Previous changes

March 2021 — reviewed. Literature searches were conducted in February 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic.

October 2020 — minor update. Reference to levomepromazine 6 mg being unlicensed has been removed from this topic as a licensed product is now available.

July 2015 to October 2016 — reviewed. Literature searches were conducted in September 2016 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. There have been structural changes to the topic and changes to the recommendations have been updated in line with NICE guidance Care of dying adults in the last days of life [NICE, 2015].

July 2015 — topic title changed to reflect broader topic coverage than specifically cancer care.

July 2014 — minor update. Update to the text to state that although the European Medicines Agency (EMA) has issued advice restricting the use of metoclopramide and domperidone, following clarification from the EMA this advice does not apply to unlicensed uses of metoclopramide (for example palliative care).

June 2013 — minor update. The 2013 QOF options for local implementation have been added to this topic.

September 2012 — reviewed. A literature search was conducted in August 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to recommendations have been made.

March 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic. Issued in April 2012.

January 2012 — minor update. McNeil Products Ltd, in collaboration with the Medicines and Healthcare products Regulatory Agency (MHRA), has published new safety data regarding the association of domperidone with an increased risk of serious ventricular arrhythmias or sudden cardiac death. This topic has been updated to reflect their advice on dosing, adverse effects, and drug interactions. Issued in February 2012.

May 2011 — minor update. The 2011/2012 QOF indicators have been added to this topic. Issued in June 2011.

February 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

July to October 2007 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail and recommendations are more clearly justified and transparently linked to the supporting evidence. A section has been added covering the management of nausea and vomiting at the end of life. The emphasis of this CKS topic is on the treatment of nausea and vomiting in a palliative care situation; malignant bowel obstruction has been included, but in less detail than previously.

January 2006 — minor update. Prescriptions for diamorphine updated to reflect the change in handwriting requirements for controlled drug prescriptions. Issued in February 2006.

October 2005 — minor technical update. Issued in November 2005.

March 2004 — written in March 2004. Validated in June 2004 and issued in July 2004.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 March 2021.

HTAs (Health Technology Assessments)

No new HTAs since 1 March 2021.

Economic appraisals

No new economic appraisals relevant to England since 1 March 2021.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 March 2021.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 March 2021.

New policies

No new national policies or guidelines since 1 March 2021.

New safety alerts

No new safety alerts since 1 March 2021.

Changes in product availability

• New product: Levorol (levomepromazine maleate) 6.25 mg Tablets. Approved for use in psychiatric conditions, e.g. schizophrenia, as an alternative to chlorpromazine particularly to reduce psychomotor activity. Also, for use as an adjunct in terminal illness for the relief of pain, distress and refractory (non-chemotherapy related) nausea. See more here.
• New product: Epzit (domperidone) 10 mg orodispersible tablet formulation of domperidone is licensed for the relief of the symptoms of nausea and vomiting. See more here.

How should I assess the person and determine the cause of nausea and vomiting?

• Use findings from the history, examination, and investigations to try and identify the cause of the nausea and vomiting, and assess the person's clinical state. See Features indicating a cause for help diagnosing the underlying cause.
• Consider whether treatment of the cause is appropriate, or whether the emphasis should be on treatment of symptoms.
• Take the following factors into account:
  • The stage of the illness and the person's prognosis.
  • The person's wishes and those of their carers and family.
  • The cause of the person's nausea or vomiting and whether it is reversible or treatable.
  • The severity of nausea or vomiting and the presence of complications (for example dehydration, poor nutrition, or diminished quality of life).
  • The urgency with which treatment is required.
  • The input of the multidisciplinary team (for more information, see the CKS topic on Palliative care - general issues).

What should I ask about the nausea and vomiting?

• Ask about:
  • Features of:
    • Nausea: onset, frequency, intensity, relieving and exacerbating factors, and relationship to vomiting.
    • Vomiting: onset, frequency, quantity, force, colour, timing, and pattern.
  • Other symptoms such as:
    • Dyspepsia, heartburn, reflux symptoms, fullness, early satiety, constipation, diarrhoea, flatus, cough, headache, or confusion.
  • Treatment history, including:
    • Simple measures — what has been tried and its effectiveness.
    • Current medication — recent changes and coinciding symptoms (especially with opiates, anticholinergics, digoxin, and antibiotics).
    • Chemotherapy — regimen and timing of last treatment.
    • Anti-emetics — current and past use, and effectiveness.
    • Radiation — area treated and number of treatments received.
  • Medical history (for example ulcers or bowel surgery).
  • Effect on nutrition (for example fluid and food intake in the past 24 hours).
  • Effect on quality of life.
• For more information, see Features indicating a cause.

