NDC 50881-0006-03 — ZYNYZ retifanlimab-dlwr 25 mg/mL Injection

🆔 Identity & classification

FDA NDC (as labeled) 50881-006-03

Product NDC 50881-006

11-digit billing NDC 50881000603

NCPDP billing unit ML — per mL (volume)

RxCUI 2632985, 2632991

UNII 2Y3T5IF01Z

Application # BLA761334

SPL Set ID 109648d0-d30a-42fc-8273-39cb1540a751

Established class (EPC) Programmed Death Receptor-1 Blocking Antibody

Mechanism of action Programmed Death Receptor-1-directed Antibody Interactions

DEA schedule Non-controlled

Marketing category BLA

Marketing status On market

FDA listing status Listed (active directory)

Marketing start 2023-03-22

Route INTRAVENOUS

Dosage form INJECTION

Substance RETIFANLIMAB

GPI-14 21357960202020

GCN Seq No 084536

GCN 53868

HICL code 048795

Ingredient (HICL) Retifanlimab-Dlwr

HIC1 code V

Therapeutic class — broad (HIC1) Neoplasms

HIC2 code V3

Therapeutic class — intermediate (HIC2) Antineoplastic Drugs (Continued 1)

HIC3 code V3R

Therapeutic class — specific (HIC3) Antineoplastic,Anti-Programmed Death-1 (Pd-1) Mab

AHFS code 10:00.00.00

AHFS class Antineoplastic Agents

FDB label name ZYNYZ 500 MG/20 ML VIAL

FDB brand name Zynyz

Legend status F — Federal legend — prescription drug or device

Biologic (Purple Book) 351(a)

Why two NDCs? The FDA registers this code as 50881-006-03 — 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 → 50881-0006-03. 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 Programmed Death Receptor-1 Blocking Antibody class.

Pharmacologic class Programmed Death Receptor-1 Blocking Antibody

Drug family (ATC) PD-1/PD-L1 (Programmed cell death protein 1/death ligand 1) inhibitors

How it works Programmed Death Receptor-1-directed Antibody Interactions

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

LabelerIncyte Corporation

FDA applicationBLA761334 (BLA)

Labeler code50881

First marketedMar 2023

Product typeHuman Prescription Drug

Portfolio22 products on file

🔎 All NDCs from Incyte Corporation

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 ZYNYZ 500 MG/20 ML VIAL Ingredient Retifanlimab-Dlwr

📗 Our plain-language guide HelloPharmacist

Zynyz is an immunotherapy — a medicine that helps your own immune system fight cancer. Depending on your diagnosis, it's been approved to treat squamous cell carcinoma of the anal...
What exactly is Zynyz and why has my doctor prescribed it for me?
Zynyz is given through an IV drip directly into your vein at a clinic or infusion center — you can't take it as a pill at home. Each infusion takes 30 minutes, though your total vi...
How will I receive Zynyz, and how long will each visit take?

📖 Read our full Retifanlimab-dlwr Injection guide →

Patient education

📘 MedlinePlus patient leaflet ↗

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.

.18 mg / 1 mL UNII Q40Q9N063P
Acetic acid is a weak organic acid commonly used in medicines as a buffer and pH adjuster. It helps maintain the proper acidity level to ensure the drug remains stable and effective in its formulation.
.1 mg / 1 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.
.95 mg / 1 mL UNII 4550K0SC9B
Sodium acetate is a salt derived from acetic acid. It acts as a buffer to help maintain the medicine's pH stability and may serve as a preservative or solubilizer in liquid formulations.
90 mg / 1 mL UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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 system	Per each	Per package
Retail pharmacies payNADAC · weekly	Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo	$743.63	$743.63 / 1 vial
Medicare drug plans payPart D · quarterly	No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9345	$30.981 / J9345 unit	—

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.

🧾 Billing & reimbursement

FDA NDC (as labeled)50881-006-03

11-digit billing NDC50881-0006-03

Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)

HCPCS J-codeJ9345

DescriptorINJECTION, RETIFANLIMAB-DLWR, 1 MG

Billing units / pkg25 units

Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)

Where does this data come from?

The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Zynyz 25 mg/mLthis 50881-0006-03	Incyte	1 vial	—	—	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

🏛️

2023

First FDA approval

Mar 2023

📍

2026

Currently FDA-listed

3 years listed

🛡️

2035

Latest patent/protection listed

not a guaranteed launch date

🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Mar 2035. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.

📅 FDA approved Mar 22, 2023 ⏳ ~8.5 yr to latest listed protection

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

Zynyzretifanlimab-dlwr

🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.

Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.

Patents & exclusivity — FDA Purple Book

Exclusivity RefProduct

2023 2025 2027 2029 2031 2033 2035

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

Code	What it grants	Expires
RefProduct	Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date	Mar 22, 2035

Common questions

Is there a biosimilar for ZYNYZ 500 MG/20 ML VIAL?

No FDA-licensed biosimilar is currently listed for this biologic in the FDA Purple Book.

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 & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 50881-0006-03, not the drug overall. Other pack sizes report separately.

💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.

📅 Q1 2025 – Q1 2026 · 5 quarters of data

ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.

Prescriptions last 4 qtrs

33

Units reimbursed last 4 qtrs

640

Gross reimbursed last 4 qtrs

$475.9K

Avg / prescription

$14,421.91

Avg / unit

$743.58

Latest quarter Q1 2026

22Rx

Fee-for-service vs managed care ⓘ

100% MCO

Fee-for-service · 0 Rx Managed care · 33 Rx

State Medicaid map

Units reimbursed · per 100k residents

0.51.9

gray = no data reported ⓘ

Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.

Tap or hover a state

…for its Medicaid breakdown

🏆 Top states by units · per 100k residents

1 Florida 1.9 /100k

2 California 0.5 /100k

National units — by quarter

💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

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

Medicare Part D (outpatient prescription) spending for Zynyz — 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 Zynyz. 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

$248.4K

Claims incl. refills

17

Beneficiaries

—

Spend / beneficiary

—

Spend / claim

$14,610.19

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 ZYNYZ (this brand).

Top reported reactions

Disease Progression8

Anal Squamous Cell Carcinoma5

Anal Cancer4

Condition Aggravated3

Death3

Malignant Neoplasm Progression3

Thrombocytopenia3

Reporter sex

Male · 50%

Female · 50%

Serious outcomes

Hospitalization7

Reports over time (by year) — tap or hover for the count & year

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 NDC	Description	Marketing start	Status
50881-0006-03 You're viewing this	1 VIAL, SINGLE-USE in 1 CARTON (50881-006-03) / 20 mL in 1 VIAL, SINGLE-USE	2023-03-22	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	— Not published for this NDC No photo available yet for this listing.
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	✓ Available
Medicaid utilization (CMS SDUD)	✓ Available

“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 50881-006-03, 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: 50881-0006-03, written without dashes as 50881000603. 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 50881-0006-03, the first segment (50881) is the labeler code FDA assigned to Incyte Corporation; the middle segment (0006) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (03) 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 Incyte Corporation. Listing status can change — the directory data on this page refreshes weekly.

Who lists this product with the FDA?

Incyte Corporation 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.

Does this product have a billing J-code?

Yes — this NDC cross-references HCPCS code J9345 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.

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 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide

🎯 Indications and Usage 191 words ▾

1 INDICATIONS AND USAGE ZYNYZ is a programmed death receptor-1 (PD-1)–blocking antibody indicated: Squamous Cell Carcinoma of the Anal Canal (SCAC) in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). ( 1.1 ) as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. ( 1.1 ) Merkel Cell Carcinoma (MCC) for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).

( 1.2 )

1.1Squamous Cell Carcinoma of the Anal Canal ZYNYZ, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). ZYNYZ, as a single agent, is indicated for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum‑based chemotherapy.

1.2Merkel Cell Carcinoma ZYNYZ is indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Administer ZYNYZ as an intravenous infusion over 30 minutes after dilution ( 2.3 ): For Squamous Cell Carcinoma of the Anal Canal (SCAC), in combination with carboplatin and paclitaxel, or as a single agent ( 2.1 ): 500 mg every 4 weeks, or 375 mg every 3 weeks For Merkel Cell Carcinoma (MCC) ( 2.1 ): 500 mg every 4 weeks See full prescribing information for dosage modifications for adverse reactions ( 2.2 ) and preparation and administration instructions. ( 2.3 )

2.1Recommended Dosage The recommended dosages of ZYNYZ are provided in Table 1. Administer ZYNYZ as an intravenous infusion after dilution, over 30 minutes, as recommended [see Dosage and Administration ( 2.3 )] . Table 1: Recommended Dosage of ZYNYZ Indication Recommended Dosage of ZYNYZ Duration of Treatment Combination Therapy Refer to the Prescribing Information for the agents administered in combination with ZYNYZ for recommended dosing information, as appropriate.

