What is Irinotecan? Irinotecan (brand name Camptosar) is an intravenous chemotherapy drug used primarily to treat colorectal cancer. It works by blocking an enzyme called topoisomerase I, which cancer cells need to copy their DNA. Irinotecan is most commonly given as part of the FOLFIRI regimen (with 5-FU and leucovorin) for metastatic colorectal cancer. It can cause severe diarrhea, which requires immediate treatment.
Drug Class
Topoisomerase I Inhibitor
Route
IV Infusion
Main Use
Colorectal Cancer
FDA Approved
1996
How Irinotecan Works
Irinotecan is a topoisomerase I inhibitor, specifically targeting an enzyme that cancer cells need to divide and grow:
The Mechanism
- Prodrug conversion: Irinotecan itself is inactive. It's converted in the body to the active metabolite SN-38, which is 100-1000 times more potent than irinotecan
- Topoisomerase I inhibition: SN-38 binds to the topoisomerase I-DNA complex, preventing the enzyme from re-sealing DNA breaks
- DNA damage: When DNA replication machinery encounters these stabilized breaks, it causes irreversible double-strand DNA breaks
- Cell death: The accumulated DNA damage triggers cell death (apoptosis), particularly in rapidly dividing cancer cells
Why Topoisomerase I Matters: During DNA replication, the DNA double helix must unwind. Topoisomerase I cuts one strand of DNA to relieve tension, allows the strand to rotate, then reseals the break. Cancer cells, which divide rapidly, depend heavily on this enzyme. By preventing the resealing step, irinotecan causes lethal DNA damage specifically in dividing cells.
The Role of UGT1A1
Understanding your UGT1A1 genetic status is crucial for safe irinotecan treatment:
UGT1A1 Testing:
- What it is: UGT1A1 is the enzyme that inactivates SN-38 (the active form of irinotecan)
- Genetic variants: About 10% of people have the UGT1A1*28/*28 variant (homozygous), meaning they have reduced enzyme activity
- Clinical impact: Patients with UGT1A1*28/*28 have higher SN-38 levels → dramatically increased risk of severe diarrhea and neutropenia
- Dose adjustment: Patients with UGT1A1*28/*28 should start with reduced irinotecan dose (especially if starting dose ≥180 mg/m²)
- Testing: FDA recommends considering UGT1A1 testing before starting irinotecan (simple blood test)
| UGT1A1 Genotype | Frequency | Enzyme Activity | Dosing Recommendation |
|---|---|---|---|
| *1/*1 (normal) | ~50-60% | Normal | Standard dose |
| *1/*28 (heterozygous) | ~30-40% | Intermediate | Standard dose, monitor closely |
| *28/*28 (homozygous) | ~10% | Reduced (~30%) | Reduce starting dose by 1 level (~30%) |
What is Irinotecan Used For?
FDA-Approved Uses
- Metastatic colorectal cancer - first-line: Combined with 5-FU and leucovorin (FOLFIRI regimen)
- Metastatic colorectal cancer - second-line: As a single agent after 5-FU-based therapy
Common Off-Label Uses
- Pancreatic cancer: FOLFIRINOX regimen (5-FU, leucovorin, irinotecan, oxaliplatin) - highly effective but toxic
- Gastric/gastroesophageal cancer
- Small cell lung cancer (second-line)
- Cervical cancer (recurrent)
- Ovarian cancer (recurrent)
- Brain tumors (pediatric use, especially medulloblastoma)
How is Irinotecan Given?
