BeneFIX Special Precautions

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity: Allergic-type hypersensitivity reactions are possible with BeneFIX. The product contains traces of hamster proteins. Potentially life-threatening anaphylactic/anaphylactoid reactions have occurred with factor IX products, including BeneFIX. 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 early signs of hypersensitivity reactions including difficult breathing, shortness of breath, swelling, hives, generalised urticaria, itching, tightness of the chest, bronchospasm, laryngospasm, wheezing, hypotension, blurred vision, and anaphylaxis.
In some cases, these reactions have progressed to severe anaphylaxis. In the case of shock, the current medical standards for treatment of shock should be observed. In case of severe allergic reactions, alternative haemostatic measures should be considered.
Inhibitors: Inhibitors are an uncommon event in previously treated patients (PTPs) receiving factor IX-containing products. As one PTP treated with BeneFIX developed a clinically relevant low responding inhibitor during clinical studies and experience on antigenicity with recombinant factor IX is still limited, patients treated with BeneFIX should be carefully monitored for the development of factor IX inhibitors that should be titrated in Bethesda Units 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. Preliminary information suggests a relationship may exist between the presence of major deletion mutations in a patient's factor IX gene and an increased risk of inhibitor formation and of acute hypersensitivity reactions. Patients known to have major deletion mutations of the factor IX gene should be observed closely for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of initial exposure to product.
Because of the risk of allergic reactions with factor IX concentrates, 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.
Thrombosis: Although BeneFIX contains only factor IX, the risk of thrombosis and disseminated intravascular coagulation (DIC) should be recognised. Since the use of factor IX complex concentrates has historically been associated with the development of thromboembolic complications, the use of factor IX-containing products may be potentially hazardous in patients with signs of fibrinolysis and in patients with disseminated intravascular coagulation (DIC). 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 BeneFIX should be weighed against the risk of these complications.
The safety and efficacy of BeneFIX administration by continuous infusion have not been established (see also Dosage & Administration and Adverse Reactions). There have been post-marketing reports of thrombotic events, including life threatening superior vena cava (SVC) syndrome in critically ill neonates, while receiving continuous infusion BeneFIX through a central venous catheter (see also Adverse Reactions).
Cardiovascular events: In patients with existing cardiovascular risk factors, substitution therapy with BeneFIX may increase the cardiovascular risk.
Nephrotic syndrome: Nephrotic syndrome has been reported following attempted immune tolerance induction in haemophilia B patients with factor IX inhibitors and a history of allergic reaction. The safety and efficacy of using BeneFIX for immune tolerance induction has not been established.
Sodium content: After reconstitution, BeneFIX contains 0.2 mmol sodium (4.6 mg) per vial, that is to say essentially 'sodium-free'. Depending on body weight of the patient and posology of BeneFIX, patients could receive multiple vials. This should be taken into consideration if the patient is on a low salt diet.
Effects on ability to drive and use machines: BeneFIX has no influence on the ability to drive or use machines.