Filgrastim-Sndz
FDA Drug Information • Also known as: Zarxio
- Brand Names
- Zarxio
- Drug Class
- Leukocyte Growth Factor [EPC]
- Route
- INTRAVENOUS, SUBCUTANEOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Filgrastim-sndz is a 175 amino acid human granulocyte colony-stimulating factor (G-CSF) manufactured by recombinant DNA technology. Filgrastim-sndz is produced by Escherichia coli ( E coli ) bacteria into which has been inserted the human granulocyte colony-stimulating factor gene. Filgrastim-sndz has a molecular weight of 18‚800 daltons. The protein has an amino acid sequence that is identical to the natural sequence predicted from human DNA sequence analysis‚ except for the addition of an N-terminal methionine necessary for expression in E coli . Because filgrastim-sndz is produced in E coli ‚ the product is non-glycosylated and thus differs from G-CSF isolated from a human cell. ZARXIO (filgrastim-sndz) injection is a sterile‚ clear‚ colorless to slightly yellowish‚ preservative-free liquid containing filgrastim-sndz at a specific activity of 1 x 10 8 U/mg (as measured by a proliferation assay). The product is available in single-dose vials and single-dose prefilled syringes for subcutaneous or intravenous use. The single-dose vials contain either 300 mcg/mL or 480 mcg/1.6 mL of filgrastim-sndz. The single-dose prefilled syringes contain either 300 mcg/0.5 mL or 480 mcg/0.8 mL of filgrastim-sndz. The ZARXIO drug product has a pH of 4.4. See Table 4 below for product composition of each single-dose vial and prefilled syringe. Table 4. Product Composition 300 mcg/mL Vial 480 mcg/1.6 mL Vial 300 mcg/0.5 mL Syringe 480 mcg/0.8 mL Syringe Filgrastim-sndz 300 mcg 480 mcg 300 mcg 480 mcg Glutamic Acid 1.471 mg 2.354 mg 0.736 mg 1.178 mg Polysorbate 80 0.04 mg 0.064 mg 0.02 mg 0.032 mg Sorbitol 50 mg 80 mg 25 mg 40 mg Sodium hydroxide q.s. q.s. q.s. q.s. Water for Injection USP q.s. ad* ad 1 mL ad 1.6 mL ad 0.5 mL ad 0.8 mL *q.s.: quantity sufficient to make
What Is Filgrastim-Sndz Used For?
1 INDICATIONS AND USAGE ZARXIO is a leukocyte growth factor indicated to
Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti‑cancer drugs associated with a significant incidence of severe neutropenia with fever ( 1.1 ) Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML) ( 1.2 ) Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) ( 1.3 ) Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis ( 1.4 ) Reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia ( 1.5 ) Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) ( 1.6 ) 1.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy ZARXIO is indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever [see Clinical Studies ( 14.1 )] . 1.2 Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy ZARXIO is indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML) [see Clinical Studies ( 14.2 )] . 1.3 Patients with Cancer Undergoing Bone Marrow Transplantation ZARXIO is indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation [see Clinical Studies ( 14.3 )]. 1.4 Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy ZARXIO is indicated for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis [see Clinical Studies ( 14.4 )] . 1.5 Patients with Severe Chronic Neutropenia ZARXIO is indicated for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia [see Clinical Studies ( 14.5 )] . 1.6 Patients Acutely Exposed to Myelosuppressive Doses of Radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) ZARXIO is...Dosage and Administration
2 DOSAGE AND ADMINISTRATION
Patients with cancer receiving myelosuppressive chemotherapy or induction and/or consolidation chemotherapy for AML o Recommended starting dose is 5 mcg/kg/day subcutaneous injection, short intravenous infusion (15 to 30 minutes), or continuous intravenous infusion. See Full Prescribing Information for recommended dosage adjustments and timing of administration ( 2.1 ) Patients with cancer undergoing bone marrow transplantation o 10 mcg/kg/day given as an intravenous infusion no longer than 24 hours. See Full Prescribing Information for recommended dosage adjustments and timing of administration. ( 2.2 ) Patients undergoing autologous peripheral blood progenitor cell collection and therapy o 10 mcg/kg/day subcutaneous injection ( 2.3 ) o Administer for at least 4 days before first