Irinotecan

Cytostatic · Topoisomerase 1 inhibitor

Indications

Second-line treatment of metastatic colorectal cancer that has failed to respond to an established 5-FU containing regimen.

Dosage

Adults: 350 mg/m² by IV infusion over 30-90 min every 3 wk. If patient develops severe neutropenia or severe diarrhoea reduce dose to 300 mg/m² and then 250 mg/m² in subsequent cycles. Continue treatment until disease progression or unacceptable toxicity. Children: Not recommended.

Administration

IV: Administer by IV Infusion, usually over 90 min. D5W (500 mL) is the preferred diluent for most doses. Solutions diluted in NS may precipitate if refrigerated. Reconstitution: Dilute in D5W or NS to a final conc of 0.12-2.8 mg/mL. Due to the relatively acidic pH, irinotecan appears to be more stable in D5W than NS, D5W (500 mL) is the preferred diluent for most doses. Compatibility: Stable in D5W, NS. Stability: Store vials at 15°C-30°C (59°F-86°F). Protect from light. Vials should remain in carton until the time of use. The diluted solution is physically and chemically stable for up to 24 hours at room temperature (approximately 25°C) and in ambient fluorescent lighting. In the case of admixtures prepared with D5W or NaCl, the solutions should be used within 6 hours if kept at room temperature 15°C-30°C (59°F-86°F). Solutions diluted in D5W and stored at refrigerated temperatures…

Adverse Effects

Delayed diarrhoea, warn patient of risk and start high dose loperamide immediately. Neutropenia, monitor neutrophil count. Anaemia, thrombocytopenia. Liver impairment; perform liver function tests. Nausea, vomiting, acute cholinergic syndrome, asthaenia, alopecia, dyspnoea, cramps, paraesthesia. Infection, blood dyscrasias, GI upset, colitis, haemorrhoids, anorexia, wt loss, cholinergic syndrome, dizziness, dysgeusia, mucosal inflammation, pyrexia, fatigue, oedema, electrolyte disturbances, dehydration, hypotension, embolism, DVT, dysphonia, raised blood creatinine, blood alkaline phosphatase and INR, hypoalbuminaemia, acute renal failure, inf related reactions. Reports of interstitial pulmonary disease.

Risk Factor (Pregnancy/Lactation)

Pregnancy: Positive evidence of risk: Use only when no safer alternative exists for a serious problem. Lactation: Contraindicated or not recommended. Contraindications: Chronic inflammatory bowel disease, bowel obstruction, hepatic impairment, renal impairment, severe myelosuppression. Precautions: Risk of severe neutropenia; instruct patient to report fever. Monitor FBCs weekly. Perform LFTs before initiating treatment and before each cycle. Asthma. Risk factors for respiratory or cardiac disorders. UGT1A1 deficiency. Previous Whipple procedure. BMI <18.5kg/m2. Asian ethnicity. Elderly. Previous abdominal or pelvic irradiation, irradiation concurrent with treatment. Risk of delayed diarrhoea; warn patient and start high-dose loperamide immediately.

Interactions

Neuromuscular blocking agents, carbamazepine, phenobarbital, phenytoin, rifampicin, azole antifungals, protease inhibitors, St John's wort, grapefruit juice, other CYP3A4 inducers or inhibitors, strong UGT1A1 inhibitors, anticoagulants, live vaccines, tacrolimus, ciclosporin, other hepatotoxic agents.

Advice to Patient

This medication is administered by infusion. Report immediately if there is redness/swelling/pain/burning at infusion site or if you experience signs of dehydration (light headedness, fainting, dizziness) or severe diarrhoea. Contact prescriber if there is fatigue, fever, chills, unusual bruising or bleeding, unrelieved nausea, vomiting, changes in appetite, purulent vaginal discharge, chest pain, palpitations, difficulty in breathing, unhealed mouth sores. Take sufficient amount of fluids (2-3 litres per day) to maintain hydration, unless restricted by the prescriber. Avoid highly crowded places to prevent infection. Do not get vaccinated without consulting prescriber.

Pharmacokinetics

Metabolism: Primarily hepatic to SN-38 (active metabolite). Bioavailability: Median: 9%; increased in presence of gefitinib (median: 42%). Half-life elimination: Children and Adolescents: Irinotecan: 2.66 hours (range: 1.82 to 4.47 hours); SN-38 (active metabolite): 1.58 hours (range: 0.29 to 8.28 hours). Adults: Irinotecan: 6 to 12 hours; SN-38: Approx. 10 to 20 hours. Time to peak: Irinotecan: Oral Children and Adolescents: 3 hours. SN-38: Following 90-minute infusion: Approx. 1 hour. Excretion: Urine: Irinotecan (11% to 20%), metabolites (SN-38 <1%, SN-38 glucuronide, 3%).

Brands with this active ingredient

Compiled by Healify Pharmacy from published drug references. How we compile it →

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