Antifungal Medications (excluding Eye Preparations)

Systemic or disseminated fungal infections usually require specialist treatment. Immunocompromised patients are at particular risk from fungal infections and may require prophylactic treatment.

Topical imidazole group:

• Clotrimazole
• Econazole
• Miconazole

Triazole drug group:

• Fluconazole
• Itraconazole
• Voriconazole

Polyene antifungals:

• Amphotericin
• Nystatin
• Griseofulvin
• Flucytosine
• Terbinafine

• Candidal vulvovaginitis:
  • Topical imidazoles are commonly used in the treatment of vulvovaginal candidiasis. No particular topical imidazole has been found to be superior to any other.¹ The efficacy of topical imidazoles does not depend on the length of the course of treatment, but is related to the total dose of drug received. A single high dose is as effective as a lower divided dose over several days.^2,3 To be effective, intravaginal application is required. However, women should apply cream to the vulva as well as inserting a pessary or intravaginal cream where possible, as this area is also commonly affected.
  • Oral fluconazole and itraconazole are as effective, but not better than topical imidazoles.
• Oral candidiasis:
  • First-line therapy is with topical treatment which may be miconazole gel or nystatin suspension.⁴
  • 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 four months of age). Offer nystatin suspension (off-label use in neonates) if miconazole oral gel is unsuitable.
• Nail infections:
  • Oral terbinafine is the first-line oral treatment - 250 mg once a day. Treat for between six weeks and three months for fingernails and for 3-6 months for toenails.⁵ Oral itraconazole is an alternative. Prescribe as pulsed therapy: 200 mg twice a day for one week, with subsequent courses repeated after a further 21 days. 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.
• Skin infections:
  • Topical antifungals should be prescribed in most cases. The imidazoles (clotrimazole, econazole, ketoconazole, miconazole and sulconazole) are all effective.⁶
  • Systemic treatment is only indicated in severe, extensive skin infection, or if there is associated systemic infection, e.g. in immunosuppressed people, or in the rare person unresponsive to topical treatment. Referral to specialist care is indicated.
• Aspergillosis - most commonly in the respiratory tract of severely immunocompromised patients, is treated with amphotericin. Recent work suggests there may be a reduction in mortality rate from using combination therapy, or liposomal amphotericin B, rather than amphotericin monotherapy.⁷
• Cryptococcosis - this is uncommon, except in immunocompromised patients, e.g. AIDS. Cryptococcal meningitis is the most common form of fungal meningitis. Treatment is with amphotericin, with or without flucytosine. Fluconazole can be given alone to AIDS patients with no disturbance of consciousness. It is also used as prophylaxis against relapse.
• Histoplasmosis - is very rare in this country. It can be life-threatening, particularly in HIV-infected patients. Itraconazole or ketoconazole orally can be given in less severe infection. Intravenous amphotericin is used in more severe infections.

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, rash - toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported.
• Griseofulvin may aggravate or precipitate SLE.
• Application of topical imidazoles can be painful in some instances where there is particularly bad inflammation.¹
• Terbinafine is associated with loss of taste (all four areas), particularly in underweight or elderly patients.⁸

1. Candida - female genital, Clinical Knowledge Summaries (2007)
2. Marrazzo J; Vulvovaginal candidiasis. BMJ. 2002 Sep 14;325(7364):586.
3. Sobel JD; Management of patients with recurrent vulvovaginal candidiasis. Drugs. 2003;63(11):1059-66. [abstract]
4. Candida - oral, Clinical Knowledge Summaries (September 2009)
5. Fungal nail infection, Clinical Knowledge Summaries (May 2009)
6. Fungal skin infection - body and groin, Clinical Knowledge Summaries (May 2009)
7. Trullas JC, Cervera C, Benito N, et al; Invasive pulmonary aspergillosis in solid organ and bone marrow transplant recipients.; Transplant Proc. 2005 Nov;37(9):4091-3. [abstract]
8. Doty RL, Haxel BR; Objective assessment of terbinafine-induced taste loss. Laryngoscope. 2005 Nov;115(11):2035-7. [abstract]