Adult patients with inoperable locally recurrent or metastatic SCAC in combination with carboplatin and paclitaxel 500 mg every 4 weeks or 375 mg every 3 weeks Until disease progression, unacceptable toxicity, or up to 12 months Monotherapy Adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy 500 mg every 4 weeks or 375 mg every 3 weeks Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with metastatic or recurrent locally advanced MCC 500 mg every 4 weeks Until disease progression, unacceptable toxicity, or up to 24 months

2.2Dosage Modifications for Adverse Reactions No dose reduction of ZYNYZ is recommended. In general, withhold ZYNYZ for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue ZYNYZ for life‑threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

Dosage modifications for ZYNYZ for adverse reactions that require management different from these general guidelines are summarized in Table 2. Table 2: Recommended Dosage Modifications for Adverse Reactions AST = aspartate aminotransferase; ALT = alanine aminotransferase; DRESS = drug rash with eosinophilia and systemic symptoms; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal. Adverse Reaction Severity Toxicity graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.

ZYNYZ Dosage Modifications Immune-Mediated Adverse Reactions [see Warnings and Precautions ( 5.1 )] Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. Grade 3 or 4 Permanently discontinue Colitis Grade 2 or 3 Withhold Grade 4 Permanently discontinue Hepatitis with no tumor involvement of the liver AST or ALT greater than 3 but no more than 8 times ULN OR Total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold AST or ALT increases to more than 8 times ULN OR Total bilirubin greater than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue ZYNYZ based on recommendations for hepatitis with no liver involvement.

Baseline AST or ALT is more than 1 and up to 3 times ULN and increases more than 5 and up to 10 times ULN OR Baseline AST or ALT is more than 3 and up to 5 times ULN and increases more than 8 and up to 10 times ULN Withhold AST or ALT increases to more t…

💊 Dosage Forms and Strengths 38 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 500 mg/20 mL (25 mg/mL) clear to slightly opalescent, colorless to pale yellow solution in a single-dose vial Injection: 500 mg/20 mL (25 mg/mL) solution in a single-dose vial. ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Immune-Mediated Adverse Reactions ( 5.1 ) Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune‑mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, and immune‑mediated dermatologic adverse reactions, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.

Withhold or permanently discontinue ZYNYZ and administer corticosteroids based on the severity of reaction. ( 2.2 ) Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue ZYNYZ based on severity of reaction. ( 2.2 , 5.2 ) Complications of Allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD‑1/PD‑L1–blocking antibody.

( 5.3 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.4 , 8.1 , 8.3 )

5.1Severe and Fatal Immune-Mediated Adverse Reactions ZYNYZ is a monoclonal antibody that belongs to a class of drugs that binds to either the programmed death receptor-1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response with the potential for breaking of peripheral tolerance and induction of immune-mediated adverse reactions. Important immune‑mediated adverse reactions listed under Warnings and Precautions may not be inclusive of all possible severe and fatal immune-mediated reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies.

Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Early identification and management of immune‐mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1–blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.

Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue ZYNYZ depending on severity [see Dosage and Administration ( 2.2 )] . In general, if ZYNYZ requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.

Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis ZYNYZ can cause immune-mediated pneumonitis.

In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.1% (14/452) of patients receiving ZYNYZ, i…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling. Severe and Fatal Immune-Mediated Adverse Reactions [see Warnings and Precautions ( 5.1 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.2 )] Complications of Allogeneic HSCT [see Warnings and Precautions ( 5.3 )] ZYNYZ in Combination with Carboplatin and Paclitaxel In patients with SCAC, the most common (≥ 20%) adverse reactions are fatigue, peripheral neuropathy, nausea, alopecia, diarrhea, musculoskeletal pain, constipation, hemorrhage, rash, vomiting, decreased appetite, pruritus, and abdominal pain.

( 6.1 ) ZYNYZ as a Single Agent In patients with SCAC, the most common (≥ 10%) adverse reactions are fatigue, musculoskeletal pain, diarrhea, non-urinary tract infections, perineal pain, hemorrhage, urinary tract infection, rash, nausea, decreased appetite, constipation, abdominal pain, dyspnea, pyrexia, vomiting, cough, pruritus, hypothyroidism, headache, and decreased weight. ( 6.1 ) In patients with MCC, the most common (≥ 10%) adverse reactions are musculoskeletal pain, fatigue, pruritus, diarrhea, rash, pyrexia, nausea, and constipation.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Incyte Corporation at 1-855-463-3463 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trial 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 practice. The safety population described in Warnings and Precautions reflects exposure to ZYNYZ 500 mg as an intravenous infusion every 4 weeks in combination with carboplatin and paclitaxel in 154 patients with SCAC enrolled in the POD1UM-303 trial, and as a single agent in 94 patients with SCAC in the POD1UM-202 trial, 107 patients with MCC in the POD1UM-201 trial, and 251 patients with other solid tumors.

