II. Indications
- FDA Approved (often combined with other agents)
- Colorectal Cancer (metastatic)
- Off-Label
- Lung Cancer (non-small cell and Small Cell Lung Cancer)
- Ovarian Cancer
- Cervical Cancer
III. Mechanism
- See Mitotic Inhibitor Chemotherapy
- Irinotecan is a semisynthetic derivative of camptothecin with antineoplastic activity
- Camptothecin extracted from the Asian tree Camptotheca acuminata ("Happy Tree")
- Camptothecin is a cytotoxic quinoline-based alkaloid
- Irinotecan is a prodrug
- Metabolized to SN-38 (7-ethyl-10-hydroxy-camptothecin) in vivo by carboxylesterase-converting enzyme
- SN-38 is a thousand times more potent than Irinotecan in its inhibition of Topoisomerase 1
- Irinotecan (and its active metabolite SN-38) is a Topoisomerase Inhibitor
- SN-38 binds to topoisomerase 1, inhibiting DNA ligation
- DNA breaks accumulate
- Inhibits DNA Replication and transcription
- Arrests cell cycle in S phase
- Results in cell apoptosis and death
- Contrast Irinotecan with Topotecan
- Both are semisynthetic derivatives of camptothecin
- However, Topotecan is active, while Irinotecan is a prodrug, reliant on metabolism to the active SN-38
IV. Medications
- Irinotecan injection solutions vary from 40 mg/2 ml to 500 mg/25 ml
V. Dosing
- See other references for disease specific dosing protocols
VI. Adverse Effects
- Colitis
-
Diarrhea (severe)
- Symptomatic management with fluid and Electrolyte replacement, Loperamide
- Consider holding Diuretics
- Interstitial Lung Disease
- Hypersensitivity
- Myelosuppression
- Neutropenia higher risk with UGT1A1*28 Allele
- Orthostatic Hypotension
- Pancreatitis
VII. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters)
- Use reliable Contraception
- Monitoring
VIII. Drug Interactions
- Strong CYP3A4 Inducers decrease Irinotecan activity
- Strong CYP3A4 Inhibitors (or UGT1A1 inhibitors) increase Irinotecan activity and toxicity
- Ketoconazole (stop at least 1 week before starting Irinotecan)
- Clarithromycin
- Itraconazole
- Voriconazole
- Lopinavir
- Indinavir
- Saquinavir
- Ritonavir
- Telaprevir
- Nelfinavir
- Atazanavir
- Gemfibrozil (UGT1A1 inhibitor)
IX. Resources
- Irinotecan Injection (DailyMed)