Ziextenzo (Pegfilgrastim-bmez): Uses, Dosage, Side Effects & Warnings

Uses

1 INDICATIONS AND USAGE ZIEXTENZO is a leukocyte growth factor indicated to
• Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. ( 1.1 )
• Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome). ( 1.2 ) Limitations of Use ZIEXTENZO is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. 1.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy ZIEXTENZO is indicated in adults and pediatric patients aged newborn and older to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia [see Clinical Studies ( 14.1 )]. Limitations of Use ZIEXTENZO is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. 1.2 Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome ZIEXTENZO is indicated to increase survival in adults and pediatric patients aged newborn and older acutely exposed to myelosuppressive doses of radiation [see Dosage and Administration ( 2.2 ) and Clinical Studies ( 14.2 )].

Dosage and administration

Patients with cancer receiving myelosuppressive chemotherapy
• For adult patients of any weight and pediatric patients weighing 45 kg and greater, the recommended dosage is 6 mg subcutaneously once per chemotherapy cycle. ( 2.1 )
• Do not administer between 14 days before and 24 hours after administration of chemotherapy. ( 2.1 ) Patients acutely exposed to myelosuppressive doses of radiation
• For adults of any weight and pediatric patients weighing 45 kg and greater, the recommended dosage is two doses, 6 mg each, subcutaneously one week apart. Administer the first dose as soon as possible after suspected or confirmed exposure to myelosuppressive doses of radiation, and a second dose one week after. ( 2.2 ) 2.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy The recommended dosage of ZIEXTENZO for adults of any weight and pediatric patients weighing at least 45 kg with cancer receiving myelosuppressive chemotherapy is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. Do not administer ZIEXTENZO between 14 days before and 24 hours after administration of chemotherapy. 2.2 Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome The recommended dosage of ZIEXTENZO for adults of any weight and pediatric patients weighing at least 45 kg with hematopoietic subsyndrome of acute radiation syndrome is two doses, 6 mg each, administered subcutaneously one week apart. Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Administer the second dose one week after the first dose. Obtain a baseline complete blood count (CBC). Do not delay administration of ZIEXTENZO if a CBC is not readily available. Estimate a patient’s absorbed radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics. 2.3 Preparation and Administration ZIEXTENZO is supplied as single-dose prefilled syringe for manual use [see Dosage Forms and Strengths ( 3 )]. Before using ZIEXTENZO:
• Remove the carton from the refrigerator and allow the ZIEXTENZO prefilled syringe to reach room temperature, 20 ° C to 25 ° C (68 ° F to 77 ° F) for a minimum of 15-30 minutes. Do not warm in any other way. Discard any prefilled syringe left at temperatures between 20°C to 35°C (68°F to 95°F) for greater than 120 hours.
• ZIEXTENZO is a clear, colorless to slightly yellowish solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer ZIEXTENZO if discoloration or particulates are observed. Prefilled Syringe for Manual Use For adult patients of any weight and pediatric patients weighing 45 kg and greater, the single-dose prefilled syringe for manual use is intended for subcutaneous administration of a single 6 mg/0.6 mL dose of ZIEXTENZO. The syringe does not bear graduation marks and therefore does not allow for direct administration of doses less than 6 mg/0.6 mL. There is no presentation for ZIEXTENZO that allows weight-based dosing for pediatric patients below 45 kg. The ZIEXTENZO syringe plunger stopper and needle cap are not made with natural rubber latex.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS ZIEXTENZO is a clear, colorless to slightly yellowish, preservative-free solution available as:
• Injection: 6 mg/0.6 mL in a single-dose prefilled syringe for manual use only. Injection: 6 mg/0.6 mL solution in a single-dose prefilled syringe for manual use only. ( 3 )

Contraindications

4 CONTRAINDICATIONS ZIEXTENZO is contraindicated in patients with a history of a serious hypersensitivity reaction to pegfilgrastim products or filgrastim products. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.3 )] . In patients with a history of serious hypersensitivity reaction to pegfilgrastim products or filgrastim products. ( 4 )

