Von Willebrand Factor Recombinant (Intravenous)

Von Willebrand recombinant is part of a faction of drugs known as recombinant protein treatments. These kinds of drugs work by providing proteins that aid in the clotting of blood.

Overview

The Food and Drug Administration (FDA) of the U.S. permitted Von Willebrand in December 2015 and it is designated for on-demand treatment and management of bleeding episodes in persons aged 18 years and above with VWD. Von Willebrand is the first and only Von Willebrand treatment for persons living with VWD. The trials are projected to end in 2019 and 2020, respectively.

In the U.S., von Willebrand recombinant is known by the brand name vonvendi. Von Willebrand recombinant is available as generics which are cheaper than the original brand.

Von Willebrand factor is available in powder form and has to be diluted with a liquid before use. Patients need to understand how to mix and store the drug well, especially if they use it at home. The diluted von Willebrand factor should be used within three hours if it has been stored at room temperature.

Vonvendi is a filtered recombinant von Willebrand factor expressed in Chinese Hamster Ovary cells. It is formulated and produced without the addition of any exogenous raw materials either human or animal origin in the purification, cell culture, or formulation of the last product.

The only proteins available in the finished container product other than rVWF are small quantities of hamster or mouse immunoglobulin from the host cell protein, and recombinant factor VIII.

Von Willebrand is administered via IV through the vein.

Conditions treated

  • von Willebrand disease

Type of medicines

  • Antihemophilic Agent

Side effects

Side effects are rare. However, a patient needs to call a medical practitioner when they see the following outlined signs and symptoms:

  • A fast heartbeat
  • Feeling very weak or tired
  • Restlessness
  • Twitching
  • Numbness, or a tingling or burning feeling that is not normal
  • Throwing up or an upset stomach
  • Flushing
  • Signs of an allergic reaction such as rashes with presence of fever or complete absence of it
  • Gasping or tightness in the throat or chest, trouble breathing or talking, unusual hoarseness or inflammation of the face, mouth, tongue lips, or throat.
  • Weakness on the left or right side of the body, change in balance, drooping on one side of the face, blurred eyesight, trouble speaking or thinking, blurred vision.
  • Medical attention should be sought if the patient has signs of a blood clot, such as shortness of breath, change of skin color, or pain in the arm or leg, trouble swallowing or speaking, or coughing up blood.
  • Dizziness or passing out.

Less common side effects include:

  • Burning, itching, crawling, pricking (needles and pins) numbness, or stinging feeling at the point of infusion
  • Feeling of warmth
  • Sudden sweating
  • Shakiness in the feet, legs, arms, or hands
  • Loss of taste
  • Redness of the neck, face, arms, and sporadically, upper chest
  • Shaking or trembling of the feet or hands
  • Change in taste

Dosage

  • For every bleeding episode, run the first dose of Vonvendi with a permitted recombinant (non-von Willebrand factor containing) factor VIII [Antihemophilic factor (Recombinant)] if factor VIII baseline levels are below 40% or are unknown.
  • The primary dose of Vonvendi is 40-80 IU per kg the dosage should be altered considering the amount and site of bleeding.
  • In cases where recombinant factor VIII is necessary, give recombinant factor VIII within 10 minutes of carrying out Vonvendi infusion at a ratio of 1:3:1.
  • Vonvendi should be administered within three hours after reconstitution.

Consider the following before use of VWF recombinant:

  • Vial, as well as diluents that are warm, should be set aside to achieve room temperature before reconstitution.
  • After adding diluents, the reconstituted product should be gently swirled or allowed to sit for about five minutes. This will ensure complete dissolution - but avoid shaking.
  • Reconstitute each vial separately in cases where more than a vial is required.
  • Only plastic syringes should be used, since proteins in the product always attach to the surface of glass syringes.
  • The product should not mix with any additional medicinal products.
  • Always see details of the manufacturer's product labeling.
  • Your doctor may teach you how to give the shot.
  • Wash hands before and after use.
  • Do not use if the drug is leaking, has particles or is unclear.
  • Refrain from the use of the product if it changes color.
  • Do not refrigerate after reconstitution.
  • The product should be used within 3 hours of reconstitution.
  • Do not recycle needles or other items.

