Vonvendi: Uses, Side Effects and Dosage

What is VONVENDI used for?

• To treat and control bleeding in patients (age ≥18) with von Willebrand disease.
• To prevent and treat bleeding during and after surgery in patients (age ≥18) with von Willebrand disease.

How does VONVENDI work?

VONVENDI (Lyophilized Powder for Intravenous Injection) is a purified recombinant protein of the clotting factor called von Willebrand Factor (VWF). Recombinant means it is not a plasma-derived product. VONVENDI is an injectable medicine used to replace the von Willebrand Factor that is not functioning or missing in people with von Willebrand disease. VONVENDI raises the level of von Willebrand Factor in the blood, to support the treatment of bleeding events or to prevent and to manage bleeding during and after surgical intervention.

What are the ingredients in VONVENDI?

Medicinal ingredient: von Willebrand Factor (Recombinant).

Non-medicinal ingredients: Glycine, Mannitol, Polysorbate 80 (Tween-80), Trehalose dihydrate, Tri-sodium citrate dihydrate

VONVENDI comes in the two dosage forms:

VWF activity of 650 IU or 1300 IU (International Units) per vial.

The 650 IU vial is supplied with 5 mL sterile water and the 1300 IU vial is supplied with 10 mL sterile water and with each vial a reconstitution device (Mix2Vial) is provided.

Do not use VONVENDI if you:

• Are allergic to any ingredients in VONVENDI
• Are allergic to mouse or hamster proteins

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take VONVENDI. Talk about any health conditions or problems you may have, including if you:

• Have or had any medical problems other than von Willebrand Disease.
• Have or had blood clots (thrombosis).
• Have liver failure or liver disease.
• Have any allergies, including allergies to mice or hamster protein.

• Are breastfeeding. It is not known if VONVENDI passes into your milk and if it can harm your baby.

• Are pregnant or planning to become pregnant. It is not known if VONVENDI may harm your unborn baby.
• Have been told that you have inhibitors to von Willebrand Factor or Factor VIII.

Other warnings you should know about:

Your body may form inhibitors to von Willebrand Factor or Factor VIII. An inhibitor is an antibody that is part of the body’s immune system. If you form inhibitors, it may stop VONVENDI from working properly. Consult with your healthcare professional to make sure you are carefully monitored with blood tests for the development of inhibitors to von Willebrand Factor or Factor VIII.

Call your healthcare professional right away if your bleeding does not stop after taking VONVENDI.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with VONVENDI:

• There are no known interactions of VONVENDI with other medications.
• Tell your doctor if you use a plasma-derived product containing both Factor VIII and von Willebrand Factor.

How to take VONVENDI:

VONVENDI is given directly into the bloodstream.

You may infuse VONVENDI at a hemophilia treatment centre, at your healthcare professional’s office or in your home. You should be trained on how to do infusions by your healthcare professional or hemophilia treatment centre. Many people with von Willebrand disease learn to infuse their VONVENDI by themselves or with the help of a family member.

The reconstituted product (after mixing the powder with the sterile water) must be used within 3 hours and cannot be stored or refrigerated. Discard any VONVENDI left in the vial at the end of your infusion as directed by your healthcare professional.

You may have blood tests done before and after getting VONVENDI to be sure that your blood levels of von Willebrand Factor and Factor VIII are high enough for your blood to clot during bleeding.

Your doctor may also prescribe recombinant factor VIII with VONVENDI.

Administration

General Preparation

• Use aseptic technique (clean and germ free) and a flat work surface during the reconstitution procedure.
• Allow the vials of VONVENDI and sterile water to reach room temperature before use.

