NIVESTIM

What it is

Nivestim is filgrastim (rbe), a recombinant human granulocyte colony stimulating factor derived from E. coli. It is available in pre-filled syringes containing 120 micrograms, 300 micrograms, or 480 micrograms filgrastim.

Approved indications

— Decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs in doses not usually requiring bone marrow transplantation. — Reducing the duration of neutropenia and clinical sequelae in patients undergoing induction and consolidation chemotherapy for acute myeloid leukaemia. — Mobilisation of autologous peripheral blood progenitor cells alone, or following myelosuppressive chemotherapy, to accelerate neutrophil and platelet recovery after myeloablative or myelosuppressive therapy in patients with non-myeloid malignancies. — Mobilisation of peripheral blood progenitor cells in normal volunteers for use in allogeneic peripheral blood progenitor cell transplantation. — Reducing the duration of neutropenia and clinical sequelae following autologous or allogeneic bone marrow transplantation in patients receiving myeloablative chemotherapy. — Chronic administration to increase neutrophil counts and reduce the incidence and duration of infections in patients with severe chronic neutropenia. — Reversal of clinically significant neutropenia and maintenance of adequate neutrophil counts in patients with HIV infection during treatment with antiviral and/or other myelosuppressive medications.

Dosing overview

Dosing varies significantly by indication. For adults and children receiving induction or consolidation chemotherapy for acute myeloid leukaemia, the recommended starting dose is 5 μg/kg/day administered as a single daily subcutaneous injection. For patients with non-myeloid malignancies receiving standard-dose cytotoxic chemotherapy, the recommended starting dose is 5 μg/kg/day 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 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 autologous peripheral blood progenitor cell mobilisation when used alone, the recommended dose is 10 μg/kg/day as a single daily subcutaneous injection or continuous 24-hour infusion. For congenital neutropenia in severe chronic neutropenia, the recommended daily starting dose is 12 μg/kg subcutaneously. For idiopathic or cyclic neutropenia, the recommended daily starting dose is 5 μg/kg subcutaneously. For reversal of neutropenia in 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 exercise caution when administering Nivestim to patients with sickle cell trait or sickle cell disease because of the reported association of filgrastim with sickle cell crisis in some cases fatal. Use of Nivestim in these patients should be considered only after careful evaluation of potential risks and benefits. Pulmonary adverse effects, in particular interstitial lung disease, have been reported after G-CSF administration. There have been occasional reports of acute respiratory distress syndrome in patients receiving filgrastim. 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 acute respiratory distress syndrome. Glomerulonephritis has been reported in patients receiving filgrastim. Generally, events of glomerulonephritis resolved after dose reduction or withdrawal of filgrastim. Urinalysis monitoring is recommended. Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment have been reported in patients treated with filgrastim. Permanently discontinue filgrastim in patients with clinically significant hypersensitivity. Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported after granulocyte colony stimulating factor administration and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.

Contraindications

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

PBS listing

Nivestim is listed on the PBS in three strengths: 120 micrograms in 0.2 mL single-use pre-filled syringe (ex-manufacturer price A$123.84), 300 micrograms in 0.5 mL single-use pre-filled syringe (ex-manufacturer price A$117.46), and 480 micrograms in 0.5 mL single-use pre-filled syringe (ex-manufacturer price A$188.30). All strengths have streamlined restrictions.

Regulatory history

Nivestim was first registered on the ARTG on 16 September 2010 with three variants approved: 120 microgram, 300 microgram, and 480 microgram pre-filled syringes. In April 2018, the PBAC recommended that filgrastim biosimilar brands including Nivestim be flagged as equivalent to Neupogen for substitution, for indications including chemotherapy-induced neutropenia, mobilisation of peripheral blood progenitor cells, assisting bone marrow transplantation, assisting autologous peripheral blood progenitor cell transplantation, and severe chronic neutropenia.