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Avopef etoposide 500 mg/25mL Injection — NDC 83831-0145-25 package photo

Avopef etoposide 500 mg/25mL Injection

by Avyxa Pharma, LLC · 1 VIAL in 1 CARTON (83831-145-25) / 25 mL in 1 VIAL
NDC 83831-0145-25
🏷️ FDA NDC (as labeled) 83831-145-25 billing pads the product segment with a zero
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) 83831-145-25
Product NDC 83831-145
11-digit billing NDC 83831014525
NCPDP billing unit ML — per mL (volume)
RxCUI 310248, 2735802
UNII 6PLQ3CP4P3
Application # NDA220200
SPL Set ID acc1e443-ef7b-486f-a638-710a20e81059
Established class (EPC) Topoisomerase Inhibitor
Mechanism of action Topoisomerase Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2026-06-24
Route INTRAVENOUS
Dosage form INJECTION
Substance ETOPOSIDE
Why two NDCs? The FDA registers this code as 83831-145-25 — 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 → 83831-0145-25. 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 Topoisomerase Inhibitor class.

Pharmacologic class Topoisomerase Inhibitor
Drug family (ATC) Podophyllotoxin derivatives
How it works Topoisomerase Inhibitors
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

LabelerAvyxa Pharma, LLC
Application holderAVYXA HOLDINGS LLC
FDA applicationNDA220200 (NDA)
Labeler code83831
First marketedJun 2026
Product typeHuman Prescription Drug
Portfolio29 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

📖 What it is MedlinePlus · NLM

Etoposide injection is used in combination with other medications to treat cancer of the testicles that has not improved or that has worsened after treatment with other medications or radiation therapy. Etoposide injection is also used in combination with other medications to treat a certain type of lung cancer (small cell lung cancer; SCLC). Etoposide is in a class of medications known as podophyllotoxin derivatives. It works by slowing or stopping the growth of cancer cells in your body.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Etoposide injection is used to treat two types of cancer: testicular cancer that hasn't responded to prior treatments (called refractory testicular tumors), and small cell lung can...
  • What cancers does etoposide injection treat?
  • The biggest concern is myelosuppression — that's when the drug lowers your blood cell counts significantly. Low white blood cells make you vulnerable to serious infections, and low...
  • What's the most important side effect I should watch out for?
📖 Read our full Etoposide Injection guide →
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.

  • UNII XF417D3PSL
    Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
  • UNII 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • UNII B697894SGQ
    Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
  • 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.

4 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 eachPer 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.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
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
Avopef 500 mg/25mLthis 83831-0145-25 Avyxa 1 vial — — FDA listed —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
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 & generic status

🏛️
2026
On the market since
Jun 2026
📍
2026
Currently FDA-listed
listed with the FDA
🔒
·
Generic approved (availability unconfirmed)
see note
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

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

Medicare Part D (outpatient prescription) spending for Etoposide (matched by generic name) — the program that covers self-administered drugs. 5 manufacturers.
⚠️ 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 Etoposide. 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
$6.6K
Claims incl. refills
133
Beneficiaries
62
Spend / beneficiary
$106.50
Spend / claim
$49.64
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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
83831-0145-25 You're viewing this 1 VIAL in 1 CARTON (83831-145-25) / 25 mL in 1 VIAL 2026-06-24 Active

🧭 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 — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
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 83831-145-25, 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: 83831-0145-25, written without dashes as 83831014525. 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 83831-0145-25, the first segment (83831) is the labeler code FDA assigned to Avyxa Pharma, LLC; the middle segment (0145) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (25) 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 Avyxa Pharma, LLC. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Avyxa Pharma, LLC 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.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning 160 words ▾

WARNING: SEVERE MYELOSUPPRESSION AVOPEF can cause severe myelosuppression resulting in infection or bleeding [see Warnings and Precautions (5.1) ] . Do not administer AVOPEF to patients with absolute neutrophil counts of less than 500 cells/mm 3 or platelets less than 50,000 cells/mm 3 [see Warnings and Precautions (5.1) ] . Monitor complete blood cell counts, prior to the administration of AVOPEF and before each subsequent cycle, and at appropriate intervals during and after therapy [see Warnings and Precautions (5.1) ] .

