Previous changes

January 2025 — minor update. A safety warning about the use of oral swabs with a foam head has been added to this topic.

July 2023 — minor update.  The manufacturer's SPC for metronidazole has been updated to note that QT prolongation has been reported (unknown frequency), particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

December 2022 — minor update. Clarification added about the use of betamethasone tablets for ulcers.

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. Minor restructuring of the topic was undertaken and recommendations updated in line with new evidence and guidelines. 

October 2018 — minor update. Adverse effects updated within prescribing information - metronidazole. 

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.

April 2015 — minor update. Link inserted.

December 2013 — minor update. Text updated to reflect that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections.

August 2013 — minor update to the text to reflect recent guidance from the European Medicines Agency regarding the use of oral ketoconazole.

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

November 2012 — minor update. The links to the electronic medicines website (www.medicines.org.uk) have been updated.

November 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.

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

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

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

December 2009 — minor update. Xerotin^®, an artificial saliva spray, is now listed in the Appliances section of the Drug Tariff, so can be prescribed on from FP10. Prescription added. 

August 2009 — minor update. Triamcinolone in an adhesive paste (Adcortyl in Orabase^®) is no longer available in either the 5 gram or the 10 gram pack size. Prescription removed. 

May 2009 — minor update. Triamcinolone in an adhesive paste (Adcortyl in Orabase^®) is no longer available in the 10 gram pack size. The 5 gram over-the-counter pack size is still available. 

October 2008 — minor update. Quench Pharma Ltd. are now distributing BioXtra^®gel. Text and prescriptions reinstated. 

August 2008 — minor update. BioXtra^®gel and nystatin pastilles discontinued; prescriptions removed and text amended. 

January to April 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. There have been no major changes to the recommendations. The primary care management of oral problems has been described in detail.

November 2005 — minor technical update. 

July 2005 — minor update to include topical artificial saliva products containing lactoperoxidase. 

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

New evidence

Evidence-based guidelines

• SPS (2021) Choosing formulations of medicines for adults with swallowing difficulties. Specialist Pharmacy Service. www.sps.nhs.uk [Free Full-text]

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

No changes in product availability since 1 March 2021.

Dry mouth

• The possible causes of a dry mouth are:
  • Dehydration due to fluid loss (for example vomiting, diarrhoea, hypercalcaemia, uncontrolled diabetes mellitus).
  • Reduction in the production of saliva:
    • Drugs that reduce the secretion of saliva (Table 2).
    • Poor oral intake (for example dysphagia).
    • Oxygen without humidification.
    • Damage to the salivary glands after radiotherapy to the head and/or neck.
    • Surgery to the buccal region or that involves the major salivary glands (parotid, submandibular, sublingual) or their ducts.
    • Obstruction, infection, or malignant destruction of the salivary glands.
    • Anxiety that can cause temporary dry mouth by reducing salivary flow.
    • Specific conditions, for example Sjögren's syndrome, sarcoidosis, HIV, hepatitis C.
  • Mouth breathing.

 [Regnard, 2022; Davies, 2015; Twycross, 2016; NHS Scotland, 2021]

Table 2. Commonly prescribed drugs that are often associated with reduced saliva.

Painful mouth

• The causes of a painful mouth include:
  • Ulceration:
    • Viral (zoster, herpes simplex) ulcers.
    • Aphthous ulcers.
    • Neutropenic ulcers.
  • Inflammation due to:
    • Oral candidiasis.
    • Dental abscess.
  • Dental pain (dentine hypersensitivity, pulpitis, periapical periodontitis).
  • Denture pain. This typically relates to physical trauma damaging the mucosa, underlying bone pathology or a prominent nerve (for example the mental nerve following alveolar resorption).
  • Mucositis (ulceration associated with diffuse erythema and pseudomembrane formation after chemotherapy/radiotherapy).
  • Neuropathic pain.
  • Oral dysaesthesias (for example burning mouth syndrome).
  • Chronic facial pain.
  • Underlying bone pathology (osteomyelitis, osteoradionecrosis or bisphosphonate osteonecrosis).
• Note that a dry mouth although not causing a painful mouth exacerbates the discomfort.

