Management of Breakthrough Nausea and Vomiting

First-Line Breakthrough Options

The National Comprehensive Cancer Network recommends adding an agent from a different drug class to the current regimen rather than replacing ondansetron entirely when ondansetron fails, with metoclopramide (10-40 mg PO/IV every 4-6 hours), prochlorperazine (10 mg PO/IV every 4-6 hours), or olanzapine (2.5-5 mg PO BID) being the most evidence-based options for breakthrough nausea and vomiting 1, 2, 3
Prochlorperazine is recommended at a dose of 10 mg PO/IV every 4-6 hours, or 25 mg suppository every 12 hours, with monitoring for dystonic reactions 1, 2
Metoclopramide is recommended at a dose of 10-40 mg PO/IV every 4-6 hours, with monitoring for dystonic reactions 1, 2, 4

Olanzapine is recommended at a dose of 2.5-5 mg PO BID, with a note of black box warning regarding type II diabetes, hyperglycemia, and death in elderly patients with dementia 1, 2, 3
Haloperidol is recommended at a dose of 0.5-2 mg PO/IV every 4-6 hours 1, 2

The National Comprehensive Cancer Network recommends switching to a different 5-HT3 antagonist, such as granisetron (1-2 mg PO daily or 1 mg PO BID), dolasetron (100 mg PO daily), or palonosetron (0.25 mg IV or 0.50 mg PO), if not already tried 1, 2, 7

Dexamethasone is recommended at a dose of 12 mg PO/IV daily, with enhanced efficacy when combined with 5-HT3 antagonists 1, 2, 7

The National Comprehensive Cancer Network recommends switching to scheduled dosing once breakthrough nausea/vomiting occurs, and escalating to a higher level of primary treatment for the next chemotherapy cycle if breakthrough occurs 1, 2
Reevaluation of the underlying cause of nausea/vomiting is recommended, with consideration of dose adjustments of the antiemetic regimen and/or switching to different therapy if nausea/vomiting persists 1, 2

Extrapyramidal symptoms, such as dystonic reactions, can occur with metoclopramide and prochlorperazine, and diphenhydramine should be readily available for treatment 1, 2, 4
Inadequate prophylaxis, rather than true drug failure, may be the cause of ondansetron failure, and ensuring appropriate combination therapy was used initially is recommended 7, 4, 3