Irinotecan Dose Preparation from 20 mg Vials for Metastatic Colorectal Cancer
The 20 mg/mL vial formulation requires dilution prior to infusion, with the specific volume withdrawn based on the patient's body surface area and chosen regimen (125-180 mg/m² for combination therapy or 125-350 mg/m² for monotherapy). 1
Standard Dosing Regimens
Combination Therapy Options
For first-line metastatic colorectal cancer, the most commonly used regimen is FOLFIRI: irinotecan 180 mg/m² IV over 30-90 minutes on day 1, combined with leucovorin 400 mg/m² and 5-FU (400 mg/m² bolus followed by 2,400 mg/m² continuous infusion over 46-48 hours), repeated every 2 weeks. 2, 3
Alternative combination regimens include:
Weekly schedule: Irinotecan 125 mg/m² IV over 90 minutes on days 1,8,15,22 with leucovorin 20 mg/m² bolus followed by 5-FU bolus on the same days, repeated every 6 weeks 2, 1
Biweekly schedule: Irinotecan 180 mg/m² IV over 90 minutes on days 1,15,29 with leucovorin 200 mg/m² over 2 hours followed by 5-FU 400 mg/m² bolus and 600 mg/m² over 22 hours on days 1,2,15,16,29,30 1
Single-Agent Therapy Options
For second-line therapy after fluorouracil failure:
Weekly regimen: 125 mg/m² IV over 90 minutes on days 1,8,15,22, followed by a 2-week rest 1
Every 3-week regimen: 350 mg/m² IV over 90 minutes on day 1, repeated every 3 weeks 1
Vial Preparation and Dilution
Critical Preparation Steps
Irinotecan 20 mg/mL must be diluted prior to infusion using aseptic technique in 5% Dextrose Injection (preferred) or 0.9% Sodium Chloride Injection to a final concentration of 0.12-2.8 mg/mL. 1
Calculate the required volume from the 20 mg/mL vial: For a patient with BSA of 1.8 m² receiving FOLFIRI (180 mg/m²), the total dose is 324 mg, requiring 16.2 mL withdrawn from the vial(s). 1
The vial is for single-dose use only; any unused portion must be discarded. 1
Prepare the infusion solution immediately prior to use and commence infusion as soon as possible after preparation. 1
If immediate use is not possible, the diluted infusion solution may be stored for up to 24 hours at 2°C to 8°C. 1
Dose Modifications for Toxicity
UGT1A1 Genetic Considerations
*For patients homozygous for UGT1A128 or *6 alleles (*28/*28, *6/*6) or compound heterozygous (6/28), reduce the starting dose by at least one level due to 3.5-fold increased risk of severe neutropenia. 2, 4, 1
The maximum tolerated doses based on UGT1A1 genotype are:
- *1/*1 genotype: 850 mg every 3 weeks 2
- *1/*28 genotype: 700 mg every 3 weeks 2
- *28/*28 genotype: 400 mg every 3 weeks 2
Toxicity-Based Adjustments
Do not begin a new cycle until granulocyte count ≥1,500/mm³, platelet count ≥100,000/mm³, and treatment-related diarrhea is fully resolved. 1
For grade 3-4 neutropenia during treatment, reduce the dose by 25-50 mg/m² depending on severity and whether neutropenic fever occurred. 1
For grade 3-4 diarrhea, omit the dose until resolved to ≤grade 2, then reduce by 25-50 mg/m² for subsequent cycles. 1
Premedication and Supportive Care
Administer antiemetic premedication at least 30 minutes before irinotecan infusion, typically dexamethasone 10 mg with a 5-HT3 blocker (ondansetron or granisetron). 1
Consider prophylactic or therapeutic atropine 0.25-1 mg IV or subcutaneous for cholinergic symptoms (early diarrhea, abdominal cramping, diaphoresis) unless clinically contraindicated. 1
Critical Safety Considerations
Monitor the infusion site carefully to avoid extravasation; if extravasation occurs, flush with sterile water and apply ice. 1
Late-onset diarrhea (occurring >24 hours post-infusion) can be life-threatening and requires immediate treatment with loperamide, fluid and electrolyte replacement, and antibiotic therapy if fever or severe neutropenia develops. 4, 1
The combination of neutropenia and diarrhea is particularly dangerous and requires close monitoring and prompt intervention. 4
Use caution and reduced doses in patients with Gilbert syndrome or elevated serum bilirubin due to impaired UGT1A1 activity. 2