 [Regnard, 2022; Davies, 2015; Twycross, 2016; NHS Scotland, 2021]

Halitosis

• Halitosis may be due to:
  • Poor oral hygiene (dental plaque, decay, or bleeding gums), dry mouth, periodontal disease.
  • Tongue coating. Long filiform papillae will act as a physical trap for shed cells and plaque and will act as a place where microbes can flourish, some of which may cause halitosis.
  • Any necrosis and sepsis in the mouth, pharynx, nasal sinuses, or lungs.
    • Acute necrotizing ulcerative gingivitis. This typically causes a severe halitosis associated with very painful gums.
    • Anaerobic infection of a malignant ulcer. The blood supply to parts of the tumour is often impaired, resulting in areas of hypoxic or necrotic tissue. These areas become infected with anaerobic bacteria, which release malodorous, volatile by-products.
  • Herpes simplex virus infection. Pain prevents good oral hygiene and the secondary infection of the ulcers causes halitosis.
  • Smoking.
  • Diet: such as garlic, onions, alcohol.
  • Perceived halitosis (the person experiences halitosis but it cannot be detected by others).

 [Regnard, 2022; Davies, 2015; Twycross, 2016]

Alteration in taste

• Factors causing alteration in taste include:
  • Local disease of the mouth and tongue caused by cancer.
  • Local surgery (elimination of the olfactory component of taste after laryngectomy, or surgical removal of the tongue or palate).
  • Alteration of the cell-renewal or cell-regenerating cycle (for example due to malnutrition, radiotherapy, drugs, metabolic disorders, dry mouth, stomatitis, and oral infections).
  • Modification of the taste receptor cells because of alteration of saliva due to metabolic agents, drugs, radiation.
  • Poor dental hygiene or other foci of sepsis.
  • Candidal infection.
  • Drugs (Table 3).
  • Neurological problems (damage to the cranial nerves V, VII, IX, X or to the central nervous system).
  • Smoking.

  [Davies, 2015; Twycross, 2016]

Table 3. Examples of drugs commonly associated with altering taste.

Excessive salivation

• Excessive salivation is uncommon but can cause discomfort and embarrassment, as well as irritation of the lips and chin. The problem is exacerbated if the person also has difficulty swallowing. True hypersalivation (an absolute increase in the volume of saliva) is rare.
• The most frequent causes include:
  • Oral pain (for example from aphthous ulcers).
  • Drugs (for example buprenorphine, clonazepam, ketamine, risperidone).
  • Oral cancer, with or without surgery causing deformity:
    • Radical mandibular resection procedures.
    • Recurrent oral cancer that suspends the mouth in an open position.
  • Dysphagia (because the saliva cannot be removed by swallowing).
  • Psychosis.
  • Saliva with altered qualities (post radiotherapy) that may be difficult to clear.

 [Twycross, 2009; Regnard, 2022; Davies, 2015]

Basis for recommendation

These recommendations are based on national guidance from the National Institute for Health and Care Excellence (NICE) and expert opinion [NICE, 2004; Regnard, 2022; Twycross, 2016].

• As symptoms are often multiple and interrelated, a systematic approach to assessment and management is necessary.
• Assessment and discussion of the person's needs for physical, psychological, social, spiritual, and financial support should be undertaken at key points (such as at diagnosis; at commencement of, during, and at the end of treatment; at relapse; and when death is approaching).
• Terminal illness may affect the relationship between the person and their family. It is important to recognize this, and to offer appropriate support and advice when needed.
• Always carry out assessments and make decisions in partnership with the person and their carers.

[NICE, 2004]

Clinical features of types of mouth ulcers

Common types of mouth ulcers in people with cancer include:

• Mucositis
  • Drug-induced and radiation-induced mucositis most commonly affects the cheeks, soft palate, lips, ventral surface of the tongue, and floor of the mouth.
  • Radiation-induced mucositis is characterized by dry mouth, taste alteration, diffuse erythema, pseudomembrane formation, and ulceration.
• Aphthous ulcers
  • Minor aphthous ulcers present as several small, painful ulcers on the buccal and labial mucosa of the floor of the mouth and the tongue, but rarely affect the soft palate.
    • The ulcers are grey/yellow, often with a raised and erythematous margin. 
    • Minor aphthous ulcers usually heal within 5–7 days.
  • Major aphthous ulcers are larger and have an irregular border.
    • They occur on the buccal and labial mucosa, tongue, and soft palate.
    • Major aphthous ulcers heal slowly over weeks or months and may lead to scarring.
  • Herpetiform ulcers are rarer and are multiple, pinpoint ulcers that can occur anywhere in the mouth cavity.
    • They tend to fuse to form much larger ulcers lasting 10–14 days. 
    • These ulcers are called 'herpetiform' because the clinical appearance suggests a viral cause. However, they are not caused by viral infection.
• Herpetic ulcers
  • Herpetic ulcers present as yellowish lesions, in crops located on the gums and hard palate. Vesicles may also appear on the lips (cold sores). 
  • They are extremely painful.
  • There may be systemic upset: fever, anorexia, and malaise.
  • Herpetic ulcers heal within 10 days in immunocompetent people, without scarring.
• Neutropenic ulcers
  • Neutropenic ulcers present as one or more lesions characterized by inflammation, regular margins, and a yellowish appearance.
  • They are often painful.
• Malignant oral ulcers
  • Many oral cancers (such as lip, tongue, gingiva, buccal mucosa, floor of the mouth) ulcerate.
  • A typical malignant ulcer is hard, with heaped-up and often everted or rolled edges and a granular floor.