All patients received ZYNYZ until disease progression or unacceptable toxicity; those in the POD1UM-202 and POD1UM-201 trials received ZYNYZ for up to 24 months and those in the POD1UM-303 trial received ZYNYZ for up to 12 months. The median duration of exposure of the pooled monotherapy population was 5.4 months (range: 1 day to 27 months). Squamous Cell Carcinoma of the Anal Canal (SCAC) Inoperable Locally Recurrent or Metastatic SCAC: ZYNYZ in Combination with Carboplatin and Paclitaxel The safety of ZYNYZ in patients with inoperable locally recurrent or metastatic SCAC was evaluated in 154 patients enrolled in the POD1UM-303 trial [see Clinical Studies ( 14.1 )] .

Patients received ZYNYZ 500 mg or placebo intravenously every 4 weeks in combination with carboplatin and paclitaxel for 6 cycles followed by ZYNYZ 500 mg or placebo every 4 weeks until disease progression or unacceptable toxicity. Among patients who received ZYNYZ, the median duration of exposure was 7.4 months (range: 1 day to 14.6 months). Serious adverse reactions occurred in 47% of patients receiving ZYNYZ in combination with carboplatin and paclitaxel.

The most frequent serious adverse reactions (≥ 2% of patients) were sepsis (3.2%), pulmonary embolism (3.2%), diarrhea (2.6%), and vomiting (2.6%). In patients receiving ZYNYZ in combination with carboplatin and paclitaxel, ZYNYZ was permanently discontinued due to an adverse reaction in 11% of patients. Adverse reactions that resulted in permanent discontinuation of ZYNYZ included immune-mediated enterocolitis (2 patients), warm autoimmune hemolytic anemia, hepatitis, adrenal insufficiency, blood bilirubin increased, AST increased, blood alkaline phosphatase increased, arthritis, encephalopathy, peripheral sensorimotor neuropathy, hypothyroidism, immune‑mediated cholangitis, pruritus, malaise, and rash (1 patient each).

Dosage interruptions due to an adverse reaction, excluding temporary interruptions due to infusion-related reactions, occur…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )

8.1Pregnancy Risk Summary Based on its mechanism of action, ZYNYZ can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on the use of ZYNYZ in pregnant women. Animal studies have demonstrated that inhibition of the PD‑1/PD‑L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death ( see Data ).

Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, retifanlimab-dlwr has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus. 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 15% to 20%, respectively.

Data Animal Data Animal reproduction studies have not been conducted with ZYNYZ to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. In murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering ZYNYZ during pregnancy include increased rates of abortion or stillbirth.

As reported in the literature, there were no malformations related to the blockade of PD-1/PD-L1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to retifanlimab-dlwr may increase the risk of developing immune-mediated disorders or altering the normal immune response.

8.2Lactation Risk Summary There is no information regarding the presence of retifanlimab-dlwr in human milk, or its effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to ZYNYZ are unknown.

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose of ZYNYZ.

8.3Females and Males of Reproductive Potential ZYNYZ can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating ZYNYZ [see Use in Specific Populations ( 8.1 )] . Contraception Advise females of reproductive potential to use effective contraception during treatment with ZYNYZ and for 4 months after the last dose.

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

8.5Geriatric Use In Combination with Carboplatin and Paclitaxel Of the 154 patients with inoperable locally recurrent or metastatic SCAC treated with ZYNYZ in combination with carboplatin and paclitaxel in POD1UM-303, 38% were 65 years or older, and 9% were 75 years or older [see Clinical Studies ( 14.1 )]. No overall differences in safety or effectiveness were observed between these patients and younger patients. As a Single Agent Of the 94 patients with locally recurrent or with metastatic SCAC treated with ZYNYZ in POD1UM‑202, 49% were 65 years or older, and 11% were 75 years or older [see Clinical Studies ( 14.1 )] .

Of the 101 patients with metastatic or recurrent locally advanced MCC treated with ZYNYZ in POD1UM-201, 76% were 65 years or older, and 39% were 75 years or older [see Clinical Studies ( 14.2 )] . Clinical studies of ZYNYZ as a single agent did not include sufficient numbers of younger adult patients to determine if patients 65 years of age and older respond differently than younger adult patients.

