Previous changes

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.

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 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.

May 2015 — reviewed and updated. A literature search was conducted in January 2015 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic structure has been altered to reflect a symptom-based approach and changes to antibiotic prescribing advice have been made.

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

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. 

April to July 2009 — 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 are no major changes to the recommendations.

September 2008 — minor correction to the Changes section. 

October to December 2005 — reviewed. Validated in March 2006 and issued in May 2006.

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

September 2002 — written. Validated in October 2002 and issued in December 2002.

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

No new product availability since 1 March 2021. 

How should I manage a malignant skin ulcer?

Ensure a professional with expertise in wound management is involved in the person's care (such as a district nurse, palliative care or tissue viability nurse).

• Discuss with the person:
  • Their treatment priorities and, if possible, address these first.
  • Their concerns about the ulcer, and its impact on their daily functioning and quality of life.
  • That healing is unlikely to be a realistic goal, and explain that the aim is to maintain or improve their quality of life.
• Assess the skin ulcer for:
  • Its location, size, and whether it is ulcerative or proliferative as these factors affect dressing choice.
  • The amount of necrotic tissue within the ulcer, as this affects the need for cleansing or debridement.
  • The condition of the surrounding skin, which may affect dressing choice, the method of securing the dressing, and the frequency of dressing changes.
• Assess for complications including:
  • Pain.
  • Bleeding.
  • Infection.
  • Exudate.
  • Odour.
  • Itch.
  • Psychological issues.
• Where appropriate, refer to an oncologist or palliative care specialist for advice if:
  • Complications are present that may require specialist management (such as vessel compression or obstruction, airway obstruction, or the presence of significant necrotic tissue that might be suitable for larval therapy).
  • Further cancer treatment may be possible (such as radiotherapy, chemotherapy, hormone therapy, or surgery).

How should I manage pain?

• Identify and manage the cause of pain where possible, for example the presence of infection, surrounding skin irritation, or dressing changes.
  • Pain can last an hour or more after a dressing change.
• Prescribe analgesia if needed. For information on pain management, see the CKS topic on Palliative cancer care - pain.
  • A topical local anaesthetic should only be used on the advice of a specialist.
• If there is pain at dressing changes:
  • Ensure a person with expertise in wound management is involved in the person's care (such as a district, palliative or tissue viability nurse) to select an appropriate dressing and, where possible, ensure the frequency of dressing changes is minimized.
  • Ensure administration of a breakthrough dose of short-acting opioid analgesia at least 30 minutes before a dressing change where possible. For more information, see the section on the Management of breakthrough pain in the CKS topic on Palliative cancer care - pain.
  • In discussion with a palliative care specialist consider the option of topically applied opioids for ulcerating wounds.

How should I manage suspected infection?

• Make a diagnosis of infection based on clinical symptoms and signs. Check for:
  • Fever or malaise, rigors or tachycardia.
  • Wound breakdown, abscess, or cellulitis.
  • Pocketing in the wound (pits or indents at sites in the wound bed).
  • Increased or altered appearance of exudate, increased pain at the site, or the presence of odour.
• If infection is suspected, cleanse the surface, then take a swab.
  • Cleanse the area using sterile water or 0.9% saline, then run the tip of the swab across the wound in a 'zig zag' manner and at the same time rotate the swab handle.
  • Use clinical judgement when interpreting a swab result, as the presence of bacteria does not always indicate that a wound is infected.
• Assess whether ulcer debridement (removal of necrotic, devitalized, sloughy, or infected tissue) is appropriate.
  • Natural (autolytic) debridement may be promoted by the use of specialist dressings.
  • Specialist referral for surgical debridement may be appropriate.
• Ensure an appropriate dressing is used with an optimum frequency of dressing change.
• If an antibiotic is indicated due to suspected infection or surrounding cellulitis, see the CKS topic on Cellulitis - acute for more information on the choice of antibiotic.
  • Review the choice of antibiotic once the swab result is available.
• If an antibiotic is indicated for odour, see the section on managing odour.

How should I manage bleeding?

