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ZARXIO filgrastim-sndz 480 ug/.8mL Injection, Solution, 1 syringe — NDC 61314-0326-63 package photo

ZARXIO filgrastim-sndz 480 ug/.8mL Injection, Solution, 1 syringe

by Sandoz Inc. · 1 BLISTER PACK in 1 CARTON (61314-326-63) / 1 SYRINGE in 1 BLISTER PACK / .8 mL in 1 SYRINGE
NDC 61314-0326-63
🏷️ FDA NDC (as labeled) 61314-326-63 billing pads the product segment with a zero
This package
Contains1 syringe Pack sizes4 compare ↓
Also priced by: Part D plans $530.16/unit — full pricing hub ↓
Also comes in: 1 syringe 61314-0326-01 5 syringes 61314-0326-10 5 syringes 61314-0326-69
Rx only Brand On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 61314-326-63
Product NDC 61314-326
11-digit billing NDC 61314032663
RxCUI 1605066, 1605071, 1605074, 1605075
UNII PVI5M0M1GW
Application # BLA125553
SPL Set ID c0d1c22b-566b-4776-bdbf-00f96dad0cae
Established class (EPC) Leukocyte Growth Factor
Physiologic effect Increased Myeloid Cell Production
Chemical class Granulocyte Colony-Stimulating Factor
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2015-03-06
Route INTRAVENOUS, SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance FILGRASTIM
GPI-14 8240152060E540
GPI class Zarxio
GCN Seq No 073645
GCN 38082
HICL code 041814
Ingredient (HICL) Filgrastim-Sndz
HIC1 code N
Therapeutic class — broad (HIC1) Bone Marrow
HIC2 code N1
Therapeutic class — intermediate (HIC2) Affecting Blood, Non-Iron Hematinics And Others
HIC3 code N1C
Therapeutic class — specific (HIC3) Leukocyte (Wbc) Stimulants
AHFS code 20:16.00.00
AHFS class Hematopoietic Agents
FDB label name ZARXIO 480 MCG/0.8 ML SYRINGE
FDB brand name Zarxio
Legend status F — Federal legend — prescription drug or device
Biologic (Purple Book) 351(k) Biosimilar · biosimilar
Reference product filgrastim
Why two NDCs? The FDA registers this code as 61314-326-63 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 61314-0326-63. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Leukocyte Growth Factor class.

Pharmacologic class Leukocyte Growth Factor
Drug family (ATC) Colony stimulating factors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerSandoz Inc.
FDA applicationBLA125553 (BLA)
Labeler code61314
First marketedMar 2015
Product typeHuman Prescription Drug
Portfolio50 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name ZARXIO 480 MCG/0.8 ML SYRINGE Ingredient Filgrastim-Sndz
📖 What it is MedlinePlus · NLM

Filgrastim injection products (Granix, Neupogen, Nivestym, Releuko, Zarxio) are used to decrease the chance of infection in people who have non myeloid cancer (cancer that does not involve the bone marrow) and are receiving chemotherapy medications that may decrease the number of neutrophils (a type of blood cell needed to fight infection). Filgrastim injection products (Neupogen, Nivestym, Releuko, Zarxio) are also used to help increase the number of white blood cells, and decrease the length of time with fever in people with acute myeloid leukemia (AML; a type of cancer of the white blood ce...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Filgrastim tells your bone marrow to make more neutrophils, which are the white blood cells that fight off bacterial infections. When chemotherapy or a condition like chronic neutr...
  • Why has my doctor prescribed filgrastim — what does it actually do for me?
  • The most common one is bone pain — it can range from mild achiness to more noticeable discomfort, especially in your back, hips, or legs, and it's more pronounced when filgrastim i...
  • What side effects are most likely, and are they serious?
📖 Read our full Filgrastim Injection guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 1.178 mg / 0.8 mL UNII 3KX376GY7L
    Glutamic acid is an amino acid used in pharmaceuticals as a buffer and pH regulator. It helps maintain the medicine's chemical stability and proper acidity level.
  • 0.032 mg / 0.8 mL UNII 6OZP39ZG8H
    Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • 40 mg / 0.8 mL UNII 506T60A25R
    Sorbitol is a natural sugar alcohol derived from glucose. It serves as a sweetener, humectant, and bulking agent in medications to improve taste and help maintain moisture in the product.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

