Previous changes

April 2023 — reviewed. A literature search was conducted in March 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes were made to recommendations. 

March 2018 — reviewed. A literature search was conducted in March 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone minor restructuring. Complications and Prognosis nodes have been added to the Background information section. The management recommendations have been updated in line with the current literature. The Prescribing Information section has been updated and expanded in line with current CKS style.

September 2014 — minor update. Update to the prescribing information text on terbinafine, to make it consistent across CKS topics. Recommendations to monitor liver function tests before and during treatment with terbinafine, and to reduce the dose of terbinafine in people with an estimated glomerular filtration rate (eGFR) of less than 50 mL/min/1.73 m² have been added.

September 2013 — reviewed. A literature search was conducted in July 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. There are no changes to the recommendations.

February 2012 — minor error corrected in prescribing information for itraconazole and terbinafine. 

January to May 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 only minor changes to the recommendations. Continuous itraconazole and topical tioconazole are no longer recommended because alternative treatments are more practical.

April 2008 — minor update to the text for oral ketoconazole which now reflects the most recent Medicines and Healthcare products Regulatory Agency (MHRA) guidance.

March 2008 — minor update. New text inserted regarding rare cases of changes in the international normalized ratio (INR) when warfarin and oral terbinafine have been given concomitantly. 

July 2006 — minor update. Amorolfine is now available to buy over-the-counter and the text has been amended to reflect this. 

October to December 2005 — written. Validated in March 2006 and issued in May 2006. This guidance superseded the CKS guidance on Fungal (dermatophyte) infections — skin and nails and Candida — skin and nails, which were withdrawn.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 March 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 March 2023.

Economic appraisals

No new economic appraisals relevant to England since 1 March 2023.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 March 2023.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 March 2023.

New policies

No new national policies or guidelines since 1 March 2023.

New safety alerts

No new safety alerts since 1 March 2023.

Changes in product availability

No changes in product availability since 1 March 2023.

Basis for recommendation

The recommendations on when to suspect fungal nail infection are based on expert opinion in the British Association of Dermatologists' Guidelines for the management of onychomycosis 2014 [Ameen, 2014], Public Health England guidance Fungal skin and nail infection: diagnosis and investigation [PHE, 2017], and expert opinion in review articles on fungal nail infection [Frazier, 2021; BMJ Best Practice, 2022; Piraccini, 2022].

• Classification (based on the morphologic pattern of involvement and mode of invasion of the nail) of different presentations of fungal nail infection is useful, as this may help to guide management options and predict prognosis [Frazier, 2021].
• Distal lateral subungual onychomycosis is the most common type (58-85%) of all cases) [Piraccini, 2022].
• The first and fifth toenails are most commonly affected, as they are more likely to be damaged by footwear [Ameen, 2014].

Taking nail samples

• When taking samples of the abnormal nail (nail clippings), and any debris between the nail and nail bed (nail scrapings):
  • Wipe off any treatment creams, lotions, or powders with 70% alcohol before sampling, to prevent contamination.
  • If a superficial infection of the nail is suspected, use a scalpel blade to obtain scrapings of the surface of the nail.
  • If a deeper infection of the nail is suspected:
    • When clipping the diseased nail, use sterile nail clippers or chiropody scissors to include the full thickness of the nail and extend as far back from the nail tip as possible (viable fungi are most likely to be found in the most proximal part of the diseased nail; distal nail samples should be avoided as contamination is common).
    • Include scrapings of debris from the area between the nail and nail bed using a sterile scalpel blade.
  • Collect the samples into folded dark paper squares, secure them with a paper clip, and place them in a plastic sample bag. Alternatively, commercially available packs are available. Label the sample clearly.
  • Keep the samples at room temperature and do not refrigerate them (dermatophytes are inhibited at low temperatures, and humidity facilitates the growth of contaminants).
  • Inform the person that microscopy results (to identify hyphae, pseudohyphae, or spores) should be available within 1–2 days and culture results (to identify the causative organism) within 2–3 weeks.
  • Be aware that testing for antifungal susceptibilities is not required.

[Ameen, 2014; UKHSA, 2017; BMJ Best Practice, 2022]

Basis for recommendation

The recommendations on assessment are based on expert opinion in the British Association of Dermatologists' (BAD) Guidelines for the management of onychomycosis 2014 [Ameen, 2014], the Public Health England (PHE) publication Fungal skin and nail infections: Diagnosis and laboratory investigation [UKHSA, 2017], and expert opinion in review articles on fungal nail infection [Tosti, 2016; Frazier, 2021; BMJ Best Practice, 2022; Piraccini, 2022].

