Pharmacology · Class
Azole antifungals !
Antifungals that block the fungal enzyme that makes ergosterol (CYP51). They also block human CYP enzymes, so drug interactions are their big risk.
Updated 2026-11-01
What they are
Two chemical groups: imidazoles (ketoconazole, clotrimazole, miconazole), now used mostly on skin and mucosa, and triazoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole), the systemic workhorses for Candida, Cryptococcus, Aspergillus and the endemic mycoses of the Americas.
Mechanism of action
Azoles inhibit lanosterol 14α-demethylase (CYP51), a fungal cytochrome P450 enzyme that turns lanosterol into ergosterol. Ergosterol runs short and 14α-methyl sterols build up, so the membrane works badly and the fungus stops growing. The human version of the enzyme is far less sensitive, but azoles do inhibit human drug-metabolising CYPs, above all CYP3A4.
Target: Lanosterol 14α-demethylase (CYP51, ERG11)
Drugs in this class
- FluconazoleTriazole antifungal by mouth or vein for Candida and Cryptococcus. It reaches the CSF, leaves through the kidneys and…Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
- ItraconazoleOral triazole for histoplasmosis, sporotrichosis, endemic mycoses and nail fungus. It needs stomach acid and can…Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
- VoriconazoleTriazole of choice for invasive aspergillosis, by mouth or vein. It causes visual changes and sun sensitivity, and its…Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
- PosaconazoleBroad triazole that prevents Aspergillus and Candida infections in severely immunocompromised patients and treats…Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
- IsavuconazoleTriazole for invasive aspergillosis and mucormycosis, given as the prodrug isavuconazonium. Unlike other azoles it…Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
- KetoconazoleImidazole antifungal. As a cream or shampoo it treats seborrhoeic dermatitis and tinea; by mouth it is a last resort…Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
- ClotrimazoleImidazole antifungal used on the skin, in the vagina and as a mouth lozenge for Candida and ringworm. Very little…Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
- MiconazoleImidazole antifungal used on the skin, in the vagina and on the gums for Candida and tinea. Even vaginal use can raise…Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
Others in the class
- econazole
- sertaconazole
- tioconazole
- oteseconazole
Test yourself
Think of the answer, then tap the question to see it.
A kidney transplant patient on tacrolimus starts voriconazole. What happens?
Voriconazole inhibits CYP3A4, so tacrolimus levels rise; its dose is reduced when the azole starts and its blood levels are checked often, to avoid nephrotoxicity.
Which azole has no activity against Aspergillus?
Fluconazole. Itraconazole, voriconazole, posaconazole and isavuconazole do cover Aspergillus.
Why does oral ketoconazole cause gynaecomastia and adrenal insufficiency?
It also inhibits human steroid-making CYP enzymes, lowering testosterone and cortisol synthesis.
What is the enzyme that azoles block in the fungus?
Lanosterol 14α-demethylase (CYP51), coded by ERG11; it converts lanosterol into ergosterol.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - FLUCONAZOLE tablet (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - VORICONAZOLE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - ITRACONAZOLE capsule (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 61 (McGraw Hill, 2023).
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Representative model, for educational purposes only.