Warnings and precautions

• Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. ( 5.1 )
• Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue ZIEXTENZO in patients with ARDS. ( 5.2 )
• Serious hypersensitivity reactions, including anaphylaxis: Permanently discontinue ZIEXTENZO in patients with serious hypersensitivity reactions. ( 5.3 )
• Fatal sickle cell crises: Discontinue ZIEXTENZO if sickle cell crisis occurs. ( 5.4 )
• Glomerulonephritis: Evaluate and consider dose-reduction or interruption of ZIEXTENZO if causality is likely. ( 5.5 )
• Thrombocytopenia: Monitor platelet counts. ( 5.7 )
• Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): Monitor patients with breast and lung cancer using ZIEXTENZO in conjunction with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML. ( 5.10 )
• Aortitis: Discontinue ZIEXTENZO if aortitis is suspected. ( 5.11 ) 5.1 Splenic Rupture Splenic rupture, including fatal cases, can occur following the administration of pegfilgrastim products. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving ZIEXTENZO. 5.2 Acute Respiratory Distress Syndrome Acute respiratory distress syndrome (ARDS) can occur in patients receiving pegfilgrastim products. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving ZIEXTENZO, for ARDS. Discontinue ZIEXTENZO in patients with ARDS. 5.3 Serious Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, can occur in patients receiving pegfilgrastim products. The majority of reported events occurred upon initial exposure. Hypersensitivity reactions, including anaphylaxis, can recur within days after the discontinuation of initial therapies to manage the reaction. Permanently discontinue ZIEXTENZO in patients with serious hypersensitivity reactions. ZIEXTENZO is contraindicated in patients with a history of a serious hypersensitivity reaction to pegfilgrastim products or filgrastim products. 5.4 Use in Patients with Sickle Cell Disorders Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving pegfilgrastim products. Discontinue ZIEXTENZO if sickle cell crisis occurs. 5.5 Glomerulonephritis Glomerulonephritis has occurred in patients receiving pegfilgrastim products. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose-reduction or discontinuation of pegfilgrastim products. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of ZIEXTENZO. 5.6 Leukocytosis White blood cell (WBC) counts of 100 x 10 9 /L or greater have been observed in patients receiving pegfilgrastim products. Monitoring of complete blood count (CBC) during ZIEXTENZO therapy is recommended. 5.7 Thrombocytopenia Pegfilgrastim products can cause thrombocytopenia. Monitor platelet counts during ZIEXTENZO therapy. 5.8 Capillary Leak Syndrome Capillary leak syndrome has been reported after G-CSF administration, including pegfilgrastim products, and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. 5.9 Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor through which pegfilgrastim products and filgrastim products act has been found on tumor cell lines. The possibility that pegfilgrastim products act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim products are not approved, cannot be excluded. 5.10 Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer MDS and AML have been associated with the use of pegfilgrastim products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for signs and symptoms of MDS/AML in these settings. 5.11 Aortitis Aortitis has been reported in patients receiving pegfilgrastim products. It may occur as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue ZIEXTENZO if aortitis is suspected. 5.12 Nuclear Imaging Increased hematopoietic activity of the bone marrow in response to growth factor therapy, including pegfilgrastim products, has been associated with transient positive bone imaging changes. This should be considered when interpreting bone imaging results.

