Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Try free for 5 days
Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

Antifungals

Last updated: June 9, 2021

Summarytoggle arrow icon

Antifungals are a class of medications that destroy or inhibit the growth of fungal organisms and are, accordingly, used to treat fungal infections (mycoses) such as candidiasis, cryptococcal disease, aspergillosis, and dermatophytosis. They are divided into three major groups according to chemical structure and spectrum of efficacy: polyenes (used for the treatment of systemic fungal infections), azoles (broad-spectrum antifungals), and allylamines (used for the treatment of onychomycosis). Topical agents (e.g., clotrimazole) generally have a more limited scope of action. Common adverse effects include hepatotoxicity, skin reactions, headaches, and gastrointestinal upset.

Overview of antifungals and their mechanisms of action [1][2][3][4][5][6][7]
Class Examples Mechanism of action Clinical use Adverse effects
Polyenes
  • Bind to ergosterol in the fungal cell membrane → formation of pores in the fungal membrane → disruption of electrolyte balance → cell lysis → cell death

Azoles Triazoles
Imidazoles
Allylamines
Echinocandins
  • Flushing
  • Hepatotoxicity
  • Gastrointestinal upset
Pyridone derivatives
  • Not fully understood
Benzofurans
  • Bind to keratin interference with microtubule function → disruption of fungal mitosis inhibition of fungal growth
Antimetabolites
  • Converted to 5-fluorouracil by fungal cytosine deaminase inhibition of DNA and RNA synthesis → inhibition of fungal growth
  • Monotherapy: select cases of non-life-threatening infections such as genitourinary candida infections that are not covered by alternative drugs
  • Combination with amphotericin B (e.g., especially cryptococcal meningitis)

Amphotericin B Burrows nice (nystatin) holes in the fungal cell membrane.

Amphotericin B has amphoterrible side effects, including nephrotoxicity, arrhythmias, and IV phlebitis.

Nystatin is too toxic for intravenous use. For oropharyngeal candidiasis, the medication should be swished around in the mouth, gargled, and then swallowed (swish and swallow).

Overview of azoles
Active substance Clinical use Adverse effects
Topical use Systemic use
Imidazole derivatives
  • Clotrimazole
  • Miconazole
  • Ketoconazole

Triazole derivatives

  • Fluconazole
  • Voriconazole
  • Itraconazole
  • Posaconazole
  • Isavuconazole
  • Contraindications
  • Special considerations
    • Inhibition of cytochrome P450 can influence serum concentrations of other medications
    • Cautious use in patients with renal and/or hepatic dysfunction
    • PPIs must be discontinued (azoles require a low pH to be absorbed)

Voriconazole is the drug of choice for inVasive aspergillosis.

The FLU easily penetrates the blood-brain barrier: FLuconazole has good CNS penetration.

Treatment of common fungal infections
Treatment
Candidiasis Oropharyngeal
Esophageal
Vaginal
Cutaneous
Systemic

Invasive aspergillosis

Cryptococcosis

Blastomycosis

Histoplasmosis

Coccidioidomycosis

Sporotrichosis

Tinea versicolor
Dermatophytosis
  1. Antifungal Drugs. https://www.merckmanuals.com/professional/infectious-diseases/fungi/antifungal-drugs. Updated: January 1, 2014. Accessed: February 20, 2017.
  2. FDA Drug Safety Communication: FDA limits usage of Nizoral (ketoconazole) oral tablets due to potentially fatal liver injury and risk of drug interactions and adrenal gland problems. https://www.fda.gov/Drugs/DrugSafety/ucm362415.htm. Updated: July 26, 2013. Accessed: February 20, 2017.
  3. FDA Drug Safety Communication: FDA warns that prescribing of Nizoral (ketoconazole) oral tablets for unapproved uses including skin and nail infections continues; linked to patient death. https://www.fda.gov/Drugs/DrugSafety/ucm500597.htm. Updated: May 19, 2016. Accessed: February 20, 2017.
  4. Terbinafine. https://www.drugs.com/pro/terbinafine.html. Updated: February 20, 2017. Accessed: February 20, 2017.
  5. Griseofulvin. https://www.drugs.com/pro/griseofulvin.html. Updated: February 20, 2017. Accessed: February 20, 2017.
  6. Nystatin. https://www.drugs.com/monograph/nystatin.html. Updated: June 1, 2007. Accessed: January 29, 2018.
  7. Castinetti F, Guignat L, Giraud P, et al.. Ketoconazole in cushing's disease: is it worth a try?. J Clin Endocrinol Metab. 2014; 99 (5): p.1623-1630. doi: 10.1210/jc.2013-3628 . | Open in Read by QxMD
  8. Hamilton-Miller JM. Chemistry and biology of the polyene macrolide antibiotics.. Bacteriol Rev. 1973; 37 (3): p.166-96.
  9. Ashley ED, Perfect JR. Pharmacology of azoles. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. http://www.uptodate.com/contents/pharmacology-of-azoles?source=search_result&search=itraconazole&selectedTitle=6~150#H19.Last updated: January 3, 2017. Accessed: February 20, 2017.
  10. Abassi M, Boulware DR, Rhein J. Cryptococcal Meningitis: Diagnosis and Management Update.. Current tropical medicine reports. 2015; 2 (2): p.90-99. doi: 10.1007/s40475-015-0046-y . | Open in Read by QxMD
  11. Amphotericin B. https://www.drugs.com/mtm/amphotericin-b.html. Updated: March 2, 2020. Accessed: September 30, 2020.