Fluconazole

Fluconazole interacts with hundreds of drugs and can often increase the levels of many drugs in the blood, which may cause dangerous interactions.

It's always important to share with your doctor and pharmacist all of the medications you are taking.

This includes not only prescriptions medications but also products that may not seem like medication, such as over-the-counter (OTC) medications, supplements like vitamins and other dietary supplements (nutritional shakes, protein powders, etc.), and herbals along with any illegal and recreational drugs.

You should not take fluconazole if you are taking the following drugs:

• Hismanal (astemizole)
• Norpace (disopyramide)
• Erythromycin-containing drugs, including drugs containing erythromycin base, erythyromycin ethylsuccinate, erythromycin lactobionate, or eryrthromyvin stearate
• Medications for irregular heartbeat like Covert (ibutilide), Norpace (disopyramide), Promestyl, Procan, or Procanbid (procainamide)
• Lozol (indapamide)
• Juxtapid (lomitapide)
• Nebupent (pentamidine)
• Orap (pimozide)
• Quinidine

You should talk to your doctor about drug options other than fluconazole if you're taking any of the following:

• Drugs for irregular heartbeat like Pacerone, Cordarone, or Nexterone (amiodarone), Betapace or Betapace AF (sotalol), Tikosyn (dofetilde), or Multaq (dronedarone)
• Medications for mood and/or depression like Pamelor (nortriptyline), Prozac (fluoxetine), Buspar (buspirone), Celexa (citalopram), and Abilify (aripiprazole)
• Statins for cholesterol like Lipitor (atorvastatin), Zocor (simvastatin), and Mevacor (lovastatin)
• Estrogen-containing drugs like birth control and hormone replacement therapy
• Foradil or Perforomist (formoterol)
• Epinephrine
• Coreg (carvedilol)
• Migergot or Cafergot (ergotamine) and Migranal (dihydroergotamine)
• Antibiotics like Biaxin (clarithromycin), Avelox (moxifloxacin), and Zithromax (azithromycin)
• Certain cancer drugs like Doxil or Adriamycin (doxorubicin), Cometriq (cabozantinib), Inlyta (axitinib), Bosulif (bosutinib), and Votrient (pazopanib)
• Psychiatric medications like Haldol (haloperidol) and Geodon (ziprasidone)
• Coumadin (warfarin)

Fluconazole and Alcohol

You should avoid or limit drinking alcohol while taking fluconazole.

Since both can cause headaches and stomach discomfort, drinking alcohol while taking fluconazole may worsen these side effects.

Fluconazole and Grapefruit Juice

The liver breaks down fluconazole and grapefruit juice the same way.

Grapefruit juice slows down how quickly the body is able to break down the fluconazole, which could cause fluconazole levels in the blood to rise dangerously high.

You should therefore avoid eating grapefruit and drinking grapefruit juice while taking fluconazole.

To avoid a possible serious reaction, do NOT take fluconazole if you are taking erythromycin, astemizole, pimozide, quinidine, and cisapride (Propulsid) since it can cause changes in heartbeat in some people if taken with fluconazole. See "Fluconazole Interactions".

Allergic reactions to fluconazole are rare, but they can be very serious if not treated right away by a doctor. If you cannot reach your doctor, go to the nearest hospital emergency room. Signs of an allergic reaction can include shortness of breath; coughing; wheezing; fever; chills; throbbing of the heart or ears; swelling of the eyelids, face, mouth, neck, or any other part of the body; or skin rash, hives, blisters or skin peeling.

Fluconazole has been linked to rare cases of serious liver damage, including deaths, mostly in patients with serious medical problems. Call your doctor if your skin or eyes become yellow, your urine turns a darker color, your stools (bowel movements) are light-colored, or if you vomit or feel like vomiting or if you have severe skin itching.

In patients with serious conditions such as AIDS or cancer, rare cases of severe rashes with skin peeling have been reported. Tell your doctor right away if you get a rash while taking fluconazole.