Basis for recommendation

Clinical features of candidal infection

• This recommendation is based on expert opinion in textbooks and a review article [Gonsalves, 2007; Samaranayake, 2009; Edwards, 2010; Davies, 2015].

Basis for recommendation

This recommendation is based on accepted standard practice, and expert opinion in the Oxford textbook of palliative medicine [Davies, 2015], a textbook of oral health [Scully, 2000], and a textbook of oral care in advanced disease [Davies, 2005].

Self-care

• Brush the teeth twice a day with a soft toothbrush and fluoride-containing toothpaste, and rinse with water, or a fluoride or antiseptic mouthwash. Note: a 'sore mouth' toothpaste or a child's toothpaste with fluoride is often better tolerated.
• Rinse the mouth after each meal and at night with warm water, which helps to remove oral debris and is soothing and nontraumatic.
• If the tongue is heavily furred (especially if causing distress), brush with a soft toothbrush twice a day and use an antiseptic mouthwash, such as chlorhexidine.
• Use chlorhexidine mouthwash if gum disease is diagnosed. For more information on mouthwashes, see Choice of mouthwash.
• Take adequate fluids.
• Clean debris from the teeth. Dental floss, or chewing pineapple, fresh or unsweetened, may help to remove debris.
• The frequency of mouth care should be increased to:
  • Every 2 hours if there is a high risk of oral problems (any persons with advanced disease or neurological impairment, and/or those undergoing advanced treatment).
  • Every hour in people at high risk or who have severe problems (for example oral infections, coma, severe mucositis, dehydration, immunosuppressed, diabetes, or needing oxygen therapy).
• Dentures should be removed at night and cleaned with a soft toothbrush and unperfumed soap or denture toothpaste. Seek the advice of a dentist regarding how to soak dentures overnight. Different strategies are used to soak dentures overnight. Some experts recommend the following options:
  • Plastic dentures should be soaked overnight in a denture solution containing sodium hypochlorite (1 part Milton^® 1 per cent to 80 parts of water).
  • Dentures with metal parts should be soaked overnight in chlorhexidine solution (as sodium hypochlorite causes metal discolouration).
  • Dentures should be rinsed well under running water before being returned to the mouth.

Choice of mouthwash

• Water or 0.9% sodium chloride solution are recommended.
  • Water and sodium chloride solution are soothing, nontraumatic, and safe to use as frequently as required. Water can be given warm or cool, depending on individual preference.
• Chlorhexidine can be used in people who have, or are at risk of, secondary bacterial infection, including people that do not have their own teeth.
  • Chlorhexidine should not be used more than twice a day. It contains alcohol, which may cause stinging, particularly in people with inflamed mucosa (for example people with mucositis). It also commonly alters taste initially, which may not be desirable.
• Note: chlorhexidine is the most commonly used mouthwash. Other mouthwashes are available, and selection is often based on personal preference.

Preventing oral problems

• Advise regular oral care to reduce the risk of oral problems. See Self care.
• For more information on preventing specific oral problems, see:
  • Preventing complications of chemo/radiotherapy.
  • Preventing oral candidiasis.
  • Preventing oral mucositis.

Preventing complications of chemo/radiotherapy

• Start preventative measures before and during early cancer treatment to reduce the number of oral complications that follow chemotherapy and radiotherapy.
• Stress the importance of regular oral care. See Self care.
• Check that the person has had a pretreatment oral assessment and that any required dental work is done.
  • A pretreatment oral assessment will usually be arranged by the oncology unit.
  • Any necessary dental treatment should be done urgently to avoid any delay in treatment.
  • Dental extractions should have a healing time of 10 days before commencement of chemotherapy or radiotherapy.
• Explain that smoking and drinking alcohol can aggravate oral mucositis.
• Advise avoidance of abrasive foods likely to traumatise soft tissue and consider referral to a dietitian for dietary advice as necessary.

