Eftrenonacog alfa

Because of the potential risk of thrombotic complications with factor IX products, clinical surveillance for early signs of thrombotic and consumptive coagulopathy should be initiated with appropriate biological testing when administering this product to patients with liver disease, to patients post-operatively, to new- born infants, or to patients at risk of thrombotic phenomena or disseminated intravascular coagulation (DIC). The benefit of treatment with eftrenonacog-alfa in these situations should be weighed against the risk of these complications.

Allergic type hypersensitivity reactions have been reported with eftrenonacog-alfa. 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 anaphylactic shock, standard medical treatment for shock should be implemented.

Animal reproduction studies have not been conducted with eftrenonacog alfa. A placental transfer study in mice was conducted. Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during pregnancy is not available. Therefore, factor IX should be used during pregnancy only if clearly indicated.

Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during breast-feeding is not available. Therefore, factor IX should be used during breast-feeding only if clearly indicated.

Fertility

There are no fertility data available. No fertility studies have been conducted in animals with eftrenonacog alfa.

Eftrenonacog alfa has no influence on the ability to drive and use machines.

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. 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 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 thromboembolic complications.

List of adverse reactions

The frequencies in the table below were observed in a total of 153 patients with severe haemophilia B in phase III clinical studies and an extension study. Adverse events were monitored for a total of 561 subject-years. The total number of exposure days was 26,106 with a median of 165 (range 1-528) exposure days per subject.

List 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 2. Adverse reactions reported for eftrenonacog alfa in clinical trials:

Metabolism and nutrition disorders

Uncommon: Decreased appetite

Nervous system disorders

Common: Headache

Uncommon: Dizziness, Dysgeusia

Cardiac disorders

Uncommon: Palpitations

Vascular disorders

Uncommon: Hypotension

Gastrointestinal disorders

Common: Paresthesia oral

Uncommon: Breath odour

Renal and urinary disorders

Common: Obstructive uropathy

Uncommon: Haematuria, Renal colic

General disorders and administration site conditions

Uncommon: Fatigue, Infusion site pain

Post Marketing Experience

In post-marketing experience, FIX inhibitor development and hypersensitivity (including anaphylaxis) have been observed.

Paediatric population

Frequency, type and severity of adverse reactions in children are expected to be similar as in adults.