Irinotecan Hydrochloride

• Metastatic colorectal cancer — first-line treatment in combination with fluorouracil and leucovorin, or as second-line therapy after failure of prior fluorouracil-based chemotherapy.
• Advanced or metastatic colorectal cancer — used alone or in combination regimens for patients with unresectable disease.
• Small cell lung cancer (extensive-stage) — in combination with cisplatin for first-line therapy.
• Other off-label/clinically accepted uses: treatment of other solid tumors including pancreatic, gastric, and ovarian cancers in selected cases or clinical trials.

Adults

• Colorectal cancer (combination therapy):
• Irinotecan 180 mg/m² IV infusion over 90 minutes every 2 weeks in combination regimens (e.g., FOLFIRI).
• Colorectal cancer (monotherapy):
• Irinotecan 350 mg/m² IV infusion over 90 minutes every 3 weeks.
• Small cell lung cancer (with cisplatin):
• Irinotecan 65 mg/m² IV on days 1, 8, and 15 of a 28-day cycle.

Dose adjustments

• Modify dosing based on hematologic and non-hematologic toxicities.
• Dose reduction or delay recommended for neutropenia, diarrhea, or other severe adverse effects.

Pediatrics

• Safety and efficacy not established; use is not routinely recommended.

Elderly

• Start with standard dosing but monitor closely for toxicity; increased risk of myelosuppression and diarrhea may occur.

Renal impairment

• No dose adjustment recommended for mild-to-moderate impairment. Monitor closely for toxicity in severe impairment.

Hepatic impairment

• Moderate to severe hepatic dysfunction requires dose adjustment or avoidance; monitor bilirubin and liver enzymes.

Administration

• Intravenous infusion over 90 minutes; premedication with antiemetics is recommended.

Irinotecan is a prodrug that is converted primarily in the liver by carboxylesterase enzymes to its active metabolite SN-38. SN-38 inhibits topoisomerase I, an enzyme essential for DNA replication and transcription, by stabilizing the cleavable complex between DNA and topoisomerase I, leading to DNA strand breaks. This causes replication arrest and apoptosis of rapidly dividing tumor cells, resulting in cytotoxic effects against cancer cells.

• Absorption: Administered intravenously; bioavailability is 100%.
• Distribution: Widely distributed; plasma protein binding approximately 65–95%.
• Metabolism: Irinotecan is converted to SN-38 (active metabolite) primarily by hepatic carboxylesterase; SN-38 is further metabolized by UGT1A1 to an inactive glucuronide conjugate (SN-38G). Genetic polymorphisms in UGT1A1 can affect toxicity.
• Elimination: Half-life of irinotecan ~6–12 hours; SN-38 half-life ~10–20 hours. Excreted mainly in bile via feces (~50%) and to a lesser extent in urine (~20%).
• Onset: Cytotoxic effects begin after metabolism to SN-38; clinical effects observed during and after infusion cycles.

• Pregnancy: Category D — evidence of human fetal risk based on adverse outcomes from animal studies and limited human data. Should not be used during pregnancy unless benefit justifies risk.
• Lactation: Unknown if excreted in human milk; potential for serious adverse reactions in nursing infants. Breastfeeding is not recommended during treatment and for a period after the last dose.
• Caution: Pregnancy testing and contraception advised for women of childbearing potential.

• Class: Antineoplastic agent
• Subclass: Topoisomerase I inhibitor, camptothecin derivative

• Known hypersensitivity to irinotecan or any component of the formulation.
• Intestinal obstruction or severe diarrhea.
• Severe bone marrow suppression prior to therapy initiation.
• Patients with Gilbert’s syndrome or known UGT1A1*28 homozygosity may require dose adjustments due to increased toxicity risk.

• Severe diarrhea: early-onset (cholinergic syndrome) and late-onset diarrhea, which can be life-threatening; requires prompt management with atropine (early) and loperamide (late).
• Myelosuppression: severe neutropenia, leukopenia, thrombocytopenia; monitor blood counts regularly.
• Hepatic impairment: dose modifications needed; monitor liver function.
• Hypersensitivity reactions: possible during infusion; monitor and discontinue if severe.
• Interstitial lung disease: rare but serious cases reported.
• Genetic polymorphisms (UGT1A1): increased risk of toxicity in patients with certain genetic variants; consider testing.
• Infusion-related reactions: observe during and after administration.

Common:

• Diarrhea (early and late onset).
• Nausea and vomiting.
• Neutropenia and other hematologic toxicities.
• Fatigue and asthenia.
• Alopecia.

Serious/Rare:

• Severe neutropenia leading to infections and sepsis.
• Severe dehydration secondary to diarrhea.
• Acute cholinergic syndrome (early diarrhea, abdominal cramping, salivation).
• Hypersensitivity and anaphylaxis.
• Interstitial lung disease/pneumonitis.

• CYP3A4 inhibitors/inducers: drugs that inhibit CYP3A4 (e.g., ketoconazole) may increase irinotecan levels and toxicity; inducers (e.g., rifampin) may reduce efficacy.
• UGT1A1 inhibitors: drugs affecting glucuronidation may increase SN-38 toxicity.
• Anticholinergic drugs: may worsen early cholinergic symptoms.
• Other myelosuppressive agents: additive bone marrow toxicity risk.
• Warfarin: irinotecan may increase bleeding risk.

• Increased emphasis on pharmacogenetic testing (UGT1A1*28) to guide dosing and reduce toxicity risk.
• Updated management protocols for diarrhea and neutropenia to improve patient safety.
• Guidelines recommend early antiemetic prophylaxis and supportive care to minimize side effects.

• Store irinotecan hydrochloride injection vials at 2°C–8°C (refrigerated).
• Protect from light.
• Do not freeze.
• Use immediately after dilution; if storage is necessary, follow manufacturer guidelines (usually up to 24 hours at 2°C–8°C).
• Avoid agitation of diluted solutions.