Preventing oral candidiasis

• Oral candidiasis is a potential adverse effect of cancer treatment, and complications may result in a further deterioration of the physical state.
  • Prevention of superficial infection is important because of its possible role in the development of systemic fungal infection. Systemic infection is difficult to diagnose early and consequently cure because it rapidly becomes advanced and disseminated, leading to considerable morbidity and mortality.
• Seek specialist advice to discuss the prophylactic prescribing of an antifungal drug.
  • Prophylactic prescribing of an antifungal is likely to be appropriate in people at high risk of oral Candida infection and in those for whom it is important to prevent the disease.
  • An antifungal drug that is partially (for example topical miconazole) or fully (for example systemic fluconazole) absorbed from the gastrointestinal tract should be used.

Preventing oral mucositis

• Start preventative measures before and during early cancer treatment to reduce the number of oral complications that follow chemotherapy and radiotherapy.
• Stress the importance of regular oral care. See Self care.
• Seek specialist advice to discuss whether any treatment to prevent or reduce the severity of oral mucositis is appropriate.

Managing underlying cause

• Treat any of the following underlying causes of dry mouth if appropriate:
  • Adverse effect of a drug being taken. Reduce the dose or change the drug if possible.
    • However, in practice, it is often very difficult to discontinue or substitute drugs causing dry mouth. Many of these drugs are necessary for symptom control, and salivary gland dysfunction is usually a drug-class adverse effect.
  • Dehydration. This should be reversed except in the terminal phase.
  • Anxiety. This becomes increasingly common towards the end of life and should be managed appropriately.
  • Candida infection. See Scenario: Oral Candida infection.
  • Supplemental oxygen. Consider humidification of oxygen.

Symptom relief

• Try simple saliva stimulatory measures first, as these will often relieve symptoms of dry mouth (even if rehydration is not undertaken):
  • Cold unsweetened drinks, frequent sips or sprays of cold water or ice cubes/crushed ice/ice lollies.
  • Rubbing petroleum jelly (for example Vaseline^®) on the lips. However, if a person is on oxygen apply a water-soluble lubricant (for example K-Y Jelly^®).
  • Sugar-free chewing gum, boiled sweets, pastilles, mints.
• If symptom relief is not adequate, consider using:
  • A topical saliva stimulant.
  • A topical artificial saliva substitute.
  • For more information on topical saliva stimulants and substitutes see Topical artificial saliva and saliva stimulant products.
• Avoid the use of acidic foods (for example pineapple) or acidic artificial saliva products (for example Glandosane^® aerosol spray) in people with their own teeth.
• Note: patient preference is likely to influence the acceptability and compliance with any suggested intervention.

When to refer or seek specialist advice

• Refer or seek specialist advice if in doubt about the diagnosis or management of any oral problem.
• Refer if any of the following are present:
  • Oral problems that are causing a decrease in oral intake or concerns about nutrition.
  • Severe oral herpes simplex infection, as intravenous administration of aciclovir may be needed.
  • Severe mucositis. This can be extremely painful and may limit future chemotherapy or radiotherapy.
  • Suspected neutropenic ulcers and neutropenia. Seek urgent medical advice.
  • Severe or persistent Candida infection.
  • Oral ulcers that are bleeding.
  • Taste disturbance that is likely to be prolonged. Refer to a dietitian where appropriate.
  • Pain that is difficult to manage.
  • Communication problems. Refer to a speech and language therapist where appropriate.

Topical pain relief

Treat the underlying cause of oral pain where possible. If this is not possible or not fully effective, treat pain symptomatically.

