What is the recommended dosing regimen for Onyda (irinotecan)?

Onyda (Irinotecan) Dosing

I cannot provide dosing information for "Onyda" as this does not appear to be a recognized formulation of irinotecan in the available evidence. However, I can provide comprehensive dosing for irinotecan based on current guidelines and FDA labeling.

Standard Irinotecan Dosing Regimens

For Metastatic Colorectal Cancer - Combination Therapy

FOLFIRI Regimen (Recommended Standard):

• Irinotecan 180 mg/m² IV infusion over 30-90 minutes on day 1 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) 1
• Repeat every 2 weeks 1

FOLFOXIRI Regimen (For Intensive Treatment):

• Irinotecan 165 mg/m² IV infusion on day 1 1
• Combined with oxaliplatin 85 mg/m², leucovorin 400 mg/m², and 5-FU 2,400-3,200 mg/m² over 48 hours 1
• Repeat every 2 weeks 1

CapIRI Regimen:

• Irinotecan 180 mg/m² IV infusion over 30-90 minutes on day 1 1
• Combined with capecitabine 1,000 mg/m² orally twice daily on days 1-7 1
• Repeat every 2 weeks 1

mXELIRI Regimen:

• Irinotecan 200 mg/m² IV infusion over 30-90 minutes on day 1 1
• Combined with capecitabine 800 mg/m² orally twice daily on days 1-14 1
• Repeat every 3 weeks 1

For Metastatic Colorectal Cancer - Single Agent Therapy

Weekly Schedule (Regimen 1):

• Starting dose: 125 mg/m² IV infusion over 90 minutes 2
• Administered on days 1,8,15, and 22, followed by a 2-week rest period 2
• Repeat every 6 weeks 2
• Dose range: 75-150 mg/m² in 25-50 mg/m² increments based on tolerance 2

Every 3-Week Schedule (Regimen 2):

• Starting dose: 350 mg/m² IV infusion over 90 minutes 2, 3
• Administered once every 3 weeks 2
• Dose range: 250-350 mg/m² in 50 mg/m² decrements based on tolerance 2

Alternative Single-Agent Schedules:

• 125 mg/m² on days 1 and 8, repeat every 3 weeks 1
• 300-350 mg/m² on day 1, repeat every 3 weeks 1

Dose Modifications for Specific Populations

Patients with UGT1A1 Polymorphisms

• Reduce starting dose by at least one dose level for patients homozygous for UGT1A1*28 or 6 alleles, or compound heterozygous for UGT1A128 and *6 2
• This applies to both combination and single-agent regimens 2

Patients with Prior Pelvic/Abdominal Radiotherapy

• Consider reducing starting dose by one dose level 2
• For every-3-week schedule: MTD is 290 mg/m² (versus 320 mg/m² without prior radiation) 3

Patients with Elevated Bilirubin

• Reduce starting dose by one dose level for bilirubin >1.0 mg/dL 2
• Dosing cannot be recommended for bilirubin >2 mg/dL due to insufficient data 2

Patients on Enzyme-Inducing Antiepileptics

• Concurrent anticonvulsants and dexamethasone enhance drug clearance, resulting in approximately 60% lower drug exposure 4
• Consider dose escalation if toxicity is minimal, though specific recommendations are not established 4

Critical Toxicity-Based Dose Modifications

For Neutropenia:

• Grade 3 (500-999/mm³): Omit dose until ≤grade 2, then decrease 1 dose level 2
• Grade 4 (<500/mm³): Omit dose until ≤grade 2, then decrease 2 dose levels 2
• Neutropenic fever: Omit dose until resolved, then decrease 2 dose levels 2

For Diarrhea:

• Grade 2 (4-6 stools/day above baseline): Omit dose until baseline, then decrease 1 dose level 2
• Grade 3 (7-9 stools/day above baseline): Omit dose until baseline, then decrease 1 dose level 2
• Grade 4 (≥10 stools/day above baseline): Omit dose until baseline, then decrease 2 dose levels 2

Treatment Delay and Discontinuation:

• Do not begin new cycle until granulocytes ≥1,500/mm³, platelets ≥100,000/mm³, and diarrhea fully resolved 2
• Delay treatment 1-2 weeks for recovery from toxicities 2
• Consider discontinuation if patient has not recovered after 2-week delay 2

Common Pitfalls to Avoid

• Diarrhea management is critical: Strict adherence to high-dose loperamide (4 mg initially, then 2 mg every 2 hours until 12 hours diarrhea-free) reduces severe diarrhea incidence from 56% to 9% 5
• Do not use bevacizumab, cetuximab, or panitumumab with irinotecan in the adjuvant setting outside clinical trials 6
• Avoid re-challenging with irinotecan-based regimens within 12 months of progression on prior irinotecan therapy 6
• Monitor for acute cholinergic syndrome (abdominal cramps, diaphoresis, lacrimation) during or shortly after infusion 3