Drugs List

Therapeutic Indications

Uses

EGFR expressing metastatic colorectal cancer in combination with cetuximab
Treatment of advanced colorectal cancer combined with other cytotoxics
Treatment of advanced colorectal cancer unresponsive to fluorouracil

As a single agent therapy in patients with advanced colorectal cancer unresponsive to fluorouracil containing regimens.

In combination with fluorouracil and folinic acid in chemotherapy naive patients with advanced colorectal cancer.

In combination with cetuximab for the treatment of epidermal growth factor receptor (EGFR) expressing, KRAS wild-type metastatic colorectal cancer, who had not received prior treatment for metastatic disease or after failure of cytotoxic therapy that included irinotecan.

In combination with fluorouracil, folinic acid and bevacizumab for first line treatment of patients with metastatic carcinoma of the colon or rectum.

In combination with capecitabine with or without bevacizumab for the first line treatment of patients with metastatic colorectal carcinoma.

Administration

Concentrate for solution for infusion
Dilute before use and give by intravenous infusion into a central or peripheral vein.

Solution for infusion
Give by intravenous infusion into a central or peripheral vein.

Contraindications

Children under 18 years
Patients with a WHO performance status above 2
Breastfeeding
Chronic inflammatory bowel disease
Gastrointestinal obstruction
Hereditary fructose intolerance
Pregnancy
Serum bilirubin above 3 times upper limit of normal
Severe myelosuppression

Precautions and Warnings

Elderly
History of radiotherapy
Patients with a WHO performance status equal to 2
Risk factors for cardiovascular disorder
UGT1A1 genetic polymorphism
Asthma
Cardiovascular disorder
Diabetes mellitus
Gilbert's syndrome
Renal impairment - glomerular filtration rate below 50ml/minute
Serum bilirubin between 1.5 and 3 times upper limit of normal

Administration of live vaccines is not recommended
Live virus vaccine should not be given for 6 months after treatment
Advise ability to drive/operate machinery may be affected by side effects
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some brands contain glucose
Concentrate must be diluted and used as an infusion
Consult local policy on the safe use of anti-cancer drugs
Febrile neutropenia should be treated with broad spectrum IV antibiotics
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Perform liver function tests before commencing therapy and during therapy
Diabetic control may need adjustment
Hospitalisation recommended for patients with severe diarrhoea
Monitor closely patient at risk of cardiovascular disorders
Monitor full blood counts weekly
Monitor patients with risk factors for respiratory symptoms
Advise patient to inform physician if/when (delayed) diarrhoea occurs
Cholinergic syndrome should be treated with subcutaneous atropine
Consider dose reduction for subsequent doses if severe diarrhoea occurs
Consider dose reduction if severe haematological events occur
Consider prophylactic atropine to prevent acute severe cholinergic syndrome
Diarrhoea to be managed with electrolyte/fluids+high dose loperamide
Prophylactic antiemetic recommended before each dose
Severe neutropenia + diarrhoea: Consider prophylactic oral antibiotic
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Male & female: Contraception required during & for 3 months after treatment
Advise on measures to take if diarrhoea occurs
Advise patients on the risk of neutropenia and the significance of fever

There is an increased risk of toxicity in patients who are UGT1A1 poor metabolisers, increasing with dose level. These patients have a higher risk of diarrhoea and severe neutropenia, and a reduced starting dose should be considered, especially for frail patients or for doses over 180mg/metre squared. Further doses can be increased depending on the patient's tolerance.

Diarrhoea
Diarrhoea must be treated immediately and appropriately at its occurrence as there is a risk that it can become life threatening. Patients who are concomitantly neutropenic are at particular risk. When diarrhoea is associated with neutropenia (neutrophil count less than 500 cells/cubic millimetre), a prophylactic broad spectrum antibiotic should also be administered.