• Distal nail infection with Candida species is uncommon and the majority of people affected also have Raynaud's phenomenon or some other form of vascular insufficiency [Ameen, 2014].
• In children with a fungal nail infection, other household members should be examined to exclude active infection [Jazdarehee, 2022].
• The recommendation to assess for fungal infection at other sites is based on the fact that toenail infection is often associated with tinea pedis, and fingernail infection is often associated with tinea corporis or tinea capitis [Tosti, 2016; BMJ Best Practice, 2022].

Advice on nail sampling and interpretation of results

• The recommendation to perform nail sampling on any person considering antifungal treatment is extrapolated from expert opinion in the BAD publication [Ameen, 2014], the PHE publication [UKHSA, 2017], and expert opinion in review articles [Frazier, 2021; Piraccini, 2022]. The detailed information on nail sampling is based on the fact that good nail specimens give the maximal chance of identifying the causative organism, and therefore targeting treatment appropriately [Ameen, 2014]. 
  • Fungal culture is important as it distinguishes dermatophyte from non-dermatophyte infections, which present similarly, as these two organisms may need different treatment approaches [Ameen, 2014; UKHSA, 2017].
  • The 50% false-negative rate for mycology culture is based on expert opinion in a review article [BMJ Best Practice, 2022]. The PHE publication notes that only 45% of mycological samples received are positive for fungal infection [UKHSA, 2017].
  • The recommendation to arrange repeat fungal microscopy and culture to confirm the presence of non-dermatophyte infection is extrapolated from the PHE publication, which states that diagnosis requires positive microscopy and culture, ideally on repeated occasions [UKHSA, 2017]. This is supported by expert opinion in the BAD guidelines, which note that non-dermatophyte organisms are often transient contaminants or commensals of uncertain clinical significance, and microscopy of nail samples is often negative. Consistent isolation of these organisms on repeat sampling suggests they are a true pathogen [Ameen, 2014].
  • The recommendation to repeat nail sampling if the result is negative and clinical suspicion of fungal nail infection is high is based on expert opinion in a review article [BMJ Best Practice, 2022].
  • The recommendation that antifungal susceptibility testing is not needed is based on the fact that antifungal resistance is rare, and there is no known correlation between antifungal susceptibilities and outcome [UKHSA, 2017].

Basis for recommendation

The information on the differential diagnosis of fungal nail infection is based on the National Institute for Health and Care Excellence (NICE) clinical guideline Suspected cancer: recognition and referral [NICE, 2021], expert opinion in the British Association of Dermatologists' Guidelines for the management of onychomycosis 2014 [Ameen, 2014], and expert opinion in review articles on fungal nail infection [Frazier, 2021; BMJ Best Practice, 2022; Piraccini, 2022].

How should I initially manage confirmed fungal nail infection?

The management of fungal nail infection depends on the site and severity of nail involvement, the causative organism, the person's symptoms, and any co-morbidities.

Discuss with the patient their expectations for successful management of the condition before starting treatment. Onychomycosis is difficult to eradicate and often recurs.

• Advise on self-care management strategies.
  • Keep nails trimmed short and filed down. Avoid sharing toenail clippers with family members.
  • Wear well-fitting non-occlusive shoes, without high heels or narrow toes. Consider replacing old footwear that could be contaminated with fungal spores.
  • Wear cotton, absorbent socks.
  • Maintain good foot hygiene, including prompt treatment of any associated tinea pedis. See the CKS topic on Fungal skin infection - foot for more information.
  • Wear protective footwear when using communal bathing places, locker rooms, and gymnasiums, to avoid re-exposure.
  • Avoid prolonged or frequent exposure to warm, damp conditions if possible.
  • Avoid trauma to the nails if possible.
• Provide information on sources of advice and support, such as:
  • The British Association of Dermatologists information leaflet Fungal infections of the nails.
  • The NHS information on Fungal nail infection.
• Advise that antifungal treatment is not needed if:
  • The person is not troubled by the appearance of the nail(s), and/or
  • Infection is asymptomatic.
• Advise on the option of antifungal treatment if:
  • Walking is uncomfortable.
  • There is significant psychological distress due to the cosmetic appearance of the nail(s).
  • There are comorbid conditions which increase the risk of complications.
  • Nail infection is a potential source of associated fungal skin infection. See the CKS topics on Fungal skin infection - body and groin, Fungal skin infection - foot, and Fungal skin infection - scalp for more information.
• If dermatophyte or Candida nail infection is confirmed, advise on the option of topical antifungal treatment in adults if there is:
  • Only very early, distal, and superficial nail involvement.
  • Superficial white onychomycosis.
  • A contraindication to oral antifungal treatment. See the sections on Oral terbinafine and Oral itraconazole in Prescribing information for more information.
  • Advise that cure rates are very low.
• If topical treatment is appropriate, advise on the use of amorolfine 5% nail lacquer.
  • This can be purchased over-the-counter and is applied once or twice weekly to the affected nail(s) after gentle nail filing.
    • Treatment should be continued for 6 months for fingernails and 9–12 months for toenails.
    • If there is Candida infection with associated paronychia, topical treatment should also be applied to the area of paronychia.
    • Advise the person to avoid cosmetic nail varnishes or artificial nails during treatment.
    • Topical treatment may be used preventatively after successful initial treatment.
    • See the section on Topical amorolfine in Prescribing information for more information.
  • Advise that the use of other topical treatments such as tea tree oil is not recommended.
• If self-care measures alone and/or topical treatment is not successful or appropriate, advise on the option of oral antifungal treatment.

