Adynovate Adverse Reactions

Summary of the safety profile: Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the injection site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed rarely after treatment with factor VIII and may in some cases progress to severe anaphylaxis (including shock).
Patients with haemophilia A may develop neutralising antibodies (inhibitors) to factor VIII. 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: The safety of ADYNOVATE has been evaluated in 6 multi-centre, prospective, open-label clinical trials and 1 ongoing study in 365 previously treated and untreated patients with severe haemophilia A (factor VIII <1% of normal), who received at least one dose of ADYNOVATE. Table 11 lists the adverse reactions reported during clinical studies. (See Table 11.)

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Description of selected adverse reactions: Immunogenicity: Inhibitor development: Formation of neutralising antibodies (inhibitors) to factor VIII can occur following administration of factor VIII products.
Clinical trial subjects were monitored for neutralising (inhibitory) antibodies to factor VIII. None of the subjects who participated in one or more of 6 completed clinical trials in previously treated patients (PTPs) developed persistent neutralising (inhibitory) antibodies against factor VIII of ≥0.6 BU/mL (based on the Nijmegen modification of the Bethesda assay). One patient developed a transient FVIII inhibitor at the lowest limit of positivity (0.6 BU) during personalised prophylaxis targeting a FVIII level of 8-12%. From an ongoing study in previously untreated patients <6 years with severe haemophilia A, preliminary reports on 9 cases of factor VIII inhibitor development associated with treatment with ADYNOVATE were received.
Binding antibodies to factor VIII, PEG-factor VII, PEG and CHO protein: Immunogenicity was also evaluated by measuring the development of binding IgG and IgM antibodies against factor VIII, PEGylated (PEG)-factor VIII, PEG and Chinese hamster ovary (CHO) protein using validated ELISA assays. No subject developed persistent treatment-emergent binding antibodies against factor VIII, PEG-factor VIII or PEG. There was no causal relationship between observed adverse events and binding antibodies except in one subject, a PUP where a causal relationship can neither be confirmed nor ruled out based on available data. No subject had pre-existing or treatment-emergent antibodies to CHO protein.
The detection of antibodies that are reactive to Factor FVIII is highly dependent on many factors, including: the sensitivity and specificity of the assay, sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to rurioctocog alfa pegol with the incidence of antibodies to other products may be misleading.
Hypersensitivity: Hypersensitivity reactions are possible with ADYNOVATE (Table 11). Allergic-type hypersensitivity reactions, including anaphylaxis, are rare complications of treatment with recombinant factor VIII, including the parent molecule, ADVATE.
Paediatric population: Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
Class reactions: Adverse reactions include: anaphylactic reaction, hypersensitivity, factor VIII inhibition.
Post-marketing adverse reactions: No additional adverse reactions, other than those from clinical trials, have been reported from post-marketing sources.
Reporting suspected adverse effects: Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product.