Adverse reactions : תופעות לוואי

4.8   Undesirable effects
Summary of the safety profile
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion 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, these reactions have progressed to severe anaphylaxis, and 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.

Very rarely development of antibodies to hamster protein with related hypersensitivity reactions has been observed.

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 centre be contacted. One case with high-titre inhibitor was reported in the clinical study which evaluated previously untreated patients. Inhibitor development has been observed in previously treated patients in the post-marketing experience with IDELVION.


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 adverse reactions.

Tabulated list of adverse reactions
The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level). The table lists adverse reactions that were reported in clinical trials and/or were identified in post-marketing use.

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.

MedDRA Standard System Organ Class              Adverse reactions             Frequency per patient 

Blood and lymphatic disorders                   FIX inhibition/Inhibitor      Not known  development

General disorders and administration site
Injection site reactions      Common conditions
Headache                      Common
Nervous system disorders
Dizziness                     Common
Immune system disorders                         Hypersensitivity              Common 
Rash                          Common
Skin and subcutaneous tissue disorders
Eczema                        Uncommon

Description of selected adverse reactions
One case with high-titre inhibitor was reported in the clinical study with previously untreated patients (refer to Section 5.1). Due to the narrow data-base no inhibitor-incidence is provided.

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
 https://sideeffects.health.gov.il/
 and emailed to the Registration Holder’s Patient Safety Unit at: PV-IL@cslbehring.com