Irinotecan (Irinotecan Hydrochloride Trihydrate)

• Irinotecan is a topoisomerase I inhibitor used in oncology for colorectal cancer management.
• Metastatic colorectal cancer: improves overall survival when combined with fluoropyrimidines and leucovorin.
• First‑line colorectal cancer therapy: administered as part of the FOLFIRI regimen for patients progressing after oxaliplatin‑based treatment.
• Second‑line colorectal cancer therapy: used after failure of initial chemotherapy to provide disease control.

• Irinotecan is converted intracellularly to its active metabolite SN‑38, which binds to the DNA‑topoisomerase I complex and stabilizes it, preventing the re‑ligation of single‑strand DNA breaks during replication. This inhibition leads to accumulation of DNA damage, triggering apoptosis in rapidly dividing tumor cells.

Irinotecan may cause a range of adverse reactions that vary in frequency and severity.

Common Side Effects

• Neutropenia: reduced white blood cell count increasing infection risk.
• Diarrhea: often severe and may require supportive care.
• Nausea and vomiting: typical chemotherapy‑related symptoms.
• Alopecia: temporary hair loss.
• Fatigue: generalized tiredness during treatment.
• Abdominal pain: discomfort in the stomach area.

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophil count requiring urgent medical attention.
• Severe colitis: life‑threatening inflammation of the colon.
• Hepatic toxicity: elevated liver enzymes indicating liver injury.
• Allergic reactions: rash, bronchospasm, or anaphylaxis.
• Tumor lysis syndrome: rapid tumor cell breakdown causing metabolic disturbances.
• Severe mucositis: painful inflammation of the mouth and gastrointestinal lining.

• Before initiating Irinotecan therapy, clinicians should assess patient-specific factors and monitor for potential complications.
• Monitor blood counts: perform regular complete blood counts to detect neutropenia.
• Assess liver function: evaluate hepatic enzymes as Irinotecan is metabolized hepatically.
• Evaluate bowel status: screen for pre‑existing diarrhea or intestinal obstruction.
• Adjust dose in renal impairment: consider reduced dosing for patients with decreased kidney function.
• Avoid use in pregnancy: Irinotecan is classified as Category D and should not be given to pregnant women.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Irinotecan can interact with other medicines, altering its efficacy or safety profile.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin): markedly reduce Irinotecan exposure.
• UGT1A1 inhibitors (e.g., atazanavir): increase SN‑38 levels and toxicity.
• Concurrent myelosuppressive agents: heighten risk of severe neutropenia.
• Anticholinergic drugs: may exacerbate diarrhea.
• High‑dose aspirin or NSAIDs: increase risk of gastrointestinal bleeding.

Moderate Interactions (Monitor Closely)

• Other hepatically metabolized drugs: may compete for metabolic pathways.
• Anticoagulants (e.g., warfarin): monitor coagulation parameters.
• Proton‑pump inhibitors: potential effect on drug absorption.
• Herbal supplements affecting liver enzymes: assess for possible interaction.
• Vaccines: consider timing to avoid overlapping immunosuppression.