Fluconazole

# Fluconazole ## Overview - **Classification**: Antifungal (Triazole) - **Mechanism**: Inhibits fungal cytochrome P450-dependent 14-alpha-demethylase, impairing ergosterol synthesis in fungal cell membranes. ## Primary Indications 1. **Oropharyngeal Candidiasis (OPC)**: Thrush, particularly in immunocompromised patients. 2. **Esophageal Candidiasis (EC)**: Fungal infection of the esophagus. 3. **Vaginal Candidiasis (VC)**: Acute yeast infection. 4. **Cryptococcal Meningitis**: Treatment and secondary prophylaxis. 5. **Candidemia/Invasive Candidiasis**: Systemic fungal infections. ## Adult Dosing ### Standard Dosing **Vaginal Candidiasis (Acute)** - **Dose**: **150 mg** - **Frequency**: Single dose - **Route**: Oral (PO) **Oropharyngeal Candidiasis** - **Dose**: **200 mg** on Day 1, then **100-200 mg** - **Frequency**: Once daily (QD) - **Route**: PO or Intravenous (IV) - **Duration**: 7-14 days **Esophageal Candidiasis** - **Dose**: **200 mg** on Day 1, then **100-400 mg** - **Frequency**: QD - **Route**: PO or IV - **Duration**: 14-21 days after symptoms resolve **Candidemia/Invasive Candidiasis** - **Dose**: **800 mg** on Day 1, then **400 mg** - **Frequency**: QD - **Route**: PO or IV - **Duration**: At least 2 weeks after last positive culture **Cryptococcal Meningitis (Suppression/Secondary Prophylaxis)** - **Dose**: **200 mg** - **Frequency**: QD - **Route**: PO or IV - **Duration**: Long-term, often lifelong for HIV pts. ### Dose Adjustments - **Renal Impairment**: Fluconazole is primarily renally eliminated. - **CrCl >50 mL/min**: No adjustment needed. - **CrCl 21-50 mL/min**: Administer 50% of the usual dose. - **CrCl 10-20 mL/min**: Administer 25% of the usual dose. - **Hemodialysis**: Give 100% of dose after each dialysis session. - **Hepatic Impairment**: No specific dose adjustment guidelines. Use with caution. - **Elderly Patients**: Adjust dose based on renal function. No age-specific adjustment if renal function is normal. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: **6-12 mg/kg** - **Frequency**: Every **72 hours** (0-14 days corrected gestational age) - **Frequency**: Every **48 hours** (15-28 days corrected gestational age) - **Special Notes**: Consider delayed renal clearance in preterm infants. ### Infants (1-12 months) - **Dose**: **6-12 mg/kg** - **Frequency**: QD - **Maximum**: **600 mg/day** for severe infections. ### Children (1-12 years) - **Dose**: **3-12 mg/kg** QD (depending on indication). - **Oropharyngeal/Esophageal**: **6 mg/kg** Day 1, then **3 mg/kg** QD. - **Systemic candidiasis**: **6-12 mg/kg** QD. - **Frequency**: QD - **Maximum**: Up to **600 mg/day**, but generally not to exceed adult dose for typical indications (e.g., 400 mg/day). ### Adolescents (13-18 years) - **Dose**: Use **adult dosing** guidelines. - **Maximum**: Up to **800 mg/day** for severe infections. ## Safety Information ### Contraindications - **Absolute**: Concomitant use with QT-prolonging drugs metabolized by CYP3A4 (e.g., terfenadine, astemizole, cisapride, pimozide). - **Absolute**: Hypersensitivity to fluconazole or other azole antifungals. ### Common Adverse Effects - **Very Common (>10%)**: Headache, Nausea, Abdominal pain. - **Common (1-10%)**: Diarrhea, Vomiting, Rash, Dyspepsia, Elevated LFTs. - **Serious but Rare**: Hepatotoxicity (severe, idiosyncratic), QTc prolongation, Torsades de Pointes, Steven-Johnson Syndrome, Anaphylaxis. ### Key Drug Interactions - **CYP2C9/2C19/3A4 Substrates**: Fluconazole is a potent inhibitor. - **Warfarin**: Increased INR, bleeding risk. Monitor INR closely. - **Statins (e.g., Simvastatin)**: Increased myopathy/rhabdomyolysis risk. Consider lower statin dose or alternative. - **Amiodarone**: Increased QTc prolongation risk. Avoid concomitant use if possible. - **Rifampin**: Decreased fluconazole levels. Consider higher fluconazole dose. - **Phenytoin**: Increased phenytoin levels. Monitor levels. - **Sulfonylureas**: Increased hypoglycemia risk. Monitor blood glucose. ## Monitoring & Follow-up - **Before Treatment**: Baseline LFTs (ALT, AST, ALP), renal function (SCr, CrCl), electrolytes. - **During Treatment**: - **LFTs**: Periodically, especially with prolonged use or baseline abnormalities. Discontinue if signs of liver disease. - **Renal function**: Monitor as needed for dose adjustments. - **Electrolytes**: Potassium, Magnesium (if QTc risk). - **INR**: If on warfarin. - **Clinical Signs**: Resolution of infection, adverse effects (rash, GI upset, jaundice). ## Clinical Pearls - 💡 **Bioavailability**: Fluconazole has excellent oral bioavailability (~90%), allowing for interchangeable PO and IV dosing. - 💡 **Penetration**: Good penetration into cerebrospinal fluid (CSF), making it effective for cryptococcal meningitis. - 💡 **Single Dose**: The **150 mg single oral dose** for vaginal candidiasis offers great patient convenience and adherence. - 💡 **Pediatric Suspension**: Oral suspension formulation is available, facilitating administration in younger patients. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.