oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
- Triazole antifungals: fluconazole, itraconazole, posaconazole, voriconazole
- Imidazole antifungals: clotrimazole, econazole, miconazole, ketoconazole and tioconazole
- Polyene antifungals: amphotericin, nystatin
- Echinocandin antifungals: anidulafungin, caspofungin and micafungin
- Other antifungals: these include flucytosine, griseofulvin and terbinafine
NB: griseofulvin tablets are still available but have been largely superseded by other antifungal agents. It is, however, still the drug of choice in trichophyton infections in children.
Indications for use
See the separate article on Vaginal and Vulval Candidiasis.
- Imidazole drugs (clotrimazole, econazole, fenticonazole, and miconazole) are effective in the treatment of vulvovaginal candidiasis.
- Oral treatment with fluconazole or itraconazole is also effective. Oral antifungal treatment should be avoided during pregnancy.
- Treatment against candidal infection may need to be extended for six months in recurrent vulvovaginal candidiasis.
See the separate article on Candidiasis.
- First-line therapy is with topical treatment which may be miconazole gel or nystatin suspension.
- Second-line therapy is with systemic anticandidal treatment. For extensive or severe candidiasis, prescribe oral fluconazole 50 mg a day for seven days. If the infection has not resolved after seven days, offer treatment for a further week.
- Children should only receive topical anticandidal treatment. Offer miconazole oral gel first-line (off-label use in children less than 4 months of age). Offer nystatin suspension (off-label use in neonates) if miconazole oral gel is unsuitable.
See the separate article on Fungal Nail Infections.
- Oral terbinafine is the first-line oral treatment. Treat for between six weeks and three months for fingernails and for between three and six months for toenails.
- Oral itraconazole is an alternative. Terbinafine is most effective against dermatophyte nail infections. It has fungistatic activity against Candida albicans. Itraconazole is highly active against Candida spp. but much less so against dermatophytes.
- Fluconazole is not licensed for nail disease, but is used for severe infection in immunosuppressed people.
- Griseofulvin is not effective against Candida spp.
- Topical antifungals should be prescribed in most cases. The imidazoles (clotrimazole, econazole, and miconazole) are all effective.
- Systemic treatment is only indicated in severe, extensive skin infection, or if there is associated systemic infection (eg, in immunosuppressed people), or in the rare person unresponsive to topical treatment. Referral to specialist care is indicated.
Fungal ear infections
See the separate article on Fungal Ear Infection (Otomycosis).
Fungal eye infections
Most fungi causing orbital infections are ubiquitous aerobic organisms that are normal commensals of the respiratory, gastrointestinal and female genital tracts, as well as sometimes being present on normal conjunctiva.
Fungal eye infections are rare in Western countries; they are more frequently seen in tropical and subtropical regions.
Fungal infections of the eye may include orbital cellulitis, dacryocystitis, conjunctivitis, keratitis and endophthalmitis. Thus, they can work at a superficial level or penetrate deeply into the eye.
Treatment is initiated and monitored by a specialist ophthalmology team. Samples such as corneal scrapes will have been obtained prior to initiation of therapy. Any steroid treatment needs to be discontinued. Antifungal preparations for the eye are not generally available and have to be specifically made up for each patient. There are three main classes of ocular antifungals:
- Polyenes, particularly amphotericin and natamycin, which have a broad spectrum of activity.
- Azoles, as derivatives of imidazoles, which are useful in yeast infections - eg, clotrimazole 1%, econazole 1%, itraconazole 1%, miconazole 1%.
- Flucytosine 1%, a synthetic fluorinated pyrimidine which is effective against yeasts.
Treatment tends to be long (in the order of weeks or months) and may involve topical ± systemic therapy, depending on the nature of the infection and its severity.
Systemic fungal infections
Specialist treatment is required in most forms of systemic or disseminated fungal infections.