Administration

  • It is given as a shot into a vein.
  • Inculcate gradually a maximum rate: 4 mL/minute.
  • In case of occurrence of tachycardia, slow down the infusion rate or stop it altogether.
  • If also running factor VIII (recombinant), run factor VIII (recombinant) within 10 minutes of completing VWF (recombinant) in the ratio of 1:3:1.

Storage

  • VWF should be stored in its original packaging.
  • VWF should be stored away from light.
  • If stored in the refrigerator, the temperature should be between 2°C and 8°C.
  • If stored at room temperature, it should be kept at 30°C for up to a year.
  • Do not at any time freeze VWF.

If you store VWF at room temperature:

  • Write the date when taken out of the refrigerator on the packaging.
  • Do not use after a year has elapsed from the date noted on the packaging or after the expiration date.
  • Do not put VWF back in the refrigerator.

Storing the mixed (reconstituted) product

  • After mixing the vile with sterile water, store the reconstituted product at room temperature that does not exceed 27 °C for up to three hours.
  • Discard when three hours lapses.

Interactions

The manufacturer has reported no drug interactions. There are no specific foods that should be avoided or excluded from the diet when getting the medication.

However, there are a number of drugs that may combine with von Willebrand factor, including over the counter medicines, prescription, herbal and vitamins products.

Contraindications

Von Willebrand factor is contraindicated in people who have had ruthless hypersensitivity response to Von Willebrand or ingredients of the drug (glycine, mannitol, tri-sodium citrate-dihydrate, polysorbate 80, trehalose-dihydrate, and mouse or hamster).

Before taking this medication, inform your doctor about all of your medical conditions. Especially if you:

  • Have any previous or current medical conditions
  • Have been tested and found to have inhibitors to blood coagulation factor VIII
  • Have any allergies, particularly in hamsters or mice
  • Are nursing a child - Von Willebrand is likely to harm the child when it passes through the milk
  • Are allergic to von Willebrand factor or any of its components
  • Are pregnant or planning to get pregnant
  • Have tested and been found to have inhibitors of von Willebrand factor

Warnings

Embolism and Thrombosis

Thromboembolic reactions, including disseminated intravascular coagulation (DIC), myocardial infarction, pulmonary embolism, venous thrombosis and stroke is likely to occur, mainly in patients with recognized threat factors for thrombosis.

Early symptoms and signs of thrombosis should be monitored such as swelling, pain, cough discoloration, syncope, dyspnea, and hemoptysis.

In patients that need frequent doses of von Willebrand with recombinant factor VIII, plasma levels for FVIII: C. Activity should be monitored since an undue rise in factor VIII levels can add to the risk of thromboembolic difficulty.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, are likely to occur. Symptoms may consist of generalized urticaria, anaphylactic shock, chest tightness, angioedema, hypotension, nausea, shock, lethargy, vomiting, restlessness, paresthesia, pruritus, and wheezing as well as acute respiratory distress.

Immediately discontinue administration of von Willebrand if symptoms and signs of harsh allergic reactions arise, and provide proper supportive care.

Neutralizing Antibodies

Neutralizing antibodies to von Willebrand factor and factor VIII is likely to happen. If the anticipated plasma levels of VWF activity are not attained, an appropriate assay is supposed to be performed to determine if anti-VWF or anti-FVIII inhibitors are there. Other therapeutic option should be considered. The patient should then be referred to a physician with understanding in the care of both von Willebrand disease and hemophilia A.

Adverse reactions

For the most part, widespread unpleasant result seen in 2% of subjects in clinical trials (n=66) was generalized pruritus as no safety alarm was identified.

Summary

Von Willebrand disease is the most frequent inherited bleeding disorder, distressing 1% of the people in the U.S., according to the FDA. A defect in von Willebrand factor, which is a protein vital for clotting, causes it.

Patients with von Willebrand disease can cause severe bleeding from the gums, nose, and intestines, as well as into joints and muscles. Women who have von Willebrand disease are likely to have substantial menstrual periods that last longer than average and also experience too much bleeding after childbirth.

Von Willebrand resolves bleeding episodes, with a median of only two infusions to take care of severe bleeds.

Resources
Last Reviewed:
December 25, 2017
Last Updated:
April 05, 2018