EMOCLOT Powder and solvent for solution for infusion Ref.[51154] Active ingredients: Coagulation factor VIII

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 EMOCLOT.

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.

Important information on the ingredients of EMOCLOT

This medicinal product contains up to 41 mg sodium for the vial of 10 ml, equivalent to 2.05% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

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 is required, risk of device-related complications including local infections, bacteraemia and catheter site thrombosis should be considered.

Viral safety

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 (HAV). 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 (fetal 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 factor VIII products.

It is strongly recommended that every time that EMOCLOT 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 medicinal product.

Paediatric population

No specific data are available for paediatric population.

No interactions of human coagulation factor VIII products with other medicinal products have been reported.

Paediatric population

No specific data are available for paediatric population.

Animal reproduction studies have not been conducted with factor VIII. Based on the rare occurrence of haemophilia A in women, experience regarding the use of factor VIII during pregnancy and breastfeeding is not available. Therefore factor VIII should be used during pregnancy and lactation only if clearly indicated.

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

Summary of the safety profile

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 rarely and may in some cases progress to severe anaphylaxis (including shock).

Fever has been also observed.

Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated with factor VIII, including with EMOCLOT. If such inhibitors occur, the condition may 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 table presented below is according to the MedDRA system organ classification (SOC) and Preferred Term Level (PT). The table reports undesirable effects associated with the use of human plasma coagulation Factor VIII.

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).

There are no robust data on the frequency of adverse reactions derived from clinical trials.

The following data is in line with the safety profile of human plasma coagulation Factor VIII, and were partially observed after the marketing of the product (the post marketing experience); as the post marketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not possible to reliably estimate the frequency of these reactions.

^* The terms of the lower level MedDRA (LLT) are more appropriate for the description of these adverse reactions; its MedDRA preferred terms (PT) are given in brackets.
^¤ Frequency is based on studies with all FVIII products which included patients with severe haemophilia A. PTPs = previously-treated patients, PUPs = previously-untreated patients.

Paediatric population

No specific data are available for paediatric population.

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 website: www.medicinesauthority.gov.mt/adrportal.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

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