FLUCONAZOLE (Generic for DIFLUCAN)

General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 3
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-INJECTABLE Drugs: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
-ORAL TABLETS/ORAL LIQUID: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.

Route-Specific Administration

Oral Administration
-May be administered without regard to meals.
Oral Liquid Formulations
Reconstitution of Suspension
-Review the reconstitution instructions for the particular product and package size, as the amount of water required for reconstitution may vary from manufacturer to manufacturer.
-Tap the bottle several times to loosen the powder. Add the specified amount of water to the bottle and shake vigorously. The resultant concentrations are typically 10 or 40 mg/mL.
-Shake well prior to each administration.
-Storage: Reconstituted suspension is stable for 14 days when stored at 5 to 30 degrees C.



Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Intermittent IV Infusion
-Available as 2 mg/mL ready-to-use IV solution; no further dilution required.
-Infuse IV at a rate not to exceed 200 mg/hour.

In children receiving fluconazole in phase II/III clinical trials in the US and Europe (n = 577), the most commonly reported adverse reactions were nausea (2%), vomiting (5%), abdominal pain (3%), and diarrhea (2%). Dyspepsia (1%) and dysgeusia (1%) have also been reported in adult patients in clinical studies. Dry mouth (xerostomia) has been reported with fluconazole in postmarketing experience.

Exfoliative skin disorders, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients taking fluconazole. Fluconazole-associated dermatologic adverse events have resulted in fatal outcomes for patients with serious underlying diseases, such as AIDS or malignancy. Monitor drug recipients for development of a rash. If a rash is observed in a patient being treated for a superficial fungal infection and the rash is attributed to fluconazole, immediately discontinue use of the drug. If a rash develops in a patient being treated for a deep-seated fungal infection, closely monitor the patient and discontinue fluconazole if the lesion progresses. Other dermatologic adverse reactions reported during postmarketing use of the drug include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), and hyperhidrosis (increased sweating). Although not reported in pediatric trials, alopecia has been reported in adults taking fluconazole.

Rarely, angioedema and anaphylactoid reactions (including facial edema and pruritus) have been reported with fluconazole in postmarketing experience after single and multiple doses.

Some azole antifungals, including fluconazole, have been associated with QT prolongation. During postmarketing experience, there have been very rare reports of QT prolongation and torsade de pointes (TdP) in patients taking fluconazole. These reports included seriously ill patients with multiple confounding risk factors that may have been contributory. Fluconazole is not likely to cause TdP at usual therapeutic dosages.

Fluconazole has been associated with rare cases of serious hepatotoxicity. These hepatic reactions have ranged from mild transient elevated hepatic enzymes 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. Fluconazole hepatotoxicity has usually, but not always, been reversible on discontinuation of therapy. Monitor patients who develop abnormal liver function tests during fluconazole therapy for the development of more severe hepatic injury. Discontinue fluconazole if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole. Elevated transaminases (alanine aminotransferase (ALT), 5%; aspartate aminotransferase (AST), 3%) and alkaline phosphatase (2%) have been reported in pediatric patients and were the most common treatment-related laboratory abnormalities in clinical trials. A higher incidence of cholestasis (direct bilirubin 2 mg/dL or more) was reported in neonates receiving more frequent dosing of fluconazole prophylaxis compared with those receiving less frequent dosing of fluconazole prophylaxis (43% vs. 29%) in a retrospective study (n = 244).

Leukopenia, including neutropenia and agranulocytosis, and thrombocytopenia have been reported during postmarketing use of fluconazole.

Although not reported in children, headache was reported commonly (13%) in adults receiving single-dose fluconazole in clinical studies. Headache was also reported in 2% of adults receiving multiple-dose fluconazole in other clinical studies. Dizziness was reported in 1% of adults receiving single-dose fluconazole in clinical studies. Seizures, drowsiness, insomnia, paresthesias, tremor, and vertigo have been reported during postmarketing use of fluconazole.

Hypokalemia, hypercholesterolemia, and hypertriglyceridemia have been reported during postmarketing use of fluconazole.

Asthenia, fatigue, fever, malaise, and myalgia have been reported during postmarketing use of fluconazole.

Reversible cases of adrenocortical insufficiency have been reported in patients receiving fluconazole. Advise patients to report any symptoms of adrenal insufficiency, including long-lasting fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, nausea, vomiting, or dizziness.

GI perforation, including ileal and small intestinal perforation, was reported at a higher incidence in premature neonates weighing less than 750 g receiving fluconazole prophylaxis (6 mg/kg/dose given twice weekly for 6 weeks) compared with placebo (7% vs. 4%) in a prospective, randomized, double-blind, multicenter study (n = 361). Other serious adverse reactions reported in the fluconazole vs. placebo groups, respectively, include necrotizing enterocolitis (NEC; 14% vs. 16%), respiratory failure (7% vs. 2%), and bacterial sepsis (5% vs. 7%). The most common fatal serious adverse reactions in the fluconazole vs. placebo groups, respectively, were NEC (5% vs. 5%), neonatal bacterial sepsis (3% vs. 4%), and respiratory failure (2% vs. 0.6%).

There have been reports of cases of superinfection with Candida species other than C. albicans, which are often inherently not susceptible to fluconazole (e.g., C. krusei). Such cases may require alternative antifungal therapy.

Anemia and acute renal failure have been reported in postmarketing experience.

Fluconazole should be used with caution in patients with azole antifungals hypersensitivity. Fluconazole may have a cross sensitivity with other azole derivatives.

Fluconazole should be administered cautiously in patients with potentially proarrhythmic conditions, including a history of torsade de pointes. Some azole antifungals, including fluconazole, have been associated with QT prolongation. During post-marketing surveillance, rare cases of QT prolongation and torsade de pointes have been reported with fluconazole use. These reports have included seriously ill patients with multiple confounding risk factors that may have been contributory, such as structural cardiac disease, electrolyte imbalance, and concomitant medications that could be associated with proarrhythmic conditions. Fluconazole is not likely to cause QT prolongation or torsade de pointes when administered at usual therapeutic dosages. Use fluconazole with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

Use caution in patients with hepatic disease as fluconazole has been associated with rare cases of severe hepatotoxicity, including fatalities. Hepatotoxicity has generally been reversible, but not always, with therapy discontinuation. Monitor patients who develop abnormal liver function tests during therapy for the development of more severe hepatic injury. If signs and symptoms of hepatotoxicity develop, discontinue fluconazole therapy.

Use caution in patients with renal impairment or renal failure as fluconazole is primarily excreted renally. Dose adjustments are recommended in patients with renal impairment.

In patients with hereditary fructose intolerance, glucose/galactose malabsorption, or sucrase-isomaltase deficiency, use of fluconazole oral suspension is not recommended due to the sucrose content.

Fluconazole may rarely cause dizziness or seizures. Advise patients and their caregivers to use caution when participating in activities requiring coordination and concentration (e.g., riding a bicycle, gymnastics, driving, operating machinery) until they are aware of how the drug affects them.

Serious rash events, including exfoliative skin disorders such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients receiving treatment with fluconazole. Fluconazole-associated dermatologic adverse events have resulted in fatal outcomes for patients with serious underlying diseases. Monitor drug recipients for development of rash. If a rash is observed on a patient being treated for a superficial fungal infection, and the rash is attributed to fluconazole, discontinue use of the drug. However, if a rash develops on a patient being treated for a deep-seated fungal infection, monitor the patient closely and discontinue the drug if the lesion progresses.

Counsel females of childbearing potential who are receiving high dose fluconazole (i.e., 400 to 800 mg/day) about the reproductive risk and contraception requirements during treatment. Advise these patients to use effective contraception during treatment and for approximately 1 week (5 to 6 half-lives) after the final dose.

