Irinotecan hydrochloride parenteral
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Infusions of irinotecan hydrochloride.
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.
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
The manufacturers do not recommend use in patients with renal impairment. However, The Renal Drug Handbook makes the following recommendations:
Glomerular filtration rate 10 to 50 ml/minute: Dose as in normal renal function and monitor closely.
Glomerular filtration rate below 10 ml/minute: Reduce dose (50 to 80 mg/square metre) and monitor closely. Increase as tolerated.
Patients with Hepatic Impairment
Blood bilirubin levels in patients with a performance status less than or equal to 2 should determine the starting dose. In these patients with hyperbilirubinemia and prothrombin time greater than 50%, the clearance of irinotecan is decreased and therefore the risk of hematotoxicity is increased.
In patients with bilirubin up to 1.5 times the upper limit of normal (ULN), the recommended dose is 350 mg/square metre of BSA.
In patients with bilirubin 1.5 to 3 times the ULN, the recommended dose is 200 mg/square metre of BSA.
Patients with a bilirubin level greater than 3 times the ULN should not be treated with irinotecan.
Additional Dosage Information
Duration of treatment:
When irinotecan is used in monotherapy, it is usually prescribed every three weeks. A weekly dosage schedule may be considered in patients who need a closer follow up or who are at risk of severe neutropenia.
Irinotecan hydrochloride should be administered after appropriate recovery of all adverse events to grade 0 or 1 of the National Cancer Institute Common Toxicity Criteria (NCI-CTC) and when treatment related diarrhoea is fully resolved.
Dosage reductions following toxicity should be made according to the specific protocol being used. Dosage should be decreased according to the worst grade of adverse events observed in the prior infusion. Treatment should be delayed by 1 to 2 weeks to allow recovery from treatment-related adverse events.
With the following adverse events, a dose reduction of 15 to 20% should be applied for irinotecan and/or fluorouracil when applicable:
- Haematological toxicity (neutropenia grade 4, febrile neutropenia (neutropenia grade 3 to 4 and fever grade 2 to 4), thrombocytopenia and leucopenia (grade 4))
- Non-haematological toxicity (grade 3 to 4)
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.
Children under 18 years
Patients with a WHO performance status above 2
Chronic inflammatory bowel disease
Hereditary fructose intolerance
Serum bilirubin above 3 times upper limit of normal
Precautions and Warnings
History of radiotherapy
Patients with a WHO performance status equal to 2
Risk factors for cardiovascular disorder
UGT1A1 genetic polymorphism
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 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
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.
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.
Acute cholinergic syndrome
Diarrhoea - delayed
Elevated amylase levels
Elevated serum lipase
Gamma glutamyl transferase (GGT) increased
Increase in alkaline phosphatase
Increases in serum transaminases (transient)
Injection site reactions
Interstitial lung disease
Peripheral vascular disorders
Serum bilirubin increased
Serum creatinine increased
Tumour lysis syndrome
Urinary tract infections
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: May 2021
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.
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