FOLFIRI Regimen (Most Common)
The standard first-line regimen for metastatic colorectal cancer:
Standard FOLFIRI Protocol (14-day cycle):
- Day 1:
- Irinotecan 180 mg/m² IV over 90 minutes
- Leucovorin 400 mg/m² IV over 2 hours (given simultaneously with irinotecan or immediately after)
- 5-FU 400 mg/m² IV bolus (immediately after leucovorin)
- 5-FU 2,400 mg/m² IV continuous infusion over 46-48 hours
- Days 2-14: Rest period
- Cycle repeats: Every 14 days
FOLFIRINOX Regimen (for Pancreatic Cancer)
More intensive regimen, requires good performance status:
FOLFIRINOX Protocol (14-day cycle):
- Day 1:
- Oxaliplatin 85 mg/m² IV over 2 hours
- Leucovorin 400 mg/m² IV over 2 hours
- Irinotecan 180 mg/m² IV over 90 minutes
- 5-FU 400 mg/m² IV bolus
- 5-FU 2,400 mg/m² IV continuous infusion over 46 hours
- Note: Very effective but more toxic than FOLFIRI. Often used with modified doses (e.g., mFOLFIRINOX with reduced or no 5-FU bolus)
Single-Agent Irinotecan
Used when patients can't tolerate combination therapy:
- Weekly schedule: 125 mg/m² IV over 90 minutes, weekly for 4 weeks, then 2-week rest (6-week cycle)
- Every-3-week schedule: 350 mg/m² IV over 90 minutes every 3 weeks
Irinotecan + Targeted Therapy
FOLFIRI is commonly combined with biologic agents:
- FOLFIRI + Bevacizumab (Avastin): Anti-VEGF antibody, improves outcomes in metastatic colorectal cancer
- FOLFIRI + Cetuximab (Erbitux): Anti-EGFR antibody, for RAS wild-type tumors only
- FOLFIRI + Panitumumab (Vectibix): Anti-EGFR antibody, for RAS wild-type tumors
Premedication
Before Each Irinotecan Infusion:
- Anti-nausea medications: Ondansetron 16-24 mg IV or palonosetron 0.25 mg IV
- Dexamethasone: 8-20 mg IV (steroid, helps prevent nausea)
- Optional: Olanzapine 10 mg PO (very effective for delayed nausea)
- Atropine: Available at bedside for acute cholinergic syndrome (see below)
Side Effects and Management
TWO TYPES OF DIARRHEA - DIFFERENT MANAGEMENT:
Irinotecan causes two distinct types of diarrhea with DIFFERENT treatments. It is CRITICAL to know the difference:
- EARLY diarrhea: During or within 24 hours of infusion (cholinergic syndrome)
- LATE diarrhea: More than 24 hours after infusion (can be life-threatening)
1. EARLY Diarrhea (Acute Cholinergic Syndrome)
- Timing: During infusion or within 24 hours
- Incidence: 40-50% of patients
- Mechanism: Irinotecan increases acetylcholine, causing cholinergic symptoms
- Symptoms:
- Diarrhea (watery, cramping)
- Abdominal cramping
- Sweating, flushing
- Increased salivation
- Rhinitis (runny nose)
- Lacrimation (tearing)
- Miosis (small pupils)
- Rarely: bradycardia (slow heart rate)
- Management:
- Atropine 0.25-1 mg IV or SC - rapidly reverses symptoms
- Usually self-limited, resolves within hours
- Prophylactic atropine for subsequent doses if severe symptoms
2. LATE Diarrhea (The Most Serious Side Effect)
MEDICAL EMERGENCY - Can Be Life-Threatening!
Late diarrhea from irinotecan can cause severe dehydration, electrolyte imbalance, and death if not treated aggressively.
- Timing: More than 24 hours after infusion (typically 3-10 days after treatment)
- Incidence: 60-80% experience some diarrhea; 20-30% experience severe (grade 3-4) diarrhea
- Risk factors: UGT1A1*28/*28, prior pelvic radiation, poor performance status, elderly age, female gender
- Mechanism: SN-38 excreted in bile → damages intestinal lining → severe diarrhea
HIGH-DOSE LOPERAMIDE PROTOCOL (CRITICAL!):
At the FIRST sign of late diarrhea (loose/watery stool more than 24 hours after treatment):
- Initial dose: Loperamide (Imodium) 4 mg (2 tablets) immediately
- Maintenance: 2 mg (1 tablet) every 2 hours around the clock, even at night
- Continue: Until diarrhea-free for 12 hours
- Maximum: Up to 24 mg per day (12 tablets)
- DO NOT WAIT: Start at first loose stool - early treatment is critical
- Hydration: Drink plenty of fluids. Oral rehydration solution (Pedialyte) recommended
If diarrhea is not controlled within 24 hours or is severe (≥7 stools/day), GO TO THE EMERGENCY ROOM or call oncologist immediately.
