Ramucirumab

What is Ramucirumab?

• Ramucirumab (Cyramza) is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist used used in the therapy of advanced colorectal, gastric and lung cancers.

What are the uses of this medicine?

This medicine is used:

• as a single agent or in combination with paclitaxel, for treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
• in combination with erlotinib, for first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.
• in combination with docetaxel, for treatment of 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.
• in combination with FOLFIRI, for the treatment of metastatic colorectal cancer with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
• as a single agent, for the treatment of hepatocellular carcinoma in patients who have an alpha fetoprotein of ≥400 ng/mL and have been treated with sorafenib.

How does this medicine work?

• Ramucirumab (ra" mue sir' ue mab) is a recombinant human monoclonal IgG1 antibody to the vascular endothelial growth factor receptor 2.
• Receptors for VEGF are present on endothelial cells, and the engagement of VEGF with these receptors promotes cell proliferation and angiogenesis. Inhibition of VEGF receptor 2 signaling decreases formation of new blood vessels, which plays an important role in growth and spread of cancer cells. When used in combination with other antineoplastic agents, ramucirumab has been shown to extend progression-free and overall survival in several forms of advanced cancer.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• No formal clinical drug interaction studies have been performed with Cyramza.

Is this medicine FDA approved?

• This medicine is approved in the year 2014.

How should this medicine be used?

• Prior to each Cyramza infusion, premedicate all patients with an intravenous histamine-1 receptor antagonist (e.g., diphenhydramine hydrochloride).

Recommended Dosage: Gastric Cancer:

• Administer Cyramza 8 mg/kg every 2 weeks as a single agent or in combination with weekly paclitaxel.

Non-Small Cell Lung Cancer:

• Administer Cyramza 10 mg/kg every 2 weeks with daily erlotinib.
• Administer Cyramza 10 mg/kg on Day 1 of a 21-day cycle prior to docetaxel.

Colorectal Cancer:

• Administer Cyramza 8 mg/kg every 2 weeks prior to FOLFIRI.

Hepatocellular Carcinoma:

• Administer Cyramza 8 mg/kg every 2 weeks.

Preparation

• Visually inspect vials for particulate matter and discoloration. Discard if particulate matter or discolorations are identified.
• Calculate the dose and the required volume of Cyramza needed for the calculated dose.
• 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.
• Do not shake. Gently invert the container to ensure adequate mixing.
• Do not dilute with other solutions or co-infuse with other electrolytes or medications.
• Do not freeze. Store diluted solution 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 any unused portion of Cyramza.

Administration

• Visually inspect the diluted solution for particulate matter and discoloration prior to administration.
• Discard if particulate matter or discolorations are identified.
• Do not administer Cyramza as an intravenous push or bolus.
• Administer diluted Cyramza solution via infusion pump through a separate infusion line.
• Use of a protein sparing 0.22 micron filter is recommended.
• Flush the line with sterile 0.9% Sodium Chloride Injection at the end of the infusion.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 100 mg/10 mL (10 mg/mL) or 500 mg/50 mL (10 mg/mL) solution in a single-dose vial

This medicine is available in fallowing brand namesː

• Cyramza

What side effects can this medication cause?

• 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.
• The most common adverse reactions observed in patients treated with Cyramza with paclitaxel were fatigue/asthenia, neutropenia, diarrhea, and epistaxis.
• The most common adverse reactions observed in patients treated with Cyramza with erlotinib were infections, hypertension, stomatitis, proteinuria, alopecia, and epistaxis increased alanine aminotransferase, increased aspartate aminotransferase, anemia, thrombocytopenia, and neutropenia.
• The most common adverse reactions observed in patients treated with Cyramza with docetaxel were neutropenia, fatigue/asthenia, and stomatitis/mucosal inflammation.
• The most common adverse reactions observed in patients treated with Cyramza with FOLFIRI were diarrhea, neutropenia, decreased appetite, epistaxis, and stomatitis.
• The most common adverse reactions observed in single agent Cyramza-treated HCC patients were fatigue, peripheral edema, hypertension, abdominal pain, decreased appetite, proteinuria, nausea, ascites, thrombocytopenia, hypoalbuminemia, and hyponatremia.

What special precautions should I follow?

• Cyramza increases the risk of hemorrhage and gastrointestinal hemorrhage, including severe and fatal events. Permanently discontinue Cyramza in patients who experience severe bleeding.
• Cyramza increases the risk of gastrointestinal perforation, which can be fatal. Permanently discontinue Cyramza in patients who experience a gastrointestinal perforation.
• Cyramza increases the risk of 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.
• Serious and sometimes fatal arterial thromboembolic events ATEs can occur with Cyramza. Permanently discontinue Cyramza in patients who experience an ATE.
• An increased incidence of severe hypertension occurred in patients receiving Cyramza. 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.
• Infusion-related reactions (IRR), including severe and life-threatening IRR, occurred in Cyramza clinical trials. 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.
• New onset or worsening encephalopathy, ascites or hepatorenal syndrome can occur in patients with Child-Pugh B or C cirrhosis.
• Posterior Reversible Encephalopathy Syndrome (PRES) (also known as Reversible Posterior Leukoencephalopathy Syndrome [RPLS]) has been reported. Permanently discontinue Cyramza.
• Proteinuria Including Nephrotic Syndrome may occur. 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.
• Thyroid dysfunction may occur. Monitor thyroid function during treatment.
• Cyramza Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Based on its mechanism of action, Cyramza can cause fetal harm when administered to a pregnant woman.
• There are no available data on Cyramza use in pregnant women.

Can this medicine be used in children?

• The safety and effectiveness of Cyramza in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient:

ramucirumab

• Inactive ingredients:

histidine histidine monohydrochloride sodium chloride glycine polysorbate 80 water

Who manufactures and distributes this medicine?

• Packager: Eli Lilly and Company

What should I know about storage and disposal of this medication?

• 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.

• Dailymed label info on Ramucirumab
• FDA Ramucirumab

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