1. Clinical Overview
Fluconazole is a synthetic, broad-spectrum triazole antifungal agent. It is a first-line oral treatment for uncomplicated vulvovaginal candidiasis (VVC) and is widely used for various systemic and superficial fungal infections. It functions by selectively inhibiting fungal cytochrome P450-dependent enzyme lanosterol 14-α-demethylase, disrupting ergosterol synthesis in the fungal cell membrane. In the Indian context, its single 150mg oral dose is a cornerstone for treating vaginal yeast infections due to its high efficacy, convenience, and over-the-counter (Schedule H1) availability.
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical improvement in symptoms like itching and discharge is typically observed within 24-72 hours after a single 150mg dose for VVC. Peak plasma concentrations are reached in 1-2 hours. | Plasma concentrations remain above the MIC90 for most Candida species for approximately 72 hours. For VVC, a single dose maintains therapeutic levels in vaginal tissue for up to 3-5 days, correlating with the treatment duration. | >90% (Excellent oral bioavailability, unaffected by food or gastric pH). |
2. Mechanism of Action
Fluconazole exerts its antifungal effect by inhibiting the fungal cytochrome P450 enzyme lanosterol 14-α-demethylase. This enzyme is crucial for converting lanosterol to ergosterol, the primary sterol component of the fungal cell membrane. Inhibition leads to depletion of ergosterol and accumulation of toxic methylated sterol precursors (e.g., 14α-methylsterols).
3. Indications & Uses
- Uncomplicated Vulvovaginal Candidiasis (VVC)
- Oropharyngeal and Esophageal Candidiasis
- Systemic Candidiasis (including candidemia, disseminated candidiasis)
- Cryptococcal Meningitis (acute treatment and maintenance therapy to prevent relapse in AIDS patients)
4. Dosage & Administration
Adult Dosage: VVC: Single 150mg oral dose. Oropharyngeal Candidiasis: 200mg on day 1, then 100mg once daily for 14 days. Esophageal Candidiasis: 200mg on day 1, then 100-200mg once daily for 14-21 days. Systemic Candidiasis: 400mg on day 1, then 200-400mg once daily. Cryptococcal Meningitis: 400mg on day 1, then 200-400mg once daily.
Administration: Can be taken with or without food. Tablet should be swallowed whole with a glass of water. For VVC, a single dose is sufficient; treatment of sexual partner is not routinely recommended unless symptomatic.
5. Side Effects
Common side effects may include:
- Headache
- Nausea
- Abdominal pain/discomfort
- Diarrhea
- Skin rash
- Dyspepsia
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Warfarin | Increased prothrombin time (PT/INR); risk of bleeding. | Major |
| Sulfonylureas (e.g., Glipizide, Glimepiride) | Increased hypoglycemic effect. | Major |
| Phenytoin | Increased phenytoin levels; risk of toxicity. | Major |
| Cyclosporine, Tacrolimus | Increased immunosuppressant levels; risk of nephrotoxicity/neurotoxicity. | Major |
| Rifampicin | Decreased fluconazole levels; reduced efficacy. | Major |
| Hydrochlorothiazide | Increased fluconazole levels due to reduced renal clearance. | Moderate |
| Oral Contraceptives | Potential for decreased efficacy; advise alternative/backup contraception. | Moderate |
| Statins (Metabolized by CYP3A4 e.g., Atorvastatin) | Increased statin levels; risk of myopathy/rhabdomyolysis. | Major |
| Midazolam, Triazolam | Increased sedative effect and prolonged sedation. | Major |
| Theophylline | Increased theophylline levels; risk of toxicity. | Moderate |
7. Patient Counselling
- DO take the tablet as a single dose for vaginal yeast infection, even if symptoms improve quickly.
- DO inform your doctor about all other medicines you are taking, including OTC, herbal (e.g., St. John's Wort), and supplements.
- DO use a backup non-hormonal method of contraception (like condoms) if you are on oral contraceptive pills, during and for one cycle after treatment.
- DONT take the medicine if you are allergic to other antifungal azoles (e.g., ketoconazole, itraconazole).
- DONT share your medication with others, even if they have similar symptoms.
8. Toxicology & Storage
Overdose: In reported cases of overdose (up to 8.2g), symptoms included hallucinations, paranoid behavior, and confusion. Nausea, vomiting, and diarrhea are also expected.
Storage: Store below 30°C, in a cool, dry place. Protect from light and moisture. Keep out of reach of children. Do not use after the expiry date printed on the pack.