Liposomal irinotecan
Vue déterministe de l'entité source de la LJAM. L'autorité clinique demeure avec les ID de la source cités et l'état d'approbation de l ́examinateur.
| ID | DRUG-LIPOSOMAL-IRINOTECAN |
|---|---|
| Type | Médicament |
| Alias | MM-398OnivydePEP02IRI-nationauxnanoliposomal irinotecanЛіпосомальний іринотекан |
| État | examiné 2026-05-08 |
| Maladies | DIS-PDAC |
| Sources | SRC-ESMO-PANCREATIC-2024 SRC-NAPOLI-3-WAINBERG-2024 SRC-NCCN-PANCREATIC-2025 |
Faits sur les drogues
| Catégorie | Topoisomerase I inhibitor (PEGylated liposomal nanoparticle formulation of irinotecan) |
|---|---|
| Mécanisme | Nanoliposomal (PEGylated) formulation of irinotecan that prolongs circulation time and enhances tumor accumulation via the enhanced permeability and retention (EPR) effect, increasing intra-tumoral conversion 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 glucuronidation by UGT1A1 to inactive SN-38G is the main inactivation pathway; UGT1A1*28 homozygotes (Gilbert-syndrome variant) and *6 carriers have impaired clearance and increased risk of severe neutropenia and diarrhea — starting-dose reduction recommended. Compared with conventional irinotecan, the liposomal carrier delivers higher and more sustained intra-tumoral SN-38 exposure at lower peak plasma drug concentrations. |
| Dose typique | NALIRIFOX (1L mPDAC, NAPOLI-3): 50 mg/m² (free base, equivalent to ~60 mg/m² salt) IV over 90 min day 1 every 14 d, with oxaliplatin 60 mg/m² + leucovorin 400 mg/m² + 5-FU 2400 mg/m² CIV over 46 h. 2L mPDAC (NAPOLI-1, with 5-FU/LV): 70 mg/m² (free base, equivalent to ~80 mg/m² salt) IV over 90 min day 1 every 14 d. UGT1A1 *28/*28 or *6/*6: reduce starting dose ~25-30% (e.g. NAPOLI-1 schedule → 50 mg/m² free base; NALIRIFOX schedule → 40 mg/m² free base starting dose, escalate to 50 mg/m² if tolerated). Bilirubin >2× ULN: do not initiate — relieve biliary obstruction first. |
| Ukraine enregistrée | Faux |
| NSZU remboursé | Faux |
| Ukraine vérifiée pour la dernière fois | 2026-05-08 |
Avertissements
- Diarrhée sévère : cholinergique précoce (dans les 24 h) et retardée tardivement (> 24 h, peut mettre en danger la vie)
- Neutropénie sévère et mettant en danger le pronostic vital (neutropénia fébrile, sepsis)
Notes
ONIVYDE (liposomal irinotecan) is FDA-approved for two PDAC indications: (1) 1L mPDAC in combination with oxaliplatin + 5-FU + leucovorin (NALIRIFOX regimen) based on NAPOLI-3 (Wainberg, Lancet 2023; FDA approval 2024); (2) 2L mPDAC after gemcitabine-based 1L therapy in combination with 5-FU + leucovorin based on NAPOLI-1 (Wang-Gillam, Lancet 2016; FDA approval 2015). Dose is expressed in free-base equivalents per FDA label — the salt-equivalent conversion (free base × ~1.15) is found in older literature and may cause confusion; NAPOLI-3 used 50 mg/m² free base (NALIRIFOX), NAPOLI-1 used 70 mg/m² free base (2L). Liposomal formulation is NOT interchangeable with conventional irinotecan — different pharmacokinetics, different approved indications, distinct dosing. UGT1A1 testing strongly recommended before initiation; *28/*28 homozygotes need starting-dose reduction. Atropine 0.25-1 mg SC/IV for acute cholinergic syndrome (within 30 min of infusion). Loperamide schedule for late diarrhea: 4 mg at first loose stool then 2 mg q2h until 12 h diarrhea-free. ONIVYDE not registered in Ukraine — significant access barrier.
Utilisé par
Protocole thérapeutique
REG-NALIRIFOX- NALIRIFOX