When should I offer oral antifungal treatment?

Offer treatment with an oral antifungal agent if an adult has confirmed fungal nail infection and self-care measures alone and/or topical treatment are not successful or appropriate.

• If dermatophyte nail infection is confirmed:
  • Prescribe oral terbinafine first-line.
    • Prescribe 250 mg once a day for between 6 weeks for fingernail infections, and for 12-24 weeks for toenail infections.
    • Advise the person that visible improvement may be seen after the end of 2 months of fingernail treatment and 3 months of toenail treatment.
    • See the section on Oral terbinafine in the section on Prescribing information for more detailed information.
  • Prescribe oral itraconazole if an alternative drug is indicated.
    • Prescribe as pulsed therapy of 200 mg twice a day for 1 week, with subsequent courses repeated after a further 21 days.
    • Prescribe two pulses for fingernail infections and three pulses for toenail infections.
    • See the section on Oral itraconazole in the section on Prescribing information for more detailed information.
  • Consider relevant comorbidities, polypharmacy, renal and hepatic insufficiency, and compliance when prescribing for older adults.
• If Candida or non-dermatophyte nail infection is confirmed:
  • Prescribe oral itraconazole first-line.
    • Prescribe as pulsed therapy of 200 mg twice a day for 1 week, with subsequent courses repeated after a further 21 days.
    • Prescribe two pulses for fingernail infections, and three pulses for toenail infections.
    • Be aware that the use of itraconazole for non-dermatophyte infections is off-label.
    • See the section on Oral itraconazole in the section on Prescribing information for more detailed information.
  • Prescribe oral terbinafine if an alternative drug is indicated.
    • Prescribe 250 mg once a day for between 6–12 weeks for fingernail infections, and for 12–24 weeks for toenail infections.
    • Be aware that the use of terbinafine for non-dermatophyte infections is off-label.
    • See the section on Oral terbinafine in the section on Prescribing information for more detailed information.
  • Consider topical treatments if both terbinafine and itraconazole are not tolerated or are contraindicated.
  • Treat any associated paronychia. See the CKS topic on Paronychia - acute for more information.
• Monitor for any subsequent nail growth 3–6 months after the start of treatment.
  • Consider filing a notch at the base of the most abnormal nail when starting oral antifungal treatment — this can help future comparisons of old with new nail growth.
  • Advise that serial photographs (for example with a mobile phone camera) may also help monitor nail growth.
    • If abnormal nail remains distal to the notch as it grows out, no further treatment is required.
    • If abnormal nail moves proximal to the notch, this indicates ongoing infection and further treatment is needed.
  • If normal nail regrowth does not occur, see the section on Treatment failure for further management options.

How should I manage treatment failure?

• If normal nail regrowth does not occur after oral antifungal treatment and there are signs of treatment failure:
  • Consider and, if possible, manage any underlying cause of treatment failure; co-existing tinea pedis is common  — use topical antifungal to treat.
  • Consider arranging re-sampling for nail clippings and/or scrapings for fungal microscopy and culture. 
  • Consider the use of a combination treatment with a topical and oral antifungal agent.
  • Note: be aware that the nail's appearance may not be restored to normal, even after successful eradication of infection.
• Consider arranging a referral to a podiatrist if:
  • Thickened toenails cause discomfort when walking.
  • There is nail trauma due to the person's footwear.
  • Deformed toenails are traumatizing adjacent toes.
• Consider arranging a referral to a paediatric dermatologist if:
  • Oral antifungal treatment is being considered for a child.
• Consider arranging a referral to a dermatologist if:
  • The diagnosis is uncertain.
  • Treatment in primary care is unsuccessful.
  • There is co-existent nail disease, such as psoriasis or lichen planus.
  • The person is immunocompromised, depending on clinical judgement.

