Irinotecan Accord (Irinotecan Hydrochloride Trihydrate)

Irinotecan is a topoisomerase I inhibitor used in the management of colorectal cancer and related disease stages.

• Colorectal cancer: administered as part of combination chemotherapy to reduce tumor size and improve survival.
• Metastatic colorectal cancer: used to control disease spread and extend progression‑free survival.
• Unresectable colorectal cancer: employed to shrink tumors and enable possible surgical intervention.

• Irinotecan is converted intracellularly to its active metabolite SN‑38, which binds to the DNA‑topoisomerase I complex. This prevents the re‑ligation of single‑strand DNA breaks during replication, leading to accumulation of DNA damage and ultimately triggering apoptosis of rapidly dividing cancer cells.

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

Common Side Effects

• Nausea: mild to moderate upset stomach.
• Vomiting: occasional episodes during infusion.
• Diarrhea: can be acute or delayed.
• Neutropenia: reduced white blood cell count.
• Alopecia: hair thinning or loss.
• Fatigue: general tiredness.

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophils.
• Severe diarrhea/colitis: may lead to dehydration.
• Allergic reactions: rash, itching, or anaphylaxis.
• Hepatic toxicity: elevated liver enzymes.
• Pulmonary toxicity: interstitial lung disease.
• Electrolyte disturbances: severe imbalances requiring monitoring.

Before initiating therapy, several safety considerations should be addressed.

• Monitor blood counts: perform regular CBC to detect neutropenia.
• Assess liver function: baseline and periodic LFTs are recommended.
• Evaluate renal function: adjust dosing if impairment is present.
• Avoid in patients with known hypersensitivity to irinotecan or its excipients.
• Use effective contraception: advise contraception during treatment and for a defined period after.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Irinotecan can interact with other medicines, influencing efficacy or toxicity.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin): may reduce irinotecan exposure.
• Concurrent myelosuppressive agents: increase risk of severe neutropenia.
• UGT1A1 inhibitors (e.g., atazanavir): can raise SN‑38 levels and toxicity.

Moderate Interactions (Monitor Closely)

• Anticoagulants (e.g., warfarin): monitor INR for altered effect.
• Antiemetics (e.g., ondansetron): watch for QT prolongation.
• Other antineoplastic drugs: dose adjustments may be required.
• Proton pump inhibitors: may affect gastrointestinal absorption.