PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Azole Antifungals

    DEA CLASS

    Rx

    DESCRIPTION

    First triazole synthetic antifungal agent
    Used for treatment of various Candida infections, cryptococcal meningitis, and prophylaxis in BMT patients
    Associated with increased incidence of Candida krusei when used for prophylaxis

    COMMON BRAND NAMES

    Diflucan

    HOW SUPPLIED

    Diflucan/Fluconazole Oral Pwd F/Recon: 1mL, 10mg, 40mg
    Diflucan/Fluconazole Oral Tab: 50mg, 100mg, 150mg, 200mg
    Diflucan/Fluconazole/Fluconazole, Dextrose Intravenous Inj Sol: 1mL, 2mg, 100mL, 200mg, 200mL, 400mg, 200-5%, 400-5%

    DOSAGE & INDICATIONS

    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 chronic disseminated (hepatosplenic) candidiasis† as step-down therapy.
    Oral dosage
    Adults

    400 mg 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.

    Infants, Children, and Adolescents

    12 mg/kg/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. In general, doses exceeding 600 mg are not recommended. Treat until lesions resolve on repeat imaging, which is usually several months.

    Intravenous dosage
    Adults

    400 mg 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.

    Infants, Children, and Adolescents

    12 mg/kg/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. In general, doses exceeding 600 mg are not recommended. Treat until lesions resolve on repeat imaging, which is usually several months.

    For the treatment of candidemia and invasive candidiasis (non-CNS).
    Oral dosage
    Adults

    800 mg PO once, then 400 mg 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. The FDA-approved dosage is 400 mg PO once daily. 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 6 months to 17 years

    12 mg/kg/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. The FDA-approved dosage is 6 to 12 mg/kg/dose PO once daily. In general, doses exceeding 600 mg are not recommended. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.

    Infants 1 to 5 months†

    12 mg/kg/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.

    Neonates†

    12 mg/kg/dose PO once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. A loading dose of 25 mg/kg PO is recommended on day 1 to achieve therapeutic concentrations faster. A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 93% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates.   However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).   Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.

    Intravenous dosage
    Adults

    800 mg IV once, then 400 mg 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. The FDA-approved dosage is 400 mg IV once daily. 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 6 months to 17 years

    12 mg/kg/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. The FDA-approved dosage is 6 to 12 mg/kg/dose IV every 24 hours. In general, doses exceeding 600 mg are not recommended. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.

    Infants 1 to 5 months†

    12 mg/kg/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.

    Neonates†

    12 mg/kg/dose IV once daily as an alternative therapy in patients who have not been receiving fluconazole prophylaxis. A loading dose of 25 mg/kg IV is recommended on day 1 to achieve therapeutic concentrations faster. A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 93% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates.   However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).   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 oropharyngeal candidiasis (thrush).
    For the initial treatment of oropharyngeal candidiasis in persons without HIV.
    Oral dosage
    Adults

    100 to 200 mg PO once daily for 7 to 14 days for moderate to severe disease. The FDA-approved dosage is 200 mg PO once, then 100 mg PO once daily for at least 14 days to decrease the likelihood of relapse.

    Infants, Children, and Adolescents 6 months to 17 years

    6 mg/kg/dose (Max: 200 mg/dose) PO once, then 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.

    Infants 1 to 5 months†

    6 mg/kg/dose PO once, then 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.

    Neonates†

    6 mg/kg/dose PO once, then 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. Although there has been some debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates with candidiasis. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.

    Intravenous dosage
    Adults

    100 to 200 mg IV once daily for 7 to 14 days for moderate to severe disease. The FDA-approved dosage is 200 mg IV once, then 100 mg IV once daily for at least 14 days to decrease the likelihood of relapse.

    Infants, Children, and Adolescents 6 months to 17 years

    6 mg/kg/dose (Max: 200 mg/dose) IV once, then 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.

    Infants 1 to 5 months†

    6 mg/kg/dose IV once, then 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.

    Neonates†

    6 mg/kg/dose IV once, then 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. Although there has been some debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates with candidiasis. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.

    For the initial treatment of oropharyngeal candidiasis in persons living with HIV.
    Oral dosage
    Adults

    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.

    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.

    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.

    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.

    Intravenous dosage
    Adults

    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.

    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.

    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.

    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.

    For the treatment of esophageal candidiasis .
    For the initial treatment of esophageal candidiasis in persons without HIV.
    Oral dosage
    Adults

    200 to 400 mg PO once daily for 14 to 21 days. The FDA-approved dosage is 200 mg PO once, then 100 mg PO once daily for a minimum of 3 weeks and for 2 weeks after resolution of symptoms.

    Infants, Children, and Adolescents 6 months to 17 years

    6 mg/kg/dose (Max: 400 mg/dose) PO once, then 3 to 6 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 to 21 days. The FDA-approved dosage is 6 mg/kg/dose PO once, then 3 mg/kg/dose PO once daily for a minimum of 3 weeks and for 2 weeks after resolution of symptoms. 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 once, then 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.