Reconstitution Steps

Steps	Image Example
1. Prepare a clean flat surface and gather all the materials you will need for the infusion. Check the expiration date, and let the VONVENDI and sterile water warm up to room temperature. Wash your hands and put on clean exam gloves.
2. Remove the caps from the VONVENDI powder and sterile water vials, to expose the center of the rubber stoppers.
3. Disinfect each stopper with a separate sterile alcohol swab (or other sterile solution suggested by your doctor) by rubbing the stopper for several seconds and allow it to dry prior to use. Place the vials on a flat surface.
4. Open the Mix2Vial device package by completely peeling away the lid, without touching the inside of the package. Do not remove the Mix2Vial device from the package.
5. Turn the package with the Mix2Vial device upside down and place it over the top of the sterile water vial. Firmly insert the blue plastic spike of the device into the center of the sterile water vial stopper by pushing straight down. Grip the package at its edge and lift it off the Mix2Vial device. Be careful not to touch the clear plastic spike. The sterile water vial now has the Mix2Vial device connected to it and is ready to be connected to the VONVENDI powder vial.
6. To connect the sterile water vial to the VONVENDI vial, turn the sterile water vial over and place it on top of the vial containing VONVENDI powder. Fully insert the clear plastic spike into the VONVENDI vial stopper by firmly pushing straight down. This should be done right away to keep the liquid free of germs. The sterile water will flow into the VONVENDI vial by vacuum. Verify that all of the sterile water is transferred into the Mix2Vial. Do not use if vacuum has been lost.
7. Gently and continuously swirl the connected vials or allow the reconstituted product to sit for 5 minutes then gently swirl to ensure the powder is completely dissolved. Do not shake. Shaking will adversely affect the product. Do not refrigerate after reconstitution. Note: Even if you have followed the reconstitution instructions correctly, it is not uncommon for some flakes or particles to remain in the reconstituted product vial. The filter included in the Mix2Vial device will remove these flakes and particles when the reconstituted product is later withdrawn from the vial.

8. Disconnect the two sides of the Mix2Vial from each other by holding the clear plastic side of the Mix2Vial device attached to the VONVENDI vial with one hand and the blue plastic side of the Mix2Vial device attached to the sterile water vial with the other hand. Turn the blue plastic side counterclockwise and gently pull the two vials apart. Do not touch the end of the plastic connector attached to the VONVENDI vial containing the dissolved product. Place the VONVENDI vial on a flat work surface. Discard the empty sterile water vial.
9. Draw air into the empty, sterile disposable plastic syringe by pulling back on the plunger. The amount of air should equal the amount of reconstituted VONVENDI that you will withdraw from the vial.
10. Leaving the VONVENDI vial (containing the dissolved powder) on your flat work surface, connect the syringe to the clear plastic connector by attaching and turning the syringe clockwise.
11. Hold the vial with one hand and use the other hand to push the entire amount of air from the syringe into the vial. The required amount of product will not be drawn into the syringe if all the air is not pushed into the vial.
12. Flip connected syringe and VONVENDI vial so the vial is on top. Be sure to keep the syringe plunger pressed in. Draw the VONVENDI into the syringe by pulling plunger back slowly (less than 1 mL per second). Do not push and pull solution back and forth between syringe and vial. Doing so may harm the integrity of the product. Inspect syringe visually for particulate matter; the solution should be clear and colourless in appearance. If flakes or particles are seen in the syringe, do not use the solution and notify your doctor.
13. When ready to infuse, disconnect the syringe by turning it counterclockwise. NOTE: If your dose requires more than one vial of VONVENDI: Leave the syringe attached to the vial until an additional vial is prepared to reduce risk of contamination. Prepare additional vial(s) of VONVENDI using a separate Mix2Vial device following the reconstitution steps above (2 to 8)

e. Hold the vial with one hand and use the other hand to slowly push air into vial by pressing the syringe plunger. Do not push any fluid from the syringe into the vial.
f. Draw reconstituted VONVENDI from second vial of VONVENDI into syringe by slowly pulling back the plunger. Do not push any fluid from the syringe into the vial. Leave syringe attached to vial until ready to infuse to reduce risk of contamination.
Note: If your dose requires more than two vials of reconstituted VONVENDI, use a NEW plastic syringe. No more than two vials of VONVENDI may be pooled into a single syringe.

Administration

• Visually inspect the reconstituted VONVENDI solution in the syringe for particulate matter and colouration prior to administration. Do not shake the reconstituted solution.

