Fluconazole !

Triazole antifungal by mouth or vein for Candida and Cryptococcus. It reaches the CSF, leaves through the kidneys and raises levels of many drugs.

Updated 2026-11-01

Class: Azole antifungals
Enzyme: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme)
ATC code: J02AC01
WHO Model List of Essential Medicines

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

The figure shows fluconazole in the active site of CYP51 from the yeast Saccharomyces cerevisiae, a close relative of the Candida enzyme.

Target in 3D: Lanosterol 14α-demethylase (CYP51, the fungal ERG11 enzyme). PDB structure 4WMZ (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Fluconazole is a highly selective inhibitor of fungal lanosterol 14α-demethylase, the cytochrome P450 enzyme that converts lanosterol into ergosterol. Ergosterol runs short and 14α-methyl sterols accumulate, which stops fungal growth (fungistatic). The human enzyme is much less sensitive. In the liver, fluconazole inhibits CYP2C19 strongly and CYP2C9 and CYP3A4 moderately, the basis of its interactions.

Fluconazole binds fungal CYP51 (lanosterol 14α-demethylase)
Lanosterol is no longer turned into ergosterol
Toxic 14α-methyl sterols build up in the membrane
Candida stops growing (fungistatic)

Pharmacokinetics

Absorption: Oral bioavailability over 90%: oral and intravenous routes give similar levels.
Distribution: Low protein binding; spreads through body water and reaches the CSF at about half or more of plasma levels.
Elimination: About 80% leaves unchanged in the urine; the dose is reduced in kidney failure and haemodialysis removes it.
Half-life: About 30 hours in adults with normal kidneys.

Indications

Vaginal candidiasis. Vulvovaginal candidiasis →
Oropharyngeal candidiasis and candidaemia or other invasive Candida infections. Candidiasis: oral, oesophageal and invasive →
Oesophageal candidiasis. Infectious and pill-induced oesophagitis (Candida, HSV, CMV) →
Cryptococcal meningitis, as consolidation and maintenance after induction (and long-term suppression in people with AIDS). Cryptococcal meningitis →
Prevention of candidiasis in bone marrow transplant recipients receiving chemotherapy or radiotherapy.

Adverse effects

Common

Headache
Nausea, abdominal pain and diarrhoea
Taste changes
Raised liver enzymes
Rash

Contraindications

Hypersensitivity to fluconazole (caution with other azole allergy)
Co-administration with QT-prolonging drugs metabolised by CYP3A4: erythromycin, pimozide, quinidine

Key interactions

Warfarin: Prothrombin time rises and bleeding has occurred; INR is checked closely.
Sulfonylureas (glibenclamide, glipizide, tolbutamide): Higher levels and hypoglycaemia; blood glucose is monitored.
Phenytoin: Phenytoin levels rise; they are measured.
Cyclosporine and tacrolimus: Levels rise; drug levels and creatinine are monitored.
Statins metabolised by CYP3A4 or CYP2C9 (atorvastatin, simvastatin, fluvastatin): Higher risk of myopathy and rhabdomyolysis.
Fentanyl, alfentanil and methadone: Slower elimination; risk of respiratory depression.
Rifampicin: Lowers fluconazole exposure.

What is monitored

Liver tests, especially with long treatment
Kidney function, which sets the dose
ECG and electrolytes in patients with QT risk factors
INR, glucose or drug levels when an interacting drug is used

Administration and safety

Oral and intravenous forms give similar exposure, so patients are switched to the oral route when they can swallow.
The dose depends on kidney function: check the current creatinine clearance before each order is prepared.
Review the full medication list for warfarin, sulfonylureas, QT-prolonging drugs and immunosuppressants before the first dose.
Take cultures and other samples before starting when possible, without delaying treatment.

Nursing care

Teach the signs of liver injury (yellow skin or eyes, dark urine, tiredness, abdominal pain) and to report them.
A new rash during treatment is reported promptly: exfoliative reactions can be severe.
In diabetic patients on sulfonylureas, watch for hypoglycaemia; with warfarin, for bruising or bleeding.
Dizziness or seizures can occur: caution with driving or machinery.

Pregnancy and breastfeeding

Avoided except in severe or life-threatening infections: high doses during most of the first trimester have caused a distinct pattern of birth defects, and even single low doses carry an uncertain risk signal.

Test yourself

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

A patient on fluconazole for candidaemia remains positive and the isolate is Candida krusei. Why?

C. krusei is intrinsically resistant to fluconazole; another antifungal (for example an echinocandin) is needed.

Why is fluconazole useful in cryptococcal meningitis while echinocandins are not?

It penetrates the CSF well and is active against Cryptococcus; echinocandins neither reach the CSF nor cover Cryptococcus.

Which organ handles fluconazole's elimination, and what follows for dosing?

The kidney, mostly as unchanged drug: the dose is reduced when creatinine clearance falls.

A woman on warfarin receives fluconazole and develops nosebleeds. What is the mechanism?

Fluconazole inhibits CYP2C9, which breaks down warfarin, so warfarin levels and the INR rise.

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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 - FLUCONAZOLE tablet (DailyMed (U.S. National Library of Medicine), 2026); Fluconazole: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2018); 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.