WARNING: SEVERE MYELOSUPPRESSION See full prescribing information for complete boxed warning . AVOPEF can cause severe myelosuppression resulting in infection or bleeding. ( 5.1 ) Do not administer AVOPEF to patients with absolute neutrophil counts of less than 500 cells/mm 3 or platelets less than 50,000 cells/mm 3 .

( 5.1 ) Monitor complete blood cell counts, prior to the administration of AVOPEF and before each subsequent cycle, and at appropriate intervals during and after therapy. ( 5.1 )

🎯 Indications and Usage 85 words ▾

1 INDICATIONS AND USAGE AVOPEF is a topoisomerase inhibitor indicated, in combination with other chemotherapy and/or immunotherapy, for the treatment of adult patients with: Refractory testicular cancer ( 1.1 ) Small cell lung cancer ( 1.2 )

1.1Refractory Testicular Cancer AVOPEF, in combination with chemotherapy, is indicated for the treatment of refractory testicular cancer in adult patients.

1.2Small Cell Lung Cancer AVOPEF, in combination with chemotherapy and immunotherapy, is indicated for the first-line treatment of small cell lung cancer (SCLC) in adult patients.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Refractory Testicular Cancer : 50 mg/m 2 to 100 mg/m 2 administered intravenously daily on Days 1 to 5, or 100 mg/m 2 administered intravenously daily on Days 1, 3 and 5. ( 2.2 ) Small Cell Lung Cancer : 35 mg/m 2 administered intravenously daily on days 1 to 4, or 50 mg/m 2 administered intravenously daily on days 1 to 5. ( 2.3 ) Dilute AVOPEF prior to intravenous infusion over 30- to 60-minutes. ( 2.5 )

2.1Important Dosage and Administration Information Dilute AVOPEF to a final concentration of 0.2 to 0.4 mg/mL prior to administration [see Dosage and Administration (2.5) ]. Administer diluted AVOPEF by intravenous infusion over 30 to 60 minutes to reduce the risk of infusion-related reactions including hypotension [see Dosage and Administration (2.5) ]. Before each AVOPEF administration and at appropriate intervals during and after therapy, monitor complete blood counts with differential and serum albumin [see Warnings and Precautions (5.1, 5.5) ].

If severe reactions occur, reduce the dosage or discontinue AVOPEF and take appropriate corrective measures according to the clinical judgment of the healthcare provider.

2.2Recommended Dosage for Refractory Testicular Cancer The recommended dosage of AVOPEF is: 50 mg/m 2 to 100 mg/m 2 administered intravenously daily on Days 1 to 5, or 100 mg/m 2 administered intravenously daily on Days 1, 3 and 5 Repeat treatment cycles every 3 to 4 weeks.

2.3Recommended Dosage for Small Cell Lung Cancer The recommended dosage of AVOPEF is: 35 mg/m 2 administered intravenously daily on Days 1 to 4, or 50 mg/m 2 administered intravenously daily on Days 1 to 5 Repeat treatment cycles every 3 to 4 weeks.

2.4Recommended Dosage in Patients with Renal Impairment No dosage modification is recommended for patients with creatinine clearance (CLcr) > 50 mL/min. The recommended dosage of AVOPEF in patients with CLcr of 15 to 50 mL/min is listed in Table 1. Table 1: Recommended Dosage of AVOPEF in Patients with Creatinine Clearance of 15 to 50 mL/min *Repeat treatment cycles every 3 to 4 weeks.

Recommended AVOPEF Dosage * Refractory Testicular Cancer 37 mg/m 2 to 75 mg/m 2 Days 1 through 5 75 mg/m 2 Days 1, 3 and 5 Small Cell Lung Cancer 26 mg/m 2 Days 1 through 4 37 mg/m 2 Days 1 through 5 A recommended dosage of AVOPEF has not been established for patients with creatinine clearance < 15 mL/min.

2.5Preparation for Intravenous Administration Preparation AVOPEF is a hazardous drug. Follow applicable special handling and disposal procedures. [see References (15) ]. Dilute AVOPEF with either 5% Dextrose Injection, USP, or 0.9% Sodium Chloride Injection, USP, to a final concentration of 0.2 to 0.4 mg/mL.