    Neonates†

    6 mg/kg/dose PO once, then 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 based on medical judgement and response to therapy. Although there has been some debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates with candidiasis. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.

    Intravenous dosage
    Adults

    200 to 400 mg IV once daily for 14 to 21 days. The FDA-approved dosage is 200 mg IV once, then 100 mg IV once daily for a minimum of 3 weeks and for 2 weeks after resolution of symptoms.

    Infants, Children, and Adolescents 6 months to 17 years

    6 mg/kg/dose (Max: 400 mg/dose) IV once, then 3 to 6 mg/kg/dose (Max: 400 mg/dose) IV once daily for 14 to 21 days. The FDA-approved dosage is 6 mg/kg/dose IV once, then 3 mg/kg/dose IV once daily for a minimum of 3 weeks and for 2 weeks after resolution of symptoms. Doses up to 12 mg/kg/day (Max: 400 mg/day) IV may be used if clinical condition warrants more aggressive dosing.

    Infants 1 to 5 months†

    6 mg/kg/dose IV once, then 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.

    Neonates†

    6 mg/kg/dose IV once, then 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 based on medical judgement and response to therapy. Although there has been some debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates with candidiasis.    However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.

    For the initial treatment of esophageal candidiasis in persons living with HIV.
    Oral dosage
    Adults

    100 to 400 mg PO once daily for 14 to 21 days.

    Adolescents

    100 to 400 mg 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.

    Infants 1 to 5 months†

    6 to 12 mg/kg/dose PO once daily for 14 to 21 days.

    Intravenous dosage
    Adults

    100 to 400 mg IV once daily for 14 to 21 days.

    Adolescents

    100 to 400 mg 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.

    Infants 1 to 5 months†

    6 to 12 mg/kg/dose IV once daily for 14 to 21 days.

    For the treatment of pneumonia caused by Candida sp..
    Oral dosage
    Adults

    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, 800 mg (12 mg/kg) PO once, then 400 mg (6 mg/kg) PO once daily is recommended by guidelines 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. The FDA-approved dosage is 400 mg PO once daily.

    Infants, Children, and Adolescents

    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, 12 mg/kg/dose PO once daily is recommended by guidelines 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. The FDA-approved dosage is 6 to 12 mg/kg/dose PO once daily. In general, doses exceeding 600 mg are not recommended.

    Neonates

    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, 12 mg/kg/dose PO once daily is recommended by guidelines as an alternative therapy to amphotericin B deoxycholate in patients who have not been receiving fluconazole prophylaxis. Others have recommended a range of 6 to 12 mg/kg/dose PO every 24 to 72 hours. There is some debate about the optimal dosing frequency in neonates; however, some pharmacokinetic data and guidelines support every 24-hour dosing. Data from a population pharmacokinetic study in neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC more than 50 for Candida species with an MIC less than 8 mcg/mL) in 90% of neonates less than 30 weeks gestational age and 80% of neonates 30 to 40 weeks gestational age. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). The FDA-approved product labeling suggests a dosing interval of every 72 hours during the first 2 weeks of life based on early pharmacokinetic data in premature neonates (gestational age 26 to 29 weeks); the approved product labeling from the United Kingdom also recommends a dosing interval of every 72 hours during the first 2 weeks of life.

    Intravenous dosage
    Adults

    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, 800 mg (12 mg/kg) IV once, then 400 mg (6 mg/kg) IV once daily is recommended by guidelines 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. The FDA-approved dosage is 400 mg IV once daily.

    Infants, Children, and Adolescents

    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, 12 mg/kg/dose IV once daily is recommended by guidelines 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. The FDA-approved dosage is 6 to 12 mg/kg/dose IV every 24 hours. In general, doses exceeding 600 mg are not recommended.

    Neonates

    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, 12 mg/kg/dose IV once daily is recommended by guidelines as an alternative therapy to amphotericin B deoxycholate in patients who have not been receiving fluconazole prophylaxis. Others have recommended a range of 6 to 12 mg/kg/dose IV every 24 to 72 hours. There is some debate about the optimal dosing frequency in neonates; however, some pharmacokinetic data and guidelines support every 24-hour dosing. Data from a population pharmacokinetic study in neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC more than 50 for Candida species with an MIC less than 8 mcg/mL) in 90% of neonates less than 30 weeks gestational age and 80% of neonates 30 to 40 weeks gestational age. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). The FDA-approved product labeling suggests a dosing interval of every 72 hours during the first 2 weeks of life based on early pharmacokinetic data in premature neonates (gestational age 26 to 29 weeks); the approved product labeling from the United Kingdom also recommends a dosing interval of every 72 hours during the first 2 weeks of life. 