Description: Fluconazole is a synthetic antifungal agent of the azole class. It is administered orally and intravenously. The antifungal spectrum for fluconazole is broader than that of the imidazole antifungals class, which includes agents such as ketoconazole, miconazole, and clotrimazole. Fluconazole is more resistant to first-pass metabolism and has lower lipophilicity and protein binding than does ketoconazole. Unlike ketoconazole, the oral absorption of fluconazole is not affected by the absence of stomach acid. Fluconazole is used for the treatment of a variety of infections caused by Candida and for the treatment of cryptococcal meningitis. Fluconazole is the primary alternative therapy to amphotericin B for neonatal candidiasis. Additionally, fluconazole is used for the prophylaxis of candidiasis, particularly in premature infants and in other high-risk patients (hematopoietic stem cell transplant recipients, patients with chemotherapy-induced neutropenia). The clearance of fluconazole is higher in children compared with adults; therefore, higher doses are recommended in children. Fluconazole is FDA-approved for use in pediatric patients as young as neonates.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Candida albicans, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Blastomyces dermatitidis, Candida pseudotropicalis, Candida stellatoidea, Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Talaromyces marneffei
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of CNS infections*, including meningitis*:
NOTE: For CNS infections caused by Cryptococcus, see Cryptococcus meningitis.
-for step-down therapy of CNS infections due to Candida sp.* after initial treatment with amphotericin B:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 9 mg/kg/dose PO once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.
Neonates 30 weeks gestation and older: 12 mg/kg/dose PO once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) PO once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 9 mg/kg/dose IV once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.
Neonates 30 weeks gestation and older: 12 mg/kg/dose IV once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) IV once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.
-for the treatment of CNS infections due to Coccidioides sp.*:
Oral dosage:
Infants and Children: 12 mg/kg/dose (Max: 800 mg/dose) PO once daily as preferred therapy. For persons living with HIV, fluconazole is recommended for 8 weeks after an initial 2-week course of amphotericin B deoxycholate or liposomal amphotericin B plus flucytosine. If amphotericin B is not tolerated, fluconazole may be given as initial therapy plus flucytosine. If flucytosine is not tolerated, fluconazole may be given as initial therapy plus amphotericin B. Continue suppressive therapy for lifelong.
Adolescents: 400 to 1,200 mg PO once daily as preferred therapy. Continue suppressive therapy for lifelong.
Intravenous dosage:
Infants and Children: 12 mg/kg/dose (Max: 800 mg/dose) IV once daily as preferred therapy. For persons living with HIV, fluconazole is recommended for 8 weeks after an initial 2-week course of amphotericin B deoxycholate or liposomal amphotericin B plus flucytosine. If amphotericin B is not tolerated, fluconazole may be given as initial therapy plus flucytosine. If flucytosine is not tolerated, fluconazole may be given as initial therapy plus amphotericin B. Continue suppressive therapy for lifelong.
Adolescents: 400 to 1,200 mg IV once daily as preferred therapy. Continue suppressive therapy for lifelong.
-for step-down therapy of CNS infections due to Histoplasma capsulatum* after initial treatment with amphotericin B in persons living with HIV:
Oral dosage:
Adolescents: 800 mg PO once daily for at least 12 months and until resolution of abnormal CSF findings in persons who are intolerant to itraconazole.

For the treatment of candidemia and invasive candidiasis (non-CNS), including chronic disseminated (hepatosplenic) candidiasis* as step-down therapy:
NOTE: For CNS infections, see dosage for meningitis.
-for the treatment of candidemia and invasive candidiasis (non-CNS):
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily as an alternative in patients who are not critically ill and are unlikely to have a fluconazole-resistant isolate, specifically no prior azole exposure for neutropenic patients. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily. Guidelines recommend fluconazole as an alternative only in patients who are not critically ill and are unlikely to have a fluconazole-resistant isolate, specifically no prior azole exposure for neutropenic patients. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily as an alternative in patients who are not critically ill and are unlikely to have a fluconazole-resistant isolate, specifically no prior azole exposure for neutropenic patients. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily. Guidelines recommend fluconazole as an alternative only in patients who are not critically ill and are unlikely to have a fluconazole-resistant isolate, specifically no prior azole exposure for neutropenic patients. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
-for the treatment of chronic disseminated (hepatosplenic) candidiasis* as step-down therapy:
Oral dosage:
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) PO once daily after initial treatment with lipid amphotericin B or an echinocandin for patients who are unlikely to have a fluconazole-resistant isolate. Treat until lesions resolve on repeat imaging, which is usually several months.
Intravenous dosage:
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) IV once daily after initial treatment with lipid amphotericin B or an echinocandin for patients who are unlikely to have a fluconazole-resistant isolate. Treat until lesions resolve on repeat imaging, which is usually several months.

For the treatment of endophthalmitis* caused by Candida sp.:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for fluconazole-susceptible isolates. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for fluconazole-susceptible isolates. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for fluconazole-susceptible isolates. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.
Infants, Children, and Adolescent on ECMO: 35 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for fluconazole-susceptible isolates. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.

For the treatment of oropharyngeal candidiasis (thrush):
-for the initial treatment of oropharyngeal candidiasis in persons without HIV:
Oral dosage:
Neonates*: 6 mg/kg/dose PO loading dose on day 1, followed by 3 to 6 mg/kg/dose PO once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Infants 1 to 5 months*: 6 mg/kg/dose PO loading dose on day 1, followed by 3 to 6 mg/kg/dose PO once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Infants, Children, and Adolescents 6 months to 17 years: 6 mg/kg/dose (Max: 200 mg/dose) PO loading dose on day 1, followed by 3 to 6 mg/kg/dose (Max: 100 mg/dose) PO once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Intravenous dosage:
Neonates*: 6 mg/kg/dose IV loading dose on day 1, followed by 3 to 6 mg/kg/dose IV once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Infants 1 to 5 months*: 6 mg/kg/dose IV loading dose on day 1, followed by 3 to 6 mg/kg/dose IV once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Infants, Children, and Adolescents 6 months to 17 years: 6 mg/kg/dose (Max: 200 mg/dose) IV loading dose on day 1, followed by 3 to 6 mg/kg/dose (Max: 100 mg/dose) IV once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
-for the initial treatment of oropharyngeal candidiasis in persons living with HIV:
Oral dosage:
Infants 1 to 5 months*: 6 to 12 mg/kg/dose PO once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Infants and Children 6 months to 12 years: 6 to 12 mg/kg/dose (Max: 200 mg/dose) PO once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Adolescents: 100 to 200 mg PO once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Intravenous dosage:
Infants 1 to 5 months*: 6 to 12 mg/kg/dose IV once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Infants and Children 6 months to 12 years: 6 to 12 mg/kg/dose (Max: 200 mg/dose) IV once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.
Adolescents: 100 to 200 mg IV once daily for 7 to 14 days. A course of at least 14 days may decrease the likelihood of relapse.

For the treatment of esophageal candidiasis:
-for the initial treatment of esophageal candidiasis in persons without HIV:
Oral dosage:
Neonates*: 6 mg/kg/dose PO loading dose on day 1, followed by 3 to 6 mg/kg/dose PO once daily for 14 to 21 days. Doses up to 12 mg/kg/day (Max: 400 mg/day) PO may be used if clinical condition warrants more aggressive dosing.
Infants 1 to 5 months*: 6 mg/kg/dose PO loading dose on day 1, followed by 3 to 6 mg/kg/dose PO once daily for 14 to 21 days. Doses up to 12 mg/kg/day PO may be used if clinical condition warrants more aggressive dosing.
Infants, Children, and Adolescents 6 months to 17 years: 6 mg/kg/dose (Max: 400 mg/dose) PO loading dose on day 1, followed by 3 to 6 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 to 21 days. Doses up to 12 mg/kg/day (Max: 400 mg/day) PO may be used if clinical condition warrants more aggressive dosing.
Intravenous dosage:
Neonates*: 6 mg/kg/dose IV loading dose on day 1, followed by 3 to 6 mg/kg/dose IV once daily for 14 to 21 days. Doses up to 12 mg/kg/day IV may be used if clinical condition warrants more aggressive dosing.
Infants 1 to 5 months*: 6 mg/kg/dose IV loading dose on day 1, followed by 3 to 6 mg/kg/dose IV once daily for 14 to 21 days. Doses up to 12 mg/kg/day IV may be used if clinical condition warrants more aggressive dosing.
Infants, Children, and Adolescents 6 months to 17 years: 6 mg/kg/dose (Max: 400 mg/dose) IV loading dose on day 1, followed by 3 to 6 mg/kg/dose (Max: 400 mg/dose) IV once daily for 14 to 21 days. Doses up to 12 mg/kg/day (Max: 400 mg/day) IV may be used if clinical condition warrants more aggressive dosing.
-for the initial treatment of esophageal candidiasis in persons living with HIV:
Oral dosage:
Infants 1 to 5 months*: 6 to 12 mg/kg/dose PO once daily for 14 to 21 days.
Infants and Children 6 months to 12 years: 6 to 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 to 21 days.
Adolescents: 100 to 400 mg PO once daily for 14 to 21 days.
Intravenous dosage:
Infants 1 to 5 months*: 6 to 12 mg/kg/dose IV once daily for 14 to 21 days.
Infants and Children 6 months to 12 years: 6 to 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 14 to 21 days.
Adolescents: 100 to 400 mg IV once daily for 14 to 21 days.

