Aleviate Special Precautions

Hypersensitivity: 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.
Haemophilia A: Inhibitors: The formation of neutralising antibodies (inhibitors) to FVIII is a known complication in the management of individuals with haemophilia A. These inhibitors are usually IgG immunoglobulins directed against the FVIII procoagulant activity, which are quantified in Bethesda Units (BU) per mL of plasma, using appropriate biological testing. The risk of developing inhibitors is correlated to the exposure to anti-haemophilic FVIII, this risk being highest within the first 20 exposure days. Rarely, inhibitors may develop after the first 100 exposure days.
Cases of recurrent inhibitor (low titre) have been observed after switching from one FVIII product to another in previously treated patients with more than 100 exposure days who have a previous history of inhibitor development. Therefore, it is recommended to monitor patients carefully for inhibitor occurrence following any product switch.
In general, all patients treated with coagulation FVIII products should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. If the expected FVIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, testing for FVIII inhibitor presence should be performed. In patients with high levels of inhibitor, FVIII therapy may not be effective and other therapeutic options should be considered. The management of such patients should be directed by physicians with experience in the care of haemophilia A patients and those with FVIII inhibitors.
Von Willebrand disease: 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 thromboembolism should be instituted for patients at risk according to the current medical standards.
When using a FVIII-containing VWF product, continued treatment may cause an excessive rise in FVIII:C. In patients receiving FVIII-containing 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, and antithrombotic measures should be considered.
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, therapy may not only be ineffective but also lead to anaphylactoid reactions and other therapeutic options should be considered.
Pathogen safety: This product is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses and theoretically Creutzfeldt-Jakob Disease (CJD) agents that can cause disease.
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 HIV, HBV and HCV, and for the non-enveloped 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 and for individuals with immunodeficiency or increased erythropoiesis.
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived products.
It is strongly recommended that every time that Aleviate 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.
Effects on fertility: Animal reproduction studies have not been conducted with Aleviate.
Genotoxicity: No genotoxicity studies have been conducted with Aleviate.
Carcinogenicity: No carcinogenicity studies have been conducted with Aleviate.
Effect on laboratory tests: FVIII and/or VWF are endogenous plasma proteins therefore no specific effects on laboratory tests are anticipated.
Use in Pregnancy & Lactation: Von Willebrand disease: Experience in the treatment of pregnant or breast-feeding women is not available. Aleviate should be administered to pregnant or breast-feeding 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 breast-feeding is not available.
Therefore, Aleviate should be used during pregnancy and breast-feeding only if clearly indicated.
Use in Children: The listed warnings and precautions apply both to adults and paediatrics.
Use in the Elderly: The safety of this product for use in the elderly population has not been established in appropriate studies.