What should I look for on examination?

• Perform an appropriate examination for the stage of the person's illness to determine, if possible, the cause of nausea or vomiting:
  • Perform a general examination (for example look for signs of dehydration, infection, confusion, drowsiness, or weakness), including temperature, pulse, and respiratory rate. 
  • Assess the condition of the oral cavity (for example look for signs of Candida, tumour, or poor dental condition).
  • Examine the abdomen for tenderness, swelling, or distension; signs of intestinal obstruction; organomegaly; or constipation.
  • If faecal impaction is suspected, perform a rectal examination.
  • If increased intracranial pressure is a possibility, check the fundi for papilloedema (although absence of papilloedema does not exclude intracranial pathology).
  • Determine whether anxiety could be contributing to the person's symptoms.

How should I investigate nausea and vomiting in palliative care?

• With the person and their carers and family, determine what investigations are appropriate for the person's stage of illness:
  • The choice of diagnostic tests should be based on the stage of disease, the person's prognosis, the risk-to-benefit ratio of the investigation, and the wishes of the person and their family.
  • Blood tests to exclude hypercalcaemia or uraemia are among the most useful investigations to do in primary care for all people with nausea or vomiting in a palliative care situation.
  • Other blood tests that may be useful include liver function tests and blood glucose level. 
  • Consider tests to exclude a urinary tract infection. 
  • Other investigations may be performed in secondary care (for example abdominal radiography to exclude constipation and ultrasonography to detect ascites), if appropriate. 

How should I manage nausea and vomiting of known cause?

• Manage the underlying cause or correct reversible causes if possible and appropriate.
• Try simple measures to relieve symptoms.
• Choose an anti-emetic according to the cause of nausea and vomiting such as:
  • Drugs (for example opioids, diuretics, nonsteroidal anti-inflammatory drugs, or antibiotics).
  • Metabolic causes (for example hypercalcaemia, renal failure, or tumour toxins).
  • Intracranial disease (for example raised intracranial pressure or brainstem/meningeal disease).
  • Movement (for example vestibular disease or tumour at the base of the skull).
  • Bowel obstruction.
  • Abdominal or pelvic tumour.
  • Gastric stasis.
  • Anxiety.
• Ascertain the most appropriate route of administration of the anti-emetic.
• Prescribe anti-emetics regularly and as required.
• Review the effectiveness of anti-emetic treatment every 24 hours.
• Continue use of anti-emetics unless nausea and vomiting has resolved (for example the cause was self-limited or has been reversed).

What simple measures may help nausea and vomiting in palliative care?

• Make sure the person has access to a large bowl, tissues, and water.
• The sight and smell of food or drink may provoke nausea:
  • Provide a calm environment away from where food is usually prepared or consumed.
  • If the person is usually responsible for cooking, make alternative arrangements.
  • Make sure that meals are small and palatable — snacks consisting of a few mouthfuls are less challenging than big meals.
  • Carbohydrate meals are often better tolerated.
  • Offer cool, fizzy drinks (citrus flavours are often preferred) — these are more palatable than still or hot drinks.
• Consider the use of complementary therapies; relaxation and acupressure bands may be useful to relieve symptoms.
• Consider cognitive behavioural therapy for anticipatory nausea or vomiting.
• In general, avoid nasogastric suction. It has no role in the management of most causes of nausea and vomiting.

How should I treat toxicity-related nausea and vomiting from drug-induced or metabolic upset?

• Review current medication use:
  • Discontinue use of any unnecessary medications.
  • Check blood levels if appropriate (for example with digoxin, phenytoin, and carbamazepine).
• For chemotherapy-induced nausea and vomiting: seek advice from the specialist who is supervising the person's chemotherapy.
• For chemically induced nausea and vomiting (most drugs, including opioids) there are three options:
  • Haloperidol via the most appropriate route of administration.
    • Usual oral dose: 1.5 mg at night or twice daily, titrate up to a maximum dose of 10 mg daily (some suggest a lower starting dose of 0.5 mg especially for frail or elderly people).
    • As-required dose: oral, 1.5 mg; subcutaneous injection, 1.25–2.5 mg.
    • Syringe driver dose per 24 hours: 2.5–5 mg.
  • Metoclopramide
    • Oral dose: 10 mg 4 times a day.
    • Subcutaneous syringe driver dose: 30–60 mg over 24 hours (off license use).
    • Monitor for extra-pyramidal adverse effects.
  • Levomepromazine
    • Subcutaneous syringe driver dose: 2.5–6.25 mg 12 hourly as needed or 6.25–12.5 mg over 24 hours by infusion. 
• To manage gastrointestinal irritation (for example due to nonsteroidal anti-inflammatory drugs, some antibiotics, or iron supplements): change the drug if possible, or consider gastroprotection.
• To manage nausea and vomiting caused by antimuscarinic drugs (for example amitriptyline, lofepramine, or opioids): treat as gastric stasis.
• If hypercalcaemia is present (corrected serum calcium concentration greater than 2.8 mmol/L), arrange hospital admission, if appropriate.
  • Management of hypercalcaemia usually involves admission for intravenous rehydration and bisphosphonates.
  • Correction of hypercalcaemia may not always be appropriate in people near the end of life.
  • For more information, see the Scenario: Known cancer in the CKS topic on Hypercalcaemia.

