Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• Prescribe anti-emetics regularly and as required up to the maximum recommended dose.
• If the maximum recommended dose of a regular anti-emetic is reached, prescribe an alternative anti-emetic for 'as required' use.
• Table 1 shows the recommended dosing regimens for anti-emetics.

• 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 patients 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 (e.g. 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 octreotide).
• Use sodium chloride as the diluent for octreotide and consider a second syringe driver if octreotide is to be co-administered with other drugs.
• Check the compatibility of drugs before mixing. Most data concern combinations of two drugs in a syringe driver, although some combinations of three or four drugs are compatible. For further information on the compatibility of drugs in syringe drivers, seek advice from the local palliative care team or hospital drug information service. If you cannot contact them, see www.palliativedrugs.com.
• Do not use solutions that are discoloured or have precipitated.

[Twycross and Wilcock, 2001; Fife Area Drug & Therapeutics Committee, 2004; Perdue, 2005]

• Do not give prokinetics concurrently with drugs with antimuscarinic activity (e.g. cyclizine, hyoscine), because antimuscarinic drugs competitively block the action of prokinetics.
• Metoclopramide:
• Metoclopramide is generally given orally three to four times a day. It may be given as a subcutaneous injection or infusion.
• Metoclopramide can induce acute dystonic reactions involving facial and skeletal muscle spasms and oculogyric crises. These reactions are more common in younger people (particularly girls and young women) and people who are also taking other drugs known to cause extrapyramidal effects. They generally occur within a few days of starting treatment and subside within 24 hours of stopping metoclopramide. Injection of procyclidine, 5–10 mg intravenously or intramuscularly, will abort a dystonic attack.
• Other adverse effects include drowsiness, restlessness, and diarrhoea.
• Domperidone:
• Domperidone can be given orally or rectally.
• Domperidone is not as effective as metoclopramide, but it is less likely to cause central adverse effects, such as sedation and dystonic reactions.

[Twycross et al, 2002]

• Haloperidol is usually given orally once or twice a day to treat chemically or metabolically induced vomiting. This is an off-licence indication for haloperidol tablets and oral solution.
• At the low doses used in palliative care, adverse effects (e.g. dystonias, dyskinesia, and akathisia) are unusual.

[Twycross et al, 2002]

• Levomepromazine is usually used as a second- or third-line anti-emetic because of its sedative effect.
• Levomepromazine may be given orally but is generally given by the subcutaneous route. It is usually given once a day but some people may benefit from dividing the daily dose to twice or three times a day, or from continuous subcutaneous infusion.
• When converting from the oral route to the subcutaneous route the dose should be divided by two.
• Levomepromazine 6 mg tablets are an off-licence preparation and are available on a named-patient basis only. They can be ordered direct from the manufacturer (but this can take up to 48 hours) or they may be available through the local palliative care team or hospice.
• If the 6 mg tablets are not available, experts suggest using a quarter of a 25 mg tablet (i.e. 6.25 mg).
• Adverse effects include sedation (particularly at doses of 25 mg or more in 24 hours), dose-dependent postural hypotension, and antimuscarinic adverse effects (dry mouth, sedation, and blurred vision). Doses less than 12.5 mg daily do not usually cause problems.

[Twycross et al, 2002]

• Cyclizine can be given two to three times a day by mouth or subcutaneous or intravenous injection; or by continuous subcutaneous infusion. Subcutaneous administration may cause skin irritation at the injection site.
• Drowsiness and antimuscarinic adverse effects (dry mouth and blurred vision) are common.

[Twycross and Wilcock, 2001]

• Dexamethasone is generally given as a single dose in the morning but may be given via a syringe driver when appropriate. If large doses cannot be taken at once because of nausea, the dose may be divided and given in the morning and at lunchtime. If possible, oral or subcutaneous dexamethasone should be taken no later than 16.00 hours, to avoid night-time restlessness.
• Regular mouth care is essential in people taking oral corticosteroids because oral candidiasis is common.
• Dyspepsia and indigestion are common. The risk of serious gastrointestinal complications (e.g. peptic ulcer or silent perforation) is markedly increased in people who are also taking nonsteroidal anti-inflammatory drugs (NSAIDs) [Piper et al, 1991]. Gastrointestinal prophylaxis with a proton pump inhibitor or misoprostol should be considered for people receiving concurrent NSAIDs or those with a history of peptic ulcer disease. Use dexamethasone in people with active peptic ulcer disease only if the benefits are likely to outweigh the risks.
• Corticosteroids may worsen diabetic control.
• Advise all people using corticosteroids to seek urgent medical attention if they come into contact with someone with chickenpox or shingles [CSM, 1998].
• Stopping use of dexamethasone in the terminal phase lacks expert consensus:
• If the oral route is no longer available, dexamethasone can be given as a single slow subcutaneous dose once a day.
• If treatment is not given, patients may become agitated and distressed because of corticosteroid withdrawal. The onset of withdrawal symptoms is highly variable, depending on the risk of adrenal suppression, the length of time that the person lives after their last treatment, and their degree of physical stress; it is highly unlikely within the first 24 hours.
• The clinician must balance the disadvantages of intrusive treatment of a dying person against the risks of not providing treatment.

• Hyoscine butylbromide must not be confused with hyoscine hydrobromide, which is used in lower doses.
• Hyoscine butylbromide is poorly absorbed orally. For the management of nausea and vomiting it should be given as a subcutaneous bolus dose or by continuous subcutaneous infusion.
• Unlike hyoscine hydrobromide, hyoscine butylbromide does not cross the blood–brain barrier and therefore does not cause drowsiness or have a central anti-emetic action.
• Antimuscarinics should be avoided in people with paralytic ileus or symptomatic acid reflux, as they relax the lower oesophageal sphincter.
• Antimuscarinics may precipitate glaucoma in people at risk, particularly the elderly.

[Twycross and Wilcock, 2001]