VIHUMA Powder and solvent for solution for injection Ref.[49914] 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

As with any intravenous protein product, allergic type hypersensitivity reactions are possible. Vihuma contains traces of human host cell 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.

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 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.

Cases of recurrent inhibitor (low titre) have been observed after switching from one factor VIII 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 all patients carefully for inhibitor occurrence following any product switch.

The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre inhibitors which are transiently present or remain consistently 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.

Paediatric population

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

Excipient related considerations (sodium content)

This medicinal product contains 18.4 mg sodium per vial, equivalent to 0.92 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

No interaction studies have been performed with Vihuma.

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 breast feeding is not available. Therefore, factor VIII should be used during pregnancy and breast-feeding only if clearly indicated. There are no fertility data available.

Vihuma 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, headache, hives, hypotension, lethargy, nausea, rash, restlessness, tachycardia, tightness of the chest, tingling, urticaria, including generalised urticaria, vomiting, wheezing) have rarely been observed with FVIII preparations 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 Vihuma. 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.

Tabulated list of adverse reactions

During clinical studies with Vihuma in previously treated paediatric (2 to 11 years, n=58), adolescent (12 to 17 years, n=3) and adult patients (n=129) with severe haemophilia A, a total of 12 adverse drug reactions (ADRs) (8 in adults, 4 in children) were reported in 8 patients (4 adults, 4 children).

Table 1 presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level). 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).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Frequency of adverse drug reactions (ADRs) in clinical studies:

^* Calculated as patients with ADR per total number of 280 study patients, of which 190 previously treated patients (PTPs) and 90 previously untreated patients (PUPs).
^# 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

A non-neutralizing anti-factor VIII antibody was detected in one adult patient (see Table 1). The sample was tested by the central laboratory at eight dilutions. The result was positive only at dilution factor 1 and the antibody titre was very low. Inhibitory activity, as measured by the modified Bethesda assay, was not detected in this patient. Clinical efficacy and in vivo recovery of Vihuma was not affected in this patient.

Paediatric population

Frequency, type and severity of adverse reactions in children and adolescents are assumed to be the same as in adults.

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 the national reporting system listed in Appendix V.

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

Only the provided injection 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 equipment.