• If there is acute bleeding from a definite point in the ulcer, assess the severity of bleeding:
  • For mild bleeding, apply gentle pressure for 10–15 minutes with a moist, non-adherent dressing. Other options include gauze soaked in adrenaline 1:1000, sucralfate suspension or alginate dressings that also have haemostatic properties. Avoid causing unnecessary pain.
  • For heavier bleeding, apply pressure and seek urgent advice from the person's oncologist or palliative care team. Admission may be appropriate depending on the stage of illness.
    • Anti-fibrinolytic treatment (for example tranexamic acid) may be useful, but should only be prescribed on specialist advice.
    • Other options that may be available in a specialist setting include haemostatic foams or sponges, sucralfate paste, radiotherapy, embolization, and cautery.
  • For severe bleeding at the end of life, use dark towels to absorb blood to minimize distress to the person and their family, and consider sedation with a benzodiazepine. For more information on prescribing, see the section on Benzodiazepines in the CKS topic on Palliative care - dyspnoea.
• Ensure that the risk of bleeding is minimized with appropriate dressing choice.
• Review and consider stopping drugs that may contribute to bleeding, for example oral anticoagulants (such as warfarin), depending on clinical judgement and the stage of the illness.
• Consider checking the person's full blood count and coagulation.

How should I manage exudate?

• Assess the volume and appearance of the exudate as changes may indicate the presence of infection.
• Ensure the area is cleansed to clear visible debris, excess slough, and exudate.
• Assess whether ulcer debridement (removal of necrotic, devitalized, sloughy, or infected tissue) is appropriate.
  • Natural (autolytic) debridement may be promoted by the use of specialist dressings.
  • Specialist referral for surgical debridement may be appropriate.
• Ensure an appropriate dressing is used with an optimum frequency of dressing change. Dressings suitable for moderate to high exudate should include alginate and hydrofibre dressings and foams. A secondary absorbent or super absorbent dressing may also be indicated, depending on the volume of exudate. 
• Ensure the surrounding skin is protected.
  • Consider using an alcohol-free film or barrier cream to prevent maceration of the surrounding skin. 
  • Alternative ways of securing dressings (such as netting or briefs) may be considered if the surrounding skin is damaged.
• If there is copious exudate:
  • Seek specialist advice (for example from the person's oncologist, palliative care team, or tissue viability nurse) as additional treatments (for example radiotherapy, use of a stoma appliance or collection pouch) may be helpful.
• Consider referral to a dietitian for nutritional support as significant amounts of protein can be lost from a discharging wound.

How should I manage odour?

• Ensure an appropriate dressing is used with an optimum frequency of dressing change.
• Prescribe topical or oral metronidazole if the appropriate dressings do not control odour.
  • Topical metronidazole (0.75%) is more effective if there is excess necrotic tissue present.
    • It is not suitable for wounds with significant exudate, as it may be 'washed off' the wound surface.
    • Advise that it should be applied liberally to the ulcer once or twice a day for 7 days. If there is a partial response, consider continuing treatment for a further 7 days.
    • For further information on the use of topical metronidazole see the Prescribing information section.
  • Oral metronidazole may be better for deep tissue infections causing odour.
    • Prescribe 400 mg three times a day for 5–7 days. If there is a partial response, consider continuing treatment for a further 7 days.
    • For further information on the use of oral metronidazole see the Prescribing information section.
  • If odour recurs after a course of metronidazole, repeat another 14-day course of topical or oral treatment.
    • If odour recurs after intermittent treatment with metronidazole, continue treatment with metronidazole long term, either topically (once or twice a day at dressing changes) or orally 200 mg twice a day (off-label use).
    • For further information on the use of metronidazole see the Prescribing information section.
• Consider seeking specialist advice from the person's oncologist or palliative care team if the odour persists or is not adequately controlled. 
• Consider additional measures to modify the person's environment to reduce odour, after discussion with the person, family, and/or carers. These include:
  • Room scents (for example essential oils on clothing or room vaporizers or vanilla or coffee scents), although strong scents may induce nausea.
  • External odour absorbers (for example a tray of cat litter or activated charcoal under the bed).

How should I manage itch?

• Consider the use of a mild topical corticosteroid such as 1% hydrocortisone cream if the skin around the ulcer is red and scaly.
  • Exclude other causes of irritation, such as a local infection or irritation from dressings or treatments applied to the area.
  • For more information on the use of topical corticosteroids, see the CKS topic on Corticosteroids - topical (skin), nose, and eyes.
• If the itch remains problematic, seek specialist advice from the person's palliative care team, as it may be difficult to treat.
  • Transcutaneous electrical nerve stimulation (TENS) may be considered in a specialist setting.

How should I manage psychosocial issues?

