Irinotecanhydrochloridetrihydraat Hikma (Irinotecan Hydrochloride Trihydrate)

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

• Metastatic colorectal cancer: improves overall survival and disease control when incorporated into combination chemotherapy regimens.

• Irinotecan is converted intracellularly to its active metabolite SN‑38, which binds to the DNA‑topoisomerase I complex and stabilizes it. This prevents relegation of single‑strand DNA breaks during replication, leading to accumulation of DNA damage, inhibition of DNA synthesis, and ultimately tumor cell death.

Irinotecan may cause a range of adverse reactions that vary in 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: hair loss during treatment cycles.
• Fatigue: generalized tiredness affecting daily activities.
• Anemia: decreased red blood cell levels causing weakness.

Serious or Rare Side Effects

• Febrile neutropenia: fever with low neutrophils requiring urgent medical attention.
• Severe dehydration from uncontrolled diarrhea.
• Acute cholinergic syndrome: abdominal cramps, sweating, and bradycardia.
• Hepatic toxicity: elevated liver enzymes or jaundice.
• Allergic reactions: rash, bronchospasm, or anaphylaxis.
• Tumor lysis syndrome: rapid tumor cell breakdown leading to metabolic disturbances.

Before initiating therapy, clinicians should assess patient suitability and monitor for potential complications.

• Monitor blood counts: perform regular complete blood counts to detect neutropenia.
• Assess liver function: evaluate hepatic enzymes and bilirubin before and during treatment.
• Evaluate bowel status: screen for pre‑existing diarrhea or intestinal obstruction.
• Dose adjustment: consider reduced dosing in patients with hepatic impairment.
• Avoid in hypersensitivity: discontinue if severe allergic reaction occurs.
• Store at ambient temperature: keep in original packaging, protect from moisture and light.

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

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole): may increase SN‑38 exposure.
• UGT1A1 inhibitors (e.g., atazanavir): can raise active metabolite levels and toxicity.
• Concurrent myelosuppressive agents: heighten risk of severe neutropenia.
• High‑dose radiation therapy: may exacerbate bone‑marrow suppression.
• Live vaccines: increased risk of infection due to immunosuppression.

Moderate Interactions (Monitor Closely)

• CYP3A4 inducers (e.g., rifampin): may reduce irinotecan effectiveness.
• Antacids containing aluminum or magnesium: can affect drug absorption.
• Warfarin: monitor INR as irinotecan may alter anticoagulation.
• Diuretics: watch for electrolyte imbalances during diarrhea.
• Herbal supplements (e.g., St. John’s wort): potential enzyme induction affecting drug levels.