Fluconazole

Antifungals, triazole derivatives

ATC code: J02AC01 (Fluconazole)

Mechanism of action

Inhibits the fungal CYP450-dependent enzyme lanosterol 14-alpha-demethylase. Disrupts ergosterol synthesis – a component of the fungal cell membrane. The membrane loses integrity and the fungal cell dies. Excellent CSF penetration – CSF/plasma ratio is 60–80 %.

Indications

Cryptococcal meningitis

First line

First-line for consolidation and maintenance phases of cryptococcal meningitis. Induction with amphotericin B plus flucytosine for 2 weeks. Then consolidation with fluconazole 400–800 mg/day for 8 weeks. Maintenance 200 mg/day until immune reconstitution. Excellent CNS penetration makes fluconazole the optimal choice.

Oropharyngeal candidiasis

First line

First-line systemic therapy for moderate to severe oropharyngeal candidiasis. Dose 100–200 mg/day for 7–14 days. Mild cases can be managed topically with nystatin or clotrimazole. In HIV-infected patients, systemic fluconazole is preferred due to higher efficacy.

Vulvovaginal candidiasis

First line

First-line for uncomplicated vulvovaginal candidiasis. Single oral dose of 150 mg. Efficacy comparable to topical azoles but with greater convenience. For recurrent candidiasis (4 or more episodes per year), 150 mg once weekly for 6 months.

Practical notes

Timing and administration

Take once daily regardless of food. Oral bioavailability exceeds 90 %. Half-life is approximately 30 hours – allowing once-daily dosing and enabling the single-dose regimen for vaginal candidiasis.

Monitoring

Strong CYP2C9 inhibitor and moderate CYP3A4 inhibitor. Increases levels of warfarin, phenytoin, cyclosporine, tacrolimus, and certain statins. When co-administered with warfarin – monitor INR. Prolongs QT interval – do not combine with QT-prolonging agents.

Safety

Contraindications

Hypersensitivity to fluconazole or other azoles
Concomitant terfenadine, astemizole, cisapride, or pimozide (arrhythmia risk)

Serious adverse effects

Hepatotoxicity – from asymptomatic transaminase elevation to fulminant hepatitis (rare)
QT prolongation, torsades de pointes
Severe skin reactions – Stevens-Johnson syndrome, toxic epidermal necrolysis (rare)
Anaphylaxis (rare)

Common adverse effects

Headache
Nausea
Abdominal pain
Diarrhea
Rash

PregnancyFDA D

FDA category D. High doses (400–800 mg/day) in the first trimester are associated with congenital anomalies – craniofacial and skeletal defects. A single 150 mg dose for vaginal candidiasis does not appear to increase risk per observational data, but topical antifungals are preferred in pregnancy.