Irinotecán Accord (Irinotecan Hydrochloride Trihydrate)

• Irinotecan is indicated for colorectal cancer and related metastatic disease, acting within the chemotherapy regimen.
• Metastatic colorectal cancer: improves overall survival when combined with fluorouracil and leucovorin.
• Advanced colorectal cancer: reduces tumor progression as part of combination therapy.
• Colorectal cancer refractory to first‑line treatment: provides an alternative therapeutic option.

• After intravenous administration, irinotecan is converted by hepatic carboxylesterases to the active metabolite SN‑38. SN‑38 binds to the DNA‑topoisomerase I complex, stabilizing it and preventing relegation of single‑strand DNA breaks during replication and transcription, ultimately leading to apoptosis of rapidly dividing cancer cells.

Irinotecan may cause a range of adverse reactions, which are categorized by 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.
• Anemia: decreased red blood cell levels.

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophils requiring urgent medical attention.
• Severe colitis or bowel perforation from intense diarrhea.
• Hypersensitivity reactions: rash, bronchospasm, or anaphylaxis.
• Hepatotoxicity: elevated liver enzymes or liver dysfunction.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis.
• Electrolyte disturbances: severe hypokalemia or hyponatremia.

• Prior to initiating therapy, clinicians should assess patient‑specific factors and monitor for potential complications.
• Monitor blood counts: perform regular CBC to detect neutropenia.
• Assess liver function: adjust dose in hepatic impairment.
• Maintain hydration: ensure adequate fluid intake to mitigate severe diarrhea.
• Avoid strong CYP3A4 inhibitors: concurrent use may increase exposure to SN‑38.
• Pregnancy considerations: use only if potential benefits justify potential risks.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Irinotecan interacts with several drug classes; awareness helps prevent adverse outcomes.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may raise SN‑38 levels.
• UGT1A1 inhibitors (e.g., atazanavir): increase risk of toxicity.
• Concurrent myelosuppressive agents: amplify bone‑marrow suppression.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inducers (e.g., rifampin): may reduce efficacy.
• Warfarin: monitor INR as irinotecan can affect coagulation.
• Other antineoplastic agents: adjust dosing and monitor overlapping toxicities.