Drugs List

Therapeutic Indications

Uses

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.

Administration

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

Contraindications

Children under 18 years
Breastfeeding
Gastrointestinal perforation
Pregnancy
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
Hyperlipidaemia
Hypertension
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

Pregnancy

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.

Lactation

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
Alopecia
Anaemia
Aneurysm
Artery dissection
Asthenia
Diarrhoea
Epistaxis
Fatigue
Febrile neutropenia
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gingival bleeding
Haemangioma
Haematemesis
Haematochezia
Headache
Hepatic encephalopathy
Hepatic pain
Hypertension
Hypoalbuminaemia
Hypokalaemia
Hyponatraemia
Infections
Infusion-related symptoms
Intestinal obstruction
Leukopenia
Mallory-Weiss syndrome
Melaena
Mucosal inflammation
Neutropenia
Oesophageal haemorrhage
Palmar-Plantar Erythrodysaesthesia syndrome
Peripheral oedema
Proteinuria
Rash
Rectal haemorrhage
Sepsis
Stomatitis
Thrombocytopenia
Thromboembolic complications
Thrombotic microangiopathy

Presentation

Infusions of ramucirumab.

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

Drugs List

Therapeutic Indications

Uses

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.

Dosage

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.

Adults

Additional Dosage Information

Administration

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

Contraindications

Children under 18 years
Breastfeeding
Gastrointestinal perforation
Pregnancy
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
Hyperlipidaemia
Hypertension
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

Pregnancy

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.

Lactation

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
Alopecia
Anaemia
Aneurysm
Artery dissection
Asthenia
Diarrhoea
Epistaxis
Fatigue
Febrile neutropenia
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gingival bleeding
Haemangioma
Haematemesis
Haematochezia
Headache
Hepatic encephalopathy
Hepatic pain
Hypertension
Hypoalbuminaemia
Hypokalaemia
Hyponatraemia
Infections
Infusion-related symptoms
Intestinal obstruction
Leukopenia
Mallory-Weiss syndrome
Melaena
Mucosal inflammation
Neutropenia
Oesophageal haemorrhage
Palmar-Plantar Erythrodysaesthesia syndrome
Peripheral oedema
Proteinuria
Rash
Rectal haemorrhage
Sepsis
Stomatitis
Thrombocytopenia
Thromboembolic complications
Thrombotic microangiopathy

Overdosage

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 ).

Further Information

Last Full Review Date: June 2019

Reference Sources

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.