Irinotesin

Irinotecan HCl trihydrate

Advanced CRC in combination w/ 5-fluorouracil (5-FU) in patients w/o prior chemotherapy for advanced disease; monotherapy in patients who failed an established 5-FU containing treatment regimen. In combination w/ cetuximab for patients w/ epidermal growth factor receptor (EGFR)-expressing metastatic CRC after failure of irinotecan including cytotoxic therapy. In combination w/ 5-FU, folinic acid & bevacizumab as 1st-line treatment in patients w/ metastatic carcinoma of colon or rectum.

Adult Monotherapy Previously treated patient 350 mg/m² by IV infusion over 30-90 min every 3 wk. Combination therapy Previously untreated patient 180 mg/m² once every 2 wk by IV infusion over 30-90 min, followed by infusion w/ folinic acid & 5-FU.

Hypersensitivity. Chronic inflammatory bowel disease &/or bowel obstruction; bilirubin >3 times ULN; severe bone marrow failure; WHO performance status >2. Concomitant use w/ St. John's wort. Pregnancy & lactation.

Not to be administered in patients w/ bilirubin >3 times ULN; bowel obstruction. Diarrhoea associated w/ fever; severe diarrhoea requiring IV hydration; persisting beyond 48 hr following initiation of high-dose loperamide therapy. Not to be given prophylactically in patients w/ delayed diarrhoea at previous cycle. Increased risk of diarrhoea in patients w/ previous abdominal/pelvic RT, baseline hyperleucocytosis, performance status ≥2 & women. Febrile neutropenia (temp >38°C & neutrophil count ≤1,000 cells/mm³); nausea & vomiting; interstitial pulmonary disease; asthma. Hereditary fructose intolerance. Wkly monitor CBC during treatment. Perform LFTs at baseline & before each cycle. Monitor resp symptoms in patients w/ risk factors for interstitial pulmonary disease before & during irinotecan therapy. Concomitant use w/ strong CYP3A4 inhibitor (eg, ketoconazole) or inducer (eg, rifampicin, carbamazepine, phenobarb, phenytoin, St. John's wort). May affect ability to drive & use machines. Hepatic impairment. Impaired renal function. Male & women of childbearing age must use contraception during & for at least 3 mth after cessation of therapy. Not to be used during pregnancy. Discontinue during lactation. Not to be used in childn. Elderly.

Severe diarrhoea, nausea & vomiting; neutropenia, anemia, peripheral thrombocytopenia; reversible alopecia. Dehydration; constipation; fever w/ severe neutropenia, thrombocytopenia; severe transient acute cholinergic syndrome, asthenia; increased serum transaminases, alkaline phosphate or bilirubin levels.

Prolonged neuromuscular blocking effects of suxamethonium. Reduced exposure & pharmacodynamic effects w/ CYP3A-inducing anticonvulsant drugs eg, carbamazepine, phenobarb or phenytoin. Decreased AUC of aminopentanoic acid derivative & increased primary amine derivative w/ ketoconazole. Altered metabolism w/ CYP450 3A4 inhibitor/inducer. Decrease in active metabolite & plasma levels w/ St. John's wort. Increased diarrhea & leukopenia adverse events w/ bevacizumab.

Cytotoxic Chemotherapy

L01CE02 - irinotecan ; Belongs to the class of Topoisomerase 1 (TOP1) inhibitors. Used in the treatment of cancer.

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