5 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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 systemPer mLPer 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 · Q2 2026 $530.16 $424.12 / 0.8 ml
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Zarxio 480 ug/.8mLthis 61314-0326-63 Sandoz 1 syringe — — FDA listed —
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & biosimilar status

🏛️
2015
First FDA approval
Mar 2015
📍
2026
Currently FDA-listed
11 years listed
🔓
2026
Biosimilars listed
4 FDA-licensed
🧬FDA-licensed biosimilars listed

4 biosimilars are FDA-licensed for this reference biologic — see the list below. (Biologics have no small-molecule generics.)

🛡️ Latest patent/protection date listed: Biosimilars are already FDA-licensed for this product — the last listed patent runs to Mar 2027.
📅 FDA approved Mar 6, 2015

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.

FDA Purple Book — biosimilars & interchangeables ⓘ
Reference product
Neupogenfilgrastim
Biosimilars 4
Nivestymfilgrastim-aafi Nypozifilgrastim-txid Releukofilgrastim-ayow Zarxiofilgrastim-sndz
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Patents & exclusivity — FDA Purple Book
Exclusivity RefProduct
2015 2017 2019 2021 2023 2025 2027
Today
LOE
Biologic patent Exclusivity
🏛️Reference-product exclusivity
A flat 12 years of FDA market protection from first licensure. No biosimilar can be licensed before it ends — regardless of patents.
🧪Listed biologic patents
Patents the reference maker lists covering the molecule, formulation, or manufacturing. A biosimilar generally can’t launch until these resolve.
🔁Interchangeability
An interchangeable biosimilar may be substituted at the pharmacy (state laws vary). The first one can earn its own exclusivity period.
🛈 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.

FDA exclusivity
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateMar 6, 2027
Common questions
Is there a biosimilar for ZARXIO 480 MCG/0.8 ML SYRINGE?
Yes — at least one FDA-licensed biosimilar is listed for this biologic. See the Purple Book family above for the available products.
Why do different websites show different biosimilar dates?
Biosimilar availability isn’t based on one single date. Some sources use the reference-product exclusivity, some use the last listed patent, and patent litigation, settlements, and licenses can all change the real-world launch date. This page shows the underlying Purple Book dates so you can see why estimates differ.
Can a biosimilar launch before the last patent expires?
Sometimes. A biosimilar maker may settle with the reference manufacturer or receive a license to launch earlier. In other cases, the last listed protection delays competition.
What does “current Purple Book estimate” mean?
It means we’re using the latest patent and exclusivity dates currently listed in the FDA Purple Book. It is not a guaranteed launch date.
What does “FDA listed” mean?
It means the product appears in the FDA’s official directory. That’s a good sign a product exists for the U.S. market, but on its own it does not confirm a pharmacy can get it today. Where we have recent retail pricing data, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Purple Book for a patent or exclusivity on the reference biologic. It can affect when a biosimilar becomes widely available — but it is not a guaranteed launch date. Settlements and licenses can move the real date earlier or later.
Built from the FDA Purple Book Patent List (patents the reference-product sponsor has publicly listed under the BPCIA) plus reference-product exclusivity. Biosimilars cannot launch until these clear; patent litigation and settlements can shift the real date. Biologics have no small-molecule generics — competition comes from FDA-licensed biosimilars, not the Orange Book.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
1 syringe61314-0326-01 2,855 Rx · $1,417,365
5 syringes61314-0326-10 2,347 Rx · $1,526,344
1 syringe this page61314-0326-63 No Medicaid data
5 syringes61314-0326-69 No Medicaid data
Drug total (last 4 qtrs): 5,202 Rx · 7,169 units · $2,943,709 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Zarxio — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Zarxio. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$9.81M
Claims incl. refills
5K
Beneficiaries
2.7K
Spend / beneficiary
$3,619.82
Spend / claim
$1,970.15
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for ZARXIO (this brand).

