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Irinotecan can cause two kinds of diarrhoea. The first comes during or soon after the drip, with sweating, watery eyes and cramps; an atropine injection stops it. The second starts a day or more later and can be serious: take 4 mg of loperamide at the first loose stool, then 2 mg every 2 hours, and call your team if it is not controlled in 24 hours, or with blood, fever or faintness.
Irinotecan causes an early diarrhoea during or shortly after the infusion, part of an acute cholinergic syndrome (rhinitis, salivation, miosis, lacrimation, sweating, flushing, cramps, sometimes bradycardia), and a late diarrhoea, generally more than 24 hours after the dose (median onset 5 days with 3-weekly and 11 days with weekly dosing), which can be prolonged and life-threatening. The US label advises considering atropine 0.25 to 1 mg intravenously or subcutaneously as prophylaxis or treatment for the cholinergic syndrome; eviQ gives 0.3 to 0.6 mg, repeated to a maximum of 1.2 mg. For late diarrhoea the label and eviQ agree on high-dose loperamide (4 mg at the first loose stool, then 2 mg every 2 hours until 12 hours free of diarrhoea, 4 mg every 4 hours at night), not for more than 48 hours because of paralytic ileus. Fever, dehydration or melaena means admission, stool tests, intravenous fluids and antibiotics; diarrhoea unresolved after a second 12 to 24 hour review is treated with octreotide. The next dose waits until bowel function has been normal without antidiarrhoeals for 24 hours, and the dose is reduced if grade 2 to 4 late diarrhoea recurs. eviQ applies the same algorithm to sacituzumab govitecan, whose label caps loperamide at 16 mg a day.
Why: People with these gene variants clear the drug's active form more slowly and are more likely to have severe side effects.
“When administered in combination with other agents, or as a single-agent, consider a reduction in the starting dose by at least one level of CAMPTOSAR for patients known to be homozygous for the UGT1A1*28 or *6 alleles (*28/*28, *6/*6) or compound heterozygous for the UGT1A1*28 and *6 alleles (*6/*28)”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
Why: Late diarrhoea can start days after the drip, at home; starting loperamide at the first loose stool stops it becoming dangerous.
“Patients should have loperamide readily available to begin treatment for late diarrhea (generally occurring more than 24 hours after administration of CAMPTOSAR).”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
Why: These come from a direct effect of the drug on the nerves of the gut and glands, and are quickly relieved by treatment.
“It may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping. Bradycardia may also occur.”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
Why: Atropine blocks the nerve signal that causes the symptoms; giving it before the next dose usually prevents them.
“Consider prophylactic or therapeutic administration of 0.25 mg to 1 mg of intravenous or subcutaneous atropine (unless clinically contraindicated).”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
Why: Late diarrhoea can last days and cause dehydration and infection; it is easiest to control at the start.
“Begin loperamide at the first episode of poorly formed or loose stools or the earliest onset of bowel movements more frequent than normal.”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
Why: This higher dose is needed for irinotecan diarrhoea; beyond 48 hours it risks stopping the bowel altogether (paralytic ileus).
“One dosage regimen for loperamide is 4 mg at the first onset of late diarrhea and then 2 mg every 2 hours until the patient is diarrhea-free for at least 12 hours. Loperamide is not recommended to be used for more than 48 consecutive hours at these doses, because of the risk of paralytic ileus.”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
Why: These are signs that the diarrhoea is becoming dangerous and needs assessment the same day.
“Patients should contact their physician if any of the following occur: diarrhea for the first time during treatment; black or bloody stools; symptoms of dehydration such as lightheadedness, dizziness, or faintness; inability to take fluids by mouth due to nausea or vomiting; or inability to get diarrhea under control within 24 hours.”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
Why: Infection and dehydration on top of irinotecan diarrhoea can be fatal and need hospital treatment.
“Monitor and replace fluid and electrolytes. Use antibiotic support for ileus, fever, or severe neutropenia.”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
Why: Octreotide reduces the fluid the bowel secretes when loperamide has not worked.
“Octreotide 100 to 150 mcg SC three times daily (if dehydration severe, escalate dose up to 500 mcg three times daily).”
Why: Giving the next dose while the bowel is still recovering makes severe diarrhoea more likely.
“Subsequent weekly chemotherapy treatments should be delayed in patients until return of pretreatment bowel function for at least 24 hours without anti-diarrhea medication.”
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
The product label is the authority for this drug-specific toxicity, and eviQ's 2024-reviewed algorithm turns it into a nurse-led pathway with review points at 12 to 24 hours, admission criteria and octreotide as the next step. The two agree on high-dose loperamide (4 mg, then 2 mg every 2 hours, at most 48 hours) and on antibiotics for fever, ileus or severe neutropenia. They differ slightly on atropine: the label gives 0.25 to 1 mg as prophylaxis or treatment, eviQ 0.3 to 0.6 mg repeated to 1.2 mg as treatment. No graded guideline for irinotecan-specific diarrhoea was found.
Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026 · eviQ, Cancer Institute NSW 2024 · National Cancer Institute 2025
Where it differs: Atropine 0.3 to 0.6 mg intravenously or subcutaneously, repeated to a maximum of 1.2 mg; the whole algorithm applies to sacituzumab govitecan, with a note that its product information caps loperamide at 16 mg a day, though higher doses may be considered in severe diarrhoea.
Evidence: Australian state cancer agency algorithm, reviewed by its medical oncology reference committee in June 2024; not graded.
Where it differs: Gives scopolamine butylbromide, another antimuscarinic, before the next irinotecan dose to people who had the cholinergic syndrome, instead of atropine.
Evidence: Single-centre study of 59 outpatients: the syndrome occurred in 50.8 per cent, and prophylaxis at the next dose reduced it to 3.4 per cent; an irinotecan dose of 150 mg/m2 or more was the only risk factor identified. Not randomised.
A cheap gene test for DPYD, UGT1A1 and TPMT or NUDT15 before fluoropyrimidines, irinotecan or thiopurines identifies people at risk of severe or fatal toxicity so their dose can be lowered. The EMA has recommended DPD testing since 2020; US uptake remains partial.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Grade 3 to 4 late diarrhoea with weekly irinotecan dosing “Grade 3–4 late diarrhea occurred in 23–31% of patients receiving weekly dosing.” | Label incidence from the registration trials (23 to 31 per cent) | Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine 2026 |
| Scopolamine butylbromide prophylaxis reduced irinotecan-related cholinergic syndrome “Scopolamine butylbromide administration significantly reduced the incidence to 3.4% (P < 0.01).” | single-centre before-and-after study, P < 0.01 | Cancer Chemotherapy and Pharmacology 2019 |
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