BENEFIX

What it is

BeneFIX contains nonacog alfa . Nonacog alfa is a purified protein produced by recombinant DNA technology for use in therapy of factor IX deficiency, known as haemophilia B or Christmas disease . BeneFIX is formulated as a sterile, non-pyrogenic, lyophilised powder preparation intended for intravenous (IV) injection . BeneFIX is not derived from human blood and contains no preservatives or added animal or human components, and is inherently free from the risk of transmission of human blood-borne pathogens such as HIV, hepatitis viruses and parvovirus .

Approved indications

— Control and prevention of haemorrhagic episodes in patients with haemophilia B (congenital factor IX deficiency or Christmas disease) — Control and prevention of bleeding in surgical settings

Dosing overview

Treatment with BeneFIX requires individualised dosage adjustment, and the dosage and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding and the patient's clinical condition, age and recovery of factor IX . Initial treatment can be started with an approximate dose of 20–50 IU/kg, and the required dose should be titrated for each patient taking the patient's pharmacokinetic data and clinical situation into consideration . In patients aged 15 years and over, on average, one IU of BeneFIX per kilogram of body weight increased the circulating activity of factor IX by 0.8 ± 0.2 IU/dL . In patients under 15 years, on average, one IU of BeneFIX per kilogram of body weight increased the circulating activity of factor IX by 0.7 ± 0.3 IU/dL . For haemorrhagic events, the factor IX activity should not fall below specified plasma activity levels: 20–30% for minor uncomplicated haemarthroses and soft tissue bleeding (1–2 days treatment), 25–50% for moderate bleeding including soft tissue with dissection and dental extractions (2–7 days treatment), and 50–100% for major bleeding including CNS and surgical procedures (7–10 days treatment) . For secondary prophylaxis, a clinical study demonstrated an average dose of 40 IU/kg twice weekly .

Key safety warnings

Pharmacokinetic studies suggest that in vivo recovery with BeneFIX is significantly lower than that achieved with plasma-derived factor IX products, and therefore dosages are higher than those usually recommended with plasma-derived products . Although BeneFIX contains no coagulation factor other than factor IX, the potential risk of thrombosis and disseminated intravascular coagulation observed with other products containing factor IX should be recognised, and caution should be exercised when administering this product to patients with liver disease, post-operative patients, neonates, patients with signs of fibrinolysis, patients at risk of thromboembolic phenomena or patients with disseminated intravascular coagulation . There have been post-marketing reports of thrombotic events, including life-threatening superior vena cava syndrome in critically ill neonates, while receiving continuous-infusion BeneFIX through a central venous catheter . Allergic type hypersensitivity reactions, including anaphylaxis, have been reported for all factor IX products, including BeneFIX, and frequently these events have occurred in close temporal association with the development of factor IX inhibitors . Patients with factor IX inhibitors may be at an increased risk of anaphylaxis upon subsequent challenge with factor IX, and patients experiencing allergic reactions should be evaluated for the presence of inhibitor .

Contraindications

Because BeneFIX is produced in a Chinese hamster ovary cell line, it may be contraindicated in patients who have had a previous allergic reaction to hamster protein . BeneFIX may also be contraindicated in patients with a known history of hypersensitivity to any of the constituents of the preparation .

Regulatory history

BeneFIX received its first approval on 27 September 2007 . Multiple strengths were registered on the Australian Register of Therapeutic Goods: 250 IU, 500 IU, 1000 IU and 2000 IU powder for injection vials were first listed on 27 September 2007, and the 3000 IU strength was first listed on 20 August 2013 .