    For the treatment of Candida urinary tract infection (UTI), including candiduria, symptomatic cystitis, and pyelonephritis.
    For the treatment of nonspecific urinary tract infections.
    Intravenous dosage
    Adults

    50 to 200 mg IV once daily is the general dosage recommended in the FDA-approved labeling for urinary tract infections.

    Oral dosage
    Adults

    50 to 200 mg PO once daily is the general dosage recommended in the FDA-approved labeling for urinary tract infections.

    For the treatment of symptomatic cystitis.
    Intravenous dosage
    Adults

    200 mg IV once daily for 14 days.

    Infants†, Children†, and Adolescents†

    6 mg/kg/dose (Max: 200 mg/dose) IV once daily for 14 days.

    Neonates†

    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.[60487] A loading dose of 25 mg/kg IV is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Oral dosage
    Adults

    200 mg PO once daily for 14 days.

    Infants†, Children†, and Adolescents†

    6 mg/kg/dose (Max: 200 mg/dose) PO once daily for 14 days.

    Neonates†


    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.[60487] A loading dose of 25 mg/kg PO is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of asymptomatic cystitis in patients undergoing urologic procedures.
    Intravenous dosage
    Adults

    400 mg IV once daily for several days before and after the urologic procedure.

    Infants†, Children†, and Adolescents†

    12 mg/kg/dose (Max: 400 mg/dose) IV once daily for several days before and after the urologic procedure.

    Neonates†

    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.[60487] A loading dose of 25 mg/kg IV is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Oral dosage
    Adults

    400 mg PO once daily for several days before and after the urologic procedure.

    Infants†, Children†, and Adolescents†

    12 mg/kg/dose (Max: 400 mg/dose) PO once daily for several days before and after the urologic procedure.

    Neonates†

    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.[60487] A loading dose of 25 mg/kg PO is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of urinary fungal balls.
    Intravenous dosage
    Adults

    200 to 400 mg IV once daily for 14 days in addition to surgical removal.

    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.

    Neonates†

    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.[60487] A loading dose of 25 mg/kg IV is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Oral dosage
    Adults

    200 to 400 mg PO once daily for 14 days in addition to surgical removal.

    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.

    Neonates†

    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.[60487] A loading dose of 25 mg/kg PO is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of asymptomatic cystitis in very-low-birth-weight infants (weight less than 1.5 kg).
    Intravenous dosage
    Neonates†

    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.[60487] A loading dose of 25 mg/kg IV is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Oral dosage
    Neonates†

    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.[60487] A loading dose of 25 mg/kg PO is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the initial treatment of asymptomatic cystitis in neutropenic patients.
    Intravenous dosage
    Adults

    800 mg IV once, then 400 mg IV once daily for 14 days is recommended by guidelines 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†

    12 mg/kg/dose IV once daily for 14 days is recommended by guidelines 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. In general, doses exceeding 600 mg are not recommended.

    Oral dosage
    Adults

    800 mg PO once, then 400 mg PO once daily for 14 days is recommended by guidelines 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†

    12 mg/kg/dose PO once daily for 14 days is recommended by guidelines 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. In general, doses exceeding 600 mg are not recommended.

    For stepdown treatment of asymptomatic cystitis in neutropenic patients.
    Intravenous dosage
    Adults

    400 mg 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.

    Infants†, Children†, and Adolescents†

    12 mg/kg/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. In general, doses exceeding 600 mg are not recommended.

    Oral dosage
    Adults

    400 mg 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.

    Infants†, Children†, and Adolescents†

    12 mg/kg/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. In general, doses exceeding 600 mg are not recommended.

    For the treatment of symptomatic ascending pyelonephritis.
    Intravenous dosage
    Adults

    200 to 400 mg IV once daily for 14 days.

    Infants†, Children†, and Adolescents†

    6 to 12 mg/kg/dose (Max: 400 mg/dose) IV once daily for 14 days.

    Neonates†

    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.[60487] A loading dose of 25 mg/kg IV is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Oral dosage
    Adults

    200 to 400 mg PO once daily for 14 days.

    Infants†, Children†, and Adolescents†

    6 to 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 days.

    Neonates†

    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.[60487] A loading dose of 25 mg/kg PO is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of vulvovaginal candidiasis (VVC).
    For the treatment of uncomplicated VVC.
    Oral dosage
    Adults

    150 mg PO as a single dose.

    Adolescents†

    150 mg PO as a single dose.

    For the treatment of severe VVC† in persons without HIV.
    Oral dosage
    Adults

    150 mg PO every 3 days for 2 to 3 doses.

    Adolescents

    150 mg PO every 3 days for 2 to 3 doses.

    For the treatment of recurrent VVC† (RVVC) in persons without HIV.
    Oral dosage
    Adults

    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.

    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† (RVVC) in persons living with HIV.
    Oral dosage
    Adults

    100 to 200 mg PO daily for at least 7 days, followed by long-term suppressive therapy.

    Adolescents

    100 to 200 mg PO daily for at least 7 days, followed by long-term suppressive therapy.