If solutions of AVOPEF are prepared at concentrations above 0.4 mg/mL, precipitation may occur. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Administration Do not administer AVOPEF by rapid intravenous injection.

To reduce the risk of infusion-related reactions including hypotension, administer diluted AVOPEF intravenously over 30 to 60 minutes. A longer duration of administration may be used if there is a large volume of fluid to be infused. Storage AVOPEF, diluted to a concentration of 0.2 mg/mL is stable for 96 hours or diluted to a concentration of 0.4 mg/mL is stable for 24 hours at room temperature (25°C) under normal room fluorescent light in polyvinyl chloride (PVC) container.

After first use, store the partially used multiple-dose vial in the original carton at controlled room temperature, 20°C to 25° C (68°F to 77° F) for up to 28 days. Discard unused portion of the multiple-dose vial after 28 days.

💊 Dosage Forms and Strengths 51 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 100 mg/5 mL (20 mg/mL) and 500 mg/25 mL (20 mg/mL) of etoposide as a sterile, clear, colorless to light yellow liquid in a multiple-dose vial. Injection: 100 mg/5 mL (20 mg/mL) and 500 mg/25 mL (20 mg/mL) in a multiple-dose vial. ( 3 )

⛔ Contraindications 27 words ▾

4 CONTRAINDICATIONS AVOPEF is contraindicated in patients with hypersensitivity to etoposide or any of its excipients. Hypersensitivity to etoposide or any of its excipients. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Severe Myelosuppression : Monitor complete blood counts before each AVOPEF administration and at appropriate intervals during and after therapy. Interrupt AVOPEF for absolute neutrophil counts below 500 cells/mm 3 or platelet counts below 50,000 cells/mm 3 . ( 5.1 ) Hypersensitivity and Infusion-Related Reactions : At the first sign of hypersensitivity, stop the infusion and administer volume expanders, corticosteroids, antihistamines, and pressor agents as appropriate.

Permanently discontinue AVOPEF in patients who experience a severe hypersensitivity reaction. Hypotension has occurred after rapid intravenous injection. ( 5.2 ) Extravasation Resulting in Tissue Necrosis : Extravasation of etoposide can result in swelling, pain, cellulitis, and tissue necrosis.

( 5.3 ) Secondary Leukemia : Secondary leukemia has occurred with use of etoposide. ( 5.4 ) Risk of Increased AVOPEF Toxicity with Low Serum Albumin : Monitor serum albumin during treatment with AVOPEF. Patients with low serum albumin may have increased concentrations of unbound etoposide and may be at an increased risk for etoposide associated adverse reactions.

( 5.5 ) Alcohol Content : The alcohol content in a dose of AVOPEF may affect the central nervous system. This may include impairment of a patient's ability to drive or use machines immediately after infusion. ( 5.6 ) Embryo-Fetal Toxicity : AVOPEF can cause fetal harm.

Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.7 )

5.1Severe Myelosuppression AVOPEF can cause severe and fatal myelosuppression, including neutropenia, febrile neutropenia, anemia, and thrombocytopenia. Monitor complete blood counts with differential before each AVOPEF administration and at appropriate intervals during and after treatment with AVOPEF. Do not administer AVOPEF to patients with absolute neutrophil counts of less than 500 cells/mm 3 or platelets less than 50,000 cells/mm 3 .

5.2Hypersensitivity and Infusion-Related Reactions AVOPEF can cause severe and fatal infusion-related reactions including anaphylactic reactions characterized by chills, fever, tachycardia, bronchospasm, dyspnea and hypotension [see Adverse Reactions (6.1) ] . Hypertension and flushing have occurred. At the first sign of hypersensitivity, stop the infusion and administer volume expanders, corticosteroids, antihistamines, and pressor agents as appropriate.

Permanently discontinue AVOPEF in patients who experience a severe hypersensitivity reaction. Hypotension due to rapid intravenous injection has also occurred. To reduce the risk of hypotension due to an infusion-related reaction, administer AVOPEF by intravenous infusion over 30 to 60 minutes [see Dosage and Administration (2.5) ].

