ZIEXTENZO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZIEXTENZO (ZIEXTENZO).
ZIEXTENZO is a recombinant methionyl human granulocyte colony-stimulating factor (G-CSF) that binds to G-CSF receptors on hematopoietic progenitor cells, stimulating proliferation, differentiation, and release of neutrophils from the bone marrow.
| Metabolism | ZIEXTENZO is a protein and is expected to be degraded into small peptides and amino acids via general protein catabolism; no specific metabolic pathways or enzymes involved. |
| Excretion | Primarily renal; filgrastim is cleared by the kidneys, with minimal biliary or fecal excretion. Approximately 70% of the dose is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 3.5 hours in healthy subjects and up to 6.5 hours in cancer patients after chemotherapy. Supports twice-daily dosing for some indications. |
| Protein binding | Approximately 70% bound to serum proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.5 L/kg, indicating limited extravascular distribution, consistent with a glycoprotein confined largely to the vascular space. |
| Bioavailability | Subcutaneous: 62% bioavailability (range 42–87%) compared to intravenous administration. Not bioavailable orally. |
| Onset of Action | Subcutaneous injection: Neutrophil count begins to rise within 24–48 hours; peak effect by 3–5 days. Intravenous: Similar but slightly faster onset; peak effect by day 3. |
| Duration of Action | Subcutaneous: Neutrophil elevation lasts for 1–2 days after discontinuation; dosing typically continued until neutrophil recovery. Clinical effect wanes with drug clearance. |
ZIEXTENZO (tbo-filgrastim) 5 mcg/kg subcutaneously once daily for up to 5 days until absolute neutrophil count (ANC) reaches 10,000/mm³ after nadir.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment is recommended for patients with renal impairment. However, data in severe renal impairment (CrCl < 30 mL/min) are limited; monitor neutrophil counts closely. |
| Liver impairment | No specific dose adjustment for hepatic impairment is provided in labeling. Use with caution in severe hepatic impairment due to limited data. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. Dosing per weight for ages 3-12 years: 5 mcg/kg subcutaneously once daily (further pediatric data extrapolated from adult studies). |
| Geriatric use | No specific dose adjustment is required for elderly patients. Due to higher incidence of renal impairment, monitor renal function and neutrophil counts. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZIEXTENZO (ZIEXTENZO).
| Breastfeeding | Excretion into human milk is unknown. Endogenous G-CSF is present in human milk. Due to high molecular weight, levels are likely low. M/P ratio not available. Consider developmental benefits of breastfeeding versus potential adverse effects from exposure. Caution is advised. |
| Teratogenic Risk | ZIEXTENZO (pegfilgrastim-cbqv) is a recombinant methionyl human granulocyte colony-stimulating factor (G-CSF). Based on limited human data, there is no evidence of increased risk for major birth defects or miscarriage. In animal studies, pegfilgrastim has been shown to cross the placenta and administration during organogenesis resulted in reduced fetal weight and minor skeletal abnormalities at doses approximately 5 times the human exposure. Risk cannot be excluded; use only if clearly needed. Trimester-specific risks are not well established due to insufficient data. |
■ FDA Black Box Warning
ZIEXTENZO should not be administered to patients with a history of serious allergic reactions, including anaphylaxis, to filgrastim or pegfilgrastim products.
| Serious Effects |
["History of serious allergic reactions to filgrastim, pegfilgrastim, or any component of ZIEXTENZO."]
| Precautions | ["Splenic rupture: Evaluate patients who report left upper quadrant or shoulder pain.","Acute respiratory distress syndrome (ARDS): Monitor for pulmonary symptoms.","Serious allergic reactions: Discontinue permanently if reaction occurs.","Sickle cell crisis: Use caution in patients with sickle cell disease.","Glomerulonephritis: Evaluate if signs of nephritis appear.","Capillary leak syndrome: Monitor and treat promptly.","Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML): Increased risk in breast and lung cancer patients.","Aortitis: Evaluate for signs of inflammation."] |
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| Fetal Monitoring | Monitor complete blood count (CBC) with white blood cell (WBC) count and absolute neutrophil count (ANC) regularly. Assess for splenic rupture (left upper quadrant pain), acute respiratory distress syndrome (ARDS), and allergic reactions. Monitor for sickle cell crisis in patients with sickle cell disease. No specific fetal monitoring required but standard prenatal care is recommended. |
| Fertility Effects | In animal studies, pegfilgrastim did not impair fertility in rats at exposures up to 5 times human exposure. No human data available on effects on fertility. Reversible suppression of spermatogenesis has been observed with other G-CSFs in animal studies, but clinical significance is unknown. |