Contraindications and cautions

• Advise people using topical amorolfine nail lacquer to avoid contact with the ears, eyes, and mucous membranes.
• Advise people that topical amorolfine nail lacquer contains 55.2% ethanol and as such is a flammable substance. It should not therefore be used near a naked flame or hair dryers.  

[ABPI, 2023; BNF, 2023]

Adverse effects

• Advise people applying topical amorolfine nail lacquer that a burning sensation, erythema, hypersensitivity reactions, itching, and occasional local irritation may occur after application.

[EMC, 2023; BNF, 2023]

Drug interactions

• No drug interaction studies have been performed regarding the use of topical amorolfine nail lacquer.

[ABPI, 2023; BNF, 2023; Preston, 2019]

Contraindications and cautions

Do not prescribe terbinafine to people with:

• Hepatic impairment — the manufacturer recommends that terbinafine should not be prescribed in people with chronic or active hepatic disease. It recommends that for other people, liver function tests (LFTs) should be performed. Hepatotoxicity may occur in people with and without pre-existing hepatic disease, therefore periodic monitoring of LFTs (after 4–6 weeks of treatment) is recommended. Terbinafine should be stopped immediately if LFTs are deranged.
• Severe renal impairment.

Prescribe terbinafine with caution to people with:

• Autoimmune disease — risk of lupus erythematosus-like effect.
• Psoriasis — increased risk of exacerbation of psoriasis.
• Renal impairment — the BNF recommends that half the normal dose of terbinafine should be used if the estimated glomerular filtration rate (eGFR) is less than 50 mL/min/1.73 m² and there is no suitable alternative. However, the manufacturer does not recommend using terbinafine in these people, as it has not been adequately studied.

[EMC, 2020; BNF, 2023]

Adverse effects

Adverse effects of terbinafine include:

• Gastrointestinal — abdominal distension, dyspepsia, nausea, abdominal pain, diarrhoea, feeling of fullness (very common), and pancreatitis (unknown frequency).
• Nervous system — headache (common); taste disturbance (uncommon); and dizziness, paraesthesia, and hypoaesthesia (rare).
• Skin and subcutaneous tissue — rash, urticarial (very common). Very rarely Stevens-Johnson syndrome, toxic epidermal necrolysis erythema multiforme, skin eruption, dermatitis exfoliative, dermatitis bullous, photosensitivity reaction, and alopecia.
• Other common or very common adverse effects include arthralgia, myalgia, and decreased appetite.
• Other rare or very rare adverse effects include:
  • Anaphylaxis.
  • Hepatic dysfunction, jaundice, hepatitis, and cholestasis — people taking terbinafine tablets should be warned to immediately report any signs and symptoms of unexplained persistent nausea, decreased appetite, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale faeces. If these symptoms develop, terbinafine treatment should be stopped, and liver function tests (LFTs) should be immediately performed.
  • Malaise, neutropenia, agranulocytosis, thrombocytopenia, and vertigo.

[EMC, 2020; BNF, 2023]

Drug interactions

Possible drug interactions with terbinafine include:

• Codeine — the analgesic effect may be reduced or abolished by terbinafine. Monitor for analgesic efficacy.
• Rifampicin — levels of terbinafine are reduced. Dose increases of terbinafine may be necessary.
• Tamoxifen — avoid concurrent use. Metabolism to an active metabolite of tamoxifen may be inhibited by terbinafine. 
• Terbinafine levels may be increased by the following drugs if taken concomitantly:
  • Amiodarone.
  • Fluconazole, ketoconazole.
• Terbinafine may increase levels of the following drugs if taken concomitantly, thereby increasing or prolonging their effects, including adverse effects:
  • Anti-arrhythmics (flecainide, mexiletine, and propafenone).
  • Aripiprazole, risperidone.
  • Beta-blockers (carvedilol, metoprolol, nebivolol, propranolol, and timolol).
  • Dextromethorphan.
  • Monoamine oxidase inhibitors Type B (MAOIs-B, such as selegiline).
  • Selective serotonin reuptake inhibitors (sertraline and paroxetine).
  • Tramadol – terbinafine may increase levels of tramadol, but not the active metabolite, which causes an increase in adverse effects, but not in analgesic effect.
  • Tricyclic antidepressants (amitriptyline, imipramine, and nortriptyline).

