Antihemophilic Factor (Recombinant), Porcine Sequence (Monograph)

Brand name: Obizur
Drug class: Hemostatics
VA class: BL500

Introduction

Biosynthetic (recombinant DNA origin) preparation of porcine blood coagulation factor VIII.

Uses for Antihemophilic Factor (Recombinant), Porcine Sequence

Acquired Hemophilia A

Treatment and prevention of bleeding episodes in patients with acquired hemophilia A, a condition caused by the development of autoantibodies (inhibitors) to antihemophilic factor (blood coagulation factor VIII).

Because of reduced cross-reactivity (about 5–10%) with human factor VIII inhibitors, may be useful in situations where human antihemophilic factor concentrates are ineffective.

Designated an orphan drug by FDA for treatment and prevention of bleeding in patients with inhibitor antibodies to human coagulation factor VIII.

Manufacturer states that safety and efficacy not established in patients with baseline anti-porcine factor VIII inhibitor titers >20 Bethesda Units.

Manufacturer states that drug not indicated for treatment of patients with congenital hemophilia A or von Willebrand disease.

Antihemophilic Factor (Recombinant), Porcine Sequence Dosage and Administration

General

• Individualize dosage and duration of therapy based on location and severity of bleeding, target factor VIII levels, and patient's clinical and pharmacokinetic (e.g., in-vivo recovery, half-life) response.

• Monitor factor VIII activity (by the one-stage clotting assay) after each dose is given to ensure that adequate levels of factor VIII are attained and maintained. (See Laboratory Monitoring under Cautions.) Careful control of dose is especially important in cases of life-threatening bleeding or major surgery.

• If administered dose is ineffective in achieving expected factor VIII levels or bleeding not controlled, consider possibility that inhibitors may have developed. (See Development of Inhibitors to Porcine Factor VIII under Cautions.)

Administration

IV Administration

Administer by slow IV injection or slow IV infusion. (See Rate of Administration under Dosage and Administration.)

Reconstitution

Reconstitute lyophilized powder with manufacturer-supplied prefilled diluent syringe. May require reconstitution of more than one vial to obtain required dose.

Prior to reconstitution, allow drug vial and diluent to warm to room temperature. After addition of diluent, gently swirl vial until powder is completely dissolved. Resultant solution should be clear and colorless; discard if particulate matter or discoloration observed.

Administer within 3 hours after reconstitution.

Do not administer reconstituted solution in the same tubing or container with other drugs.

Consult manufacturer's labeling for specific instructions on reconstitution and preparation.

Rate of Administration

Administer at a rate of 1–2 mL per minute.

Dosage

Dosage and potency expressed in terms of international units (IU, units) of antihemophilic factor activity. Potency is determined by a one-stage clotting assay calibrated using WHO standard.

Adults

Acquired Hemophilia A

Treatment and Prevention of Bleeding Episodes

IV

Manufacturer recommends initial dose of 200 units/kg.

Adjust subsequent dose and dosing frequency (every 4–12 hours recommended by manufacturer) based on individual clinical response and postinfusion levels of factor VIII to maintain the following target trough factor VIII levels:

Minor or moderate bleeding (e.g., superficial muscle without neurovascular compromise, joint bleed): 50–100% of normal.

Major bleeding (e.g., moderate to severe intramuscular, retroperitoneal, GI, or intracranial bleeding): 100–200% of normal to control acute bleeding episode, then maintain at 50–100% of normal if subsequent dosing required.

Do not exceed plasma factor VIII levels of 200% of normal (200 units/dL) at any time.

Cautions for Antihemophilic Factor (Recombinant), Porcine Sequence

Contraindications

• Life-threatening hypersensitivity reactions to antihemophilic factor (recombinant), porcine sequence or any of its components (e.g., hamster protein).

Warnings/Precautions

Warnings

Development of Inhibitors to Porcine Factor VIII

Risk of development of inhibitory antibodies (inhibitors) to porcine factor VIII. Reported in approximately 26% of patients in principal efficacy study.

Monitor patients for development of inhibitors with appropriate clinical observation and laboratory tests. (See Laboratory Monitoring under Cautions.) Suspect presence of inhibitors if patient fails to respond to adequate therapy. Consider other therapeutic options if inhibitors suspected and lack of response present.

Laboratory Monitoring

Monitor factor VIII activity (with one-stage clotting assay) after each dose to confirm that adequate levels have been attained and maintained. Obtain plasma factor VIII level 30 minutes and 3 hours after initial dose, and 30 minutes after each subsequent dose.

Monitor for development of inhibitors to porcine factor VIII. Perform appropriate laboratory test (i.e., modified version of Bethesda assay [Nijmegen]) to confirm presence of an inhibitor. (See Development of Inhibitors to Porcine Factor VIII under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Risk of hypersensitivity reactions.

Contains trace amounts of baby hamster kidney (BHK) proteins, which may stimulate antibody production and cause hypersensitivity reactions; anti-BHK antibodies not detected in principal clinical study.

Observe for manifestations of hypersensitivity (e.g., angioedema, chest tightness, dyspnea, hypotension, wheezing, urticaria, pruritus, anaphylaxis). If a hypersensitivity reaction occurs, immediately discontinue drug and initiate appropriate therapy.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether distributed into human milk; use with caution.

Pediatric Use

Safety and efficacy not established in pediatric patients. Acquired hemophilia A occurs very rarely in children.

Geriatric Use

No overall differences in efficacy and safety observed between geriatric patients ≥65 years of age and younger adults in principal clinical study; however, small number of patients in this age group precludes definitive conclusions.

Common Adverse Effects

Development of inhibitors to porcine factor VIII.

Antihemophilic Factor (Recombinant), Porcine Sequence Pharmacokinetics

Formal pharmacokinetic studies not conducted.

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original package to protect from light; do not freeze.

Store reconstituted solution at room temperature prior to administration; use within 3 hours of reconstitution.

Actions

• Biosynthetic (recombinant DNA origin) preparation of B domain-deleted porcine coagulation factor VIII. Structurally and functionally similar to endogenous human factor VIII.

• Patients with acquired hemophilia A have a functional deficiency of factor VIII due to the development of autoantibodies (inhibitors) against the coagulation factor, resulting in a hemorrhagic tendency. Typical bleeding pattern includes bleeding into skin, muscles, soft tissues, and/or mucous membranes; hemarthrosis occurs less frequently, unlike in patients with congenital hemophilia A.

• Antihemophilic factor (recombinant), porcine sequence therapy temporarily replaces the inhibited factor VIII required for effective hemostasis in patients with acquired hemophilia A. Reduced cross-reactivity (about 5–10%) to human factor VIII inhibitors enables the drug to function effectively in the presence of autoantibodies to factor VIII.

• Produced by recombinant DNA technology in a BHK cell line; undergoes a series of purification and viral inactivation/removal processes (e.g., solvent/detergent treatment, nanofiltration). Final preparation is free of additives of human or animal origin.

Advice to Patients

• Importance of advising patients to report to their clinician any adverse reactions or other issues following administration of antihemophilic factor (recombinant), porcine sequence.

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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