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Obizur

Generic Name: Antihemophilic Factor (Recombinant), Porcine Sequence
Class: Hemostatics
VA Class: BL500

Introduction

Biosynthetic (recombinant DNA origin) preparation of porcine blood coagulation factor VIII.1 14 15

Uses for Obizur

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).1 2 3 4

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.6 7 8 14 15

Designated an orphan drug by FDA for treatment and prevention of bleeding in patients with inhibitor antibodies to human coagulation factor VIII.2

Manufacturer states that safety and efficacy not established in patients with baseline anti-porcine factor VIII inhibitor titers >20 Bethesda Units.1

Manufacturer states that drug not indicated for treatment of patients with congenital hemophilia A or von Willebrand disease.1

Obizur 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.1

  • 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.1 (See Laboratory Monitoring under Cautions.) Careful control of dose is especially important in cases of life-threatening bleeding or major surgery.1

  • If administered dose is ineffective in achieving expected factor VIII levels or bleeding not controlled, consider possibility that inhibitors may have developed.1 (See Development of Inhibitors to Porcine Factor VIII under Cautions.)

Administration

IV Administration

Administer by slow IV injection or slow IV infusion.1 (See Rate of Administration under Dosage and Administration.)

Reconstitution

Reconstitute lyophilized powder with manufacturer-supplied prefilled diluent syringe.1 May require reconstitution of more than one vial to obtain required dose.1

Prior to reconstitution, allow drug vial and diluent to warm to room temperature.1 After addition of diluent, gently swirl vial until powder is completely dissolved.1 Resultant solution should be clear and colorless; discard if particulate matter or discoloration observed.1

Administer within 3 hours after reconstitution.1

Do not administer reconstituted solution in the same tubing or container with other drugs.1

Consult manufacturer's labeling for specific instructions on reconstitution and preparation.1

Rate of Administration

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

Dosage

Dosage and potency expressed in terms of international units (IU, units) of antihemophilic factor activity.1 Potency is determined by a one-stage clotting assay calibrated using WHO standard.1

Adults

Acquired Hemophilia A
Treatment and Prevention of Bleeding Episodes
IV

Manufacturer recommends initial dose of 200 units/kg.1

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:1

Minor or moderate bleeding (e.g., superficial muscle without neurovascular compromise, joint bleed): 50–100% of normal.1

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.1

Do not exceed plasma factor VIII levels of 200% of normal (200 units/dL) at any time.1

Cautions for Obizur

Contraindications

  • Life-threatening hypersensitivity reactions to antihemophilic factor (recombinant), porcine sequence or any of its components (e.g., hamster protein).1

Warnings/Precautions

Warnings

Development of Inhibitors to Porcine Factor VIII

Risk of development of inhibitory antibodies (inhibitors) to porcine factor VIII.1 Reported in approximately 26% of patients in principal efficacy study.1

Monitor patients for development of inhibitors with appropriate clinical observation and laboratory tests.1 (See Laboratory Monitoring under Cautions.) Suspect presence of inhibitors if patient fails to respond to adequate therapy.1 Consider other therapeutic options if inhibitors suspected and lack of response present.1

Laboratory Monitoring

Monitor factor VIII activity (with one-stage clotting assay) after each dose to confirm that adequate levels have been attained and maintained.1 Obtain plasma factor VIII level 30 minutes and 3 hours after initial dose, and 30 minutes after each subsequent dose.1

Monitor for development of inhibitors to porcine factor VIII.1 Perform appropriate laboratory test (i.e., modified version of Bethesda assay [Nijmegen]) to confirm presence of an inhibitor.1 (See Development of Inhibitors to Porcine Factor VIII under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Risk of hypersensitivity reactions.1

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.1

Observe for manifestations of hypersensitivity (e.g., angioedema, chest tightness, dyspnea, hypotension, wheezing, urticaria, pruritus, anaphylaxis).1 If a hypersensitivity reaction occurs, immediately discontinue drug and initiate appropriate therapy.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether distributed into human milk; use with caution.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1 Acquired hemophilia A occurs very rarely in children.10

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.1

Common Adverse Effects

Development of inhibitors to porcine factor VIII.1

Obizur Pharmacokinetics

Formal pharmacokinetic studies not conducted.3

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original package to protect from light; do not freeze.1

Store reconstituted solution at room temperature prior to administration; use within 3 hours of reconstitution.1

Actions

  • Biosynthetic (recombinant DNA origin) preparation of B domain-deleted porcine coagulation factor VIII.1 14 15 Structurally and functionally similar to endogenous human factor VIII.1 14 15

  • 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.1 5 6 7 8 9 15 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.5 6 7 8

  • Antihemophilic factor (recombinant), porcine sequence therapy temporarily replaces the inhibited factor VIII required for effective hemostasis in patients with acquired hemophilia A.1 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.3 6 7 8 14 15

  • 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).1 3 15 Final preparation is free of additives of human or animal origin.1

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.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (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.

Antihemophilic Factor (Recombinant), Porcine Sequence

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

number of units indicated on label (nominally 500 units)

Obizur (with sterile water for injection prefilled diluent syringe; available with vial adapter)

Baxter

AHFS DI Essentials. © Copyright 2017, Selected Revisions January 30, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Baxter. Obizur antihemophilic factor (recombinant), porcine sequence prescribing information. Westlake Village, CA; 2014 Oct.

2. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD. From FDA web site.

3. Food and Drug Administration. Summary Basis for Regulatory Action: BLA#STN 125512/0. From FDA website.

4. Food and Drug Administration. Final Clinical Review: STN 125512/0. From FDA website.

5. Giangrande P. Acquired hemophilia. Treatment of Hemophilia. 2012; 38. From the World Federation of Hemophilia website.

6. Franchini M, Mannucci PM. Acquired haemophilia A: a 2013 update. Thromb Haemost. 2013; 110:1114-20. [PubMed 24008306]

7. W Collins P, Chalmers E, Hart D et al. Diagnosis and management of acquired coagulation inhibitors: a guideline from UKHCDO. Br J Haematol. 2013; 162:758-73. [PubMed 23889317]

8. Coppola A, Favaloro EJ, Tufano A et al. Acquired inhibitors of coagulation factors: part I-acquired hemophilia A. Semin Thromb Hemost. 2012; 38:433-46. [PubMed 22740182]

9. Zeng Y, Zhou R, Duan X et al. Interventions for treating acute bleeding episodes in people with acquired hemophilia A. Cochrane Database Syst Rev. 2014; 8:CD010761.

10. Franchini M, Zaffanello M, Lippi G. Acquired hemophilia in pediatrics: a systematic review. Pediatr Blood Cancer. 2010; 55:606-11. [PubMed 20589621]

11. Franchini M, Lippi G. The use of desmopressin in acquired haemophilia A: a systematic review. Blood Transfus. 2011; 9:377-82. [PubMed 21839010]

12. Baudo F, Collins P, Huth-Kühne A et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood. 2012; 120:39-46. [PubMed 22618709]

13. Collins P, Baudo F, Knoebl P et al. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). Blood. 2012; 120:47-55. [PubMed 22517903]

14. Giangrande PL. Porcine factor VIII. Haemophilia. 2012; 18:305-9. [PubMed 22531020]

15. Toschi V. OBI-1, porcine recombinant Factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies against human Factor VIII. Curr Opin Mol Ther. 2010; 12:617-25. [PubMed 20886394]

215. World Federation of Hemophilia. Guidelines for the management of hemophilia 2nd edition. 2012. From the World Federation of Hemophilia website.

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