Top reported reactions

Death628
Fatigue172
White Blood Cell Count Decreased168
Diarrhoea134
Nausea113
Hospitalisation92
Pyrexia88

Age at onset

Child1
Adolescent3
Adult145
Elderly128

Reporter sex

0 reports
Male · 42%
Female · 57%
Unknown · 0%

Serious outcomes

Death740
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 705 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
61314-0326-01 1 BLISTER PACK in 1 CARTON (61314-326-01) / 1 SYRINGE in 1 BLISTER PACK / .8 mL in 1 SYRINGE $533.41 / mL $426.73 2018-02-22 Active
61314-0326-10 2 BLISTER PACK in 1 CARTON (61314-326-10) / 5 SYRINGE in 1 BLISTER PACK (61314-326-05) / .8 mL in 1 SYRINGE — — 2018-02-22 Active
61314-0326-63 You're viewing this 1 BLISTER PACK in 1 CARTON (61314-326-63) / 1 SYRINGE in 1 BLISTER PACK / .8 mL in 1 SYRINGE — — 2026-06-12 Active
61314-0326-69 2 BLISTER PACK in 1 CARTON (61314-326-69) / 5 SYRINGE in 1 BLISTER PACK (61314-326-65) / .8 mL in 1 SYRINGE — — 2026-06-12 Active

This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 61314-0326-63?
NDC 61314-0326-63 contains 1 syringe — 1 blister pack in 1 carton / 1 syringe in 1 blister pack / .8 ml in 1 syringe.
What is the difference between NDC 61314-0326-63 and NDC 61314-0326-01?
Both are ZARXIO filgrastim-sndz 480 ug/.8mL Injection, Solution — the drug itself is identical. NDC 61314-0326-63 is the 1 syringe package, while NDC 61314-0326-01 is the 1 syringe package.
What NDC number is used to bill for this package of ZARXIO filgrastim-sndz 480 ug/.8mL Injection, Solution?
Bill NDC 61314-0326-63 — the 11-digit billing format is 61314032663. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

🧭 About this NDC listing & data coverage

Finished prescription product
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 ✓ Available
Inactive ingredients (structured) ✓ 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 — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 61314-326-63, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 61314-0326-63, written without dashes as 61314032663. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 61314-0326-63, the first segment (61314) is the labeler code FDA assigned to Sandoz Inc.; the middle segment (0326) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (63) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Sandoz Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 3 other package presentations of this same product, including 1 syringe (61314-0326-01), 5 syringes (61314-0326-10), 5 syringes (61314-0326-69). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Sandoz Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage ~2 min read ▾

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 )

1.1Patients 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 )] .

1.2Patients 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 )] .

1.3Patients 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 )].

1.4Patients 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 )] .

1.5Patients 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 )] .

1.6Patients Acutely Exposed to Myelosuppressive Doses of Radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) ZARXIO is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation [see Clinical Studies ( 14.6 )].

⏱️ Dosage and Administration ~3 min read ▾

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 )

2.1Dosage 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.

2.2Dosage 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 intravenous infusion no longer than 24 hours. Administer the first dose of ZARXIO at least 24 hours after cytotoxic chemotherapy and at least 24 hours after bone marrow infusion. Monitor CBCs and platelet counts frequently following marrow transplantation.

During the period of neutrophil recovery‚ titrate the daily dosage of ZARXIO against the neutrophil response (see Table 1). Table 1. Recommended Dosage Adjustments During Neutrophil Recovery in Patients with Cancer Following BMT Absolute Neutrophil Count ZARXIO Dosage Adjustment When ANC greater than 1,000/mm 3 for 3 consecutive days Reduce to 5 mcg/kg/day If ANC decreases to less than 1,000/mm 3 at any time during the 5 mcg/kg/day administration‚ increase ZARXIO to 10 mcg/kg/day‚ and then follow the above steps.