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on its mechanism of action, ZYNYZ can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on the use of ZYNYZ in pregnant women. Animal studies have demonstrated that inhibition of the PD‑1/PD‑L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death ( see Data ).

Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, retifanlimab-dlwr has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus. 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 15% to 20%, respectively.

Data Animal Data Animal reproduction studies have not been conducted with ZYNYZ to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. In murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering ZYNYZ during pregnancy include increased rates of abortion or stillbirth.

As reported in the literature, there were no malformations related to the blockade of PD-1/PD-L1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to retifanlimab-dlwr may increase the risk of developing immune-mediated disorders or altering the normal immune response.

🧒 Pediatric Use 16 words ▾

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

🧓 Geriatric Use 174 words ▾

8.5Geriatric Use In Combination with Carboplatin and Paclitaxel Of the 154 patients with inoperable locally recurrent or metastatic SCAC treated with ZYNYZ in combination with carboplatin and paclitaxel in POD1UM-303, 38% were 65 years or older, and 9% were 75 years or older [see Clinical Studies ( 14.1 )]. No overall differences in safety or effectiveness were observed between these patients and younger patients. As a Single Agent Of the 94 patients with locally recurrent or with metastatic SCAC treated with ZYNYZ in POD1UM‑202, 49% were 65 years or older, and 11% were 75 years or older [see Clinical Studies ( 14.1 )] .

Of the 101 patients with metastatic or recurrent locally advanced MCC treated with ZYNYZ in POD1UM-201, 76% were 65 years or older, and 39% were 75 years or older [see Clinical Studies ( 14.2 )] . Clinical studies of ZYNYZ as a single agent did not include sufficient numbers of younger adult patients to determine if patients 65 years of age and older respond differently than younger adult patients.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Retifanlimab-dlwr binds to the PD-1 receptor, blocks interaction with its ligands PD-L1 and PD‑L2, and potentiates T-cell activity.

12.2Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for safety and effectiveness of retifanlimab-dlwr have not been fully characterized.

12.3Pharmacokinetics The pharmacokinetics of retifanlimab-dlwr were evaluated in patients with various solid tumors, including patients with SCAC and patients with MCC. Retifanlimab-dlwr exposures (maximum concentration [C max ] and area under the curve [AUC]) increased proportionally over a dosage range from 375 mg to 750 mg (0.75- to 1.5-fold of the approved recommended dose). Following repeated administration of retifanlimab-dlwr, steady-state concentrations were achieved by approximately 3 months with approximately 1.3-fold systemic accumulation.

Distribution The geometric mean volume of distribution at steady state for retifanlimab-dlwr is

6.0L (coefficient of variation [CV]: 20%). Elimination The elimination half-life of retifanlimab-dlwr at steady state is 19 days (CV: 30%). Clearance of retifanlimab-dlwr after the first dose was

0.3L/day (CV: 38%) and decreased over time by approximately 23%, resulting in a steady-state clearance of

0.23L/day. Specific Populations The following factors have no clinically meaningful effect on the pharmacokinetics of retifanlimab-dlwr: age (18 to 94 years), sex, body weight (33 to 133 kg), race (White, Black, Asian), albumin level (17 to 54 g/L), Eastern Cooperative Oncology Group (ECOG) score (0 to 2), tumor burden (sum of the target lesion diameters: 0 to 360 mm), HIV status, renal function (estimated glomerular filtration rate ≥ 26 mL/min/1.73 m 2 ), or mild hepatic impairment (total bilirubin less than or equal to the ULN and AST greater than ULN or total bilirubin greater than ULN and less than or equal to 1.5 times ULN and any AST).

The pharmacokinetics of retifanlimab-dlwr have not been studied in patients with moderate or severe hepatic impairment.

12.6Immunogenicity The observed incidence of anti-drug antibodies (ADAs) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADAs in the studies described below with the incidence of ADAs in other studies, including those of ZYNYZ or of other retifanlimab products. ADAs were tested in 153 patients with SCAC who received ZYNYZ in POD1UM-303 and 94 patients with SCAC who received ZYNYZ in POD1UM-202.

The incidence of retifanlimab treatment-emergent ADAs was determined using a bridging enzyme-linked immunosorbent assay following a median exposure time of 226 days in POD1UM-303 and 85 days in POD1UM‑202. None of the patients in POD1UM‑303 or POD1UM-202 tested positive for retifanlimab treatment-emergent ADAs. ADAs were tested in 106 patients with MCC who received ZYNYZ in POD1UM-201.

