OCTANINE Powder for solution for injection Ref.[51133] Active ingredients: Coagulation factor IX

Hypersensitivity

Allergic type hypersensitivity reactions are possible with OCTANINE. The product contains traces of human proteins other than factor IX and heparin 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 shock, standard medical treatment for shock should be implemented.

Inhibitors

After repeated treatment with human coagulation factor IX products, patients should be monitored for the development of neutralising antibodies (inhibitors) that should be quantified in Bethesda Units (BU) using appropriate biological testing

There have been reports in the literature showing a correlation between the occurrence of a factor IX inhibitor and allergic reactions. Therefore, patients experiencing allergic reactions should be evaluated for the presence of an inhibitor. It should be noted that patients with factor IX inhibitors may be at an increased risk of anaphylaxis with subsequent challenge with factor IX.

Because of the risk of allergic reactions with factor IX products, the initial administrations of factor IX should, according to the treating physician’s judgement, be performed under medical observation where proper medical care for allergic reactions could be provided

Thromboemolism

Because of the potential risk of thrombotic complications, 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 postoperatively, to new-born infants, or to patients at risk of thrombotic phenomena or disseminated intravascular coagulation (DIC). In each of these situations, the benefit of treatment with OCTANINE should be weighed against the risk of these complications

Cardiovascular events

In patients with existing cardiovascular risk factors, substitution therapy with FIX may increase the cardiovascular risk.

Catheter-related complications

If a central venous access device (CVAD) is required, risk of CVAD-related complications including local infections, bacteraemia and catheter site thrombosis should be considered.

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) and for the non-enveloped virus hepatitis A virus (HAV). The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).

Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived factor IX concentrates.

It is strongly recommended that every time that OCTANINE is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product

Patients on controlled sodium diet

This medicinal product contains up to 69 mg sodium for 1 vial OCTANINE 500 IU, equivalent to 3.45% of the WHO recommended maximum daily intake of 2 g sodium for an adult and up to 138 mg sodium for 1 vial OCTANINE 1000 IU, equivalent to 6.9% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

To be taken into consideration by patients on a controlled sodium diet.

Paediatric population

The listed warnings and precautions apply both to adults and children.

No interactions of human coagulation factor IX products with other medicinal products have been reported.

Animal reproduction studies have not been conducted with factor IX. Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during pregnancy and breast-feeding is not available. Therefore, factor IX should be used during pregnancy and lactation only if clearly indicated.

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

Summary of 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 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). 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.

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 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.

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.

For safety with respect to transmissible agents, see 4.4.

Tabulated list of adverse reactions

The table 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).

^* MedDRA lowest level term (LLT)

Description of selected adverse reactions

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 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.

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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Only the provided injection/infusion sets should be used because treatment failure can occur as a consequence of human coagulation factor IX adsorption to the internal surfaces of some injection/infusion equipment.