Then, if ANC remains greater than 1,000/mm 3 for 3 more consecutive days Discontinue ZARXIO Then, if ANC decreases to less than 1,000/mm 3 Resume at 5 mcg/kg/day

2.3 Dosage in Patients Undergoing Autologous Peripheral Blood Progen…

💊 Dosage Forms and Strengths 110 words ▾

3 DOSAGE FORMS AND STRENGTHS ZARXIO is a clear, colorless to slightly yellowish solution available as: Vial: • Injection: 300 mcg/mL in a single-dose vial • Injection: 480 mcg/1.6 mL (300 mcg/mL) in a single-dose vial Prefilled Syringe: • Injection: 300 mcg/0.5 mL in a single-dose prefilled syringe • Injection: 480 mcg/0.8 mL in a single-dose prefilled syringe Vial • Injection: 300 mcg/mL in a single-dose-vial ( 3 ) • Injection: 480 mcg/1.6 mL (300 mcg/mL) in a single-dose-vial ( 3 ) Prefilled Syringe • Injection: 300 mcg/0.5 mL in a single-dose prefilled syringe ( 3 ) • Injection: 480 mcg/0.8 mL in a single-dose prefilled syringe ( 3 )

⛔ Contraindications 57 words ▾

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 )

⚠️ Warnings and Cautions ~2 min read ▾

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 and lung infiltrates or respiratory distress for ARDS. Discontinue ZARXIO in patients with ARDS.

( 5.2 ) • Serious allergic reactions, including anaphylaxis : Permanently discontinue ZARXIO in patients with serious allergic reactions. ( 5.3 ) • Fatal sickle cell crises : Discontinue ZARXIO if sickle cell crisis occurs. ( 5.4 ) • Glomerulonephritis : Evaluate and consider dose-reduction or interruption of ZARXIO if causality is likely.

( 5.5 ) • Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) : Monitor patients with breast and lung cancer using ZARXIO in conjunction with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML. ( 5.8 ) • Thrombocytopenia : Monitor platelet counts. ( 5.9 ) • Aortitis: Aortitis has been reported in patients receiving filgrastim products.

Discontinue ZARXIO if aortitis is suspected. ( 5.15 )

5.1Splenic Rupture Splenic rupture, including fatal cases, has been reported following the administration of filgrastim products. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

5.2Acute Respiratory Distress Syndrome Acute respiratory distress syndrome (ARDS) has been reported in patients receiving filgrastim products. Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue ZARXIO in patients with ARDS.

5.3Serious Allergic Reactions Serious allergic reactions, including anaphylaxis, have been reported in patients receiving filgrastim products. The majority of reported events occurred upon initial exposure. Provide symptomatic treatment for allergic reactions.

Allergic reactions, including anaphylaxis, in patients receiving filgrastim products can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue ZARXIO in patients with serious allergic reactions. 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.

5.4Sickle Cell Disorders Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim products. Discontinue ZARXIO if sickle cell crisis occurs.

5.5Glomerulonephritis Glomerulonephritis has occurred in patients receiving filgrastim 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 filgrastim products. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of ZARXIO.

5.6Alveolar Hemorrhage and Hemoptysis Alveolar hemorrhage manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization have been reported in healthy donors treated with filgrastim products undergoing peripheral blood progenitor cell (PBPC) collection mobilization. Hemoptysis resolved with discontinuation of filgrastim products. The use of ZARXIO for PBPC mobilization in healthy donors is not an approved indication.

5.7Capillary Leak Syndrome Capillary leak syndrome (CLS) has been reported after G-CSF administration, including filgrastim 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.

5.8Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) Patients with Severe Chronic Neutr…

🤒 Adverse Reactions ~3 min read ▾

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.

6.1Clinical 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. 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 adm…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy 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 on prenatal development have been studied in rats and rabbits. No malformations were observed in either species.

Filgrastim has been shown to have adverse effects in pregnant rabbits at doses 2 to 10 times higher than the human doses. In pregnant rabbits showing signs of maternal toxicity, reduced embryo-fetal survival (at 20 and 80 mcg/kg/day) and increased abortions (at 80 mcg/kg/day) were observed. In pregnant rats, no maternal or fetal effects were observed at doses up to 575 mcg/kg/day, which is approximately 58 times higher than the human dose of 10 mcg/kg/day.

Offspring of rats administered filgrastim during the peri-natal and lactation periods exhibited a delay in external differentiation and growth retardation (≥ 20 mcg/kg/day) and slightly reduced survival rate (100 mcg/kg/day).

