Von Willebrand Factor (recombinant) (Monograph)

Brand name: Vonvendi
Drug class: Hemostatics
Chemical name: Blood-coagulation factor VIII, von Willebrand's
Molecular formula: C₉₇₁₂H₁₅₃₇₃N₂₇₃₇O₃₀₃₂S₂₁₀
CAS number: 109319-16-6

Introduction

Von Willebrand factor (recombinant) is a hemostatic.

Uses for Von Willebrand Factor (recombinant)

Von Willebrand factor (recombinant) has the following uses:

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 (VWD).

Von Willebrand Factor (recombinant) Dosage and Administration

General

Von Willebrand factor (recombinant) is available in the following dosage form(s) and strength(s):

Von Willebrand factor (recombinant) is available as a lyophilized powder in single-use vials containing nominally 650 or 1300 international units von Willebrand factor activity (VWF:RCo).

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

For intravenous use after reconstitution only.

• For each bleeding episode, administer the first dose of von Willebrand factor (recombinant) with an approved recombinant (non-von Willebrand factor containing) factor VIII [antihemophilic factor (recombinant)] if factor VIII baseline levels are below 40% or are unknown.

• Initial dose is 40 to 80 international units (IU) per kg body weight. Adjust the dosage based on the extent and location of bleeding.

^a If recombinant factor VIII is administered, see recombinant factor VIII package insert for reconstitution and administration instructions.

^b A bleed could be considered major if red blood cell transfusion is either required or potentially indicated or if bleeding occurs in a critical anatomical site (e.g., intracranial or gastrointestinal hemorrhage).

• If recombinant factor VIII is required, give recombinant factor VIII within 10 minutes of completing von Willebrand factor (recombinant) infusion at a ratio of 1.3:1 (i.e., 30% more von Willebrand factor [recombinant] than recombinant factor VIII, based on the approximate mean recoveries of 1.5 and 2.0 IU/dL for von Willebrand factor [recombinant] and recombinant factor VIII, respectively). Consult the package insert for the specific factor VIII product for dosing recommendations.

• Administer von Willebrand factor (recombinant) within 3 hours after reconstitution.

Cautions for Von Willebrand Factor (recombinant)

Contraindications

Do not use in patients who have had life-threatening hypersensitivity reactions to von Willebrand factor (recombinant) or its components (mannitol, trehalose, sodium chloride, histidine, Tris, calcium chloride, polysorbate 80, and hamster or mouse proteins).

Warnings/Precautions

Thromboembolic Reactions

Thromboembolic reactions, including disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, can occur, particularly in patients with known risk factors for thrombosis. Monitor for early signs and symptoms of thrombosis such as pain, swelling, discoloration, dyspnea, cough, hemoptysis, and syncope.

In patients requiring frequent doses of von Willebrand factor (recombinant) with recombinant factor VIII, monitor plasma levels for FVIII:C activity because an excessive rise in factor VIII levels can increase the risk of thromboembolic complications.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, may occur. Symptoms can include anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, wheezing, and/or acute respiratory distress. If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of von Willebrand factor (recombinant) and provide appropriate supportive care.

Von Willebrand factor (recombinant) contains trace amounts of mouse immunoglobulin G (MuIgG) and hamster proteins less than or equal to 2 ng/IU von Willebrand factor (recombinant). Patients treated with this product may develop hypersensitivity reactions to non-human mammalian proteins.

Neutralizing Antibodies

Neutralizing antibodies (inhibitors) to von Willebrand factor 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-FVIII inhibitors are present. Consider other therapeutic options and direct the patient to a physician with experience in the care of either von Willebrand disease or hemophilia A.

In patients with high levels of inhibitors to VWF or factor VIII, von Willebrand factor (recombinant) 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.

Monitoring Laboratory Tests

• Monitor plasma levels of VWF:RCo and factor VIII activities in patients receiving von Willebrand factor (recombinant) to avoid sustained excessive von Willebrand factor and/or factor VIII activity levels, which may increase the risk of thrombotic events, particularly in patients with known clinical or laboratory risk factors.

• Monitor for development of von Willebrand factor and/or factor VIII inhibitors when suspected. Perform appropriate inhibitor assays to determine if von Willebrand factor and/or factor VIII inhibitors are present if bleeding is not controlled with the expected dose of von Willebrand factor (recombinant).

Specific Populations

Pregnancy

There are no studies of von Willebrand factor (recombinant) use in pregnant women. The background risk of major birth defects and miscarriage in the indicated population is unknown; however, the background risk of major birth defects in the U.S. general population is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. Animal reproduction studies have not been conducted with von Willebrand factor (recombinant). It is not known whether von Willebrand factor (recombinant) can cause fetal harm when administered to a pregnant woman or whether it can affect reproduction capacity. Von Willebrand factor (recombinant) should be given to a pregnant woman only if clearly needed.

Nursing Mothers

There is no information regarding the presence of von Willebrand factor (recombinant) in human milk, its effects on the breastfed infant, or its effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for von Willebrand factor (recombinant) and any potential adverse effects on the breastfed infant from von Willebrand factor (recombinant) or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Geriatric Use

Clinical trials of von Willebrand factor (recombinant) did not include subjects aged 65 and over to determine whether they respond differently compared to younger subjects.

Common Adverse Effects

The most common adverse reaction observed (≥2% of subjects) was generalized pruritus.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

In VWD patients, von Willebrand factor (recombinant) acts to promote hemostasis by mediating platelet adhesion to damaged vascular subendothelial matrix (e.g., collagen) and platelet aggregation, and as a carrier protein for factor VIII2, protecting it from rapid proteolysis. The adhesive activity of VWF depends on the size of its multimers, with large multimers being the most effective in supporting interactions with collagen and platelet receptors. The factor VIII binding capacity and affinity to von Willebrand factor (recombinant) is comparable to that of VWF present in plasma and platelets, allowing for von Willebrand factor (recombinant) to reduce factor VIII clearance.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Advise patients of the early signs of hypersensitivity reactions, including anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, wheezing, and/or acute respiratory distress. Advise patients to discontinue use of the product if these symptoms occur and seek immediate emergency treatment with resuscitative measures.

Advise patients to contact their physician or treatment center for further treatment and/or assessment if they experience a lack of clinical response to von Willebrand factor therapy, as this may be a manifestation of an inhibitor.

Advise patients to consult with their physicians or healthcare provider prior to travel. While traveling, advise patients to bring an adequate supply of von Willebrand factor (recombinant) based on their current regimen of treatment.

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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