• For mild to moderate oral pain, use topical non-opioid analgesia.
  • For localized pain:
    • Choline salicylate gel — short-lived effect. Excessive use should be avoided because it can lead to ulceration, particularly if the gel is trapped under dentures.
    • Benzydamine spray — relatively short duration of action, and numbness and stinging are sometimes a problem.
    • Lidocaine 5% ointment or 10% spray — duration of action of topical local anaesthetics, such as lidocaine, is relatively short, and these agents will not provide continuous pain relief throughout the day. Care should also be taken not to anaesthetize the pharynx before meals, as this might lead to aspiration or choking. Ideally, use of topical local anaesthetics should be reserved for severe pain (for example chemotherapy- or radiotherapy-induced mucosal pain/mucositis).
  • For diffuse oral pain:
    • Benzydamine mouthwash — diluting the mouthwash in an equal volume of water before use reduces stinging.
    • For moderate to severe pain relief use a combination of topical and systemic analgesia.
• For severe oral pain, consider the combined use of topical and systemic preparations. Topical opioids, for example morphine, may help and are recommended by some specialists, but usually systemic opioids are required for severe pain. Note: some liquid-based analgesics have an alcohol component that may cause irritation to the mucosa. Seek specialist advice if pain is difficult to manage.
• See the CKS topic on Palliative cancer care - pain for more information.

Systemic pain relief

Treat the underlying cause of oral pain where possible. If this is not possible or not fully effective, treat pain symptomatically.

• Use systemic analgesia if the person prefers this option or as an alternative/addition to topical analgesia in cases where oral pain is extensive and not controlled by topical analgesia.
  • Topical treatment is preferred to systemic treatment because of the lower incidence of significant adverse effects. Some drugs have both topical and systemic actions (for example dispersible diclofenac).
• The choice of systemic analgesia depends on the severity of pain and the benefits compared with risks for the individual person.
  • Mild pain: nonsteroidal anti-inflammatory drug (NSAID) or paracetamol.
  • Mild to moderate pain: full-dose weak opioid plus paracetamol or NSAID.
  • Moderate to severe pain: strong opioid (for example morphine) plus paracetamol or NSAID.
• Oral analgesia is preferred where possible, but if the person cannot eat or drink (for example mucositis), consider using a 24-hour continuous subcutaneous infusion of an opioid (for example diamorphine).
  • See the CKS topic on Palliative cancer care - pain for further information on starting and titrating oral morphine.
  • See the CKS topic on Analgesia - mild-to-moderate pain for prescribing information on NSAIDs, paracetamol, and weak opioids.
• Seek specialist advice if pain is difficult to manage.
• See the CKS topic on Palliative cancer care - pain for more information.

Oral Candida infection

• Manage predisposing local and systemic risk factors for oral Candida infection in conjunction with anticandidal treatment.
• In immunocompetent people:
  • Topical nystatin or miconazole is recommended as first-line treatment.
  • Oral fluconazole is recommended for persistent candidiasis that does not respond to topical treatment.
• In immunocompromised people, high-dose oral fluconazole is generally preferred for first-line treatment.
• Chlorhexidine should be used to clean dentures, and may be used as an adjunct to topical or oral treatment.
• For more information, see Prescribing information.
• If oral candidiasis persists, seek specialist advice.

Aphthous ulcers

• Correct any underlying iron, folate, or vitamin B12 deficiency if appropriate. 
• Treatment choices should be guided by disease severity (pain), the frequency of flare-ups, and the tolerability of medication.
  • Topical corticosteroids:
    • Hydrocortisone lozenges are best used in the prodromal period, before the ulcer develops.
    • Beclomethasone spray or betamethasone soluble tablets are more potent and are generally reserved for use when ulceration is extensive, or is at a difficult-to-reach site.
  • Chlorhexidine mouthwash can be used to prevent secondary bacterial infection.
    • Chlorhexidine gluconate 0.2% mouthwash is used for aphthous ulcers (particularly if it is too painful to brush teeth). It should not be used at the same time as nystatin because it reduces the activity of nystatin.
  • For management of pain associated with aphthous ulcers, see Scenario: Oral pain.
  • For severe persistent ulceration, seek specialist advice.
  • For more detailed information see the CKS topic Aphthous ulcers. 

Mucositis

• Self care of the mouth before, during, and after treatment with chemotherapy or radiotherapy reduces the severity of mucositis and helps prevent secondary infection.
• Seek urgent specialist advice if mucositis is severe as it may limit the person's ability to tolerate chemotherapy or radiotherapy.
• Seek urgent specialist advice if spontaneous gingival bleeding occurs.
• Prevention of secondary infection, oral hygiene, and supportive therapy are very important. For more information, see Scenario: Prevention.
• Use ice chips to soothe the affected area.
• Treat any infection (such as Candida). See Scenario: Oral Candida infection.
• Avoid spicy and acidic foods sweets, alcohol, tobacco, and hot or fizzy drinks. Advise consumption of soft foods with a low salt content.
• Ensure frequent oral care and use of sterile saline mouth rinsing.
• Avoid acidic mouthwashes.
• Morphine may be required for pain.

