⚠️ Warnings
Traceability
In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.
Hypersensitivity
Allergic-type hypersensitivity reactions (including anaphylaxis) have been reported with ADVATE. The product contains traces of mouse and hamster proteins. If symptoms of hypersensitivity occur, patients must immediately discontinue use of the product and contact their physician. Patients should be informed about the early signs of hypersensitivity reactions including urticaria, generalised urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis.
In the event of shock, standard medical treatment for shock should be implemented.
In the case of a hypersensitivity reaction, due to the reduced volume of ADVATE reconstituted in 2 ml of water for injection, there is less time to react, i.e. to stop the injection. Therefore, caution is recommended during the injection of ADVATE reconstituted in 2 ml of water for injection, especially in children.
Inhibitors
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 procoagulant activity of factor VIII, which are quantified in Bethesda Units (BU) per ml of plasma using the modified assay. The risk of developing inhibitors is related 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 risk of insufficient clinical response than high-titre inhibitors.
In general, all patients treated with coagulation factor VIII products must be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. If the expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, testing for the presence of factor VIII inhibitor 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.
Improper administration of ADVATE
With ADVATE reconstituted in 2 ml of water for injection, improper administration (intra-arterial or paravenous) may lead to mild, short-lived reactions at the injection site, such as bruising and erythema.
Cardiovascular events
In patients with existing cardiovascular risk factors, substitution therapy with factor VIII may increase the cardiovascular risk.
Catheter-related complications
If a central venous access device (CVAD) is required, the risk of CVAD-related complications including local infections, bacteraemia, and catheter site thrombosis should be considered.
Excipient-related considerations
Sodium
This medicinal product contains 10 mg of sodium per vial, equivalent to 0.5% of the WHO recommended maximum daily sodium intake for an adult of 2 g.
It is strongly recommended that every time ADVATE is administered to a patient, the name and batch number of the product are recorded in order to maintain a clear link between the patient and the batch of the medicinal product.
Paediatric population
The listed warnings and precautions apply to both adults and children.
