Complete SPL Sections#
1 INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
OBIZUR ® , Antihemophilic Factor (Recombinant), Porcine Sequence, is a recombinant DNA derived, antihemophilic factor indicated for the on-demand treatment and control of bleeding episodes in adults with acquired hemophilia A.
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
For intravenous use after reconstitution only.
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
OBIZUR is available as a white lyophilized powder in single-dose glass vials containing nominally 500 units per vial.
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
OBIZUR is contraindicated in patients: Who have had life-threatening hypersensitivity reactions to OBIZUR or its components (including traces of hamster proteins). With congenital hemophilia A with inhibitors (CHAWI) due to the high incidence of anamnestic reactions to human factor VIII (hFVIII) and porcine factor VIII (pFVIII) [see Adverse Reactions (6.1) ] .
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
Common adverse reactions observed in greater than 5% of subjects in the clinical trial were development of inhibitors to porcine factor VIII.
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
11 DESCRIPTION
DESCRIPTION SECTION
The active ingredient in OBIZUR is a recombinant (r) analogue of porcine factor VIII (pFVIII) with an approximate molecular weight of 170 kDa. The rpFVIII molecule in OBIZUR is a glycoprotein containing a 90 kDa heavy chain and a 80 kDa light chain. The B-domain normally present in naturally occurring porcine factor VIII has been replaced with a twenty-four amino acid linker. Once activated, the resulting rpFVIIIa has a comparable activity to the endogenous human FVIIIa. OBIZUR is expressed in a genetically engineered baby hamster kidney (BHK) cell line which secretes rpFVIII into the cell culture medium, and the rpFVIII protein is purified using a series of chromatography and filtration steps. The production process includes two dedicated viral clearance steps - a solvent/detergent treatment step for viral inactivation and a nanofiltration step through a series of two 15-nm filters for removal of viruses. No additives of human or animal origin are used in the formulation of OBIZUR. OBIZUR is formulated as a sterile, non-pyrogenic, lyophilized powder for intravenous injection after reconstitution with the diluent (Sterile Water for Injection). OBIZUR is available in single-dose vials that nominally contain 500 units (U) per vial. When reconstituted with the diluent, the product contains the following components per mL: 8.8 mg sodium chloride, 0.04 mg Tris-base, 0.73 mg Tris-HCl, 1.47 mg tri-sodium citrate dehydrate, 0.15 mg calcium chloride dehydrate, 1.9 mg sucrose, and 0.05 mg polysorbate 80. Each vial of OBIZUR is labeled with the actual rpFVIII activity expressed in units determined by a one-stage clotting assay, using a reference rpFVIII material calibrated against the World Health Organization (WHO) 8 th International Standard for human FVIII concentrates. The specific activity of OBIZUR is in the range of 11000 to 18000 U per milligram of protein. The potency values of OBIZUR determined by the chromogenic assay vary and are approximately 20 to 50% lower than those of the one-stage clotting assay.
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
14 CLINICAL STUDIES
CLINICAL STUDIES SECTION
The efficacy of OBIZUR for the treatment of serious bleeding episodes in subjects with acquired hemophilia A was investigated in a prospective, open-label trial (N=29). The trial was conducted in 18 Caucasian, 6 African-American, and 5 Asian subjects diagnosed with acquired hemophilia A (AHA), having auto-immune inhibitory antibodies to human factor VIII, and experiencing serious bleeding episodes that required hospitalization. Subjects with a prior history of bleeding disorders other than AHA, anti-porcine factor VIII antibody titer >20 Bethesda Units (BU), or in whom the bleeding episode was judged likely to resolve on its own were excluded. One subject was considered evaluable at study entry; however, it was later determined that this subject did not have AHA, leaving 28 subjects evaluable for efficacy. An initial dose of 200 units per kg OBIZUR was administered to subjects for the treatment of life- or limb-threatening initial bleeding episodes. Patients were treated with OBIZUR until resolution of bleeding or dosing was continued at the physician's discretion according to the clinical assessment. These bleeding episodes included 19 intramuscular or joint bleeding episodes, 4 post-surgical bleeding episodes, 2 intracranial episodes, 2 surgeries, 1 retroperitoneal hemorrhage, and 1 periorbital bleed. Hemostatic response was assessed by the study site investigator at specified time points after initiation of OBIZUR treatment using a pre-specified rating scale that was based on subjective clinical assessments combined with objective factor VIII activity levels achieved. An assessment of effective or partially effective was considered as a positive response ( see Table 3 for definitions ). Table 3 Response to OBIZUR Treatment Evaluation Assessment of efficacy Control of bleeding Clinical Assessment Factor VIII levels Response Effective bleeding stopped clinical control ≥50% positive Partially effective bleeding reduced clinical stabilization or improvement; or alternative reason for bleeding ≥20% positive Poorly effective bleeding slightly reduced or unchanged not clinically stable
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Inform patients: of early signs and symptoms of hypersensitivity reactions (including angioedema, chest tightness, dyspnea, hypotension, wheezing, urticaria and pruritus) and anaphylaxis. Instruct patients to discontinue use and contact their physician. that new or increase in existing inhibitory antibodies to OBIZUR may develop and this may result in a lack of control of their bleeding. to report any adverse reactions or problems following OBIZUR administration to their physician or healthcare provider.
SPL UNCLASSIFIED SECTION
SPL UNCLASSIFIED SECTION
Takeda Pharmaceuticals U.S.A., Inc. Cambridge, MA 02142 USA U.S. License No. 1898 OBIZUR is a registered trademark of Baxalta Incorporated. Takeda and are registered trademarks of Takeda Pharmaceutical Company Limited. ©2024 Takeda Pharmaceutical Company Limited. All rights reserved. OBZ363 Rev 12/2024
PRINCIPAL DISPLAY PANEL - Kit Carton
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 0944-5001-01 OBIZUR ® Antihemophilic Factor (Recombinant), Porcine Sequence Single-dose vial, lyophilized powder for solution For Intravenous Administration After Reconstitution Only 500 units range* Rx Only * Refer to actual potency
