Trade name Diflucan
Administered by oral, IV, or topical routes.
Has a bioavailability of greater than 90%.
Protein binding of 11–12%, and has hepatic metabolism of 11%, half-life of 30 hours and renal excretion 61-88%.
An antifungal medication used for a number of fungal infections: including candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor.
Active against Candida spp. (except Candida glabrata and krusei), Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum, Sporothrix schenckii, and ringworm.
It is first-choice treatment for certain Candida and cryptococcal infections as well as nonmeningeal coccidioidal infections.
Fluconazole as a single dose of 150 mg is effective for the treatment of vaginal candidiasis.
Oropharyngeal and esophageal candidiasis can be treated with 100 to 200 mg daily for 14 to 21 days, and loading dose of 200 to 400 mg can be given the first day.
As effective as amphotericin B for the treatment of candidemia in nonneutropenic patients.[104]
Used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts, or on corticosteroid.
Is given either by mouth or by intravenous injection.
Trade name Diflucan.
Pregnancy category C.
Routes of administration by mouth, IV, topical
Bioavailability >90% orally.
Protein binding 11–12%.
Metabolism by liver 11%.
Biological half-life 30 hours with range 20-50 hours.
Excretion by the kidney 61-88%.
Eighty percent is excreted unchanged in the urine
Fluconazole is water soluble and it is very well absorbed from the gastrointestinal tract.
Absorption is not affected by food or gastric pH.
Hepatic CYP2C9 enzyme plays a minor role in its metabolism
Diffuses readily in body fluids and cerebrospinal fluid (CSF).
Drug concentration is about 70% of serum in body fluids and CSF.
The dose should be halved for creatinine clearance below 50 mL/min, and 100% of the regular dose should be given after hemodialysis.
An initial double dose is recommended as a loading dose but is not always used.
Common side effects include vomiting, diarrhea, rash, and increased liver enzymes.
Serious side effects may include liver problems, QT prolongation, and seizures.
Generally well tolerated.
Serious adverse events, mainly liver toxicity, are rare.
Headache, nausea, vomiting, abdominal pain, and diarrhea are among the most common complaints.
With prolonged treatment, headache, alopecia, and anorexia are common as well as eosinophilia and aspartate aminotransferase (AST) elevation.
Alopecia is reversible and dose dependent, commonly seen in chronic treatment with doses above 400 mg daily.
A first-generation triazole antifungal medication.
It differs from earlier azole antifungals because its structure contains a triazole ring instead of an imidazole ring.
Triazole antifungals are pref2242ed when systemic treatment is required because of their improved safety and predictable absorption when administered orally.
Spectrum of activity includes most Candida species. Cryptococcus neoformans, some dimorphic fungi, and dermatophytes, among others.
It is not effective for Candida krusei or Candida glabrata.
Commonly used for non-systemic Candida infections of the vagina, throat, and mouth.
Systemic Candida infections, including infections of the bloodstream, kidney, or joints, while other antifungals are usually pref2242ed when the infection is in the heart or central nervous system, and for the treatment of active infections in people with weak immune systems.
The prevention of Candida infections in people with weak immune systems, such as those neutropenic due to cancer chemotherapy, those with advanced HIV infections, transplant patients, and premature infants, and chronic corticosteroid exposure.
As a second-line agent for the treatment of cryptococcal meningoencephalitis, a fungal infection of the central nervous system.
Fungal resistance occurs gradually over the course of prolonged drug therapy, resulting in clinical failure in immunocompromised patients.
Resistance mechanism employed by both C. albicans and C. glabrata is manifested by increasing rate of efflux of the azole drug from the cell, by both ATP-binding and superfamily transporters increasing resistance.
Resistance among Candida strains in the U.S. is about 7%.
Fluconazole is contraindicated in patients who:
have known hypersensitivity to other azole medicines, are taking terfenadine, concomitant administration with quinidine, and SSRIs such as fluoxetine or sertraline.
Adverse drug reactions associated with fluconazole therapy include:
Rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes.
Infrequent reactions 0.1–1% of patients: anorexia, fatigue, constipation.
Rare less than 0.1% of patients.: Oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions, prolonged QT interval, torsades de pointes.
Chronic, high doses of fluconazole during the first trimester of pregnancy may be associated with a rare and distinct set of birth defects in infants.
Use of fluconazole in lactating mothers is not recommended.
Associated with QT interval prolongation, which may lead to serious cardiac arrhythmias.
Rarely associated with severe or lethal hepatotoxicity.
Some azole drugs may disrupt estrogen production in pregnancy, affecting pregnancy outcome.
Women using flucanozol during pregnancy have a 50% higher risk of spontaneous abortion.
Fluconazole is an inhibitor of the human cytochrome P450 system, particularly the isozyme CYP2C19,CYP3A4 and CYP2C9 to lesser extent.
