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Approved Indications:

• Oropharyngeal and esophageal candidiasis: Treatment and prophylaxis in immunocompromised patients, including HIV/AIDS.
• Vulvovaginal candidiasis: Acute and recurrent episodes caused by susceptible Candida species.
• Cryptococcal meningitis: Treatment and maintenance therapy to prevent relapse, particularly in HIV-infected patients.
• Systemic candidiasis: Including candidemia and disseminated candidiasis.
• Coccidioidomycosis: Treatment of infections caused by Coccidioides immitis.
• Other fungal infections: Such as infections due to Blastomyces dermatitidis, Histoplasma capsulatum, and Paracoccidioides brasiliensis.

Off-label / Clinically Accepted Uses:

• Prophylaxis of fungal infections in neutropenic patients.
• Treatment of tinea infections and dermatophytosis.
• Treatment of fungal urinary tract infections.
• Occasionally used for onychomycosis.

• Adults:
• Oropharyngeal candidiasis: 100 mg orally once daily for 7–14 days.
• Esophageal candidiasis: 200 mg on day 1, then 100 mg daily for at least 14–30 days.
• Vulvovaginal candidiasis: 150 mg single oral dose.
• Cryptococcal meningitis: 400 mg (6 mg/kg) on day 1, then 200–400 mg daily for at least 6–8 weeks.
• Systemic fungal infections: 400 mg daily or higher depending on severity.
• Pediatrics:
• Dose based on body weight, typically 3–12 mg/kg/day orally or IV.
• For cryptococcal meningitis: loading dose 12 mg/kg, then 6–12 mg/kg daily.
• Elderly:
• No specific adjustment generally required; monitor renal function.
• Renal Impairment:
• Reduce dose by 50% in moderate to severe impairment (creatinine clearance <50 mL/min).
• Hepatic Impairment:
• No dosage adjustment typically needed but monitor liver function.
• Administration:
• Oral tablets or suspension taken with or without food.
• Intravenous formulations available for severe infections.
• Duration:
• Depends on infection type and clinical response; may range from single dose (vaginal candidiasis) to several months (cryptococcal meningitis).

Fluconazole is a triazole antifungal that selectively inhibits fungal cytochrome P450 enzyme 14α-demethylase. This enzyme is critical for the conversion of lanosterol to ergosterol, an essential component of the fungal cell membrane. Inhibition leads to depletion of ergosterol and accumulation of toxic methylated sterols, disrupting membrane integrity and function, which inhibits fungal growth (fungistatic effect) and leads to cell death in susceptible fungi.

• Absorption:
  Excellent oral bioavailability (>90%), unaffected by food.
• Distribution:
  Widely distributed throughout body tissues and fluids, including cerebrospinal fluid, sputum, saliva, and vaginal secretions.
• Metabolism:
  Minimal hepatic metabolism.
• Elimination:
  Primarily excreted unchanged by the kidneys. Half-life approximately 30 hours, allowing once-daily dosing.

• Pregnancy:
  FDA Category D for high-dose or prolonged therapy due to risk of fetal abnormalities; Category C for single-dose use such as vaginal candidiasis. Use only if benefits outweigh risks.
• Lactation:
  Fluconazole is excreted in breast milk; caution advised. Use only if necessary.

• Primary class: Antifungal agent
• Subclass: Triazole antifungal

• Known hypersensitivity to fluconazole or other azole antifungals.
• Concurrent use with drugs contraindicated due to QT prolongation risk (unless benefits outweigh risks).
• Coadministration with terfenadine, cisapride, or other agents known to cause serious ventricular arrhythmias.

• Risk of hepatotoxicity; monitor liver function tests, especially with prolonged therapy.
• Potential QT interval prolongation; caution in patients with cardiac disease or electrolyte abnormalities.
• Rare but serious skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Monitor renal function in patients with impairment or on nephrotoxic drugs.
• Caution in immunocompromised patients due to risk of resistance.

Common Adverse Effects:

• Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea
• Headache
• Rash

Serious/Rare Side Effects:

• Hepatotoxicity (elevated liver enzymes, rare hepatic failure)
• QT prolongation and arrhythmias
• Severe hypersensitivity reactions
• Blood dyscrasias (rare)

• CYP450 interactions: Fluconazole inhibits CYP3A4 and CYP2C9, increasing plasma levels of drugs metabolized by these enzymes (e.g., warfarin, phenytoin, cyclosporine).
• Rifampin: Reduces fluconazole levels; dosage adjustment may be needed.
• Oral hypoglycemics: Increased risk of hypoglycemia with sulfonylureas.
• Digoxin: Possible increased digoxin levels; monitor accordingly.
• QT-prolonging drugs: Increased risk of arrhythmias when combined.

• Emphasis on avoiding high doses during pregnancy unless essential.
• Updated warnings regarding rare severe skin reactions.
• Recommendations for liver function monitoring during long-term therapy.
• Guidelines continue to support fluconazole as first-line therapy for many candidiasis forms and cryptococcal meningitis.

• Store at controlled room temperature between 20°C and 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original packaging until use.
• Oral suspension should be stored at room temperature and discarded after the recommended period.
• Keep out of reach of children.