Introduction
Zarxio (filgrastim-sndz) is a biosimilar to Neupogen (filgrastim), which is a human granulocyte colony-stimulating factor (G-CSF) produced by recombinant DNA technology. It is the first biosimilar approved by the US Food and Drug Administration (FDA) in March 2015. Zarxio is used to stimulate neutrophil production in various clinical settings where neutropenia poses a significant risk.
Mechanism of Action
Zarxio works by binding to specific cell surface receptors on hematopoietic cells, stimulating their proliferation, differentiation, and commitment to the neutrophil lineage. It enhances neutrophil progenitor cell development and activates mature neutrophils, ultimately increasing circulating neutrophil counts. The drug also promotes neutrophil migration from the bone marrow into the bloodstream.
Indications
FDA-approved indications include:
- Reduction in duration of febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy
- Reduction in time to neutrophil recovery in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy
- Mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis
- Chronic administration to reduce incidence and duration of neutropenia in patients with severe chronic neutropenia (congenital, cyclic, or idiopathic)
- Reduction in duration of neutropenia in patients undergoing myeloablative chemotherapy followed by bone marrow transplantation
Dosage and Administration
Oncology patients:- 5 mcg/kg/day subcutaneously or intravenously
- Begin at least 24 hours after chemotherapy completion
- Continue until neutrophil recovery (ANC ≥ 10,000/mm³)
- Starting dose: 6 mcg/kg subcutaneously twice daily
- Adjust based on patient response and ANC levels
- 10 mcg/kg/day subcutaneously for 4-7 days
- Begin at least 4 days before first leukapheresis
Dosage adjustments required for patients with renal impairment (creatinine clearance <30 mL/min)
Pharmacokinetics
Absorption: Bioavailability approximately 60% following subcutaneous administration Distribution: Volume of distribution approximately 150 mL/kg; binds to neutrophils and neutrophil precursors Metabolism: Primarily cleared by neutrophils and neutrophil precursors via receptor-mediated endocytosis and degradation Elimination: Half-life approximately 3.5 hours; clearance approximately 0.5-0.7 mL/min/kg Excretion: Primarily renal clearance of degraded fragmentsContraindications
- Hypersensitivity to filgrastim products or E. coli-derived proteins
- Simultaneous administration with chemotherapy or radiation therapy
- Patients with known hypersensitivity to filgrastim or any component of the formulation
Warnings and Precautions
Splenic rupture: Fatal cases reported; evaluate patients with left upper abdominal or shoulder tip pain Acute respiratory distress syndrome: Monitor patients closely for respiratory symptoms Serious allergic reactions: Including anaphylaxis Sickle cell crisis: Increased risk in patients with sickle cell disorders Glomerulonephritis: Generally resolves with dose reduction or discontinuation Leukocytosis: White blood cell counts ≥100,000/mm³ observed Capillary leak syndrome: Monitor for hypotension and hypoalbuminemia Potential for tumor growth: G-CSF receptors present on various tumor cells Aortitis: Rare cases reported within 2 weeks of starting G-CSFDrug Interactions
- Lithium: May potentiate release of neutrophils
- Chemotherapeutic agents: Do not administer within 24 hours before or after chemotherapy
- Other bone marrow stimulants: Potential additive effects requiring careful monitoring
Adverse Effects
Common (≥10%):- Bone pain (up to 34%)
- Injection site reactions
- Headache
- Fatigue
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Myalgia
- Arthralgia
- Splenic rupture
- Acute respiratory distress syndrome
- Anaphylaxis
- Sickle cell crisis
- Glomerulonephritis
- Capillary leak syndrome
- Leukocytosis
- Aortitis
- Myelodysplastic syndrome/acute myeloid leukemia (in patients with breast/lung cancer receiving chemotherapy and radiotherapy)
Monitoring Parameters
- Complete blood count with differential (at least twice weekly during therapy)
- Platelet count and hematocrit
- Renal function (baseline and periodically)
- Signs of splenic enlargement (physical examination)
- Respiratory status
- Signs of allergic reactions
- Injection site reactions
- Bone pain assessment
Patient Education
- Proper injection technique and rotation of injection sites
- Importance of timely administration after chemotherapy
- Recognition and reporting of bone pain (usually manageable with analgesics)
- Signs requiring immediate medical attention: left upper quadrant pain, shoulder tip pain, difficulty breathing, swelling, rash, fever
- Proper storage and handling (refrigeration required, avoid freezing)
- Needle and syringe disposal procedures
- Importance of regular blood test monitoring
- Potential side effects and management strategies
References
1. US Food and Drug Administration. (2015). Zarxio prescribing information. 2. Blackwell K, et al. (2015). Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. Journal of Clinical Oncology. 3. Aapro M, et al. (2016). Biosimilar filgrastim: improving access and optimizing therapy to reduce the incidence of febrile neutropenia. Annals of Oncology. 4. National Comprehensive Cancer Network. (2023). NCCN Guidelines: Myeloid Growth Factors. 5. Kuter DJ, et al. (2018). Updated clinical experience with filgrastim-sndz across various patient populations. Annals of Hematology. 6. American Society of Clinical Oncology. (2023). Guidelines for Use of Hematopoietic Colony-Stimulating Factors. 7. European Medicines Agency. (2023). Zarzio (filgrastim) European Public Assessment Report.