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In advanced cancer, nausea and vomiting often have a cause that can be found and treated, such as constipation, a high calcium level, a medicine, or a blocked bowel. Your team will look for the cause, stop medicines that may worsen it, and choose an anti-sickness medicine that suits it, under the skin or by a small pump if tablets will not stay down. Say if it is not improving.
MASCC/ESMO (2016, the latest statement) found the evidence minimal and of low quality, and recommend metoclopramide titrated to effect as the drug of choice, with haloperidol, levomepromazine or olanzapine as alternatives; for bowel obstruction, octreotide with an antiemetic (haloperidol), or an anticholinergic antisecretory agent where octreotide is not an option. MASCC's 2021 update keeps octreotide as the drug of choice in inoperable bowel obstruction and suggests olanzapine or metoclopramide for partial obstruction. The Scottish Palliative Care Guidelines (2025) take a cause-based approach: identify and treat reversible causes, deprescribe, choose the antiemetic for the likely mechanism (haloperidol first for chemical or drug causes, metoclopramide for gastric stasis once complete obstruction is excluded, cyclizine for raised intracranial pressure or vestibular causes, levomepromazine as a broad-spectrum agent), use non-oral routes when needed, avoid combining prokinetics with anticholinergics, consider an ECG for QTc, and start olanzapine or mirtazapine only on specialist advice. In the one randomised comparison of the two approaches (185 people), a cause-based regimen worked faster at 24 hours but was no better than haloperidol alone at 72 hours. Methotrimeprazine (levomepromazine) was no better than haloperidol in a double-blind trial, and olanzapine 5 mg markedly reduced chronic nausea against placebo in a pilot trial of 30 people.
Why: The cause decides which medicine works best, and some causes can be removed altogether.
“Always try to identify the underlying causes of nausea and vomiting and treat if possible”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: Treating the cause can stop the nausea without long-term antiemetics.
“Correct any reversible causes of nausea and vomiting when possible (eg renal failure, hypercalcaemia, hyponatraemia, hyperglycaemia, constipation, symptomatic ascites, cerebral oedema or raised intracranial pressure).”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: Opioids, antibiotics, antidepressants and many other drugs can cause nausea, and fewer tablets are easier to keep down.
“Deprescribe potentially inappropriate medication to reduce tablet burden and polypharmacy where possible”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: Obstruction needs a different treatment: octreotide reduces the fluid in the gut that causes vomiting, and some antiemetics can worsen colic.
“For bowel obstruction, the recommendation is to use octreotide given alongside an antiemetic (haloperidol) and where octreotide is not an option to use an anticholinergic antisecretory agent.”
Why: Different causes act through different nerve pathways, each blocked best by a different drug.
“Select an antiemetic appropriate to the likely identified cause.”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: A drug that pushes the gut forward can cause severe cramping pain against a complete blockage.
“Before commencing a prokinetic it is important to ensure that the patient is not in complete obstruction and is not experiencing colic.”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: Metoclopramide is the agent MASCC/ESMO prefer, though the trials behind every choice are small.
“The drug of choice for managing N & V in advanced cancer is metoclopramide titrated to effect. Alternative options include haloperidol, levomepromazine, or olanzapine.”
Why: Nausea slows the stomach and vomiting loses tablets, so medicine by mouth may not work.
“the transdermal or parenteral route may be used if the oral route is not appropriate or to reduce tablet burden.”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: The anticholinergic cancels out the prokinetic's effect on the gut.
“Try to avoid the concurrent prescribing of prokinetics (eg metoclopramide) and anticholinergics (eg cyclizine) medication. The anticholinergics will diminish the prokinetic effect.”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: Several antiemetics can disturb the heart rhythm, especially in combination or at higher doses.
“Consider the appropriateness of performing an electrocardiogram (ECG) to measure QTc as many antiemetics increase the risk of QTc prolongation.”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: Simple measures reduce triggers and make eating and drinking easier.
“Non-pharmacological measures should be considered alongside the prescribing of appropriate antiemetics.”
Healthcare Improvement Scotland (Right Decision Service) 2025
Why: Persistent nausea often has more than one cause, and specialists can add drugs whose use in this setting is less established.
“Olanzapine and mirtazapine should only be commenced on specialist advice.”
Healthcare Improvement Scotland (Right Decision Service) 2025
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.
Two current approaches disagree on the first drug. MASCC/ESMO (2016, the latest international statement) recommend metoclopramide titrated to effect for most people, with haloperidol, levomepromazine or olanzapine as alternatives. The Scottish Palliative Care Guidelines (2025, the most recent national guideline read) choose by cause: haloperidol first for chemical and drug-induced nausea, metoclopramide for gastric stasis, cyclizine for intracranial or vestibular causes, levomepromazine for multifactorial nausea. Both rest on weak evidence: the one randomised comparison found a cause-based regimen faster at 24 hours but no better than haloperidol alone at 72 hours. They agree on finding and correcting reversible causes, on octreotide with an antiemetic for inoperable bowel obstruction (reaffirmed by MASCC in 2021), and on keeping olanzapine for when first-line drugs fail. NICE's Clinical Knowledge Summary could not be read.
