NDC 00002-7669-01 — CYRAMZA ramucirumab 10 mg/mL Solution

🆔 Identity & classification

FDA NDC (as labeled) 0002-7669-01

Product NDC 0002-7669

11-digit billing NDC 00002766901

NCPDP billing unit ML — per mL (volume)

RxCUI 1657775, 1657777, 1657780, 1657781

UNII D99YVK4L0X

Application # BLA125477

SPL Set ID c6080942-dee6-423e-b688-1272c2ae90d4

Established class (EPC) Vascular Endothelial Growth Factor Receptor 2 Antagonist

Mechanism of action VEGFR2 Inhibitors

DEA schedule Non-controlled

Marketing category BLA

Marketing status On market

FDA listing status Listed (active directory)

Marketing start 2014-04-21

Route INTRAVENOUS

Dosage form SOLUTION

Substance RAMUCIRUMAB

GPI-14 21335070002020

GPI class Cyramza

GCN Seq No 072293

GCN 36444

HICL code 041109

Ingredient (HICL) Ramucirumab

HIC1 code V

Therapeutic class — broad (HIC1) Neoplasms

HIC2 code V3

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

HIC3 code V3P

Therapeutic class — specific (HIC3) Antineoplastic - Vegfr Antagonist

AHFS code 10:00.00.00

AHFS class Antineoplastic Agents

FDB label name CYRAMZA 100 MG/10 ML VIAL

FDB brand name Cyramza

Legend status F — Federal legend — prescription drug or device

Biologic (Purple Book) 351(a)

Why two NDCs? The FDA registers this code as 0002-7669-01 — a 4-4-2 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 labeler segment → 00002-7669-01. 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 Vascular Endothelial Growth Factor Receptor 2 Antagonist class.

Pharmacologic class Vascular Endothelial Growth Factor Receptor 2 Antagonist

Drug family (ATC) VEGF/VEGFR (Vascular Endothelial Growth Factor / -Receptor) inhibitors

How it works VEGFR2 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

LabelerEli Lilly and Company

FDA applicationBLA125477 (BLA)

Labeler code00002

First marketedApr 2014

Product typeHuman Prescription Drug

Portfolio192 products on file

🔎 All NDCs from Eli Lilly and Company

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 CYRAMZA 100 MG/10 ML VIAL Ingredient Ramucirumab

📖 What it is MedlinePlus · NLM

Ramucirumab injection is used alone and in combination with another chemotherapy medication to treat stomach cancer or cancer located in the area where the stomach meets the esophagus (the tube between the throat and stomach) when these conditions do not improve after treatment with other medications. Ramucirumab is also used in combination with docetaxel to treat a certain type of non-small cell lung cancer (NSCLC) that has spread to other parts of the body in people who have already been treated with other chemotherapy medications and have not improved or worsened. It is also used in combina...

Read the full MedlinePlus article ↗

📗 Our plain-language guide HelloPharmacist

Cyramza works by blocking a signal that tumors use to grow new blood vessels. Without that blood supply, the cancer has a harder time growing and spreading. It's used for certain a...
What exactly does Cyramza do, and why was it prescribed for me?
No, Cyramza is given as an IV infusion at an infusion clinic or cancer center, not at home. You'll be connected to an IV drip, usually for about 60 minutes for your first treatment...
How will I actually receive this medicine — do I take it at home?

📖 Read our full Ramucirumab 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.

9.98 mg / 1 mL UNII TE7660XO1C
Glycine is an amino acid used in medicines as a buffer to help stabilize pH and improve taste. It may also serve as a filler or binder to give the product proper form and consistency.
0.65 mg / 1 mL UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
1.22 mg / 1 mL UNII 1D5Q932XM6
An amino acid salt used in medicines as a buffer and pH regulator. It helps maintain the proper acidity level in liquid formulations to keep the drug stable and effective.
0.1 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.
4.38 mg / 1 mL UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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.

6 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 mL	Per package
Retail pharmacies payNADAC · weekly	Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo	$130.66	$1,306.63 / 10 ml
Medicare drug plans payPart D · quarterly	No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9308	$76.565 / J9308 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)0002-7669-01

11-digit billing NDC00002-7669-01

Format4-4-2 as registered → padded to 5-4-2 for billing (zero added to the labeler segment)

HCPCS J-codeJ9308

DescriptorInjection, ramucirumab, 5 mg

Billing units / pkg20 units

Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk

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
Cyramza 10 mg/mLthis 00002-7669-01	Eli	1 vial	—	—	FDA listed	—
Cyramza 10 mg/mL 00002-7678-01	Eli	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

🏛️

2014

First FDA approval

Apr 2014

📍

2026

Currently FDA-listed

12 years listed

🔓

·

Biosimilar pathway open

listed protections lapsed 2026

🧬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: The latest listed FDA patent/protection lapsed Apr 2026 — those protections no longer apply, though a biosimilar still needs FDA licensure and a manufacturer to market it.

