CYRAMZA ramucirumab 10 mg/mL Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Vascular Endothelial Growth Factor Receptor 2 Antagonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- 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?
Patient education
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🧪 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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per 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 | $142.37 | $7,118.40 / 50 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 | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Cyramza 10 mg/mLthis 00002-7678-01 | Eli | 1 vial | — | — | FDA listed | — |
| Cyramza 10 mg/mL 00002-7669-01 | Eli | 1 vial | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Apr 21, 2026 |
Is there a biosimilar for CYRAMZA 500 MG/50 ML VIAL?
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Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00002-7678-01 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (0002-7678-01) / 50 mL in 1 VIAL, SINGLE-DOSE | 2014-04-21 | Active |
🧭 About this NDC listing & data coverage
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| 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 |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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 ▾
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 ▾
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 ▾
4 CONTRAINDICATIONS None None ( 4 )
⚠️ Warnings and Cautions ▾
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 ▾
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 ▾
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 ▾
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 ▾
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 ▾
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 ▾
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 ▾
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 ▾
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 ▾
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 ▾
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.
All rights reserved. CYR-0020-USPI-20250819