5.3Extravasation Resulting in Tissue Necrosis Extravasation of etoposide can result in swelling, pain, cellulitis, and tissue necrosis.

5.4Secondary Leukemia Secondary leukemia has occurred with use of etoposide.

5.5Risk of Increased AVOPEF Toxicity with Low Serum Albumin Etoposide is highly protein-bound. Patients with low serum albumin may have increased concentrations of unbound etoposide and may be at an increased risk for etoposide associated adverse reactions. Monitor for increased adverse reactions during treatment with AVOPEF in patients with low serum albumin.

5.6Alcohol Content The alcohol content in a dose of AVOPEF may affect the central nervous system and should be taken into account for patients in whom alcohol intake should be avoided or minimized. Consideration should be given to the alcohol content in AVOPEF on the ability to drive or use machines immediately after the infusion. Each administration of AVOPEF at 100 mg/m 2 delivers 1.5 g/m 2 of ethanol.

For a patient with a BSA of 2.0 m 2 this would deliver 3.0 grams of ethanol [see Description (11) ]. Other etoposide products may have a different amount of alcohol or no alcohol.

5.7 Embryo-Fetal Toxicity Based on findings from animal studies…

🤒 Adverse Reactions ~1 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in more detail in other sections of the labeling. Severe Myelosuppression [see Warnings and Precautions (5.1) ] Hypersensitivity and Infusion-Related Reactions [see Warnings and Precautions (5.2) ] Extravasation Resulting in Tissue Necrosis [see Warnings and Precautions (5.3) ] Secondary Leukemia [see Warnings and Precautions (5.4) ] Risk of Increased AVOPEF Toxicity with Low Serum Albumin [see Warnings and Precautions (5.5) ] Alcohol Content [see Warnings and Precautions (5.6) ] The most common adverse reactions are myelosuppression, hypersensitivity, nausea/vomiting, and alopecia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avyxa Pharma, LLC at 1-888-520-0954 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 to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Blood and lymphatic system disorders : acute leukemia, myelosuppression Eye disorders : transient cortical blindness Gastrointestinal disorders : abdominal pain, anorexia, constipation, diarrhea, dysgeusia, dysphagia, esophagitis, mucositis, nausea, stomatitis and vomiting General disorders and administration site conditions : fatigue, fever, and infusion site extravasation with necrosis Hepatobiliary disorders : hepatotoxicity, metabolic acidosis Immune system disorders : allergic reaction, anaphylactic reaction (including chills, fever, tachycardia, bronchospasm, dyspnea, hypotension, hypertension, flushing, facial swelling, tongue swelling, coughing, diaphoresis, cyanosis, tightness in throat, laryngospasm, back pain, loss of consciousness, hypersensitivity-associated apnea), hypersensitivity, infusion-related reaction.

Infections : febrile neutropenia Nervous system disorders : optic neuritis, peripheral neuropathy and seizure Respiratory, thoracic and mediastinal disorders : interstitial pneumonitis and pulmonary fibrosis Skin and subcutaneous tissue disorders : alopecia, pigmentation changes (including pigmented bands in nails, skin darkening and discoloration of tongue and teeth), pruritic erythematous maculopapular rash, pruritus, radiation recall dermatitis, rash, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and urticaria Vascular disorders : hypotension following rapid intravenous administration [see Dosage and Administration (2.5) ] , perivasculitis

🔄 Drug Interactions 173 words ▾

7 DRUG INTERACTIONS CYP3A Inhibitors and CYP3A Inducers : Avoid concomitant use of strong CYP3A inhibitors and strong CYP3A inducers with AVOPEF. ( 7.1 ) Vitamin K Antagonists : Monitor INR more frequently and modify the dosage of the vitamin K antagonists as appropriate. Co-administration of AVOPEF with warfarin can result in elevated international normalized ratio (INR). ( 7.2 )

7.1Effect of Other Drugs on AVOPEF CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors. Etoposide is a CYP3A4 substrate. Strong CYP3A inhibitors may increase etoposide exposure, which may increase the risk of AVOPEF-associated adverse reactions [see Clinical Pharmacology (12.3) ].

