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VONVENDI [ von Willebrand factor ( Recombinant )] Brief Summary of Prescribing Information . Please see package insert for full Prescribing Information
INDICATIONS AND USAGE
VONVENDI [ von Willebrand factor ( Recombinant )] is a recombinant von Willebrand factor indicated for on-demand treatment and control of bleeding episodes in adults ( age 18 and older ) diagnosed with von Willebrand disease .
CONTRAINDICATIONS
VONVENDI is contraindicated in patients who have had lifethreatening hypersensitivity reactions to VONVENDI or constituents of the product ( tri-sodium citrate-dihydrate , glycine , mannitol , trehalosedihydrate , polysorbate 80 , and hamster or mouse proteins ).
WARNINGS AND PRECAUTIONS
Embolism and Thrombosis Thromboembolic reactions , including disseminated intravascular coagulation ( DIC ), venous thrombosis , pulmonary embolism , myocardial infarction , and stroke , can occur , particularly in patients with known risk factors for thrombosis . Monitor for early signs and symptoms of thrombosis such as pain , swelling , discoloration , dyspnea , cough , hemoptysis , and syncope .
In patients requiring frequent doses of VONVENDI with recombinant factor VIII , monitor plasma levels for FVIII : C activity because an excessive rise in factor VIII levels can increase the risk of thromboembolic complications .
Hypersensitivity Reactions Hypersensitivity reactions , including anaphylaxis , may occur . Symptoms can include anaphylactic shock , generalized urticaria , angioedema , chest tightness , hypotension , shock , lethargy , nausea , vomiting , paresthesia , pruritus , restlessness , wheezing and / or acute respiratory distress . If signs and symptoms of severe allergic reactions occur , immediately discontinue administration of VONVENDI and provide appropriate supportive care .
VONVENDI contains trace amounts of mouse immunoglobulin G ( MuIgG ) and hamster proteins less than or equal to 2 ng / IU VONVENDI . Patients treated with this product may develop hypersensitivity reactions to non-human mammalian proteins .
Neutralizing Antibodies Neutralizing antibodies ( inhibitors ) to von Willebrand factor and / or factor VIII can occur . If the expected plasma levels of VWF activity ( VWF : RCo ) are not attained , perform an appropriate assay to determine if anti-VWF or anti-FVIII inhibitors are present . Consider other therapeutic options and direct the patient to a physician with experience in the care of either von Willebrand disease or hemophilia A .
In patients with high levels of inhibitors to VWF or factor VIII , VONVENDI therapy may not be effective and infusion of this protein may lead to severe hypersensitivity reactions . Since inhibitor antibodies can occur concomitantly with anaphylactic reactions , evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors .
Monitoring Laboratory Tests
• Monitor plasma levels of VWF : RCo and factor VIII activities in patients receiving VONVENDI to avoid sustained excessive von Willebrand factor and / or factor VIII activity levels , which may increase the risk of thrombotic events , particularly in patients with known clinical or laboratory risk factors .
• Monitor for development of von Willebrand factor and / or factor VIII inhibitors when suspected . Perform appropriate inhibitor assays to determine if von Willebrand factor and / or factor VIII inhibitors are present if bleeding is not controlled with the expected dose of VONVENDI .
ADVERSE REACTIONS
The most common adverse reaction observed in ≥2 % of subjects in clinical trials ( n = 66 ) was generalized pruritus .
Clinical Trials Experience Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice .
The safety profile of VONVENDI was evaluated in three prospective , multicenter trials ; two were conducted in subjects with von Willebrand disease ( n = 66 ) and one was conducted in subjects with hemophilia A ( n = 12 ). The adverse reactions reported in the two von Willebrand disease trials are listed in Table 1 .
Table 1 : Summary of Adverse Reactions in Patients with von Willebrand Disease a
System Organ Class ( SOC )
Adverse Reaction a
This trial was done using ADVATE [ Antihemophilic factor ( Recombinant )], a recombinant factor VIII .
Immunogenicity The immunogenicity of VONVENDI was assessed in clinical trials by assessing the development of neutralizing antibodies against rVWF and rFVIII , as well as binding antibodies against rVWF , rFurin , Chinese hamster ovary ( CHO ) protein and mouse IgG . No treatment-related development of binding or neutralizing antibodies against VWF or of neutralizing antibodies against FVIII was observed . Moreover , binding antibodies against potential impurities such as rFurin , CHO-protein or mouse IgG did not develop after treatment with VONVENDI .
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 , it may be misleading to compare the incidence of antibodies to VONVENDI in the studies described above with the incidence of antibodies in other studies or to other products .
© 2016 Shire US Inc ., Lexington , MA 02421 . All rights reserved . 1-800-828-2088 .
BAXALTA and VONVENDI are trademarks or registered trademarks of Baxalta Incorporated , a wholly owned , indirect subsidiary of Shire plc . SHIRE and the Shire Logo are trademarks or registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates . Patented : see www . shire . com / productpatents /.
Baxalta US Inc . Westlake Village , CA 91362 USA U . S . License No . 2020 Printed in USA Issued : 12 / 2015
S24720 11 / 16
Number of Subjects (%) ( n = 66 )
Number of Infusions (%) ( n = 355 )
Cardiac Disorders Tachycardia 1 ( 1.52 %) 1 ( 0.28 %)
Gastrointestinal Disorders
General Disorders and Administration Site Conditions
Skin and Subcutaneous Tissues Disorders
Vascular Disorder
Nervous System Disorders
Nausea 1 ( 1.52 %) 1 ( 0.28 %)
Infusion site paresthesia
1 ( 1.52 %) 1 ( 0.28 %)
Chest discomfort 1 ( 1.52 %) 1 ( 0.28 %)
Generalized pruritus
2 ( 3.03 %) 2 ( 0.56 %)
Hot flush 1 ( 1.52 %) 1 ( 0.28 %) Hypertension 1 ( 1.52 %) 2 ( 0.56 %) Dizziness 1 ( 1.52 %) 1 ( 0.28 %) Dysgeusia 1 ( 1.52 %) 1 ( 0.28 %) Tremor 1 ( 1.52 %) 1 ( 0.28 %)
Investigations Heart rate increase 1 ( 1.52 %) 1 ( 0.28 %)
Electrocardiogram T wave inversions 1 ( 1.52 %) 1 ( 0.28 %)