MASCC/ESMO, Supportive Care in Cancer 2017 · Healthcare Improvement Scotland (Right Decision Service) 2025 · BMC Cancer 2018 · MASCC, Supportive Care in Cancer 2021 · NICE 2021
Where it differs: First line by mechanism: haloperidol for chemical or drug-induced nausea; metoclopramide or domperidone for gastric stasis, with erythromycin second line; cyclizine or prochlorperazine for raised intracranial pressure, vestibular or oral and oesophageal causes; levomepromazine second line or for multifactorial nausea; lorazepam for anxiety-related nausea. Dexamethasone for raised intracranial pressure or extrinsic compression.
Evidence: National guideline based on an evidence review and, where evidence was lacking, the expert opinion of its development group; recommendations are not individually graded.
Healthcare Improvement Scotland (Right Decision Service) 2025
Where it differs: Gives haloperidol to all, titrated, instead of choosing by cause.
Evidence: Open-label randomised trial of 185 people: response at 24 hours was higher with cause-based treatment (49 against 32 per cent among those completing each day), but at 72 hours the intention-to-treat response was 49 and 53 per cent, with no significant difference. The Cochrane review of haloperidol (2015) found only one eligible randomised trial.
BMC Cancer 2018 · Cochrane Database of Systematic Reviews 2015
Where it differs: Uses the broad-spectrum antipsychotic levomepromazine first.
Evidence: Double-blind trial at 11 Australian palliative care sites: response at 72 hours 63 per cent with methotrimeprazine 6.25 mg and 75 per cent with haloperidol 1.5 mg, with no difference, and a trend to more sedation with methotrimeprazine. The 2015 Cochrane review found no published randomised trial.
BMJ Open 2019 · Cochrane Database of Systematic Reviews 2015
Where it differs: Olanzapine 5 mg by mouth daily.
Evidence: Placebo-controlled pilot trial of 30 outpatients with chronic nausea not related to recent treatment: median nausea scores fell from 9 to 1 out of 10 at one week with olanzapine against 9 on placebo; no excess sedation reported. MASCC/ESMO list it as an alternative, and the Scottish guideline keeps it for specialist use.
JAMA Oncology 2020 · MASCC/ESMO, Supportive Care in Cancer 2017 · Healthcare Improvement Scotland (Right Decision Service) 2025
| Recommendation | Grade, as printed | Source |
|---|---|---|
| The quality of evidence for antiemetics in advanced cancer “The evidence base in this field is minimal with largely poor quality trials or uncontrolled trials and case studies. The level of evidence in most studies is low.” | MASCC/ESMO: low level of evidence in most studies | MASCC/ESMO, Supportive Care in Cancer 2017 |
| Octreotide in inoperable malignant bowel obstruction “The panel recommends octreotide in non-operable MBO.” | MASCC recommendation (level and category not shown in the abstract read) | MASCC, Supportive Care in Cancer 2021 |
| Cause-based treatment against single-agent haloperidol at 72 hours “Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59).” | open-label randomised trial, n = 185, p = 0.59 | BMC Cancer 2018 |
| No randomised trial of levomepromazine in palliative care “As in the initial review, we identified no published randomised controlled trials examining the use of levomepromazine for the management of nausea and vomiting in adults receiving palliative care” | Cochrane systematic review, 2015 | Cochrane Database of Systematic Reviews 2015 |
Shares Somatostatin analogues (octreotide, lanreotide), Multinational Association of Supportive Care in Cancer, Early integrated palliative care, Dexamethasone and the tags protocol, palliative.
Shares Antiemetics for chemotherapy-induced nausea and vomiting, Dexamethasone and the tags protocol, nausea-and-vomiting.
Shares Syringe pumps and subcutaneous syringe drivers, Pain relief and palliative care are unavailable to most, Early integrated palliative care.
Shares Somatostatin analogues (octreotide, lanreotide), Multinational Association of Supportive Care in Cancer, European Society for Medical Oncology (ESMO) and the tag protocol.
Shares Multinational Association of Supportive Care in Cancer, Antiemetics for chemotherapy-induced nausea and vomiting, European Society for Medical Oncology (ESMO), Dexamethasone.
Shares Multinational Association of Supportive Care in Cancer, European Society for Medical Oncology (ESMO), Dexamethasone and the tag protocol.
Shares European Society for Medical Oncology (ESMO) and the tag protocol.
Shares European Society for Medical Oncology (ESMO) and the tag protocol.