    For the treatment of severe VVC† in persons living with HIV.
    Oral dosage
    Adults

    100 to 200 mg PO daily for at least 7 days.

    Adolescents

    100 to 200 mg PO daily for at least 7 days.

    For the treatment of recurrent VVC (RVVC) in combination with oteseconazole to reduce the incidence in persons with a history of RVVC who are not of reproductive potential.
    Oral dosage
    Adults

    150 mg PO once daily on days 1, 4, and 7, followed by oteseconazole therapy for 12 weeks.

    For the treatment of cryptococcal meningitis.
    Persons living with HIV.
    Oral dosage
    Adults

    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.

    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.

    Infants and Children 6 months to 12 years

    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 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 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.

    Infants 1 to 5 months†

    12 mg/kg/dose PO on day 1, then 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.

    Neonates†

    12 mg/kg/dose PO on day 1, then 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. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Intravenous dosage
    Adults

    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.

    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.

    Infants and Children 6 months to 12 years

    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 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 dose 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.

    Infants 1 to 5 months†

    12 mg/kg/dose IV on day 1, then 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.

    Neonates†

    12 mg/kg/dose IV on day 1, then 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. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Organ transplant recipients.
    Oral dosage
    Adults

    400 to 800 mg PO once daily for 8 weeks after the initial 2-week course of induction therapy, followed by 200 to 400 mg PO once daily for 6 to 12 months. 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.

    Infants, Children, and Adolescents 6 months to 17 years

    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 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.

    Infants 1 to 5 months†

    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.

    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. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates.   However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Non-HIV, nontransplant patients.
    Oral dosage
    Adults

    400 mg PO once daily for 8 weeks after the initial at least 4-week course of induction therapy or 800 mg PO once daily for 8 weeks after an initial 2-week course of induction therapy, followed by 200 mg PO once daily for 6 to 12 months. 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.

    Infants, Children, and Adolescents 6 months to 17 years

    10 to 12 mg/kg/dose (Max: 800 mg/dose) PO once daily for 8 weeks after the initial at least 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.

    Infants 1 to 5 months†

    10 to 12 mg/kg/dose PO once daily for 8 weeks after the initial at least 2-week course of induction therapy, followed by 6 mg/kg/dose PO once daily for 6 to 12 months.

    Neonates†

    10 to 12 mg/kg/dose PO once daily for 8 weeks after the initial at least 2-week course of induction therapy, followed by 6 mg/kg/dose PO once daily for 6 to 12 months. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates.   However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    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
    Adults

    400 to 800 mg PO once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.[60487]

    Infants, Children, and Adolescents

    12 mg/kg/dose PO once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.[60487] In general, doses more than 600 mg/day are not recommended.[28674]

    Neonates

    12 mg/kg/dose PO once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.[60487] A loading dose of 25 mg/kg PO is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).[28674] [32700] [53057]

    Intravenous dosage
    Adults

    400 to 800 mg IV once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.[60487]

    Infants, Children, and Adolescents

    12 mg/kg/dose IV once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.[60487] In general, doses more than 600 mg/day are not recommended.[60686]

    Neonates

    12 mg/kg/dose IV once daily until resolution of all signs and symptoms and CSF and radiologic abnormalities.[60487] A loading dose of 25 mg/kg IV is recommended on day 1 to achieve therapeutic concentrations faster.[53037] [53038] [60487] A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 96% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing.[53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life.[53038] The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of CNS infections due to Coccidioides sp.†.
    Oral dosage
    Adults

    400 to 1,200 mg PO once daily. Guidelines recommend fluconazole as preferred therapy. Continue suppressive therapy for lifelong.

    Adolescents

    400 to 1,200 mg PO once daily. Guidelines recommend fluconazole as preferred therapy. Continue suppressive therapy for lifelong.[34362] [61514]

    Infants and Children

    12 mg/kg/dose (Max: 800 mg/dose) PO once daily.[34361] Guidelines recommend fluconazole as preferred therapy.[61514] 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.[34361] Continue suppressive therapy for lifelong.[34361] [61514]

    Intravenous dosage
    Adults

    400 to 1,200 mg IV once daily if unable to take orally. Guidelines recommend fluconazole as preferred therapy. Continue suppressive therapy for lifelong.

    Adolescents

    400 to 1,200 mg IV once daily if unable to take orally. Guidelines recommend fluconazole as preferred therapy. Continue suppressive therapy for lifelong.