Patients who have previously had abdominal/pelvic radiotherapy, with baseline hyperleukocytosis, a performance status greater than or equal to 2 and women, have an increased risk of experiencing diarrhoea.

Patients should be made aware of the risk of delayed diarrhoea occurring more than 24 hours after the administration of irinotecan and at any time before the next administration.

Patients should be advised to inform their physician of the occurrence of diarrhoea. Large amounts of fluid containing electrolytes and the appropriate antidiarrhoeal therapy should be taken as soon as diarrhoea occurs, the appropriate treatment should be available for immediate administration at the occurrence of diarrhoea.

The recommended diarrhoea treatment is loperamide at doses of 4 mg initially and then 2 mg every 2 hours. Therapy should continue for 12 hours (a total dose of 16 mg) after the last bout of diarrhoea. Loperamide should not be administered at these doses for more than 48 hours (risk of paralytic ileus) or for less than 12 hours. Loperamide should not be given prophylactically, even in patients who have experienced diarrhoea at previous cycles.

Prophylactic treatment with antiemetics is recommended before each treatment. Patients who experience vomiting associated with delayed diarrhoea should be hospitalised for treatment as soon as possible.

Risk factors associated with the development of interstitial pulmonary (presenting as pulmonary infiltrates) disease include the use of pneumotoxic drugs, radiation therapy and colony stimulating factors. Patients with risk factors should be monitored for respiratory symptoms before and during therapy.

Patients with underlying or known risk factors for cardiac disease, or have had previous cytotoxic chemotherapy should be monitored closely following treatment with irinotecan. Action should be taken to try and minimise modifiable risk factors such as smoking, hypertension and hyperlipidaemia.

Pregnancy and Lactation

Pregnancy

Irinotecan is contraindicated during pregnancy.

The manufacturer recommends that irinotecan should not be used during pregnancy. However, Briggs concludes that as colorectal cancer can be fatal, if a woman requires irinotecan and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus. There is limited information on the use of irinotecan in pregnant women, however it has been shown to be embryotoxic, foetotoxic and teratogenic in animals.

Lactation

Irinotecan is contraindicated during breastfeeding.

The manufacturer recommends that women receiving irinotecan should not breastfeed. It is not known if irinotecan is excreted in human breast milk but it has been detected in the milk of lactating animals.

Side Effects

Abdominal pain
Acute cholinergic syndrome
Allergic reaction
Alopecia
Anaemia
Anaphylactic reaction
Angina pectoris
Asthenia
Bradycardia
Breast pain
Circulatory collapse
Colitis
Confusion
Constipation
Cutaneous reactions
Decreased appetite
Dehydration
Diarrhoea - delayed
Dizziness
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Extravasation
Febrile neutropenia
Fever
Flushing
Fungal infection
Gait abnormality
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Headache
Hepatic steatosis
Hiccups
Hypersalivation
Hypertension
Hypokalaemia
Hyponatraemia
Hypotension
Hypovolaemia
Ileus
Increase in alkaline phosphatase
Increases in serum transaminases (transient)
Infections
Injection site reactions
Interstitial lung disease
Intestinal obstruction
Ischaemic colitis
Mucositis
Muscular cramps
Myocardial infarction
Myocardial ischaemia
Myosis
Nausea
Neutropenia
Pain
Paraesthesia
Peripheral vascular disorders
Pseudomembranous colitis
Pulmonary infiltrates
Renal impairment
Sepsis
Serum bilirubin increased
Serum creatinine increased
Speech disturbances
Sweating
Syncope
Thrombocytopenia
Thromboembolism
Tumour lysis syndrome
Typhlitis
Ulcerative colitis
Urinary tract infections
Viral infection
Visual disturbances
Vomiting

Presentation

Infusions of irinotecan hydrochloride.

Drugs List

Therapeutic Indications

Uses

EGFR expressing metastatic colorectal cancer in combination with cetuximab
Treatment of advanced colorectal cancer combined with other cytotoxics
Treatment of advanced colorectal cancer unresponsive to fluorouracil

As a single agent therapy in patients with advanced colorectal cancer unresponsive to fluorouracil containing regimens.