 [EMC, 2020; BNF, 2023; Preston, 2019]

Contraindications and cautions

Do not prescribe itraconazole to people with:

• Acute porphyria.
• Ventricular dysfunction or a history of heart failure — itraconazole has been shown to have a negative inotropic effect.

Prescribe itraconazole with caution to people:

• At high risk of heart failure, including people on treatment with negative inotropic drugs (such as calcium-channel blockers).
• Who are immunocompromised (AIDS, neutropenia, or transplants).
• With acute liver disease or a history of hepatotoxicity with other drugs — consider monitoring liver function tests (LFTs). Advise immediate LFTs if symptoms of possible liver toxicity develop, such as anorexia, nausea, vomiting, fatigue, abdominal pain, or dark urine.
• With renal impairment.
• Taking drugs such as astemizole, pimozide, quinidine, or terfenadine that may prolong the QT interval, as there is a risk of cardiac arrhythmias.

[ABPI, 2018; BNF, 2023]

Adverse effects

Adverse effects of itraconazole include:

• Gastrointestinal — nausea and abdominal pain (common); vomiting, diarrhoea, constipation, dyspepsia, taste disturbance, and flatulence (uncommon); and pancreatitis (rare).
• Hepatobiliary — hyperbilirubinaemia (uncommon). Rarely hepatotoxicity (including acute liver failure).
• Nervous system — headache, dizziness, and paraesthesia (uncommon).
• Skin and subcutaneous tissue — rash (common) and alopecia, urticaria, and pruritus (uncommon).
• Other adverse effects include arthralgia, myalgia, heart failure, erectile dysfunction, menstrual disorders, oedema, tinnitus, and visual disturbance.

  [ABPI, 2018; BNF, 2023]

Drug interactions

Itraconazole is metabolized by the cytochrome p450 3A4 (isoenzyme CYP34A) and it interacts with a number of liver enzyme-inducing and liver enzyme-inhibiting drugs.

• Itraconazole levels may be reduced by the following drugs:
  • Carbamazepine, phenobarbital, and phenytoin — monitor itraconazole efficacy and increase the dose if necessary.
  • Rifampicin and rifabutin — monitor itraconazole efficacy and increase the dose if necessary.
  • St John’s wort — avoid concurrent use.
• Itraconazole levels may be increased by the following drugs:
  • HIV protease inhibitors (ritonavir and indinavir) — monitor for adverse effects.
  • Clarithromycin and erythromycin — monitor for adverse effects.
• Itraconazole may increase levels of the following drugs:
  • Aliskiren — monitor for adverse effects.
  • Aripiprazole, quetiapine, and risperidone — dose reductions may be necessary.
  • Quetiapine — concurrent use with itraconazole is contraindicated. If considered necessary, monitor for adverse effects and adjust the dose.
  • Phospodiesterase-5 inhibitors (avanafil, sildenafil, and vardenafil) — avoid concurrent use with avanafil; reduce the dose of sildenafil or vardenafil.
  • Benzodiazepines (alprazolam, triazolam, and midazolam) — dose reductions may be required.
  • Calcium-channel blockers (amlodipine and verapamil) — monitor for adverse effects.
  • Colchicine — dose adjustment may be necessary.
  • Corticosteroids (budesonide and dexamethasone) — avoid concurrent use.
  • Digoxin — monitor the effects of digoxin; digoxin dose may need to be reduced by 50–75%.
  • Disopyramide — avoid concurrent use.
  • Domperidone — possible increased risk of ventricular arrhythmias. Avoid concurrent use.
  • Eplerenone — concurrent use is contraindicated.
  • Ergot alkaloids (such as ergotamine and ergometrine) — increased risk of ergotism. Concurrent use is contraindicated.
  • Ivabradine — concurrent use is contraindicated.
  • Mizolastine — monitor for adverse effects.
  • Oral anticoagulants (warfarin, apixaban, and dabigatran). Monitor for adverse effects and adjust doses if required.
  • Pimozide — increased risk of QT interval prolongation. Concurrent use is contraindicated.
  • Quinidine — increased risk of torsades de pointes. Concurrent use is contraindicated, but if considered necessary, monitor for adverse effects and reduce dose if required.
  • Ranolazine — increased risk of QT interval prolongation. Concurrent use is contraindicated.
  • Reboxetine — monitor for adverse effects and adjust dose if required.
  • Solifenacin — restrict dose of solifenacin to 5 mg daily.
  • Statins (lovastatin, simvastatin) — avoid concurrent use. 

[ABPI, 2018; BNF, 2023; Preston, 2019]