How should I treat nausea and vomiting due to intracranial disease?

• For nausea and vomiting due to intracranial disease: give cyclizine via the most appropriate route of administration.
  • Usual oral dose: 25–50 mg every 8 hours up to a maximum dose of 150 mg daily.
  • Immediate/as-required dose: oral and subcutaneous injection, 25–50 mg every 8 hours.
  • Syringe driver dose per 24 hours: 50–150 mg.
• If intracranial pressure is raised:
  • Consider referral for radiotherapy for all people with raised intracranial pressure due to a tumour.
  • Consider adding high-dose dexamethasone to cyclizine:
    • A suitable dose might be 8–16 mg daily for up to 7 days. If dexamethasone has been given for longer than 5 days, or there is a risk of recurrent severe symptoms, or repeated courses of dexamethasone have been given, dexamethasone should be reduced by 2 mg daily every 5–7 days.
    • Stop dexamethasone therapy if there is no obvious benefit within 3–7 days, or if it becomes ineffective.
• Second-line therapy – levomepromazine 3–6 mg twice daily orally or 2.5–5 mg by subcutaneous injection 12 hourly as needed or 5–15 mg in 24 hours by continuous subcutaneous infusion.

How should I treat movement-related nausea and vomiting?

• For vestibular disturbance (for example diseases of the inner ear and motion sickness): give cyclizine via the most appropriate route of administration.
  • Usual oral dose: 25–50 mg every 8 hours up to a maximum dose of 150 mg daily.
  • As-required dose: oral and subcutaneous injection, 25–50 mg every 8 hours.
  • Syringe driver dose/24 hours: 50–150 mg.
• Alternative therapeutic options include: 
  • Hyoscine hydrobromide: 150–300 micrograms orally, 200–400 micrograms subcutaneously or 1 mg/72 hours via transdermal patch.
  • Cinnarizine: 30 mg orally initially then 15 mg three times a day.
  • Levomepromazine: 3–6 mg twice daily orally or 2.5–5 mg by subcutaneous injection 12 hourly as needed or 5–15 mg in 24 hours by continuous subcutaneous infusion.
  • Prochlorperazine: 3 mg buccal or 5–15 mg oral medication. 
• Be aware that movement may intensify symptoms of abdominal and pelvic tumour. For more details see Nausea and vomiting related to an abdominal or pelvic tumour.

How should I treat nausea and vomiting due to bowel obstruction?

• Bowel obstruction may be due to peristaltic failure or mechanical obstruction. When managing nausea and vomiting due to bowel obstruction:
  • If necessary, seek specialist advice early as management can be complex.
  • A syringe driver may be needed because the oral route is often unreliable.
• To manage bowel obstruction due to peristaltic failure:
  • If possible, stop drugs that decrease peristalsis (for example cyclizine, tricyclic antidepressants, or opioids).
  • If there is no colic: start a prokinetic anti-emetic (for example metoclopramide, 30–100 mg/24 hours) via continuous subcutaneous infusion (CSCI).
  • If colic develops: stop the prokinetic anti-emetic and treat as for mechanical obstruction.
• To manage bowel obstruction due to mechanical obstruction:
  • Exclude constipation, or treat if present:
    • To relieve and prevent constipation, docusate or Movicol^® should be titrated to produce a comfortable stool without colic. For more information, see the CKS topic on Palliative care - constipation.
  • Treat nausea with cyclizine, 50–150 mg/24 hours via CSCI:
    • If nausea persists, add haloperidol, 2.5–10 mg/24 hours or as a single night-time dose, or levomepromazine, 5–25 mg/24 hours or as a single night-time dose.
    • Avoid prokinetics.
  • Treat colic with an antimuscarinic drug (for example hyoscine butylbromide, 20 mg immediately by subcutaneous injection, then 60–100 mg/24 hours via CSCI).
  • Manage large-volume vomiting with an antisecretory drug (for example hyoscine butylbromide or octreotide).
    • Hyoscine will reduce secretions and treat colic, but its full antisecretory effect is achieved after about 3 days.
    • If large volume vomiting persists, consider using octreotide if a more rapid or profound antisecretory effect is required. This may require admission, depending on the experience of the primary healthcare professional and the availability of octreotide in the community.