  • The appearance of VONVENDI in the syringe should be a clear, colourless solution, free from particles.
  • Do not administer the solution if flakes or particles, or colouration or cloudiness are seen in the syringe, and notify your doctor.
• Administer VONVENDI as soon as possible, but no later than 3 hours after reconstitution. Do not refrigerate.
• If you need to infuse recombinant factor VIII, reconstitute recombinant factor VIII as instructed in the package insert for that product. Do not administer your recombinant factor VIII until you have infused your complete dose of VONVENDI.
• Always follow your doctor’s specific directions.

Administration Steps:

Steps	Image Example
1. Attach the infusion needle to a syringe containing VONVENDI solution. For comfort, a winged (butterfly) infusion set is preferred. Point the needle up and remove any air bubbles by gently tapping the syringe with your finger and slowly and carefully pushing air out of the syringe and needle.
2. Apply a tourniquet and get the infusion site ready by wiping the skin well with a sterile alcohol swab (or other suitable sterile solution suggested by your doctor or hemophilia treatment centre). Reconstituted product should be inspected visually prior to administration. After withdrawal from the vial, the reconstituted solution within the syringe should be a clear, colourless solution, free from particles. Do not administer if particulate matter, or discolouration or cloudiness is found in the syringe
3. Insert the needle into the vein and remove the tourniquet. Slowly infuse VONVENDI. Do not infuse any faster than 4 mL per minute. Disconnect the empty syringe. If your dose requires multiple syringes, attach and administer each additional syringe of VONVENDI one at a time. Note: Do not remove butterfly needle until all syringes have been infused and do not touch the Luer port that connects to the syringe. If your doctor has prescribed recombinant factor VIII, administer recombinant factor VIII within 10 minutes after you have infused your complete dose of VONVENDI.
4. Take the needle out of the vein and use sterile gauze to put pressure on the infusion site for several minutes.

Usual Dose

Your VONVENDI treatment regimen will be personalized to meet your needs. Your healthcare professional will tell you how much VONVENDI to use based on your individual weight, level of physical activity, the severity of your von Willebrand disease, and where you are bleeding. Your healthcare professional may adjust your dose or frequency to provide you with the levels of von Willebrand factor protection that you need.

Your healthcare professional may measure your individual pharmacokinetics to confirm or adjust your VONVENDI treatment regimen.

Overdose:

The effects of higher than recommended doses of VONVENDI have not been characterized.

Missed Dose:

Talk to your doctor if you have missed a dose.

What are possible side effects from using VONVENDI?

You can have an allergic reaction to VONVENDI. This reaction may sometimes be serious. Call your healthcare professional right away and stop treatment if you get a rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, face-swelling, dizziness, nausea or fainting.

Side effects that have been reported with VONVENDI include: nausea, vomiting, tingling or burning at infusion site, chest discomfort, headache, dizziness, hot flashes, itching, high blood pressure, shaking (tremor), unusual taste, blood clots and increased heart rate.

These are not all the possible side effects you may feel when taking VONVENDI. If you experience any side effects not listed here, contact your healthcare professional.

If you have a troublesome symptom or side effect that is not listed here or any unexpected experience that becomes bad enough to interfere with your daily activities, talk to your healthcare professional.

Reporting Side Effects

Storage:

• Store below 30°C. Do not freeze.
• Do not use beyond the expiration date printed on the carton or vial.
• Store vials in their original box and protect them from extreme exposure to light
• Use the reconstituted product (after mixing dry product with supplied sterile water) immediately or within 3 hours of reconstitution. Do not refrigerate after reconstitution. Discard any unused reconstituted product after 3 hours.

Keep out of reach and sight of children.

If you want more information about VONVENDI:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website: (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html); the manufacturer’s website https://www.takeda.com/en-ca, or by calling 1-800-268-2772.

Takeda Canada Inc.

22 Adelaide Street West, Suite 3800

Toronto ON M5H 4E3

Last Revised NOV 28, 2023

VONVENDI^® is a registered trademark of Baxalta Incorporated.

TAKEDA and are registered trademarks of Takeda Pharmaceutical Company Limited, used under license.