Ketoconazole !

Imidazole antifungal. As a cream or shampoo it treats seborrhoeic dermatitis and tinea; by mouth it is a last resort because it harms the liver.

Updated 2026-11-01

Class: Azole antifungals
Enzyme: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
ATC code: J02AB02

Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)Ketoconazole

The figure shows ketoconazole bound to human CYP51, the human counterpart of the fungal enzyme; ketoconazole's binding to human P450 enzymes explains part of its toxicity.

Target in 3D: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme). PDB structure 3LD6 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Ketoconazole blocks fungal lanosterol 14α-demethylase, so methylated sterols accumulate and ergosterol is depleted. Taken by mouth it also inhibits human steroid-making P450 enzymes, lowering testosterone and cortisol synthesis, and is a strong CYP3A4 inhibitor.

Ketoconazole blocks fungal CYP51
Ergosterol is depleted and the membrane weakens
Orally it also blocks human steroid synthesis

Pharmacokinetics

Absorption: A weak base that needs stomach acid to dissolve; antacids, H2 blockers and PPIs reduce absorption.
Distribution: Penetrates the CSF poorly, so it is not used for fungal meningitis.
Metabolism: Liver.

Indications

Seborrhoeic dermatitis and dandruff (cream, shampoo). Seborrheic dermatitis →
Pityriasis (tinea) versicolor (shampoo, cream). Pityriasis versicolor →
Tinea corporis, cruris and pedis (cream). Dermatophytosis (tinea) and onychomycosis →
Oral form only when other therapy has failed or is not tolerated: paracoccidioidomycosis, histoplasmosis, blastomycosis, coccidioidomycosis, chromomycosis. Paracoccidioidomycosis →

Adverse effects

Common

Topical: irritation, itching or stinging where applied
Oral: nausea, vomiting, diarrhoea, abdominal pain, taste changes
Oral: gynaecomastia and lower testosterone

Contraindications

Oral: acute or chronic liver disease
Oral: dofetilide, quinidine, pimozide, cisapride, methadone, disopyramide, dronedarone, ranolazine, simvastatin, lovastatin, oral midazolam, triazolam, ergot alkaloids, among others
Oral: not for onychomycosis, skin dermatophyte or Candida infections

Key interactions

QT-prolonging CYP3A4 substrates (dofetilide, quinidine, pimozide, methadone): Contraindicated with the oral form: torsade de pointes.
Antacids, H2 blockers and PPIs: Reduce absorption of the tablets; antacids are separated in time.
Simvastatin and lovastatin: Contraindicated with the oral form: rhabdomyolysis.

What is monitored

Oral: liver tests before and during treatment
Oral: adrenal function in patients at risk or under stress
Topical: response of the skin lesions

Administration and safety

Check which form is ordered: topical forms are common and safe; oral tablets are restricted.
Separate antacids from the tablets (at least an hour before or two hours after).
Shampoo and cream are for external use only.

Nursing care

With oral ketoconazole, teach the signs of liver injury and to report them at once.
Ask about palpitations or fainting; review all medicines for contraindicated combinations.
With topical use, report spreading redness, blisters or swelling.

Pregnancy and breastfeeding

Oral ketoconazole was teratogenic in rats; used in pregnancy only if the benefit justifies the risk.

Test yourself

Think of the answer, then tap the question to see it.

Why is oral ketoconazole no longer used for nail or skin fungus?

Its risks (serious hepatotoxicity, QT interactions, adrenal insufficiency) outweigh benefits when safer options exist.

Why can ketoconazole cause gynaecomastia?

It inhibits human P450 enzymes that make steroids, lowering testosterone.

What is the most common use of ketoconazole today?

Topical: cream or shampoo for seborrhoeic dermatitis, dandruff, pityriasis versicolor and tinea.

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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 - KETOCONAZOLE tablet (DailyMed (U.S. National Library of Medicine), 2026); Ketoconazole Topical: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2016); 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.