubing or container with other medications.
Storage
Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Store the original package to protect from light. Use within 3 hours after reconstitution; discard any unused solution if not used within 3 hours after reconstitution.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
>10%: Immunologic: Antibody development (26%)
<1%, postmarketing, and/or case reports: Hypersensitivity reaction
Warnings/Precautions
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. If inhibitory antibodies are suspected and there is a lack of clinical response, consider other therapy.
- 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.
Monitoring Parameters
Heart rate and blood pressure (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; signs of bleeding; hemoglobin, hematocrit.
Pregnancy
Pregnancy Considerations
Pregnant hemophilia A carriers may have an increased bleeding risk following abortion, invasive procedures, miscarriage, 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 <0.5 IU/mL 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 2013]).
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?)
- Have patient report immediately to prescriber dizziness, passing out, severe loss of strength and energy, nausea, vomiting, agitation, burning or numbness feeling, or shortness of breath (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.