📅 FDA approved Apr 21, 2014

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

Cyramzaramucirumab

🔒 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

2014 2016 2018 2020 2022 2024 2026

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	Apr 21, 2026

Common questions

Is there a biosimilar for CYRAMZA 100 MG/10 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 00002-7669-01, 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 – Q4 2025 · 4 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

1.1K

Units reimbursed last 4 qtrs

35.8K

Gross reimbursed last 4 qtrs

$4.68M

Avg / prescription

$4,092.70

Avg / unit

$130.67

Latest quarter Q4 2025

166Rx

Fee-for-service vs managed care ⓘ

20% FFS 80% MCO

Fee-for-service · 230 Rx Managed care · 914 Rx

State Medicaid map

Units reimbursed · per 100k residents

2.854.2

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 Indiana 54.2 /100k

2 New York 37.5 /100k

3 California 27.1 /100k

4 Michigan 16.4 /100k

5 Illinois 15.7 /100k

6 Pennsylvania 15.5 /100k

7 Massachusetts 13.7 /100k

8 Connecticut 12.8 /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 Cyramza — 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 Cyramza. 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

$1.54M

Claims incl. refills

148

Beneficiaries

59

Spend / beneficiary

$26,090.29

Spend / claim

$10,400.86

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 CYRAMZA (this brand).

Top reported reactions

Malignant Neoplasm Progression810

Death589

Interstitial Lung Disease299

Neutropenia263

Febrile Neutropenia262

Decreased Appetite231

Diarrhoea228

Age at onset

Adolescent14

Adult532

Elderly653

Reporter sex

Male · 66%

Female · 34%

Serious outcomes

Hospitalization2,369

Life-threatening340

Disabling107

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
00002-7669-01 You're viewing this	1 VIAL, SINGLE-DOSE in 1 CARTON (0002-7669-01) / 10 mL in 1 VIAL, SINGLE-DOSE	2014-04-21	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	✓ 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 0002-7669-01, 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: 00002-7669-01, written without dashes as 00002766901. 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 00002-7669-01, the first segment (00002) is the labeler code FDA assigned to Eli Lilly and Company; the middle segment (7669) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) 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 Eli Lilly and Company. Listing status can change — the directory data on this page refreshes weekly.

Who lists this product with the FDA?

Eli Lilly and Company 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 J9308 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

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE CYRAMZA ® is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist indicated: as a single agent or in combination with paclitaxel, for treatment of adults with advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. ( 1.1 ) in combination with erlotinib, for first-line treatment of adults with metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.

( 1.2 ) in combination with docetaxel, for treatment of adults with metastatic non-small cell lung cancer with disease progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA. ( 1.2 ) in combination with FOLFIRI, for the treatment of adults with metastatic colorectal cancer with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

( 1.3 ) as a single agent, for the treatment of adults with hepatocellular carcinoma in patients who have an alpha fetoprotein of ≥400 ng/mL and have been treated with sorafenib. ( 1.4 )

1.1Gastric Cancer CYRAMZA ® , as a single agent or in combination with paclitaxel, is indicated for the treatment of adults with advanced or metastatic, gastric or gastro-esophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

1.2Non-Small Cell Lung Cancer CYRAMZA, in combination with erlotinib, is indicated for the first-line treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. CYRAMZA, in combination with docetaxel, is indicated for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA.

1.3Colorectal Cancer CYRAMZA, in combination with FOLFIRI (irinotecan, folinic acid, and fluorouracil), is indicated for the treatment of adults with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

1.4Hepatocellular Carcinoma CYRAMZA, as a single agent, is indicated for the treatment of adults with hepatocellular carcinoma (HCC) who have an alpha fetoprotein (AFP) of ≥400 ng/mL and have been treated with sorafenib.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For intravenous infusion only. Do not administer as an intravenous push or bolus. ( 2.7 ) Premedicate before each infusion.

