Fluconazole is a first-generation synthetic triazole antifungal agent. It is a broad-spectrum fungistatic agent that inhibits fungal cytochrome P450 14α-demethylase, disrupting ergosterol synthesis in fungal cell membranes. It is highly effective against Candida species, Cryptococcus neoformans, and some dimorphic fungi. Its excellent oral bioavailability, long half-life, and good tissue penetration make it a cornerstone of systemic antifungal therapy in India, widely used for both mucosal and systemic mycoses.
Adult: Varies by indication. Esophageal Candidiasis: 200mg on first day, then 100-200mg once daily for 2-3 weeks. Systemic Candidiasis: 400mg on first day, then 200-400mg once daily. Cryptococcal Meningitis: 400mg on first day, then 200-400mg once daily for 10-12 weeks for induction. Maintenance: 200mg once daily. Vaginal Candidiasis: Single 150mg dose is standard; 200mg may be used in complicated/recurrent cases.
Note: Can be taken with or without food. Tablet should be swallowed whole with a glass of water. For once-daily dosing, take at approximately the same time each day. Complete the full course of therapy even if symptoms improve earlier.
Fluconazole is a potent and selective inhibitor of fungal cytochrome P450-dependent enzyme lanosterol 14-α-demethylase. This enzyme is crucial for converting lanosterol to ergosterol, the principal sterol component of the fungal cell membrane. Inhibition leads to accumulation of 14-α-methyl sterols and depletion of ergosterol, disrupting membrane structure and function. This results in increased membrane permeability, inhibition of fungal cell growth, and ultimately fungistatic activity.
Pregnancy: Pregnancy Category D (as per some older classifications) / Use during pregnancy only if potential benefit justifies potential fetal risk. Data from human pregnancy registries do not show a clear increase in major birth defects with standard doses, but high-dose, long-term therapy may be associated with congenital abnormalities (multiple skeletal/ craniofacial defects). Avoid in first trimester unless essential.
Driving: May cause dizziness or seizures. Patients should be cautioned about driving or operating machinery until they are sure the medication does not affect them adversely.
| Warfarin | Increases anticoagulant effect (increases INR); risk of bleeding. | Major |
| Sulfonylureas (e.g., Glimepiride, Glipizide) | Increases hypoglycemic effect; risk of severe hypoglycemia. | Major |
| Phenytoin | Increases phenytoin levels; risk of phenytoin toxicity. Fluconazole levels may decrease. | Major |
| Rifampicin | Decreases fluconazole levels significantly by inducing metabolism. | Major |
| Cyclosporine, Tacrolimus, Sirolimus | Increases calcineurin inhibitor levels; risk of nephrotoxicity and neurotoxicity. | Major |
| Statins (Metabolized by CYP3A4: Atorvastatin, Simvastatin) | Increases statin levels; increased risk of myopathy/rhabdomyolysis. | Major |
| Midazolam, Triazolam | Increases benzodiazepine levels and sedation. | Moderate |
| Hydrochlorothiazide | Increases fluconazole levels by reducing renal clearance. | Moderate |
| Oral Contraceptives | Potential for decreased efficacy; advise alternative/backup contraception. | Moderate |
| Amitriptyline, Nortriptyline | Increases tricyclic antidepressant levels. | Moderate |
| Theophylline | Increases theophylline levels; risk of toxicity. | Moderate |
| Zidovudine (AZT) | Increases AZT levels; may increase hematological toxicity. | Moderate |
| Isoniazid | Potential increased risk of hepatotoxicity. | Moderate |