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Pharmacology · Azole antifungals

Posaconazole !

Broad triazole that prevents Aspergillus and Candida infections in severely immunocompromised patients and treats aspergillosis.

Updated 2026-11-01

  • Class: Azole antifungals
  • Enzyme: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
  • ATC code: J02AC04

The figure shows posaconazole bound to CYP51 from Candida albicans.

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

Mechanism of action

Posaconazole blocks fungal lanosterol 14α-demethylase, so methylated sterol precursors accumulate and ergosterol is depleted, weakening the fungal membrane. It covers Aspergillus and Candida and has more activity than other azoles against the moulds that cause mucormycosis. It is a strong CYP3A4 inhibitor.

  1. Posaconazole blocks fungal CYP51
  2. Ergosterol is depleted and methylated sterols build up
  3. Mould and yeast growth stops

Pharmacokinetics

Absorption
Delayed-release tablets can be given with or without food; the oral suspension needs food and is not substitutable with the tablets.
Distribution
Large volume of distribution and over 98% protein-bound.
Elimination
Mostly in the stool, largely unchanged.
Half-life
Long, about a day.

Indications

  • Prevention of invasive Aspergillus infections in severely immunocompromised patients (stem cell transplant with graft-versus-host disease, haematological cancers with prolonged neutropenia). Aspergillosis →
  • Prevention of invasive Candida infections in the same patients. Candidiasis: oral, oesophageal and invasive →
  • Treatment of invasive aspergillosis; alternative in mucormycosis when amphotericin B is not tolerated. Aspergillosis →

Adverse effects

Common

  • Diarrhoea
  • Fever
  • Nausea

Contraindications

  • Hypersensitivity to posaconazole or other azoles
  • Sirolimus
  • QT-prolonging CYP3A4 substrates such as pimozide and quinidine
  • Statins cleared mainly by CYP3A4 (atorvastatin, lovastatin, simvastatin)
  • Ergot alkaloids; venetoclax at initiation in chronic lymphocytic leukaemia

Key interactions

Sirolimus
Contraindicated: sirolimus levels rise about nine-fold.
Cyclosporine and tacrolimus
Levels rise; dose reduction and frequent level checks.
Midazolam
Levels rise about five-fold: prolonged sedation.
Vincristine
Neurotoxicity (seizures, neuropathy, paralytic ileus); azoles are reserved for when no alternative exists.
Statins cleared by CYP3A4
Contraindicated: rhabdomyolysis.

What is monitored

  • Liver tests at the start and during treatment
  • Potassium, magnesium and calcium; blood pressure
  • Calcineurin-inhibitor levels if used together
  • ECG in patients with arrhythmia risk

Administration and safety

  • Tablets, oral suspension, powder for suspension and injection have different strengths and doses and are not substitutable: check the exact form ordered.
  • Delayed-release tablets are swallowed whole (not divided, crushed or chewed), with or without food.
  • Correct electrolyte disturbances before and during treatment.

Nursing care

  • Report severe diarrhoea or vomiting: absorption falls and breakthrough infection can occur.
  • Check blood pressure and potassium (pseudoaldosteronism).
  • Teach signs of liver injury and palpitations or fainting.
  • Watch sedation when benzodiazepines are also used.

Pregnancy and breastfeeding

Animal studies showed skeletal malformations; used in pregnancy only if the benefit justifies the risk.

Test yourself

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

What is the main labelled use of posaconazole delayed-release tablets?

Prevention of invasive Aspergillus and Candida infections in severely immunocompromised patients, such as stem cell transplant recipients with graft-versus-host disease.

Why is sirolimus contraindicated with posaconazole?

Posaconazole strongly inhibits CYP3A4 and sirolimus levels rise about nine-fold, causing toxicity.

Can the oral suspension be swapped for the tablets at the same dose?

No. The formulations are dosed differently and are not substitutable.

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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 - POSACONAZOLE tablet, delayed release (DailyMed (U.S. National Library of Medicine), 2026); Posaconazole: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); 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.