( 2.1 ) Gastric Cancer : Administer CYRAMZA 8 mg/kg every 2 weeks as a single agent or in combination with weekly paclitaxel. ( 2.2 ) Non-Small Cell Lung Cancer : Administer CYRAMZA 10 mg/kg every 2 weeks with daily erlotinib. ( 2.3 ) Administer CYRAMZA 10 mg/kg on Day 1 of a 21-day cycle prior to docetaxel.

( 2.3 ) Colorectal Cancer : Administer CYRAMZA 8 mg/kg every 2 weeks prior to FOLFIRI. ( 2.4 ) Hepatocellular Carcinoma : Administer CYRAMZA 8 mg/kg every 2 weeks. ( 2.5 )

2.1Premedication Prior to each CYRAMZA infusion, premedicate all patients with an intravenous histamine-1 receptor antagonist (e.g., diphenhydramine hydrochloride) [see Warnings and Precautions ( 5.6 )] . For patients who have experienced a Grade 1 or 2 IRR, premedicate with a histamine-1 receptor antagonist, dexamethasone (or equivalent), and acetaminophen prior to each CYRAMZA infusion [see Dosage and Administration ( 2.6 )] .

2.2Recommended Dosage for Gastric Cancer The recommended dosage of CYRAMZA, either as a single agent or in combination with weekly paclitaxel, is 8 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.

When given in combination with paclitaxel, administer CYRAMZA prior to administration of paclitaxel. Refer to the prescribing information for paclitaxel for dosage information.

2.3Recommended Dosage for Non-Small Cell Lung Cancer EGFR Exon 19 Deletions or Exon 21 (L858R) Substitution Mutations – CYRAMZA in Combination with Erlotinib The recommended dosage of CYRAMZA is 10 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.

Refer to the prescribing information for erlotinib for dosage information. Disease Progression On Or After Platinum-based Chemotherapy – CYRAMZA in Combination with Docetaxel The recommended dosage of CYRAMZA is 10 mg/kg administered by intravenous infusion over 60 minutes on Day 1 of a 21-day cycle prior to docetaxel infusion. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes.

Continue CYRAMZA until disease progression or unacceptable toxicity. Refer to the prescribing information for docetaxel for dosage information.

2.4Recommended Dosage for Colorectal Cancer The recommended dosage of CYRAMZA is 8 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes prior to FOLFIRI administration. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.

Refer to the prescribing information for fluorouracil, leucovorin, and irinotecan for dosage information.

2.5Recommended Dosage for Hepatocellular Carcinoma The recommended dosage of CYRAMZA is 8 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.

2.6Dosage Modifications for Adverse Reactions Reduce dose, withhold dose, or discontinue CYRAMZA to manage adverse reactions as described in Table 1 . Table 1: Dosage Modifications for CYRAMZA Adverse Reaction Severity a Dosage Modification a National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0 used to identify adverse reactions Hemorrhage [see Warnings and Precautions ( 5.1 )] Grade 3 or 4 Permanently discontinue CYRAMZA Gastrointestinal Perforation [see Warnings and Pre…

💊 Dosage Forms and Strengths 50 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 100 mg/10 mL (10 mg/mL) or 500 mg/50 mL (10 mg/mL) clear to slightly opalescent, colorless to slightly yellow solution in a single-dose vial Injection: 100 mg/10 mL (10 mg/mL) or 500 mg/50 mL (10 mg/mL) solution in a single-dose vial ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None None ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Hemorrhage : CYRAMZA increases the risk of hemorrhage and gastrointestinal hemorrhage, including severe and fatal events. Permanently discontinue CYRAMZA in patients who experience severe bleeding. ( 5.1 ) Gastrointestinal Perforations : CYRAMZA increases the risk of gastrointestinal perforation, which can be fatal.

Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation. ( 5.2 ) Impaired Wound Healing : Withhold CYRAMZA for 28 days prior to elective surgery. Do not administer CYRAMZA for at least 2 weeks following a major surgical procedure and until adequate wound healing.

The safety of resumption of CYRAMZA after resolution of wound healing complications has not been established. ( 5.3 ) Arterial Thromboembolic Events (ATEs) : Serious and sometimes fatal ATEs can occur with CYRAMZA. Permanently discontinue CYRAMZA in patients who experience an ATE.

( 5.4 ) Hypertension : Monitor blood pressure and treat hypertension. Withhold CYRAMZA for severe hypertension. Permanently discontinue CYRAMZA for hypertension that cannot be controlled with antihypertensive therapy and for hypertensive crisis or hypertensive encephalopathy.

