Fluconazole is a triazole antifungal medication primarily prescribed to treat infections caused by fungi, most commonly the Candida species. The drug works by inhibiting a fungal enzyme necessary for producing ergosterol, a component of the fungal cell membrane. Fluconazole is widely used for both systemic and superficial mycoses because it is highly effective and has a long half-life, permitting once-daily dosing. Determining the appropriate dose depends entirely on the specific fungal species, the infection’s location, and the unique characteristics of the patient.
Common Infections and Standard Dosing Regimens
Fluconazole dosing is customized to the type of infection, ranging from a single, low dose for localized conditions to prolonged, high-dose regimens for deep-seated systemic disease. For uncomplicated vaginal candidiasis, the standard approach is a single oral dose of 150 milligrams (mg). This single-dose treatment is effective because fluconazole achieves high concentrations in the vaginal tissue and has a long duration of action.
For infections of the mouth and throat, known as oropharyngeal or esophageal candidiasis (thrush), dosing requires a multiple-day course. A typical regimen begins with a loading dose of 200 mg on the first day, followed by a maintenance dose of 100 mg once daily. Treatment for oropharyngeal thrush usually continues for at least two weeks, while esophageal infections require a minimum of three weeks to prevent symptom recurrence.
In contrast, severe systemic infections, such as candidemia (a bloodstream infection) or cryptococcal meningitis, require substantially higher doses and much longer treatment durations. For these invasive conditions, initial doses often reach 400 mg on the first day, followed by 200 mg to 400 mg daily. Some systemic infections may even require up to 800 mg per day, with treatment courses extending for several months to fully suppress the pathogen and prevent relapse.
Patient-Specific Factors Influencing Dosage
Beyond the type of infection, the patient’s individual physiology dictates significant modifications to the standard fluconazole dose. The drug is primarily eliminated from the body unchanged through the kidneys, meaning renal function is a defining factor in clearance. When kidney function is impaired, the drug accumulates in the body, which can increase the risk of toxicity.
For patients with a creatinine clearance (CrCl) of 50 milliliters per minute or less, the daily maintenance dose must be reduced by 50%. If a patient is undergoing regular hemodialysis, the entire recommended dose is typically administered immediately after each session, as the procedure removes approximately half of the drug from the plasma. However, the initial loading dose is usually not adjusted, regardless of renal impairment, to quickly saturate the body’s tissues.
Age and body weight are important considerations, particularly when treating pediatric patients. Dosing for children is often calculated based on weight, expressed as milligrams per kilogram (mg/kg) of body weight, rather than a fixed adult dose. For instance, a child with esophageal candidiasis may receive a loading dose of 6 mg/kg on the first day, followed by a maintenance dose of 3 mg/kg daily. A deep-seated infection, such as cryptococcal meningitis, requires a higher pediatric dose of up to 12 mg/kg daily.
Administration Schedules and Timing
The schedule for taking fluconazole is structured to maintain a steady and effective concentration of the drug in the body over time. A common strategy involves using a loading dose, which is often double the subsequent daily maintenance dose, to help the drug reach a therapeutic level in the bloodstream faster.
The maintenance dose is calculated to replace the amount of drug naturally cleared by the kidneys each day. Fluconazole can be taken orally as a tablet, capsule, or liquid suspension, with or without food, as its absorption is unaffected by gastric contents. Patients are advised to take their dose at the same time each day to ensure a predictable drug level. Completing the full course of treatment, even if symptoms improve quickly, is necessary to prevent the infection from returning and minimize the development of drug-resistant fungi.
Medication Interactions Requiring Dose Adjustment
Fluconazole is known to interact with numerous other medications, necessitating careful dose adjustments or substitution of one of the drugs. These interactions occur because fluconazole acts as an inhibitor of specific liver enzymes within the Cytochrome P450 (CYP) system. Specifically, it is a strong inhibitor of the CYP2C9 and CYP2C19 enzymes, and a moderate inhibitor of CYP3A4.
By inhibiting these enzymes, fluconazole slows the metabolism and clearance of other drugs, causing their concentration in the bloodstream to increase. For example, fluconazole can intensify the effect of the blood thinner Warfarin by interfering with its metabolism via CYP2C9, increasing the patient’s risk of bleeding and requiring close monitoring. Similarly, co-administration with certain statin medications, such as lovastatin or simvastatin, can lead to elevated statin levels, increasing the risk of serious muscle damage like rhabdomyolysis. Patients must inform a healthcare provider of all current medications before beginning fluconazole therapy.