What it's for (Indications)
- Irinotecan is indicated for the treatment of metastatic carcinoma of the colon or rectum.
- It is used as a single agent or in combination with fluorouracil and leucovorin for patients whose disease has recurred or progressed following initial fluorouracil-based therapy.
- It is also used as a component of first-line therapy in combination with fluorouracil and leucovorin for patients with metastatic colorectal cancer.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | Dosage and administration vary based on the specific regimen and whether it is monotherapy or combination therapy for metastatic colorectal cancer. A common monotherapy dose is 125 mg/m² intravenous infusion over 90 minutes weekly for 4 weeks followed by a 2-week rest. For combination therapy (e.g., FOLFIRI regimen), a typical dose is 180 mg/m² intravenous infusion over 30 to 90 minutes every 2 weeks, followed by fluorouracil and leucovorin. Doses should be adjusted based on individual patient tolerance, severity of neutropenia, and diarrhea. Lower starting doses or dose adjustments are recommended for patients with UGT1A1*28 allele homozygosity or moderate hepatic impairment. Anti-diarrheal agents (e.g., loperamide) should be readily available for managing delayed diarrhea. All dosages must be individualized under the supervision of an oncologist. |
Safety & Warnings
Common Side Effects
- Common and severe side effects include: **Gastrointestinal**: Severe, delayed diarrhea (may be life-threatening), acute cholinergic syndrome (early diarrhea, abdominal cramping, rhinitis, lacrimation, salivation, miosis, diaphoresis, flushing, bradycardia), nausea, vomiting, abdominal pain, constipation, stomatitis.
- **Hematologic**: Severe myelosuppression (neutropenia, leukopenia, anemia, thrombocytopenia), which can be life-threatening and lead to febrile neutropenia.
- **Other**: Alopecia, asthenia, fever, infections, dehydration, headache, dizziness, insomnia, pulmonary toxicity (interstitial lung disease), elevated liver enzymes, skin rash.
Serious Warnings
- Black Box Warning: Irinotecan can cause severe diarrhea (delayed diarrhea) and severe myelosuppression (neutropenia), which can be life-threatening or fatal. Close monitoring of patients and appropriate management, including aggressive hydration, anti-diarrheal agents, and granulocyte-colony stimulating factors (G-CSFs) if necessary, are essential. Patients homozygous for the UGT1A1*28 allele are at increased risk for severe neutropenia and diarrhea and may require a reduced starting dose.
- Patients should be carefully monitored for severe delayed diarrhea and myelosuppression, which can be dose-limiting and potentially fatal.
- Prophylactic or early initiation of loperamide is crucial for managing delayed diarrhea.
- Patients with reduced UGT1A1 activity (e.
- g.
- , UGT1A1*28 allele homozygotes) are at increased risk for severe neutropenia and diarrhea; dose reductions may be necessary.
- Acute cholinergic syndrome should be managed with atropine.
- Monitor for signs of dehydration, electrolyte imbalance, and infections.
- Caution in patients with pre-existing hepatic impairment due to increased exposure to SN-38.
- Pulmonary toxicity, including interstitial lung disease, has been reported.
- Avoid during pregnancy and breastfeeding.
How it Works (Mechanism of Action)
Irinotecan and its active metabolite, SN-38, act by inhibiting topoisomerase I, an enzyme critical for DNA replication, transcription, and repair. By binding to the topoisomerase I-DNA complex, irinotecan and SN-38 prevent the re-ligation of the DNA strand breaks, leading to DNA damage, ultimately resulting in apoptosis and cell death.
Commercial Brands (Alternatives)
No other brands found for this formula.