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WARNING:  CYRAMZA increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding [see Dosage and Administration, Warnings and Precautions ]. 


CYRAMZA (ramucirumab) is a recombinant human IgG1 monoclonal antibody that specifically binds to vascular endothelial growth factor receptor 2. CYRAMZA has an approximate molecular weight of 147 kDa. CYRAMZA is produced in genetically engineered mammalian NS0 cells.

CYRAMZA is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution for intravenous infusion following dilution and preparation. 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.

Clinical pharmacology

Mechanism of Action:
Ramucirumab is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist that specifically binds VEGF Receptor 2 and blocks binding of VEGFR ligands, VEGF-A, VEGF-C, and VEGF-D. As a result, ramucirumab inhibits ligand-stimulated activation of VEGF Receptor 2, thereby inhibiting ligand-induced proliferation, and migration of human endothelial cells. Ramucirumab inhibited angiogenesis in an in vivo animal model.

Indications and usage 


Gastric Cancer
CYRAMZATM as a single-agent is indicated for the treatment of patients with advanced or metastatic, gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.





  1. Arterial Thromboembolic Events (ATEs): Serious, sometimes fatal ATEs have been reported in clinical trials. Discontinue CYRAMZA for severe ATEs.
  2. Hypertension: Monitor blood pressure and treat hypertension. Temporarily suspend CYRAMZA for severe hypertension. Discontinue CYRAMZA for hypertension that cannot be medically controlled.
  3. Infusion Related Reactions: Monitor for signs and symptoms during infusion.
  4. Gastrointestinal perforation: Discontinue CYRAMZA.
  5. Impaired Wound Healing: Withhold CYRAMZA prior to surgery.
  6. Clinical Deterioration in Patients with Cirrhosis: New onset or worsening encephalopathy, ascites, or hepatorenal syndrome can occur in patients with Child-Pugh B or C cirrhosis.
  7. Reversible Posterior Leukoencephalopathy Syndrome: Discontinue CYRAMZA.

Adverse reactions

The most common adverse reactions observed in CYRAMZA-treated patients at a rate of ≥10% and ≥2% higher than placebo were hypertension and diarrhea.

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


Dosage and administration 

DOSAGE AND ADMINISTRATION: ------------------------------------
Recommended Dose and Schedule
The recommended dose of CYRAMZA is 8 mg/kg every 2 weeks administered as an intravenous infusion over 60 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.

Do not administer CYRAMZA as an intravenous push or bolus.

Prior to each CYRAMZA infusion, premedicate all patients with an intravenous histamine H1 antagonist (e.g., diphenhydramine hydrochloride).
For patients who have experienced a Grade 1 or 2 infusion reaction, also premedicate with dexamethasone (or equivalent) and acetaminophen prior to each CYRAMZA infusion.

Dose Modifications:
Infusion Related Reactions (IRR)
Reduce the infusion rate of CYRAMZA by 50% for Grade 1 or 2 IRRs.
Permanently discontinue CYRAMZA for Grade 3 or 4 IRRs [see Dosage and Administration and Warnings and Precautions ].

Interrupt CYRAMZA for severe hypertension until controlled with medical management.
Permanently discontinue CYRAMZA for severe hypertension that cannot be controlled with antihypertensive therapy [see Warnings and Precautions].

Interrupt CYRAMZA for urine protein levels ≥2 g/24 hours. Reinitiate treatment at a reduced dose of 6 mg/kg every 2 weeks once the urine protein level returns to <2 g/24 hours. If the protein level ≥2 g/24 hours reoccurs, interrupt CYRAMZA and reduce the dose to 5 mg/kg every 2 weeks once the urine protein level returns to <2 g/24 hours.
Permanently discontinue CYRAMZA for urine protein level >3 g/24 hours or in the setting of nephrotic syndrome [see Adverse Reactions].

Wound Healing Complications
Interrupt CYRAMZA prior to scheduled surgery until the wound is fully healed [see Warnings and Precautions].

Arterial Thromboembolic Events, Gastrointestinal Perforation, or Grade 3 or 4 Bleeding
Permanently discontinue CYRAMZA [see Warnings and Precautions]

Preparation for Administration-------------------------------------------
Inspect vial contents for particulate matter and discoloration prior to dilution [see Description]. Discard the vial, if particulate matter or discolorations are identified. Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of use. Keep the vial in the outer carton in order to protect from light.

  • Calculate the dose and the required volume of CYRAMZA needed to prepare the infusion solution. Vials contain either 100 mg/10 mL or 500 mg/50 mL at a concentration of 10 mg/mL solution of CYRAMZA.
  • Withdraw the required volume of CYRAMZA and further dilute with only 0.9% Sodium Chloride Injection in an intravenous infusion container to a final volume of 250 mL. Do not use dextrose containing solutions.
  • Gently invert the container to ensure adequate mixing.
  • DO NOT FREEZE OR SHAKE the infusion solution. DO NOT dilute with other solutions or co-infuse with other electrolytes or medications.
  • Store diluted infusion for no more than 24 hours at 2°C to 8°C (36°F to 46°F) or 4 hours at room temperature (below 25°C [77°F]).
  • Discard vial with any unused portion of CYRAMZA.

Visually inspect the diluted solution for particulate matter and discoloration prior to administration. If particulate matter or discolorations are identified, discard the solution.

Administer diluted CYRAMZA infusion via infusion pump over 60 minutes through a separate infusion line. Use of a protein sparing 0.22 micron filter is recommended. Flush the line with sterile sodium chloride (0.9%) solution for injection at the end of the infusion.

How supplied

100 mg/10 mL (10 mg per mL) solution, single-dose vial
500 mg/50 mL (10 mg per mL) solution, single-dose vial

Storage and Handling
Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of use. Keep the vial in the outer carton in order to protect from light. DO NOT FREEZE OR SHAKE the vial.

For product diluted in 0.9% sodium chloride, the chemical and physical stability have been demonstrated for up to 24 hours at 2°C to 8°C (36°F to 46°F) or for 4 hours at room temperature (below 25°C [77°F]). DO NOT FREEZE OR SHAKE the diluted product.


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