    Infants and Children

    12 mg/kg/dose (Max: 800 mg/dose) IV once daily.[34361] Guidelines recommend fluconazole as preferred therapy.[61514] 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.[34361] Continue suppressive therapy for lifelong.[34361] [61514]

    For step-down therapy of CNS infections due to Blastomyces dermatitidis† after initial treatment with amphotericin B.
    Oral dosage
    Adults

    800 mg PO once daily for at least 12 months and until resolution of CSF abnormalities.[34215]

    For step-down therapy of CNS infections due to Histoplasma capsulatum† after initial treatment with amphotericin B in persons living with HIV.
    Oral dosage
    Adults

    800 mg PO once daily for at least 12 months and until resolution of abnormal CSF findings in persons who are intolerant to itraconazole.[34362]

    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.[34362]

    For the treatment of endophthalmitis† caused by Candida sp..
    Oral dosage
    Adults

    800 mg (12 mg/kg) PO once, then 400 to 800 mg (6 to 12 mg/kg) 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

    12 mg/kg/dose PO once daily for fluconazole-susceptible isolates. In general, doses exceeding 600 mg are not recommended. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.

    Neonates

    12 mg/kg/dose PO once daily is recommended by guidelines as an alternative therapy to amphotericin B deoxycholate in patients who have not been receiving fluconazole prophylaxis. Others have recommended a range of 6 to 12 mg/kg/dose PO every 24 to 72 hours. There is some debate about the optimal dosing frequency in neonates; however, some pharmacokinetic data and guidelines support every 24-hour dosing. Data from a population pharmacokinetic study in neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC more than 50 for Candida species with an MIC less than 8 mcg/mL) in 90% of neonates less than 30 weeks gestational age and 80% of neonates 30 to 40 weeks gestational age. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). The FDA-approved product labeling suggests a dosing interval of every 72 hours during the first 2 weeks of life based on early pharmacokinetic data in premature neonates (gestational age 26 to 29 weeks); the approved product labeling from the United Kingdom also recommends a dosing interval of every 72 hours during the first 2 weeks of life. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.

    Intravenous dosage
    Adults

    800 mg (12 mg/kg) IV once, then 400 to 800 mg (6 to 12 mg/kg) 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 Adolescents

    12 mg/kg/dose IV once daily for fluconazole-susceptible isolates. In general, doses exceeding 600 mg are not recommended. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.

    Neonates

    12 mg/kg/dose IV once daily is recommended by guidelines as an alternative therapy to amphotericin B deoxycholate in patients who have not been receiving fluconazole prophylaxis. Others have recommended a range of 6 to 12 mg/kg/dose IV every 24 to 72 hours. There is some debate about the optimal dosing frequency in neonates; however, some pharmacokinetic data and guidelines support every 24-hour dosing. Data from a population pharmacokinetic study in neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC more than 50 for Candida species with an MIC less than 8 mcg/mL) in 90% of neonates less than 30 weeks gestational age and 80% of neonates 30 to 40 weeks gestational age. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). The FDA-approved product labeling suggests a dosing interval of every 72 hours during the first 2 weeks of life based on early pharmacokinetic data in premature neonates (gestational age 26 to 29 weeks); the approved product labeling from the United Kingdom also recommends a dosing interval of every 72 hours during the first 2 weeks of life. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.

    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
    Adults

    400 to 800 mg (6 to 12 mg/kg) 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.

    Infants, Children, and Adolescents

    12 mg/kg/dose PO once daily as step-down therapy after lipid amphotericin B or echinocandin therapy in stable patients with negative blood cultures. In general, doses exceeding 600 mg are not recommended. 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

    12 mg/kg/dose PO once daily as an alternative therapy to amphotericin B deoxycholate in patients who have not been receiving fluconazole prophylaxis. Others have recommended a range of 6 to 12 mg/kg/dose PO every 24 to 72 hours. There is some debate about the optimal dosing frequency in neonates; however, some pharmacokinetic data and guidelines support every 24-hour dosing. Data from a population pharmacokinetic study in neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC more than 50 for Candida species with an MIC less than 8 mcg/mL) in 90% of neonates less than 30 weeks gestational age and 80% of neonates 30 to 40 weeks gestational age. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). The FDA-approved product labeling suggests a dosing interval of every 72 hours during the first 2 weeks of life based on early pharmacokinetic data in premature neonates (gestational age 26 to 29 weeks); the approved product labeling from the United Kingdom also recommends a dosing interval of every 72 hours during the first 2 weeks of life. 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
    Adults

    400 to 800 mg (6 to 12 mg/kg) 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.

    Infants, Children, and Adolescents

    12 mg/kg/dose IV once daily as step-down therapy after lipid amphotericin B or echinocandin therapy in stable patients with negative blood cultures. In general, doses exceeding 600 mg are not recommended. 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

    12 mg/kg/dose IV once daily as an alternative therapy to amphotericin B deoxycholate in patients who have not been receiving fluconazole prophylaxis. Others have recommended a range of 6 to 12 mg/kg/dose IV every 24 to 72 hours. There is some debate about the optimal dosing frequency in neonates; however, some pharmacokinetic data and guidelines support every 24-hour dosing. Data from a population pharmacokinetic study in neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC more than 50 for Candida species with an MIC less than 8 mcg/mL) in 90% of neonates less than 30 weeks gestational age and 80% of neonates 30 to 40 weeks gestational age. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). The FDA-approved product labeling suggests a dosing interval of every 72 hours during the first 2 weeks of life based on early pharmacokinetic data in premature neonates (gestational age 26 to 29 weeks); the approved product labeling from the United Kingdom also recommends a dosing interval of every 72 hours during the first 2 weeks of life. 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 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
    Adults

    800 mg PO once, then 400 mg PO once daily. The FDA-approved dosage is 50 to 200 mg PO once daily.

