Irinotecan Accord (Irinotecan Hydrochloride Trihydrate)

• Irinotecan is a topoisomerase I inhibitor used in the treatment of colorectal and certain lung cancers.
• Metastatic colorectal cancer: used in combination regimens to inhibit tumor growth and improve response rates.
• Small cell lung cancer: employed as part of multi‑agent chemotherapy to achieve disease control.
• Adjuvant colon cancer therapy: administered after surgery to reduce recurrence risk in selected patients.

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

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: often severe and may require antidiarrheal therapy.
• Nausea and vomiting: typical chemotherapy‑related gastrointestinal upset.
• Alopecia: hair loss that is usually reversible.
• Fatigue: persistent tiredness affecting daily activities.
• Anemia: decreased red blood cell count causing weakness.

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophils requiring urgent care.
• Severe colitis: life‑threatening inflammation of the colon.
• Hypersensitivity reactions: rash, bronchospasm, or anaphylaxis.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis.
• Hepatic dysfunction: elevated liver enzymes or jaundice.
• Tumor lysis syndrome: rapid tumor cell breakdown causing metabolic disturbances.

• When using Irinotecan, clinicians should observe several safety measures to minimise risks.
• Monitor blood counts: perform regular CBC to detect neutropenia.
• Assess liver function: adjust dose in patients with hepatic impairment.
• Maintain hydration: ensure adequate fluid intake to reduce severity of diarrhea.
• Avoid strong CYP3A4 inhibitors: concurrent use may increase Irinotecan exposure.
• Pregnancy: contraindicated unless potential benefit justifies the risk.
• Store below 25°C: keep in original packaging, protect from moisture.

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

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): may raise plasma levels of Irinotecan.
• UGT1A1 inhibitors (e.g., atazanavir): increase exposure to SN‑38, heightening toxicity.
• Concurrent myelosuppressive agents: can exacerbate neutropenia and anemia.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., fluconazole): require dose adjustment and monitoring.
• Anticoagulants (e.g., warfarin): increased bleeding risk due to potential platelet effects.
• Antidiarrheal drugs (e.g., loperamide) used at high doses: may mask early signs of severe diarrhea.