( 5.5 ) Infusion-Related Reactions (IRR) : Monitor for signs and symptoms during infusion. Reduce the infusion rate for Grade 1 or 2 IRR and permanently discontinue for Grade 3 or 4 IRR. ( 5.6 ) Worsening of Pre-existing Hepatic Impairment : New onset or worsening encephalopathy, ascites or hepatorenal syndrome can occur in patients with Child-Pugh B or C cirrhosis.

( 5.7 ) Posterior Reversible Encephalopathy Syndrome : Permanently discontinue CYRAMZA. ( 5.8 ) Proteinuria Including Nephrotic Syndrome : Monitor for proteinuria. Withhold CYRAMZA for urine protein levels greater than or equal to 2 g per 24 hours.

Permanently discontinue CYRAMZA for urine protein levels greater than 3 g per 24 hours or nephrotic syndrome. ( 5.9 ) Thyroid Dysfunction : Monitor thyroid function during treatment. ( 5.10 ) Embryo-Fetal Toxicity : Can cause fetal harm.

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.11 , 8.1 , 8.3 )

5.1Hemorrhage CYRAMZA increased the risk of hemorrhage and gastrointestinal hemorrhage, including Grade ≥3 hemorrhagic events. Across six clinical studies in 2137 patients with various cancers treated with CYRAMZA, the incidence of all Grade hemorrhage ranged from 13-55%. Grade 3-5 hemorrhage incidence ranged from 2-5% [see Adverse Reactions ( 6.1 )] .

Patients with gastric cancer receiving nonsteroidal anti-inflammatory drugs (NSAIDs) were excluded from enrollment in REGARD and RAINBOW; therefore, the risk of gastric hemorrhage in CYRAMZA-treated patients with gastric tumors receiving NSAIDs is unknown. Patients with NSCLC receiving therapeutic anticoagulation or with evidence of major airway invasion by cancer were excluded from REVEL. In addition, patients with NSCLC with a recent history of gross hemoptysis, those receiving chronic therapy with NSAIDs or other anti-platelet therapy other than once daily aspirin, or with radiographic evidence of major blood vessel invasion or intratumor cavitation were excluded from REVEL and RELAY; therefore, the risk of pulmonary hemorrhage in these groups of patients is unknown.

Permanently discontinue CYRAMZA in patients who experience severe (Grade 3 or 4) bleeding [see Dosage and Administration ( 2.6 )] .

5.2Gastrointestinal Perforations CYRAMZA can increase the risk of gastrointestinal perforation, a potentially fatal event. Across six clinical studies in 2137 patients with various cancers treated with CYRAMZA, the incidence of all Grade and Grade 3-5 gastrointestinal perforations ranged from <1-2% [see Adverse Reactions ( 6.1 )] . Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation [see Dosage and Administration ( 2.6 )] .

5.3 Impaired Wound Healing Impaired wound healing can occur in patients who…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Hemorrhage [see Warnings and Precautions ( 5.1 )] . Gastrointestinal Perforations [see Warnings and Precautions ( 5.2 )] . Impaired Wound Healing [see Warnings and Precautions ( 5.3 )] .

Arterial Thromboembolic Events [see Warnings and Precautions ( 5.4 )] . Hypertension [see Warnings and Precautions ( 5.5 )] . Infusion-Related Reactions [see Warnings and Precautions ( 5.6 )] .

Worsening of Pre-existing Hepatic Impairment [see Warnings and Precautions ( 5.7 )] . Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions ( 5.8 )] . Proteinuria Including Nephrotic Syndrome [see Warnings and Precautions ( 5.9 )] .

Thyroid Dysfunction [see Warnings and Precautions ( 5.10 )] . The most common adverse reactions observed in single agent CYRAMZA-treated gastric cancer patients at a rate of ≥10% and ≥2% higher than placebo were hypertension and diarrhea. ( 6.1 ) The most common adverse reactions observed in patients treated with CYRAMZA with paclitaxel at a rate of ≥30% and ≥2% higher than placebo with paclitaxel were fatigue/asthenia, neutropenia, diarrhea, and epistaxis.

( 6.1 ) The most common adverse reactions observed in patients treated with CYRAMZA with erlotinib at a rate of ≥30% and ≥2% higher than placebo with erlotinib were, infections, hypertension, stomatitis, proteinuria, alopecia, and epistaxis. The most common laboratory abnormalities at a rate of ≥30% and ≥2% higher difference in incidence between arms were increased alanine aminotransferase, increased aspartate aminotransferase, anemia, thrombocytopenia, and neutropenia. ( 6.1 ) The most common adverse reactions observed in patients treated with CYRAMZA with docetaxel at a rate of ≥30% and ≥2% higher than placebo with docetaxel were neutropenia, fatigue/asthenia, and stomatitis/mucosal inflammation.

