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Ramucirumab parenteral

Updated 2 Feb 2023 | Ramucirumab


Infusions of ramucirumab.

These products have been produced by recombinant technology using murine NSO cells.

Drugs List

  • CYRAMZA 100mg/10ml concentrate for solution for infusion
  • CYRAMZA 500mg/50ml concentrate for solution for infusion
  • ramucirumab 100mg/10ml concentrate for solution for infusion
  • ramucirumab 500mg/50ml concentrate for solution for infusion
  • Therapeutic Indications


    Advanced gastric carcinoma: second line treatment
    Advanced gastro-oesophageal adenocarcinoma: second line treatment
    Advanced/metastatic non-small cell lung cancer with EGFR-TK mutations
    Hepatocellular carcinoma
    Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)
    Metastatic colorectal cancer

    Advanced gastric cancer or gastro-oesophageal junction (GEJ) adenocarcinoma with disease progression after platinum or fluoropyrimidine, in combination with paclitaxel or as monotherapy.
    Metastatic colorectal cancer (mCRC) with disease progression on or after therapy with bevacizumab, oxaliplatin and a fluoropyrimidine, in combination with FOLFIRI.
    First line treatment for metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations, in combination with erlotinib.
    Locally advanced or metastatic non-small cell lung cancer (NSCLC) with disease progression after platinum, in combination with docetaxel.
    Advanced or unresectable hepatocellular carcinoma (HCC) who have a serum alpha fetoprotein (AFP) of greater than or equal to 400ng/ml after prior therapy with sorafenib, as monotherapy.


    Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

    Treatment should be continued until disease progression or unacceptable toxicity occurs.


    Gastric cancer and gastro-oesophageal junction (GEJ) adenocarcinoma
    8mg/kg every 2 weeks.

    In combination with paclitaxel (see prescribing information for paclitaxel)
    8mg/kg of ramucirumab on days 1 and 15 of a 28 day cycle.

    Administration is prior to paclitaxel. The manufacturer of ramucirumab recommends that there are additional criteria that must be met prior to the administration of paclitaxel.

    Colorectal cancer (CRC)
    8mg/kg every 2 weeks.

    Administration is prior to administration of FOLFIRI. The manufacturer of ramucirumab recommends that there are additional criteria that must be met prior to the administration of FOLFIRI.

    Non-small cell lung cancer (NSCLC)
    In combination with erlotinib (see prescribing information for erlotinib)
    10mg/kg every 2 weeks.

    In combination with docetaxel (see prescribing information for docetaxel)
    10mg/kg on day 1 of a 21 day cycle.

    Administration is prior to docetaxel.

    Hepatocellular carcinoma (HCC)
    8mg/kg every 2 weeks.

    Additional Dosage Information

    Pre-medication with a histamine H1 antagonist is recommended prior to each ramucirumab infusion. If a patient experiences a grade 1 or 2 infusion reaction premedicate all subsequent infusions with a histamine H1 antagonist. If a second grade 1 or 2 infusion reaction occurs administer dexamethasone, premedicate all subsequent infusions with dexamethasone, paracetamol and histamine H1 antagonist.

    Infusion reactions
    Grade 1 or 2 infusion reaction: Reduce rate by 50% for the duration of the infusion and for all subsequent infusions and administer dexamethasone.

    Proteinuria greater than or equal to 2g/24 hours
    8mg/kg schedule
    1st occurrence: Suspend treatment until levels are below 2g/24 hours, reduce dose to 6mg/kg every 2 weeks.
    2nd occurrence: Suspend treatment until levels are below 2g/24 hours, reduce dose to 5mg/kg every 2 weeks.

    10mg/kg schedule
    1st occurrence: Suspend treatment until levels are below 2g/24 hours, reduce dose to 8mg/kg every 2 weeks.
    2nd occurrence: Suspend treatment until levels are below 2g/24 hours, reduce dose to 6mg/kg every 2 weeks.

    The manufacturer of ramucirumab recommends that there are additional dose reductions required for paclitaxel, docetaxel and FOLFIRI based on toxicities.


    Administered as an intravenous infusion over approximately 60 minutes, the maximum infusion rate should remain below 25mg/minute.


