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ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS › ANTINEOPLASTIC AGENTS › PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS › Topoisomerase 1 (TOP1) inhibitors
irinotecan
L01CE02
Forms & Strengths
- Injection: 40 mg/2 mL solution
- Injection: 100 mg/5 mL solution
- Injection: 300 mg/15 mL solution
- Liposomal injection: 43 mg/10 mL
Adult Dosing
- Colorectal cancer (combination regimens): 125 mg/m2 IV over 90 minutes weekly for 4 weeks every 6 weeks, or 180 mg/m2 IV every 2 weeks
- Colorectal cancer (single agent): 350 mg/m2 IV every 3 weeks (or 125 mg/m2 weekly for 4 weeks every 6 weeks)
- Liposomal irinotecan (metastatic pancreatic cancer): 70 mg/m2 IV every 2 weeks in combination with fluorouracil and leucovorin
Pediatric Dosing
- Safety and efficacy in pediatric patients have not been established
- Investigational trials in refractory solid tumors have utilized doses ranging from 20 mg/m2/day to 50 mg/m2/day for 5 consecutive days repeated every 3 weeks
Indications
- First-line metastatic colorectal cancer in combination with 5-fluorouracil and leucovorin
- Metastatic colorectal cancer resistant or progressive to 5-fluorouracil-based therapy
- Metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy (liposomal formulation)
Mechanism of Action
- Topoisomerase I inhibitor
- Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex, preventing religation of single-strand breaks
- Causes DNA damage leading to replication arrest and apoptotic cell death
Contraindications
- Hypersensitivity to irinotecan or its excipients
- Chronic inflammatory bowel disease and/or bowel obstruction
- Severe bone marrow suppression
Adverse Reactions
- Early and late diarrhea (frequent, dose-limiting toxicity requiring aggressive loperamide management)
- Severe myelosuppression (neutropenia, leukopenia, anemia, thrombocytopenia)
- Acute cholinergic syndrome (early diarrhea, abdominal cramping, diaphoresis, rhinitis, lacrimation during or shortly after infusion)
- Nausea, vomiting, alopecia, fatigue, elevated transaminases and bilirubin
Drug Interactions
- CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) decrease exposure to irinotecan and SN-38
- CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) increase exposure to irinotecan and SN-38
- UGT1A1 inhibitors (e.g., atazanavir, gemfibrozil) may increase SN-38 toxicity
- Neuromuscular blocking agents: prolonged effects may occur with concurrent use
Curated Content: Needs Vetting Before Put to Clinical Use