( 6.1 ) The most common adverse reactions observed in patients treated with CYRAMZA with FOLFIRI at a rate of ≥30% and ≥2% higher than placebo with FOLFIRI were diarrhea, neutropenia, decreased appetite, epistaxis, and stomatitis. ( 6.1 ) The most common adverse reactions observed in single agent CYRAMZA-treated HCC patients at a rate of ≥15% and ≥2% higher than placebo were fatigue, peripheral edema, hypertension, abdominal pain, decreased appetite, proteinuria, nausea, and ascites. The most common laboratory abnormalities at a rate of ≥30% and a ≥2% higher difference in incidence between arms were thrombocytopenia, hypoalbuminemia, and hyponatremia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) 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 practice. The data described in the Warnings and Precautions section reflect exposure to CYRAMZA in 2137 patients from six studies: REGARD, RAINBOW, RAISE, REVEL, REACH-2, and RELAY. Gastric Cancer The safety of CYRAMZA was evaluated in REGARD and RAINBOW [see Clinical Studies ( 14.1 )] .

Patients in both trials had locally advanced or metastatic gastric cancer (including GEJ adenocarcinoma) and had previously received platinum- or fluoropyrimidine-containing chemotherapy. Patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Both trials excluded patients with uncontrolled hypertension, major surgery within 28 days, or patients receiving chronic anti-platelet therapy other than once daily aspirin.

REGARD excluded patients with bilirubin ≥1.5 mg/dL and RAINBOW excluded patients with bilirubin >1.5 times the upper limit of normal (ULN). CYRAMZA Administered as a Single Agent (REGARD) Patients received either CYRAMZA 8 mg/kg or placebo intra…

👥 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 [see Clinical Pharmacology ( 12.1 )] , CYRAMZA can cause fetal harm when administered to a pregnant woman. There are no available data on CYRAMZA use in pregnant women. Animal models link angiogenesis, VEGF and VEGFR2 to critical aspects of female reproduction, embryo-fetal development, and postnatal development.

No animal studies have been conducted to evaluate the effect of ramucirumab on reproduction and fetal development. Advise a pregnant woman 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 2-4% and 15-20%, respectively.

Data Animal Data No animal studies have been specifically conducted to evaluate the effect of ramucirumab on reproduction and fetal development. In mice, loss of the VEGFR2 gene resulted in embryo-fetal death and these fetuses lacked organized blood vessels and blood islands in the yolk sac. In other models, VEGFR2 signaling was associated with development and maintenance of endometrial and placental vascular function, successful blastocyst implantation, maternal and feto-placental vascular differentiation, and development during early pregnancy in rodents and non-human primates.

Disruption of VEGF signaling has also been associated with developmental anomalies including poor development of the cranial region, forelimbs, forebrain, heart, and blood vessels.

8.2Lactation Risk Summary There is no information on the presence of ramucirumab in human milk or its effects on the breastfed child or on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because of the potential risk for serious adverse reactions in breastfed children from ramucirumab, advise women not to breastfeed during treatment with CYRAMZA and for 2 months after the last dose.

8.3Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating CYRAMZA [see Use in Specific Populations ( 8.1 )] . Contraception Based on its mechanism of action, CYRAMZA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Females Advise females of reproductive potential to use effective contraception during treatment with CYRAMZA and for 3 months after the last dose.

Infertility Females Advise females of reproductive potential that based on animal data CYRAMZA may impair fertility [see Nonclinical Toxicology ( 13.1 )] .

8.4Pediatric Use The safety and effectiveness of CYRAMZA in pediatric patients have not been established. The safety and effectiveness of CYRAMZA were assessed but not established in a single-arm, multicenter, open-label trial [NCT02564198] that included 23 pediatric patients aged 1 year to <17 years with relapsed or refractory solid tumors who received CYRAMZA as a single agent and two multicenter, randomized, controlled trials [NCT04145700 and NCT04145349] that included 16 pediatric patients aged 1 to <17 years with relapsed, recurrent, or progressive desmoplastic small round cell tumors or synovial sarcoma who received CYRAMZA in combination with chemotherapy versus chemotherapy alone.