Fluconazole can cause dizziness. Do not drive or operate machinery until you know how fluconazole will affect you.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of fluconazole, there are no specific foods that you must exclude from your diet.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C if you are using a single 150 mg tablet for vaginal candidiasis infection. There are no well-done studies of fluconazole in pregnant women. Available human data do not suggest an increased risk of abnormalities single dose of 150 mg.

This medication falls into category D for all other types of infections. It has been shown that use of fluconazole in pregnant women caused some babies to be born with problems. However, in some serious situations, the benefit of using this medication may be greater than the risk of harm to the baby.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Fluconazole has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from fluconazole, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

Take fluconazole exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The fluconazole dose your doctor recommends will be based on the following the condition being treated

• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your age

The recommended dose of fluconazole for the treatment of vaginal candidiasis in adults is 150 mg as a one-time dose.

The recommended dose of fluconazole for the treatment of oropharyngeal candidiasis in adults is 200 mg on the first day, followed by 100 mg once daily.

The recommended dose of fluconazole for the treatment of esophageal candidiasis in adults is 200 mg on the first day, followed by 100 mg to 400 mg once daily.

The recommended dose of fluconazole for the treatment of systemic candida infections in adults is up to 400 mg once daily.

The recommended dose of fluconazole for the treatment of UTIs and peritonitis in adults is 50 mg to 200 mg once daily.

The recommended dose of fluconazole for the treatment of cryptococcal meningitis in adults is 400 mg on the first day, followed by 200 mg to 400 mg once daily.

The recommended dose of fluconazole to prevent infection in adults undergoing bone marrow transplant is 400 mg once daily.

The recommended dose of fluconazole for the treatment of oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily.

The recommended dose of fluconazole for the treatment of esophageal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg to 12 mg/kg once daily.

The recommended dose of fluconazole for the treatment of systemic candida infections in children is 6-12 mg/kg once daily.

The recommended dose of fluconazole for the treatment of cryptococcal meningitis in children is 12 mg/kg on the first day, followed by 6 mg/kg to 12 mg/kg once daily.

Fluconazole is an antifungal antibiotic.

Fluconazole is used to treat infections caused by fungus, which can invade any part of the body including the mouth, throat, esophagus, lungs, bladder, genital area, and the blood.

Fluconazole is also used to prevent fungal infection in people with weak immune systems caused by cancer treatment, bone marrow transplant, or diseases such as AIDS.

Fluconazole may also be used for purposes not listed in this medication guide.

DIFLUCAN is generally well tolerated.

In some patients, particularly those with serious underlying diseases such as AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities have been observed during treatment with fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain.

In Patients Receiving A Single Dose For Vaginal Candidiasis

During comparative clinical studies conducted in the United States, 448 patients with vaginal candidiasis were treated with DIFLUCAN, 150 mg single dose. The overall incidence of side effects possibly related to DIFLUCAN was 26%. In 422 patients receiving active comparative agents, the incidence was 16%. The most common treatment-related adverse events reported in the patients who received 150 mg single dose fluconazole for vaginitis were headache (13%), nausea (7%), and abdominal pain (6%). Other side effects reported with an incidence equal to or greater than 1% included diarrhea (3%), dyspepsia (1%), dizziness (1%), and taste perversion (1%). Most of the reported side effects were mild to moderate in severity. Rarely, angioedema and anaphylactic reaction have been reported in marketing experience.

In Patients Receiving Multiple Doses For Other Infections

Sixteen percent of over 4000 patients treated with DIFLUCAN (fluconazole) in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1.5% of patients due to adverse clinical events and in 1.3% of patients due to laboratory test abnormalities.

Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similar in the two groups (1.5%).

The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving DIFLUCAN for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1.5%.

In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with DIFLUCAN. (See WARNINGS.) The spectrum of these hepatic reactions has ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. Instances of fatal hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly AIDS or malignancy) and often while taking multiple concomitant medications. Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. In each of these cases, liver function returned to baseline on discontinuation of DIFLUCAN.

In two comparative trials evaluating the efficacy of DIFLUCAN for the suppression of relapse of cryptococcal meningitis, a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking DIFLUCAN concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents.

