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:

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).

Please see VONVENDI full Detailed Important Risk Information at the end of this video.

In this video, you will learn how to prepare and reconstitute VONVENDI [von Willebrand factor (Recombinant)]. For complete instructions, please see the full prescribing information.

Before you begin, make sure you have enough VONVENDI kits for a full dose. If the patient requires more than one vial of VONVENDI per injection, reconstitute each vial according to the instructions in this video.

Depending on your patient’s need as determined by monitoring levels and clinical judgement, you may also need to infuse recombinant factor VIII to control bleeding. If you are also administering recombinant factor VIII, make sure you have enough recombinant factor VIII for the patient’s full dose.

VONVENDI can be stored at refrigerated temperature 2 degrees Celsius to 8 degrees Celsius (36 degrees Fahrenheit to 46 degrees Fahrenheit) or room temperature not to exceed 30 degrees Celsius (86 degrees Fahrenheit) for the life of the product. Do not freeze VONVENDI. VONVENDI should be administered immediately after reconstitution. If VONVENDI is not used immediately after reconstitution, store at room temperate not to exceed 25 degrees Celsius (77 degrees Fahrenheit) for up to 3 hours. Discard any unused product after 3 hours.

Step 1: Prepare Materials

Begin by gathering your infusion supplies on a clean, flat surface. Supplies for reconstitution include VONVENDI product kit or kits, which contain VONVENDI, Sterile Water for Injection—or diluent, and the Mix2Vial device, and alcohol swabs or other suitable sterile solution.

Check the dosage and expiration date listed on the product kit or vials of VONVENDI. Allow both VONVENDI and diluent to reach room temperature before preparation and reconstitution. Then, wash your hands and put on clean exam gloves.

Step 2: Sterilization

Next, place both vials on a flat surface, and remove the caps from the VONVENDI vial and the diluent vial to expose the centers of both rubber stoppers. Clean each vial stopper with a sterile alcohol swab and allow the stoppers to dry. Then, peel back the cover of the Mix2Vial transfer device. To maintain sterility, leave the Mix2Vial device in the clear plastic packaging.

Step 3: Connect Vials

While using one hand to firmly hold the diluent vial on your work surface, use your other hand to pick up the Mix2Vial device in its plastic package and invert it over the diluent vial. Connect the Mix2Vial to the diluent vial by firmly pushing the blue plastic cannula of the Mix2Vial straight down through the rubber stopper. Carefully remove the plastic package, leaving Mix2Vial device attached to the diluent vial.

Now, hold VONVENDI vial firmly on your work surface with one hand, and use your other hand to quickly invert the diluent vial with the Mix2Vial device attached and firmly push the transparent plastic cannula end of the Mix2Vial straight down through the stopper of the VONVENDI vial. The vacuum effect will automatically draw the diluent into the VONVENDI vial. Look closely to verify that the diluent transfer is complete. If for some reason the vacuum seal was lost, discard the product and start again.

Step 4: Reconstitution

With both vials still attached, gently swirl the connected vials. Allow the reconstituted product to sit for 5 minutes, then gently swirl it to ensure the powder is completely dissolved. Do not shake; shaking will adversely affect the integrity of the product.

Please note that some flakes or particles may remain in the reconstituted vial. The filter included in the Mix2Vial device will remove extraneous flakes or particles and the resulting solution in the syringe should be clear and colorless.
Next, firmly hold both the transparent and the blue parts of the Mix2Vial, and unscrew the Mix2Vial into two separate pieces. Be careful not to touch the exposed connector. Discard the empty diluent vial and the blue side of the Mix2Vial.

Please note that the Mix2Vial is intended for one time use with a single vial of VONVENDI and diluent only. If your patient’s dose requires more than one vial of VONVENDI, reconstitute each vial separately. Repeat reconstitution steps above for all VONVENDI product vials needed for your dose prior to continuing on the next step. Do not refrigerate product after reconstitution.