8.2Lactation Risk Summary There is published literature documenting transfer of filgrastim into human milk. There are a few case reports describing the use of filgrastim in breastfeeding mothers with no adverse effects noted in the infants. There are no data on the effects of filgrastim products 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 ZARXIO and any potential adverse effects on the breastfed child from ZARXIO or from the underlying maternal condition.

8.4Pediatric Use ZARXIO prefilled syringe with BD UltraSafe Passive ® Needle Guard may not accurately measure volumes less than 0.3 mL due to the needle spring mechanism design. Therefore, the direct administration of a volume less than 0.3 mL using ZARXIO prefilled syringe is not recommended due to the potential for dosing errors. For direct administration of doses less than 0.3 mL (180 mcg) use ZARXIO single-dose vial.

In patients with cancer receiving myelosuppressive chemotherapy‚…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy 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 on prenatal development have been studied in rats and rabbits. No malformations were observed in either species.

Filgrastim has been shown to have adverse effects in pregnant rabbits at doses 2 to 10 times higher than the human doses. In pregnant rabbits showing signs of maternal toxicity, reduced embryo-fetal survival (at 20 and 80 mcg/kg/day) and increased abortions (at 80 mcg/kg/day) were observed. In pregnant rats, no maternal or fetal effects were observed at doses up to 575 mcg/kg/day, which is approximately 58 times higher than the human dose of 10 mcg/kg/day.

Offspring of rats administered filgrastim during the peri-natal and lactation periods exhibited a delay in external differentiation and growth retardation (≥ 20 mcg/kg/day) and slightly reduced survival rate (100 mcg/kg/day).

🧒 Pediatric Use ~2 min read ▾

8.4Pediatric Use ZARXIO prefilled syringe with BD UltraSafe Passive ® Needle Guard may not accurately measure volumes less than 0.3 mL due to the needle spring mechanism design. Therefore, the direct administration of a volume less than 0.3 mL using ZARXIO prefilled syringe is not recommended due to the potential for dosing errors. For direct administration of doses less than 0.3 mL (180 mcg) use ZARXIO single-dose vial.

In patients with cancer receiving myelosuppressive chemotherapy‚ 15 pediatric patients median age 2.6 (range 1.2 to 9.4) years with neuroblastoma were treated with myelosuppressive chemotherapy (cyclophosphamide‚ cisplatin‚ doxorubicin‚ and etoposide) followed by subcutaneous filgrastim at doses of 5, 10, or 15 mcg/kg/day for 10 days (n=5/dose) (Study 8). The pharmacokinetics of filgrastim in pediatric patients after chemotherapy are similar to those in adults receiving the same weight-normalized doses, suggesting no age-related differences in the pharmacokinetics of filgrastim.

In this population‚ filgrastim was well tolerated. There was one report of palpable splenomegaly and one report of hepatosplenomegaly associated with filgrastim therapy; however‚ the only consistently reported adverse event was musculoskeletal pain‚ which is no different from the experience in the adult population. The safety and effectiveness of ZARXIO have been established in pediatric patients with SCN [see Clinical Studies ( 14.5 )] .

In a phase 3 study (Study 7) to assess the safety and efficacy of filgrastim in the treatment of SCN, 123 patients with a median age of 12 years (range 7 months to 76 years) were studied. Of the 123 patients, 12 were infants (7 months to 2 years of age), 49 were children (2 to 12 years of age), and 9 were adolescents (12 to 16 years of age). Additional information is available from a SCN postmarketing surveillance study, which includes long-term follow-up of patients in the clinical studies and information from additional patients who entered directly into the postmarketing surveillance study.

Of the 731 patients in the surveillance study, 429 were pediatric patients < 18 years of age (range 0.9 to 17) [see Indications and Usage ( 1.5 ), Dosage and Administration ( 2.6 ), and Clinical Studies ( 14.5 )] . Long-term follow-up data from the postmarketing surveillance study suggest that height and weight are not adversely affected in patients who received up to 5 years of filgrastim treatment. Limited data from patients who were followed in the phase 3 study for 1.5 years did not suggest alterations in sexual maturation or endocrine function.