Side effects

The following clinically significant 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 Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )]
• Use in Patients with Sickle Cell Disorders [see Warnings and Precautions ( 5.4 )]
• Glomerulonephritis [see Warnings and Precautions ( 5.5 )]
• Leukocytosis [see Warnings and Precautions ( 5.6 )]
• Thrombocytopenia [see Warnings and Precautions ( 5.7 )]
• Capillary Leak Syndrome [see Warnings and Precautions ( 5.8 )]
• Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions ( 5.9 )]
• Myelodysplastic syndrome [see Warnings and Precautions ( 5.10 )]
• Acute myeloid leukemia [see Warnings and Precautions ( 5.10 )]
• Aortitis [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (≥ 5% difference in incidence compared to placebo) are bone pain and pain in extremity. ( 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 ZIEXTENZO 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. Pegfilgrastim clinical trials safety data are based upon 932 patients receiving pegfilgrastim in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n = 823), lung and thoracic tumors (n = 53) and lymphoma (n = 56) received pegfilgrastim after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles. The following adverse reaction data in Table 1 are from a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer receiving docetaxel 100 mg/m 2 every 21 days (Study 3). A total of 928 patients were randomized to receive either 6 mg pegfilgrastim (n = 467) or placebo (n = 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and < 1% Asian, Native American, or other. The most common adverse reactions occurring in ≥ 5% of patients and with a between-group difference of ≥ 5% higher in the pegfilgrastim arm in placebo-controlled clinical trials are bone pain and pain in extremity. Table 1. Adverse Reactions with ≥ 5% Higher Incidence in Pegfilgrastim Patients Compared to Placebo in Study 3 Body System Adverse Reaction Placebo (N = 461) Pegfilgrastim 6 mg SC on Day 2 (N = 467) Musculoskeletal and connective tissue disorders Bone pain 26% 31% Pain in extremity 4% 9% Leukocytosis In clinical studies, leukocytosis (WBC counts > 100 x 10 9 /L) was observed in less than 1% of 932 patients with non-myeloid malignancies receiving pegfilgrastim. No complications attributable to leukocytosis were reported in clinical studies. 6.3 Postmarketing Experience The following adverse reactions have been identified during post approval use of pegfilgrastim products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Splenic rupture and splenomegaly (enlarged spleen) [see Warnings and Precautions ( 5.1 )]
• Acute respiratory distress syndrome (ARDS) [see Warnings and Precautions ( 5.2 )]
• Allergic reactions/hypersensitivity, including anaphylaxis, skin rash, urticaria, generalized erythema, and flushing [see Warnings and Precautions ( 5.3 )]
• Sickle cell crisis [see Warnings and Precautions ( 5.4 )]
• Glomerulonephritis [see Warnings and Precautions ( 5.5 )]
• Leukocytosis [see Warnings and Precautions ( 5.6 )]
• Thrombocytopenia [see Warnings and Precautions ( 5.7 )]
• Capillary Leak Syndrome [see Warnings and Precautions ( 5.8 )]
• Injection site reactions
• Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis
• Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer receiving chemotherapy and/or radiotherapy [see Warnings and Precautions ( 5.10 )]
• Aortitis [see Warnings and Precautions ( 5.11 )]
• Alveolar hemorrhage

Use in specific populations

8.1 Pregnancy Risk Summary Although available data with pegfilgrastim product use in pregnant women are insufficient to establish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant women exposed to filgrastim products. These studies have not established an association of filgrastim product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, no evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area). In pregnant rabbits, increased embryolethality and spontaneous abortions occurred at 4 times the maximum recommended human dose simultaneously with signs of maternal toxicity (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 Animal Data Pregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis. At cumulative doses ranging from the approximate human dose to approximately 4 times the recommended human dose (based on body surface area), the treated rabbits exhibited decreased maternal food consumption, maternal weight loss, as well as reduced fetal body weights and delayed ossification of the fetal skull; however, no structural anomalies were observed in the offspring from either study. Increased incidences of post-implantation losses and spontaneous abortions (more than half the pregnancies) were observed at cumulative doses approximately 4 times the recommended human dose, which were not seen when pregnant rabbits were exposed to the recommended human dose. Three studies were conducted in pregnant rats dosed with pegfilgrastim at cumulative doses up to approximately 10 times the recommended human dose at the following stages of gestation: during the period of organogenesis, from mating through the first half of pregnancy, and from the first trimester through delivery and lactation. No evidence of fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately 3 and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers (detected at the end of gestation but no longer present in pups evaluated at the end of lactation). 8.2 Lactation Risk Summary There are no data on the presence of pegfilgrastim products in human milk, the effects on the breastfed child, or the effects on milk production. Other filgrastim products are secreted poorly into breast milk, and filgrastim products are not absorbed orally by neonates. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZIEXTENZO and any potential adverse effects on the breastfed child from ZIEXTENZO or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of ZIEXTENZO for chemotherapy-induced neutropenia and hematopoietic subsyndrome of acute radiation syndrome have been established in pediatric patients aged newborn and older. Use of ZIEXTENZO in pediatric patients for chemotherapy-induced neutropenia is based on adequate and well-controlled studies of pegfilgrastim in adults with additional pharmacokinetic and safety data of pegfilgrastim in pediatric patients aged 8 months and older with sarcoma [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )]. The use of ZIEXTENZO to increase survival in pediatric patients acutely exposed to myelosuppressive doses of radiation is based on efficacy studies of pegfilgrastim conducted in animals and clinical data supporting the use of pegfilgrastim in patients with cancer receiving myelosuppressive chemotherapy. Efficacy studies of pegfilgrastim products could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Results from population modeling and simulation indicate that two doses of pegfilgrastim, administered one week apart provide pediatric patients with exposures comparable to that in adults receiving two 6 mg doses one week apart [see Dosage and Administration ( 2.1 , 2.2 ), Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.2 )]. 8.5 Geriatric Use Of the 932 patients with cancer who received pegfilgrastim in clinical studies, 139 (15%) were aged 65 and over, and 18 (2%) were aged 75 and over. No overall differences in safety or effectiveness were observed between patients aged 65 and older and younger patients.