Step 5: Syringe Preparation

Next, draw air into an empty, sterile disposable plastic syringe. The amount of air you draw in should equal the amount of reconstituted VONVENDI you will withdraw from the vial. Be careful not to touch the exposed connector.

Holding the VONVENDI vial firmly on your work surface, connect the syringe to the plastic connector by attaching and turning it clockwise, taking care not to touch the barrel of the plunger.

Continue holding the vial on your work surface and use the other hand to slowly push the entire amount of air from the syringe down into the vial. Be sure to push all the air into the vial, or the required amount of product will not be drawn into the syringe.

Step 6: Drawing the Syringe

Now, flip the connected syringe and VONVENDI vial so the vial is on top. Make sure to keep the syringe plunger pressed in. Next, draw VONVENDI into the syringe by slowly pulling back the plunger. Do not push and pull the solution back and forth between the syringe and the vial, as doing so could harm the integrity of the product. To avoid contamination, leave the syringe attached to the vial until you are ready to infuse. Be sure to use VONVENDI within three hours, and to keep it at room temperature, no warmer than 25 degrees Celsius (77 degrees Fahrenheit).

Carefully inspect your syringe or syringes for discoloration and particulate matter prior to administration. The solution should look clear, or slightly opalescent in appearance. If you do observe particulate matter, discoloration, or cloudiness, do not administer, and notify Takeda Customer Service at 1.888.423.8283.

When ready to infuse, firmly hold the barrel of the syringe—keeping the syringe plunger facing down—and detach the Mix2Vial from the syringe. Discard the transparent plastic part of the Mix2Vial and the empty VONVENDI vial.

If the patient is to receive more than one vial of VONVENDI, the contents of up to two vials may be drawn into a single syringe. When pushing air into a second vial of VONVENDI to be pooled into a syringe, position the vial and connected syringe so that the vial is on top.

Please note that no more than two vials of VONVENDI may be pooled into a single syringe. Pooling of more than two vials into a syringe may result in formation of filaments, which requires discarding of the solution in the syringe. If a patient is to receive more than one vial of VONVENDI, leave the syringe attached to the vial, or cover the syringe top with a suitable sterile cap until ready to infuse to reduce risk of contamination. Do not mix VONVENDI with other medical products.

Now you're ready to infuse your patient with VONVENDI.

Thank you for watching.

Indications and Detailed Important Risk Information

Indications
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:

Detailed Important Risk Information
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).

WARNINGS AND PRECAUTIONS

Embolism and Thrombosis

Thromboembolic reactions, including disseminated intravascular coagulation, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur, particularly in patients with known risk factors for thrombosis, including low ADAMTS13 levels. Monitor for early signs and symptoms of thrombosis such as pain, swelling, discoloration, dyspnea, cough, hemoptysis, and syncope, and institute prophylaxis measures against thromboembolism based on current recommendations.

In patients requiring frequent doses of VONVENDI in combination with recombinant factor VIII, monitor plasma levels for FVIII:C activity because sustained excessive factor VIII plasma levels can increase the risk of thromboembolic events.

One out of 100 subjects treated with VONVENDI in clinical trials developed proximal deep vein thrombosis in perioperative period after total hip replacement surgery.

Hypersensitivity Reactions

Hypersensitivity reactions have occurred with VONVENDI. These reactions can include anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, blurred vision, wheezing and/or acute respiratory distress. Discontinue VONVENDI if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies (Inhibitors)

Inhibitors to VWF 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-factor VIII inhibitors are present. Consider other therapeutic options and direct the patient to a physician with experience in the care of either VWD 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.

ADVERSE REACTIONS

In clinical trials, the most common adverse reactions observed in ≥2% of subjects (n=100) were headache, vomiting, nausea, dizziness, arthralgia, joint injury, vertigo, ALT increased and generalized pruritus.

One subject treated with VONVENDI in perioperative setting developed deep vein thrombosis after total hip replacement surgery.

Please see VONVENDI full Prescribing Information at VONVENDIPRO.com.