Adverse reactions : תופעות לוואי

4.8         Undesirable effects

System Organ Class                             Rare                     Very rare Immune system disorders              hypersensitivity reaction      anaphylactic shock 
Vascular disorders                                                       embolism Renal and urinary disorders                                         nephrotic syndrome General disorders and                                                 heparin induced administration site                                                  thrombocytopenia conditions pyrexia
Investigations                                                    anti factor IX antibody positive
 rare (≥1/10,000 to <1/1,000 very rare (<1/10,000), including isolated reports

• 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 infrequently in patients treated with factor IX containing products. 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 4.4).

• 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. A study in 25 children with Haemophilia B was conducted, thereof 6 patients were previously untreated and had a median no. of exposure days to OCTANINE F of 38 (range 8-90). All patients had a factor IX inhibitor level of <0.4 BU at baseline. No inhibitor was observed during the study.
• Nephrotic syndrome has been reported following attempted immune tolerance induction in haemophilia B patients with factor IX inhibitors and a history of allergic reaction.
• On rare occasions, fever has been observed.
• 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.
• Due to the amount of heparin contained, a sudden, allergy induced reduction of the blood platelet count below 100,000/µl or 50% of the starting count may be observed (thrombocytopenia type II) in rare cases. In patients not previously hypersensitive to heparin, this decrease in thrombocytes may occur 6-14 days after the start of treatment. In patients with a previous heparin hypersensitivity this reduction may set in a few hours after treatment.
This severe form of blood platelet reduction may be accompanied by, or result in, arterial and venous thrombosis, thromboembolism, severe clotting disorder (consumptive coagulopathy), skin necrosis in the area of injection, flea bite-like bleeding (petechial haemorrhages), purpura and tarry stool. If the specified allergic reactions are observed, the injections with OCTANINE F should be stopped immediately. The patient should be advised not to use any heparin containing medicinal products in the future. Because of this rarely occurring heparin induced effect on the blood platelets, the patient’s blood platelet count should be monitored closely, especially at the initiation of treatment.
•     For safety with respect to transmissible agents, see 4.4.

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=AdversEffec tMedic@moh.gov.il