Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: Biotest Pharma GmbH, Landsteinerstrasse 5, 63303 Dreieich, Germany, Phone: +49 6103 801-0, Fax: +49 6103 801-150, mail@biotest.de
Hypersensitivity to the active substance, to any of the excipients or to heparin.
Allergic type hypersensitivity reactions are possible with Haemonine. The product contains traces of human proteins other than factor IX. 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 chest, wheezing, hypotension, and anaphylaxis.
In case of shock, standard medical treatment for shock should be implemented.
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.
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 post-operatively, to new-born infants, or to patients at risk of thrombotic phenomena or DIC. In each of these situations, the benefit of treatment with Haemonine should be weighed against the risk of these complications.
Due to potential additive or synergistic pharmacodynamic effects, coadministration of antifibrinolytic agents with anti-inhibitor coagulant complex or factor IX complex could increase the risk of thrombosis.
In patients with existing cardiovascular risk factors, substitution therapy with FIX may increase the cardiovascular risk.
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 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 products.
It is strongly recommended that every time that Haemonine 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.
The listed warnings and precautions apply both to adults and children aged 6 years and older (see also section 4.2).
This medicinal product contains a maximum of 4.9 mmol (113 mg) sodium per standard dose of 2000 IU. To be taken into consideration by patients on a controlled sodium diet.
No interaction studies have been performed. No interactions of human coagulation factor IX products with other medicinal products have been reported.
The listed interactions apply both to adults and children aged 6 years and older (see also section 4.2).
Fertility data are not available.
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.
Haemonine has no or negligible influence on the ability to drive and use machines.
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.
Haemonine may contain traces of heparin below the limit of quantitation (0.1 IU/ml) which may cause hypersensitivity reactions and reduced blood cell counts which may affect the blood clotting system. Patients with a history of heparin-induced allergic reactions should avoid the use of heparin-containing medicines.
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 such side effects.
For safety information with respect to transmissible agents, see section 4.4.
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
Frequency of Adverse Drug Reactions (ADRs) in clinical studies with Haemonine (Frequencies are calculated per patients treated (n=36)):
Very common*: Hypersensitivity
Common: Anxiety
Common: Hyperaesthesia
Common: Nausea
Common: Dermatitis allergic, Urticaria
Common: Back pain
Common: Hot flush
Common: Dyspnoea
Common: Feeling cold, Injection site reaction (including e.g. pain and rash)
Not known**: factor IX inhibition
* Hypersensitivity can be allergic or non-allergic reactions. True allergic reactions are rare.
** Reported from post-marketing sources.
The development of inhibitory antibodies is a known complication in the management of individuals with haemophilia B. There is no experience with previously untreated patients (PUPs) so far.
During clinical development no factor IX inhibitor induction was observed in previously treated patients (PTPs, n=36) during 1,493 exposure days.
Frequency, type and severity of adverse reactions in children aged 6 years and older are expected to be the same as in adults (see also section 4.2).
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 listed in Appendix V*.
This medicinal product must not be mixed with other medicinal products.
Use only the provided injection sets because treatment failure can occur as a consequence of human coagulation factor IX adsorption to the internal surfaces of some injection equipment.
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