Immunocompromised patients are at increased risk of fungal infections and may need prophylactic antifungal drugs.
Oral triazole antifungals are the drugs of choice for prophylaxis. Fluconazole is more reliably absorbed than itraconazole but is not effective against Aspergillus spp. Therefore, itraconazole is preferred in patients at risk of invasive aspergillosis.
Posaconazole can be used for prophylaxis in patients who are undergoing haematopoietic stem cell transplantation or receiving chemotherapy for acute myeloid leukaemia and myelodysplastic syndrome, if they are intolerant of fluconazole or itraconazole. Micafungin can be used when fluconazole, itraconazole or posaconazole cannot be used.
Amphotericin by intravenous infusion or caspofungin is used for the empirical treatment of serious fungal infections. Caspofungin is not effective against fungal infections of the central nervous system.
Cautions and contra-indications
- Amphotericin has a risk of toxicity when given parenterally. It should only be used parenterally in hospitalised patients, or for those under close clinical observation.
- If serum creatinine exceeds 260 μmol/L the drug should be discontinued or the dosage markedly reduced until renal function is improved.
- Weekly blood counts and serum potassium levels are also advisable.
- Low serum magnesium levels have also been noted.
- Therapy should be discontinued if LFT results (elevated alkaline phosphatase and bilirubin) are abnormal.
- Fluconazole carries a risk of hepatic impairment. Use with caution in pregnancy, breast-feeding and impaired liver function.
- Oral ketoconazole (for any indication) is not recommended, as the risks outweigh the benefits.
- Griseofulvin may impair the ability to perform skilled tasks - eg, driving. The toxic effects of alcohol are increased. It is CONTRA-INDICATED in severe liver disease and systemic lupus erythematosus (SLE).
- Ketoconazole is CONTRA-INDICATED in hepatic disease, pregnancy and breast-feeding.
- Miconazole is CONTRA-INDICATED in liver disease.
- Terbinafine should be used with caution in liver or kidney disease, pregnancy or breast-feeding.
NB: many nystatin preparations are now withdrawn. This includes vaginal cream, pessaries, pastilles and Tri-Adcortyl Otic®.
Many antifungals have similar adverse effects. They all may cause gastrointestinal upset, rashes, headaches, etc. In addition:
- Amphotericin may cause muscle and joint pain, hypokalaemia/hypomagnesaemia, hearing loss, diplopia, convulsions or peripheral neuropathy.
- Fluconazole may cause LFT abnormalities, and rash - toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported.
- Griseofulvin may aggravate or precipitate SLE.
- Flucytosine may cause marrow aplasia
- Application of topical imidazoles can be painful in some instances where there is particularly bad inflammation.
- Terbinafine is associated with loss of taste (all four areas), particularly in underweight or elderly patients.
Further reading & references
- Fungal skin infection - foot; NICE CKS, May 2009
- Fungal skin infection - scalp; NICE CKS, May 2009
- Fungal skin infections; DermNet NZ
- Candida - female genital; NICE CKS, August 2012
- Candida - oral; CKS NICE, September 2009
- Fungal nail infection (onychomycosis); NICE CKS, May 2009
- Fungal skin infection - body and groin; NICE CKS, May 2009
- Nayak N; Fungal infections of the eye--laboratory diagnosis and treatment. Nepal Med Coll J. 2008 Mar;10(1):48-63.
- Kaur IP, Rana C, Singh H; Development of effective ocular preparations of antifungal agents. J Ocul Pharmacol Ther. 2008 Oct;24(5):481-93.
- British National Formulary
- Press release: oral ketoconazole - containing medicines should no longer be used for fungal infections; Medicines and Healthcare products Regulatory Agency, July 2013
- Doty RL, Haxel BR; Objective assessment of terbinafine-induced taste loss. Laryngoscope. 2005 Nov;115(11):2035-7.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Hayley Willacy
Dr Colin Tidy
Dr Adrian Bonsall