Ramucirumab
FDA Drug Information • Also known as: Cyramza
- Brand Names
- Cyramza
- Drug Class
- Vascular Endothelial Growth Factor Receptor 2 Antagonist [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
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.
What Is Ramucirumab Used For?
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 ) 1.1 Gastric 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. 1.2 Non-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. 1.3 Colorectal 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. 1.4 Hepatocellular 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 ) 2.1 Premedication 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 )] . 2.2 Recommended 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. 2.3 Recommended 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. 2.4 Recommended 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...
Side Effects (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. 6.1 Clinical 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...
Contraindications
4 CONTRAINDICATIONS None None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy 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.
How Supplied
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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.