SELECTED IMPORTANT SAFETY INFORMATION: Jivi is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, polyethylene glycol (PEG), mouse or hamster proteins, or other constituents of the product. CONTINUE READING BELOW

Jivi® antihemophilic factor (recombinant), PEGylated-aucl Logo

SELECTED IMPORTANT SAFETY INFORMATION: Jivi is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, polyethylene glycol (PEG), mouse or hamster proteins, or other constituents of the product. CONTINUE READING BELOW

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    The small size of the patient cohort could be a potential limitation of this study.2

    Study design for crossover study comparing PK characteristics and PK assessment. Jivi. Adynovate.

    PK, pharmaokinetic; AUC(0-tlast), area under the curve (from time 0 to last data point).

    Adapted from Solms et al.

    Area under the curve is the total amount of a drug that reaches the bloodstream, measured by plasma concentration, over time.2

    Potency-adjusted PK analyses of Jivi® and Adynovate®2*

    The preplanned analysis was followed by a post hoc analysis

    • In the preplanned analysis, the 50 IU/kg doses administered in this study were calculated based on the 1000 IU nominal potencies provided on the vial labels of the 2 products
    • In this study, the actual potencies were 1030 IU/vial for Jivi® and 1141 IU/vial for Adynovate®. This resulted in actual administered doses which were approximately:
      • 3% higher than the planned 50 IU/kg dose for Jivi®
      • 14.1% higher than the planned 50 IU/kg dose for Adynovate®
    • A subsequent post hoc analysis of PK parameters was conducted using the actual potencies of the 2 products being compared

    *Adapted from Solms et al. (1355)

    Comparative PK results for Jivi® vs Adynovate®2

     

    The small size of the patient cohort could be a potential limitation of this study.2

    Graph representing comparative PK results, including mean AUC, clearance, and mean terminal half-life. Jivi. Adynovate

    PK, pharmacokinetic; AUC(0-tlast), area under the curve (from 0 to last data point); AUCnorm, dose normalized area under the curve; CI, confidence interval

    Half-life and CI are not weight-dependent parameters, so they are not normalized.

    Area under the curve is the total amount of a drug that reaches the bloodstream, measured by plasma concentration over time.3

    Clearance is the rate by which a drug is eliminated from the body.4

    Half-life is the time it takes for the amount of drug in the blood to decrease by one half.5

    Geometric least squares.2

    Median time to target FVIII Threshold levels with Jivi® vs Adynovate®2

    Estimated from a population PK model (N = 18) based on potency-adjusted results2*

    Chart representing Median time to target FVIII threshold levels. Jivi. Adynovate.

    PK, pharmacokinetic.

    Adapted from Solms et al. A population PK model was developed based on data obtained by a one-stage assay to simulate time to reach FVIII thresholds of 1%, 3%, 5%, and 10% FVIII.2

    INDICATIONS

    Jivi antihemophilic factor (recombinant), PEGylated-aucl, is a recombinant DNA-derived, Factor VIII concentrate indicated for use in previously treated adults and adolescents (12 years of age and older) with hemophilia A (congenital Factor VIII deficiency) for:

    On-demand treatment and control of bleeding episodes

    Perioperative management of bleeding

    Routine prophylaxis to reduce the frequency of bleeding episodes

    Limitations of use:

    Jivi is not indicated for use in children less than 12 years of age due to a greater risk for hypersensitivity reactions.

    Jivi is not indicated for use in previously untreated patients (PUPs).

    Jivi is not indicated for the treatment of von Willebrand disease.

    IMPORTANT SAFETY INFORMATION

    Jivi is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, polyethylene glycol (PEG), mouse or hamster proteins, or other constituents of the product.

    Hypersensitivity reactions, including severe allergic reactions, have occurred with Jivi. Monitor patients for hypersensitivity symptoms. Early signs of hypersensitivity reactions, which can progress to anaphylaxis, may include chest or throat tightness, dizziness, mild hypotension and nausea. If hypersensitivity reactions occur, immediately discontinue administration and initiate appropriate treatment.

    Jivi may contain trace amounts of mouse and hamster proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

    Hypersensitivity reactions may also be related to antibodies against polyethylene glycol (PEG).

    Neutralizing antibody (inhibitor) formation can occur following administration of Jivi. Carefully monitor patients for the development of Factor VIII inhibitors, using appropriate clinical observations and laboratory tests. If expected plasma Factor VIII activity levels are not attained or if bleeding is not controlled as expected with administered dose, suspect the presence of an inhibitor (neutralizing antibody).