Additional Measures for Severe Diarrhea
- Hospitalization: May be needed for IV fluids, electrolyte replacement
- Antibiotics: Ciprofloxacin 500 mg twice daily (intestinal bacteria convert irinotecan metabolites to more toxic forms; antibiotics may help)
- Octreotide: 100-150 mcg SC three times daily for refractory diarrhea
- Budesonide: Oral corticosteroid, may reduce intestinal inflammation
- Dietary modification: BRAT diet (bananas, rice, applesauce, toast), avoid dairy, high-fat foods, high-fiber foods
Diarrhea Grading and Dose Modifications
| Grade | Severity | Management | Dose Modification |
|---|---|---|---|
| 1 | Increase of <4 stools/day | High-dose loperamide | None |
| 2 | Increase of 4-6 stools/day | High-dose loperamide, fluids | Consider dose reduction |
| 3 | Increase of ≥7 stools/day, IV fluids needed | Hospitalization, IV fluids, antibiotics | Reduce dose by 20-25% |
| 4 | Life-threatening, hemodynamic collapse | ICU care, aggressive support | Discontinue irinotecan |
3. Bone Marrow Suppression (Myelosuppression)
- Neutropenia: Most common, occurs in 15-30% (severe in 5-15%)
- Timing: Nadir (lowest point) typically days 7-10
- Risk factors: UGT1A1*28/*28, prior chemotherapy, baseline low counts
- Monitoring: CBC before each treatment cycle
- Management:
- Dose reduction if severe (ANC <1,000)
- Growth factors (G-CSF, pegfilgrastim) if febrile neutropenia or recurrent severe neutropenia
- Antibiotics for fever ≥100.4°F with neutropenia
4. Nausea and Vomiting
- Incidence: 60-80% experience some nausea; vomiting in 30-50%
- Timing: Can be acute (during/immediately after) or delayed (2-5 days after)
- Prevention:
- Aggressive pre-medication (ondansetron or palonosetron + dexamethasone)
- Olanzapine 10 mg daily for days 1-4 (very effective for delayed nausea)
- NK-1 antagonist (aprepitant/Emend) for FOLFIRINOX (more emetogenic)
5. Hair Loss (Alopecia)
- Incidence: 40-60%, usually moderate hair thinning, sometimes complete
- Timing: Usually starts 2-3 weeks after first dose
- Recovery: Hair regrows after treatment ends
- Note: More significant with combination regimens (FOLFIRI, FOLFIRINOX)
6. Other Common Side Effects
- Fatigue (60-80%): Cumulative, can be significant. Rest as needed, light exercise helpful
- Mucositis/stomatitis (15-30%): Mouth sores. Use soft toothbrush, salt/baking soda rinses, avoid alcohol-based mouthwashes
- Anorexia/weight loss (30-40%): Common. Small, frequent, high-calorie meals. Nutrition support if severe
- Abdominal pain/cramping (50-60%): Often related to diarrhea. Antispasmodics may help
- Fever (45%): Can occur without infection as a drug reaction. Call doctor for fever ≥100.4°F
7. Rare but Serious Side Effects
- Interstitial pneumonitis: Rare (<2%), can be fatal. Report new/worsening cough, shortness of breath
- Thromboembolic events: Blood clots (DVT, PE). Report leg swelling, chest pain, shortness of breath
- Colitis/bowel perforation: Rare. Severe abdominal pain requires immediate evaluation
- Renal impairment: From severe dehydration due to diarrhea
Monitoring During Treatment
Required Blood Tests
| Test | Frequency | Purpose |
|---|---|---|
| Complete blood count (CBC) | Before each cycle | Monitor bone marrow function |
| Comprehensive metabolic panel | Before each cycle | Liver/kidney function, electrolytes |
| UGT1A1 genetic testing | Once before starting (recommended) | Predict toxicity risk |
| CEA (carcinoembryonic antigen) | Before treatment, then periodically | Monitor tumor response (colorectal cancer) |
Imaging During Treatment
- CT scans: Every 8-12 weeks (every 4-6 cycles) to assess tumor response
- Response assessment: RECIST criteria used to determine complete response, partial response, stable disease, or progression
How Well Does Irinotecan Work?
