Irinotecan (Irinotecan Hydrochloride Trihydrate)

Irinotecan is a topoisomerase I inhibitor used primarily in colorectal cancer therapy.

• Metastatic colorectal cancer: used in combination chemotherapy regimens to improve overall survival.
• Advanced colorectal adenocarcinoma: administered after first‑line treatment failure to achieve disease control.
• Colorectal cancer refractory to other agents: incorporated into salvage therapy protocols to reduce tumor progression.

• After intravenous administration, irinotecan is converted by hepatic carboxylesterases to the active metabolite SN‑38. SN‑38 binds to the DNA‑topoisomerase I complex and stabilizes it, preventing the re‑ligation of single‑strand DNA breaks generated during replication. This inhibition leads to accumulation of DNA damage, triggering apoptosis in rapidly proliferating tumor cells. The drug’s effect is selective for cells with high replication rates, which contributes to its antitumor activity.

Irinotecan is associated with a range of adverse reactions that vary in frequency and severity.

Common Side Effects

• Neutropenia: reduced white blood cell count increasing infection risk.
• Diarrhea: may be severe and require supportive care.
• Nausea: often managed with anti‑emetics.
• Fatigue: general tiredness experienced during treatment.

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophils, a medical emergency.
• Severe colitis: inflammation of the colon causing intense abdominal pain.
• Cholinergic syndrome: characterized by sweating, salivation, and muscle cramps.
• Hepatic toxicity: elevated liver enzymes indicating liver injury.

Before and during irinotecan therapy, clinicians should observe several safety measures.

• Monitor blood counts: perform regular CBC to detect neutropenia early.
• Assess liver function: evaluate hepatic enzymes before each cycle.
• Ensure adequate hydration: maintain fluid intake to lessen the severity of diarrhea.
• Avoid strong CYP3A4 inhibitors: concomitant use may increase SN‑38 exposure.
• Pregnancy: use only if potential benefit justifies risk; data are limited.
• Store at below 25°C: keep in the original container, protect from light and moisture.

Irinotecan may interact with other medicines, requiring careful management.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole): may increase SN‑38 exposure and toxicity.
• UGT1A1*28 homozygosity: genetic variant associated with heightened risk of severe neutropenia and diarrhea.
• Concurrent myelosuppressive agents: additive bone‑marrow suppression can occur.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., erythromycin): may modestly raise irinotecan exposure.
• Anticholinergic drugs: may exacerbate cholinergic syndrome symptoms.
• Warfarin: may affect INR; monitor coagulation parameters regularly.