Irinotecan Accord (Irinotecan Hydrochloride Trihydrate)

• Irinotecan is a topoisomerase I inhibitor used primarily in colorectal cancer therapy and related solid‑tumor regimens.
• Metastatic colorectal cancer: improves overall survival when combined with fluoropyrimidine‑based chemotherapy.
• Small cell lung cancer: used in combination regimens to achieve tumor response.
• Advanced gastric cancer: incorporated into multi‑drug protocols to enhance disease control.

• Irinotecan is a pro‑drug converted intracellularly to SN‑38, a potent inhibitor of topoisomerase I. By stabilizing the transient DNA‑topoisomerase I complex, it prevents relegation of single‑strand breaks during DNA replication, leading to accumulation of DNA damage and apoptosis of rapidly dividing tumor cells. The conversion is mediated primarily by carboxylesterases, and the active metabolite is further detoxified by UGT1A1 glucuronidation.

Irinotecan may cause a range of adverse reactions, varying from mild to severe.

Common Side Effects

• Nausea and vomiting
• Diarrhea
• Neutropenia
• Fatigue
• Alopecia
• Abdominal pain

Serious or Rare Side Effects

• Febrile neutropenia
• Severe diarrhea (colitis)
• Allergic reactions including anaphylaxis
• Hepatic toxicity
• Pulmonary toxicity
• Cardiac ischemia

• Before initiating therapy, clinicians should consider several safety measures.
• Monitor blood counts: perform regular complete blood count testing to detect neutropenia.
• Assess liver function: evaluate hepatic enzymes before and during therapy.
• Evaluate gastrointestinal status: screen for bowel obstruction before dosing.
• Use antiemetic prophylaxis: administer appropriate anti‑emetic agents to reduce nausea and vomiting.
• Adjust dose in hepatic impairment: consider reduced dosing for patients with elevated bilirubin.
• Store at ambient temperature: keep in original container, protect from moisture and light.

Irinotecan interacts with several medicines that may alter its efficacy or safety.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole): may increase SN‑38 exposure and toxicity.
• UGT1A1 inhibitors (e.g., atazanavir): can reduce SN‑38 clearance, raising risk of severe neutropenia.
• Live vaccines: immunosuppression may lead to infection.
• Anticoagulants (warfarin): heightened bleeding risk due to hepatic effects.
• Concurrent use with other myelosuppressive agents: may exacerbate bone‑marrow suppression.

Moderate Interactions (Monitor Closely)

• CYP3A4 inducers (e.g., rifampin): may lower efficacy by reducing SN‑38 levels.
• Diuretics: potential for electrolyte disturbances during dehydration from diarrhea.
• Other chemotherapy agents: overlapping toxicities require dose adjustments.
• Radiation therapy: combined effect may increase tissue toxicity.
• Herbal supplements (e.g., St. John’s wort): may alter drug metabolism.