IRINOTECAN HYDROCHLORIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Irinotecan is a prodrug that is converted to its active metabolite SN-38, which inhibits topoisomerase I, leading to DNA damage and cell death.

What the body does with it

Metabolism	Irinotecan is hydrolyzed to its active metabolite SN-38 by carboxylesterases. SN-38 undergoes glucuronidation by UGT1A1 to form an inactive glucuronide. Irinotecan also undergoes CYP3A4-mediated oxidative metabolism to APC and NPC metabolites.
Excretion	Primarily biliary/fecal (approx. 60-65% as parent drug and metabolites); renal excretion accounts for <25% (mostly metabolites, <10% unchanged).
Half-life	Terminal elimination half-life of irinotecan is approximately 6-12 hours; the active metabolite SN-38 has a terminal half-life of 10-20 hours. In patients with hepatic impairment, half-life may be prolonged.
Protein binding	Irinotecan is approximately 30-68% bound to plasma proteins, primarily albumin. SN-38 is approximately 95% bound to albumin.
Volume of Distribution	Volume of distribution at steady state (Vdss) for irinotecan is approximately 150-300 L/m² (or about 3-6 L/kg based on 1.7 m² body surface area and 70 kg), indicating extensive tissue distribution.
Bioavailability	Not applicable; irinotecan is administered intravenously due to poor oral bioavailability (<10% in preclinical studies).
Onset of Action	Intravenous administration: onset of antitumor effect occurs within days to weeks, depending on tumor sensitivity and dosing schedule.
Duration of Action	The cytotoxic effect persists for several days following a single dose, correlating with the presence of SN-38. Clinical duration of response varies with regimen and tumor type.

Classification & Brands

Dosing & administration

125 mg/m² intravenous over 90 minutes on days 1, 8, 15, 22 of a 6-week cycle (weekly regimen); or 350 mg/m² intravenous over 30-90 minutes every 3 weeks (once-every-3-weeks regimen).

Dosage form	INJECTABLE
Renal impairment	CrCl ≥20 mL/min: no dose adjustment required. CrCl <20 mL/min: insufficient data; avoid use. Monitor renal function and adjust based on tolerability.
Liver impairment	Child-Pugh Class A: no dose adjustment. Child-Pugh Class B: reduce dose by 25-50% (e.g., 300 mg/m² every 3 weeks or 100 mg/m² weekly). Child-Pugh Class C: not recommended.
Pediatric use	50 mg/m² intravenous over 60 minutes on days 1-5 every 21 days; alternative: 20 mg/m² daily for 5 days every 3 weeks. Adjust for toxicity and body surface area.
Geriatric use	No initial dose reduction required for age alone; monitor for increased myelosuppression and diarrhea. Consider starting at lower end of dosing range (e.g., 300 mg/m² every 3 weeks) and adjust based on tolerability.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP3A4 inducers or inhibitors may alter levels Can cause severe delayed diarrhea and myelosuppression.

Breastfeeding	Irinotecan and its active metabolite SN-38 are excreted into breast milk in animal models; human data lacking. M/P ratio unknown. Discontinue nursing during therapy and for at least 7 days after last dose.
Teratogenic Risk	Irinotecan is embryotoxic and fetotoxic in animal studies; no adequate human data. Advise against use in pregnancy, especially first trimester due to potential teratogenicity. Second and third trimester use may cause fetal harm and should only be used if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

Irinotecan can cause severe or life-threatening diarrhea and myelosuppression. Early and intensive management of diarrhea is required. Patients with UGT1A1*28 homozygosity (Gilbert's syndrome) are at increased risk for severe neutropenia and diarrhea. Dose reduction should be considered in these patients.

Side Effect Profile

Common Effects	Diarrhea
Serious Effects

Absolute Contraindications

["Hypersensitivity to irinotecan or its excipients","Severe bone marrow suppression (e.g., absolute neutrophil count < 1500/mm³)","Severe hepatic impairment (bilirubin > 2 mg/dL)","Pregnancy (teratogenic effects)","Lactation (discontinue breastfeeding)"]

Clinical Precautions

Precautions

["Severe diarrhea: both early-onset (cholinergic) and late-onset (secretory) forms require aggressive management.","Myelosuppression: neutropenia is dose-limiting; monitor blood counts.","UGT1A1 genotype testing: homozygous *28 allele increases SN-38 exposure and toxicity risk.","Hypersensitivity reactions: including anaphylaxis.","Extravasation: may cause tissue necrosis."]