Post-Marketing Experience

In addition, the following adverse events have occurred during post-marketing experience.

Immunologic: In rare cases, anaphylaxis (including angioedema, face edema and pruritus) has been reported.

Body as a Whole: Asthenia, fatigue, fever, malaise.

Cardiovascular: QT prolongation, torsade de pointes. (See PRECAUTIONS.)

Central Nervous System: Seizures, dizziness.

Hematopoietic and Lymphatic: Leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

Metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Gastrointestinal: Cholestasis, dry mouth, hepatocellular damage, dyspepsia, vomiting.

Other Senses: Taste perversion.

Musculoskeletal System: myalgia.

Nervous System: Insomnia, paresthesia, somnolence, tremor, vertigo.

Skin and Appendages: Acute generalized exanthematous-pustulosis, drug eruption, increased sweating, exfoliative skin disorders including Stevens-Johnson syndrome and toxic epidermal necrolysis (see WARNINGS), alopecia.

Adverse Reactions In Children

The pattern and incidence of adverse events and laboratory abnormalities recorded during pediatric clinical trials are comparable to those seen in adults.

In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with DIFLUCAN at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment-related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase.

Percentage of Patients With Treatment-Related Side Effects

Read the entire FDA prescribing information for Diflucan (Fluconazole)

Fluconazole USP, the first of a new subclass of synthetic triazole antifungal agents, is available as tablets for oral administration.

Fluconazole USP is designated chemically as 2,4-difluoro-α,α1-bis(1H-1,2,4-triazol-1-ylmethyl) benzyl alcohol with an empirical formula of C13H12F2N6O and molecular weight of 306.3. The structural formula is:

Fluconazole USP is a white crystalline solid which is slightly soluble in water and saline.

Fluconazole tablets USP contain 50, 100, 150, or 200 mg of Fluconazole USP and the following inactive ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous, FD&C Red No. 40 aluminum lake dye, magnesium stearate, microcrystalline cellulose and povidone.

(1) Hepatic injury: Fluconazole should be administered with caution to patients with liver dysfunction. Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions. In cases of Fluconazole-associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of the patient has been observed. Fluconazole hepatotoxicity has usually, but not always, been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during Fluconazole therapy should be monitored for the development of more severe hepatic injury. Fluconazole should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to Fluconazole.

(2) Anaphylaxis: In rare cases, anaphylaxis has been reported.

(3) Dermatologic: Exfoliative skin disorders during treatment with Fluconazole have been reported. Fatal outcomes have been reported in patients with serious underlying diseases. Patients with deep seated fungal infections who develop rashes during treatment with Fluconazole should be monitored closely and the drug discontinued if lesions progress. Fluconazole should be discontinued in patients treated for superficial fungal infection who develop a rash that may be attributed to Fluconazole.

(4) Use in Pregnancy: There are no adequate and well-controlled studies of Fluconazole in pregnant women. Available human data do not suggest an increased risk of congenital anomalies following a single maternal dose of 150 mg. A few published case reports describe a rare pattern of distinct congenital anomalies in infants exposed in-utero to high dose maternal Fluconazole (400-800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. (See PRECAUTIONS. Pregnancy)

Fluconazole is generally well tolerated.

In some patients, particularly those with serious underlying diseases such as AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities have been observed during treatment with Fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain.

In Patients Receiving a Single Dose for Vaginal Candidiasis:

During comparative clinical studies conducted in the United States, 448 patients with vaginal candidiasis were treated with Fluconazole, 150 mg single dose. The overall incidence of side effects possibly related to Fluconazole was 26%. In 422 patients receiving active comparative agents, the incidence was 16%. The most common treatment-related adverse events reported in the patients who received 150 mg single dose Fluconazole for vaginitis were headache (13%), nausea (7%), and abdominal pain (6%). Other side effects reported with an incidence equal to or greater than 1% included diarrhea (3%), dyspepsia (1%), dizziness (1%), and taste perversion (1%). Most of the reported side effects were mild to moderate in severity. Rarely, angioedema and anaphylactic reaction have been reported in marketing experience.