    A clinical immune response associated with IgM anti-PEG antibodies, manifested as symptoms of acute hypersensitivity and/or loss of drug effect, has been observed primarily in patients < 6 years of age. The symptoms of the clinical immune response were transient. Anti-PEG IgM titers decreased over time to undetectable levels. No immunoglobulin class switching was observed.

    In case of clinical suspicion of loss of drug effect, conduct testing for Factor VIII inhibitors and Factor VIII recovery. A low post-infusion Factor VIII level in the absence of detectable Factor VIII inhibitors indicates that loss of drug effect is likely due to anti-PEG antibodies. Discontinue Jivi and switch patients to a previously effective Factor VIII product.

    The most frequently (≥5%) reported adverse reactions in clinical trials in previously treated patients (PTPs) ≥12 years of age were headache, cough, nausea, and fever.

    For additional important risk and use information, please see the full Prescribing Information.

    You are encouraged to report side effects or quality complaints of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
    1-800-FDA-1088.

    INDICATIONS

    Jivi antihemophilic factor (recombinant), PEGylated-aucl, is a recombinant DNA-derived, Factor VIII concentrate indicated for use in previously treated adults and adolescents (12 years of age and older) with hemophilia A (congenital Factor VIII deficiency) for:

    On-demand treatment and control of bleeding episodes

    Perioperative management of bleeding

    Routine prophylaxis to reduce the frequency of bleeding episodes

    Limitations of use:

    Jivi is not indicated for use in children less than 12 years of age due to a greater risk for hypersensitivity reactions.

    Jivi is not indicated for use in previously untreated patients (PUPs).

    Jivi is not indicated for the treatment of von Willebrand disease.

    IMPORTANT SAFETY INFORMATION

    Jivi is contraindicated in patients who have a history of hypersensitivity reactions to the active substance, polyethylene glycol (PEG), mouse or hamster proteins, or other constituents of the product.

    Hypersensitivity reactions, including severe allergic reactions, have occurred with Jivi. Monitor patients for hypersensitivity symptoms. Early signs of hypersensitivity reactions, which can progress to anaphylaxis, may include chest or throat tightness, dizziness, mild hypotension and nausea. If hypersensitivity reactions occur, immediately discontinue administration and initiate appropriate treatment.

    Jivi may contain trace amounts of mouse and hamster proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

    Hypersensitivity reactions may also be related to antibodies against polyethylene glycol (PEG).

    Neutralizing antibody (inhibitor) formation can occur following administration of Jivi. Carefully monitor patients for the development of Factor VIII inhibitors, using appropriate clinical observations and laboratory tests. If expected plasma Factor VIII activity levels are not attained or if bleeding is not controlled as expected with administered dose, suspect the presence of an inhibitor (neutralizing antibody).

    A clinical immune response associated with IgM anti-PEG antibodies, manifested as symptoms of acute hypersensitivity and/or loss of drug effect, has been observed primarily in patients < 6 years of age. The symptoms of the clinical immune response were transient. Anti-PEG IgM titers decreased over time to undetectable levels. No immunoglobulin class switching was observed.

    In case of clinical suspicion of loss of drug effect, conduct testing for Factor VIII inhibitors and Factor VIII recovery. A low post-infusion Factor VIII level in the absence of detectable Factor VIII inhibitors indicates that loss of drug effect is likely due to anti-PEG antibodies. Discontinue Jivi and switch patients to a previously effective Factor VIII product.

    The most frequently (≥5%) reported adverse reactions in clinical trials in previously treated patients (PTPs) ≥12 years of age were headache, cough, nausea, and fever.

    For additional important risk and use information, please see the full Prescribing Information.

    You are encouraged to report side effects or quality complaints of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

    References: 1.Jivi® Prescribing Information.Whippany, NJ: Bayer LLC;2018.  2.Solms A, Shah A, Bemtrop E, et al. Direct comparison of two extended half-life PEGylated recombinant FVIII products: a randomized, crossover pharmacokinetics study in patients with severe hemophilia A, Ann Hematol.Published online September 24,2020. doi.10.1007/s00277-020-04280-3.  3.Anderson PL The ABCs of pharmacokinetics. http://www.thebody.com/content/art875.html.Accessed April 2018.  4.Dhillon S,Gill K. Basic pharmacokinetics. In: Dhillon S, Kostrzewski A,eds. Clinical Pharmacokinetics. London, UK: Pharmaceutical Press; 2006.  5.Ratain MJ, Plunkett WK Jr. Principles of pharmacokinetics. IN: Kufe DW, Pollock RE, Weichselbaum RR, Et al,eds.Holland-Frei Cancer Medicine.6th ed. Hamilton, Ontario: BC Decker;2003.