    Infants, Children, and Adolescents

    12 mg/kg/dose (Max: 800 mg/dose) PO once daily. The FDA-approved dosage is 6 to 12 mg/kg/dose (Max: 600 mg/dose) PO every 24 hours.

    Neonates

    12 mg/kg/dose PO once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. A loading dose of 25 mg/kg PO is recommended on day 1 to achieve therapeutic concentrations faster. A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 93% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates.   However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Intravenous dosage
    Adults

    800 mg IV once, then 400 mg IV once daily. The FDA-approved dosage is 50 to 200 mg IV once daily.

    Infants, Children, and Adolescents

    12 mg/kg/dose (Max: 800 mg/dose) IV once daily. The FDA-approved dosage is 6 to 12 mg/kg/dose (Max: 600 mg/dose) IV every 24 hours.

    Neonates

    12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. A loading dose of 25 mg/kg IV is recommended on day 1 to achieve therapeutic concentrations faster. A Monte Carlo simulation showed that the target systemic exposure at 24 hours of therapy increases from 30% to 93% when a loading dose is used. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of peritoneal dialysis-related peritonitis† due to Candida.
    Oral dosage
    Adults

    200 mg PO loading dose, then 50 to 100 mg PO once daily for at least 14 days after catheter removal.

    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
    Adults

    200 mg IV loading dose, then 50 to 100 mg IV once daily for at least 14 days after catheter removal.

    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†
    Adults

    200 mg intraperitoneally every 24 to 48 hours.

    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
    Adults

    200 mg PO loading dose, then 50 to 100 mg PO once daily for at least 14 to 21 days.

    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† and infectious arthritis†) caused by Candida sp..
    Oral dosage
    Adults

    400 mg (6 mg/kg) PO once daily for 6 to 12 months for osteomyelitis or 6 weeks for infectious arthritis.

    Infants, Children, and Adolescents

    12 mg/kg/dose PO once daily for 6 to 12 months for osteomyelitis or 6 weeks for infectious arthritis. In general, doses exceeding 600 mg are not recommended.

    Neonates

    12 mg/kg/dose PO once daily as alternative therapy to amphotericin B deoxycholate in patients who have not been receiving fluconazole prophylaxis. Others have recommended a range of 6 to 12 mg/kg/dose PO every 24 to 72 hours. There is some debate about the optimal dosing frequency in neonates; however, some pharmacokinetic data and guidelines support every 24-hour dosing. Data from a population pharmacokinetic study in neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC more than 50 for Candida species with an MIC less than 8 mcg/mL) in 90% of neonates less than 30 weeks gestational age and 80% of neonates 30 to 40 weeks gestational age. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). The FDA-approved product labeling suggests a dosing interval of every 72 hours during the first 2 weeks of life based on early pharmacokinetic data in premature neonates (gestational age 26 to 29 weeks); the approved product labeling from the United Kingdom also recommends a dosing interval of every 72 hours during the first 2 weeks of life. Treat for 6 to 12 months for osteomyelitis or 6 weeks for infectious arthritis.

    Intravenous dosage
    Adults

    400 mg (6 mg/kg) IV once daily for 6 to 12 months for osteomyelitis or 6 weeks for infectious arthritis.

    Infants, Children, and Adolescents

    12 mg/kg/dose IV once daily for 6 to 12 months for osteomyelitis or 6 weeks for infectious arthritis. In general, doses exceeding 600 mg are not recommended.

    Neonates

    12 mg/kg/dose IV once daily as alternative therapy to amphotericin B deoxycholate in patients who have not been receiving fluconazole prophylaxis. Others have recommended a range of 6 to 12 mg/kg/dose IV every 24 to 72 hours. There is some debate about the optimal dosing frequency in neonates; however, some pharmacokinetic data and guidelines support every 24-hour dosing. Data from a population pharmacokinetic study in neonates revealed that a dose of at least 12 mg/kg/day is necessary to achieve target exposure (AUC/MIC more than 50 for Candida species with an MIC less than 8 mcg/mL) in 90% of neonates less than 30 weeks gestational age and 80% of neonates 30 to 40 weeks gestational age. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). The FDA-approved product labeling suggests a dosing interval of every 72 hours during the first 2 weeks of life based on early pharmacokinetic data in premature neonates (gestational age 26 to 29 weeks); the approved product labeling from the United Kingdom also recommends a dosing interval of every 72 hours during the first 2 weeks of life. Treat for 6 to 12 months for osteomyelitis or 6 weeks for infectious arthritis.

