Irinotecan Cell Pharm (Irinotecan)

Irinotecan is indicated for colorectal cancer and related solid tumours, acting on the topoisomerase I pathway.

• Metastatic colorectal cancer: improves overall survival when used in combination chemotherapy regimens.
• Adjuvant treatment of colorectal cancer: reduces risk of disease recurrence after surgical resection.
• Other solid tumours (clinical judgment): may be incorporated into protocols for selected gastrointestinal or pancreatic cancers.

• Irinotecan is a pro‑drug that is converted in vivo to the active metabolite SN‑38. SN‑38 binds to the DNA‑topoisomerase I complex, preventing relegation of single‑strand DNA breaks during replication. Accumulation of unrepaired DNA breaks triggers apoptosis in rapidly dividing tumour cells, particularly those of colorectal origin.

Irinotecan may cause a range of adverse reactions, which are categorised by frequency and severity.

Common Side Effects

• Neutropenia: reduced white‑blood‑cell count increasing infection risk.
• Diarrhoea: often delayed and may be severe.
• Nausea and vomiting: typical chemotherapy‑related symptoms.
• Alopecia: temporary hair loss.
• Fatigue: generalized tiredness during treatment.
• Abdominal cramping: related to gastrointestinal irritation.

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophil count requiring urgent care.
• Severe diarrhoea (colitis): can lead to dehydration and electrolyte imbalance.
• Cholinergic syndrome: sweating, lacrimation, bradycardia, and bronchospasm.
• Hypersensitivity reactions: rash, urticaria, or anaphylaxis.
• Hepatic dysfunction: elevated transaminases or bilirubin.
• Severe electrolyte disturbances: especially hypokalemia and hypomagnesemia.

Before initiating therapy, clinicians should assess patient‑specific risk factors and monitor for toxicity.

• Monitor blood counts: perform regular complete blood counts to detect neutropenia.
• Assess liver function: evaluate hepatic enzymes and bilirubin prior to each cycle.
• Evaluate gastrointestinal status: avoid use in patients with active bowel obstruction.
• Pregnancy risk: contraindicated in pregnancy (Category D) due to fetal toxicity.
• Dose adjustment: consider reduced dosing in patients with moderate hepatic impairment.
• Store at ambient temperature: keep in original container, protect from light and moisture.

Irinotecan interacts with several drug classes that can alter its metabolism or increase toxicity.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): raise SN‑38 levels and risk of severe neutropenia.
• UGT1A1 inhibitors (e.g., atazanavir, indinavir): impair SN‑38 glucuronidation, increasing toxicity.
• Concurrent myelosuppressive agents: additive bone‑marrow suppression.

Moderate Interactions (Monitor Closely)

• Anticoagulants (e.g., warfarin): enhanced bleeding risk due to mucosal injury.
• Antidiarrhoeal agents (e.g., loperamide): may mask early signs of severe diarrhoea.
• Electrolyte‑altering drugs (e.g., diuretics): monitor for hypokalaemia and hypomagnesaemia.