In Patients Receiving Multiple Doses for Other Infections:

Sixteen percent of over 4000 patients treated with Fluconazole in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1.5% of patients due to adverse clinical events and in 1.3% of patients due to laboratory test abnormalities.

Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similar in the two groups (1.5%).

The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving Fluconazole for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1.5%.

Hepatobiliary: In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with Fluconazole. (See WARNINGS). The spectrum of these hepatic reactions has ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. Instances of fatal hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly AIDS or malignancy) and often while taking multiple concomitant medications. Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. In each of these cases, liver function returned to baseline on discontinuation of Fluconazole.

In two comparative trials evaluating the efficacy of Fluconazole for the suppression of relapse of cryptococcal meningitis, a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in Fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking Fluconazole concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents.

Post-Marketing Experience

In addition, the following adverse events have occurred during post-marketing experience.

Immunologic: In rare cases, anaphylaxis (including angioedema, face edema and pruritus) has been reported.

Body as a Whole: Asthenia, fatigue, fever, malaise.

Cardiovascular: QT prolongation, torsade de pointes. (See PRECAUTIONS.)

Central Nervous System: Seizures, dizziness.

Hematopoietic and Lymphatic: Leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

Metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Gastrointestinal: Cholestasis, dry mouth, hepatocellular damage, dyspepsia, vomiting.

Other Senses: Taste perversion.

Musculoskeletal System: myalgia.

Nervous System: Insomnia, paresthesia, somnolence, tremor, vertigo.

Skin and Appendages: Acute generalized exanthematous-pustulosis, drug eruption, increased sweating, exfoliative skin disorders including Stevens-Johnson syndrome and toxic epidermal necrolysis (see WARNINGS), alopecia.

Adverse Reactions in Children:

The pattern and incidence of adverse events and laboratory abnormalities recorded during pediatric clinical trials are comparable to those seen in adults.

In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with Fluconazole at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment-related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase.

• Diflucan

• Diflucan

Interferes with fungal cytochrome P450 activity (lanosterol 14-α-demethylase), decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation

Absorption

Oral: Well absorbed; food does not affect extent of absorption

Distribution

Vd: ~0.6 L/kg; widely throughout body with good penetration into CSF, eye, peritoneal fluid, sputum, skin, and urine

Relative diffusion blood into CSF: Adequate with or without inflammation (exceeds usual MICs)

CSF:blood level ratio: Normal meninges: 50% to 90%; Inflamed meninges: ~80%

Excretion

Urine (80% as unchanged drug)

Time to Peak

Oral: 1 to 2 hours

Half-Life Elimination

Normal renal function: ~30 hours (range: 20 to 50 hours); Elderly: 46.2 hours; Neonates (gestational age 26 to 29 weeks): 73.6 to 46.6 hours (decreases with increasing postnatal age); Pediatric patients 9 months to 15 years: 19.5 to 25 hours

Protein Binding

Plasma: 11% to 12%

Hypersensitivity to fluconazole or any component of the formulation (cross-reaction with other azole antifungal agents may occur, but has not been established; use caution); coadministration of terfenadine in adult patients receiving multiple doses of 400 mg or higher or with CYP3A4 substrates which may lead to QTc prolongation (eg, astemizole, cisapride, erythromycin, pimozide, or quinidine)

The daily dose of fluconazole is the same for both oral and IV administration

Usual dosage range: Oral, IV: 150 mg once or Loading dose: 200 to 800 mg; maintenance: 200 to 800 mg once daily; duration and dosage depend on location and severity of infection

Indication-specific dosing:

Blastomycosis (off-label use): Oral: CNS disease: Consolidation: 800 mg daily for ≥12 months and until resolution of CSF abnormalities (Chapman 2008)

Candidiasis:

Candidemia (neutropenic and non-neutropenic patients) (off-label dose) (IDSA [Pappas 2016]): Oral, IV:

Initial therapy (ie, first-line): Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg daily (6 mg/kg/day) for 14 days after first negative blood culture and resolution of signs/symptoms. Note: Not recommended as first-line therapy in patients with previous azole exposure, critical illness, or if at high risk of C. glabrata infection (elderly, diabetic, malignancy)

Step down therapy (ie, after patient has responded to initial therapy): Oral:

Isolates other than C. glabrata: 400 mg daily

Isolates of C. glabrata (fluconazole-susceptible): 800 mg daily

Duration: Continue for 14 days after first negative blood culture and resolution of signs/symptoms; step-down therapy to fluconazole (usually after 5 to 7 days in non-neutropenic patients) is recommended only in clinically stable patients with negative repeat cultures and fluconazole-susceptible isolates

Chronic, disseminated (hepatosplenic) (fluconazole-susceptible isolates): Oral: 400 mg daily (6 mg/kg/day) following several weeks of initial therapy with an amphotericin B lipid formulation or an echinocandin. Continue fluconazole until lesion resolution (usually several months) (IDSA [Pappas 2016])

CNS candidiasis: Oral, IV: 400 to 800 mg daily (6 to 12 mg/kg/day) as step-down therapy following initial therapy with liposomal amphotericin B (with or without flucytosine); continue fluconazole until signs/symptoms and CSF/radiological abnormalities have resolved (IDSA [Pappas 2016])

Empiric therapy, suspected invasive candidiasis (non-neutropenic patients in the ICU) (alternative therapy) (off-label use): Oral, IV: Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg daily (6 mg/kg/day); treatment should continue for 14 days in patients with clinical improvement. Consider discontinuing after 4 to 5 days in patients with no clinical response. Note: Not recommended for patients with previous azole exposure or those colonized with azole-resistant Candida spp. (Pappas [IDSA 2016])

Endophthalmitis (with or without vitritis): Oral, IV: Loading dose: 800 mg (12 mg/kg) on day 1, then 400 to 800 mg daily (6 to 12 mg/kg/day) for at least 4 to 6 weeks until examination indicates resolution; for patients with vitritis or with macular involvement (with or without vitritis), an intravitreal injection with voriconazole or amphotericin B deoxycholate is also recommended (IDSA [Pappas 2016])

Esophageal: Oral, IV:

Manufacturer’s labeling: Loading dose: 200 mg on day 1, then maintenance dose of 100 to 400 mg daily for 21 days and for at least 2 weeks following resolution of symptoms

Alternate recommendations: 200 to 400 mg daily for 14 to 21 days; chronic suppressive therapy of 100 to 200 mg 3 times weekly may be used for recurrent infections (IDSA [Pappas 2016])

Intertrigo (off-label use): Oral, IV: 50 mg daily or 150 mg once weekly (Coldiron 1991; Nozickova 1998; Stengel 1994)

Intra-abdominal infections: Oral, IV: Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg daily (6 mg/kg/day); duration of therapy determined by clinical response and source control (IDSA [Pappas 2016])

Intravascular infections (IDSA [Pappas 2016]): Oral, IV:

Endocarditis, native or prosthetic valve: 400 to 800 mg daily (6 to 12 mg/kg/day) for at least 6 weeks after valve replacement surgery (longer durations recommended in patients with perivalvular abscesses or other complications); fluconazole should only be used as step-down therapy in clinically stable, culture-negative patients following initial therapy with an amphotericin B lipid formulation (with or without flucytosine) or an echinocandin; long-term or chronic suppressive therapy with fluconazole in absence of valve replacement surgery or in patients with a prosthetic valve endocarditis: 400 to 800 mg daily

Implantable cardiac devices (eg, pacemaker, ICD, VAD) infection: 400 to 800 mg daily (6 to 12 mg/kg/day) for 4 to 6 weeks after device removal (4 weeks for infections limited to generator pockets and at least 6 weeks for infections involving the wires); fluconazole should only be used as step-down in clinically stable, culture-negative patients following initial therapy with an amphotericin B lipid formulation (with or without flucytosine) or an echinocandin; chronic suppressive therapy with fluconazole (following initial antifungal therapy) when VAD cannot be removed and as long as device remains in place: 400 to 800 mg daily

Thrombophlebitis, suppurative: 400 to 800 mg daily (6 to 12 mg/kg/day) for at least 2 weeks after candidemia has cleared; fluconazole may be used as initial therapy or as step-down therapy following initial therapy with an amphotericin B lipid formulation or an echinocandin in clinically stable patients with fluconazole-susceptible isolates.

