1. Clinical Overview
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.
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical improvement is typically observed within 24-72 hours for symptomatic relief in conditions like oropharyngeal candidiasis. Peak plasma concentrations are achieved 1-2 hours after oral administration. | The prolonged half-life (approximately 30 hours) allows for once-daily dosing. The fungistatic effect persists for the dosing interval, with tissue concentrations often exceeding plasma levels for extended periods. | >90% following oral administration, unaffected by food or gastric pH. |
2. Mechanism of Action
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.
3. Indications & Uses
- Oropharyngeal and esophageal candidiasis (thrush)
- Vaginal candidiasis (single-dose therapy typically uses 150mg, but 50mg may be used in specific regimens)
- Cryptococcal meningitis (maintenance therapy to prevent relapse in HIV patients)
- Prevention of candidiasis in immunocompromised patients (e.g., post-chemotherapy, transplant recipients)
4. Dosage & Administration
Adult Dosage: 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.
Administration: 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.
5. Side Effects
Common side effects may include:
- Headache
- Nausea
- Abdominal pain/discomfort
- Diarrhea
- Skin rash
- Dyspepsia
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| 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 |
7. Patient Counselling
- DO complete the full course of therapy even if you feel better.
- DO take the medication at the same time each day for consistency.
- DO inform your doctor about all other medications, including OTC drugs, vitamins, and herbal supplements.
- DO get regular blood tests (like liver function tests) if advised by your doctor, especially for long-term therapy.
- DONT stop the medication abruptly without consulting your doctor.
- DONT take a double dose to make up for a missed one. Take it as soon as you remember, or skip it if it's almost time for the next dose.
- DONT share your medication with others.
8. Toxicology & Storage
Overdose: In reported cases of overdose (up to 8.4g), symptoms included hallucinations, paranoid behavior, and confusion. Nausea, vomiting, and diarrhea are also possible. Due to the long half-life, effects may be prolonged.
Storage: Store below 30°C, protected from light and moisture. Keep out of reach of children. Do not use after the expiry date printed on the pack.