Irinotecan Hydrochloride

What it is and how it works

Mechanism of Action 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. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks.

Indications

• Irinotecan Hydrochloride Injection, USP 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. • Irinotecan Hydrochloride Injection, USP is indicated for patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy. Irinotecan Hydrochloride Injection, USP is a topoisomerase inhibitor indicated for: • First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum. • Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy.

Dosage and administration (summary)

• Colorectal cancer combination regimen 1: Irinotecan Hydrochloride Injection, USP 125 mg/m 2 intravenous infusion over 90 minutes on days 1, 8,15, 22 with LV 20 mg/m 2 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 Hydrochloride Injection, USP 180 mg/m 2 intravenous infusion over 90 minutes on days 1, 15, 29 with LV 200 mg/m 2 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.

Contraindications

• Irinotecan Hydrochloride Injection, USP is contraindicated in patients with a known hypersensitivity to the drug or its excipients. • Hypersensitivity to Irinotecan Hydrochloride Injection, USP or its excipients

Warnings and precautions

• Diarrhea and Cholinergic Reactions: Early diarrhea (occurring during or shortly after infusion of Irinotecan Hydrochloride Injection, USP) is usually transient and may be accompanied by cholinergic symptoms. Consider prophylactic or therapeutic administration of 0.25 mg to 1 mg of intravenous or subcutaneous atropine (unless clinically contraindicated). Late diarrhea (generally occurring more than 24 hours after administration of Irinotecan Hydrochloride Injection, USP) can occur. Monitor and replace fluid and electrolytes. Treat with loperamide. Use antibiotic support for ileus and fever.

Pregnancy

Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, Irinotecan Hydrochloride Injection, USP can cause fetal harm when administered to a pregnant woman .

Storage and supply

Store at 20° to 25°C (68° to 77°F). See USP Controlled Room Temperature (excursions permitted to 15° to 30°C (59° to 86°F)). Protect from light. It is recommended that the vial should remain in the carton until the time of use. Protect from freezing. Store Upright.

Source: Irinotecan Hydrochloride (Irinotecan Hydrochloride) — US FDA prescribing information, 2025-11-03, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.