For the treatment of Candida infections of the cardiovascular system, including endocarditis*, suppurative thrombophlebitis*, and infected pacemaker*, implantable cardiac defibrillator (ICD)*, or ventricular assist devices (VAD)*:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) PO once daily as step-down therapy after lipid amphotericin B or echinocandin therapy in stable patients with negative blood cultures. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) IV once daily as step-down therapy after lipid amphotericin B or echinocandin therapy in stable patients with negative blood cultures. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

For the treatment of pneumonia caused by Candida sp.:
NOTE: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. In cases where pneumonia is associated with disseminated infection, treatment is recommended.
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily as an alternative to echinocandin therapy in patients who are not critically ill and are unlikely to have a fluconazole-resistant isolate, specifically no prior azole exposure for neutropenic patients.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily. Guidelines recommend fluconazole as an alternative to echinocandin therapy only in patients who are not critically ill and are unlikely to have a fluconazole-resistant isolate, specifically no prior azole exposure for neutropenic patients.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily as an alternative to echinocandin therapy in patients who are not critically ill and are unlikely to have a fluconazole-resistant isolate, specifically no prior azole exposure for neutropenic patients.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily. Guidelines recommend fluconazole as an alternative to echinocandin therapy only in patients who are not critically ill and are unlikely to have a fluconazole-resistant isolate, specifically no prior azole exposure for neutropenic patients.

For the treatment of intraabdominal infections, including peritonitis, intraabdominal candidiasis, neonatal necrotizing enterocolitis*, peritoneal dialysis-related peritonitis*, and peritoneal dialysis catheter-related infection*:
-for the treatment of intraabdominal candidiasis:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily.
-for the treatment of peritoneal dialysis-related peritonitis* due to Candida:
Oral dosage:
Infants, Children, and Adolescents: 6 to 12 mg/kg/dose (Max: 400 mg/dose) PO every 24 to 48 hours for at least 14 days after catheter removal.
Intravenous dosage:
Infants, Children, and Adolescents: 6 to 12 mg/kg/dose (Max: 400 mg/dose) IV every 24 to 48 hours for at least 14 days after catheter removal.
Intermittent Intraperitoneal dosage*:
Infants, Children, and Adolescents: 6 to 12 mg/kg/dose (Max: 400 mg/dose) intraperitoneally every 24 to 48 hours.
-for the treatment of peritoneal dialysis catheter-related infection*:
Oral dosage:
Infants, Children, and Adolescents: 6 mg/kg/dose (Max: 400 mg/dose) PO every 24 to 48 hours for at least 14 to 28 days.

For the treatment of bone and joint infections* (i.e., osteomyelitis*, infectious arthritis*) caused by Candida sp.:
-for the treatment of osteomyelitis:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 6 to 12 months as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 6 to 12 months as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 6 to 12 months as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 6 to 12 months as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 6 to 12 months.
Infants, Children, Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 6 to 12 months.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 6 to 12 months as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 6 to 12 months as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 6 to 12 months as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 6 to 12 months as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 6 to 12 months.
Infants, Children, Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 6 to 12 months.
-for the treatment of infectious arthritis:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 6 weeks as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 6 weeks as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 6 weeks as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 6 weeks as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 6 weeks.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 6 weeks.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 6 weeks as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 6 weeks as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 6 weeks as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 6 weeks as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 6 weeks.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 6 weeks.

For the treatment of asymptomatic candiduria* and Candida urinary tract infection (UTI)*, including cystitis* and pyelonephritis*:
-for the initial treatment of asymptomatic candiduria* in neutropenic persons:
Oral dosage:
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 days as an alternative to echinocandin therapy in patients who are not critically ill and have had no prior azole exposure. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic patients; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) PO loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 days. Guidelines recommend fluconazole as an alternative to echinocandin therapy only in patients who are not critically ill and have had no prior azole exposure. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic patients; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Intravenous dosage:
Infants, Children, and Adolescents: 25 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 14 days as an alternative to echinocandin therapy in patients who are not critically ill and have had no prior azole exposure. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic patients; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Infants, Children, and Adolescents on ECMO: 35 mg/kg (Max: 800 mg/dose) IV loading dose on day 1, followed by 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 14 days. Guidelines recommend fluconazole as an alternative to echinocandin therapy only in patients who are not critically ill and have had no prior azole exposure. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic patients; therefore, candiduria should be treated as disseminated candidiasis in these patients.
-for stepdown treatment of asymptomatic candiduria* in neutropenic persons:
Oral dosage:
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) PO once daily to complete a 14-day course as stepdown therapy after initial echinocandin or amphotericin B therapy. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic patients; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Intravenous dosage:
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) IV once daily to complete a 14-day course as stepdown therapy after initial echinocandin or amphotericin B therapy. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic patients; therefore, candiduria should be treated as disseminated candidiasis in these patients.
-for the treatment of asymptomatic candiduria* in very-low-birth-weight infants (weight less than 1.5 kg):
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
-for the treatment of asymptomatic candiduria* in persons undergoing urologic procedures:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for several days before and after the urologic procedure as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for several days before and after the urologic procedure as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for several days before and after the urologic procedure as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for several days before and after the urologic procedure as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for several days before and after the urologic procedure.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for several days before and after the urologic procedure as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for several days before and after the urologic procedure as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for several days before and after the urologic procedure as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for several days before and after the urologic procedure as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for several days before and after the urologic procedure.
-for the treatment of cystitis*:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 6 mg/kg/dose (Max: 200 mg/dose) PO once daily for 14 days.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 6 mg/kg/dose (Max: 200 mg/dose) IV once daily for 14 days.
-for the treatment of ascending pyelonephritis*:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 6 to 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 days.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 14 days as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 6 to 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 14 days.
-for the treatment of urinary fungal balls*:
Oral dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 14 days in addition to surgical removal as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg PO loading dose on day 1, followed by 9 mg/kg/dose PO once daily for 14 days in addition to surgical removal as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 14 days in addition to surgical removal as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg PO loading dose on day 1, followed by 12 mg/kg/dose PO once daily for 14 days in addition to surgical removal as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 6 to 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 days in addition to surgical removal.
Intravenous dosage:
Neonates younger than 30 weeks gestation and 0 to 90 days: 25 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 14 days in addition to surgical removal as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates younger than 30 weeks gestation and 0 to 90 days on ECMO: 35 mg/kg IV loading dose on day 1, followed by 9 mg/kg/dose IV once daily for 14 days in addition to surgical removal as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older: 25 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 14 days in addition to surgical removal as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Neonates 30 weeks gestation and older on ECMO: 35 mg/kg IV loading dose on day 1, followed by 12 mg/kg/dose IV once daily for 14 days in addition to surgical removal as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis.
Infants, Children, and Adolescents: 6 to 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 14 days in addition to surgical removal.