CYP3A Inducers Avoid concomitant use of strong CYP3A inducers. Etoposide is a CYP3A4 substrate. Strong CYP3A inducers may reduce etoposide exposure, which may decrease the effectiveness of AVOPEF [see Clinical Pharmacology (12.3) ].

7.2Effect of AVOPEF on Other Drugs Vitamin K Antagonists Monitor INR more frequently and modify the dosage of the vitamin K antagonists as appropriate. Co-administration of AVOPEF with warfarin can result in elevated international normalized ratio (INR).

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 ) Renal Impairment : Reduce the recommended dose for patients with creatinine clearance of 15 to 50 mL/min. ( 2.4 )

8.1Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ], AVOPEF can cause fetal harm when administered to a pregnant woman. There are no available data on the use of AVOPEF in pregnant women to inform a drug-associated risk. AVOPEF contains alcohol which can interfere with neurobehavioral development [see Clinical Considerations] .

In animal reproduction studies, intravenous or intraperitoneal administration of etoposide to pregnant animals during the period of organogenesis caused embryo-fetal mortality and structural abnormalities at doses below the recommended human dose of 50 mg/m 2 based on body surface area (BSA). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with AVOPEF and for 6 months after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1) ] .

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and of miscarriage is 15% to 20%, respectively. Clinical Considerations AVOPEF contains alcohol [see Warnings and Precautions (5.6) ] . Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development.

Data Animal Data In rats, an intravenous etoposide dose of 0.4 mg/kg/day (approximately 0.05 times the human dose of 50 mg/m 2 based on BSA) during organogenesis caused maternal toxicity, embryotoxicity, and teratogenicity (skeletal abnormalities, exencephaly, encephalocele, and anophthalmia); higher doses of 1.2 and 3.6 mg/kg/day (approximately 0.14- and 0.5-times the human dose of 50 mg/m 2 based on BSA) resulted in 90% and 100% embryonic resorptions, respectively. In mice, a single etoposide dose of 1.0 mg/kg (approximately 0.06 times the human dose of 50 mg/m 2 based on BSA) administered intraperitoneally on Days 6, 7, or 8 of gestation caused embryotoxicity, cranial abnormalities, and major skeletal malformations.

An intraperitoneal dose of 1.5 mg/kg (approximately 0.10-times the human dose 50 mg/m 2 based on BSA) on Day 7 of gestation caused an increase in the incidence of intrauterine death, fetal malformations, and a significant decrease in the average fetal body weight.

8.2Lactation Risk Summary There is no information regarding the presence of etoposide or its metabolites in human milk or the effects on a breastfed child or on milk production. Because the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with AVOPEF and for 1 week after the last dose.

8.3Females and Males of Reproductive Potential Based on animal data and its mechanism of action, AVOPEF can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify the pregnancy status of female patients of reproductive potential prior to initiating AVOPEF. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with AVOPEF and for 6 months after the last dose [see Use in Specific Populations (8.1) and Nonclinical Toxicology (13.1) ] .

Males Due to the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with AVOPEF and for 4 months after the last dose [see Nonclinical Toxicology (13.1) ]. Infertility Females In females of reproductive potential, AVOPEF may cause infertility and result in amenorrhea. Premature menopause can occur with AVOPEF.

Recovery of men…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ], AVOPEF can cause fetal harm when administered to a pregnant woman. There are no available data on the use of AVOPEF in pregnant women to inform a drug-associated risk. AVOPEF contains alcohol which can interfere with neurobehavioral development [see Clinical Considerations] .

In animal reproduction studies, intravenous or intraperitoneal administration of etoposide to pregnant animals during the period of organogenesis caused embryo-fetal mortality and structural abnormalities at doses below the recommended human dose of 50 mg/m 2 based on body surface area (BSA). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with AVOPEF and for 6 months after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1) ] .

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and of miscarriage is 15% to 20%, respectively. Clinical Considerations AVOPEF contains alcohol [see Warnings and Precautions (5.6) ] . Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development.

