[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Azole antifungals](https://durgical.com/en/pharmacology/classes/azole-antifungals/) › Itraconazole

[Pharmacology](https://durgical.com/en/pharmacology/) · [Azole antifungals](https://durgical.com/en/pharmacology/classes/azole-antifungals/)

# 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](https://durgical.com/en/pharmacology/classes/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](https://www.rcsb.org/structure/5V5Z) · Drag to rotate · pinch to zoom

## 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 →](https://durgical.com/en/conditions/histoplasmosis/)
- Blastomycosis, pulmonary and extrapulmonary; indolent coccidioidomycosis. [Endemic mycoses: blastomycosis and coccidioidomycosis →](https://durgical.com/en/conditions/endemic-mycoses-blastomycosis-and-coccidioidomycosis/)
- Paracoccidioidomycosis, frequent in rural Latin America. [Paracoccidioidomycosis →](https://durgical.com/en/conditions/paracoccidioidomycosis/)
- Cutaneous and extracutaneous sporotrichosis. [Sporotrichosis and other subcutaneous mycoses →](https://durgical.com/en/conditions/sporotrichosis-and-other-subcutaneous-mycoses/)
- Aspergillosis in patients intolerant of or refractory to amphotericin B. [Aspergillosis →](https://durgical.com/en/conditions/aspergillosis/)
- Onychomycosis of toenails and fingernails due to dermatophytes. [Dermatophytosis (tinea) and onychomycosis →](https://durgical.com/en/conditions/dermatophytosis-and-onychomycosis/)

## Adverse effects

### Common

- Nausea and vomiting
- Rash
- Raised liver enzymes

### Serious (rare, important)

- Congestive heart failure (negative inotropic effect)
- Serious hepatotoxicity, including liver failure, sometimes in the first week
- QT prolongation and torsade de pointes when combined with contraindicated drugs
- Transient or permanent hearing loss
- Peripheral neuropathy

## 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.

## Memory aid

«ITRA needs a meal, acid and a strong heart»: with food, without PPIs, and never for nails in heart failure.

## 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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## Related drugs

- [Fluconazole](https://durgical.com/en/pharmacology/fluconazole/)
- [Voriconazole](https://durgical.com/en/pharmacology/voriconazole/)
- [Ketoconazole](https://durgical.com/en/pharmacology/ketoconazole/)
- [Terbinafine](https://durgical.com/en/pharmacology/terbinafine/)

## Related conditions

- [Histoplasmosis](https://durgical.com/en/conditions/histoplasmosis/)
- [Endemic mycoses: blastomycosis and coccidioidomycosis](https://durgical.com/en/conditions/endemic-mycoses-blastomycosis-and-coccidioidomycosis/)
- [Paracoccidioidomycosis](https://durgical.com/en/conditions/paracoccidioidomycosis/)
- [Sporotrichosis and other subcutaneous mycoses](https://durgical.com/en/conditions/sporotrichosis-and-other-subcutaneous-mycoses/)
- [Aspergillosis](https://durgical.com/en/conditions/aspergillosis/)
- [Dermatophytosis (tinea) and onychomycosis](https://durgical.com/en/conditions/dermatophytosis-and-onychomycosis/)

[← Back to the class: Azole antifungals](https://durgical.com/en/pharmacology/classes/azole-antifungals/)

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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2ab38a8a-3708-4b97-9f7f-8e554a15348d) (DailyMed (U.S. National Library of Medicine), 2026); [Itraconazole: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a692049.html) (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.

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