Oral herpes simplex infection

• Advise maintenance of adequate fluid intake and use of antipyretics where necessary.
• In immunocompetent people who are in the early stages of an uncomplicated herpes simplex infection in the locality of the lips, commence topical aciclovir or penciclovir.
  • Aciclovir 5% cream, apply to cold sore every 4 hours, five times a day for 5 days.
  • Penciclovir 1% cream, apply to cold sore every 2 hours (during waking hours) for 4 days.
• In immunocompetent people who are in the early stages of an intraoral herpes infection, commence oral aciclovir 200 mg tablets five times a day for 5 days.
• In immunocompromised people urgently commence oral aciclovir 400 mg tablets five times a day for 5 days wherever the herpes simplex infection is located.
• Prevent secondary infection with regular mouth care. Twice-daily chlorhexidine mouthwashes can also be used in the short term but may not be suitable for all people, as the alcohol content can sting. See Choice of mouthwash for more information.
• Treat the pain of the ulcer (see Scenario: Oral pain for further information).
• Admit people with severe infection or people who are severely immunocompromised.

Malodorous malignant oral ulcers

 Ensure effective wound cleansing through regular mouth care. For more information, see Scenario: Prevention.

• If anaerobic organisms are present (as indicated by a foul smell), metronidazole is recommended. Long-term use of metronidazole may be appropriate in some people. Discuss the dose and length of treatment with a specialist.
• For bleeding ulcers, seek the advice of a specialist.
• Treat the pain of the ulcer (see Scenario: Oral pain for further information).

Neutropenic ulcers

• Seek urgent specialist advice if neutropenia is suspected from the appearance of the ulcer (see Clinical features of types of mouth ulcers) or if confirmed by a blood test.

Halitosis due to an oral problem

• Encourage:
  • Regular oral hygiene, including tongue cleaning and good care of dentures.
  • Fluid intake.
  • Modification of diet (for example exclude garlic and onions).
  • Smoking cessation.
• Regular use of a gargle or mouthwash containing an antimicrobial agent (for example chlorhexidine) may reduce breath odour.
• Consider artificial saliva if the mouth is very dry.
• Treat any underlying cause. For more information, see the CKS topic on Halitosis, also Scenario: Oral Candida infection and Malodorous malignant oral ulcers in the Scenario: Mouth ulcers and mucositis.

Excessive salivation

• Correct the underlying cause if possible, note that motor neurone disease, Parkinson's disease, and multiple sclerosis can cause this issue. 
• The cause is usually impaired swallowing of saliva rather than increase in saliva production. 
• Modification of dentures may help.
• Review drug causes such as buprenorphine, clonazepam, haloperidol, risperidone, and venlafaxine. 
• Head positioning (such as preventing the chin/jaw from dropping and avoiding a flexed neck) with or without suction may help.
• Local palliative care guidelines on excessive salivation should be followed. If these are not available, specialist advice should be sought regarding off-licence drug management of excessive salivation.
  • Consider a trial of an antimuscarinic agent such as glycopyrronium bromide oral solution 200 micrograms 8 hourly or hyoscine hydrobromide 75–150 micrograms sublingually every 8–12 hours or applying hyoscine hydrobromide 1 mg/72-hour patches.
  • Alternative options are to use drugs with antimuscarinic adverse effects such as amitriptyline 10–25 mg at night or atropine eye drops 1% 4 drops orally every 4 hours, an off-license usage. 
• If swallowing problems are present refer to a specialist (usually a speech and language therapist).

Alteration in taste

• Stress the importance of good oral hygiene. See Self care.
• Treat dry mouth if present. See Scenario: Dry mouth.
• Treat oral candidiasis. See Scenario: Oral Candida infection.
• Withdraw treatment with drugs that may induce or increase symptoms (for examples, see Table 3 in Alteration in taste).
• Refer to a dietitian where appropriate. Give general advice whilst awaiting an appointment. The following may be tried:
  • Encourage eating tart foods (for example lemon juice, pickles, vinegar), if stomatitis or mouth ulcers are not present.
  • Recommend food that leaves its own taste (for example fresh fruit, hard sweets).
  • Add or reduce sugar as appropriate.
  • Reduce the urea content of the diet by eating white meats, eggs, and dairy products.
  • Mask the bitter taste of food containing urea:
    • Add wine or beer to soups and sauces.
    • Marinate chicken, meat, and fish.
    • Use more and stronger seasonings.
    • Eat food cold or at room temperature.
    • Drink more liquids.
• If loss of taste follows radiotherapy, reassure the person that taste acuity is partially restored 20–60 days after radiotherapy and is usually fully restored within 2–4 months.

