Vonvendi

Generic name: von Willebrand factor (recombinant)
Drug class: Miscellaneous coagulation modifiers

Medically reviewed by A Ras MD.

What is Vonvendi used for?

Vonvendi is a prescription medicine that is used to treat von Willebrand disease. It is used to stop bleeding.

Description

VONVENDI is a purified rVWF expressed in Chinese Hamster Ovary (CHO) cells. VONVENDI is produced and formulated without the addition of any exogenous raw materials of human or animal origin in the cell culture, purification, or formulation of the final product. Proteins present in the final container product other than rVWF are trace quantities of mouse immunoglobulin (IgG, from the immunoaffinity purification), host cell (i.e., CHO) protein, rFurin (used to further process rVWF), and recombinant factor VIII (rFVIII).

Von Willebrand factor is a large multimeric glycoprotein that is normally found in plasma, and stored as ultra-large multimers in alpha-granules of platelets and intracellular organelles known as Weibel-Palade bodies, prior to secretion into the blood.1 Once the VWF is released to the blood stream and in contact with ADAMTS13 (a proteolytic enzyme in blood), it is cleaved to smaller sizes that can be detected with SDS agarose gels as multimer bands, representing the various species of VWF within the circulation. VONVENDI is rVWF that contains ultra-large multimers in addition to all of the multimers found in plasma as it is not exposed to proteolysis by ADAMTS13 during the manufacturing process.

VONVENDI is formulated as a sterile, non-pyrogenic, white to off-white friable powder for intravenous injection after reconstitution. VONVENDI in a single-dose vial contains nominally 650 or 1300 IU VWF:RCo.

The product contains no preservative. When reconstituted with the provided Sterile Water for Injection the final solution contains the following stabilizers and excipients (Table 7) in targeted amounts:

Table 7: Concentration of Stabilizer and Excipient after Reconstitution
Stabilizer and Excipient	Targeted Concentration for Nominal Strengths (650, 1300 IU)
Tri-Sodium Citrate-dihydrate	15 mM
Glycine	15 mM
Mannitol	20 g/L
Trehalose-dihydrate	10 g/L
Polysorbate 80	0.1 g/L

Each vial of VONVENDI is labeled with the specific number of units of VWF:RCo expressed in IU, which are based on the current World Health Organization (WHO) standard for VWF concentrate. After reconstitution of the lyophilized powder and filtration/withdrawal into a syringe, all dosage strengths yield a clear, colorless solution, free from particles.

Mechanism of Action

In VWD patients, VONVENDI acts 1) to promote hemostasis by mediating platelet adhesion to damaged vascular sub-endothelial matrix (e.g., collagen) and platelet aggregation, and 2) as a carrier protein for factor VIII, protecting it from rapid proteolysis. The adhesive activity of VWF depends on the size of its multimers, with larger multimers being the most effective in supporting interactions with collagen and platelet receptors.1 The binding capacity and affinity of VONVENDI to factor VIII in plasma is comparable to that of endogenous VWF, allowing for VONVENDI to reduce factor VIII clearance.2

Before taking Vonvendi, tell your doctor:

If you are allergic to Vonvendi; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Vonvendi with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Vonvendi?

Tell all of your health care providers that you take Vonvendi. This includes your doctors, nurses, pharmacists, and dentists.
Allergic side effects may rarely happen.
Have blood work checked as you have been told by the doctor. Talk with the doctor.
Blood clots have happened with Vonvendi. Sometimes, blood clots like heart attack and stroke have happened. Talk with the doctor.
Call the doctor right away if the normal dose does not work as well.
Talk with the doctor before you travel. You will need to bring enough of Vonvendi for use during travel.
Tell your doctor if you are pregnant, plan on getting pregnant, or are breast-feeding. You will need to talk about the benefits and risks to you and the baby.

How is Vonvendi best taken?

Use Vonvendi as ordered by your doctor. Read all information given to you. Follow all instructions closely.

It is given as a shot into a vein.
If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
Wash your hands before and after use.
This medicine needs to be mixed before use. Follow how to mix as you were told by the doctor.
If stored in a refrigerator, let Vonvendi come to room temperature before mixing. Do not heat Vonvendi.
Do not shake.
Do not use if the solution is cloudy, leaking, or has particles.
Do not use if solution changes color.
After mixing, do not refrigerate.
Use within 3 hours of making.
Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

Call your doctor to find out what to do.

What are the side effects of Vonvendi that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Signs of high or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
Hot flashes.
A burning, numbness, or tingling feeling that is not normal.
Upset stomach or throwing up.
Feeling very tired or weak.
Restlessness.
Blurred eyesight.
A fast heartbeat.
Twitching.
Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.

What are some other side effects of Vonvendi?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

Change in taste.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Vonvendi?

Store at room temperature or in a refrigerator. Do not freeze.
Store in the original container to protect from light.
Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

Label

PRINCIPAL DISPLAY PANEL – 650 IU VIAL LABEL

NDC 0944-7550-01
VONVENDI
von Willebrand factor
(Recombinant)
Single-use vial, lyophilized powder, sterile
Rx Only
For Intravenous Administration After
Reconstitution Only.
Baxalta US Inc.
Lexington, MA 02421 USA
U.S. License No. 2020

PRINCIPAL DISPLAY PANEL – 5 ML VIAL LABEL

5 mL
NDC 0944-0013-05
Takeda
Sterile Water for Injection, USP
for reconstitution of accompanying product
Do not use unless clear. No antimicrobial agent or other substance
has been added. Do not use for intravascular injection without making
approximately isotonic by addition of suitable solute.
Rx Only
0754013
Single-dose container
Nonpyrogenic