Fluconazole, a triazole antifungal, inhibits fungal cytochrome P450-dependent lanosterol 14α-demethylase, an enzyme critical for ergosterol synthesis. Depletion of ergosterol disrupts fungal cell membrane integrity, increasing permeability and inhibiting growth. Fluconazole is fungistatic against most Candida species but fungicidal at higher concentrations. It targets:

• Candida albicans, C. tropicalis, C. parapsilosis.
• Cryptococcus neoformans.
• Dermatophytes (e.g., Trichophyton).
  Resistance arises via mutations in the ERG11 gene or efflux pump overexpression (Lippincott).

Fluconazole is indicated for:

1. Candidiasis:
   • Vulvovaginal: Single 150 mg oral dose (BNF).
   • Oropharyngeal/Esophageal: 50–200 mg daily for 7–21 days.
   • Systemic: 400–800 mg/day for invasive infections (e.g., candidemia).
2. Cryptococcal Meningitis:
   • Induction: 400–800 mg/day with amphotericin B.
   • Maintenance: 200–400 mg/day (Lange).
3. Prophylaxis:
   • Immunocompromised patients (e.g., HIV, chemotherapy) at 50–400 mg/day.
4. Off-Label:

Tinea infections, coccidioidomycosis, and prophylaxis in ICU settings

Adults:

• Uncomplicated Vaginal Candidiasis: 150 mg single dose.
• Oropharyngeal Candidiasis: 50–100 mg daily for 7–14 days.
• Systemic Infections: 200–800 mg/day (dose depends on severity).

Children:

• 3 mg/kg/day for mucosal candidiasis; 6–12 mg/kg/day for systemic infections.

Renal Impairment:

• CrCl <50 mL/min: Reduce dose by 50% or extend dosing interval (BNF).

• Common: Nausea, headache, rash, abdominal pain.
• Serious:
  • Hepatotoxicity: Elevated LFTs (monitor baseline and periodically).
  • QT Prolongation: Risk of torsades de pointes in predisposed patients.
  • Adrenal Insufficiency: Rare, with prolonged high-dose therapy.
  • Stevens-Johnson Syndrome: Discontinue immediately if rash develops.

1. Hepatic/Renal Impairment: Monitor LFTs and adjust dose.
2. Pregnancy:
   • Avoid high doses (teratogenic in first trimester; Category D).
   • Single 150 mg dose for vaginal candidiasis is considered low-risk (BNF).
3. Lactation: Excreted in breast milk; use with caution.

Cardiac Conditions: Avoid in patients with prolonged QT interval

Fluconazole inhibits CYP3A4 and CYP2C9, leading to:

• Warfarin: Increased INR (monitor closely).
• Sulfonylureas: Hypoglycemia (e.g., glipizide).
• Phenytoin: Elevated levels (risk of toxicity).
• Cyclosporine/Tacrolimus: Nephrotoxicity (monitor levels).
• Rifampicin: Reduces fluconazole levels (avoid combination).
• Statins: Increased risk of myopathy (e.g., simvastatin).

• Generic: Fluconazole.
• Brand Names: Diflucan (oral/IV), Trican (regional variations).