Metastatic Colorectal Cancer - First-Line Treatment
FOLFIRI is one of the two standard first-line regimens (the other being FOLFOX):
FOLFIRI Outcomes in Metastatic Colorectal Cancer:
- Response rate: 40-50% (tumors shrink)
- Median progression-free survival: 8-10 months
- Median overall survival: 20-24 months
- With bevacizumab: Median survival extends to ~24-30 months
- With anti-EGFR (RAS wild-type): Median survival ~28-30+ months
FOLFIRI vs. FOLFOX
These two regimens are equally effective for first-line treatment:
- Efficacy: Equivalent overall survival and response rates
- Side effect profiles differ:
- FOLFIRI: More diarrhea
- FOLFOX: More peripheral neuropathy
- Choice factors: Patient preference, comorbidities, prior neuropathy
- Sequential use: Many patients receive FOLFIRI first-line, then FOLFOX at progression (or vice versa)
Pancreatic Cancer - FOLFIRINOX
FOLFIRINOX for Metastatic Pancreatic Cancer:
- Landmark trial (2011): FOLFIRINOX vs. gemcitabine
- Median survival: 11.1 months vs. 6.8 months (gemcitabine alone)
- 1-year survival: 48% vs. 21%
- Response rate: 32% vs. 9%
- Caveat: More toxic, requires good performance status (ECOG 0-1), age typically <75
How Long is Treatment?
Metastatic Disease
- Typical duration: Continue until disease progression or unacceptable toxicity
- Average: Most patients receive 6-12 cycles (3-6 months) before progression
- Maintenance therapy: Some oncologists use "maintenance" approach (stop irinotecan after 4-6 months, continue 5-FU/leucovorin or bevacizumab alone to reduce toxicity)
- Long-term responders: Some patients with excellent response continue for 12-18+ months
Adjuvant Setting (After Surgery)
- Not standard: FOLFIRI is NOT standard adjuvant therapy for colon cancer (FOLFOX or CAPOX are preferred)
- Duration if used: 6 months (12 cycles) is typical adjuvant duration
Drug Interactions and Precautions
Important Drug Interactions
- Strong CYP3A4 inhibitors: Ketoconazole, clarithromycin, ritonavir → may increase irinotecan levels → increased toxicity. Avoid if possible
- Strong CYP3A4 inducers: Rifampin, phenytoin, St. John's Wort → may decrease irinotecan efficacy. Avoid
- Other myelosuppressive drugs: Increased bone marrow toxicity
- Live vaccines: AVOID (e.g., MMR, varicella, yellow fever). Inactivated vaccines okay but may be less effective
Special Populations
- Pregnancy: Category D - can cause fetal harm. Effective contraception required during treatment and for 6 months after (both men and women)
- Breastfeeding: Do not breastfeed during treatment
- Elderly patients: Increased risk of severe diarrhea. Consider dose reduction or more intensive monitoring
- Liver disease: Dose reduction recommended for elevated bilirubin. Do not use if bilirubin >2 mg/dL
- Kidney disease: Use with caution; not studied extensively in severe renal impairment
- Prior pelvic radiation: Significantly increased risk of severe diarrhea. Consider dose reduction
Cost and Insurance Coverage
Medication Cost
- Generic irinotecan: $1,500-3,000 per dose (varies widely by dose and pharmacy)
- Per cycle cost (FOLFIRI): ~$3,000-6,000 for drugs alone (not including infusion/clinic fees)
- Total treatment cost: $20,000-50,000+ for several months of treatment
- Liposomal irinotecan (Onivyde): Much more expensive ($10,000-15,000 per dose), used for pancreatic cancer
Insurance Coverage
- Coverage: Generally well-covered for FDA-approved indications (colorectal cancer)
- Prior authorization: Usually required for off-label uses
- Patient responsibility: Varies by plan; can be several hundred to several thousand dollars per treatment
Financial Assistance
- Patient assistance programs: Available through various pharmaceutical manufacturers and foundations
- CancerCare Co-Payment Assistance: 1-866-552-6729
- Patient Advocate Foundation: 1-800-532-5274
- Hospital financial counseling: Most cancer centers have financial counselors to help navigate costs
Alternatives and Comparisons
Other First-Line Options for Metastatic Colorectal Cancer
- FOLFOX: Oxaliplatin + 5-FU + leucovorin. Equally effective, different side effect profile (neuropathy instead of diarrhea)
- CAPOX: Capecitabine + oxaliplatin. Oral alternative to FOLFOX. Slightly less effective but more convenient
- FOLFOXIRI: All three drugs (5-FU, oxaliplatin, irinotecan). More effective but much more toxic. For fit patients with high disease burden
Second-Line Options After Irinotecan Failure
- Regorafenib (Stivarga): Oral multi-kinase inhibitor
- TAS-102 (Lonsurf): Oral chemotherapy
- Anti-EGFR antibodies: If not used first-line and RAS wild-type
Recent Advances and Ongoing Research
Liposomal Irinotecan (Onivyde)
- Formulation: Irinotecan encapsulated in liposomes (tiny fat bubbles)
- Benefits: Longer circulation time, higher tumor concentrations, potentially less toxicity
- FDA approval: For metastatic pancreatic cancer after gemcitabine failure (combined with 5-FU/leucovorin)
- Current research: Being studied for colorectal cancer and other GI malignancies
Biomarker-Guided Dosing
- UGT1A1-guided dosing: Ongoing studies to optimize doses based on genetic testing
- Therapeutic drug monitoring: Measuring SN-38 levels to personalize dosing
Novel Combinations
- Irinotecan + immunotherapy: Checkpoint inhibitors being tested with chemotherapy for MSI-high and other tumors
- Irinotecan + novel targeted agents: Combination with newer targeted therapies under investigation
Frequently Asked Questions
Q: What's the difference between early and late diarrhea, and why does it matter?