The effect on open tibial growth plates in pediatric patients who received CYRAMZA has not been adequately studied; however, one patient had progressive widening of distal femoral growth plate. No other new safety signals were observed in pediatric patients. The pharmacokinetic (PK) parameters for these pediatric patients who received CYRAMZA as a single agent or in combination was within the range of the values previously observed in adults given the same dose per body weight.

Juvenile Animal Toxicity Data In animal studies, effects on epiphyse…

🤰 Pregnancy 214 words ▾

8.1Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology ( 12.1 )] , CYRAMZA can cause fetal harm when administered to a pregnant woman. There are no available data on CYRAMZA use in pregnant women. Animal models link angiogenesis, VEGF and VEGFR2 to critical aspects of female reproduction, embryo-fetal development, and postnatal development.

No animal studies have been conducted to evaluate the effect of ramucirumab on reproduction and fetal development. Advise a pregnant woman 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 2-4% and 15-20%, respectively.

Data Animal Data No animal studies have been specifically conducted to evaluate the effect of ramucirumab on reproduction and fetal development. In mice, loss of the VEGFR2 gene resulted in embryo-fetal death and these fetuses lacked organized blood vessels and blood islands in the yolk sac. In other models, VEGFR2 signaling was associated with development and maintenance of endometrial and placental vascular function, successful blastocyst implantation, maternal and feto-placental vascular differentiation, and development during early pregnancy in rodents and non-human primates.

Disruption of VEGF signaling has also been associated with developmental anomalies including poor development of the cranial region, forelimbs, forebrain, heart, and blood vessels.

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use The safety and effectiveness of CYRAMZA in pediatric patients have not been established. The safety and effectiveness of CYRAMZA were assessed but not established in a single-arm, multicenter, open-label trial [NCT02564198] that included 23 pediatric patients aged 1 year to <17 years with relapsed or refractory solid tumors who received CYRAMZA as a single agent and two multicenter, randomized, controlled trials [NCT04145700 and NCT04145349] that included 16 pediatric patients aged 1 to <17 years with relapsed, recurrent, or progressive desmoplastic small round cell tumors or synovial sarcoma who received CYRAMZA in combination with chemotherapy versus chemotherapy alone.

The effect on open tibial growth plates in pediatric patients who received CYRAMZA has not been adequately studied; however, one patient had progressive widening of distal femoral growth plate. No other new safety signals were observed in pediatric patients. The pharmacokinetic (PK) parameters for these pediatric patients who received CYRAMZA as a single agent or in combination was within the range of the values previously observed in adults given the same dose per body weight.

Juvenile Animal Toxicity Data In animal studies, effects on epiphyseal growth plates were identified. In cynomolgus monkeys, anatomical pathology revealed adverse effects on the epiphyseal growth plate (thickening and osteochondropathy) at all doses tested (5-50 mg/kg). Ramucirumab exposure at the lowest weekly dose tested in the cynomolgus monkey was 0.2 times the exposure in humans at the recommended dose of ramucirumab as a single agent.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Of the 563 CYRAMZA-treated patients in REGARD and RAINBOW, 205 (36%) were 65 and over, while 41 (7%) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Of the 221 patients who received CYRAMZA with erlotinib in RELAY, 119 (54%) were 65 and over, while 29 (13%) were 75 and over.

Overall, no clinically meaningful differences in effectiveness were observed between these patients and younger patients. Adverse reactions occurring at a 10% or higher incidence in patients receiving CYRAMZA with erlotinib and with a 10% or greater difference between patients aged 65 or older compared to patients aged less than 65 years were: diarrhea (75% versus 65%), hypertension (50% versus 40%), increased ALT (49% versus 35%), increased AST (49% versus 33%), stomatitis (46% versus 36%), decreased appetite (32% versus 19%), dysgeusia (23% versus 12%), and weight loss (19% versus 6%).

Of the 1253 patients in REVEL, 455 (36%) were 65 and over and 84 (7%) were 75 and over. Of the 627 patients who received CYRAMZA with docetaxel in REVEL, 237 (38%) were 65 and over, while 45 (7%) were 75 and over. In an exploratory subgroup analysis of REVEL, the hazard ratio for overall survival in patients less than 65 years old was 0.74 (95% CI: 0.62, 0.87) and in patients 65 years and over was 1.10 (95% CI: 0.89, 1.36).

Of the 529 patients who received CYRAMZA with FOLFIRI in RAISE, 209 (40%) were 65 and over, while 51 (10%) were 75 and over. Overall, no differences in safety or effectiveness were observed between these subjects and younger subjects. Of the 197 patients who received CYRAMZA in REACH-2, 95 (48%) were 65 years and over, while 37 (19%) were 75 years and over.

