Safety profile

The safety profile of VONVENDI was associated with a low rate of adverse reactions in 3 prospective, multicenter studies of patients with von Willebrand disease (VWD).1

Summary of adverse reactions in patients with VWD1,a
System Organ Class Adverse
Reaction
Number of participants (%)b (n=80) Number of infusions
(%)c (n=476)
Cardiac disorders Tachycardia 1 (1.25%) 1 (0.21%)
Gastrointestinal disorders Vomiting Nausea 3 (3.75%) 3 (3.75%) 4 (0.84%) 3 (0.63%)
General disorders and administration site conditions Infusion site paresthesia 1 (1.25%) 1 (0.21%)
Chest
discomfort
1 (1.25%) 1 (0.21%)
Skin and subcutaneous tissue disorders Generalized pruritus 2 (2.50%) 2 (0.42%)
Vascular disorders Hot flush 1 (1.25%) 1 (0.21%)
Hypertension 1 (1.25%) 2 (0.42%)
Deep vein thrombosis 1 (1.25%) 2 (0.42%)
Nervous system disorders Dizziness Vertigo Dysgeusia Tremor 3 (3.75%) 2 (2.50%) 1 (1.25%) 1 (1.25%) 3 (0.63%) 3 (0.63%) 1 (0.21%) 1 (0.21%)
Investigations Heart rate increase 1 (1.25%) 1 (0.21%)
Electro-
cardiogram
T wave
inversions
1 (1.25%) 1 (0.21%)

Single patient treated with VONVENDI in a clinical trial developed infusion related reaction. This patient was previously exposed to VONVENDI without any symptoms. He developed chest discomfort and increased heart rate 3 minutes after the infusion was started. The patient was treated with supportive care and symptoms were resolved in 3 hours.

  • The most common adverse reactions observed in ≥2% of patients in clinical trials with VONVENDI (n=80) were generalized pruritus, vomiting, nausea, dizziness, and vertigo1
  • One patient treated with VONVENDI in the perioperative setting developed deep vein thrombosis (DVT) after undergoing total hip replacement surgery1

Adverse events (AEs) from the pivotal, on-demand study2

The phase 3, open-label study evaluating the efficacy and safety of VONVENDI on demand—with and without recombinant factor VIII (rFVIII)—in adults with severe VWD (N=37) noted AEs related to administration of the treatment:

  • A total of 8/125 (6.4%) of the AEs observed during the study were considered to have a causal relationship to VONVENDI and were subsequently resolved
  • 6/8 (75%) of AEs in 4 subjects were not serious (mild infusion site paresthesia, moderate dysgeusia, moderate tachycardia [n=1], mild electrocardiogram T wave inversion, mild generalized pruritus, mild hot flush [n=1 each])
  • One patient experienced 2 simultaneous serious AEs (chest discomfort and increased heart rate); symptoms improved after 10 minutes of oxygen therapy with a full recovery within 3 hours

Treatment-emergent AEs were reported in 6 patients in the pivotal, surgical phase 3 study (N=15)3

  • 11 of 12 AEs were considered unrelated to treatment: acne, anemia, DVT, diverticulitis, dizziness, dry skin, headache, joint swelling, nasopharyngitis, pelvic pain, and peripheral swelling
  • 1 DVT event, considered possibly related to VONVENDI, was managed throughout the postoperative period; it subsequently resolved

aThese studies also used a recombinant factor VIII.
bPercentages by subject were calculated using the number of all subjects who had the listed adverse events, including ALL AEs that are related.
cTotal number of unique infusions after which at least one AE was reported of the respective ADR preferred term divided by total number of infusions (N) and multiplied by 100.

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Dosing and Administration

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References: 1. VONVENDI [von Willebrand factor (recombinant)] Prescribing Information 2. Gill JC, Castaman G, Windyga J, et al. Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood. 2015;126(17):2038-2046. 3. Peyvandi F, Mamaev A, Wang JD, et al. Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery. J Thromb Haemost. 2019;17(1):52-62.

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:

  • On-demand treatment and control of bleeding episodes
  • Perioperative management of bleeding

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 80 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=80) were generalized pruritus, vomiting, nausea, dizziness, and vertigo.

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

Please see VONVENDI full Prescribing Information.