Fluconazole
Fluconazole is an oral and parenteral triazole antifungal used in adults and children for vulvovaginal and oropharyngeal candidiasis, candidaemia, cryptococcal meningitis and prophylaxis in immunocompromised hosts. It is part of the World Health Organization List of Essential Medicines.
- Chemical formula
- C13H12F2N6O
- CAS number
- 86386-73-4
- ATC code
- J02AC01
- Molecular weight
- 306.27 g/mol
- Drug class
- Triazole antifungal
- Also known as
- UK-49858, Fluconazol
What is it?
Fluconazole was approved for clinical use in 1990 and is supplied as oral capsules, oral suspension and parenteral solution. Fluconazole is dispensed both with and without prescription depending on the indication and country, with single-dose oral formulations for vulvovaginal candidiasis available over the counter in many markets. It is part of the World Health Organization List of Essential Medicines and is widely used in routine and specialised care.
Mechanism of action
Fluconazole is a triazole antifungal that inhibits the cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase, blocking the synthesis of ergosterol from lanosterol. Ergosterol is an essential component of the fungal cell membrane, so depletion produces membrane dysfunction and growth inhibition. Fluconazole has activity against most Candida species (with reduced susceptibility in C. glabrata and C. krusei) and Cryptococcus neoformans.
Pharmacokinetics
Oral fluconazole is well absorbed, with bioavailability greater than 90%. Plasma protein binding is low (12%). The drug penetrates well into most body fluids and tissues, including the cerebrospinal fluid (about 80% of plasma concentrations), making it useful for cryptococcal meningitis. Fluconazole is excreted predominantly unchanged in urine. The plasma half-life is approximately 30 hours, supporting once-daily dosing. Renal impairment requires dose reduction.
Indications
Fluconazole is approved in adults and children for the treatment of vulvovaginal candidiasis, oropharyngeal and oesophageal candidiasis, urinary tract candidiasis, peritonitis and other invasive candidiasis caused by susceptible species, including candidaemia, and for cryptococcal meningitis (induction with amphotericin B and flucytosine, then fluconazole consolidation and maintenance). It is also used for prophylaxis in immunocompromised patients and in selected dermatomycoses in some markets.
Safety profile
Common adverse effects include headache, nausea and abdominal pain. Hepatic enzyme elevations occur in some patients and rare cases of serious hepatotoxicity have been reported. Fluconazole prolongs the QT interval and has been associated with rare cases of torsades de pointes. Fluconazole is a moderate CYP2C9 and CYP3A4 inhibitor, with multiple clinically relevant drug interactions. According to the prescribing information, dose adjustment is required in renal impairment.
Products containing this ingredient
Frequently asked questions
When is single-dose fluconazole appropriate for vaginal candidiasis? ▾
Uncomplicated acute vulvovaginal candidiasis in non-pregnant immunocompetent women generally responds to a single oral dose of fluconazole 150mg, with comparable efficacy to longer courses of topical antifungals. According to international guidelines, this regimen is widely used. Recurrent (four or more episodes per year), severe or complicated candidiasis requires longer regimens and evaluation by a clinician.
Why is fluconazole used in cryptococcal meningitis? ▾
Fluconazole achieves high concentrations in the cerebrospinal fluid (about 80% of plasma) and is active against Cryptococcus neoformans, making it useful for the consolidation and maintenance phases of cryptococcal meningitis treatment. According to international guidelines, induction is with amphotericin B (preferably liposomal) plus flucytosine, followed by consolidation with fluconazole at high doses, then long-term maintenance to prevent relapse.
What are the main drug interactions? ▾
Fluconazole is a moderate CYP2C9 and CYP3A4 inhibitor, with clinically relevant interactions including increased concentrations of warfarin (with bleeding risk), phenytoin, sulfonylureas, ciclosporin, tacrolimus, statins and several other drugs. It can also prolong the QT interval, increasing the risk when combined with other QT-prolonging drugs. According to the prescribing information, the medication list must be reviewed by a clinician before any prescription.
Is fluconazole safe in pregnancy? ▾
Single-dose fluconazole 150mg has been used for vaginal candidiasis without consistent evidence of harm, but high-dose long-term fluconazole during pregnancy has been associated with birth defects. According to several regulatory communications, single-dose fluconazole should be avoided when possible during pregnancy in favour of topical antifungals, and high doses are contraindicated. The medical history must be reviewed by a clinician.
What are the main contraindications for fluconazole? ▾
Fluconazole is contraindicated in known hypersensitivity to fluconazole or other azoles, in concurrent use with several QT-prolonging or strongly metabolised drugs (e.g. terfenadine, cisapride, pimozide and others depending on dose). Caution is required in renal and hepatic impairment, in QT prolongation, in pregnancy (high doses) and breastfeeding. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription.
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