Overall, no differences in efficacy were observed between these subjects and younger subjects.

🧬 Clinical Pharmacology ~1 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Ramucirumab is a VEGFR2 antagonist that specifically binds VEGFR2 and blocks binding of VEGFR ligands, VEGF-A, VEGF-C, and VEGF-D. As a result, ramucirumab inhibits ligand-stimulated activation of VEGFR2, thereby inhibiting ligand-induced proliferation, and migration of human endothelial cells. Ramucirumab inhibited angiogenesis in an in vivo animal model.

12.3Pharmacokinetics The pharmacokinetics (PK) of ramucirumab were studied in patients with various cancers over a dose range of 6-12 mg/kg administered every two or three weeks. The PK characteristics of ramucirumab are similar for patients across cancer types based on a population PK analysis. Ramucirumab systemic exposure increased dose proportionally at doses of 8 mg/kg and above and steady state concentrations were achieved at approximately 12 weeks.

Distribution The mean (% coefficient of variation [CV%]) volume of distribution of ramucirumab at steady-state (Vss) was

5.4L (15%). Elimination The mean (CV%) clearance of ramucirumab was 0.015 L/hour (30%) and the mean elimination half-life was 14 days (20%). Specific Populations Age (19-88 years), sex (68% male), race (70% White, 24% Asian), renal impairment (creatinine clearance [CLcr] calculated by Cockcroft-Gault, 15-89 mL/min, mild hepatic impairment (total bilirubin within ULN and AST>ULN or total bilirubin >1 to 1.5 times ULN and any AST), or moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN) had no clinically meaningful effect on the PK of ramucirumab.

The effect of severe hepatic impairment (total bilirubin >3 times ULN and any AST) on the PK of ramucirumab is unknown. Drug Interaction Studies No clinically meaningful changes in the exposure of either ramucirumab or its concomitant drugs in the approved combinations, including paclitaxel, docetaxel, irinotecan (or its active metabolite, SN-38), and erlotinib were observed in patients with solid tumors.

🧬 Mechanism of Action 51 words ▾

12.1Mechanism of Action Ramucirumab is a VEGFR2 antagonist that specifically binds VEGFR2 and blocks binding of VEGFR ligands, VEGF-A, VEGF-C, and VEGF-D. As a result, ramucirumab inhibits ligand-stimulated activation of VEGFR2, thereby inhibiting ligand-induced proliferation, and migration of human endothelial cells. Ramucirumab inhibited angiogenesis in an in vivo animal model.

📦 How Supplied / Storage and Handling 80 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING CYRAMZA (ramucirumab) injection is a clear to slightly opalescent and colorless to slightly yellow, preservative-free solution supplied in single-dose vials. NDC 0002-7669-01 100 mg/10 mL (10 mg/mL), individually packaged in a carton NDC 0002-7678-01 500 mg/50 mL (10 mg/mL), individually packaged in a carton Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use. Do not freeze or shake the vial.

📋 Description 105 words ▾

11 DESCRIPTION Ramucirumab is a human VEGFR2 antagonist. It is a recombinant human IgG1 monoclonal antibody. Ramucirumab has an approximate molecular weight of 147 kDa.

Ramucirumab is produced in genetically engineered mammalian NS0 cells. CYRAMZA (ramucirumab) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution. CYRAMZA is supplied at a concentration of 10 mg/mL in either 100 mg (10 mL) or 500 mg (50 mL) single-dose vials.

CYRAMZA is formulated in glycine (9.98 mg/mL), histidine (0.65 mg/mL), histidine monohydrochloride (1.22 mg/mL), polysorbate 80 (0.1 mg/mL), sodium chloride (4.383 mg/mL), and Water for Injection, USP, pH 6.0.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Hemorrhage Advise patients that CYRAMZA can cause severe bleeding. Advise patients to contact their health care provider for bleeding or symptoms of bleeding including lightheadedness [see Warnings and Precautions ( 5.1 )] . Gastrointestinal Perforations Advise patients to notify their health care provider for severe diarrhea, vomiting, or severe abdominal pain [see Warnings and Precautions ( 5.2 )] .

Impaired Wound Healing Advise patients that CYRAMZA has the potential to impair wound healing. Instruct patients not to undergo surgery without first discussing this potential risk with their health care provider [see Warnings and Precautions ( 5.3 )] . Arterial Thromboembolic Events Advise patients of an increased risk of an arterial thromboembolic event [see Warnings and Precautions ( 5.4 )] .