For candidiasis prophylaxis*:
-for candidiasis prophylaxis in very low birthweight and extremely low birthweight premature neonates*:
Oral dosage:
Premature Neonates weighing less than 750 g: 3 to 6 mg/kg/dose PO twice weekly for 6 weeks in nurseries with high rates (more than 10%) of invasive candidiasis. Twice weekly regimens have been found to be as effective as more frequent schedules. Additionally, in a retrospective study, the incidence of cholestasis was higher in neonates who received more frequent dosing compared to those who received the twice weekly regimen (42.9% vs. 28.8%; p = 0.035). Although guidelines and several published studies recommend the use of fluconazole prophylaxis for neonates weighing less than 1,000 g, the safety and efficacy of fluconazole for the prophylaxis of invasive candidiasis in premature neonates weighing less than 750 g have not been established. In a prospective, randomized, double-blind, placebo-controlled, multicenter study (n = 361) evaluating fluconazole prophylaxis (6 mg/kg/dose given twice weekly for 6 weeks) in premature neonates weighing less than 750 g, the primary endpoint of death or candidiasis by study day 49 was similar in those who received fluconazole vs. placebo (17.5% vs. 22%; difference, -4.4 (95% CI: -12.6 to 3.8); p = 0.3). Death occurred in approximately 14% of patients in each group and candidiasis occurred in 3% and 9% of patients in the fluconazole and placebo groups, respectively. In another study evaluating the long-term outcomes (8 to 10 life years) of fluconazole prophylaxis (n = 38) in extremely low birth weight infants, no differences in neurodevelopment or quality of life were noted between fluconazole-treated patients and placebo-treated patients.
Premature Neonates weighing 750 to 1,500 g: 3 to 6 mg/kg/dose PO twice weekly for 6 weeks in nurseries with high rates (more than 10%) of invasive candidiasis. Twice weekly regimens have been found to be as effective as more frequent schedules. Additionally, in a retrospective study, the incidence of cholestasis was higher in neonates who received more frequent dosing compared to those who received the twice weekly regimen (42.9% vs. 28.8%; p = 0.035). Guidelines and several published studies limit the use of fluconazole prophylaxis to neonates weighing less than 1,000 g; however, some experts suggest considering prophylaxis for those neonates weighing less than 1,500 g who are at particularly high risk. In a study evaluating the long-term outcomes (8 to 10 life years) of fluconazole prophylaxis (n = 38) in extremely low birth weight infants, no differences in neurodevelopment or quality of life were noted between fluconazole-treated patients and placebo-treated patients.
Intravenous dosage:
Premature Neonates weighing less than 750 g: 3 to 6 mg/kg/dose IV twice weekly for 6 weeks in nurseries with high rates (more than 10%) of invasive candidiasis. Twice weekly regimens have been found to be as effective as more frequent schedules. Additionally, in a retrospective study, the incidence of cholestasis was higher in neonates who received more frequent dosing compared to those who received the twice weekly regimen (42.9% vs. 28.8%; p = 0.035). Although guidelines and several published studies recommend the use of fluconazole prophylaxis for neonates weighing less than 1,000 g, the safety and efficacy of fluconazole for the prophylaxis of invasive candidiasis in premature neonates weighing less than 750 g have not been established. In a prospective, randomized, double-blind, placebo-controlled, multicenter study (n = 361) evaluating fluconazole prophylaxis (6 mg/kg/dose given twice weekly for 6 weeks) in premature neonates weighing less than 750 g the primary endpoint of death or candidiasis by study day 49 was similar in those who received fluconazole vs. placebo (17.5% vs. 22%; difference, -4.4 (95% CI: -12.6 to 3.8); p = 0.3). Death occurred in approximately 14% of patients in each group and candidiasis occurred in 3% and 9% of patients in the fluconazole and placebo groups, respectively. In another study evaluating the long-term outcomes (8 to 10 life years) of fluconazole prophylaxis (n = 38) in extremely low birth weight infants, no differences in neurodevelopment or quality of life were noted between fluconazole-treated patients and placebo-treated patients.
Premature Neonates weighing 750 to 1,500 g: 3 to 6 mg/kg/dose IV twice weekly for 6 weeks in nurseries with high rates (more than 10%) of invasive candidiasis. Twice weekly regimens have been found to be as effective as more frequent schedules. Additionally, in a retrospective study, the incidence of cholestasis was higher in neonates who received more frequent dosing compared to those who received the twice weekly regimen (42.9% vs. 28.8%; p = 0.035). Guidelines and several published studies limit the use of fluconazole prophylaxis to neonates weighing less than 1,000 g; however, some experts suggest considering prophylaxis for those neonates weighing less than 1,500 g who are at particularly high risk. In a study evaluating the long-term outcomes (8 to 10 life years) of fluconazole prophylaxis (n = 38) in extremely low birth weight infants, no differences in neurodevelopment or quality of life were noted between fluconazole-treated patients and placebo-treated patients.
-for candidiasis prophylaxis in hematopoietic stem cell transplant (HSCT) recipients and patients with chemotherapy-induced neutropenia*:
Oral dosage:
Infants and Children: 3 to 6 mg/kg/dose (Max: 600 mg/dose) PO once daily. Higher doses (8 mg/kg/day; Max: 400 mg/day) have been reported in pediatric HSCT recipients. For patients receiving chemotherapy, initiate prophylaxis with induction chemotherapy and continue for the duration of neutropenia. Guidelines for preventing opportunistic infections in HSCT recipients recommend initiating antifungal prophylaxis at the start of conditioning and continuing until engraftment or 7 days after the ANC is more than 1,000 cells/mm3.
Adolescents: 3 to 6 mg/kg/dose (Max: 400 mg/dose) PO once daily. Higher doses (8 mg/kg/day; Max: 400 mg/day) have been reported in pediatric HSCT recipients. For patients receiving chemotherapy, initiate prophylaxis with induction chemotherapy and continue for the duration of neutropenia. Guidelines for preventing opportunistic infections in HSCT recipients recommend initiating antifungal prophylaxis at the start of conditioning and continuing until engraftment or 7 days after the ANC is more than 1,000 cells/mm3.
Intravenous dosage:
Infants and Children: 3 to 6 mg/kg/dose (Max: 600 mg/dose) IV once daily. Higher doses (8 mg/kg/day; Max: 400 mg/day) have been reported in pediatric HSCT recipients. For patients receiving chemotherapy, initiate prophylaxis with induction chemotherapy and continue for the duration of neutropenia. Guidelines for preventing opportunistic infections in HSCT recipients recommend initiating antifungal prophylaxis at the start of conditioning and continuing until engraftment or 7 days after the ANC is more than 1,000 cells/mm3.
Adolescents: 3 to 6 mg/kg/dose (Max: 400 mg/dose) IV once daily. Higher doses (8 mg/kg/day; Max: 400 mg/day) have been reported in pediatric HSCT recipients. For patients receiving chemotherapy, initiate prophylaxis with induction chemotherapy and continue for the duration of neutropenia. Guidelines for preventing opportunistic infections in HSCT recipients recommend initiating antifungal prophylaxis at the start of conditioning and continuing until engraftment or 7 days after the ANC is more than 1,000 cells/mm3.
-for secondary oropharyngeal candidiasis prophylaxis* (i.e., long-term suppressive therapy) in persons living with HIV:
Oral dosage:
Infants and Children: 3 to 6 mg/kg/dose (Max: 200 mg/dose) PO once daily may be considered for persons with frequent or severe recurrences. Discontinuation of secondary prophylaxis is reasonable when the CD4 count or percentage has risen to CDC Immunologic Category 1 or 2. Routine primary candidiasis prophylaxis is not recommended.
Adolescents: 100 mg PO once daily or 3 times weekly may be considered for persons who have frequent or severe recurrences. Discontinuation of secondary prophylaxis is reasonable when the CD4 count is more than 200 cells/mm3 after the start of antiretroviral therapy. Routine primary candidiasis prophylaxis is not recommended.
-for secondary esophageal candidiasis prophylaxis* (i.e., long-term suppressive therapy) in persons living with HIV:
Oral dosage:
Infants and Children: 3 to 6 mg/kg/dose (Max: 200 mg/dose) PO once daily may be considered for persons with frequent or severe recurrences. Discontinuation of secondary prophylaxis is reasonable when the CD4 count or percentage has risen to CDC Immunologic Category 1 or 2. Routine primary candidiasis prophylaxis is not recommended.
Adolescents: 100 to 200 mg PO once daily may be considered for persons with frequent or severe recurrences. Discontinuation of secondary prophylaxis is reasonable when the CD4 count is more than 200 cells/mm3 after the start of antiretroviral therapy. Routine primary candidiasis prophylaxis is not recommended.

For surgical infection prophylaxis* in patients undergoing transplantation:
Intravenous dosage:
Infants, Children, and Adolescents: 6 mg/kg/dose IV as a single dose (Max: 400 mg/dose) within 60 minutes prior to the surgical incision. Fluconazole is recommended for patients at high risk for Candida infection (e.g., enteric drainage of pancreas) undergoing liver, kidney, or pancreas transplantation. No intraoperative redosing and a duration of prophylaxis less than 24 hours are recommended by guidelines.

For the treatment of vulvovaginal candidiasis* (VVC):
-for the treatment of uncomplicated VVC*:
Oral dosage:
Adolescents: 150 mg PO as a single dose.
-for the treatment of severe VVC* in persons without HIV:
Oral dosage:
Adolescents: 150 mg PO every 3 days for 2 to 3 doses.
-for the treatment of severe VVC* in persons living with HIV:
Oral dosage:
Adolescents: 100 to 200 mg PO daily for at least 7 days.
-for the treatment of recurrent VVC* in persons without HIV:
Oral dosage:
Adolescents: 100 to 200 mg PO every 3 days for a total of 3 doses or daily therapy with oral fluconazole for 10 to 14 days, followed by long-term suppressive therapy.
-for the treatment of recurrent VVC* in persons living with HIV:
Oral dosage:
Adolescents: 100 to 200 mg PO daily for at least 7 days, followed by long-term suppressive therapy.

