Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Baxalta Innovations GmbH, Industriestraße 67, 1221 Vienna, Austria
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Known allergic reaction to mouse or hamster proteins.
In actively bleeding patients it is recommended to co-administer a FVIII product with VEYVONDI as a first line treatment and depending on the FVIII activity levels (see section 4.2).
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity reactions (including anaphylaxis) have occurred. Patients and/or their caregivers should be informed of the early signs of hypersensitivity reactions, which may include but are not limited to tachycardia, tightness of the chest, wheezing and/or acute respiratory distress, hypotension, generalised urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, restlessness, and may progress to anaphylactic shock. In case of shock, standard medical treatment for shock should be implemented.
Patients should be closely monitored and carefully observed for any symptoms throughout the infusion period. If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of VEYVONDI and provide appropriate supportive care.
Adequate medical treatment and provisions should be available for immediate use for a potential anaphylactic reaction, especially for patients with a history of allergic reactions.
VEYVONDI contains trace amounts of mouse immunoglobulin G (MuIgG) and Hamster proteins (less than or equal to 2 ng/IU VEYVONDI). Patients treated with this product may develop hypersensitivity reactions to these non-human mammalian proteins. VEYVONDI contains trace amounts of recombinant coagulation factor VIII.
There is a risk of occurrence of thrombotic events, particularly in patients with known clinical or laboratory risk factors for thrombosis including low ADAMTS13 levels. Therefore, patients at risk have to be monitored for early signs of thrombosis, and prophylaxis measures against thromboembolism should be instituted according to current recommendations and standard of care.
In patients requiring frequent doses of VEYVONDI in combination with recombinant factor VIII, plasma levels for FVIII:C activity should be monitored to avoid sustained excessive FVIII:C plasma levels, which may increase the risk of thrombotic events.
Any FVIII that would be administered along with VEYVONDI should be a pure FVIII product. A combination with a FVIII product containing VWF would pose an additional risk of thrombotic events.
Patients with VWD, especially Type 3, may develop neutralising antibodies (inhibitors) to von Willebrand factor. If the expected plasma levels of (VWF:RCo) are not attained, or if bleeding is not controlled with an appropriate dose, an appropriate assay should be performed to determine if a von Willebrand factor inhibitor is present. In patients with high levels of anti-VWF antibodies, von Willebrand factor therapy may not be effective and other therapeutic options should be considered.
Treatment of VWD patients who have high-titer binding antibodies (due to previous treatment with pdVWF) may require a higher dose to overcome the binding antibody effect and such patients could be managed clinically by administration of higher doses of vonicog alfa based on the PK data for each individual patient.
This medicinal product contains 5.2 mg sodium in each 650 IU vial or 10.4 mg sodium in each 1300 IU vial. This is equivalent to 2.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult, assuming a body weight of 70 kg and a dose of 80 IU/kg body weight. This is to be taken into consideration by patients on a controlled sodium diet.
No interactions of human von Willebrand factor products with other medicinal products are known.
Animal reproduction studies have not been conducted with VEYVONDI.
Experience in the treatment of pregnant or breast-feeding women is not available. VEYVONDI should be administered to pregnant woment only if clearly indicated, taking into consideration that delivery confers an increased risk of haemorrhagic events in these patients.
It is unknown whether VEYVONDI is excreted in human milk.Therefore, VEYVONDI should be administered to lactating von Willebrand factor deficient women only if clearly indicated. Healthcare professionals should balance the potential risks and only prescribe VEYVONDI if needed
The effects of VEYVONDI on fertility have not been established.
VEYVONDI has no or negligible influence on the ability to drive and use machines.
During treatment with VEYVONDI the following adverse reactions may occur:
Hypersensitivity or allergic reactions, thromboembolic events, inhibitor formation against VWF.
The table 4 lists the adverse reactions reported in clinical trials, post-authorisation safety studies or post-marketing reporting.