• Manage exudate and odour as effectively as possible.
  • Odour is often the most distressing complication for the person, their family, and carers.
• Aim for a good cosmetic effect with dressings, for example:
  • Use dressings to fill any defect (for example a cavity in an ulcer).
  • Ensure dressings protect clothing.
  • Use a less bulky dressing material if the person is going out (this may mean using a less absorbent dressing).
• For more information on the social, psychological, and spiritual aspects of palliative care, see the CKS topic on Palliative care - general issues.

End of life care

• 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. For more information see the CKS topic on Palliative care - general issues. 
• An individualized care plan including the areas of symptom control and anticipatory prescribing should be created. For more information see the CKS topic on Palliative care - general issues.

Contraindications and cautions

• Metronidazole is contraindicated in people with known hypersensitivity to nitroimidazoles [ABPI, 2021].
• 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. 
• Prescribe oral metronidazole with caution:
  • In people with active or chronic severe peripheral and central nervous system disease, due to the risk of neurological aggravation.
  • In people with severe liver disease and hepatic encephalopathy, due to substantial impairment of metronidazole clearance. The daily dosage should be reduced to one-third and may be administered once daily [BNF, 2021].
  • For prolonged use, as prolonged therapy may be associated with peripheral neuropathy or leucopenia. Both effects are usually reversible. It is recommended that a full blood count be carried out regularly and that people should be monitored for adverse reactions such as peripheral or central neuropathy (including paraesthesia, ataxia, dizziness, or convulsive seizures).
• Prescribe topical metronidazole with caution:
  • Near the eyes as it can cause lacrimation, contact with the eyes should be avoided.
  • In areas exposed to direct sunlight as it is inactivated by ultraviolet light exposure. Treatment sites should not be exposed to strong sunlight.

[ABPI, 2021]

Drug interactions

• Important drug interactions associated with oral metronidazole include:
  • Alcohol — some people taking oral metronidazole experience a disulfiram-like reaction (flushing, increased respiratory rate, increased pulse rate, nausea, headache, and dizziness) with alcohol.
    • Although there is no conclusive evidence to support this interaction, warn the person that they might experience this reaction if they drink alcohol whilst taking metronidazole. Alcohol should be avoided for 24–48 hours.
  • Anticoagulants — the anticoagulant effects of warfarin can be markedly increased by metronidazole.
    • Monitor the international normalized ratio (INR) if metronidazole is given with warfarin and adjust the warfarin dose accordingly.
    • Warn the person of the possible risk of increased bruising and bleeding. Advise when to seek medical help.
  • Ciclosporin — the Summary of Product Characteristics (SPC) states that when co-administration of metronidazole and ciclosporin are necessary serum ciclosporin and creatinine should be closely monitored.
  • Lithium — seek expert advice regarding the concurrent use of metronidazole and lithium as lithium dose adjustments may be required. Plasma concentrations of lithium, creatinine, and electrolytes should be monitored in people being treated with lithium while receiving metronidazole.
  • Contraceptives — additional contraceptive precautions are not required during or after courses of metronidazole.
    • Advise women on the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the section on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.
  • 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.

[BNF, 2021; EMC, 2023]

Adverse effects

Oral metronidazole

• Gastrointestinal disturbances (including nausea and vomiting), taste disturbances, furred tongue, oral mucositis, anorexia; very rarely hepatitis, jaundice, pancreatitis, drowsiness, dizziness, headache, ataxia, psychotic disorders, darkening of urine, thrombocytopenia, pancytopenia, myalgia, arthralgia, visual disturbances, rash, pruritis, and erythema multiforme [BNF, 2021].
• Warn people about the potential for drowsiness, dizziness, confusion, hallucinations, convulsions, or transient visual disorders. Advise them not to drive or operate machinery if these symptoms occur.
• 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 [ABPI, 2021].

Topical metronidazole

• Topical metronidazole has fewer systemic adverse effects compared to oral metronidazole, but may sting on application.
• Lacrimation has been reported if topical metronidazole is applied too close to the eyes [ABPI, 2015].

Pregnancy or breastfeeding

Oral metronidazole

• The Summary of Product Characteristics (SPC) states that oral metronidazole has been in wide use for many years without clinical issues. However it states it should not be given during pregnancy or breastfeeding unless essential, and short, high-dose regimes are not recommended [ABPI, 2021].

Topical metronidazole

• The SPC states that there is no safety data regarding the use of topical metronidazole in pregnancy. Blood levels are significantly lower than those from oral metronidazole, but a clinical decision is recommended regarding balancing the risks and benefits of treatment during breastfeeding [ABPI, 2015].