How to 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.

How should I manage oral care in the terminal phase?

• The management of dry mouth should be included in the person's care plan.
• Consider changing or stopping medications that are causing dry mouth.
• Carry out mouth care as often as necessary to maintain a clean mouth.
  • In people who are conscious, the mouth can be moistened every 30 minutes with water from a water spray or dropper, or ice chips can be placed in the mouth.
  • In unconscious people, moisten the mouth at least once an hour with water from a water spray, dropper, or sponge stick or ice chips placed in the mouth.
    • Note: the MHRA medical device alert for oral swabs with foam heads (sponge sticks) advises that the heads may detach during use which can cause a choking hazard. If it is necessary to use them, they should be used with caution and the manufacturer's advice followed.  
  • To prevent cracking of the lips, smear petroleum jelly (for example Vaseline^®) on the lips. However, if a person is on oxygen apply a water-soluble lubricant (for example K-Y Jelly^®).
  • When the weather is dry and hot, if possible, use a room humidifier or air conditioning.
  • Ensure help is offered to clean teeth or dentures.
  • Manage pain symptomatically, using analgesics via a suitable route. Stop treatment of the underlying cause of pain when the burden of treatment outweighs the benefits. See Scenario: Oral pain.
  • See Self-care for further information.

• For more information on managing hydration see Care adjustments in the terminal phase in Palliative care - general issues.

Product choice to treat dry mouth

• Any topical artificial saliva and saliva stimulant product available on prescription in the UK can be tried to treat the symptoms of dry mouth.
• In people with their own teeth, the use of acidic artificial saliva products should generally be avoided in order to minimize damage to tooth enamel.

How to use

• Topical artificial saliva and saliva stimulant products should generally be used as frequently as needed, including before and during meals.
• Enough artificial saliva should be used to cover the whole mouth. Applying the artificial saliva under the tongue can help to spread the artificial saliva around the whole mouth [UKOMiC, 2019].

Adverse effects

• Long-term use of acidic products may cause demineralization of tooth enamel, especially if used long term. The importance of this depends on the person's prognosis and whether they still have teeth.

Nystatin suspension

Miconazole

• To maximize effectiveness, miconazole oral gel should be kept in the mouth for as long as possible and be given after food and drink.
  • For localized lesions of the mouth, a small amount of gel may be applied directly to the affected area with a clean finger.
  • Dentures should be removed at night and brushed with the gel.
  • Note: miconazole oral gel is adhesive. 
• For adults: place 5–10 mL in the mouth after food and retain near lesions, four times daily for 7 days.
• Treatment should be continued for 2 days after the lesions have healed [ABPI, 2021].
• Dentures should be removed before using a topical antifungal drug.
• Systemic absorption of topical miconazole may occur, and potential drug interactions need to be considered. 
  
  • Warfarin. Interaction between miconazole oral gel and warfarin has been reported, resulting in an increase in the international normalized ratio (INR)
    • People prescribed warfarin should inform the INR clinic when using miconazole oral gel, especially if the medication is bought over the counter.
  • Tolbutamide and sulphonylureas. The interaction between miconazole and these antidiabetic drugs is established and clinically important, but of uncertain (and probably low) incidence. The interaction can result in hypoglycaemia, therefore concurrent use need not be avoided, but it should be monitored and the dosage of the sulphonylurea reduced if necessary. People taking these antidiabetic drugs should be warned of this interaction.
  • The manufacturer of miconazole oral gel advises that CYP3A4 metabolized HMG-CoA reductase inhibitors, such as simvastatin, should not be used during treatment with the topical antifungal. 

[ABPI, 2021; BNF, 2021]

Dose

• For the treatment of oral candidiasis:
  • Adults with mild oral candidiasis not responding to topical therapy: fluconazole 50 mg daily for 7–14 days. 
  • Adults who have unusually stubborn oral candidiasis: fluconazole 100 mg daily for 7–14 days depending on response. 
  • Fluconazole may be taken for 14–30 days in people with mucosal infections such as oesophagitis. 
• As fluconazole is predominately excreted by the kidneys, the dose needs to be adjusted for those with renal impairment:
  • For people with impaired renal function, the normal recommended dose should be given on the first day, followed by a daily dose based on:
    • Creatinine clearance greater than 50 mL/min: dose remains as the standard recommended dose.
    • Creatinine clearance of 50 mL/min or less (no dialysis): reduce the dose by 50%.
    • Regular dialysis: give 100% of recommended dose after each dialysis.