For suppressive therapy for bacterial vaginosis*:
Oral dosage:
Adolescents: 150 mg PO once monthly plus metronidazole for recurrent bacterial vaginosis.

For the treatment of pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis*:
NOTE: For CNS disease, see meningitis.
-for the treatment of pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis* in persons without HIV:
Oral dosage:
Neonates: 6 to 12 mg/kg/dose PO once daily.
Infants and Children: 6 to 12 mg/kg/dose (Max: 400 mg/dose) PO once daily. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
Adolescents: 400 mg PO once daily. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
Intravenous dosage:
Neonates: 6 to 12 mg/kg/dose IV once daily.
Infants and Children: 6 to 12 mg/kg/dose (Max: 400 mg/dose) IV once daily. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
Adolescents: 400 mg IV once daily. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
-for the treatment of mild to moderate pulmonary coccidioidomycosis* in persons living with HIV:
NOTE: Mild to moderate infections may include patients with focal pneumonia or positive serology but with mild or without illness.
Oral dosage:
Infants and Children: 6 to 12 mg/kg/dose (Max: 400 mg/dose) PO once daily. Consider long-term suppressive therapy if CD4 count is less than 250 cells/mm3 or CD4% is less than 15%.
Adolescents: 400 mg PO once daily as preferred therapy. May discontinue therapy in patients who have clinically responded to 3 months or more of antifungal therapy and who have a CD4 count of 250 cells/mm3 or more, virological suppression on antiretrovirals, and continued monitoring for recurrence can be performed using serial chest radiograph and coccidioidal serology.
Intravenous dosage:
Infants and Children: 6 to 12 mg/kg/dose (Max: 400 mg/dose) IV once daily. Consider long-term suppressive therapy if CD4 count is less than 250 cells/mm3 or CD4% is less than 15%.
Adolescents: 400 mg IV once daily as preferred therapy. May discontinue therapy in patients who have clinically responded to 3 months or more of antifungal therapy and who have a CD4 count of 250 cells/mm3 or more, virological suppression on antiretrovirals, and continued monitoring for recurrence can be performed using serial chest radiograph and coccidioidal serology.
-for the treatment of severe pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis* in persons living with HIV:
Oral dosage:
Infants and Children: 12 mg/kg/dose (Max: 800 mg/dose) PO once daily after clinical improvement on amphotericin B. Continue therapy for at least 12 months, followed by long-term suppressive therapy. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
Adolescents: 400 mg PO once daily after clinical improvement on amphotericin B. Continue therapy for at least 12 months, followed by long-term suppressive therapy; discontinuation is dependent on clinical and serological response. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
Intravenous dosage:
Infants and Children: 12 mg/kg/dose (Max: 800 mg/dose) IV once daily after clinical improvement on amphotericin B. Continue therapy for at least 12 months, followed by long-term suppressive therapy. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
Adolescents: 400 mg IV once daily after clinical improvement on amphotericin B. Continue therapy for at least 12 months, followed by long-term suppressive therapy; discontinuation is dependent on clinical and serological response. Some experts will also add an azole to amphotericin B during the acute phase of treatment.

For coccidioidomycosis prophylaxis* (long-term suppressive therapy*):
-for primary coccidioidomycosis prophylaxis* (long-term suppressive therapy*) in persons living with HIV:
Oral dosage:
Adolescents: 400 mg PO once daily for asymptomatic persons with a new positive IgM or IgG serologic test and CD4 count less than 250 cells/mm3. Discontinue therapy when have a CD4 count of 250 cells/mm3 or more with virologic suppression on antivirals. Close clinical follow-up is recommended after discontinuation of the antifungal therapy.
-for secondary coccidioidomycosis prophylaxis* (long-term suppressive therapy*) in persons living with HIV after treatment for mild to moderate pulmonary coccidioidomycosis:
Oral dosage:
Infants and Children: 6 mg/kg/dose (Max: 400 mg) PO once daily. May consider discontinuation of therapy when have clinically responded and have a CD4 count of 250 cells/mm3 or more or CD4% of 15% or more.
Adolescents: 400 mg PO once daily. Discontinue therapy when have clinically responded to 3 months or more of antifungal therapy, a CD4 count of 250 cells/mm3 or more, virological suppression on antiretrovirals, and continued monitoring for recurrence can be performed using serial chest radiograph and coccidioidal serology.
-for secondary coccidioidomycosis prophylaxis* (long-term suppressive therapy*) in persons living with HIV after treatment for severe pulmonary or nonmeningeal, extrapulmonary disease:
Oral dosage:
Infants and Children: 6 mg/kg/dose (Max: 400 mg) PO once daily. Prophylaxis is lifelong.
Adolescents: 400 mg PO once daily. Prophylaxis may be lifelong; discontinuation is dependent on clinical and serological response.
-for secondary coccidioidomycosis prophylaxis* (long-term suppressive therapy*) after treatment for meningitis:
Oral dosage:
Infants and Children: 6 mg/kg/dose (Max: 400 mg) PO once daily. Prophylaxis is lifelong.
Adolescents: 400 mg PO once daily. Prophylaxis is lifelong.

For the treatment of disseminated (nonmeningeal) or pulmonary cryptococcosis*:
NOTE: For the treatment of CNS infections, see cryptococcal meningitis.
-for the treatment of focal pulmonary disease or isolated cryptococcal antigenemia (serum LFA titer less than 1:320) in persons living with HIV:
Oral dosage:
Neonates: 12 mg/kg/dose PO loading dose on day 1, followed by 6 to 12 mg/kg/dose PO once daily; treatment duration is dependent on site/severity of infection and clinical response. After initial therapy, 6 mg/kg/dose PO once daily for at least 1 year as chronic suppressive therapy.
Infants and Children: 12 mg/kg/dose (Max: 600 mg/dose) PO loading dose on day 1, followed by 6 to 12 mg/kg/dose (Max: 600 mg/dose) PO once daily; treatment duration is dependent on site/severity of infection and clinical response. After initial therapy, 6 mg/kg/dose (Max: 200 mg/dose) PO once daily for at least 1 year as chronic suppressive therapy. Suppressive therapy may be discontinued after at least 1 year on chronic suppressive therapy in children 6 years and older if the patient remains asymptomatic and the CD4 count is 100 cells/mm3 or more with an undetectable viral load for more than 3 months on antiretroviral therapy. Restart suppressive therapy if CD4 count is less than 100 cells/mm3.
Adolescents: 400 to 800 mg PO once daily for 10 weeks, followed by 200 mg PO once daily for a total of 6 months.
Intravenous dosage:
Neonates: 12 mg/kg/dose IV loading dose on day 1, followed by 6 to 12 mg/kg/dose IV once daily; treatment duration is dependent on site/severity of infection and clinical response. After initial therapy, continue oral chronic suppressive therapy for at least 1 year.
Infants and Children: 12 mg/kg/dose (Max: 600 mg/dose) IV loading dose on day 1, followed by 6 to 12 mg/kg/dose (Max: 600 mg/dose) IV once daily; treatment duration is dependent on site/severity of infection and clinical response. After initial therapy, continue oral chronic suppressive therapy for at least 1 year.
-for the treatment of extrapulmonary or diffuse pulmonary disease or isolated cryptococcal antigenemia (serum LFA titer more than 1:640) in persons living with HIV:
Oral dosage:
Neonates: 12 mg/kg/dose PO loading dose on day 1, followed by 6 to 12 mg/kg/dose PO once daily; treatment duration is dependent on site/severity of infection and clinical response. After initial therapy, 6 mg/kg/dose PO once daily for at least 1 year as chronic suppressive therapy.
Infants and Children: 12 mg/kg/dose (Max: 600 mg/dose) PO loading dose on day 1, followed by 6 to 12 mg/kg/dose (Max: 600 mg/dose) PO once daily; treatment duration is dependent on site/severity of infection and clinical response. After initial therapy, 6 mg/kg/dose (Max: 200 mg/dose) PO once daily for at least 1 year as chronic suppressive therapy. Suppressive therapy may be discontinued after at least 1 year on chronic suppressive therapy in children 6 years and older if the patient remains asymptomatic and the CD4 count is 100 cells/mm3 or more with an undetectable viral load for more than 3 months on antiretroviral therapy. Restart suppressive therapy if CD4 count is less than 100 cells/mm3.
Adolescents: 800 or 1,200 mg PO once daily plus amphotericin B deoxycholate, liposomal amphotericin B, or flucytosine or 1,200 mg PO once daily as monotherapy for at least 2 weeks as an alternate induction therapy, followed by 800 mg PO once daily for at least 8 weeks as consolidation therapy. After 2 weeks, may reduce dose to 400 mg PO once daily for clinically stable patients with negative CSF cultures; increase dose to 1,200 mg PO once daily if CSF remains positive and repeat lumbar puncture in 2 weeks. Continue consolidation therapy for 8 weeks from negative CSF culture, followed by 200 mg PO once daily as chronic suppressive therapy. May increase dose to 400 mg PO once daily if fluconazole MIC is 8 mcg/mL or more. Suppressive therapy may be discontinued at least 1 year from start of antifungal therapy if patient remains asymptomatic and the CD4 count is 100 cells/mm3 or more with suppressed HIV RNA in response to effective antiretroviral therapy. Restart suppressive therapy if CD4 count is less than 100 cells/mm3.
Intravenous dosage:
Neonates: 12 mg/kg/dose IV loading dose on day 1, followed by 6 to 12 mg/kg/dose IV once daily; treatment duration is dependent on site/severity of infection and clinical response. After initial therapy, continue oral chronic suppressive therapy for at least 1 year.
Infants and Children: 12 mg/kg/dose (Max: 600 mg/dose) IV loading dose on day 1, followed by 6 to 12 mg/kg/dose (Max: 600 mg/dose) IV once daily; treatment duration is dependent on site/severity of infection and clinical response. After initial therapy, continue oral chronic suppressive therapy for at least 1 year.
Adolescents: 800 or 1,200 mg IV once daily plus amphotericin B deoxycholate, liposomal amphotericin B, or flucytosine or 1,200 mg IV once daily as monotherapy for at least 2 weeks as an alternate induction therapy, followed by oral fluconazole consolidation therapy and chronic suppressive therapy.
-for the treatment of mild to moderate non-CNS disease in organ transplant recipeints:
Oral dosage:
Neonates: 6 to 12 mg/kg/dose PO once daily for 6 to 12 months.
Infants, Children, and Adolescents: 6 to 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 6 to 12 months.
-for the treatment of moderately severe to severe non-CNS or disseminated disease in organ transplant recipients:
Oral dosage:
Neonates: 10 to 12 mg/kg/dose PO once daily for 8 weeks after the initial 2-week course of induction therapy, followed by 6 mg/kg/dose PO once daily for 6 to 12 months.
Infants, Children, and Adolescents: 10 to 12 mg/kg/dose (Max: 800 mg/dose) PO once daily for 8 weeks after the initial 2-week course of induction therapy, followed by 6 mg/kg/dose (Max: 400 mg/dose) PO once daily for 6 to 12 months.