Pregnancy

8.1 Pregnancy Risk Summary Although available data with pegfilgrastim product use in pregnant women are insufficient to establish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant women exposed to filgrastim products. These studies have not established an association of filgrastim product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, no evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area). In pregnant rabbits, increased embryolethality and spontaneous abortions occurred at 4 times the maximum recommended human dose simultaneously with signs of maternal toxicity (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 Animal Data Pregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis. At cumulative doses ranging from the approximate human dose to approximately 4 times the recommended human dose (based on body surface area), the treated rabbits exhibited decreased maternal food consumption, maternal weight loss, as well as reduced fetal body weights and delayed ossification of the fetal skull; however, no structural anomalies were observed in the offspring from either study. Increased incidences of post-implantation losses and spontaneous abortions (more than half the pregnancies) were observed at cumulative doses approximately 4 times the recommended human dose, which were not seen when pregnant rabbits were exposed to the recommended human dose. Three studies were conducted in pregnant rats dosed with pegfilgrastim at cumulative doses up to approximately 10 times the recommended human dose at the following stages of gestation: during the period of organogenesis, from mating through the first half of pregnancy, and from the first trimester through delivery and lactation. No evidence of fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately 3 and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers (detected at the end of gestation but no longer present in pups evaluated at the end of lactation).

Pediatric use

8.4 Pediatric Use The safety and effectiveness of ZIEXTENZO for chemotherapy-induced neutropenia and hematopoietic subsyndrome of acute radiation syndrome have been established in pediatric patients aged newborn and older. Use of ZIEXTENZO in pediatric patients for chemotherapy-induced neutropenia is based on adequate and well-controlled studies of pegfilgrastim in adults with additional pharmacokinetic and safety data of pegfilgrastim in pediatric patients aged 8 months and older with sarcoma [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )]. The use of ZIEXTENZO to increase survival in pediatric patients acutely exposed to myelosuppressive doses of radiation is based on efficacy studies of pegfilgrastim conducted in animals and clinical data supporting the use of pegfilgrastim in patients with cancer receiving myelosuppressive chemotherapy. Efficacy studies of pegfilgrastim products could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Results from population modeling and simulation indicate that two doses of pegfilgrastim, administered one week apart provide pediatric patients with exposures comparable to that in adults receiving two 6 mg doses one week apart [see Dosage and Administration ( 2.1 , 2.2 ), Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.2 )].

Geriatric use

8.5 Geriatric Use Of the 932 patients with cancer who received pegfilgrastim in clinical studies, 139 (15%) were aged 65 and over, and 18 (2%) were aged 75 and over. No overall differences in safety or effectiveness were observed between patients aged 65 and older and younger patients.

