Irinotecan Hydrochloride Accord Healthcare (Irinotecan Hydrochloride Trihydrate)

Irinotecan is a topoisomerase I inhibitor used in oncology to target specific cancer types.

• Metastatic colorectal cancer: improves survival and disease control in patients with advanced disease.
• Adjuvant colon cancer: reduces risk of recurrence after surgical resection.
• Small cell lung cancer (in combination therapy): contributes to tumor response when used with other chemotherapeutic agents.

• Irinotecan is a prodrug converted intracellularly to SN‑38, a potent inhibitor of topoisomerase I. By stabilizing the enzyme‑DNA cleavable complex, it prevents relegation of single‑strand DNA breaks during replication, leading to accumulation of DNA damage and apoptosis of rapidly dividing tumor cells. The active metabolite binds to the DNA‑topoisomerase I complex, interfering with the religation step and causing irreversible DNA strand breaks, which trigger cell‑cycle arrest and programmed cell death in malignant cells while sparing most normal tissues.

Irinotecan may cause a range of adverse reactions, which are categorized by frequency and severity.

Common Side Effects

• Diarrhea: often severe and may require antidiarrheal therapy.
• Neutropenia: reduced white blood cell count increasing infection risk.
• Nausea and vomiting: may be managed with antiemetics.
• Fatigue: general tiredness affecting daily activities.
• Abdominal pain: discomfort in the stomach area.
• Alopecia: hair loss occurring during treatment.

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophil count requiring urgent care.
• Severe colitis or intestinal perforation: life‑threatening bowel complications.
• Cholinergic syndrome: abdominal cramping, sweating, and bradycardia.
• Hypersensitivity reactions: rash, itching, or anaphylaxis.
• Hepatic toxicity: elevated liver enzymes or liver failure.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis.

When using Irinotecan, clinicians should consider several safety precautions to minimize risks.

• Renal impairment: dose adjustment or close monitoring is recommended.
• Hepatic impairment: use with caution as metabolism may be reduced.
• Pre‑existing diarrhea: monitor closely and treat early to prevent severe episodes.
• Concomitant myelosuppressive agents: increased risk of bone‑marrow suppression.
• Pregnancy and lactation: avoid unless benefits outweigh potential risks.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

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

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin): may lower irinotecan exposure.
• Strong CYP3A4 inhibitors (e.g., ketoconazole): may increase toxicity.
• Other myelosuppressive chemotherapy: additive bone‑marrow suppression.
• Anticholinergic drugs: may exacerbate cholinergic syndrome.

Moderate Interactions (Monitor Closely)

• Warfarin: potential increase in bleeding risk.
• UGT1A1 inhibitors (e.g., atazanavir): may raise active metabolite levels.
• Concurrent use of other cytotoxic agents: overlapping toxicities require dose adjustments.