[EMC, 2023a; BNF, 2021]

Adverse effects of fluconazole

• The most common adverse effects associated with fluconazole are nausea, diarrhoea, abdominal discomfort, flatulence, headache, and rash [EMC, 2023a]. 

Drug interactions

• Cisapride: 
  • There have been reports of cardiac events including Torsades de Pointes in patients to whom fluconazole and cisapride were co-administered. A controlled study found that concomitant fluconazole 200 mg once daily and cisapride 20 mg four times a day yielded a significant increase in cisapride plasma levels and prolongation of QTc interval. Concomitant treatment with fluconazole and cisapride is contraindicated.
• Erythromycin:
  • Concomitant use of fluconazole and erythromycin has the potential to increase the risk of cardiotoxicity (prolonged QT interval, Torsades de Pointes) and consequently sudden heart death. Co-administration of fluconazole and erythromycin is contraindicated. 
• Warfarin:
  • On the basis of kinetic studies, it has been determined that an approximately 20% reduction in the warfarin dose may be needed when using fluconazole 50 mg daily, although this can vary considerably between people. 
  • Consequently, prothrombin times should be closely monitored, and the anticoagulant dosage reduced as necessary. 
• Sulphonylureas:
  • The increased plasma concentration of sulphonylureas in people receiving this combination requires monitoring for possible hypoglycaemic episodes.
  • However there are only case reports of fluconazole causing episodes of hypoglycaemia in people taking gliclazide or glibenclamide.
• Interactions with antineoplastics, antivirals, and immunosuppressants:
  • Antineoplastics. Preliminary evidence suggests that the pharmacokinetics of fluconazole are less likely than itraconazole to be affected by antineoplastics. Fluconazole may be the antifungal drug of choice in people receiving chemotherapy. 
  • Antiviral drugs. There are few clinically significant drug interactions with fluconazole.
  • Immunosuppressants:
    • Serum levels of tacrolimus given orally may be considerably increased by oral fluconazole, and tacrolimus dose reductions may be needed.
    • Increased plasma concentration of ciclosporin has been observed. Monitor for possible toxicity and dose adjustment.

[EMC, 2023a]

Adverse effects

• Chlorhexidine can stain teeth brown when used regularly.
• The stain is not usually permanent and can be reduced by avoiding drinks that contain tannin (for example tea, coffee, or red wine) and by brushing teeth before use.
• If usual tooth brushing does not remove the discolouration, it can be easily removed by a dentist or dental hygienist.

Drug interactions

• The combined use of nystatin and chlorhexidine mouthwash is not recommended as they will inactivate each other. They should be used 1 hour apart.
• Some ingredients in toothpaste can inactivate chlorhexidine, therefore rinse the mouth well with water after brushing the teeth and also do not use chlorhexidine for 30 minutes after the use of toothpaste.

[ABPI, 2020b]

Adverse effects

• Topical aciclovir and penciclovir may cause transient stinging, burning, itchiness, and numbing of the skin.
• Oral aciclovir is generally well tolerated. Gastrointestinal adverse effects (for example nausea, vomiting, diarrhoea, and abdominal pain) and skin rashes (including photosensitivity and urticaria) are the most common adverse effects.

Prescribing metronidazole

• Common adverse effects include a metallic taste and gastrointestinal irritation (in particular nausea and vomiting). These are more common at higher doses.
• Severe bullous skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) have been reported. If symptoms/signs are present, treatment must be immediately discontinued.
• Some people taking oral metronidazole experience disulfiram-like reactions to alcohol (flushing, increased respiratory rate, increased pulse rate). Although no conclusive evidence supports an interaction between metronidazole and alcohol, people taking metronidazole should be advised to avoid alcohol because of the possible interaction.
• The manufacturers SPC also notes that QT prolongation has been reported (unknown frequency), particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
• Do not prescribe metronidazole to a person with:
  • Known metronidazole or nitroimidazole hypersensitivity.
  • Cockayne syndrome. Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome have been reported with products containing metronidazole for systemic use (oral and suppositories). For people with Cockayne syndrome specialist advice should therefore be sought before prescribing metronidazole. 

[BNF, 2021; EMC, 2023b]