The incidence of retifanlimab treatment-emergent ADAs was 2.8% (3/106) using a bridging enzyme‑linked immunosorbent assay following a median exposure time of 312 days. Neutralizing antibodies were detected in 2 of 3 patients with treatment-emergent ADAs. The effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of retifanlimab products is unknown.

🧬 Mechanism of Action 68 words ▾

12.1Mechanism of Action Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Retifanlimab-dlwr binds to the PD-1 receptor, blocks interaction with its ligands PD-L1 and PD‑L2, and potentiates T-cell activity.

📦 How Supplied / Storage and Handling 64 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ZYNYZ (retifanlimab-dlwr) injection is a 25 mg/mL clear to slightly opalescent, colorless to pale yellow solution. It is supplied in a carton containing 1 single-dose vial of: 500 mg/20 mL (NDC 50881-006-03) Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake.

📋 Description 104 words ▾

11 DESCRIPTION Retifanlimab-dlwr is a programmed death receptor-1 (PD-1)–blocking antibody. Retifanlimab‑dlwr is a humanized IgG4 kappa monoclonal antibody produced in Chinese hamster ovary cells. Retifanlimab-dlwr has an approximate molecular weight of 148 kDa.

ZYNYZ (retifanlimab-dlwr) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution for intravenous use. The solution is free from visible particles. Each single-dose vial contains 500 mg of retifanlimab-dlwr in 20 mL of solution.

Each mL contains 25 mg of retifanlimab-dlwr, glacial acetic acid (0.18 mg), polysorbate 80 (0.1 mg), sodium acetate (0.57 mg), sucrose (90 mg), and Water for Injection, USP. The pH is 5.1.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Immune-Mediated Adverse Reactions Advise patients that ZYNYZ can cause immune-mediated adverse reactions, including the following [see Warnings and Precautions ( 5.1 )] : Pneumonitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of pneumonitis, including new or worsening symptoms of cough, chest pain, or shortness of breath. Colitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of colitis, including diarrhea, blood or mucus in stools, or severe abdominal pain.

Hepatitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of hepatitis. Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, or type 1 diabetes mellitus. Nephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis.

Dermatologic Adverse Reactions: Advise patients to contact their healthcare provider immediately if they develop a new rash. Other immune-mediated adverse reactions: - Advise patients that immune-mediated adverse reactions can occur and may involve any organ system, and to contact their healthcare provider immediately for any new or worsening signs or symptoms [see Warnings and Precautions ( 5.1 )] . - Advise patients of the risk of solid organ transplant rejection and other transplant (including corneal graft) rejection [see Warnings and Precautions ( 5.1 )].

Infusion-Related Reactions Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions ( 5.2 )] . Complications of Allogeneic HSCT or Solid Organ Transplant Rejection Advise patients to contact their healthcare provider immediately if they develop signs or symptoms of post-allogeneic HSCT complications. [see Warnings and Precautions ( 5.3 )] . Embryo-Fetal Toxicity Advise females of reproductive potential that ZYNYZ can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.1 , 8.3 )] .

Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of ZYNYZ [see Use in Specific Populations ( 8.3 )] . Lactation Advise female patients not to breastfeed while taking ZYNYZ and for 4 months after the last dose [see Use in Specific Populations ( 8.2 )] . Manufactured by: Incyte Corporation Wilmington, DE 19803 U.S.

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE ZYNYZ ® (ZYE-niz) (retifanlimab-dlwr) injection What is the most important information I should know about ZYNYZ? ZYNYZ is a medicine that may treat certain types of cancers by working with your immune system. ZYNYZ can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work.

These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: Lung problems. cough shortness of breath chest pain Intestinal problems. diarrhea (loose stools) or more frequent bowel movements than usual stools that are black, tarry, sticky, or have blood or mucus severe stomach-area (abdomen) pain or tenderness Liver problems. yellowing of your skin or the whites of your eyes severe nausea or vomiting pain on the right side of your stomach area (abdomen) dark urine (tea colored) bleeding or bruising more easily than normal Hormone gland problems. headaches that will not go away or unusual headaches eye sensitivity to light eye problems rapid heartbeat increased sweating extreme tiredness weight gain or weight loss feeling more hungry or thirsty than usual urinating more often than usual hair loss feeling cold constipation your voice gets deeper dizziness or fainting changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness Kidney problems. decrease in your amount of urine blood in your urine swelling of your ankles loss of appetite Skin problems. rash itching skin blistering or peeling painful sores or ulcers in your mouth or nose, throat, or genital area fever or flu-like symptoms swollen lymph nodes Problems can also happen in other organs and tissues.

