ZARZIO

What it is

Zarzio is filgrastim (rbe), a recombinant human granulocyte colony stimulating factor (rmetHuG-CSF) derived from E. coli. It is a sterile, clear, colourless to slightly yellowish, preservative-free liquid for parenteral administration, available in single use pre-filled syringes. Zarzio is available in two strengths: 300 μg/0.5 mL and 480 μg/0.5 mL.

Approved indications

— To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs in doses not usually requiring bone marrow transplantation. — To reduce the duration of neutropenia and clinical sequelae in patients undergoing induction and consolidation chemotherapy for acute myeloid leukaemia (AML). — To mobilise autologous peripheral blood progenitor cells alone, or following myelosuppressive chemotherapy, in order to accelerate neutrophil and platelet recovery by infusion of such cells after myeloablative or myelosuppressive therapy in patients with non-myeloid malignancies. — To mobilise peripheral blood progenitor cells, in normal volunteers, for use in allogeneic peripheral blood progenitor cell (PBPC) transplantation. — To reduce the duration of neutropenia and clinical sequelae following autologous or allogeneic bone marrow transplantation in patients receiving myeloablative chemotherapy. — For chronic administration to increase neutrophil counts and to reduce the incidence and duration of infections in patients with severe chronic neutropenia (SCN). — In patients with HIV infection, for reversal of clinically significant neutropenia and subsequent maintenance of adequate neutrophil counts during treatment with antiviral and/or other myelosuppressive medications.

Dosing overview

In adults and children receiving induction or consolidation chemotherapy for AML, the recommended starting dose is 5 μg/kg/day administered as a single daily subcutaneous injection. In patients with non-myeloid malignancies receiving standard-dose cytotoxic chemotherapy, the recommended starting dose is 5 μg/kg/day, administered as a single daily subcutaneous injection or short intravenous infusion (over 15 to 30 minutes). For patients with non-myeloid malignancies receiving high-dose cytotoxic chemotherapy with autologous or allogeneic bone marrow or peripheral blood progenitor cell transplantation, the recommended starting dose is 10 μg/kg/day given by continuous subcutaneous infusion or by intravenous infusion over 4 to 24 hours. For severe chronic neutropenia, the recommended daily starting dose is 12 μg/kg subcutaneously every day for congenital neutropenia, or 5 μg/kg subcutaneously every day for idiopathic or cyclic neutropenia. For patients with HIV infection, the recommended starting dose is 1 μg/kg/day administered daily by subcutaneous injection with titration up to a maximum of 5 μg/kg/day.

Key safety warnings

Splenic rupture has been reported following administration of filgrastim; some cases were fatal. Left upper abdominal pain and/or shoulder tip pain accompanied by rapid increase in spleen size should be carefully monitored due to the uncommon but serious risk of splenic rupture. Clinicians should use caution and monitor patients accordingly when administering filgrastim to patients with sickle cell trait or sickle cell disease because of the reported association with sickle cell crisis (in some cases fatal). Use in patients with sickle cell disease should be considered only after careful evaluation of the potential risks and benefits. There have been occasional reports of adult respiratory distress syndrome (ARDS) in patients receiving filgrastim. Patients with a recent history of pulmonary infiltrates or pneumonia may be at higher risk. The onset of pulmonary signs, such as cough, fever and dyspnoea in association with radiological signs of lung infiltration and deterioration in pulmonary function may be preliminary signs leading to respiratory failure or ARDS. Filgrastim should be immediately discontinued and appropriate treatment given. Pulmonary haemorrhage and haemoptysis requiring hospitalisation have been reported in G-CSF-treated healthy donors undergoing peripheral blood progenitor cell collection mobilisation. Haemoptysis resolved with discontinuation of G-CSF. Glomerulonephritis has been reported in patients receiving filgrastim. Generally, after dose reduction or withdrawal of filgrastim, events of glomerulonephritis resolved. Monitoring of urinalysis is recommended. Aortitis has been reported in patients receiving filgrastim and may present with generalised signs and symptoms such as fever and increased inflammatory markers. Consider aortitis in patients who develop these signs and symptoms without known aetiology.

Contraindications

Zarzio is contraindicated in patients with known hypersensitivity to E coli-derived products, filgrastim, any of the excipients, or any other component of the product.

PBS listing

Zarzio 300 micrograms in 0.5 mL is listed on the PBS with a streamlined restriction at an ex-manufacturer price of A$58.73. Zarzio 480 micrograms in 0.5 mL is listed on the PBS with a streamlined restriction at an ex-manufacturer price of A$94.15.

Regulatory history

Zarzio was first registered on the ARTG on 7 May 2013, with two entries for the 300 microgram and 480 microgram strengths in pre-filled syringes. The TGA approved Zarzio for registration on the Australian Register of Therapeutic Goods in May 2013, following an evaluation that found the product acceptable on manufacturing, quality, and nonclinical grounds, with the Advisory Committee on Prescription Medicines accepting the similarity of the product to its reference. Nonclinical studies supported the proposed biosimilarity of Zarzio to the reference product, Neupogen.