Irinotecan
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-IRINOTECAN |
|---|---|
| Type | Drug |
| Aliases | CPT-11CamptosarOnivyde (liposomal nal-IRI)Іринотекан |
| Status | reviewed 2026-04-26 | pending_clinical_signoff |
| Diseases | DIS-CRC DIS-PDAC |
| Sources | SRC-ESMO-COLON-2024 SRC-NCCN-COLON-2025 |
Drug Facts
| Class | Topoisomerase I inhibitor (semi-synthetic camptothecin) |
|---|---|
| Mechanism | Prodrug hydrolyzed by carboxylesterases to active metabolite SN-38 (~100-1000× more potent than parent). SN-38 stabilizes the topoisomerase-I/DNA cleavable complex, producing single-strand DNA breaks that become lethal double-strand breaks during S-phase replication. SN-38 is glucuronidated by UGT1A1 to inactive SN-38G; patients homozygous for UGT1A1*28 (Gilbert-syndrome variant) or *6 have impaired clearance and severe neutropenia + diarrhea risk — CPIC and FDA label both recommend testing before high-dose use. |
| Typical dosing | FOLFIRI: 180 mg/m² IV over 90 min day 1 every 14 d. FOLFIRINOX: 180 mg/m² IV over 90 min day 1 every 14 d. CRC monotherapy 2L (q3w): 350 mg/m² IV over 90 min every 21 d. CRC monotherapy 2L (weekly): 125 mg/m² IV weekly × 4, then 2 weeks off. Liposomal nal-IRI (Onivyde) for PDAC 2L: 70 mg/m² (free base) IV every 14 d with 5-FU/LV. UGT1A1 *28/*28 or *6/*6: reduce starting dose by ~25-30%. |
| Ukraine registered | True |
| NSZU reimbursed | True |
| Ukraine last verified | 2026-04-27 |
Warnings
- Severe diarrhea — early cholinergic (within 24 h) and late delayed (>24 h, can be life-threatening)
- Severe myelosuppression (febrile neutropenia, sepsis)
Notes
UGT1A1 testing strongly recommended for FOLFIRINOX (intensive dose). Loperamide schedule: 4 mg at first loose stool then 2 mg q2h (q4h overnight) until 12 h diarrhea-free; consider octreotide (100-150 mcg SC TID, escalate to 500 mcg) for refractory diarrhea. Hospitalize for Grade 3-4 diarrhea + IV fluids + broad-spectrum antibiotics if febrile. Atropine 0.25-1 mg SC/IV for acute cholinergic syndrome (premedicate in patients with prior episodes).
Used By
Regimens
REG-FOLFIRI-BEV- FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided)REG-FOLFIRINOX- FOLFIRINOXREG-FOLFOXIRI-BEV- FOLFOXIRI + BevacizumabREG-MFOLFIRINOX- mFOLFIRINOX (modified FOLFIRINOX, PRODIGE-24 protocol)