Itraconazole !

Oral triazole for histoplasmosis, sporotrichosis, endemic mycoses and nail fungus. It needs stomach acid and can worsen heart failure.

Updated 2026-11-01

Class: Azole antifungals
Enzyme: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
ATC code: J02AC02
WHO Model List of Essential Medicines

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

The figure shows itraconazole bound to CYP51 from Candida albicans.

Target in 3D: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme). PDB structure 5V5Z (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Itraconazole inhibits the cytochrome P450-dependent 14α-demethylation step of ergosterol synthesis in the fungus, so the membrane lacks ergosterol. Unlike fluconazole it is active against Aspergillus. It is also a potent inhibitor of human CYP3A4, which makes many combinations dangerous.

Itraconazole blocks fungal CYP51
Ergosterol is not made and methyl sterols build up
Fungal growth stops, including Aspergillus and dimorphic fungi

Pharmacokinetics

Absorption: About half of an oral dose is absorbed; capsules are best absorbed right after a full meal and poorly when stomach acid is low (PPIs, H2 blockers, achlorhydria). Capsule and oral solution give different exposure.
Distribution: Over 99% protein-bound and fat-loving; tissue levels (lung, kidney, liver, bone) are higher than in plasma.
Metabolism: Mainly in the liver; non-linear kinetics, so it accumulates with repeated doses.

Indications

Histoplasmosis, including chronic cavitary lung disease and disseminated non-meningeal disease. Histoplasmosis →
Blastomycosis, pulmonary and extrapulmonary; indolent coccidioidomycosis. Endemic mycoses: blastomycosis and coccidioidomycosis →
Paracoccidioidomycosis, frequent in rural Latin America. Paracoccidioidomycosis →
Cutaneous and extracutaneous sporotrichosis. Sporotrichosis and other subcutaneous mycoses →
Aspergillosis in patients intolerant of or refractory to amphotericin B. Aspergillosis →
Onychomycosis of toenails and fingernails due to dermatophytes. Dermatophytosis (tinea) and onychomycosis →

Adverse effects

Common

Nausea and vomiting
Rash
Raised liver enzymes

Contraindications

Onychomycosis in patients with ventricular dysfunction or a history of heart failure
Co-administration with many CYP3A4 substrates: methadone, quinidine, dofetilide, dronedarone, pimozide, simvastatin, lovastatin, oral midazolam, triazolam, ergot alkaloids, among others
Onychomycosis in pregnancy or when pregnancy is planned
Hypersensitivity to itraconazole

Key interactions

Simvastatin and lovastatin: Contraindicated: their levels rise and rhabdomyolysis can occur.
QT-prolonging CYP3A4 substrates (quinidine, dofetilide, pimozide, methadone): Contraindicated: ventricular arrhythmias, including torsade de pointes.
Oral midazolam and triazolam: Contraindicated: prolonged, deep sedation.
Antacids, H2 blockers and proton pump inhibitors: Lower absorption of the capsules; antacids are separated in time.
Rifampicin, isoniazid, phenytoin and carbamazepine: Lower itraconazole levels and may cause treatment failure.

What is monitored

Liver tests, considered in every patient
Signs of heart failure: weight, oedema, breathlessness
Hearing and peripheral nerves
Blood levels in selected patients

Administration and safety

Capsules are given right after a full meal to maximise absorption.
Capsules and oral solution are not interchangeable: check which form was ordered.
Separate antacids from the capsules by a couple of hours before or after.
Screen the medication list against the contraindicated CYP3A4 substrates before the first dose.

Nursing care

Weigh the patient and look for oedema, breathlessness or fatigue that may signal heart failure.
Teach the signs of liver injury (fatigue, loss of appetite, nausea, jaundice, dark urine, pale stools) and to stop and report them.
Ask about hearing loss, tingling or numbness.
For nail treatment in women who could become pregnant, effective contraception is needed.

Pregnancy and breastfeeding

Teratogenic in animals; not used for nail infections in pregnancy, and for systemic mycoses only if the benefit outweighs the risk.

Test yourself

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

A patient with heart failure asks for oral itraconazole for nail fungus. What is the problem?

Itraconazole has negative inotropic effects; it is contraindicated for onychomycosis in ventricular dysfunction or heart failure.

Why can omeprazole make itraconazole capsules fail?

Capsules need stomach acid to dissolve and be absorbed; acid suppression lowers its levels.

Which endemic Latin American mycoses are classic indications for itraconazole?

Paracoccidioidomycosis, histoplasmosis and sporotrichosis (mild to moderate forms).

Why is simvastatin contraindicated with itraconazole?

Itraconazole inhibits CYP3A4, which clears simvastatin; its levels rise and can cause rhabdomyolysis.

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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 - ITRACONAZOLE capsule (DailyMed (U.S. National Library of Medicine), 2026); Itraconazole: MedlinePlus Drug Information (MedlinePlus (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.