WILATE Powder and solvent for solution for injection Ref.[50681] Active ingredients: Coagulation factor VIII Von Willebrand factor

Traceability

In order to improve traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity

Allergic type hypersensitivity reactions are possible with Wilate. The product contains traces of human proteins other than factor VIII. If symptoms of hypersensitivity occur, patients should be advised to discontinue use of the medicinal product immediately and contact their physician.

Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.

In case of shock, standard medical treatment for shock should be implemented.

Transmissible agents

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), and for the non-enveloped hepatitis A virus. The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19.

Parvovirus B19 infection may be serious for pregnant women (foetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).

Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived VWF/factor VIII products.

It is strongly recommended that every time that Wilate 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.

Von Willebrand disease (VWD)

Thromboembolic events

When using a FVIII-containing VWF product, the treating physician should be aware that continued treatment may cause an excessive rise in FVIII:C. In patients receiving FVIIIcontaining VWF 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.

There is a risk of occurrence of thrombotic events when using FVIII-containing VWF products, 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 thromboembolism should be instituted, according to the current recommendations.

Inhibitors

Patients with VWD, especially type 3 patients, may develop neutralising antibodies (inhibitors) to VWF. If the expected VWF:RCo activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, an appropriate assay should be performed to determine if a VWF inhibitor is present. In patients with high levels of inhibitor, VWF therapy may not be effective and other therapeutic options should be considered. Management of such patients should be directed by physicians with experience in the care of patients with haemostatic disorders.

Haemophilia A

Inhibitors

The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the management of individuals with haemophilia A. These inhibitors are usually IgG immunoglobulins directed against the factor VIII pro-coagulant activity, which are quantified in Bethesda Units (BU) per ml of plasma using the modified assay. The risk of developing inhibitors is correlated to the severity of the disease as well as the exposure to factor VIII, this risk being highest within the first 50 exposure days but continues throughout life although the risk is uncommon.

The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre posing less of a risk of insufficient clinical response than high titre inhibitors. In general, all patients treated with coagulation factor VIII products should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. If the expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, testing for factor VIII inhibitor presence should be performed. In patients with high levels of inhibitor, factor VIII therapy may not be effective and other therapeutic options should be considered. Management of such patients should be directed by physicians with experience in the care of haemophilia and factor VIII inhibitors.

Cardiovascular events

In patients with existing cardiovascular risk factors, substitution therapy with FVIII may increase the cardiovascular risk.

Catheter-related complications

If a central venous access device (CVAD) is required, risk of CVAD-related complications including local infections, bacteraemia and catheter site thrombosis should be considered.

This medicinal product contains up to 58.7 mg sodium per vial for 500 IU VWF and FVIII/vial, and up to 117.3 mg sodium per vial for 1000 IU VWF and FVIII/vial, equivalent to 2.94% and 5.87%, respectively, of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Paediatric population

The listed warnings and precautions apply to both adults and children.

No interactions with other medicinal products are known.

Animal reproduction studies have not been conducted with VWF/factor VIII.

Von Willebrand disease (VWD)

Experience in the treatment of pregnant or lactating women is not available.

Wilate should be administered to pregnant or lactating VWF deficient women only if clearly indicated, taking into consideration that delivery confers an increased risk of haemorrhagic events in these patients.

Haemophilia A

Based on the rare occurrence of haemophilia A in women, experience regarding the treatment during pregnancy and breastfeeding is not available. Therefore, Wilate should be used during pregnancy and lactation only if clearly indicated.

Wilate has no influence on the ability to drive and use machines.

Summary of the safety profile

Hypersensitivity or allergic reactions (which may include angiooedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, erythema, pruritus, rash, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, dyspnoea, tingling, vomiting, wheezing) have been observed rarely, and may in some cases progress to severe anaphylaxis (including shock).

Von Willebrand disease (VWD)

Patients with VWD, especially type 3 patients, may very rarely develop neutralising antibodies to VWF. If such inhibitors occur, the condition will manifest itself as an inadequate clinical response. Such antibodies occur in close association with anaphylactic reactions. Therefore, patients experiencing anaphylactic reaction should be evaluated for the presence of an inhibitor.

In all such cases, it is recommended that a specialised haemophilia centre be contacted.

No cases of inhibitors for von Willebrand factor have been reported from clinical studies or from post marketing experience for Wilate so far.

There is a risk of occurrence of thrombotic events, particularly in patients with known clinical or laboratory risk factors. Prophylaxis against venous thromboembolism should be instituted, according to the current recommendations.

In patients receiving FVIII-containing VWF products sustained excessive FVIII:C plasma levels may increase the risk of thrombotic events.

Haemophilia A

Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated with factor VIII, including with Wilate see section 5.1. If such inhibitors occur, the condition will manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia centre be contacted.

For safety information with respect to transmissible agents, see section 4.4

Tabulated list of adverse reactions

The following table shows an overview of adverse reactions observed in clinical studies, postmarketing safety studies, and from other post-marketing sources, categorised according the MedDRA System Organ Class (SOC), Preferred Term Level (PT) and frequency.

Frequencies have been evaluated 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).

For spontaneously reported post-marketing adverse reactions, the reporting frequency is categorised as not known.

^* Frequency is based on studies with all FVIII products which included patients with severe haemophilia A.
PTPs = previously-treated patients, PUPs = previously-untreated patients

Description of selected adverse reactions

For description of selected adverse reactions, see section 4.4.

Reporting of suspected adverse reactions

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products or administered simultaneously with other intravenous preparation in the same infusion set.

Only the provided injection/infusion sets should be used because treatment failure can occur as a consequence of factor VIII/von Willebrand factor adsorption to the internal surfaces of some injection/infusion equipment.