XYNTHA

What it is

XYNTHA is formulated as a sterile, non-pyrogenic, lyophilised powder for intravenous injection. The active ingredient is moroctocog alfa. Moroctocog alfa is a purified protein produced by recombinant DNA technology for use in therapy of factor VIII deficiency (haemophilia A or classic haemophilia). It is available in single use vials and in single use prefilled dual chamber syringes containing the labelled amount of factor VIII activity, expressed in IUs. Each vial contains nominally 250, 500, 1000 or 2000 IU of XYNTHA per vial, and each prefilled dual chamber syringe contains nominally 250, 500, 1000, 2000 or 3000 IU of XYNTHA per syringe.

Approved indications

— Control and prevention of haemorrhagic episodes in patients with haemophilia A — Control and prevention of bleeding in surgical settings XYNTHA does not contain von Willebrand factor and should not be used by patients with von Willebrand's disease.

Dosing overview

Dosage and duration of treatment depend on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient's clinical condition. On average 1 IU of factor VIII per kg body weight raises the plasma factor VIII activity by approximately 2 IU/dL. For minor haemorrhages such as early haemarthrosis, superficial muscle or soft tissue and oral bleeds, a factor VIII level of 20-40% is required, with doses repeated every 12 to 24 hours as necessary until resolved, for at least 1 day depending upon the severity of the haemorrhage. For moderate haemorrhages into muscles, mild head trauma, minor operations including tooth extraction, and haemorrhages into the oral cavity, a factor VIII level of 30-60% is required, with infusion repeated every 12-24 hours for 3-4 days or until adequate wound healing. For major haemorrhages including gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic haemorrhages, fractures and major operations, a factor VIII level of 60-100% is required, with infusion repeated every 8-24 hours until threat is resolved or until adequate wound healing, then therapy for at least another 7 days. For routine prophylaxis to prevent or reduce the frequency of spontaneous musculoskeletal haemorrhage in patients with haemophilia A, doses of 10 to 50 IU of factor VIII per kg body weight should be given at least twice a week. XYNTHA has been administered prophylactically at a dose of 30 ± 5 IU/kg given 3 times weekly in a pivotal clinical trial in adolescent and adult previously treated patients.

Key safety warnings

Allergic type hypersensitivity reactions are possible as with any intravenous protein product, and patients should be informed of the early signs including hives, generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. If allergic or anaphylactic reactions occur, administration of XYNTHA should be stopped immediately, and appropriate medical management should be given, which may include treatment for shock. Activity neutralising antibodies (inhibitors) may develop in patients receiving coagulation factor VIII-containing products, and patients should be monitored for the development of inhibitors that should be titrated in Bethesda Units using appropriate biological testing. The risk of developing inhibitors is correlated to the exposure to anti-haemophilic factor VIII, with this risk being highest within the first 20 exposure days, and rarely inhibitors may develop after the first 100 exposure days. Reports of less than expected therapeutic effect, both in the prophylaxis and on demand setting, have been received during clinical trials and in the post-marketing setting for XYNTHA, occurring at a rate of 0.4% during prophylaxis and 0.5% during on-demand treatment in a pivotal clinical trial.

Contraindications

XYNTHA is contraindicated in patients with a known history of hypersensitivity to any of the constituents of the preparation and in patients with a known history of hypersensitivity to hamster proteins.

PBS listing

No source document containing PBS listing information for XYNTHA was provided.

Regulatory history

XYNTHA received its first approval on 26 June 2009. ARTG registration records show vial presentations containing 250 IU, 500 IU, 1000 IU and 2000 IU first listed on 2009-06-26, with prefilled dual chamber syringe presentations containing 250 IU, 500 IU, 1000 IU, 2000 IU and 3000 IU first listed on 2011-10-04.