Lyophilized Powder for Solution for Intravenous Injection
Brief Summary of Prescribing Information : Please see package insert for full Prescribing Information .
INDICATIONS AND USAGE
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 .
Limitations of Use :
• Safety and efficacy of OBIZUR has not been established in patients with baseline anti-porcine factor VIII inhibitor titer greater than 20 BU .
• OBIZUR is not indicated for the treatment of congenital hemophilia A or von Willebrand disease .
CONTRAINDICATIONS
OBIZUR is contraindicated in patients who have had lifethreatening hypersensitivity reactions to OBIZUR or its components ( including traces of hamster proteins ).
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions can occur with OBIZUR . OBIZUR contains trace amounts of hamster proteins . Early signs of allergic reactions , which can progress to anaphylaxis , include angioedema , chest-tightness , dyspnea , hypotension , wheezing , urticaria , and pruritus . Immediately discontinue administration and initiate appropriate treatment if allergic or anaphylactic-type reactions occur .
Inhibitory Antibodies
Inhibitory antibodies to OBIZUR , including anamnestic reactions with rise in human FVIII inhibitors and / or porcine FVIII inhibitors , have occurred . Monitor patients for the development of antibodies to OBIZUR by appropriate assays . If the plasma factor VIII level fails to increase as expected , or if bleeding is not controlled after OBIZUR administration , suspect the presence of an anti-porcine factor VIII antibody .
If such inhibitory antibodies are suspected and there is a lack of clinical response , consider management options such as discontinuing OBIZUR and initiating other therapeutics such as a factor VIII bypassing agent .
Monitoring Laboratory Tests
• Perform one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and maintained . – Monitor factor VIII activity 30 minutes and 3 hours after initial dose .
– Monitor factor VIII activity 30 minutes after subsequent doses .
• Monitor the development of inhibitory antibodies to OBIZUR . Perform a Nijmegen Bethesda inhibitor assay if expected plasma factor VIII activity levels are not attained or if bleeding is not controlled with the expected dose of OBIZUR . Use Bethesda Units ( BU ) to report inhibitor levels .
ADVERSE REACTIONS
Common adverse reactions observed in greater than 5 % of subjects in the clinical trial were development of inhibitors to porcine factor VIII .
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions , adverse reaction ( AR ) rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice .
The safety and efficacy of OBIZUR was evaluated in a multicenter , prospective , open-label , clinical trial that investigated adult patients with acquired hemophilia A . Twenty-nine adult subjects were enrolled in the study , received at least one dose of OBIZUR and were evaluable for safety . Of the 29 adult subjects , 10 were between the ages of 40 and 65 , and 19 were 65 years of age or older ( 18 Caucasian , 6 African-American , and 5 Asian ). Ten ( 34 %) subjects were female .
The most frequently reported adverse reaction in patients with acquired hemophilia A was the development of inhibitors to porcine factor VIII .
Immunogenicity
All subjects were monitored for development of inhibitory antibodies to OBIZUR using the Nijmegen modification of the Bethesda inhibitor assay . A subject was considered to have developed an OBIZUR inhibitor if the titer was ≥0.6 Bethesda Units ( BU )/ mL .
Of the 29 subjects treated with OBIZUR , 19 subjects were negative for anti-porcine factor VIII antibodies at baseline . Five of the 19 ( 26 %) developed anti-porcine factor VIII antibodies following exposure to OBIZUR . Of the 10 subjects with detectable anti-porcine factor VIII antibodies at baseline , 2 ( 20 %) experienced an increase in titer and eight ( 80 %) experienced a decreasing to a non-detectable titer .
All subjects were also monitored for development of binding antibodies to baby hamster kidney ( BHK ) protein by a validated sequential ELISA ( enzyme-linked immunosorbent assay ). No patients developed de novo anti-BHK antibodies .
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay . Additionally , the observed incidence of antibody ( including neutralizing antibody ) positivity in an assay may be influenced by several factors , including assay methodology , sample handling , timing of sample collection , concomitant medications , and underlying disease . For these reasons , comparison of the antibodies to other products may be misleading .
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of OBIZUR . Because these reactions are reported voluntarily from a population of uncertain size , it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure .
Copyright © 2020 Takeda Pharmaceutical Company Limited . 300 Shire Way , Lexington , MA 02421 . 1-800-828-2088 . All rights reserved . TAKEDA and the TAKEDA logo are trademarks or registered trademarks of Takeda Pharmaceutical Company Limited . OBIZUR is a registered trademark of Baxalta Incorporated , a Takeda company .
Manufactured by : Baxalta US Inc . Lexington , MA 02421 USA U . S . License No . 2020 US-OBI-0124v1.0 07 / 20