How should I treat nausea and vomiting due to an abdominal or pelvic tumour?

• To manage nausea and vomiting due to distension, compression, or disturbance of abdominal or pelvic organs (for example bowel or liver): give cyclizine via the most appropriate route of administration.
  • Usual oral dose: 25–50 mg every 8 hours up to a maximum dose of 150 mg daily.
  • As-required dose: oral and subcutaneous injection, 25–50 mg every 8 hours.
  • Syringe driver dose per 24 hours: 50–150 mg.
• If bowel obstruction is suspected: see Bowel obstruction-related nausea and vomiting.

How should I treat nausea and vomiting due to gastric stasis?

• To manage nausea and vomiting due to gastric stasis: give metoclopramide.
  • Unless gastric stasis is mild, start metoclopramide parenterally (10–20 mg every 8 hours by subcutaneous injection or 30–100 mg/24 hours via continuous subcutaneous infusion).
  • If extrapyramidal effects are a problem with metoclopramide, use domperidone (30–60 mg rectally every 4–8 hours).
• Do not give prokinetics concurrently with drugs with antimuscarinic activity (for example cyclizine and hyoscine).

How should I treat anxiety-related nausea and vomiting?

• Manage anxiety independently, according to the person's prognosis.
• Consider non-drug interventions including cognitive behavioural therapy, if appropriate to the stage of disease. 
• Consider a benzodiazepine (for example lorazepam, 0.5–1 mg sublingually) or levomepromazine (3–6 mg orally or 2.5–6.25 mg by subcutaneous injection).

Managing nausea and vomiting with an unknown cause

• Try simple measures to relieve symptoms.
• Review the person's history, examination results, and medication(s), and consider checking blood for signs of renal failure, hypercalcaemia, liver failure, or blood glucose abnormalities.
• If the cause is still uncertain or further investigation is not appropriate then a trial of medication is appropriate.
• The options for a therapeutic trial include:
  • Levomepromazine
    • Usual dose 3–6 mg twice daily orally or 2.5–5 mg by subcutaneous injection 12 hourly as needed or 5–15 mg in 24 hours by continuous subcutaneous infusion.
  • Metoclopramide
    • Usual dose 10 mg 4 times a day. 
  • Haloperidol
    • Usual oral dose: 1.5 mg at night or twice daily and titrate up to a maximum of 10 mg daily (some experts suggest a lower starting dose of 0.5 mg).
    • As-required dose: oral, 1.5 mg; subcutaneous injection,1.25–2.5 mg.
    • Syringe driver dose per 24 hours: 2.5–10 mg.
  • Cyclizine
    • Usual oral dose: 25–50 mg every 8 hours up to a maximum dose of 150 mg daily.
    • As-required dose for oral and subcutaneous injection: 1.5 mg.
    • Syringe driver dose per 24 hours: 50–150 mg.
• If these options are ineffective, consider a trial of dexamethasone (seek specialist advice first).
• In addition:
  • Ascertain the most appropriate route of administration of the anti-emetic(s).
  • Prescribe anti-emetics regularly and as required.
  • Review the effectiveness of anti-emetic treatment every 24 hours.
  • Continue anti-emetics unless nausea and vomiting has resolved.

What should I do if a first-line anti-emetic has not worked?

• If a single first-line anti-emetic does not relieve nausea and vomiting:
  • Optimize the dose of the first-line anti-emetic.
  • Consider the need for an alternative route of administration.
• If nausea and vomiting persist after two or three doses of optimal first-line anti-emetic:
  • Change to an anti-emetic with a different action, or combine anti-emetics with complementary action.
    • Do not combine prokinetics (metoclopramide or domperidone) with antimuscarinics (for example hyoscine, cyclizine, or levomepromazine).
    • About one-third of people with advanced cancer who experience nausea and vomiting will require more than one anti-emetic to control their nausea and vomiting.
• Refer to a specialist palliative care team if symptoms remain uncontrolled after 24 hours.

How do I recognize the terminal phase?