A: This is THE most important thing to understand about irinotecan. EARLY diarrhea happens during or within 24 hours of infusion, is part of cholinergic syndrome (sweating, cramping, runny nose), and is treated with ATROPINE. LATE diarrhea happens more than 24 hours after infusion (usually 3-10 days later), can be severe and life-threatening, and is treated with HIGH-DOSE LOPERAMIDE. Late diarrhea is the most serious side effect and requires immediate aggressive treatment. Never confuse the two - they need different treatments.
Q: Should I get UGT1A1 genetic testing before starting irinotecan?
A: The FDA recommends considering UGT1A1 testing, especially if you'll receive high doses (≥180 mg/m²). About 10% of people have the UGT1A1*28/*28 variant, which dramatically increases risk of severe diarrhea and neutropenia. If you have this variant, your oncologist will likely start with a reduced dose. However, testing is not absolutely required - many oncologists don't routinely test and instead monitor closely and adjust doses based on tolerance. Discuss with your oncologist whether testing makes sense for you.
Q: How quickly should I start loperamide if I get diarrhea?
A: At the FIRST loose or watery stool more than 24 hours after treatment, start the high-dose loperamide protocol immediately: 4 mg (2 tablets) right away, then 2 mg every 2 hours around the clock until diarrhea-free for 12 hours. DO NOT WAIT to see if it gets worse. Early aggressive treatment is critical to prevent severe, potentially life-threatening diarrhea. Keep loperamide with you at all times during the week after treatment. If not controlled within 24 hours or if severe (≥7 stools/day), contact your oncologist or go to the ER.
Q: Is FOLFIRI or FOLFOX better for metastatic colorectal cancer?
A: They're equally effective - same response rates, progression-free survival, and overall survival. The choice is based on side effect profiles and patient factors: FOLFIRI causes more diarrhea but no neuropathy; FOLFOX causes peripheral neuropathy (especially cold sensitivity) but less diarrhea. If you have pre-existing neuropathy, FOLFIRI may be better. If you have inflammatory bowel disease or prior pelvic radiation, FOLFOX may be better. Many patients eventually receive both - one first-line, the other at progression.
Q: Why do I get sweating and cramping during the irinotecan infusion?
A: This is acute cholinergic syndrome, caused by increased acetylcholine levels during the infusion. Symptoms include diarrhea, abdominal cramping, sweating, runny nose, tearing, and sometimes slow heart rate. It happens in 40-50% of patients. If severe, atropine 0.25-1 mg IV immediately reverses symptoms. Tell your infusion nurse if you experience these symptoms - they can give atropine. For subsequent infusions, you may receive prophylactic atropine before irinotecan to prevent symptoms.
Q: Can I take Imodium before treatment to prevent diarrhea?
A: No, do NOT take loperamide prophylactically (before diarrhea starts). Taking loperamide before late diarrhea occurs can worsen outcomes by slowing intestinal transit and prolonging exposure to toxic metabolites. Start high-dose loperamide only AFTER the first loose stool (more than 24 hours post-treatment). The exception is if you experience early cholinergic diarrhea during infusion - that's treated with atropine, not loperamide.
Q: Will my hair fall out with irinotecan?
