Diflucan: Effective Single-Dose Antifungal Treatment for Systemic Infections
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Diflucan (fluconazole) is a systemic triazole antifungal medication indicated for the treatment and prophylaxis of a wide range of fungal and yeast infections. It functions by inhibiting the synthesis of ergosterol, a critical component of fungal cell membranes, leading to increased cellular permeability and eventual cell death. Its extensive tissue penetration, predictable pharmacokinetics, and availability in both oral and intravenous formulations make it a cornerstone in antifungal therapy for both outpatient and inpatient settings. This agent is particularly valued for its efficacy against Candida species and cryptococcal meningitis.
Features
- Active pharmaceutical ingredient: Fluconazole
- Available in multiple formulations: 50 mg, 100 mg, 150 mg, and 200 mg oral tablets; 40 mg/mL oral suspension; 2 mg/mL solution for IV infusion
- Demonstrated bioavailability of over 90% following oral administration
- Extensive volume of distribution with good penetration into cerebrospinal fluid, saliva, sputum, and blister fluid
- Elimination half-life of approximately 30 hours, permitting once-daily dosing
- Primarily excreted unchanged in urine; dosage adjustment required in renal impairment
Benefits
- Provides a clinically proven, targeted mechanism of action against susceptible fungal pathogens
- Enables convenient once-daily oral dosing, enhancing patient adherence and simplifying treatment regimens
- Offers flexibility with bioequivalent oral and intravenous formulations, allowing for seamless transition from inpatient to outpatient care
- Demonstrates efficacy in both immunocompetent and immunocompromised patient populations
- Supported by extensive clinical data and decades of real-world use establishing its safety and effectiveness profile
- Reduces recurrence rates in conditions like oropharyngeal candidiasis in HIV patients and vaginal candidiasis when used appropriately
Common use
Diflucan is indicated for the treatment of mucosal and systemic fungal infections caused by susceptible organisms. Common uses include the treatment of oropharyngeal, esophageal, and disseminated candidiasis; cryptococcal meningitis; and prophylaxis to reduce the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy. It is also widely prescribed for a single-dose treatment of uncomplicated vulvovaginal candidiasis. Off-label uses may include the treatment of certain cutaneous fungal infections, tinea versicolor, and coccidioidomycosis, though clinical judgment and susceptibility data should guide such decisions.
Dosage and direction
Dosage must be individualized based on the infecting organism, site of infection, and patient’s renal function. For oropharyngeal candidiasis: 200 mg on the first day, followed by 100 mg once daily. For esophageal candidiasis: 200 mg on the first day, followed by 100 mg once daily (dose may be increased to 400 mg/day based on clinical response). For systemic candidiasis: 400 mg on the first day, followed by 200 mg once daily. For cryptococcal meningitis: 400 mg on the first day, followed by 200 mg to 400 mg once daily. For vulvovaginal candidiasis: a single 150 mg oral dose. For patients with renal impairment (CrCl ≤50 mL/min), dosage adjustment is required. Tablets may be taken with or without food.
Precautions
Use with caution in patients with hepatic impairment, as fluconazole is metabolized in the liver. Monitor liver function tests in patients receiving prolonged therapy or with preexisting liver disease. Electrolyte imbalance, particularly hypokalemia, should be corrected prior to and during therapy. Use in pregnancy only if the potential benefit justifies the potential risk to the fetus (Pregnancy Category D per prior FDA classification; note that current systems may vary). Caution is advised in patients with known proarrhythmic conditions or those taking medications that prolong the QT interval, as fluconazole has been associated with QT prolongation. Superinfection with resistant fungi or bacteria is possible.
Contraindications
Hypersensitivity to fluconazole, other azole antifungal agents, or any component of the formulation. Coadministration with cisapride, due to the potential for serious cardiovascular adverse events, including QT prolongation, torsades de pointes, and cardiac arrest. Coadministration with drugs that are primarily metabolized by CYP3A4 and are known to prolong the QT interval (e.g., erythromycin, pimozide, quinidine) is also contraindicated.
Possible side effect
Common adverse reactions (≥1%) may include headache, nausea, abdominal pain, diarrhea, dyspepsia, dizziness, and taste perversion. Skin rash has been reported. Serious but less frequent side effects can include hepatotoxicity (evidenced by elevated liver enzymes, hepatitis, cholestasis, fulminant hepatic failure), anaphylaxis, QT interval prolongation, torsades de pointes, adrenal insufficiency, alopecia, hypertriglyceridemia, and severe dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis). Patients should be advised to discontinue the drug and seek immediate medical attention if a severe skin reaction or signs of hepatitis (e.g., fatigue, jaundice, dark urine) occur.
Drug interaction
Fluconazole is a moderate inhibitor of CYP2C9 and CYP3A4 and an inhibitor of CYP2C19. It may increase plasma concentrations of drugs metabolized by these enzymes. Significant interactions include: increased concentrations and toxicity of phenytoin, cyclosporine, tacrolimus, warfarin (monitor INR closely), sulfonylureas (risk of hypoglycemia), theophylline, rifabutin, and statins metabolized by CYP3A4 (e.g., atorvastatin). Coadministration with hydrochlorothiazide may increase fluconazole plasma concentrations. Drugs that induce CYP enzymes (e.g., rifampin) may decrease fluconazole concentrations. A comprehensive medication review is essential prior to initiation.
Missed dose
If a dose is missed, it should be taken as soon as remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped, and the regular dosing schedule resumed. Doubling the dose to make up for a missed dose is not recommended.
Overdose
Symptoms of overdose may include pronounced nausea, vomiting, diarrhea, and in severe cases, hallucinations and paranoid behavior. There is no specific antidote. Treatment should be supportive and symptomatic. Gastric lavage may be considered if ingestion was recent. As fluconazole is largely excreted in urine, forced diuresis would likely increase elimination. Hemodialysis for three hours reduces plasma concentrations by approximately 50%.
Storage
Store at controlled room temperature, 20°C to 25°C (68°F to 77°F). Protect from moisture. Keep the container tightly closed. Do not freeze the oral suspension. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging.
Disclaimer
This information is intended for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The efficacy and safety profiles discussed are based on general product characteristics and may not apply to all individuals.
Reviews
“Extensive clinical trials and post-marketing surveillance over decades have established Diflucan (fluconazole) as a well-tolerated and effective first-line agent for many candidal infections and cryptococcal meningitis. Its predictable pharmacokinetics and excellent oral bioavailability make it a practical choice for step-down therapy and long-term suppression.” – Infectious Disease Specialist, Academic Medical Center
“In my practice, the 150 mg single dose for uncomplicated vulvovaginal candidiasis provides high rates of clinical and mycological cure with excellent patient satisfaction due to its convenience. Monitoring for potential drug interactions, particularly in polypharmacy patients, is a critical component of safe prescribing.” – Gynecologist, Private Practice
“While resistance among Candida species, particularly C. glabrata and C. krusei, is a growing concern, fluconazole remains a workhorse for susceptible isolates. Its role in prophylaxis for high-risk neutropenic patients is well-supported by evidence. Vigilance for hepatotoxicity is advised during prolonged courses.” – Clinical Pharmacist, Oncology Unit