leukapheresis procedure and continue until last leukapheresis ( 2.3 ) Patients with congenital neutropenia o Recommended starting dose is 6 mcg/kg subcutaneous injection twice daily ( 2.4 ) Patients with cyclic or idiopathic neutropenia o Recommended starting dose is 5 mcg/kg subcutaneous injection daily ( 2.4 ) Patients acutely exposed to myelosuppressive doses of radiation o 10 mcg/kg/day subcutaneous injection ( 2.5 ) Direct administration of less than 0.3 mL (180 mcg) using ZARXIO prefilled syringe is not recommended due to potential for dosing errors ( 2.6 ) 2.1 Dosage in Patients with Cancer Receiving Myelosuppressive Chemotherapy or Induction and/or Consolidation Chemotherapy for AML The recommended starting dosage of ZARXIO is 5 mcg/kg/day‚ administered as a single daily injection by subcutaneous injection‚ by short intravenous infusion (15 to 30 minutes)‚ or by continuous intravenous infusion. Obtain a complete blood count (CBC) and platelet count before instituting ZARXIO therapy and monitor twice weekly during therapy. Consider dose escalation in increments of 5 mcg/kg for each chemotherapy cycle‚ according to the duration and severity of the absolute neutrophil count (ANC) nadir. Recommend stopping ZARXIO if the ANC increases beyond 10‚000/mm 3 [see Warnings and Precautions ( 5.10 )] . Administer ZARXIO at least 24 hours after cytotoxic chemotherapy. Do not administer ZARXIO within the 24-hour period prior to chemotherapy [see Warnings and Precautions ( 5.13 )] . A transient increase in neutrophil count is typically seen 1 to 2 days after initiation of ZARXIO therapy. Therefore, to ensure a sustained therapeutic response‚ administer ZARXIO daily for up to 2 weeks or until the ANC has reached 10‚000/mm 3 following the expected chemotherapy-induced neutrophil nadir. The duration of ZARXIO therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed. 2.2 Dosage in Patients with Cancer Undergoing Bone Marrow Transplantation The recommended dosage of ZARXIO following bone marrow transplantation (BMT) is 10 mcg/kg/day given as an...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
Splenic Rupture [see Warnings and Precautions ( 5.1 )] Acute Respiratory Distress Syndrome [see Warnings and Precautions ( 5.2 )] Serious Allergic Reactions [see Warnings and Precautions ( 5.3 )] Sickle Cell Disorders [see Warnings and Precautions ( 5.4 )] Glomerulonephritis [see Warnings and Precautions ( 5.5 )] Alveolar Hemorrhage and Hemoptysis [see Warnings and Precautions ( 5.6 )] Capillary Leak Syndrome [see Warnings and Precautions ( 5.7 )] Myelodysplastic Syndrome [see Warnings and Precautions ( 5.8 )] Acute Myeloid Leukemia [see Warnings and Precautions ( 5.8 )] Thrombocytopenia [see Warnings and Precautions ( 5.9 )] Leukocytosis [see Warnings and Precautions ( 5.10 )] Cutaneous Vasculitis [see Warnings and Precautions ( 5.11 )] Aortitis [see Warnings and Precautions ( 5.15 )] Most common adverse reactions in patients: With nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs (≥ 5% difference in incidence compared to placebo) are pyrexia, pain, rash, cough, and dyspnea. ( 6.1 ) With AML (≥ 2% difference in incidence) are pain, epistaxis and rash. ( 6.1 ) With nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT (≥ 5% difference in incidence) is rash. ( 6.1 ) Undergoing peripheral blood progenitor cell mobilization and collection (≥ 5% incidence) are bone pain, pyrexia and headache. ( 6.1 ) With severe chronic neutropenia (SCN) (≥ 5% difference in incidence) are pain, anemia, epistaxis, diarrhea, hypoesthesia and alopecia. ( 6.1 ) *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of ZARXIO has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information. To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Patients with Cancer Receiving Myelosuppressive Chemotherapy The following adverse reaction data in Table 2 are from three randomized, placebo-controlled studies in patients with: small cell lung cancer receiving standard dose chemotherapy with cyclophosphamide‚ doxorubicin‚ and etoposide (Study 1) small cell lung cancer receiving ifosfamide, doxorubicin‚ and etoposide (Study 2), and non-Hodgkin’s lymphoma (NHL) receiving doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, and methotrexate (“ACVBP”) or mitoxantrone, ifosfamide, mitoguazone, teniposide, methotrexate, folinic