Adverse reactions : תופעות לוואי

4.8   Undesirable effects
The following adverse reactions are based on post-marketing experience as well as scientific literature.

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 and may in some cases progress to severe anaphylaxis (including shock).
In some cases, they have occurred in close temporal association with development of factor IX inhibitors (see also section 4.4).

Nephrotic syndrome has been reported following attempted immune tolerance induction in haemophilia B patients with factor IX inhibitors and a history of allergic reaction.
Patients with haemophilia B may develop neutralising antibodies (inhibitors) to factor IX. If such inhibitors occur, the condition will manifest itself as an insufficient clinical response.
In such cases, it is recommended that a specialised haemophilia clinical centre be contacted.

There is a potential risk of thromboembolic episodes following the administration of factor IX products, with a higher risk for low purity preparations. The use of low purity factor IX products has been associated with instances of myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism. The use of high purity factor IX is rarely associated with such side effects.

Tabulated list of adverse reactions

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 Renal and urinary disorders      Nephrotic syndrome                Very rare Vascular Disorders               Thromboembolic episodes           Not known General Disorders and            Fever                             Rare Administration Site
Conditions
Immune System Disorders    Hypersensitivity (allergic              Rare reactions)
Blood and Lymphatic System FIX inhibition                          Very rare Disorders

Description of selected adverse reactions

In a clinical study 2 of 51 (4 %) previously untreated patients (PUPs) developed inhibitors, and in one of these patients, this was associated with an anaphylactoid reaction on two occasions.

For information on viral safety see section 4.4.

Paediatric population
Frequency, type and severity of adverse reactions in children are expected 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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic @moh.gov.il and emailed to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com