In combination with fluorouracil and folinic acid in chemotherapy naive patients with advanced colorectal cancer.

In combination with cetuximab for the treatment of epidermal growth factor receptor (EGFR) expressing, KRAS wild-type metastatic colorectal cancer, who had not received prior treatment for metastatic disease or after failure of cytotoxic therapy that included irinotecan.

In combination with fluorouracil, folinic acid and bevacizumab for first line treatment of patients with metastatic carcinoma of the colon or rectum.

In combination with capecitabine with or without bevacizumab for the first line treatment of patients with metastatic colorectal carcinoma.

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

Concentrate for solution for infusion
Dilute before use and give by intravenous infusion into a central or peripheral vein.

Solution for infusion
Give by intravenous infusion into a central or peripheral vein.

Contraindications

Children under 18 years
Patients with a WHO performance status above 2
Breastfeeding
Chronic inflammatory bowel disease
Gastrointestinal obstruction
Hereditary fructose intolerance
Pregnancy
Serum bilirubin above 3 times upper limit of normal
Severe myelosuppression

Precautions and Warnings

Elderly
History of radiotherapy
Patients with a WHO performance status equal to 2
Risk factors for cardiovascular disorder
UGT1A1 genetic polymorphism
Asthma
Cardiovascular disorder
Diabetes mellitus
Gilbert's syndrome
Renal impairment - glomerular filtration rate below 50ml/minute
Serum bilirubin between 1.5 and 3 times upper limit of normal

Administration of live vaccines is not recommended
Live virus vaccine should not be given for 6 months after treatment
Advise ability to drive/operate machinery may be affected by side effects
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some brands contain glucose
Concentrate must be diluted and used as an infusion
Consult local policy on the safe use of anti-cancer drugs
Febrile neutropenia should be treated with broad spectrum IV antibiotics
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Perform liver function tests before commencing therapy and during therapy
Diabetic control may need adjustment
Hospitalisation recommended for patients with severe diarrhoea
Monitor closely patient at risk of cardiovascular disorders
Monitor full blood counts weekly
Monitor patients with risk factors for respiratory symptoms
Advise patient to inform physician if/when (delayed) diarrhoea occurs
Cholinergic syndrome should be treated with subcutaneous atropine
Consider dose reduction for subsequent doses if severe diarrhoea occurs
Consider dose reduction if severe haematological events occur
Consider prophylactic atropine to prevent acute severe cholinergic syndrome
Diarrhoea to be managed with electrolyte/fluids+high dose loperamide
Prophylactic antiemetic recommended before each dose
Severe neutropenia + diarrhoea: Consider prophylactic oral antibiotic
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Male & female: Contraception required during & for 3 months after treatment
Advise on measures to take if diarrhoea occurs
Advise patients on the risk of neutropenia and the significance of fever

There is an increased risk of toxicity in patients who are UGT1A1 poor metabolisers, increasing with dose level. These patients have a higher risk of diarrhoea and severe neutropenia, and a reduced starting dose should be considered, especially for frail patients or for doses over 180mg/metre squared. Further doses can be increased depending on the patient's tolerance.

Diarrhoea
Diarrhoea must be treated immediately and appropriately at its occurrence as there is a risk that it can become life threatening. Patients who are concomitantly neutropenic are at particular risk. When diarrhoea is associated with neutropenia (neutrophil count less than 500 cells/cubic millimetre), a prophylactic broad spectrum antibiotic should also be administered.

Patients who have previously had abdominal/pelvic radiotherapy, with baseline hyperleukocytosis, a performance status greater than or equal to 2 and women, have an increased risk of experiencing diarrhoea.

Patients should be made aware of the risk of delayed diarrhoea occurring more than 24 hours after the administration of irinotecan and at any time before the next administration.