A: Hair thinning or loss occurs in 40-60% of patients on FOLFIRI. It's usually moderate thinning rather than complete baldness, though some patients do lose most/all hair. Hair loss typically starts 2-3 weeks after the first treatment and is cumulative. With FOLFIRINOX (adding oxaliplatin), hair loss is often more significant. The good news is hair regrows after treatment ends. Many patients get a short haircut before starting or wear hats/scarves during treatment.
Q: What foods should I eat or avoid during irinotecan treatment?
A: During the days after treatment (when at risk for late diarrhea), follow a low-residue diet: white rice, white bread, bananas, applesauce, boiled chicken, eggs, well-cooked vegetables without skins. AVOID: dairy products (lactose intolerance common during treatment), high-fiber foods (raw vegetables, whole grains, beans), high-fat/greasy foods, caffeine, alcohol, spicy foods. If diarrhea occurs, switch to BRAT diet (bananas, rice, applesauce, toast) and drink plenty of fluids including oral rehydration solution (Pedialyte).
Q: How long will I be on FOLFIRI?
A: For metastatic colorectal cancer, treatment continues until disease progression or unacceptable toxicity. The average is 6-12 cycles (3-6 months), though some patients with excellent response and good tolerance continue longer. Some oncologists use "maintenance" strategy - stop irinotecan after 4-6 months, continue 5-FU/leucovorin ± bevacizumab to reduce cumulative toxicity while maintaining disease control. This is an individualized decision based on response, side effects, and your preferences.
Q: I had severe diarrhea with my last cycle. Will my dose be reduced?
A: Yes, almost certainly. Grade 3-4 diarrhea (≥7 stools/day or requiring hospitalization) typically results in a 20-25% dose reduction for subsequent cycles. Your oncologist may also check UGT1A1 status if not already done. Dose reduction doesn't necessarily mean less effectiveness - it's about finding the highest dose you can tolerate safely. Some patients do very well on reduced doses with much better quality of life and fewer complications.
Living with Irinotecan Treatment
Practical Tips for Treatment Days
- Bring entertainment: FOLFIRI infusion takes 4-5 hours. Bring books, tablet, headphones
- Stay hydrated: Drink plenty of water before and after treatment
- Dress comfortably: Layers are good (infusion rooms can be cold)
- Arrange transportation: You may feel tired; having someone drive you is helpful
- Pump education: If getting 46-hour 5-FU infusion, ensure you understand pump operation and have emergency numbers
Managing Life Between Treatments
- Keep loperamide handy: Always have it available days 2-10 after treatment
- Monitor stools: Count and note consistency each day during high-risk period
- Stay near bathroom: Plan activities accordingly during days 3-7 (peak diarrhea risk)
- Hydration: Drink 8-10 glasses of water daily, more if diarrhea occurs
- Gentle exercise: Light walking helpful for energy and mood, but don't overdo it
When to Call Your Doctor
Contact your oncology team immediately for:
- Diarrhea ≥7 stools/day or not controlled by loperamide within 24 hours
- Severe abdominal pain
- Fever ≥100.4°F (38°C)
- Signs of dehydration (dizziness, decreased urination, very dark urine, rapid heartbeat)
- Blood in stool (beyond minor streaking)
- Persistent vomiting despite anti-nausea medications
- Unusual bleeding or bruising
- Shortness of breath, chest pain, leg swelling
Support Resources
- Colorectal Cancer Alliance: 877-422-2030, www.ccalliance.org
- Fight Colorectal Cancer: www.fightcolorectalcancer.org
- CancerCare: Free counseling and support, 800-813-4673
- American Cancer Society: 24/7 support, 1-800-227-2345
- Colontown (online community): Private Facebook groups for colorectal cancer patients
Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Every patient's situation is unique. Always consult your oncologist and healthcare team about your specific condition, treatment plan, and any questions or concerns you have. Irinotecan-induced diarrhea can be life-threatening if not managed properly - follow your treatment team's instructions carefully and seek immediate medical attention for severe symptoms. If you have a medical emergency, call 911 or go to the nearest emergency room immediately.
Sources: This guide is based on FDA prescribing information, National Comprehensive Cancer Network (NCCN) guidelines for colon, rectal, and pancreatic cancers, landmark clinical trials (FOLFIRI development, FOLFIRINOX trial), Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for UGT1A1 testing, peer-reviewed medical literature on irinotecan toxicity management, and clinical practice guidelines from major cancer centers. Content reviewed for medical accuracy and updated to reflect current standards of care as of 2025.