[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Topoisomerase inhibitors](https://durgical.com/en/pharmacology/classes/topoisomerase-inhibitors/) › Irinotecan

[Pharmacology](https://durgical.com/en/pharmacology/) · [Topoisomerase inhibitors](https://durgical.com/en/pharmacology/classes/topoisomerase-inhibitors/)

# Irinotecan

A camptothecin prodrug for colorectal cancer. Its active form SN-38 traps topoisomerase I; early and late diarrhoea and neutropenia are the key risks.

Updated 2026-11-01

- Class: [Topoisomerase inhibitors](https://durgical.com/en/pharmacology/classes/topoisomerase-inhibitors/)
- Enzyme: DNA topoisomerase I
- ATC code: L01CE02
- WHO Model List of Essential Medicines

## ⚠ High-alert medication

An error with this medicine can cause serious harm: double checks and protocols are used.

✂**DNA topoisomerase I**Irinotecan

ⓘ The figure shows camptothecin, the parent compound of irinotecan's active metabolite SN-38, bound to the human topoisomerase I–DNA complex.

**Target in 3D:** DNA topoisomerase I. PDB structure 1T8I (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/1T8I) · Drag to rotate · pinch to zoom

## Mechanism of action

Carboxylesterases convert irinotecan into SN-38, which is far more active. SN-38 binds the topoisomerase I–DNA complex and prevents the single-strand nick from being resealed. When a replication fork hits the trapped complex, a double-strand break forms and the cell dies. SN-38 is inactivated by glucuronidation through UGT1A1, so people with low UGT1A1 activity are exposed to more SN-38.

- Carboxylesterases turn irinotecan into SN-38
- SN-38 traps topoisomerase I on nicked DNA
- Replication forks collide: double-strand breaks
- UGT1A1 inactivates SN-38; low activity means more toxicity

## Pharmacokinetics

**Absorption**
Intravenous infusion only.

**Metabolism**
Activated to SN-38 by carboxylesterases; oxidised by CYP3A4 to inactive products; SN-38 is glucuronidated by UGT1A1.

## Indications

- Metastatic colorectal carcinoma: first line with fluorouracil and folinic acid, and after progression on fluorouracil. [Colorectal cancer →](https://durgical.com/en/conditions/colorectal-cancer/)

## Adverse effects

### Common

- Early cholinergic syndrome: runny nose, salivation, small pupils, tearing, sweating, flushing, cramps, slow heart rate
- Late diarrhoea
- Neutropenia
- Nausea, vomiting, fatigue and hair loss

### Serious (rare, important)

- Severe late diarrhoea with dehydration, electrolyte loss or sepsis (boxed warning)
- Severe myelosuppression and neutropenic sepsis, more likely with UGT1A1*28 or *6 variants
- Acute kidney failure from volume loss
- Interstitial lung disease; hypersensitivity reactions

## Contraindications

- Known hypersensitivity to irinotecan or its excipients

## Key interactions

**Strong CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine, rifampicin, St John's wort)**
Substantially lower irinotecan and SN-38 exposure; they are not given together.

**Strong CYP3A4 or UGT1A1 inhibitors (e.g. ketoconazole)**
Raise exposure to irinotecan and SN-38; not given together.

**Diuretics and laxatives**
Avoided while the patient has diarrhoea, because they worsen dehydration.

## What is monitored

- Blood count before each dose
- Number and type of stools, fluids and electrolytes
- UGT1A1 genotype may be tested before starting
- Bilirubin and respiratory symptoms

## Administration and safety

- Antiemetic premedication before each dose; atropine is kept ready for early cholinergic symptoms.
- Extravasation: the site is flushed with sterile water and ice is applied.
- Hazardous drug: prepared and given following hazardous-drug handling procedures (impervious gloves, no skin contact) and disposed of as cytotoxic waste.

## Nursing care

- Independent double check of drug, patient, route and cycle before giving it (high-alert medicine).
- During and soon after the infusion, watch for sweating, salivation, cramps or early diarrhoea and give atropine as ordered.
- Teaching: start the prescribed antidiarrhoeal at the first loose stool after leaving, drink plenty of fluids, and call if diarrhoea persists or comes with fever or dizziness.
- Blood count before each cycle; fever with neutropenia is treated as an emergency.

## Pregnancy and breastfeeding

Can cause fetal harm; effective contraception is used during treatment by women and by men with female partners.

## Memory aid

IRINOtecan makes you «RUN to the loo»: early diarrhoea is cholinergic (atropine), late diarrhoea is dangerous. Low UGT1A1 (as in Gilbert) means more SN-38.

## Test yourself

Think of the answer, then tap the question to see it.

## What are the two types of diarrhoea caused by irinotecan, and how is each managed?

Early cholinergic diarrhoea, which responds to atropine; late diarrhoea, which can be life-threatening and is treated promptly with loperamide and fluids.

## Which enzyme converts irinotecan into its active form, and which enzyme inactivates that form?

Carboxylesterases form SN-38; UGT1A1 glucuronidates and inactivates it.

## Why might a patient with Gilbert syndrome have more neutropenia on irinotecan?

Reduced UGT1A1 glucuronidation leaves more active SN-38 in the body.

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## Related drugs

- [Topotecan](https://durgical.com/en/pharmacology/topotecan/)
- [Etoposide](https://durgical.com/en/pharmacology/etoposide/)
- [Oxaliplatin](https://durgical.com/en/pharmacology/oxaliplatin/)
- [Calcium folinate](https://durgical.com/en/pharmacology/calcium-folinate/)

## Related conditions

- [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/)

[← Back to the class: Topoisomerase inhibitors](https://durgical.com/en/pharmacology/classes/topoisomerase-inhibitors/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - IRINOTECAN HYDROCHLORIDE injection, solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c527c2e-9062-4afe-dbbb-f650db3a340f) (DailyMed (U.S. National Library of Medicine), 2025); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 70 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01CE02) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025).

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Representative model, for educational purposes only.

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