- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Infusions of ramucirumab.
These products have been produced by recombinant technology using murine NSO cells.
Advanced gastric carcinoma: second line treatment
Advanced gastro-oesophageal adenocarcinoma: second line treatment
Advanced/metastatic non-small cell lung cancer with EGFR-TK mutations
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.
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
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.
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
Severe thromboembolic disorder
Precautions and Warnings
Patients over 70 years
Predisposition to haemorrhage
Restricted sodium intake
Giant cell arteritis
Hepatic cirrhosis with ascites
History of aneurysm
Ischaemic heart disease
Occlusive peripheral arterial disease
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
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.
Palmar-Plantar Erythrodysaesthesia syndrome
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 ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: June 2019
MHRA Drug Safety Update July 2020
Available at: https://www.gov.uk/drug-safety-update/systemically-administered-vegf-pathway-inhibitors-risk-of-aneurysm-and-artery-dissection
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
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.