Irotecan Injection is indicated as a component of first-line therapy in combination with 5- Fluorouracil (5-FU) and Leucovorin (LV) for patients with metastatic carcinoma of the colon or rectum. Irotecan is indicated for patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial Fluorouracil-based therapy.

Irinotecan is a derivative of Camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks.

Colorectal cancer combination regimen 1: Irinotecan 125 mg/m2 intravenous infusion over 90 minutes on days 1, 8,15, 22 with LV 20 mg/m2 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/m2 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/m2 intravenous infusion over 90 minutes on days 1, 8, 15, 22 then 2-week rest.

Colorectal cancer single agent regimen 2: Irinotecan 350 mg/m2 intravenous infusion over 90 minutes on day 1 every 3 weeks.

Diuretics increase risks of dehydration secondary to vomiting/diarrhoea; prophylactic dexamethasone as an antiemetic may enhance lymphocytopenia; prochlorperazine may increase incidence of akathisia; antineoplastic agents (myelosuppression and diarrhoea). St John's wort, ketoconazole may reduce irinotecan exposure.

Irinotecan Injection is contraindicated in patients with a known hypersensitivity to the drug or its excipients.

Common adverse reactions (>30%) observed in combination therapy clinical studies are: Nausea, vomiting, abdominal pain, diarrhea, constipation, anorexia, mucositis, neutropenia, leukopenia (including lymphocytopenia), anemia, thrombocytopenia, asthenia, pain, fever, infection, abnormal bilirubin, and alopecia.

Pregnancy category D. Irinotecan can cause fetal harm when administered to a pregnant woman. Radioactivity appeared in rat milk within 5 minutes of intravenous administration of radiolabeled Irinotecan and was concentrated up to 65-fold at 4 hours after administration relative to plasma concentrations. It is not non weather this drug excreted in human male.

Diarrhea and Cholinergic Reactions: Early diarrhea (occurring during or shortly after infusion of Irotecan)is usually transient and infrequently severe. It may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyper peristalsis that can cause abdominal cramping. Bradycardia may also occur. Early diarrhea and other cholinergic symptoms may be prevented or treated. Consider prophylactic or therapeutic administration of 0.25 mg to 1 mg of intravenous or subcutaneous atropine (unless clinically contraindicated). These symptoms are expected to occur more frequently with higher Irotecan doses. Late diarrhea (generally occurring more than 24 hours after administration of Irotecan) can be life threatening since it may be prolonged and may lead to dehydration, electrolyte imbalance, or sepsis. Grade 3-4 late diarrhea occurred in 23-31% of patients receiving weekly dosing.

Myelosuppression: Deaths due to sepsis following severe neutropenia have been reported in patients treated with Irotecan. In the clinical studies evaluating the weekly dosage schedule, neutropenic fever (concurrent NCI grade 4 neutropenia and fever of grade 2 or greater) occurred in 3% of the patients; 6% of patients received G-CSF for the treatment of neutropenia. Manage febrile neutropenia promptly with antibiotic support.

Patients with Reduced UGT1A1 Activity: Individuals who are homozygous for the UGT1A1*28 allele (UGT1A1 7/7 genotype) are at increased risk for neutropenia following initiation of Irotecan treatment.

Pediatric Use: The effectiveness of Irotecan in pediatric patients has not been established.

Geriatric Use: Patients greater than 65 years of age should be closely monitored because of a greater risk of early and late diarrhea in this population. The starting dose of Irotecan in patients 70 years and older for the once-every-3-week-dosage schedule should be 300 mg/m2.

Renal Impairment: The influence of renal impairment on the of Irotecan has not been evaluated. Therefore, use caution in patients with impaired renal function. Irotecan is not recommended for use in patients on dialysis.

Hepatic Impairment: Irotecan clearance is diminished in patients with hepatic impairment while exposure to the active metabolite SN-38 is increased relative to that in patients with normal hepatic function.

Store at controlled room temperature 15° to 30°C. Protect from light. Keep the vial in the carton until the time of use.