Frequency categories are defined according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in the order of decreasing seriousness.
Table 4. Summary of Adverse Reactions reported in Clinical Trials, Post-authorisation safety studies or post-marketing with VEYVONDI in von Willebrand Disease:
| MedDRA System Organ Class (SOC) | Adverse Reaction by Preferred Term (PT) | Frequency Category by Subject | Number and Frequency by Subjecta (N=80) n (%) |
|---|---|---|---|
| Nervous system disorders | Dizziness | Common | 3 (3.75) |
| Vertigo | Common | 2 (2.50) | |
| Dysgeusia | Common | 1 (1.25) | |
| Tremor | Common | 1 (1.25) | |
| Cardiac disorders | Tachycardia | Common | 1 (1.25) |
| Vascular disorders | Deep venous thrombosis | Common | 1 (1.25) |
| Hypertension | Common | 1 (1.25) | |
| Hot flush | Common | 1 (1.25) | |
| Gastrointestinal disorders | Vomiting | Common | 3 (3.75) |
| Nausea | Common | 3 (3.75) | |
| Skin and subcutaneous tissue disorders | Pruritus generalized | Common | 2 (2.50) |
| General disorders and administration site conditions | Chest discomfort | Common | 1 (1.25) |
| Infusion site paraesthesia | Common | 1 (1.25) | |
| Infusion-related reaction (including tachycardia, flushing, rash, dyspnoea, blurred vision) | Not known | ||
| Investigations | Electrocardiogram T wave inversion | Common | 1 (1.25) |
| Heart rate increased | Common | 1 (1.25) | |
| Immune system disorders | Anaphylactic reaction | Not known |
a Frequency by Subject: Total number of subjects experiencing the AE (related and unrelated) divided by total number of subjects (N) and multiplied by 100. Not known: cannot be estimated from the available data (observed during post-marketing surveillance).
In clinical trials, one case of clinically asymptomatic deep vein thrombosis (DVT) was reported for a subject in the surgery study who had total hip replacement.
In addition, one post-marketing case of DVT has been reported spontaneously for an elderly patient.
There is a possibility of developing hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, rhinoconjunctivitis, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) which may in some cases progress to anaphylaxis (including shock).
Patients with von Willebrand disease, especially Type 3, may very rarely develop neutralising antibodies (inhibitors) to von Willebrand factor. If such inhibitors occur, the condition may manifest itself as an inadequate clinical response. Such antibodies may occur in close association with hypersensitivity or anaphylactic reactions. Therefore, patients experiencing hypersensitivity or anaphylactic reactions should be tested and evaluated for the presence of an inhibitor.
In all such cases, it is recommended that a specialised haemophilia centre be contacted.
There is a risk of occurrence of thrombotic events, particularly in patients with known clinical or laboratory risk factors including low ADAMTS13 levels. Therefore, patients at risk have to be monitored for early signs of thrombosis, and prophylaxis measures against thromboembolism should be instituted according to current recommendations and standard of care.
The immunogenicity of VEYVONDI was assessed in clinical trials by monitoring the development of neutralizing antibodies against VWF and FVIII, as well as binding antibodies against VWF, Furin, Chinese Hamster Ovary (CHO) protein and mouse IgG. No treatment-emergent development of neutralizing antibodies against human VWF or neutralizing antibodies against human rFVIII was observed. One of the 80 subjects who received VEYVONDI peri-operatively in clinical studies developed treatment-emergent binding antibodies against VWF following a surgery for whom no adverse events or lack of haemostatic efficacy has been reported. Binding antibodies against impurities such as rFurin, CHO-protein or mouse IgG were not observed after treatment with VEYVONDI.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Clinical and compatibility studies were conducted to administer vonicog alfa (human von Willebrand factor) with octocog alfa (human coagulation factor) in the same syringe. The rVWF and rFVIII can be pre-mixed in a single syringe to achieve the appropriate dose (see section 4.2 for mode of administration). This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
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