Oropharyngeal: Oral, IV:

Manufacturer's labeling: Loading dose: 200 mg on day 1; maintenance dose 100 mg daily for ≥2 weeks. Note: Therapy with 100 mg daily is associated with resistance development (Rex 1995).

Alternate recommendations: 100 to 200 mg daily for 7 to 14 days for moderate-to-severe disease; in patients with recurrent infection, chronic therapy of 100 mg 3 times weekly is recommended, if required (IDSA [Pappas 2016])

Osteoarticular (osteomyelitis or septic arthritis): Oral, IV: 400 mg daily (6 mg/kg/day) for 6 to 12 months (osteomyelitis) or 6 weeks (septic arthritis); alternatively, fluconazole 400 mg daily for 6 to 12 months (osteomyelitis) or at least 4 weeks (septic arthritis) may also be used following 2 weeks of initial treatment with an echinocandin or an amphotericin B lipid formulation. In patients with fluconazole-susceptible isolates and septic arthritis involving a prosthetic device which cannot be removed, chronic suppressive therapy with fluconazole 400 mg daily is recommended (IDSA [Pappas 2016])

Peritonitis: Oral, IV: 50-200 mg/day. Note: Some clinicians do not recommend using <200 mg daily (Chen 2004).

Prophylaxis: Oral, IV:

Bone marrow transplant: 400 mg once daily. Patients anticipated to have severe granulocytopenia should start therapy several days prior to the anticipated onset of neutropenia and continue for 7 days after the neutrophil count is >1000 mm3.

High-risk ICU patients in units with high incidence of invasive candidiasis (off-label use): Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg once daily (6 mg/kg/day) (IDSA [Pappas 2016])

Peritoneal dialysis associated infection (concurrently treated with antibiotics), prevention of secondary fungal infection: 200 mg every 48 hours (Restrepo 2010)

Solid organ transplant: 200 to 400 mg once daily for at least 7 to 14 days (Pappas 2009)

Surgical (perioperative) prophylaxis in high-risk patients undergoing liver, pancreas, kidney, or pancreas-kidney transplantation (off-label use): IV: 400 mg given in the perioperative period and continued in the postoperative period for ≤28 days. Time of initiation and duration varies with transplant type and operative protocol (Bratzler 2013).

Urinary tract infections:

Manufacturer’s labeling: UTI: Oral, IV: 50 to 200 mg once daily

Alternate recommendations (IDSA [Pappas 2016]):

Candiduria (asymptomatic), patients undergoing a urologic procedure: Oral: 400 mg once daily (6 mg/kg/day) several days before and after the procedure.

Cystitis (symptomatic): Oral: 200 mg once daily (3 mg/kg/day) for 2 weeks

Fungus balls: Oral: 200 to 400 mg once daily (3 to 6 mg/kg/day); concomitant irrigation of amphotericin B deoxycholate via nephrostomy tubes, if present, is also recommended

Pyelonephritis: Oral: 200 to 400 mg once daily for 2 weeks

Vaginal/Vulvovaginal: Oral:

Uncomplicated: Manufacturer's labeling: 150 mg as a single dose

Complicated or severe: 150 mg every 72 hours for 2 or 3 doses (Pappas [IDSA 2016]) or 150 mg every 72 hours for 2 doses (CDC [Workowski 2015])

Recurrent: 150 mg once daily for 10 to 14 days, followed by 150 mg once weekly for 6 months (Pappas 2009) or fluconazole 100 mg, 150 mg, or 200 mg every 72 hours (day 1, 4, and 7) for a total of 3 doses, then 100 mg, 150 mg, or 200 mg once weekly for 6 months (CDC [Workowski 2015])

Coccidioidomycosis, treatment (off-label use):

HIV-infected (HHS [OI adult 2015]):

Meningeal infections (consultation with specialist is advised): IV, Oral: 400 to 800 mg once daily; patients who complete initial therapy should be considered for lifelong suppressive therapy using fluconazole 400 mg once daily if CD4 counts remain <250 cells/mm3.