For the treatment of cryptococcal meningitis:
-for the treatment of cryptococcal meningitis in persons living with HIV:
Oral dosage:
Neonates*: 12 mg/kg/dose PO loading dose on day 1, followed by 10 to 12 mg/kg/dose PO once daily plus amphotericin B or flucytosine for at least 2 weeks as an alternate induction therapy, followed by 10 to 12 mg/kg/dose PO once daily for at least 8 weeks as consolidation therapy. If induction therapy did not include fluconazole, begin consolidation therapy at 12 mg/kg/dose PO on day 1, then 10 to 12 mg/kg/dose PO once daily. Continue consolidation therapy for at least 8 weeks, followed by 6 mg/kg/dose PO once daily as chronic suppressive therapy.
Infants and Children: 12 mg/kg/dose (Max: 800 mg/dose) PO loading dose on day 1, followed by 10 to 12 mg/kg/dose (Max: 800 mg/dose) PO once daily plus amphotericin B or flucytosine for at least 2 weeks as an alternate induction therapy, followed by 10 to 12 mg/kg/dose (Max: 800 mg/dose) PO once daily for at least 8 weeks as consolidation therapy. If induction therapy did not include fluconazole, begin consolidation therapy at 12 mg/kg/dose (Max: 800 mg/dose) PO on day 1, then 10 to 12 mg/kg/dose (Max: 800 mg/dose) PO once daily. Continue consolidation therapy for at least 8 weeks, followed by 6 mg/kg/dose (Max: 200 mg/dose) PO once daily for at least 1 year as chronic suppressive therapy. Suppressive therapy may be discontinued after at least 1 year on chronic suppressive therapy in children 6 years and older if the patient remains asymptomatic and the CD4 count is 100 cells/mm3 or more with an undetectable viral load for more than 3 months on antiretroviral therapy. Restart suppressive therapy if CD4 count is less than 100 cells/mm3. The FDA-approved dosage is 12 mg/kg/dose PO on day 1, followed by 6 to 12 mg/kg/dose PO once daily for 10 to 12 weeks after CSF becomes negative, then 6 mg/kg/dose PO once daily.
Adolescents: 800 or 1,200 mg PO once daily plus amphotericin B deoxycholate, liposomal amphotericin B, or flucytosine or 1,200 mg PO once daily as monotherapy for at least 2 weeks as an alternate induction therapy, followed by 800 mg PO once daily for at least 8 weeks as consolidation therapy. After 2 weeks, may reduce dose to 400 mg PO once daily for clinically stable patients with negative CSF cultures; increase dose to 1,200 mg PO once daily if CSF remains positive and repeat lumbar puncture in 2 weeks. Continue consolidation therapy for 8 weeks from negative CSF culture, followed by 200 mg PO once daily as chronic suppressive therapy. May increase dose to 400 mg PO once daily if fluconazole MIC is 8 mcg/mL or more. Suppressive therapy may be discontinued at least 1 year from start of antifungal therapy if patient remains asymptomatic and the CD4 count is 100 cells/mm3 or more with suppressed HIV RNA in response to effective antiretroviral therapy. Restart suppressive therapy if CD4 count is less than 100 cells/mm3. The FDA-approved dose is 400 mg PO on day 1, followed by 200 to 400 mg PO once daily for 10 to 12 weeks after CSF becomes negative, then 200 mg PO once daily.
Intravenous dosage:
Neonates*: 12 mg/kg/dose IV loading dose on day 1, followed by 10 to 12 mg/kg/dose IV once daily plus amphotericin B or flucytosine for at least 2 weeks as an alternate induction therapy, followed by 10 to 12 mg/kg/dose IV once daily for at least 8 weeks as consolidation therapy. If induction therapy did not include fluconazole, begin consolidation therapy at 12 mg/kg/dose IV on day 1, then 10 to 12 mg/kg/dose IV once daily. Continue consolidation therapy for at least 8 weeks, followed by oral chronic suppressive therapy.
Infants and Children: 12 mg/kg/dose (Max: 800 mg/dose) IV loading dose on day 1, followed by 10 to 12 mg/kg/dose (Max: 800 mg/dose) IV once daily plus amphotericin B or flucytosine for at least 2 weeks as an alternate induction therapy, followed by 10 to 12 mg/kg/dose (Max: 800 mg/dose) IV once daily for at least 8 weeks as consolidation therapy. If induction therapy did not include fluconazole, begin consolidation therapy at 12 mg/kg/dose (Max: 800 mg/dose) IV on day 1, then 10 to 12 mg/kg/dose (Max: 800 mg/dose) IV once daily. Continue consolidation therapy for at least 8 weeks, followed by oral chronic suppressive therapy. The FDA-approved dosage is 12 mg/kg/dose IV on day 1, followed by 6 to 12 mg/kg/dose IV once daily for 10 to 12 weeks after CSF becomes negative, then 6 mg/kg/dose IV once daily.
Adolescents: 800 or 1,200 mg IV once daily plus amphotericin B deoxycholate, liposomal amphotericin B, or flucytosine or 1,200 mg IV once daily as monotherapy for at least 2 weeks as an alternate induction therapy, followed by oral fluconazole consolidation therapy and chronic suppressive therapy. The FDA-approved dose is 400 mg IV on day 1, followed by 200 to 400 mg IV once daily for 10 to 12 weeks after CSF becomes negative, then 200 mg IV once daily.
-for the treatment of cryptococcal meningitis in organ transplant recipients:
Oral dosage:
Neonates*: 10 to 12 mg/kg/dose PO once daily for 8 weeks after the initial 2-week course of induction therapy, followed by 6 mg/kg/dose PO once daily for 6 to 12 months.
Infants, Children, and Adolescents: 10 to 12 mg/kg/dose (Max: 800 mg/dose) PO once daily for 8 weeks after the initial 2-week course of induction therapy, followed by 6 mg/kg/dose (Max: 400 mg/dose) PO once daily for 6 to 12 months. The FDA-approved dosage is 12 mg/kg/dose PO on day 1, followed by 6 to 12 mg/kg/dose PO once daily for 10 to 12 weeks after CSF becomes negative, then 6 mg/kg/dose PO once daily.
-for the treatment of cryptococcal meningitis in non-HIV, nontransplant patients:
Oral dosage:
Neonates*: 10 to 12 mg/kg/dose PO once daily for 8 weeks after the initial 2-week course of induction therapy, followed by 6 mg/kg/dose PO once daily for 6 to 12 months.
Infants, Children, and Adolescents: 10 to 12 mg/kg/dose (Max: 800 mg/dose) PO once daily for 8 weeks after the initial 2-week course of induction therapy, followed by 6 mg/kg/dose (Max: 200 mg/dose) PO once daily for 6 to 12 months. The FDA-approved dose is 12 mg/kg/dose PO on day 1, followed by 6 to 12 mg/kg/dose PO once daily for 10 to 12 weeks after CSF becomes negative, then 6 mg/kg/dose PO once daily.

