Voriconazole !

Triazole of choice for invasive aspergillosis, by mouth or vein. It causes visual changes and sun sensitivity, and its levels vary with CYP2C19 genes.

Updated 2026-11-01

Class: Azole antifungals
Enzyme: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
ATC code: J02AC03
WHO Model List of Essential Medicines

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

The figure shows voriconazole bound to CYP51 from the yeast Saccharomyces cerevisiae, a model of the fungal enzyme.

Target in 3D: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme). PDB structure 5HS1 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Voriconazole inhibits the fungal cytochrome P450-mediated 14α-demethylation of lanosterol, an essential step of ergosterol synthesis. 14α-methyl sterols accumulate and ergosterol is lost, which stops the fungus. Its spectrum includes Aspergillus, Candida, Scedosporium and Fusarium. It is metabolised by CYP2C19, CYP2C9 and CYP3A4 and inhibits them, so interactions are many.

Voriconazole blocks fungal CYP51
Ergosterol is lost and methyl sterols build up
Aspergillus hyphae stop growing

Pharmacokinetics

Absorption: Good oral absorption; tablets are given at least an hour away from meals.
Metabolism: Liver, mainly by CYP2C19, which is genetically polymorphic (poor metabolisers have higher levels); saturable, non-linear kinetics with high variability between patients.
Elimination: As metabolites; the intravenous vehicle (a cyclodextrin, SBECD) accumulates in moderate or severe kidney impairment.
Half-life: Dose-dependent, so it does not predict accumulation.

Indications

Invasive aspergillosis (first-line). Aspergillosis →
Candidaemia in non-neutropenic patients and other deep Candida infections. Candidiasis: oral, oesophageal and invasive →
Oesophageal candidiasis. Infectious and pill-induced oesophagitis (Candida, HSV, CMV) →
Serious infections by Scedosporium and Fusarium in patients intolerant of or refractory to other therapy.

Adverse effects

Common

Visual disturbances: blurred or altered vision, photophobia, altered colour vision
Transient visual or auditory hallucinations
Fever, nausea, vomiting, headache
Rash and photosensitivity
Raised liver tests; tachycardia

Contraindications

Hypersensitivity to voriconazole
CYP3A4 substrates with serious toxicity: sirolimus, pimozide, quinidine, ergot alkaloids, rifabutin, among others
Strong inducers that make it fail: rifampicin, carbamazepine, long-acting barbiturates, St John's wort, high-dose ritonavir and efavirenz

Key interactions

Sirolimus: Contraindicated: sirolimus levels rise sharply.
Tacrolimus and cyclosporine: Levels rise; their dose is reduced at the start and blood levels are checked often.
Rifampicin and carbamazepine: Contraindicated: voriconazole levels fall and treatment fails.
Warfarin and other coumarins: Prothrombin time rises; INR is monitored.
Phenytoin: Two-way interaction: phenytoin lowers voriconazole and voriconazole raises phenytoin; doses are adjusted.

What is monitored

Liver tests and bilirubin at the start, then weekly during the first month
Potassium, magnesium and calcium before and during treatment; creatinine
Visual acuity, visual field and colour vision if treatment lasts more than 28 days
Blood levels (therapeutic drug monitoring), given the large variability
Skin examination during long treatment

Administration and safety

Intravenous: slow infusion only, never as a bolus.
Do not infuse at the same time as blood products or short infusions of concentrated electrolytes, even through separate lines.
Correct low potassium, magnesium and calcium before starting.
In moderate or severe kidney impairment the oral route is preferred, because the intravenous vehicle accumulates.
Oral tablets: at least one hour before or after a meal.

Nursing care

Warn that blurred vision or light sensitivity are common; patients should not drive at night during treatment.
Teach strict sun protection (clothing, high-SPF sunscreen), especially in children.
Report hallucinations, palpitations or fainting.
Watch for signs of liver injury and for symptoms of adrenal insufficiency or Cushing syndrome when corticosteroids are also used.
Women who can become pregnant need effective contraception.

Pregnancy and breastfeeding

Can cause fetal harm (malformations in animals); effective contraception is advised during treatment.

Test yourself

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

What is the first-line drug for invasive aspergillosis in most guidelines?

Voriconazole (isavuconazole is an alternative; amphotericin B for intolerance or resistance).

Why are voriconazole blood levels so variable?

It is cleared mainly by CYP2C19, which is genetically polymorphic, and its metabolism saturates, giving non-linear kinetics.

A patient on voriconazole describes flashes of light and brighter colours. What is it?

The common visual adverse effect of voriconazole; it is usually transient, but vision is checked if treatment is long.

Why is oral voriconazole preferred in moderate kidney impairment?

The intravenous vehicle, a cyclodextrin (SBECD), accumulates when the kidneys fail.

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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 - VORICONAZOLE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - VORICONAZOLE injection, powder, lyophilized, for solution (DailyMed (U.S. National Library of Medicine), 2026); Voriconazole: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2022); 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.