Fluconazol

Fluconazole is a triazole antifungal agent that acts by inhibiting the fungal enzyme lanosterol 14-alpha-demethylase, a component of the cytochrome P450 system essential for the synthesis of ergosterol in the fungal cell membrane.

Without adequate ergosterol, the cell membrane becomes unstable, leading to fungal cell death.

Fluconazole has a broad spectrum of activity against Candida species, Cryptococcus neoformans, dermatophytes, and certain dimorphic fungi.

It is licensed for the treatment of mucosal candidiasis (oropharyngeal, oesophageal, vaginal), systemic candidiasis, cryptococcal meningitis, and the prevention of fungal infections in immunocompromised patients.

A single 150 mg oral dose is the standard treatment for uncomplicated vaginal candidiasis (thrush), with a cure rate exceeding 90% in clinical studies.

Fluconazole is well absorbed orally with bioavailability exceeding 90%, and its pharmacokinetic profile permits once-daily dosing.

The BNF lists fluconazole as a first-line option for mucosal candidiasis.

Swallow capsules whole with water. Fluconazole may be taken with or without food. For uncomplicated vaginal thrush, a single dose of 150 mg is sufficient.

For other indications, follow the prescribed course exactly; do not discontinue early even if symptoms resolve, as incomplete treatment promotes antifungal resistance.

For oropharyngeal candidiasis, treatment is typically 7-14 days.

Patients with recurrent vulvovaginal candidiasis (4 or more episodes per year) may require a longer maintenance regimen, usually 150 mg once weekly for 6 months.

Ensure adequate hydration throughout treatment.

Vaginal candidiasis: 150 mg as a single oral dose.

Oropharyngeal candidiasis: 50-100 mg once daily for 7-14 days.

Oesophageal candidiasis: 50-200 mg once daily for 14-30 days.

Systemic candidiasis: 400 mg on day 1, then 200-400 mg once daily; duration depends on clinical response.

Cryptococcal meningitis: 400 mg on day 1, then 200-400 mg daily for 6-8 weeks minimum.

In renal impairment (creatinine clearance <50 mL/min), halve the standard dose after a normal loading dose. In children, dosing is weight-based at 3-12 mg/kg/day depending on the indication.

Side effect frequencies are from pooled clinical trial and post-marketing data.

Common (≥1/100 to <1/10): Headache, nausea, abdominal pain, diarrhoea, vomiting, rash, elevated liver transaminases (ALT, AST).

Uncommon (≥1/1,000 to <1/100): Flatulence, dyspepsia, taste disturbance, dizziness, insomnia, drowsiness, pruritus, urticaria, increased bilirubin.

Rare (≥1/10,000 to <1/1,000): Hepatotoxicity (including rare fatal cases), Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, QT prolongation, torsade de pointes, agranulocytosis, thrombocytopenia, hypokalaemia, alopecia.

Most adverse effects are mild and transient with short-course therapy.

The risk of hepatotoxicity increases with higher doses and prolonged treatment, particularly in patients with serious underlying conditions.

Fluconazole is a potent inhibitor of CYP2C9 and a moderate inhibitor of CYP3A4, leading to significant drug interactions.

Concomitant use with warfarin increases INR (monitor closely); combine with caution with statins (rhabdomyolysis risk), ciclosporin, tacrolimus, and oral hypoglycaemics.

QT prolongation has been reported; avoid concomitant use with drugs known to prolong the QT interval (e.g. erythromycin, domperidone, class IA/III antiarrhythmics).

The MHRA advises liver function monitoring during prolonged therapy. Discontinue fluconazole if clinical signs of liver disease develop.

Teratogenic effects have been observed with high-dose, prolonged fluconazole use during the first trimester; single-dose treatment for vaginal candidiasis is not associated with increased risk.

Fluconazole is contraindicated in patients with known hypersensitivity to fluconazole, other azole antifungals, or any excipient.

Co-administration with terfenadine (at fluconazole doses ≥400 mg/day), astemizole, cisapride, pimozide, or quinidine is contraindicated due to the risk of QT prolongation and cardiac arrhythmia.

High-dose, prolonged use should be avoided in pregnancy, particularly the first trimester; a single 150 mg dose for vaginal thrush is considered acceptable if topical treatment is not feasible.