Hypertension Advise patients to undergo routine blood pressure monitoring and to contact their health care provider if blood pressure is elevated or if symptoms from hypertension occur including severe headache, lightheadedness, or neurologic symptoms [see Warnings and Precautions ( 5.5 )] . Posterior Reversible Encephalopathy Syndrome Advise patients to inform their health care provider if they develop neurological symptoms consistent with PRES (seizure, headache, nausea/vomiting, blindness, or altered consciousness) [see Warnings and Precautions ( 5.8 )] .

Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus. Advise females to inform their health care provider of a known or suspected pregnancy and to use effective contraception during CYRAMZA treatment and for 3 months after the last dose [see Warnings and Precautions ( 5.11 ), Use in Specific Populations ( 8.1 , 8.3 )] . Lactation Advise women not to breastfeed during CYRAMZA treatment and for 2 months after the last dose [see Use in Specific Populations ( 8.2 )] .

Infertility Advise females of reproductive potential that CYRAMZA may impair fertility [see Use in Specific Populations ( 8.3 )] . Eli Lilly and Company, Indianapolis, IN 46285, USA US License No. 1891 Copyright © 2014, 2025, Eli Lilly and Company.

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

in vivo: In a living person or animal rather than in a laboratory dish.

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

active metabolite: A substance made when the body breaks down a medicine that still has an effect of its own.

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.

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.

antagonist: A substance that blocks a target in the body so a natural signal or another medicine cannot produce its usual effect.

ascites: A buildup of fluid inside the belly.

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

asthenia: Unusual weakness or lack of physical strength and energy.

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

bolus: A single dose given all at once, often as a quick push into a vein.

Child-Pugh: A scoring system doctors use to grade how severe long-term liver disease is, often to help set the right medicine dose.

cirrhosis: Long-term scarring of the liver that gradually replaces healthy tissue and reduces how well the liver works.

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.

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.

creatinine clearance: An estimate of how fast the kidneys filter waste from the blood, often used to choose the right medicine dose.

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.

dysgeusia: A changed or unpleasant sense of taste, such as a metallic taste.

edema: Swelling caused by extra fluid trapped in the body's tissues.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

eGFR: Estimated glomerular filtration rate, a blood-test-based estimate of how well the kidneys filter; lower numbers mean weaker function.

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

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.

epistaxis: A nosebleed.

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

fertility: The natural ability to become pregnant or to father a child.

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

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

hazard ratio: A number comparing how quickly an event happens in one group versus another; above 1 means more often, below 1 means less often.

hemoptysis: Coughing up blood or bloody mucus from the lungs or airways.

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.

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

hypertension: Blood pressure that stays higher than normal, commonly called high blood pressure.

hypertensive crisis: A dangerous, sudden rise in blood pressure to very high levels.

hyponatremia: A lower-than-normal level of sodium (salt) in the blood.

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.

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

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

metabolite: A new substance formed when the body breaks a medicine down.

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

neonatal: Relating to a newborn baby during its first four weeks of life.

neutropenia: A low level of neutrophils, a type of white blood cell that fights infection, which can make it easier to catch infections.

Nonclinical Toxicology: The label section summarizing safety findings from laboratory and animal studies, rather than from studies in people.

open-label: A study in which both the patients and their doctors know which treatment each person is receiving.

overall survival: In a study, the length of time that patients stay alive after starting a treatment.

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

perforation: A hole that forms all the way through the wall of the stomach or intestine.

peripheral edema: Swelling, usually in the feet, ankles, or legs, caused by extra fluid building up in the tissues.

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.

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

proteinuria: Protein leaking into the urine, which can be a sign that the kidneys' filters are damaged.

randomized: Assigned to a treatment group purely by chance, like a coin flip, so the groups being compared start out fair and similar.

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

refractory: Describing a disease that does not respond to, or improve with, treatment.

renal impairment: Reduced kidney function, meaning the kidneys do not filter waste and fluid from the blood as well as normal.

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

seizure: A sudden burst of abnormal electrical activity in the brain that can cause shaking, staring, confusion, or loss of awareness.

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.

stomatitis: Soreness, swelling, or sores on the lining inside the mouth.

subgroup analysis: A closer look at results within a smaller part of a study, such as one age or sex, to see if the effect differs.

thrombocytopenia: A low level of platelets, the blood cells that help form clots, which can lead to easier bruising or bleeding.

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.

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

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