    For candidiasis prophylaxis, including vulvovaginal candidiasis prophylaxis†.
    For candidiasis prophylaxis in patients hospitalized in the intensive care unit (ICU)†.
    Oral dosage
    Adults

    800 mg PO on day 1, followed by 400 mg PO once daily may be considered for high-risk patients in ICUs with a high rate of invasive candidiasis (more than 5%).

    Intravenous dosage
    Adults

    800 mg IV on day 1, followed by 400 mg IV once daily may be considered for high-risk patients in ICUs with a high rate of invasive candidiasis (more than 5%).

    For candidiasis prophylaxis in bone marrow transplant (BMT) patients, including hematopoietic stem cell transplant (HSCT) recipients, and other high-risk cancer patients†.
    Oral dosage
    Adults

    400 mg PO once daily. For BMT patients who are anticipated to experience a neutrophil count of less than 500/mm3, begin therapy several days prior to the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises back above 1000/mm3. For neutropenic patients receiving chemotherapy, use prophylaxis during the period of neutropenia or risk of neutropenia. In allogeneic HSCT recipients, the optimal prophylaxis duration has not been defined.

    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.

    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.

    Intravenous dosage
    Adults

    400 mg IV once daily. For BMT patients who are anticipated to have ANC less than 500 cells/mm3, begin therapy several days prior to the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises back above 1000 cells/mm3. For neutropenic patients receiving chemotherapy, use prophylaxis during the period of neutropenia or risk of neutropenia. In allogeneic HSCT recipients, the optimal prophylaxis duration has not been defined.

    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.

    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.

    For candidiasis prophylaxis in very low birthweight and extremely low birthweight premature neonates†.
    Oral dosage
    Premature Neonates weighing less than 1.5 kg

    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. In a 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), 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 1.5 kg

    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. In a 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), no differences in neurodevelopment or quality of life were noted between fluconazole-treated patients and placebo-treated patients.

    For secondary oropharyngeal prophylaxis† (i.e., long-term suppressive therapy) in persons living with HIV.
    Oral dosage
    Adults

    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.

    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.

    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.

    For secondary oropharyngeal candidiasis prophylaxis† (i.e., long-term suppressive therapy) in persons without HIV.
    Oral dosage
    Adults

    100 mg PO 3 times weekly may be considered for persons who have recurrent infections.

    For secondary esophageal candidiasis prophylaxis† (i.e., long-term suppressive therapy) in persons without HIV.
    Oral dosage
    Adults

    100 to 200 mg PO 3 times weekly may be considered in persons who have recurrent infections.

    For secondary esophageal candidiasis prophylaxis† (i.e., long-term suppressive therapy) in persons living with HIV.
    Oral dosage
    Adults

    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.

    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.

    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.

    For secondary vulvovaginal candidiasis prophylaxis† (i.e., long-term suppressive therapy) in persons living with HIV.
    Oral dosage
    Adults

    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.

    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.

    For secondary vulvovaginal candidiasis prophylaxis† (i.e., long-term suppressive therapy) in persons without HIV.
    Oral dosage
    Adults

    100 to 200 mg PO once weekly for 6 months may be considered for persons who have recurrent infections.

    Adolescents

    100 to 200 mg PO once weekly for 6 months may be considered for persons who have recurrent infections.

    For surgical infection prophylaxis† in patients undergoing transplantation.
    Intravenous dosage
    Adults

    400 mg IV as a single 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.

    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 suppressive therapy for bacterial vaginosis†.
    Oral dosage
    Adults

    150 mg PO once monthly plus metronidazole for recurrent bacterial vaginosis.

    Adolescents

    150 mg PO once monthly plus metronidazole for recurrent bacterial vaginosis.

    For the treatment of mild to moderate pulmonary or disseminated extrapulmonary blastomycosis†.
    NOTE: For CNS infections, see dosage for meningitis.
    Oral dosage
    Adults

    400 to 800 mg PO once daily for 6 to 12 months in patients unable to take itraconazole.[34215]

    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
    Adults

    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.[61514]

    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.

    Infants and Children

    6 to 12 mg/kg/dose (Max: 400 or 800 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.

    Neonates

    6 to 12 mg/kg/dose PO once daily.

    Intravenous dosage
    Adults

    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.

    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.

    Infants and Children

    6 to 12 mg/kg/dose (Max: 400 or 800 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.

    Neonates

    6 to 12 mg/kg/dose IV once daily.

    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.[34362]
    Oral dosage
    Adults

    400 mg PO once daily as preferred therapy. 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.[34362] [61514]

    Adolescents

    400 mg PO once daily as preferred therapy. 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.[34362] [61514]

    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%.

    Intravenous dosage
    Adults

    400 mg IV once daily as preferred therapy. 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.[34362] [61514]

    Adolescents

    400 mg IV once daily as preferred therapy. 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.[34362] [61514]

    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%.

    For the treatment of severe pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis† in persons living with HIV.
    Oral dosage
    Adults

    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.

    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.