Patients should be advised to inform their physician of the occurrence of diarrhoea. Large amounts of fluid containing electrolytes and the appropriate antidiarrhoeal therapy should be taken as soon as diarrhoea occurs, the appropriate treatment should be available for immediate administration at the occurrence of diarrhoea.

The recommended diarrhoea treatment is loperamide at doses of 4 mg initially and then 2 mg every 2 hours. Therapy should continue for 12 hours (a total dose of 16 mg) after the last bout of diarrhoea. Loperamide should not be administered at these doses for more than 48 hours (risk of paralytic ileus) or for less than 12 hours. Loperamide should not be given prophylactically, even in patients who have experienced diarrhoea at previous cycles.

Prophylactic treatment with antiemetics is recommended before each treatment. Patients who experience vomiting associated with delayed diarrhoea should be hospitalised for treatment as soon as possible.

Risk factors associated with the development of interstitial pulmonary (presenting as pulmonary infiltrates) disease include the use of pneumotoxic drugs, radiation therapy and colony stimulating factors. Patients with risk factors should be monitored for respiratory symptoms before and during therapy.

Patients with underlying or known risk factors for cardiac disease, or have had previous cytotoxic chemotherapy should be monitored closely following treatment with irinotecan. Action should be taken to try and minimise modifiable risk factors such as smoking, hypertension and hyperlipidaemia.

Pregnancy and Lactation

Pregnancy

Irinotecan is contraindicated during pregnancy.

The manufacturer recommends that irinotecan should not be used during pregnancy. However, Briggs concludes that as colorectal cancer can be fatal, if a woman requires irinotecan and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus. There is limited information on the use of irinotecan in pregnant women, however it has been shown to be embryotoxic, foetotoxic and teratogenic in animals.

Lactation

Irinotecan is contraindicated during breastfeeding.

The manufacturer recommends that women receiving irinotecan should not breastfeed. It is not known if irinotecan is excreted in human breast milk but it has been detected in the milk of lactating animals.

Side Effects

Abdominal pain
Acute cholinergic syndrome
Allergic reaction
Alopecia
Anaemia
Anaphylactic reaction
Angina pectoris
Asthenia
Bradycardia
Breast pain
Circulatory collapse
Colitis
Confusion
Constipation
Cutaneous reactions
Decreased appetite
Dehydration
Diarrhoea - delayed
Dizziness
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Extravasation
Febrile neutropenia
Fever
Flushing
Fungal infection
Gait abnormality
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Headache
Hepatic steatosis
Hiccups
Hypersalivation
Hypertension
Hypokalaemia
Hyponatraemia
Hypotension
Hypovolaemia
Ileus
Increase in alkaline phosphatase
Increases in serum transaminases (transient)
Infections
Injection site reactions
Interstitial lung disease
Intestinal obstruction
Ischaemic colitis
Mucositis
Muscular cramps
Myocardial infarction
Myocardial ischaemia
Myosis
Nausea
Neutropenia
Pain
Paraesthesia
Peripheral vascular disorders
Pseudomembranous colitis
Pulmonary infiltrates
Renal impairment
Sepsis
Serum bilirubin increased
Serum creatinine increased
Speech disturbances
Sweating
Syncope
Thrombocytopenia
Thromboembolism
Tumour lysis syndrome
Typhlitis
Ulcerative colitis
Urinary tract infections
Viral infection
Visual disturbances
Vomiting

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: May 2021

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Campto 20 mg/ml, concentrate for solution for infusion. Pfizer Ltd. Revised April 2022.

Summary of Product Characteristics: Irinotecan Hydrochloride Accord 20 mg/ml concentrate for solution for infusion. Accord Healthcare Ltd. Revised October 2020.

Summary of Product Characteristics: Irinotecan 1.5mg/ml solution for infusion. Sun Pharmaceuticals Industries Europe B.V. Revised February 2020.