These are not all of the signs and symptoms of immune system problems that can happen with ZYNYZ. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath, or swelling of ankles confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight persistent or severe muscle pain or weakness, muscle cramps low red blood cells, bruising Infusion reactions that can sometimes be severe.

Signs and symptoms of infusion reactions may include: chills or shaking itching or rash flushing shortness of breath or wheezing dizziness feel like passing out fever back or neck pain Rejection of a transplanted organ or tissue. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ or tissue transplant that you have had. Complications, including graft-versus-host disease, in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic).

These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with ZYNYZ. Your healthcare provider will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with ZYNYZ. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines.

Your healthcare provider may also need to delay or completely stop treatment with ZYNYZ if you have severe side effects. What is ZYNYZ? ZYNYZ is a prescription medicine used to treat adults with: a type of anal cancer called squamous cell carcinoma of the anal canal (SCAC).

ZYNYZ may be used in combination with the chemo…

Glossary — plain-language definitions of medical terms used in this label:

immunosuppressive: Describes something that lowers the activity of the immune system.

abdominal pain: Pain, cramping, or discomfort felt anywhere in the belly area.

accumulation: A buildup of a medicine in the body when new doses are taken before earlier ones are fully removed.

adrenal insufficiency: A condition where the adrenal glands do not make enough of certain needed hormones, such as cortisol, a stress hormone.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

alkaline phosphatase: An enzyme measured in a blood test; higher levels can point to problems with the liver, bile ducts, or bones.

alopecia: Loss of hair from the scalp or body.

ALT: A liver enzyme (alanine aminotransferase) checked by a blood test; raised levels can signal that the liver is irritated or damaged.

anemia: A low level of red blood cells or the oxygen-carrying protein inside them, which can cause tiredness, weakness, and paleness.

animal reproduction studies: Tests in pregnant animals used to check whether a medicine might harm a developing baby.

AST: A liver enzyme (aspartate aminotransferase) measured in a blood test; higher levels may point to liver or sometimes muscle injury.

AUC: A measure of total drug exposure over time, showing how much medicine the blood is exposed to overall.

autoimmune: Describes a condition in which the body's defense system mistakenly attacks its own healthy cells or tissues.

baseline: A person's starting condition, measured before treatment begins, used to see how much they change later on.

bilirubin: A yellow substance the liver normally clears from the blood; high levels can turn the skin or the whites of the eyes yellow.

clearance: How quickly the body removes a medicine from the blood, usually through the liver and kidneys.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

Clinical Studies: The label section summarizing the research trials used to show that a medicine works and is acceptably safe.

colitis: Swelling and irritation of the inner lining of the large intestine, or colon.

constipation: Having bowel movements less often than usual, or passing stools that are hard, dry, and difficult to move.

contraception: Methods used to prevent pregnancy, such as birth control pills, condoms, or an intrauterine device.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

diarrhea: Loose, watery bowel movements that happen more often than normal.

Distribution: How a medicine spreads from the blood into the body's tissues and organs after it is absorbed.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

dose reduction: Lowering the amount of a medicine, often to ease side effects or fit a person's needs.

dyspnea: The medical word for shortness of breath, or the feeling that you cannot get enough air.

Elimination: The overall removal of a medicine from the body by breaking it down and passing it out.

embolism: A blockage of a blood vessel by a clot or other material that has traveled from elsewhere in the body.

embryo-fetal toxicity: Harm to a developing baby in the womb, such as birth defects, slowed growth, or loss of the pregnancy.

encephalopathy: Any condition that affects how the brain works, causing confusion, memory problems, or changes in alertness.

eosinophilia: A higher-than-normal level of eosinophils, a type of white blood cell often linked to allergies or drug reactions.

estimated background risk: The normal chance that any pregnancy will have a birth defect or problem, even without taking any medicine.

fetal harm: Injury or damage to a developing baby while it is growing inside the womb.

flushing: Temporary redness and warmth of the skin, often on the face and neck, from widening of small blood vessels.

Full Prescribing Information: The complete, detailed label for a prescription medicine that follows the summary highlights.

Half-life: The time it takes for the amount of medicine in the blood to drop by half.

hemolytic anemia: A shortage of red blood cells caused by them breaking apart faster than the body can replace them.

hemorrhage: Bleeding, especially heavy or uncontrolled bleeding, either inside the body or from an outside wound.

hepatic impairment: Reduced liver function, meaning the liver does not work as well as normal at processing substances, including medicines.

hepatitis: Inflammation of the liver, which can be caused by infections, alcohol, or certain medicines.