• It can often be difficult to be certain that a person is dying, but it is essential to recognize the signs of dying in order to appropriately care for people at the end of life.
• The terminal phase may last hours to several days.
• People are likely to be in the terminal phase of their illness when they:
  • Deteriorate day by day or more rapidly.
  • Have reduced mobility and become progressively weak and fatigued without an apparent cause (for example hypercalcaemia).
  • Express a realization that they are dying.
  • Have reduced cognition, ability to communicate, and social withdrawal.
  • Have a deterioration in level of consciousness.
  • Are delirious, characterized by increased restlessness, confusion, and agitation.
  • Are bed-bound.
  • Take little food or fluid, and have difficulty taking oral medication.
  • Are peripherally cyanosed, have mottled skin, and are cold to the touch.
  • Have apnoea (whether awake or asleep) or an altered breathing pattern, such as Cheyne-Stokes breathing.
• For further details, see the CKS topic on Palliative cancer care - general issues.

How should I manage nausea and vomiting at the end of life?

• Assess for likely causes of nausea or vomiting in the dying person. See Scenario: Assessment.
• Discuss the options for treating nausea and vomiting with the dying person and those people important to them.
• Consider non-pharmacological simple measures for treating nausea and vomiting.
• When choosing medicines to manage nausea or vomiting in a person in the last days of life, take into account:
  • The likely cause and if it is reversible.
  • The side effects, including sedative effects, of the medicine.
  • Other symptoms the person has.
  • The desired balancing of effects when managing other symptoms.
  • Compatibility and drug interactions with other medicines the person is taking.
• If an anti-emetic already controls symptoms well:
  • Continue with the same drug.
  • Give the same drug by syringe driver if the person becomes unable to take oral medication. If an injectable form is not available, use a drug with a similar mode of action.
• For new or uncontrolled nausea and vomiting:
  • If appropriate, try to determine the underlying cause of nausea and vomiting and manage accordingly. See Scenario: Known cause.
  • Otherwise give levomepromazine 6.25 mg once daily by subcutaneous injection. Repeat the dose after 1 hour if needed.
  • If a repeat dose is needed, start levomepromazine by continuous subcutaneous injection:
    • Start at a dose of 12.5 mg in 24 hours, plus a 6.25 mg subcutaneous injection as needed.
    • If one or more extra doses are needed, increase the dose to 25 mg in 24 hours.
• For people in the last days of life with obstructive bowel disorders who have nausea or vomiting, consider:
  • Hyoscine butylbromide (off-label indication) as the first-line pharmacological treatment.
  • If the symptoms do not improve within 24 hours of starting hyoscine the recommended second-line treatment is octreotide (off-label indication).
  • If symptoms remain uncontrolled, contact the local palliative care team for advice.
  • Review the effectiveness of anti-emetic treatment every 24 hours.
  • For more information on recognizing the terminal phase and issues relating to caring for a person and their family at this time, see the CKS topic on Palliative care - general issues.

What route of administration should I use?

• Oral administration is the route of choice. However, this may not be appropriate for people:
  • Who cannot swallow.
  • With compromised absorption.
  • Who have persistent nausea and vomiting.
  • In whom swallowing causes them to vomit.
  • With gastric stasis or bowel obstruction.
• If the oral route is not appropriate, give anti-emetics parenterally (subcutaneously or intravenously) or rectally. The intramuscular route is not recommended as people with advanced cancer tend to be cachectic.
• If the person has continuous or severe nausea or frequent vomiting, continuous subcutaneous infusion via a syringe driver is the route of choice.
  • Continuous subcutaneous infusion (via a syringe driver) is used for drug delivery if the person cannot take medicines by mouth (for example because of persistent nausea and vomiting, dysphagia, severe weakness, poor oral absorption, or coma).
  • Use only drugs that are known to be safe and effective by the subcutaneous route. These include metoclopramide, haloperidol, cyclizine, hyoscine butylbromide, and levomepromazine.
  • Use water for injection as the diluent when mixing drugs in a syringe driver except for levomepromazine, dexamethasone, octreotide, and ketorolac. Use sodium chloride as the diluent for these drugs and consider a second syringe driver if they are to be co-administered with other drugs.
  • Before mixing drugs, check their compatibility.
    • Always follow local palliative care guidelines or seek advice from local palliative care services or hospital pharmacy drug information services before mixing drugs in a syringe driver.
    • Data are most often available on combinations of two drugs in a syringe driver, although some combinations of three or four drugs are compatible.
    • If you cannot contact the appropriate authorities for further guidance, see www.palliativedrugs.com/syringe-driver-database-introduction.html (registration required).
  • Do not use solutions that are discoloured or have precipitated.

[Wilcock, 2020; NHS Scotland, 2021]