Diflucan (fluconazole) Oral Tablets and Suspension for Fungal Infections

Diflucan is an antifungal medication available as oral tablets and powder for oral suspension. It treats fungal infections caused by susceptible fungi by inhibiting an enzyme essential for fungal cell membrane synthesis. It offers high oral bioavailability and penetrates well into various body fluids and tissues.

Diflucan is used to treat infections caused by fungi, including those caused by Candida albicans, Candida glabrata (some isolates), Candida parapsilosis, Candida tropicalis, and Cryptococcus neoformans. Its clinical indications cover a broad range of fungal infections where fluconazole susceptibility is demonstrated. The medicine is intended for oral administration.

fluconazole

Fluconazole, the active ingredient in Diflucan, selectively inhibits fungal cytochrome P450 enzyme lanosterol 14-α-demethylase. This enzyme converts lanosterol to ergosterol, a critical component of the fungal cell membrane. By blocking this step, fluconazole disrupts membrane synthesis, causing accumulation of abnormal sterols and halting fungal growth. The drug is much less active against mammalian cells, reducing toxicity.

Resistance may develop via mutations altering the target enzyme, increased enzyme production, or increased efflux of fluconazole from fungal cells. Some fungal species may show reduced susceptibility to fluconazole.

Coadministration with quinidine is contraindicated due to the risk of QT interval prolongation and rare occurrences of torsade de pointes.

Important: Dose adjustments may be necessary in patients with impaired renal function as fluconazole is primarily excreted unchanged in urine. Use with caution in the elderly, considering reduced renal clearance common in this group.

Fluconazole has the potential for drug interactions that can alter the levels of other medicines, including oral anticoagulants, phenytoin, cyclosporine, zidovudine, theophylline, sulfonylurea oral hypoglycemics, rifampin, warfarin, midazolam, and others. Some interactions may increase side effects or alter therapeutic response (see Precautions).

Coadministration with quinidine is contraindicated due to risk of QT prolongation and torsade de pointes.

Fluconazole can interact with multiple drugs by inhibiting cytochrome P450 enzymes, leading to increased plasma concentrations of coadministered drugs such as:

• Oral anticoagulants (e.g., warfarin): Increased prothrombin time, requiring monitoring.
• Phenytoin: Increased drug levels and toxicity risk.
• Cyclosporine: Increased blood levels.
• Zidovudine: Increased exposure.
• Theophylline: Increased half-life and plasma concentration.
• Sulfonylurea hypoglycemics (e.g., tolbutamide, glipizide, glyburide): Increased plasma levels and risk of hypoglycemia.
• Rifampin: Decreased fluconazole exposure due to increased clearance.
• Midazolam: Increased AUC and pharmacodynamic effects; oral midazolam effects are more pronounced.
• Voriconazole: Increased plasma levels when coadministered.
• Tofacitinib: Increased exposure.
• Abrocitinib: Significantly increased systemic exposure.

Contraindicated interaction: Co-administration with quinidine is contraindicated due to risk of serious heart rhythm disturbances.