Youyoli Irinotecan Hydrochloride Liposome Injection (II)

1. Indications and Usage
Metastatic Pancreatic Cancer: Treatment of adult patients with locally advanced or metastatic pancreatic adenocarcinoma who have progressed during or after gemcitabine-based therapy.
Combination Requirement: Must be used in combination with 5-fluorouracil (5-FU) and leucovorin (LV). It is not approved for monotherapy.
2. Dosage and Administration
Route of Administration: Intravenous infusion ONLY. Do not administer as an IV push or bolus.
Recommended Dosage: 70 mg/m² administered as an IV infusion over 90 minutes every 2 weeks.
UGT1A1*28 Homozygous Patients: Initial dose should be reduced to 50 mg/m².
Critical Administration Instructions:
Pre-medication: Administer dexamethasone and a 5-HT3 antagonist at least 30 minutes prior to infusion.
Order of Administration: Administer Irinotecan Liposome first, followed by LV, and then 5-FU.
Dilution: Dilute in 5% Dextrose or 0.9% Sodium Chloride to a total volume of 500 mL.
Dose Adjustments: Based on severity of Grade 3/4 adverse reactions (e.g., neutropenia, delayed diarrhea).
3. Mechanism of Action
Topoisomerase I Inhibition: Irinotecan is encapsulated in liposomal vesicles. Inside the tumor cell, it is converted to its active metabolite, SN-38.
Cytotoxicity: SN-38 binds to and stabilizes the Topoisomerase I-DNA complex, preventing re-ligation of single-strand breaks. This leads to DNA damage and cell death during the S-phase of the cell cycle.
4. Safety and Warnings
Severe Neutropenia: Monitor complete blood counts weekly. Febrile neutropenia and sepsis can be fatal.
Severe Diarrhea: Includes early-onset (cholinergic) and late-onset diarrhea. Early-onset should be managed with atropine; late-onset requires immediate and aggressive loperamide.
Interstitial Lung Disease (ILD): Discontinue if new or progressive dyspnea, cough, or fever occurs.
Embryo-Fetal Toxicity: Can cause fetal harm; effective contraception is required during treatment.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: Diarrhea, nausea, vomiting, anorexia, fatigue, neutropenia, and anemia.
Clinical Research Highlights: The NAPOLI-1 trial demonstrated that Irinotecan Liposome plus 5-FU/LV significantly improved overall survival compared to 5-FU/LV monotherapy in the second-line setting.
6. Drug Interactions
CYP3A4 and UGT1A1 Inhibitors: Strong inhibitors (e.g., ketoconazole) can increase SN-38 exposure and toxicity; avoid concomitant use where possible.
CYP3A4 Inducers: Strong inducers (e.g., rifampicin) can decrease efficacy; avoid concomitant use.
Anticholinergics: May be required to manage early-onset diarrhea (cholinergic crisis).
7. Pharmaceutical Information
Chemical Composition: Active Ingredient: Irinotecan Hydrochloride (encapsulated in liposomes).
Appearance: Sterile, opaque, yellowish liposomal dispersion.
Packaging: Single-dose vials (10 mL containing 43 mg Irinotecan).
Storage: Store at 2°C to 8°C; do not freeze or shake.