Decreases the metabolism and increases the concentration of any drug metabolized by these enzymes.
Its potential effect on QT interval increases the risk of cardiac arrhythmia if used concurrently with other drugs that prolong the QT interval.
May decrease the metabolism of benzodiazepines.
May increase the serum concentration of Citalopram.
May increase the serum concentration of Erythromycin.
Inhibits the fungal cytochrome P450 enzyme 14α-demethylase, preventing the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane, and subsequent accumulation of 14α-methyl sterols.
It is primarily fungistatic; however, it may be fungicidal against organisms in a dose-dependent manner, specifically Cryptococcus.
Following oral dosing, it is almost completely absorbed within two hours.
Following oral dosing concentrations measured in the urine, tears, and skin are approximately 10 times the plasma concentration.
The saliva, sputum, and vaginal fluid concentrations are approximately equal to the plasma concentration, following a standard dose range of between 100 mg and 400 mg per day.
Only 10% of drug elimination is due to metabolism, the remainder being excreted in urine and sweat.
Patients with impaired renal function are at risk of overdose.
A triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections.
Inhibits the fungal cytochrome P450 enzyme 14α-demethylase, preventing the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane.
Is primarily fungistatic, but it may be fungicidal against Cryptococcus.
Active antifungal agent against: Blastomyces dermatitidis, Candida spp. ,except C. krusei and C. glabrata, Coccidioides immitis, Cryptococcus neoformans, Epidermophyton spp.,Histoplasma capsulatum, Microsporum spp, and Trichophyton spp.
Prophylactically administered to critically ill surgical patients prevents invasive candidal infections.
Effective for preventing candida infections but does not affect aspergillus and other molds.
Oral fluconazole is not associated with significant increase risk of birth defects overall or of the 14 of the 15 specific birth defects of previous concern, but does confirm an increase risk tetralogy of Fallot (Malgaard D et al).
Use of fluconazole in pregnancy for vaginal candidiasis associated with an increased risk of spontaneous abortion and should be avoided. Almost completely absorbed within two hours of oral intake.
Concentrations measured in the urine, tears, and skin are approximately 10 times the plasma concentration.
Saliva, sputum, and vaginal fluid concentrations are approximately equal to the plasma concentration.
10% of drug elimination is due to metabolism, and the remainder being excreted in urine and sweat.
Patients with impaired renal function will be at risk of overdose.
Indicated for the treatment: of Candidiasis caused by susceptible strains of Candida, Tinea corporis, tinea cruris or tinea pedis, onychomycosis, Cryptococcal meningitis.
Used first-line for the following indications:
Coccidioidomycosis
Cryptococcosis
Histoplasmosis
Fluconazole is also used for the treatment of cryptococcal meningitis in HIV- and non-HIV-infected patients.
Prophylaxis of candidiasis in immunocompromised people
Has no intrinsic activity against mucormycosis, Aspergillus, and Fusarium species or against C krusei.
Dosage varies with indication, ranging from a two-week course of 150 mg/day for vulvovaginal candidiasis to 150–300 mg once weekly for resistant skin infections or some prophylactic indications.
A dosage of 500–600 mg/day may be used for systemic or severe infections, and, in urgent infections such as meningitis caused by yeast, 800 mg/day have been used.
Pediatric doses are 6–12 mg/kg/d.
A loading dose indicated when entering a daily dosage schedule.
Contraindications: in patients with known hypersensitivity to other azole medicine, Are taking terfenadine, concomitant administration of quinidine, especially when fluconazole is administered in high dosages, in pregnancy.
Fluconazole is secreted in human milk, so use of fluconazole in lactating mothers is not recommended.
Associated with QT interval prolongation, which may lead to serious cardiac arrhythmias.
Used with caution in patients with risk factors for prolonged QT interval, such as electrolyte imbalance or use of other drugs that may prolong the QT interval.
Rarely associated with severe or lethal hepatotoxicity, so liver function tests are usually performed regularly during prolonged fluconazole therapy.
Used with caution in patients with pre-existing liver disease.
At a dose of 150 mg is in FDA pregnancy category C.
High doses of 400 mg to 800 mg a day have been associated with a rare and distinct set of birth defects in infants, and at these doses, the pregnancy category is changed from category C to category D.
Adverse drug reactions include: rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes, anorexia, fatigue, constipation, oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including hepatic failure, anaphylactic/anaphylactoid reactions, prolonged QT interval, and torsades de pointes.
An inhibitor of the human cytochrome P450 system, particularly the isozyme CYP2C9 and CYP3A4 to lesser extent.
Fecreases the metabolism and increases the concentration of any drug metabolised by these enzymes.
Potential effect on QT interval increases the risk of cardiac arrhythmia if used concurrently with other drugs that prolong the QT interval.