TEVAGRASTIM

What it is

Tevagrastim is filgrastim (rbe), a recombinant human granulocyte colony stimulating factor (r-metHuG-CSF) derived from E. coli. Tevagrastim is a 175 amino acid protein manufactured by recombinant DNA technology. It is a sterile, clear, colourless, preservative-free liquid for parenteral administration, formulated in a 10 mM sodium acetate buffer at pH 4.0. The product is available in single use pre-filled syringes containing either 120 μg filgrastim at a fill volume of 0.2 mL or 300 μg or 480 μg filgrastim at a fill volume of 0.5 mL.

Approved indications

— To decrease 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. — To reduce the duration of neutropenia and clinical sequelae in patients undergoing induction and consolidation chemotherapy for acute myeloid leukaemia (AML). — For mobilisation of autologous peripheral blood progenitor cells (PBPCs) 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. — For mobilisation of PBPCs, in normal volunteers, for use in allogeneic peripheral blood progenitor cell (PBPC) transplantation. — In patients receiving myeloablative chemotherapy, to reduce the duration of neutropenia and clinical sequelae following autologous or allogeneic bone marrow transplantation. — 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/consolidation chemotherapy for AML, the recommended starting dose is 5 μg/kg/day administered as a single daily subcutaneous (SC) injection. In patients with non-myeloid malignancies receiving standard-dose cytotoxic chemotherapy, the recommended starting dose of Tevagrastim is 5 μg/kg/day administered as a single daily SC injection or short intravenous (IV) 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 SC infusion or by IV infusion over 4 to 24 hours. For autologous PBPC collection and therapy, the recommended dose for PBPC mobilisation when used alone is 10 μg/kg/day given as a single daily SC injection or a continuous 24-hour infusion. For PBPC mobilisation after myelosuppressive chemotherapy, the recommended dose is 5 μg/kg/day given daily by SC injection from 24 hours after completion of chemotherapy until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range. For PBPC mobilisation in normal donors, Tevagrastim should be administered at 10 μg/kg/day subcutaneously for 4 to 5 consecutive days. For patients with severe chronic neutropenia, the recommended daily starting dose for congenital neutropenia is 12 μg/kg subcutaneously every day (single or divided doses), and for idiopathic or cyclic neutropenia is 5 μg/kg subcutaneously every day (single or divided doses). For patients with HIV infection requiring reversal of neutropenia, the recommended starting dose is 1 μg/kg/day administered daily by SC injection with titration up to a maximum of 5 μg/kg/day until a normal neutrophil count is reached and can be maintained (ANC ≥ 2.0 × 10⁹/L).

Key safety warnings

Splenic rupture has been reported following administration of filgrastim; some of these 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 (≥ 1/1,000 and < 1/100) but serious risk of splenic rupture. Clinicians should exercise caution and monitor patients accordingly when administering Tevagrastim 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 Tevagrastim in patients with sickle cell trait or sickle cell disease should be considered only after careful evaluation of the 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 the occurrence of acute respiratory distress syndrome (ARDS) 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 ARDS. Tevagrastim should be immediately discontinued and appropriate treatment given. Glomerulonephritis has been reported in patients receiving filgrastim. Generally, events of glomerulonephritis resolved after dose reduction or withdrawal of filgrastim and pegfilgrastim. 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. Do not administer filgrastim to patients with a history of hypersensitivity to filgrastim or pegfilgrastim.

Contraindications

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

PBS listing

The source documents do not contain information regarding PBS listing status, item number, restriction type, or ex-manufacturer price for Tevagrastim.

Regulatory history

Tevagrastim filgrastim 300 microgram/0.5mL injection was first listed on the ARTG on 29 August 2011, and Tevagrastim filgrastim 480 microgram/0.8mL injection was first listed on 29 August 2011 in the RE licence category. The AusPAR for this brand was approved on 16 August 2011 with indications to decrease the incidence of infection as manifested by febrile neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs in doses not usually requiring bone marrow transplantation.