Pediatric patients with congenital types of neutropenia (Kostmann’s syndrome, congenital agranulocytosis, or Schwachman-Diamond syndrome) have developed cytogenetic abnormalities and have undergone transformation to MDS and AML while receiving chronic filgrastim treatment. The relationship of these events to filgrastim product administration is unknown [see Warnings and Precautions ( 5.8 ) and Adverse Reactions ( 6 )] . The use of ZARXIO to increase survival in pediatric patients acutely exposed to myelosuppressive doses of radiation is based on studies of filgrastim conducted in animals and clinical data supporting the use of filgrastim in other approved indications [see Dosage and Administration ( 2.1 to 2.4 ) and Clinical Studies ( 14.6 )] .

🧓 Geriatric Use 84 words ▾

8.5Geriatric Use Among 855 subjects enrolled in 3 randomized, placebo-controlled trials of filgrastim treated-patients receiving myelosuppressive chemotherapy, there were 232 subjects age 65 or older, and 22 subjects age 75 or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Clinical studies of filgrastim in other approved indications (i.e., BMT recipients, PBPC mobilization, and SCN) did not include sufficient numbers of subjects aged 65 and older to determine whether elderly subjects respond differently from younger subjects.

🆘 Overdosage 79 words ▾

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.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation. Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens).

G-CSF is not species-specific and has been shown to have minimal direct in vivo or in vitro effects on the production or activity of hematopoietic cell types other than the neutrophil lineage.

12.2Pharmacodynamics In phase 1 studies involving 96 patients with various nonmyeloid malignancies‚ administration of filgrastim resulted in a dose-dependent increase in circulating neutrophil counts over the dose range of 1 to 70 mcg/kg/day. This increase in neutrophil counts was observed whether filgrastim was administered intravenous (1 to 70 mcg/kg twice daily)‚ subcutaneous (1 to 3 mcg/kg once daily)‚ or by continuous subcutaneous infusion (3 to 11 mcg/kg/day). With discontinuation of filgrastim therapy‚ neutrophil counts returned to baseline in most cases within 4 days.

Isolated neutrophils displayed normal phagocytic (measured by zymosan-stimulated chemiluminescence) and chemotactic (measured by migration under agarose using N-formyl-methionyl-leucyl‑phenylalanine [fMLP] as the chemotaxin) activity in vitro. The absolute monocyte count was reported to increase in a dose-dependent manner in most patients receiving filgrastim; however‚ the percentage of monocytes in the differential count remained within the normal range. Absolute counts of both eosinophils and basophils did not change and were within the normal range following administration of filgrastim.

Increases in lymphocyte counts following filgrastim administration have been reported in some normal subjects and patients with cancer. White blood cell (WBC) differentials obtained during clinical trials have demonstrated a shift towards earlier granulocyte progenitor cells (left shift)‚ including the appearance of promyelocytes and myeloblasts‚ usually during neutrophil recovery following the chemotherapy-induced nadir. In addition‚ Dohle bodies‚ increased granulocyte granulation‚ and hypersegmented neutrophils have been observed.

Such changes were transient and were not associated with clinical sequelae, nor were they necessarily associated with infection.

12.3Pharmacokinetics Filgrastim products exhibit nonlinear pharmacokinetics. Clearance is dependent on filgrastim product concentration and neutrophil count: G-CSF receptor-mediated clearance is saturated by high concentration of filgrastim products and is diminished by neutropenia. In addition, filgrastim products are cleared by the kidney.

Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. After intravenous administration, the volume of distribution averaged 150 mL/kg and the elimination half-life was approximately 3.5 hours in both normal subjects and subjects with cancer. Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg.

Single parenteral doses or daily intravenous doses‚ over a 14-day period‚ resulted in comparable half-lives. The half-lives were similar for intravenous administration (231 minutes‚ following doses of 34.5 mcg/kg) and for subcutaneous administration (210 minutes‚ following filgrastim dosages of 3.45 mcg/kg). Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-st…

🧬 Mechanism of Action 122 words ▾

12.1Mechanism of Action Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation. Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens).

G-CSF is not species-specific and has been shown to have minimal direct in vivo or in vitro effects on the production or activity of hematopoietic cell types other than the neutrophil lineage.

