Source: Medicines Authority (MT) Revision Year: 2019 Publisher: CSL Behring GmbH, Emil-von-Behring-Str. 76, 35041 Marburg, Germany
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In order to improve traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Allergic type hypersensitivity reactions are possible. 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, the current medical standards for shock treatment should be observed.
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 procoagulant 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.
In patients with existing cardiovascular risk factors, substitution therapy with FVIII may increase the cardiovascular risk.
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.
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 viruses hepatitis A (HAV) and parvovirus B19.
Appropriate vaccination (hepatitis A and hepatitis B) should be generally considered for patients in regular/repeated receipt of human plasma-derived Factor VIII products.
The listed warnings and precautions apply both to adults and children.
Beriate 250 IU and 500 IU contain less than 1mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.
Beriate 1000 IU and 2000 IU contain 27.55 mg sodium per vial, equivalent to 1.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
No interactions of human coagulation factor VIII products with other medicinal products have been reported.
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 breastfeeding only if clearly indicated.
There are no data on fertility available.
Beriate has no influence on the ability to drive and use machines.
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 very rarely, and may in some cases progress to severe anaphylaxis (including shock).
Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated with factor VIII, including with Beriate. 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.
The following adverse reactions are based on postmarketing experience as well as scientific literature.
The table presented below is according to the MedDRA system organ classification.
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).
| MedDRA SOC | Adverse Reaction | Frequency |
|---|---|---|
| Blood and lymphatic system disorders | FVIII inhibition | Uncommon* (PTPs) Very common* (PUPs) |
| General disorders and administration site conditions | Fever | Very rare |
| Immune system disorders | Hypersensitivity (allergic reactions | Very rare |
* Frequency is based on studies with all FVIII products which included patients with severe haemophilia A. PTPs = previously-treated patients, PUPs = previously-untreated patients
For information on viral safety see 4.4.
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
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 national reporting system at http://www.medicinesauthority.gov.mt/adrportal.
This medicinal product must not be mixed with other medicinal products, solvents and diluents except those mentioned in section 6.1.
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