    Children under 18 years
    Gastrointestinal perforation
    Severe thromboembolic disorder
    Uncontrolled hypertension

    Precautions and Warnings

    Patients over 70 years
    Predisposition to haemorrhage
    Restricted sodium intake
    Tobacco smoking
    Behcet's disease
    Cerebrovascular disorder
    Diabetes mellitus
    Giant cell arteritis
    Hepatic cirrhosis
    Hepatic cirrhosis with ascites
    Hepatic encephalopathy
    Hepato-renal syndrome
    History of aneurysm
    Ischaemic heart disease
    Marfan syndrome
    Occlusive peripheral arterial disease
    Renal impairment - creatinine clearance below 30 ml/minute
    Severe hepatic impairment
    Takayasu arteritis
    Vascular Ehlers-Danlos syndrome

    Administration of live vaccines is not recommended
    Sodium content of formulation may be significant
    Advise ability to drive/operate machinery may be affected by side effects
    Confirm EGFR mutation status of tumour prior to treatment
    Ensure hypertension is controlled prior to treatment
    Premedication with antihistamine recommended
    Treatment to be initiated and supervised by a specialist
    Consult local policy on the safe use of anti-cancer drugs
    Record name and batch number of administered product
    Reduce infusion rate by 50% if grade 1 or 2 infusion reaction
    Resuscitation facilities must be immediately available
    Staff: Not to be handled by pregnant staff
    Monitor for proteinuria before and periodically during treatment
    Monitor blood pressure
    Monitor for hypersensitivity reactions during infusion
    Monitor for signs and symptoms of hepatic encephalopathy
    Monitor patient for infusion-associated reactions (IARs)
    Risk of gastrointestinal haemorrhage
    Discontinue if Grade 3 or 4 bleeding occurs
    Potential for increased risk of bleeding
    Treatment may adversely affect wound healing
    Discontinue 4 weeks prior to major elective surgery
    Discontinue at once if hepatic encephalopathy occurs
    Discontinue if arterial thromboembolism develops
    Discontinue if fistulae develop during treatment
    Discontinue if grade 3 or higher infusion reaction occurs
    Discontinue if hepatorenal syndrome occurs
    Discontinue if nephrotic syndrome occurs
    Discontinue if persistent hypertension unresponsive to therapy occurs
    Discontinue treatment if gastrointestinal perforation occurs
    Discontinue treatment if proteinuria is >3g/24 hours
    Interrupt therapy if severe hypertension requiring medical treatment occurs
    Suspend treatment and/or reduce dose if proteinuria is 2-3g/ 24 hours
    Suspend treatment until wound healing complications are fully healed
    May cause impaired fertility
    Female: Contraception required during and for 3 months after treatment
    Breastfeeding: Do not breastfeed during & for 3 months after treatment
    Advise patient on giving up smoking

    Ramucirumab should not be used in NSCLC where there is tumour cavitation or tumour involvement of major vessels.

    Patients with a predisposition to bleeding should have blood counts and anticoagulation parameters measured regularly during treatment.

    Patients with HCC with evidence of portal hypertension or prior history of oesophageal variceal bleeding should be screened for and treated for oesophageal varices prior to starting treatment with ramucirumab.

    Patients with NSCLC should have EGFR mutation status determined prior to starting treatment with ramucirumab.

    Risk factors for aneurysm and artery dissection
    Use of systemic VEGF inhibitors may promote the formation of aneurysms or artery dissections, mainly in relation to aortic aneurysm rupture and aortic dissection. It is therefore important to consider the risk of aneurysm and artery dissection in patients with risk factors such as hypertension, history of aneurysm, smoking, diabetes, coronary, cerebrovascular or peripheral arterial disease, and hyperlipidaemia. Other risk factors include Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, and the use of fluoroquinolones. In patients receiving VEGF inhibitors, any modifiable risk factors such as smoking and hypertension should be reduced as far as possible.

    Pregnancy and Lactation


    Ramucirumab is contraindicated during pregnancy.

    The manufacturer does not recommend using ramucirumab during pregnancy. At the time of writing there is limited published information regarding the use of ramucirumab during pregnancy. Potential risks are unknown.


    Ramucirumab is contraindicated during breastfeeding.

    Use of ramucirumab is contraindicated during breastfeeding and for 3 months after by the manufacturer. The presence of ramucirumab in human breast milk is unknown. A risk to infants cannot be excluded.

    Side Effects

    Abdominal pain
    Artery dissection
    Febrile neutropenia
    Gastro-intestinal haemorrhage
    Gastro-intestinal perforation
    Gingival bleeding
    Hepatic encephalopathy
    Hepatic pain
    Infusion-related symptoms
    Intestinal obstruction
    Mallory-Weiss syndrome
    Mucosal inflammation
    Oesophageal haemorrhage
    Palmar-Plantar Erythrodysaesthesia syndrome
    Peripheral oedema
    Rectal haemorrhage
    Thromboembolic complications
    Thrombotic microangiopathy


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: June 2019

    Reference Sources

    MHRA Drug Safety Update July 2020
    Available at:
    Last accessed: 10 November 2020

    Summary of Product Characteristics: Cyramza concentrate for solution for infusion. Eli Lilly. Revised January 2020.

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    Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content

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    FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.