Irinotecan Injection is used as a first-line treatment in combination with 5-Fluorouracil (5-FU) and Leucovorin (LV) for patients with metastatic cancer of the colon or rectum. It is also indicated for patients whose colorectal cancer has recurred or progressed after initial treatment with fluorouracil-based therapy.

Irinotecan is a derivative of camptothecin. It works by interacting with the enzyme topoisomerase I, which helps relieve torsional strain in DNA by causing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent the rejoining of these strands, ultimately inhibiting DNA replication and leading to cancer cell death.

Colorectal cancer combination regimen 1: Irinotecan 125 mg/m intravenous infusion over 90 minutes on days 1,
8,15, 22 with LV 20 mg/m intravenous bolus infusion on days 1, 8, 15, 22 followed by 5-FU intravenous bolus infusion
on days 1, 8, 15, 22 every 6 weeks.
Colorectal cancer combination regimen 2: Irinotecan 180 mg/m2 intravenous infusion over 90 minutes on days 1, 15, 29 with LV 200 mg/m intravenous infusion over 2 hours on days 1, 2, 15, 16, 29, 30 followed by 5-FU 400 mg/m 2 intravenous bolus infusion on days 1, 2, 15, 16, 29, 30 and 5-FU 600 mg/m 2 intravenous infusion over 22 hours on
days 1, 2, 15, 16, 29, 30.
Colorectal cancer single agent regimen 1: Irinotecan 125 mg/m intravenous infusion over 90 minutes on days 1, 8,
15, 22 then 2-week rest.
Colorectal cancer single agent regimen 2: Irinotecan 350 mg/m intravenous infusion over 90 minutes on day 1
every 3 weeks.

Diuretics may increase the risk of dehydration due to vomiting and diarrhea. Prophylactic dexamethasone used as an antiemetic may increase the risk of lymphocytopenia. Prochlorperazine may increase the incidence of akathisia. Concurrent use with other antineoplastic agents may enhance myelosuppression and diarrhea. Herbal products like St. John’s wort and drugs such as ketoconazole may reduce exposure to irinotecan.

Irinotecan Injection is contraindicated in patients with known hypersensitivity to irinotecan or any of its components.

Common adverse effects include nausea, vomiting, abdominal pain, diarrhea, constipation, loss of appetite, mucositis, neutropenia, leukopenia (including lymphocytopenia), anemia, thrombocytopenia, weakness, pain, fever, infection, abnormal bilirubin levels, and hair loss (alopecia).

Pregnancy Category D. Irinotecan may cause harm to the fetus if administered during pregnancy. In animal studies, the drug was found in breast milk shortly after administration and reached significantly higher concentrations compared to plasma. It is not known whether irinotecan is excreted in human breast milk.

Diarrhea and Cholinergic Reactions: Early diarrhea (occurring during or shortly after irinotecan infusion) is usually temporary and rarely severe. It may be associated with cholinergic symptoms such as rhinitis, increased salivation, miosis, lacrimation, sweating, flushing, and increased intestinal activity leading to abdominal cramps. Bradycardia may also occur. Early diarrhea and related symptoms can be prevented or treated. Consider prophylactic or therapeutic use of atropine (0.25 mg to 1 mg IV or subcutaneous), unless contraindicated. These effects are more frequent at higher doses. Late diarrhea (occurring more than 24 hours after administration) can be serious and prolonged, potentially leading to dehydration, electrolyte imbalance, or sepsis. Grade 3–4 late diarrhea has been reported in 23–31% of patients on weekly dosing.

Myelosuppression: Fatal cases due to sepsis following severe neutropenia have been reported in patients treated with irinotecan. In clinical studies using weekly dosing, neutropenic fever occurred in about 3% of patients, and 6% required G-CSF treatment. Prompt management with antibiotics is necessary.

Patients with Reduced UGT1A1 Activity: Patients who are homozygous for the UGT1A128 allele (UGT1A17/7 genotype) have a higher risk of neutropenia after starting irinotecan therapy.

Pediatric Use: The safety and effectiveness of irinotecan in children have not been established.

Geriatric Use: Patients over 65 years should be closely monitored due to a higher risk of early and late diarrhea. In patients aged 70 years or older, the recommended starting dose for a once-every-3-week regimen is 300 mg/m².

Renal Impairment: The effect of renal dysfunction on irinotecan has not been fully studied. Use with caution in such patients, and it is not recommended in patients undergoing dialysis.

Hepatic Impairment: Irinotecan clearance is reduced in patients with liver dysfunction, while exposure to its active metabolite SN-38 is increased compared to those with normal liver function.

Cytotoxic Chemotherapy

Store at 15°C to 30°C, protected from light. Keep the vial in its original carton until use.