Yimailin Irinotecan Hydrochloride Injection

1. Indications and Usage
Metastatic Colorectal Cancer (mCRC):
Irinotecan is indicated for the treatment of patients with adenocarcinoma of the colon or rectum after failure of prior fluorouracil-based therapy.
Combination Therapy:
It is also indicated for use in combination with fluorouracil and leucovorin as first-line treatment for metastatic colorectal cancer.
2. Dosage and Administration
Route of Administration:
For Intravenous (IV) Infusion ONLY.
Warning: NOT for Intrathecal or Intramuscular injection.
Recommended Dosage:
Single Agent: 125 mg/m² administered weekly for 4 weeks, followed by a 2-week rest (every 6 weeks).
Combination (FOLFIRI): 180 mg/m² administered once every 2 weeks (30–90 minutes infusion) in combination with leucovorin and fluorouracil.
Administration Instructions:
Dilute in 5% Dextrose Injection or 0.9% Sodium Chloride Injection. Must be infused over 30–90 minutes .
3. Mechanism of Action
Topoisomerase I Inhibition:
Irinotecan is a prodrug converted in vivo to the active metabolite SN-38.
DNA Damage:
SN-38 binds to the Topoisomerase I-DNA complex, preventing the religation of single-strand DNA breaks. This results in DNA double-strand breaks during DNA replication, leading to cell death (S-phase specific) .
4. Safety and Warnings
Severe Diarrhea (Black Box Warning):
Irinotecan causes two types of diarrhea:
1. Early-Onset (Cholinergic): Occurs during or shortly after infusion. Can be prevented/treated with Atropine .
2. Delayed-Onset: Occurs >24 hours after infusion. This is dose-limiting and potentially fatal. Patients must be instructed to start antidiarrheal therapy (e.g., Loperamide) immediately upon the first loose stool and continue for at least 12 hours .
Severe Neutropenia:
Severe neutropenia is common. Patients with fever (≥38.5°C) or signs of infection require immediate evaluation and broad-spectrum antibiotics .
Pulmonary Toxicity:
Interstitial Lung Disease (ILD) has been reported. Monitor patients for dyspnea and cough.
5. Adverse Reactions
Most Common:
Gastrointestinal: Delayed diarrhea, nausea, vomiting, anorexia.
Hematologic: Neutropenia, anemia, leukopenia.
General: Alopecia (hair loss), fatigue, cholinergic syndrome (sweating, abdominal cramping).
6. Drug Interactions
CYP3A4 Substrate:
Irinotecan is metabolized by CYP3A4.
Inducers (e.g., Dexamethasone, Rifampin): May increase toxicity.
Inhibitors (e.g., Ketoconazole): May increase exposure to SN-38 and toxicity.
UGT1A1 Inhibitors:
May increase SN-38 exposure.
Anticholinergics:
May be used to treat cholinergic syndrome but should be avoided if contraindicated.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Irinotecan Hydrochloride Trihydrate.
Appearance: Clear, yellow-green solution .
Storage: Store at 20°C–25°C (68°F–77°F); protect from light.