For the treatment of pulmonary or less severe disseminated histoplasmosis* in persons living with HIV:
-for the treatment of acute primary pulmonary histoplasmosis*:
Oral dosage:
Infants and Children: 3 to 6 mg/kg/dose (Max: 200 mg/dose) PO once daily for 12 months as an alternative to itraconazole.
-for the treatment of less severe disseminated histoplasmosis*:
Oral dosage:
Infants and Children: 5 to 6 mg/kg/dose (Max: 300 mg/dose) PO twice daily for at least 12 months as an alternative to itraconazole.
Adolescents: 800 mg PO once daily for at least 12 months as an alternative in patients who are intolerant to itraconazole.
Intravenous dosage:
Infants and Children: 5 to 6 mg/kg/dose (Max: 300 mg/dose) IV twice daily for 12 months as an alternative to itraconazole.

For secondary histoplasmosis prophylaxis* (i.e., long-term suppressive therapy) in persons living with HIV:
Oral dosage:
Infants and Children: 3 to 6 mg/kg/dose (Max: 200 mg/dose) PO once daily as an alternative to itraconazole for patients who remain immunosuppressed and in those who relapse despite appropriate initial therapy. Consider discontinuation if patients have received treatment for at least 1 year, have negative blood cultures, have a serum or urine Histoplasma antigen below the level of quantification, have an undetectable viral load, and have a CD4 percentage greater than 15% at any age or CD4 count of more than 150 cells/mm3 if older than 6 years. Resume secondary prophylaxis if the parameters are not met.
Adolescents: 400 mg PO once daily as an alternative to itraconazole for patients with severe disseminated or CNS infection after completing at least 12 months of therapy and relapse despite appropriate initial therapy. Consider discontinuation if patients have received treatment for at least 1 year, have negative blood cultures, have a serum or urine Histoplasma antigen below the level of quantification, have an undetectable viral load, and have more than 150 CD4 cells/mm3 on antiretroviral therapy for at least 6 months. Resume secondary prophylaxis if the CD4 count decreases below 150 cells/mm3.

For primary talaromycosis prophylaxis* in HIV-infected patients:
-for primary talaromycosis prophylaxis in HIV-infected patients residing in endemic areas*:
Oral dosage:
Adolescents: 400 mg PO once weekly as alternative therapy. Recommended for patients with CD4 count less than 100 cells/mm3 who are unable to have antiretroviral therapy (ART) or have treatment failure without access to effective ART options and who reside in the highly endemic regions in northern Thailand, Vietnam, or southern China. May discontinue if the CD4 count is more than 100 cells/mm3 for 6 months or more in response to ART or virologic suppression is achieved for 6 months or more on ART. Restart prophylaxis if CD4 count is less than 100 cells/mm3 and patient still resides in high-risk areas.
-for primary talaromycosis prophylaxis in HIV-infected patients traveling to endemic areas*:
Oral dosage:
Adolescents: 400 mg PO once weekly starting 3 days before travel and continuing for 1 week after leaving the endemic area as alternative therapy. Recommended for patients with CD4 count less than 100 cells/mm3 who are unable to have antiretroviral therapy (ART) or have treatment failure without access to effective ART options and who are from countries outside the highly endemic regions in northern Thailand, Vietnam, or southern China and must travel to the region. Restart prophylaxis if CD4 count is less than 100 cells/mm3 and patient still travels to high-risk areas.

For the treatment of cutaneous leishmaniasis*:
Oral dosage:
Infants, Children, and Adolescents: 5 mg/kg/dose PO once daily (Max: 200 mg/day). Higher doses (8 mg/kg/day) may be needed for incomplete clinical response.

For the treatment of tinea capitis*:
Oral dosage:
Infants, Children, and Adolescents: 6 mg/kg/dose (Usual Max: 400 mg/dose) PO once daily for 3 to 6 weeks or 8 mg/kg/dose (Usual Max: 400 mg/dose) PO once weekly for 8 to 12 weeks.

For vulvovaginal candidiasis prophylaxis*:
-for secondary vulvovaginal candidiasis prophylaxis* (i.e., long-term suppressive therapy) in persons without HIV:
Oral dosage:
Adolescents: 100 to 200 mg PO once weekly for 6 months may be considered for persons who have recurrent infections.
-for secondary vulvovaginal candidiasis prophylaxis* (i.e., long-term suppressive therapy) in persons living with HIV:
Oral dosage:
Adolescents: 150 mg PO once weekly may be considered for persons with frequent or severe recurrences. Discontinuation of secondary prophylaxis is reasonable when the CD4 count is more than 200 cells/mm3 after the start of antiretroviral therapy. Routine primary candidiasis prophylaxis is not recommended.

Maximum Dosage Limits:
-Neonates
younger than 30 weeks gestation and 0 to 90 days postnatal age: 25 mg/kg (35 mg/kg for patients on ECMO) PO/IV loading dose, then 9 mg/kg/day PO/IV.
30 weeks gestation and older: 25 mg/kg (35 mg/kg for patients on ECMO) PO/IV loading dose, then 12 mg/kg/day PO/IV.
-Infants
25 mg/kg (35 mg/kg for patients on ECMO) PO/IV loading dose, then 12 mg/kg/day PO/IV.
-Children
25 mg/kg (35 mg/kg for patients on ECMO) PO/IV loading dose (Max: 800 mg/dose), then 12 mg/kg/day (Max: 400 mg/day) PO/IV is FDA-approved maximum; however, doses up to 800 mg/day PO/IV have been used off-label.
-Adolescents
25 mg/kg (35 mg/kg for patients on ECMO) PO/IV loading dose (Max: 800 mg/dose), then 12 mg/kg/day (Max: 400 mg/day) PO/IV is FDA-approved maximum; however, doses up to 1,200 mg/day PO/IV have been used off-label.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
NOTE: No dosage adjustments are required for single-dose therapy. For multiple-dose regimens, the following adjustments are suggested; further adjustments may be needed depending upon the clinical situation.

Neonates*

Serum creatinine (SCr) less than 1.3 mg/dL: No dosage adjustment needed
Serum creatinine (SCr) 1.3 mg/dL or more: Consider extending the dosage interval (e.g., every 48 to 72 hours) depending on the degree of renal impairment.

Infants, Children, and Adolescents

CrCl more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
CrCl 10 to 50 mL/minute/1.73 m2: Administer usual loading dose, then reduce maintenance dose by 50%.
CrCl less than 10 mL/minute/1.73 m2: Administer usual loading dose, then reduce maintenance dose by 50% and administer every 48 hours.

Intermittent hemodialysis
NOTE: A 3-hour hemodialysis session decreases plasma concentrations by approximately 50%.

FDA-approved labeling
Administer 100% of the usual daily dose after each dialysis session; on non-dialysis days, administer a reduced dose based on creatinine clearance. Further adjustments may be needed depending upon the clinical situation.

Alternative*
Administer usual loading dose, then reduce maintenance dose by 50% and administer every 48 hours (after dialysis).

Peritoneal hemodialysis*
Administer usual loading dose, then reduce maintenance dose by 50% and administer every 48 hours.

Continuous renal replacement therapy (CRRT)*
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered. Pediatric recommendations are based on limited study data, mainly derived from adult patients, and extrapolation of CRRT clearance based on fluconazole pharmacokinetic parameters.
6 mg/kg/dose IV or PO every 24 hours has generally been suggested for CRRT. Specific recommendations for patients receiving CAVH/CVVH and CAVHD/CVVHD based on dialysate flow rate include the following:
Dialysate flow rate (ultrafiltration rate + dialysis inflow rate) less than 1,500 mL/m2/hour: Administer usual loading dose, then administer 3 to 12 mg/kg/dose IV or PO every 24 hours.
Dialysate flow rate (ultrafiltration rate + dialysis inflow rate) 1,500 mL/m2/hour or more: Administer usual loading dose, then administer 6 to 12 mg/kg/dose IV or PO every 24 hours.

