Fluconazole is a synthetic, broad-spectrum, first-generation triazole antifungal agent. It is a potent inhibitor of fungal cytochrome P450-dependent enzyme lanosterol 14α-demethylase, leading to depletion of ergosterol, an essential component of fungal cell membranes, and accumulation of toxic methylated sterols. The 50mg strength is commonly used for maintenance therapy, minor localized infections, and specific prophylactic regimens in the Indian context. It is well-absorbed orally with excellent bioavailability, allowing for oral therapy in many systemic infections.
Adult: Varies by indication. For oropharyngeal candidiasis: 200mg on day 1, then 100mg once daily. For maintenance therapy (e.g., cryptococcal meningitis): 200mg once daily. The 50mg tablet is often used for long-term maintenance (e.g., 50mg daily) or in adjusted regimens. For vaginal candidiasis prophylaxis: 50-100mg daily.
Note: Can be taken with or without food. Tablet should be swallowed whole with a glass of water. For patients on hemodialysis, administer one dose after each dialysis session. Timing is not critical due to long half-life, but taking it at the same time each day is advisable.
Fluconazole exerts its antifungal effect by selectively inhibiting the fungal cytochrome P450 enzyme lanosterol 14α-demethylase. This enzyme is crucial for the conversion of lanosterol to ergosterol, the principal sterol component of the fungal cell membrane. Inhibition leads to depletion of ergosterol and accumulation of 14α-methyl sterols (e.g., lanosterol), which disrupts the structure and function of the membrane. This results in increased membrane permeability, inhibition of fungal cell growth and replication, and ultimately a fungistatic effect.
Pregnancy: Pregnancy Category D (Australian categorization; US FDA Category D). Evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. Use only if the potential benefit justifies the potential risk to the fetus. High-dose, long-term therapy is associated with multiple congenital abnormalities in humans. Avoid in first trimester.
Driving: May cause dizziness or seizures in rare cases. Patients should be cautioned about operating machinery or driving until they are sure the medication does not affect them adversely.
| Warfarin | Fluconazole inhibits metabolism, increasing anticoagulant effect and risk of bleeding. | Major |
| Sulfonylureas (e.g., Glipizide, Glimepiride) | Increased hypoglycemic effect. | Major |
| Phenytoin | Fluconazole increases phenytoin levels; phenytoin may decrease fluconazole levels. Mutual dose adjustment needed. | Major |
| Rifampicin | Decreases fluconazole levels by ~25% via enzyme induction. | Moderate |
| Cyclosporine, Tacrolimus | Fluconazole increases levels of these immunosuppressants, increasing risk of nephrotoxicity and neurotoxicity. | Major |
| Theophylline | Fluconazole may increase theophylline levels. | Moderate |
| Zidovudine (AZT) | Fluconazole may increase AZT levels, potentially increasing toxicity. | Moderate |
| Hydrochlorothiazide | Increases fluconazole levels by reducing renal clearance. | Moderate |
| Statins (Metabolized by CYP3A4, e.g., Atorvastatin) | Increased risk of myopathy/rhabdomyolysis. | Major |
| Midazolam, Triazolam | Increased and prolonged sedative effect. | Major |