# Neratinib: diarrhoea prevention with loperamide or dose escalation

Source: https://onco.cc/protocols/neratinib-diarrhoea-prophylaxis-and-dose-escalation/  
OnCo record `neratinib-diarrhoea-prophylaxis-and-dose-escalation` (Protocol). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Neratinib, a tablet for HER2-positive breast cancer, causes diarrhoea in almost everyone. Prevent it in one of two ways agreed before you start: loperamide on a fixed schedule from the first tablet for eight weeks, or a lower starting dose built up over two weeks. Drink about two litres a day, and call your team at once if diarrhoea is severe or comes with weakness, dizziness or fever.

## Summary

Without prophylaxis, diarrhoea occurred in 95 per cent of people in ExteNET, grade 3 in 40 per cent, with a median onset of grade 3 or worse at day 8. The US label now offers two strategies from the first dose. Either loperamide prophylaxis for the first 56 days (4 mg three times daily in weeks 1 and 2, 4 mg twice daily in weeks 3 to 8, then as needed up to 16 mg a day, titrated to one or two bowel movements a day), or a two-week neratinib dose escalation (120 mg a day in week 1, 160 mg in week 2, 240 mg from week 3) with loperamide as needed. In the open-label phase II CONTROL trial, six non-comparative cohorts of 563 people starting extended adjuvant neratinib all had less grade 3 diarrhoea than historical controls; it was lowest with the two-week escalation (13 per cent) and highest with colestipol plus loperamide as needed (33 per cent), and diarrhoea-related discontinuations were 3 per cent with the two-week escalation against 20 per cent with loperamide alone. The label's dose modification table sets when to adjust antidiarrhoeals, interrupt, reduce or stop.

## Fields

- Kind: Protocol
- Last checked: 2026-11-11
- Also known as: neratinib diarrhoea prophylaxis; Nerlynx loperamide schedule; neratinib dose escalation; CONTROL trial strategies
- Tags: protocol; diarrhoea; supportive-care

## Connected records

- protocols: [Diarrhoea from chemotherapy, targeted therapy and radiotherapy: grading, loperamide, octreotide and when to admit](https://onco.cc/protocols/treatment-induced-diarrhoea-grading-and-management/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Neratinib](https://onco.cc/drugs/neratinib/)
- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/)
- fronts: [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- technologies: [HER2 tyrosine kinase inhibitors](https://onco.cc/technologies/her2-tyrosine-kinase-inhibitors/)
- companies: [Puma Biotechnology](https://onco.cc/companies/puma-biotechnology/)
- terms: [CTCAE toxicity grading (grade 3-4 adverse events)](https://onco.cc/terms/ctcae-grading/)
- trials: [NALA](https://onco.cc/trials/nala/)
- ideas: [Start neratinib at a lower dose and build up over two weeks, as the default](https://onco.cc/ideas/idea-upgrade-neratinib-two-week-dose-escalation-by-default/)

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