Irinotekan Accord (Irinotecan Hydrochloride Trihydrate)

Irinotecan is a topoisomerase I inhibitor used in the treatment of colorectal cancer.

• Metastatic colorectal cancer: improves survival when combined with fluoropyrimidine‑based regimens.
• Colorectal cancer (adjuvant setting): reduces risk of recurrence after surgical resection.
• Colorectal cancer (first‑line therapy): administered with leucovorin and 5‑FU as part of the FOLFIRI regimen.

• 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. This results in accumulation of DNA damage, inhibition of DNA replication and transcription, and ultimately triggers apoptosis of rapidly dividing tumor cells.

Irinotecan may cause a range of adverse reactions, some of which are common and others that are serious or rare.

Common Side Effects

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

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophils requiring urgent medical attention.
• Severe colitis: intense inflammation of the colon that can be life‑threatening.
• Allergic reactions: including rash, bronchospasm, or anaphylaxis.
• Hepatotoxicity: elevated liver enzymes indicating liver injury.

Prior to initiating therapy, clinicians should assess patient‑specific factors and monitor for potential complications.

• Monitor blood counts: watch for neutropenia and adjust treatment as needed.
• Assess liver function: dose adjustments may be required in hepatic impairment.
• Maintain adequate hydration: helps reduce the severity of diarrhea.
• Avoid strong CYP3A4 inhibitors: concurrent use can increase irinotecan exposure.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Irinotecan can interact with other medicines, affecting its safety and efficacy.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole): may raise irinotecan plasma levels.
• CYP3A4 inducers (e.g., rifampin): can reduce therapeutic effect.
• Concurrent myelosuppressive agents: increase risk of severe bone‑marrow suppression.

Moderate Interactions (Monitor Closely)

• Warfarin: may enhance anticoagulant effect, requiring INR monitoring.
• NSAIDs: can exacerbate gastrointestinal toxicity.
• Other antineoplastic drugs: may require dose adjustments and close observation.