Mild infections (eg, focal pneumonia): Oral: 400 mg once daily; patients who complete initial therapy should be considered for lifelong suppressive therapy using fluconazole 400 mg once daily if CD4 counts remain <250 cells/mm3.

Non-HIV infected:

Extrapulmonary, bone and/or joint infection: Oral: A minimum dose of 800 mg once daily for 3 years to lifetime, depending on severity and host immunocompetence. Note: Amphotericin B may be used initially for severe disease and then switched to fluconazole (IDSA [Galgiani 2016])

Extrapulmonary, soft tissue infection (not associated with bone infection): Oral: 400 mg once daily (some experts use up to 800 mg once daily) for a minimum of 6 to 12 months (IDSA [Galgiani 2016])

HSCT (allogenic or autologous) or solid organ transplant clinically stable patients with active pulmonary infections (acute or chronic): Oral: 400 mg once daily, continued indefinitely or until discontinuation of antirejection therapy (IDSA [Galgiani 2016])

Meningitis: Oral: Initial: 400 to 1200 mg once daily with a lifelong duration (IDSA [Galgiani 2016])

Pneumonia, uncomplicated: Oral: 400 mg once daily (some experts use 800 mg once daily) for 3 to 6 months or longer, depending on response. Note: Antifungal treatment is recommended only for patients with severely debilitating illness or with extensive pulmonary involvement, concurrent diabetes, or frailty due to age or comorbidities (IDSA [Galgiani 2016])

Pneumonia, symptomatic chronic cavitary: Oral: 400 mg once daily for 12 months (Galgiani 2000; IDSA [Galgiani 2016])

Coccidioidomycosis, prophylaxis (off-label use): Oral:

HIV-infected patients (HHS [OI adult 2015]):

Primary prophylaxis in patients with a new positive IgM or IgG serologic test who live in disease-endemic areas and have CD4 counts <250 cells/mm3: 400 mg once daily

Chronic suppressive therapy (secondary prophylaxis): 400 mg once daily

Non-HIV-infected patients:

Solid organ transplant patients: Note: The suggested regimens are for patients without active coccidioiomycosis who are undergoing organ transplantation in an endemic area.

Seronegative patients: 200 mg once daily for 6 to 12 months (IDSA [Galgiani 2016]

Seropositive patients: 400 mg once daily for 6 to 12 months (IDSA [Galgiani 2016]

Cryptococcosis:

Meningitis:

Manufacturer's labeling: Oral, IV: 400 mg for 1 dose, then 200 to 400 mg once daily for 10 to 12 weeks following negative CSF culture

Alternate dosing: HIV-infected:

Induction (alternative to preferred therapy): Oral, IV: 800 to 1,200 mg once daily with concomitant flucytosine for 6 weeks (Perfect 2010) or 400 to 800 mg once daily with concomitant flucytosine for at least 2 weeks (HHS [OI adult 2015]) or 1,200 mg once daily as monotherapy for at least 2 weeks (HHS [OI adult 2015])

Consolidation (preferred therapy): Oral, IV: 400 mg once daily for at least 8 weeks (HHS [OI adult 2015])

Maintenance (suppression) (preferred therapy): Oral: 200 mg once daily for at least 12 months; maintenance therapy may be stopped if the following criteria are fulfilled: induction, consolidation, and at least 12 months of maintenance therapy has been completed, patient remains asymptomatic from cryptococcal infection, and CD4 count ≥100 cells/mm3 for ≥3 months and HIV RNA suppressed in response to effective ART (HHS [OI adult 2015])

Pulmonary (immunocompetent) (off-label use): 400 mg once daily for 6 to 12 months (Perfect 2010)

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.