Data Animal Data In rats, an intravenous etoposide dose of 0.4 mg/kg/day (approximately 0.05 times the human dose of 50 mg/m 2 based on BSA) during organogenesis caused maternal toxicity, embryotoxicity, and teratogenicity (skeletal abnormalities, exencephaly, encephalocele, and anophthalmia); higher doses of 1.2 and 3.6 mg/kg/day (approximately 0.14- and 0.5-times the human dose of 50 mg/m 2 based on BSA) resulted in 90% and 100% embryonic resorptions, respectively. In mice, a single etoposide dose of 1.0 mg/kg (approximately 0.06 times the human dose of 50 mg/m 2 based on BSA) administered intraperitoneally on Days 6, 7, or 8 of gestation caused embryotoxicity, cranial abnormalities, and major skeletal malformations.

An intraperitoneal dose of 1.5 mg/kg (approximately 0.10-times the human dose 50 mg/m 2 based on BSA) on Day 7 of gestation caused an increase in the incidence of intrauterine death, fetal malformations, and a significant decrease in the average fetal body weight.

🧒 Pediatric Use 17 words ▾

8.4Pediatric Use The safety and effectiveness of AVOPEF have not been established in pediatric patients .

🧓 Geriatric Use 106 words ▾

8.5Geriatric Use Clinical studies of etoposide for the treatment of refractory testicular tumors did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Other reported clinical experience demonstrated that patients 65 years and older experienced more myelosuppression, anorexia, mucositis, dehydration, somnolence, elevated blood urea nitrogen (BUN), infectious complications and alopecia compared to younger patients. In general, dosage selection for an older patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Etoposide causes the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals, leading to cell cycle arrest, primarily at the G2 stage of the cell cycle, and cell death.

12.2Pharmacodynamics Etoposide exposure-response relationships and the time course of pharmacodynamic response are unknown.

12.3Pharmacokinetics Etoposide total systemic exposure (AUC) and the maximum plasma concentration (C max ) increases in dose proportional manner over dosage range of 100 to 600 mg/m 2 (6 times the maximum approved recommended dose). Etoposide does not accumulate following daily administration of 100 mg/m 2 for 4 to 5 days. Distribution Etoposide mean volume of distribution at steady state is 7 L/m 2 to 17 L/m 2 .

No clinically significant amount of etoposide distributes into the CSF. Etoposide plasma protein binding is 97% in vitro (primarily albumin). Elimination Etoposide elimination half-life is 4 hours to 11 hours.

Total body clearance is 16 mL/min/m 2 to 36 mL/min/m 2 over a range of 100 mg/m 2 to 600 mg/m 2 (6 times the maximum approved recommended dose). The mean renal clearance of etoposide is 7 mL/min/m 2 to 10 mL/min/m 2 over a dose range of 80 mg/m 2 to 600 mg/m 2 (6 times the maximum approved recommended dose). Metabolism Etoposide is metabolized by opening of the lactone ring, O-demethylation and conjugation (i.e., glucuronidation and sulfation.

O-demethylation occurs through CYP3A to the active catechol metabolite. Excretion After intravenous administration of 14 C-etoposide [100 to 124 mg/m 2 (1.2 times the maximum approved recommended dose)], mean recovery of radioactivity in the urine was 56% of the dose at 120 hours, 45% of which was excreted as etoposide; fecal recovery of radioactivity was 44% of the dose at 120 hours. Specific Populations No clinically significant differences in pharmacokinetic parameters of etoposide were observed based on age and sex.

Patients with Renal Impairment Patients with impaired renal function have exhibited reduced total body clearance, increased AUC, and a lower volume of distribution at steady state. Drug Interactions In vitro studies Phenylbutazone, sodium salicylate, and aspirin displaced protein-bound etoposide in vitro.

🧬 Mechanism of Action 41 words ▾

12.1Mechanism of Action Etoposide causes the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals, leading to cell cycle arrest, primarily at the G2 stage of the cell cycle, and cell death.

📦 How Supplied / Storage and Handling 152 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING AVOPEF (etoposide) Injection, 100 mg/5 mL (20 mg/mL) and 500 mg/25 mL (20 mg/mL) is a sterile, clear, colorless to light yellow liquid available in multiple-dose glass vials as follows: NDC Number Strength Package 83831-144-05 100 mg/5 mL (20 mg/mL) 1 multiple-dose vial in 1 carton. 83831-145-25 500 mg/25 mL (20 mg/mL) 1 multiple-dose vial in 1 carton. This container closure is not made with natural rubber latex.

