ZIEXTENZO pegfilgrastim-bmez 6 mg/.6mL Injection, 1 syringe
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Leukocyte Growth Factor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Chemotherapy works by targeting fast-growing cells — but that includes the cells in your bone marrow that make white blood cells. When white blood cell counts drop too low, your bo...
- Why do I need this injection if I'm already getting chemotherapy?
- It's given as a shot just under the skin — subcutaneously. Depending on the product and your situation, you might receive it via a manual prefilled syringe, or with the Neulasta on...
- The most common side effects are bone pain and aching in your arms and legs — your bones are working harder to produce white blood cells, so some discomfort is normal. But call you...
Patient education
Supplement & herbal interactions
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · Q5120 | $132.096 / Q5120 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Ziextenzo 6 mg/.6mLthis 61314-0866-01 | Sandoz | 1 syringe | — | — | Discontinued | — |
Where does this data come from?
⏳ Availability & biosimilar status
8 biosimilars are FDA-licensed for this reference biologic — see the list below. (Biologics have no small-molecule generics.)
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Nov 4, 2031 |
Is there a biosimilar for ZIEXTENZO 6 MG/0.6 ML SYRINGE?
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💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 61314-0866-01 You're viewing this | 1 BLISTER PACK in 1 CARTON (61314-866-01) / 1 SYRINGE in 1 BLISTER PACK / .6 mL in 1 SYRINGE | 2019-11-04 | Discontinued by firm |
| 61314-0866-02 | 1 BLISTER PACK in 1 CARTON (61314-866-02) / 1 SYRINGE in 1 BLISTER PACK / .6 mL in 1 SYRINGE | 2025-03-03 | Active |
Pack size FAQ
What quantity is in NDC 61314-0866-01?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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.
1.1Patients 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.
1.2Patients 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 ▾
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 )
2.1Patients 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.
2.2Patients 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.
2.3Preparation 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 Cautions ▾
5 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 )
5.1Splenic 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.
5.2Acute 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.
5.3Serious 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.
5.4Use 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.
5.5Glomerulonephritis 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.
5.6Leukocytosis 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.
5.7Thrombocytopenia Pegfilgrastim products can cause thrombocytopenia. Monitor platelet counts during ZIEXTENZO therapy.
5.8Capillary 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.
5.9Potential 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…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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.
6.1Clinical 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.
6.3Postmarketing Experience The following adverse reactions have been identified during post approval use of pegfilgrastim products. Because these reactions are repo…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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).
8.2Lactation 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.
8.4Pediatric 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 acut…
🤰 Pregnancy ▾
8.1Pregnancy 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 ▾
8.4Pediatric 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 ▾
8.5Geriatric 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 ▾
10 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics Animal data and clinical data in humans suggest a correlation between pegfilgrastim products’ exposure and the duration of severe neutropenia as a predictor of efficacy. Selection of the dosing regimen of ZIEXTENZO is based on reducing the duration of severe neutropenia.
12.3Pharmacokinetics The pharmacokinetics of pegfilgrastim was studied in 379 patients with cancer. The pharmacokinetics of pegfilgrastim was nonlinear, and clearance decreased with increases in dose. Neutrophil receptor binding is an important component of the clearance of pegfilgrastim, and serum clearance is directly related to the number of neutrophils.
In addition to numbers of neutrophils, body weight appeared to be a factor. Patients with higher body weights experienced higher systemic exposure to pegfilgrastim after receiving a dose normalized for body weight. A large variability in the pharmacokinetics of pegfilgrastim was observed.
The half-life of pegfilgrastim ranged from 15 to 80 hours after subcutaneous injection. Specific Populations No gender-related differences were observed in the pharmacokinetics of pegfilgrastim, and no differences were observed in the pharmacokinetics of geriatric patients (≥ 65 years of age) compared with younger patients (< 65 years of age) [see Use in Specific Populations ( 8.5 )]. Renal Impairment In a study of 30 subjects with varying degrees of renal dysfunction, including end stage renal disease, renal dysfunction had no effect on the pharmacokinetics of pegfilgrastim.
Pediatric Patients with Cancer Receiving Myelosuppressive Chemotherapy The pharmacokinetics and safety of pegfilgrastim were studied in 37 pediatric patients with sarcoma in Study 4 [see Clinical Studies ( 14.1 ) ] . The mean (± standard deviation [SD]) systemic exposure (AUC 0-inf ) of pegfilgrastim after subcutaneous administration at 100 mcg/kg was 47.9 (± 22.5) mcg·hr/mL in the youngest age group (0 to 5 years, n = 11), 22.0 (± 13.1) mcg·hr/mL in the 6 to 11 years age group (n = 10), and 29.3 (± 23.2) mcg·hr/mL in the 12 to 21 years age group (n = 13).
The terminal elimination half-lives of the corresponding age groups were 30.1 (± 38.2) hours, 20.2 (± 11.3) hours, and 21.2 (± 16.0) hours, respectively. Patients Acutely Exposed to Myelosuppressive Doses of Radiation The pharmacokinetics of pegfilgrastim products is not available in patients acutely exposed to myelosuppressive doses of radiation. Based on limited pharmacokinetic data in irradiated non-human primates, the area under the concentration-time curve (AUC), reflecting the exposure to pegfilgrastim in non-human primates following a 300 mcg/kg dose of pegfilgrastim, appears to be greater than in humans receiving a 6 mg dose.
Results from population modeling and simulation indicate that two 6 mg doses of pegfilgrastim administered one week apart in adults result in clinically relevant effects on duration of grade 3 and 4 neutropenia. In addition, weight-based dosing in pediatric patients weighing less than 45 kg provides exposures comparable to those in adults receiving two 6 mg doses one week apart.
12.6Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of pegfilgrastim or of other pegfilgrastim products. Binding antibodies to pegfilgrastim were detected using a BIAcore assay.
The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6%…
🧬 Mechanism of Action ▾
12.1Mechanism 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 / Storage and Handling ▾
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.
📋 Description ▾
11 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.
💬 Information for Patients ▾
17 PATIENT COUNSELING 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