How Supplied/Storage and Handling: The label section describing the forms and strengths a medicine comes in and how to store it properly.

hyperthyroidism: A condition where the thyroid gland makes too much thyroid hormone, which can speed the body up.

hypothyroidism: A condition where the thyroid gland makes too little thyroid hormone, which can slow the body down.

immunogenicity: The tendency of a medicine to make the body produce antibodies against it, which can affect how well it works or cause reactions.

incidence: How often a new event, such as a side effect, happens in a group of people over a set period of time.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

infusion: Slowly delivering fluid or medicine into a vein over a period of time, usually through a drip.

intravenous: Given directly into a vein through a needle or thin tube; often written as IV.

irritability: Getting annoyed, frustrated, or angry more easily than usual.

lactation: The making and release of milk from a mother's breasts after giving birth.

malaise: A general feeling of being unwell, uneasy, or low on energy, without one clear symptom.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

Medication Guide: An FDA-approved handout written for patients that explains important safety information about certain medicines in plain language.

monotherapy: Treatment using a single medicine by itself.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

peripheral neuropathy: Damage to the nerves outside the brain and spinal cord, often causing numbness, tingling, or pain in the hands and feet.

Pharmacokinetics: The study of how the body takes in a medicine, spreads it around, breaks it down, and removes it over time.

placebo: An inactive treatment with no real medicine in it, such as a sugar pill, used for comparison in a study.

pneumonitis: Inflammation of the lung tissue that is not caused by an infection and can lead to cough and breathlessness.

Prescribing Information: The official, detailed document approved by the FDA that tells health professionals how to use a prescription medicine.

pruritus: Itching of the skin.

pulmonary embolism: A blood clot that has traveled to the lungs and blocks blood flow there, which can make breathing hard.

pyrexia: A raised body temperature; a fever.

receptor: A special docking spot on a cell that a medicine or natural body chemical attaches to in order to trigger an effect.

reproductive potential: The ability to have children, meaning a person who could become pregnant or could father a child.

sepsis: A serious, body-wide reaction to an infection in which the body's own response can start to injure its tissues and organs.

single-dose vial: A small container holding one dose of medicine, meant to be used once and then thrown away.

steady state: The point where the amount of medicine going in equals the amount leaving, so blood levels stay fairly even.

Stevens-Johnson syndrome: A rare, serious reaction causing painful blistering and peeling of the skin and the moist linings of the mouth, eyes, and other areas.

stillbirth: The death of a baby in the womb late in pregnancy or during birth.

taper: Gradually lowering a dose in steps before stopping, rather than quitting all at once.

tolerance: When the body gets used to a medicine over time, so a larger dose is needed to get the same effect.

toxic epidermal necrolysis: A rare, life-threatening reaction in which large areas of the top layer of skin blister and peel away, like a severe burn.

treatment-emergent: Describes a side effect that first appears, or gets worse, after a person starts taking a treatment.

ULN: The highest value considered normal for a lab test; results above it are flagged as elevated.

upper limit of normal: The highest value considered normal for a lab test; results above it are flagged as elevated.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

volume of distribution: A calculated value showing how widely a medicine spreads into body tissues versus staying in the blood.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

wheezing: A high-pitched whistling sound made while breathing, usually when the airways are narrowed.

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

🔗 Related NDC lookups

🧪 All Retifanlimab-Dlwr NDCsSame ingredient 🏭 All Incyte labeler NDCsLabeler code 50881 📚 All Programmed Death Receptor-1 Blocking Antibody NDCsDrug class 🧾 J9345 billing & NDC crosswalkJ-code

💊 Related drugs in this class

Other drugs that share this product’s specific therapeutic class — Antineoplastic,Anti-Programmed Death-1 (Pd-1) Mab.

Nivolumab-Hyaluronidase-Nvhy 00003-3120-01 Nivolumab 00003-3734-13 Pembrolizumab 00006-3026-02 Pembrolizum-Berahyaluron-Pmph 00006-3083-01 Dostarlimab-Gxly 00173-0898-03 Cemiplimab-Rwlc 61755-0008-01 Toripalimab-Tpzi 70114-0340-01 Tislelizumab-Jsgr 72579-0121-01

Where does this data come from?

Other drugs sharing this product’s First Databank therapeutic class (HIC3). Each links to that NDC’s page in our directory.