Storage and Handling Store at 20°C to 25° C (68°F to 77° F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. After first use, store the partially used multiple-dose vial in the original carton at controlled room temperature, 20°C to 25°C (68°F to 77°F) for up to 28 days [see Dosage and Administration (2.5) ] . AVOPEF is a hazardous drug.

Follow applicable special handling and disposal procedures [see References (15) ] .

📋 Description 145 words ▾

11 DESCRIPTION AVOPEF injection contains etoposide, a topoisomerase inhibitor. The chemical name for etoposide is 4'-Demethylepipodophyllotoxin 9-[4,6-O-( R )-ethylidene-β-D glucopyranoside] and has the following structural formula: Etoposide is a white or off-white crystalline powder with the molecular formula C 29 H 32 O 13 and a molecular weight of 588.56. It is sparingly soluble in acetone, slightly soluble in methanol or in chloroform, very slightly soluble in ethanol and practically insoluble in water.

AVOPEF (etoposide) Injection is a sterile, clear, colorless to light yellow liquid available in 100 mg/5 mL and 500 mg/25 mL multiple-dose vials containing 20 mg/mL of etoposide for intravenous administration. Each mL contains 20 mg etoposide, 37.8% v/v (1490 mg) dehydrated alcohol, 600 mg polyethylene glycol 400, and 80 mg polysorbate 80. The pH is adjusted with anhydrous citric acid and is between 3 to 4.

Vial headspace contains nitrogen. Image

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Severe Myelosuppression Inform patients that AVOPEF can cause severe myelosuppression. Advise patients that periodic monitoring of their blood counts is required during treatment with AVOPEF. Advise patients to contact their healthcare provider for any signs or symptoms of myelosuppression [see Warnings and Precautions (5.1) ] .

Hypersensitivity and Infusion-Related Reactions Inform patients that AVOPEF can cause severe infusion-related reactions, allergic reactions and anaphylaxis. Advise patients to immediately call their healthcare provider to report any signs or symptoms of an infusion-related reaction, allergic reaction or anaphylaxis [see Warnings and Precautions (5.2) ]. Risk of Increased AVOPEF Toxicity with Low Serum Albumin Inform patients that the risk of AVOPEF toxicity is increased with low serum albumin.

Advise patients that periodic monitoring of their serum albumin is required during treatment with AVOPEF. Advise patients to contact their healthcare provider if they experience signs or symptoms of low serum albumin or AVOPEF toxicity [see Warnings and Precautions (5.5) ]. Secondary Leukemia Inform patients that AVOPEF can cause secondary leukemia.

Advise patients that periodic monitoring is recommended during and after treatment with AVOPEF and to contact their healthcare provider if they experience signs or symptoms of leukemia [see Warnings and Precautions (5.4) ]. Alcohol Content Advise patients of the effects of alcohol in AVOPEF, including possible effects on the central nervous system. Advise patients in whom alcohol should be avoided or minimized to consider the alcohol content of AVOPEF.

AVOPEF at 100 mg/m 2 delivers 1.5 g/m 2 of ethanol. For a patient with a BSA of 2.0 m 2 this delivers 3.0 grams of ethanol [see Description (11) ] . Alcohol impairs the ability to drive or use machines [see Warnings and Precautions (5.6) ].

Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider with a known or suspected pregnancy [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with AVOPEF and for 6 months after the last dose [see Use in Specific Populations (8.3) ]. Advise males with female partners of reproductive potential to use effective contraception during treatment with AVOPEF and for 4 months after the last dose [see Nonclinical Toxicology (13.1) ].

Lactation Advise women not to breastfeed during treatment with AVOPEF and for 1 week after the last dose [see Use in Specific Populations (8.2) ]. Infertility Advise males and females of reproductive potential that AVOPEF may impair fertility [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1) ]. Manufactured for: Avyxa Pharma, LLC New Jersey 07054, USA Made in China Image

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 83831-0144-05 · Avyxa 83831-0147-05 · Avyxa →
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.