Overdosage

Overdosage of pegfilgrastim products may result in leukocytosis and bone pain. Events of edema, dyspnea, and pleural effusion have been reported in a single patient who administered pegfilgrastim on 8 consecutive days in error. In the event of overdose, the patient should be monitored for adverse reactions [see Adverse Reactions ( 6 )]. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

Description

Pegfilgrastim-bmez is a covalent conjugate of recombinant methionyl human G-CSF and monomethoxypolyethylene glycol. Recombinant methionyl human G-CSF is a water-soluble 175 amino acid protein with a molecular weight of approximately 19 kilodaltons (kD). Recombinant methionyl human G-CSF is obtained from the bacterial fermentation of a strain of E coli transformed with a genetically engineered plasmid containing the human G-CSF gene. To produce pegfilgrastim-bmez, a 20 kD monomethoxypolyethylene glycol molecule is covalently bound to the N-terminal methionyl residue of recombinant methionyl human G-CSF. The average molecular weight of pegfilgrastim-bmez is approximately 39 kD. ZIEXTENZO for manual subcutaneous injection is supplied in 0.6 mL prefilled syringes. The prefilled syringe does not bear graduation marks and is designed to deliver the entire contents of the syringe (6 mg/0.6 mL). The delivered 0.6 mL dose from the prefilled syringe for manual subcutaneous injection contains 6 mg pegfilgrastim-bmez (based on protein weight) in a sterile, clear, colorless to slightly yellowish, preservative-free solution (pH 4.0, sodium hydroxide may be added as necessary to adjust pH) containing acetic acid (0.36 mg), polysorbate 20 (0.02 mg), sorbitol (30 mg), and Water for Injection, USP.

Mechanism of action

12.1 Mechanism of Action Pegfilgrastim products are colony-stimulating factors that act on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING ZIEXTENZO single-dose prefilled syringe for manual use ZIEXTENZO injection is a clear, colorless to slightly yellowish solution supplied in a prefilled single-dose syringe for manual use containing 6 mg pegfilgrastim-bmez, supplied with a 29-gauge, 1/2-inch needle with an UltraSafe Passive TM Needle Guard. The ZIEXTENZO syringe plunger stopper and needle cap are not made with natural rubber latex. ZIEXTENZO is provided in a carton containing one sterile 6 mg/0.6 mL prefilled syringe (NDC 61314-866-02). ZIEXTENZO prefilled syringe does not bear graduation marks and is intended only to deliver the entire contents of the syringe (6 mg/0.6 mL) for direct administration. Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light or physical damage. Discard syringes stored at temperatures between 20°C to 35°C (68°F to 95°F) for more than 120 hours. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard syringe if frozen more than once. Do not shake.

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Advise patients of the following risks and potential risks with ZIEXTENZO:
• Splenic rupture and splenomegaly
• Acute Respiratory Distress Syndrome
• Serious hypersensitivity reactions
• Sickle cell crisis
• Glomerulonephritis
• Increased risk of Myelodysplastic Syndrome and/or Acute Myeloid Leukemia in patients with breast and lung cancer who receive ZIEXTENZO in conjunction with chemotherapy and/or radiation therapy
• Capillary Leak Syndrome
• Aortitis Advise patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome) that efficacy studies of pegfilgrastim products for this indication could not be conducted in humans for ethical and feasibility reasons and that, therefore, approval of this use was based on efficacy studies conducted in animals [see Clinical Studies ( 14.2 )]. Instruct patients who self-administer ZIEXTENZO using the single-dose prefilled syringe of the:
• Importance of following the Instructions for Use.
• Dangers of reusing syringes.
• Importance of following local requirements for proper disposal of used syringes. Manufactured by: Sandoz Inc. Princeton, NJ 08540 US License No. 2003

Active ingredients

Pegfilgrastim in 1 product

Ziextenzo NDC products (1)

NDC	Strength & form	Labeler	Type
61314-866	Pegfilgrastim 6 mg/.6mL Injection	Sandoz Inc	BLA

Frequently asked questions

What is Ziextenzo used for?

1 INDICATIONS AND USAGE ZIEXTENZO is a leukocyte growth factor indicated to • Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. ( 1.1 ) • Increase survival in patients acutely exposed to myelosuppressive doses of…

What are the side effects of Ziextenzo?

The following clinically significant 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 Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] • Use in Patients with Sickle Cell Disorders [see Warnings and… See the full label for the complete list.

Who makes Ziextenzo?

Ziextenzo is listed by 1 labeler in the FDA NDC directory, including Sandoz Inc.