Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2015 Publisher: LFB-BIOMEDICAMENTS, 3, avenue des Tropiques, BP 40305 LES ULIS, 91958 Courtabœuf Cedex, FRANCE
Hypersensitivity to the active substance or any of the excipients listed in section 6.1.
In actively bleeding patients it is recommended to co-administer a FVIII product with the von Willebrand factor product with a low FVIII content as a first line treatment.
As with any intravenous administration of a plasma-derived protein, allergy type hypersensitivity reactions are possible. Patients must be closely monitored and carefully observed for any symptoms throughout the injection period. Patients should be informed of the early signs of hypersensitivity reactions such as hives, generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. If these symptoms occur, administration should be discontinued immediately. In case of shock, standard medical treatment for shock should be implemented.
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses.
Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). The measures taken may be of limited value against non-enveloped viruses such as hepatitis A and parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (foetal infection) and for individuals with immunodeficiency or increased erythropoesis (e.g. haemolytic anaemia).
Appropriate vaccination (hepatitis A and hepatitis B) should be considered for patients regularly receiving human plasma-derived von Willebrand factor.
It is strongly recommended that every time Willfact is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
There is a risk of occurrence of thrombotic events, particularly in patients with known clinical or laboratory risk factors. Therefore, patients at risk must be monitored for early signs of thrombosis. Prophylaxis against venous thromboembolisms should be instituted according to the current recommendations.
When using a FVIII-containing VWF preparation, the treating physician should be aware that continued treatment may cause an excessive rise in FVIII:C. In patients receiving factor VIII-containing von Willebrand factor products, plasma levels of FVIII:C should be monitored to avoid sustained excessive FVIII:C plasma levels, which may increase the risk of thrombotic events.
Patients with von Willebrand disease, especially Type 3 patients, may develop neutralising antibodies (inhibitors) to VWF. If the expected VWF:RCo activity plasma levels are not attained, or if the bleeding cannot be controlled with an appropriate dose, an assay should be performed to determine if a VWF inhibitor is present. In patients with high levels of inhibitor, von Willebrand factor therapy may not be effective and other therapeutic options should be considered.
This medicinal product contains sodium. For more than 3300 IU injected (more than 1 mmol sodium), 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 studies are insufficient to assess its safety with respect to fertility, reproduction, pregnancy, embryonic/fœtal development or peri- and postnatal development.
The safety of Willfact during pregnancy and lactation has not been investigated in controlled clinical studies.
Willfact should be administered to pregnant and lactating von Willebrand factor deficient women only if clearly indicated.
No effects on the ability to drive or use machines have been observed.
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed infrequently, and may in some cases progress to severe anaphylaxis (including shock).
On rare occasions, fever has been observed.
Patients with von Willebrand disease, especially type 3 patients, may very rarely develop neutralising antibodies (inhibitors) to VWF. Patients treated with VWF should be carefully monitored for the development of inhibitors using appropriate clinical observations and laboratory tests. If such inhibitors occur, the condition will manifest itself as an inadequate clinical response. Such antibodies are precipitating and occur in close association with anaphylactic reactions. In all such cases, it is recommended that a specialised haemophilia centre be contacted.
Therefore, patients experiencing anaphylactic reaction should be evaluated for the presence of an inhibitor.
After correction of the factor Willebrand deficiency, due to the risk of a thrombotic episode in certain risk situations, monitoring for early signs of thrombosis or disseminated intravascular coagulation and prevention of thromboembolic complications should be undertaken according to current practices.
In patients receiving FVIII-containing VWF products sustained excessive FVIII:C plasma levels may increase the risk of thrombotic events.
For safety information with respect to transmissible agents, see section 4.4.
The frequency of adverse event occurrence has been estimated according 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).
Uncommon: Hypersensitivity or allergic reactions. These may in some cases progress to severe anaphylaxis (including shock).
Uncommon: Restlessness
Uncommon: Headache, tingling, lethargy
Uncommon: Tachycardia
Uncommon: Hypotension, flushing
Uncommon: Wheezing
Uncommon: Nausea, vomiting
Uncommon: Angioedema, generalised urticaria, hives
Uncommon: Burning and stinging at the infusion site, chills, tightness of the chest
Rare: Fever
Very rare: Neutralising antibodies (inhibitors) to VWF
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: “Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard”.
Willfact must not be mixed with other medicinal products except for plasma-derived coagulation FVIII produced by LFB-BIOMEDICAMENTS, with which a compatibility study was carried out. This FVIII coagulation factor is however not marketed in all European countries.
Only licensed polypropylene injection sets should be used, because treatment failure can occur as a consequence of human von Willebrand factor adsorption to the internal surface of some injection equipment.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
