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)
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Related Studies
| Definition (NCI_NCI-GLOSS) | The active ingredient in a drug used alone or with other drugs to treat colon cancer or rectal cancer that has spread to other parts of the body or has come back after treatment with fluorouracil. It is also being studied in the treatment of other types of cancer. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill cancer cells. It is a type of topoisomerase inhibitor and a type of camptothecin analog. |
| Definition (NCI) | A semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. Because ongoing DNA synthesis is necessary for irinotecan to exert its cytotoxic effects, it is classified as an S-phase-specific agent. |
| Definition (CSP) | DNA topoisomerase I inhibitor. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | C051890 |
| SnomedCT | 108783005, 372538008 |
| English | irinotecan, (+)-(4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidino-piperidino)carbonyloxy]-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinol-3,14,(4H,12H)-dione, [1,4'-bipiperidine]-1'-carboxylic acid (S)-4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl ester, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, (+)-7-ethyl-10-hydroxycamptothecine 10-[1,4'-bipiperidine]-1'-carboxylate, Irrinotecan, irinotecan [Chemical/Ingredient], IRINOTECAN, Irinotecan (product), Irinotecan (substance), Irinotecan |
| Spanish | irinotecano, irinotecano (producto), irinotecán (producto), irinotecano (sustancia), irinotecán (sustancia), irinotecán |