acid, methylprednisolone, and methotrexate (“VIM3”) (Study 3). A total of 451 patients were randomized to receive subcutaneous filgrastim 230 mcg/m 2 (Study 1), 240 mcg/m 2 (Study 2) or 4 or 5 mcg/kg/day (Study 3) (n=294) or placebo (n=157). The patients in these studies were median age 61 (range 29 to 78) years and 64% were male. The ethnicity was 95% Caucasian, 4% African American, and 1% Asian. Table 2. Adverse Reactions in Patients with Cancer Receiving Myelosuppressive Chemotherapy (With ≥ 5% Higher Incidence in Filgrastim Compared to Placebo) System Organ Class Preferred Term Filgrastim (N=294) Placebo (N=157) Blood and lymphatic system disorders Thrombocytopenia 38% 29% Gastrointestinal disorders Nausea 43% 32% General disorders and...Contraindications
4 CONTRAINDICATIONS ZARXIO is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim products or pegfilgrastim products [see Warnings and Precautions ( 5.3 )] . Patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim products or pegfilgrastim products. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data from published studies, including several observational studies of pregnancy outcomes in women exposed to filgrastim products and those who were unexposed, have not established an association with filgrastim product use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Reports in the scientific literature have described transplacental passage of filgrastim in pregnant women when administered ≤ 30 hours prior to preterm delivery (≤ 30 weeks gestation). In animal reproduction studies, effects of filgrastim on prenatal development have been studied in rats and rabbits. No malformations were observed in either species. No maternal or fetal effects were observed in pregnant rats at doses up to 58 times the human doses. Filgrastim has been shown to have adverse effects in pregnant rabbits at doses 2 to 10 times higher than the human doses (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively. Data Human Data Several observational studies based on the Severe Chronic Neutropenia International Registry (SCNIR) described pregnancy outcomes in women with severe chronic neutropenia (SCN) who were exposed to filgrastim products during pregnancy and women with SCN who were unexposed. No major differences were seen between treated and untreated women with respect to pregnancy outcome (including miscarriage and preterm labor), newborn complications (including birth weight), and infections. Methodological limitations of these studies include small sample size and lack of generalizability due to the underlying maternal condition. Animal Data Effects of filgrastim...
Overdosage
10 OVERDOSAGE The maximum tolerated dose of filgrastim products has not been determined. In filgrastim clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ WBC counts > 100‚000/mm 3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the BMT studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING ZARXIO injection is a clear, colorless to slightly yellowish, preservative-free solution supplied as: Vial: The vial is supplied in a carton containing one single-dose vial providing:
300 mcg/mL of filgrastim-sndz solution (NDC 61314-246-71) 480 mcg/1.6 (300 mcg/mL) mL of filgrastim-sndz solution (NDC 61314-266-73) Latex sensitive individuals: The vial stopper is not made with natural rubber latex. Prefilled syringe (BD UltraSafe Passive ® Needle Guard): Single-dose prefilled syringe containing 300 mcg/0.5 mL of filgrastim-sndz solution. Pack of 1 prefilled syringe (NDC 61314-318-01) Pack of 10 (multipack) prefilled syringes (NDC 61314-318-10) Single-dose prefilled syringe containing 480 mcg/0.8 mL of filgrastim-sndz solution. Pack of 1 prefilled syringe (NDC 61314-326-01) Pack of 10 (multipack) prefilled syringes (NDC 61314-326-10) Latex-sensitive individuals: The removable needle cap of ZARXIO prefilled syringe contains natural rubber latex which may cause allergic reaction. The safe use of ZARXIO in latex-sensitive individuals has not been studied. Storage: Store ZARXIO in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original pack to protect from light. Do not leave ZARXIO in direct sunlight. Avoid shaking. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard ZARXIO if frozen more than once.About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.