Irinotecan Vial Preparation and Dosing
Irinotecan is supplied as a sterile, pale yellow aqueous solution at 20 mg/mL concentration and must be diluted in either 5% Dextrose Injection (preferred) or 0.9% Sodium Chloride Injection prior to intravenous infusion. 1
Vial Preparation Standards
The FDA-approved formulation contains 20 mg of irinotecan hydrochloride per milliliter, with 45 mg sorbitol and 0.9 mg lactic acid, adjusted to pH 3.5 (range 3.0-3.8). 1
Dilute the calculated dose in 5% Dextrose Injection (D5W) as the preferred diluent, or alternatively in 0.9% Sodium Chloride Injection, before administration. 1
The solution is stable as a sterile, clear, pale yellow liquid that requires dilution before the 30-90 minute intravenous infusion. 1
Standard Dosing Regimens for Metastatic Colorectal Cancer
Biweekly (Every 2 Weeks) Schedules
For FOLFIRI regimen: Administer irinotecan 180 mg/m² IV infusion over 30-90 minutes on day 1, combined with leucovorin 400 mg/m² and 5-FU (400 mg/m² bolus, then 2,400 mg/m² continuous infusion over 46-48 hours), repeated every 2 weeks. 2, 3
For FOLFOXIRI regimen: Administer irinotecan 165 mg/m² IV on day 1, combined with oxaliplatin 85 mg/m², leucovorin 400 mg/m², and 5-FU 2,400-3,200 mg/m² over 48 hours, repeated every 2 weeks. 2, 3
For CapIRI regimen: Administer irinotecan 180 mg/m² IV infusion over 30-90 minutes on day 1, combined with capecitabine 1,000 mg/m² orally twice daily on days 1-7, repeated every 2 weeks. 2, 3
Three-Weekly (Every 3 Weeks) Schedules
For mXELIRI regimen: Administer irinotecan 200 mg/m² IV infusion over 30-90 minutes on day 1, combined with capecitabine 800 mg/m² orally twice daily on days 1-14, repeated every 3 weeks. 2, 3
For single-agent therapy: Administer irinotecan 300-350 mg/m² IV infusion over 30-90 minutes on day 1, repeated every 3 weeks. 2, 3
Alternative single-agent schedule: Administer irinotecan 125 mg/m² on days 1 and 8, repeated every 3 weeks. 2, 3
Dosing for Specific Populations
For patients ≥70 years old using the once-every-3-week schedule: Reduce starting dose to 300 mg/m² due to significantly higher rates of grade 3-4 late diarrhea (40% vs 23% in younger patients, p=0.002). 1
For patients with hepatic impairment: Exercise caution as irinotecan clearance is diminished and SN-38 exposure increases proportionally to liver dysfunction severity; no specific dosing recommendations exist for bilirubin >2 mg/dL. 1
For patients with renal impairment or on dialysis: Irinotecan is not recommended, as pharmacokinetic data are insufficient and severe toxicity has been reported, including fatal outcomes in hemodialysis patients. 1, 4
Critical Safety Considerations
Monitor elderly patients (≥65 years) closely for early and late diarrhea, which occurs at significantly higher rates than in younger patients. 1
The active metabolite SN-38 is approximately 1000 times more potent than irinotecan as a topoisomerase I inhibitor but represents only 2-8% of plasma AUC; SN-38 is 95% protein-bound compared to 50% for irinotecan. 1, 5
Dose-limiting toxicities are primarily delayed diarrhea (occurring 7-10 days post-treatment) and neutropenia; high-dose loperamide effectively manages diarrhea and allows dose escalation. 5, 6
In hemodialysis patients, irinotecan is partially dialyzable but SN-38 is not, leading to accumulation and potentially fatal toxicity including grade 4 diarrhea and febrile neutropenia. 4