ZIEXTENZO

What it is

Ziextenzo contains pegfilgrastim (rbe), a long-acting form of recombinant human Granulocyte Colony-Stimulating Factor (G-CSF). Ziextenzo is a biosimilar medicinal product that has been demonstrated to be similar in quality, safety and efficacy to the reference medicinal product, Neulasta. Ziextenzo is a sterile, clear, colourless, preservative-free liquid for subcutaneous administration.

Approved indications

— Treatment of cancer patients following chemotherapy, to decrease the duration of severe neutropenia and so reduce the incidence of infection, as manifested by febrile neutropenia.

Dosing overview

The recommended dosage of Ziextenzo is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. Ziextenzo should be administered approximately 24 hours after the administration of cytotoxic chemotherapy.

Key safety warnings

**Splenic rupture.** Cases of splenic rupture, including some fatal cases, have been reported following administration of pegfilgrastim. Patients who report left upper abdominal pain and/or shoulder tip pain should be evaluated for an enlarged spleen or splenic rupture. **Sickle cell crisis.** Sickle cell crises have been associated with the use of pegfilgrastim in patients with sickle cell disease. Clinicians should exercise caution, monitor patients accordingly when administering pegfilgrastim to patients with sickle cell trait or sickle cell disease and only consider use after careful evaluation of the potential benefits and risks. **Pulmonary haemorrhage.** 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. **Acute respiratory distress syndrome.** In patients with sepsis receiving pegfilgrastim, the physician should be alert to the possibility of acute respiratory distress syndrome due to the possible influx of neutrophils at the site of inflammation. **Glomerulonephritis.** Glomerulonephritis has been reported in patients receiving pegfilgrastim. Generally, after withdrawal of pegfilgrastim, events of glomerulonephritis resolved. Monitoring of urinalysis is recommended. **Myelodysplastic syndrome and acute myeloid leukaemia.** In the post-marketing observational study setting, myelodysplastic syndrome and acute myeloid leukaemia have been associated with the use of pegfilgrastim in conjunction with chemotherapy and/or radiotherapy in breast and lung cancer patients. Monitor patients for signs and symptoms of MDS/AML in these settings. **Thrombocytopenia.** Thrombocytopenia has been reported in patients receiving pegfilgrastim. Platelet counts should be monitored closely. **Aortitis.** Aortitis has been reported in patients receiving pegfilgrastim 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. **Stevens-Johnson syndrome.** Stevens-Johnson syndrome, which can be life-threatening or fatal, has been reported rarely in association with pegfilgrastim treatment. If the patient has developed SJS with the use of pegfilgrastim, treatment with pegfilgrastim must not be restarted in this patient at any time.

Contraindications

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

PBS listing

Ziextenzo is listed on the PBS as an injection of 6 mg in 0.6 mL single use pre-filled syringe with 2 PBS items and streamlined restriction status, with an ex-manufacturer price of A$77.52.

Regulatory history

The TGA approved Ziextenzo as a biosimilar to Neulasta on 9 July 2019. This decision was based on comprehensive data demonstrating its quality, bioequivalence, efficacy, and safety profile are comparable to the reference product. Ziextenzo was first listed on the ARTG on 6 September 2019. The PBAC recommended Ziextenzo for listing in November 2019 under the Highly Specialised Drugs Program with streamlined authority required restriction for chemotherapy-induced neutropenia.