Hybrid hemodialysis*
NOTE: Hybrid treatments include prolonged intermittent renal replacement therapy (PIRRT), sustained low-efficiency dialysis (SLED), slow extended daily dialysis/diafiltration (SLEDD-f), and extended daily dialysis (EDD). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), the type of infection, the duration of renal replacement therapy, the ultrafiltration rate, the dialysis flow rate, and how often dialysis sessions occur.
Fluconazole dosing data are not available in pediatric patients receiving hybrid hemodialysis. Based on adult data, dosage adjustments may be necessary.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Fluconazole is a fungistatic antifungal agent with concentration-independent activity. Like other azole antifungals, fluconazole exerts its effect by altering the fungal cell membrane. Fluconazole inhibits ergosterol synthesis by interacting with 14-alpha demethylase, a cytochrome P450 enzyme that is needed to convert lanosterol to ergosterol, an essential component of the membrane. Inhibition of ergosterol synthesis results in increased cellular permeability causing leakage of cellular contents. Fluconazole does not appear to have the same activity on human cholesterol synthesis. Other antifungal effects of azole compounds have been proposed and include inhibition of endogenous respiration, interaction with membrane phospholipids, and inhibition of the transformation of yeasts to mycelial forms. Other mechanisms may involve inhibition of purine uptake and impairment of triglyceride and/or phospholipid biosynthesis.

The Clinical and Laboratory Standards Institute (CLSI) defines minimum inhibitory concentrations (MICs) for C. albicans, C. parapsilosis, and C. tropicalis as susceptible at 2 mcg/mL or less, susceptible dose-dependent (SDD) at 4 mcg/mL, and resistant at 8 mcg/mL or more. For C. glabrata, isolates are defined as SDD at 32 mcg/mL or less and resistant at 64 mcg/mL or more. C. krusei is considered intrinsically resistant to fluconazole.

The emergence of fungal organisms resistant to fluconazole, especially Candida species, is problematic. Increased frequency of non-Candida albicans species as causes of fungemia has been correlated in epidemiologic studies with the increased use of fluconazole both for prophylaxis and treatment. These non-Candida albicans species are often more resistant to fluconazole. Data indicate the annual incidence of fluconazole-resistant oropharyngeal candidiasis in persons with AIDS is roughly 5%. Consider susceptibility testing of invasive C. albicans isolates for persons with persistent candidemia or progressive disseminated candidiasis, despite fluconazole therapy, and on non-Candida albicans isolates (e.g., C. glabrata, C. tropicalis, or C. parapsilosis) from persons with candidemia or invasive disease.

Pharmacokinetics: Fluconazole is administered orally and intravenously. The pharmacokinetics of both IV and oral fluconazole are similar. Peak serum concentrations and AUC increase in proportion to the dose. Steady-state fluconazole plasma concentrations are achieved within 5 to 10 days at doses within the adult dosage range of 50 to 400 mg/day, and within 2 days when a loading dose of twice the usual daily dosage is given on the first day of therapy. Fluconazole is widely distributed into body tissues and fluids; the apparent volume of distribution approximates that of total body water. Saliva, sputum, nail, blister, and vaginal tissue concentrations are approximately equal to plasma concentrations. Urine and skin concentrations are approximately 10 times that of plasma concentrations. Fluconazole distributes well into the CSF, and achieves CSF concentrations that are 50% to 90% of plasma concentrations, regardless of the degree of meningeal inflammation. Plasma protein binding is low and ranges from 11% to 12%. Fluconazole does not appear to undergo first-pass metabolism. Elimination is mainly renal; about 65% to 80% of a dose is excreted in the urine unchanged and 11% as metabolites. A clearance of approximately 0.23 mL/kg/minute has been reported for adults. Small amounts of fluconazole are excreted in the feces. Plasma elimination half-life in adults with normal renal function is approximately 30 hours (range: 20 to 50 hours).

Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9, CYP2C19, CYP3A4, UGT2B7
Fluconazole potently inhibits CYP2C19 and moderately inhibits CYP2C9 and CYP3A4. The extent of CYP3A4 inhibition is less than with ketoconazole or itraconazole. In vitro studies have also shown fluconazole to be a concentration-dependent inhibitor of uridine diphosphoglucuronosyltransferase UGT2B7.


-Route-Specific Pharmacokinetics
Oral Route
Fluconazole is well absorbed after oral administration with a bioavailability of approximately 90%. Peak concentrations are reached approximately 1 to 2 hours after administration. Food does not affect the absorption. Bioequivalence has been established between the suspension and tablet formulations.

Intravenous Route
Peak concentrations are reached approximately 1 to 2 hours after administration.


-Special Populations
Pediatrics
Neonates and Infants 1 to 2 months

Clearance of fluconazole is prolonged in neonates and young infants compared with children and adults and increases with postnatal age (PNA). In a pharmacokinetic study in premature neonates (gestational age (GA) 26 to 29 weeks), mean total clearance corrected for weight was 0.18 mL/minute/kg (n = 7), 0.33 mL/minute/kg (n = 7), and 0.52 mL/minute/kg (n = 4) at postnatal ages 1 day, 7 days, and 13 days, respectively. Corresponding mean elimination half-lives were 88.6 hours, 67.5 hours, and 55.2 hours, respectively. In another study in 8 neonates and young infants (GA 35 to 38 weeks; PNA 6 to 59 days), the mean clearance and elimination half-life were 0.29 mL/minute/kg and 54.2 hours, respectively. Volume of distribution of fluconazole is also greatest in the neonatal period, with values of approximately 1 to 2.25 L/kg reported. Because of the large volume of distribution and slow elimination, the use of a loading dose on day 1 of therapy is recommended to achieve therapeutic serum concentrations faster. In a study of 13 premature and term patients (median GA of 37 weeks, range: 24 to 39 weeks; median PNA 19 days, range: 5 to 262 days), of the 12 patients who received a 25 mg/kg loading dose, 9 patients achieved an AUC0-24 of more than 400 mg x hour/L in the first 24 hours. A population pharmacokinetic model using data from 55 pediatric patients (GA 23 to 40 weeks, PNA 1 to 88 days) found that a loading dose of 25 mg/kg is necessary to reach target AUC more than 400 mg x hour/L within 24 hours of initiating therapy in patients younger than 3 months. Additionally, data from a population pharmacokinetic study using Monte Carlo simulations of premature and term neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC of 50 or more for Candida species with an MIC of 8 mcg/mL or less) in 90% of neonates younger than 30 weeks gestation and 80% of neonates 30 to 40 weeks gestation. A maintenance dose of 9 mg/kg once daily is recommended in neonates younger than 30 weeks GA and 12 mg/kg once daily is recommended in neonates 30 weeks GA and older.

Infants, Children, and Adolescents 3 months to 17 years

The clearance of fluconazole is greater in pediatric patients compared to adults. A clearance and elimination half-life of approximately 0.4 to 0.66 mL/kg/minute and 15 to 25 hours, respectively, have been reported in pediatric patients 9 months and older. Volume of distribution is also greater in children compared with adults. A mean volume of distribution of 0.95 L/kg and 0.7 L/kg has been reported for children and adolescents, respectively. The value in adolescents is similar to what has been reported in adults.

Pediatric Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)
A population PK model using data from 21 pediatric patients ages from birth to 17 years supported with ECMO and 19 pediatric non-ECMO patients ages from birth to 2 years found that clearance was related to serum creatinine, while a higher volume of distribution was related to presence of ECMO support. The median volume of distribution was 1.3 L/kg in pediatric patients on ECMO and 0.9 L/kg in those not on ECMO. Simulations suggested that a loading dose of 35 mg/kg is needed to achieve the target AUC0-24 more than 400 mg x hour/L within the first 24 hours in pediatric patients on ECMO.

Renal Impairment
Fluconazole clearance is significantly reduced in patients with renal impairment. A 3-hour hemodialysis session reduces plasma concentrations by approximately 50%. In a study in 17 children with renal impairment, the elimination half-life of fluconazole was approximately 72 hours in patients requiring peritoneal dialysis (PD) compared with approximately 31 hours in children in the non-PD group (mild renal impairment; mean CrCl 26 mL/minute/1.73 m2).