📦 How Supplied / Storage and Handling 212 words ▾

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 mL (300 mcg/mL) of filgrastim-sndz solution (NDC 61314-266-73) The vial stopper is not made with natural rubber latex. Prefilled syringe (BD UltraSafe Passive ® Needle Guard): Single-dose prefilled syringe with a 29 gauge, ½ inch needle and with BD UltraSafe Passive ® Needle Guard, containing 300 mcg/0.5 mL of filgrastim-sndz solution. • Pack of 1 prefilled syringe (NDC 61314-318-63) • Pack of 10 (multipack) prefilled syringes (NDC 61314-318-69) Single-dose prefilled syringe with a 29 gauge, ½ inch needle and with BD UltraSafe Passive ® Needle Guard, containing 480 mcg/0.8 mL of filgrastim-sndz solution. • Pack of 1 prefilled syringe (NDC 61314-326-63) • Pack of 10 (multipack) prefilled syringes (NDC 61314-326-69) The prefilled syringe with safety guard is not made with natural rubber latex.

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.

📋 Description ~1 min read ▾

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

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Review the steps for direct patient administration with patients and caregivers. Training by the healthcare provider should aim to ensure that patients and caregivers can successfully perform all of the steps in the Instructions for Use of ZARXIO vial and prefilled syringe, including showing the patient or caregiver how to measure the required dose, particularly if a patient is on a dose other than the entire prefilled syringe.

If a patient or caregiver is not able to demonstrate that they can measure the dose and administer the product successfully, you should consider whether the patient is an appropriate candidate for self-administration of ZARXIO or whether the patient would benefit from a different ZARXIO presentation. Advise patients of the following risks and potential risks with ZARXIO: • Rupture or enlargement of the spleen may occur. Symptoms include left upper quadrant abdominal pain or left shoulder pain.

Advise patients to report pain in these areas to their physician immediately [see Warnings and Precautions ( 5.1 )] . • Dyspnea, with or without fever, progressing to Acute Respiratory Distress Syndrome, may occur. Advise patients to report dyspnea to their physician immediately [see Warnings and Precautions ( 5.2 )] . • Serious allergic reactions may occur, which may be signaled by rash‚ facial edema‚ wheezing‚ dyspnea‚ hypotension‚ or tachycardia. Advise patients to seek immediate medical attention if signs or symptoms of hypersensitivity reaction occur [see Warnings and Precautions ( 5.3 )] . • In patients with sickle cell disease, sickle cell crisis and death have occurred.

Discuss potential risks and benefits for patients with sickle cell disease prior to the administration of human granulocyte colony-stimulating factors [see Warnings and Precautions ( 5.4 )] . • Glomerulonephritis may occur. Symptoms include swelling of the face or ankles, dark colored urine or blood in the urine, or a decrease in urine production. Advise patients to report signs or symptoms of glomerulonephritis to their physician immediately [see Warnings and Precautions ( 5.5 )] . • There may be an increased risk of Myelodysplastic Syndrome and/or Acute Myeloid Leukemia in patients with congenital neutropenia who receive filgrastim products and in patients with breast and lung cancer who receive filgrastim products in conjunction with chemotherapy and/or radiation therapy.

Symptoms of MDS and AML may include tiredness, fever, and easy bruising or bleeding. Advise patients to report to their physician signs and symptoms of MDS/AML [see Warnings and Precautions ( 5.8 )]. • Cutaneous vasculitis may occur, which may be signaled by purpura or erythema. Advise patients to report signs or symptoms of vasculitis to their physician immediately [see Warnings and Precautions ( 5.11 )] . • Aortitis may occur.

Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Advise patients to report signs and symptoms of aortitis to their physician immediately [see Warnings and Precautions ( 5.15 )] . Advise patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) that efficacy studies of filgrastim 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 ( 14.6 )].

Instruct patients who self-administer ZARXIO using the prefilled syringe or single-dose vial of the: • Importance of following the applicable Instructions for Use. • Dangers of reusing needles, syringes or unused portions of single-dose vials. • Importance of following local requirements for proper disposal of used syringes, needles, and unused vials. • Importance of informing the healthcare provider if…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.