For: von Willebrand's Disease
Vonvendi [von Willebrand factor (recombinant)] is a recombinant von Willebrand factor (VWF) indicated for on-demand treatment and control of bleeding episodes in adults diagnosed with von Willebrand disease. These highlights do not include all the information needed to use VONVENDI safely and effectively. See full prescribing information for VONVENDI.
VONVENDI [von Willebrand factor (recombinant)]
lyophilized powder for solution, for intravenous injection.
Initial U.S. Approval: 2015
RECENT MAJOR CHANGES
Indication and Usage (1) 4/2018
Dosage and Administration, Recommended Dose and Schedule (2.1) 4/2018
Warnings and Precautions, Embolism and Thrombosis (5.1) 4/2018
INDICATIONS AND USAGE
VONVENDI [von Willebrand factor (recombinant)] is a recombinant von Willebrand factor (rVWF) indicated for use in adults (age 18 and older) diagnosed with von Willebrand disease (VWD) for: (1)
On-demand treatment and control of bleeding episodes. (1)
Perioperative management of bleeding. (1)
DOSAGE AND ADMINISTRATION
For intravenous use after reconstitution only (2)
On-demand Treatment and Control of Bleeding Episodes:
For each bleeding episode, administer the first dose of VONVENDI with an approved recombinant (non-von Willebrand factor containing) factor VIII, if factor VIII baseline levels are below 40% or are unknown.(2.1)
Initial dose is 40 to 80 International Units (IU) per kg body weight. Adjust the dosage based on the extent and location of bleeding. (2.1)
Bleeding Episode Initial Dose Subsequent Dose
Minor 40 to 50 IU/kg 40 to 50 IU/kg every 8 to 24 hours
Major 50 to 80 IU/kg 40 to 60 IU/kg every 8 to 24 hours for approximately 2 to 3 days
Perioperative Management of Bleeding:
For elective surgical procedure:
A dose of VONVENDI may be given 12 to 24 hours prior to surgery to allow the endogenous factor VIII levels to increase to at least 30 IU/dL (minor surgery) or 60 IU/dL (major surgery). (2.1)
Assess FVIII:C levels within 3 hours prior to surgery; If the FVIII:C levels are at or above the recommended minimum target levels, administer a dose of VONVENDI alone within 1 hour prior to the procedure. If the FVIII:C levels are below the recommended minimum target levels, administer recombinant factor VIII in addition to VONVENDI to raise VWF:RCo and FVIII:C. (2.1)
For emergency surgery:
Assess baseline VWF:RCo and FVIII:C levels within 3 hours prior to surgery. If not available, use weight based dosing calculation (2.1)
Administer VONVENDI one hour before surgery with or without recombinant factor VIII and adjust the dose to raise VWF:RCo and FVIII:C to adequate level.(2.1)
Type of Surgery Target Peak Plasma Level Calculation of rVWF Dose
(IU VWF:RCo required)
VWF:RCo FVIII:C
Minor 50 to 60 IU/dL 40 to 50 IU/dL ? VWF:RCo � BW (kg) /IR
Major 100 IU/dL 80 to100 IU/dL
Continue to monitor the VWF:RCo and FVIII:C plasma levels after surgical procedure. (2.1)
DOSAGE FORMS AND STRENGTHS
VONVENDI is available as a lyophilized powder in single-use vials containing nominally 650 or 1300 international units VWF:RCo. (3)
CONTRAINDICATIONS
Do not use in patients who have had life-threatening hypersensitivity reactions to VONVENDI or its components (tri-sodium citrate dihydrate, glycine, mannitol, trehalose-dihydrate polysorbate 80, and hamster or mouse proteins). (4)
WARNINGS AND PRECAUTIONS
Thromboembolic reactions can occur, particularly in patients with risk factors for thrombosis. Monitor for early signs of thrombosis and have prophylaxis measures against thromboembolism instituted according to current recommendations. One out of 80 VWD subjects treated with VONVENDI in clinical trials developed proximal deep vein thrombosis in perioperative period after undergoing total hip replacement surgery. In patients requiring frequent doses of VONVENDI in combination with recombinant factor VIII, monitor plasma levels for FVIII:C because sustained excessive factor VIII plasma levels can increase the risk for thromboembolic events. (5.1)
Hypersensitivity reactions, including anaphylaxis, may occur. Discontinue VONVENDI if hypersensitivity symptoms occur and administer appropriate emergency treatment. (5.2)
Inhibitors to von Willebrand factor (VWF) and/or factor VIII can occur. If the expected plasma levels of VWF activity (VWF:RCo) are not attained, or if bleeding is not controlled with an appropriate dose, perform an appropriate assay to determine if an anti-VWF or anti-factor VIII inhibitors are present. (5.3)
ADVERSE REACTIONS
The most common adverse reactions observed (?2% of subjects) were generalized pruritus, vomiting, nausea, dizziness, and vertigo. (6.1)
One subject treated with VONVENDI in perioperative setting developed deep vein thrombosis after undergoing total hip replacement surgery. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Baxalta US Inc. at 1-800-999-1785 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 2/2019