Drug interactions

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IRINOTECAN HYDROCHLORIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Irinotecan is a prodrug that is converted to its active metabolite SN-38, which inhibits topoisomerase I, leading to DNA damage and cell death.

What the body does with it

Metabolism	Irinotecan is hydrolyzed to its active metabolite SN-38 by carboxylesterases. SN-38 undergoes glucuronidation by UGT1A1 to form an inactive glucuronide. Irinotecan also undergoes CYP3A4-mediated oxidative metabolism to APC and NPC metabolites.
Excretion	Primarily biliary/fecal (approx. 60-65% as parent drug and metabolites); renal excretion accounts for <25% (mostly metabolites, <10% unchanged).
Half-life	Terminal elimination half-life of irinotecan is approximately 6-12 hours; the active metabolite SN-38 has a terminal half-life of 10-20 hours. In patients with hepatic impairment, half-life may be prolonged.
Protein binding	Irinotecan is approximately 30-68% bound to plasma proteins, primarily albumin. SN-38 is approximately 95% bound to albumin.
Volume of Distribution	Volume of distribution at steady state (Vdss) for irinotecan is approximately 150-300 L/m² (or about 3-6 L/kg based on 1.7 m² body surface area and 70 kg), indicating extensive tissue distribution.
Bioavailability	Not applicable; irinotecan is administered intravenously due to poor oral bioavailability (<10% in preclinical studies).
Onset of Action	Intravenous administration: onset of antitumor effect occurs within days to weeks, depending on tumor sensitivity and dosing schedule.
Duration of Action	The cytotoxic effect persists for several days following a single dose, correlating with the presence of SN-38. Clinical duration of response varies with regimen and tumor type.

Classification & Brands

Dosing & administration

125 mg/m² intravenous over 90 minutes on days 1, 8, 15, 22 of a 6-week cycle (weekly regimen); or 350 mg/m² intravenous over 30-90 minutes every 3 weeks (once-every-3-weeks regimen).

Dosage form	INJECTABLE
Renal impairment	CrCl ≥20 mL/min: no dose adjustment required. CrCl <20 mL/min: insufficient data; avoid use. Monitor renal function and adjust based on tolerability.
Liver impairment	Child-Pugh Class A: no dose adjustment. Child-Pugh Class B: reduce dose by 25-50% (e.g., 300 mg/m² every 3 weeks or 100 mg/m² weekly). Child-Pugh Class C: not recommended.
Pediatric use	50 mg/m² intravenous over 60 minutes on days 1-5 every 21 days; alternative: 20 mg/m² daily for 5 days every 3 weeks. Adjust for toxicity and body surface area.
Geriatric use	No initial dose reduction required for age alone; monitor for increased myelosuppression and diarrhea. Consider starting at lower end of dosing range (e.g., 300 mg/m² every 3 weeks) and adjust based on tolerability.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP3A4 inducers or inhibitors may alter levels Can cause severe delayed diarrhea and myelosuppression.

Breastfeeding	Irinotecan and its active metabolite SN-38 are excreted into breast milk in animal models; human data lacking. M/P ratio unknown. Discontinue nursing during therapy and for at least 7 days after last dose.
Teratogenic Risk	Irinotecan is embryotoxic and fetotoxic in animal studies; no adequate human data. Advise against use in pregnancy, especially first trimester due to potential teratogenicity. Second and third trimester use may cause fetal harm and should only be used if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Common Effects	Diarrhea
Serious Effects

IRINOTECAN HYDROCHLORIDE

How it works

What the body does with it

Classification & Brands

Dosing & administration

Use during pregnancy

Warnings & precautions

Side Effect Profile

Absolute Contraindications

Clinical Precautions

Drug interactions

IRINOTECAN HYDROCHLORIDE

How it works

What the body does with it

Classification & Brands

Dosing & administration

Use during pregnancy

Warnings & precautions

Side Effect Profile

Absolute Contraindications

Clinical Precautions

Drug interactions

Clinical Tips & Counseling