    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.

    Intravenous dosage
    Adults

    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.

    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.

    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.

    For coccidioidomycosis prophylaxis† (long-term suppressive therapy†).
    For primary coccidioidomycosis prophylaxis† (long-term suppressive therapy†) in persons living with HIV.
    Oral dosage
    Adults

    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.

    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
    Adults

    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.

    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.

    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.

    For secondary coccidioidomycosis prophylaxis† (long-term suppressive therapy†) in persons living with HIV after treatment for severe pulmonary or nonmeningeal, extrapulmonary disease.
    Oral dosage
    Adults

    400 mg PO once daily. Prophylaxis may be lifelong; discontinuation is dependent on clinical and serological response.

    Adolescents

    400 mg PO once daily. Prophylaxis may be lifelong; discontinuation is dependent on clinical and serological response.

    Infants and Children

    6 mg/kg/dose (Max: 400 mg) PO once daily. Prophylaxis is lifelong.

    For secondary coccidioidomycosis prophylaxis† (long-term suppressive therapy†) after treatment for meningitis.
    Oral dosage
    Adults

    400 mg PO once daily. Prophylaxis is lifelong.

    Adolescents

    400 mg PO once daily. Prophylaxis is lifelong.

    Infants and Children

    6 mg/kg/dose (Max: 400 mg) PO once daily. Prophylaxis is lifelong.

    For primary coccidioidomycosis prophylaxis† (long-term suppressive therapy†) in organ transplant recipients without active disease in endemic areas.
    Oral dosage
    Adults

    200 to 400 mg PO once daily for 6 to 12 months after transplant.

    For primary coccidioidomycosis prophylaxis† (long-term suppressive therapy†) in organ transplant recipients with evidence of past infection.
    Oral dosage
    Adults

    400 mg PO once daily for at least 12 months after transplant.

    For the treatment of disseminated (nonmeningeal) or pulmonary cryptococcosis†.
    NOTE: For the treatment of CNS infections, see cryptococcal meningitis.
    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
    Adults

    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.

    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.

    Infants and Children

    12 mg/kg/dose (Max: 600 mg/dose) PO 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.

    Neonates

    12 mg/kg/dose PO 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 (Max: 200 mg/dose) PO once daily for at least 1 year as chronic suppressive therapy. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Intravenous dosage
    Adults

    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. 

    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. 

    Infants and Children

    12 mg/kg/dose (Max: 600 mg/dose) IV 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.

    Neonates

    12 mg/kg/dose IV 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. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of moderately severe to severe non-CNS or disseminated disease in organ transplant recipients.
    Oral dosage
    Adults

    400 to 800 mg PO once daily for 8 weeks after the initial 2-week course of induction therapy, followed by 200 to 400 mg 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.

    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. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates.   However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    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
    Adults

    400 to 800 mg PO once daily for 10 weeks, followed by 200 mg PO once daily for a total of 6 months.

    Adolescents

    400 to 800 mg PO once daily for 10 weeks, followed by 200 mg PO once daily for a total of 6 months.

    Infants and Children

    12 mg/kg/dose (Max: 600 mg/dose) PO 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.

    Neonates

    12 mg/kg/dose PO 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 (Max: 200 mg/dose) PO once daily for at least 1 year as chronic suppressive therapy. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    Intravenous dosage
    Infants and Children

    12 mg/kg/dose (Max: 600 mg/dose) IV 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.

    Neonates

    12 mg/kg/dose IV 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. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of mild to moderate non-CNS disease in organ transplant recipeints.
    Oral dosage
    Adults

    400 mg 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.

    Neonates

    6 to 12 mg/kg/dose PO once daily for 6 to 12 months. Although there has been debate about the optimal dosing frequency in neonates, data and guidelines support every 24-hour dosing for neonates. However, for premature neonates less than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. The FDA and European product labeling suggest a dosing interval of every 72 hours during the first 2 weeks of life; however, recommendations are based on early and very limited pharmacokinetic data in premature neonates (n = 12; 26 to 29 weeks gestation).

    For the treatment of pulmonary or mild disseminated histoplasmosis† in persons living with HIV.
    NOTE: For CNS infections, see meningitis indication.
    For the treatment of mild disseminated histoplasmosis.
    Oral dosage
    Adults

    800 mg PO once daily for at least 12 months for patients who are intolerant to itraconazole. Long-term suppressive therapy is recommended for those who relapse despite receipt of appropriate therapy.

    Adolescents

    800 mg PO once daily for at least 12 months for patients who are intolerant to itraconazole. Long-term suppressive therapy is recommended for those who relapse despite receipt of appropriate therapy.

    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 and followed by chronic suppressive therapy.

    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 and followed by chronic suppressive therapy.

    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 and followed by chronic suppressive therapy.

    For secondary histoplasmosis prophylaxis† (i.e., long-term suppressive therapy) in HIV-infected patients.
    Oral dosage
    Adults

    400 mg PO once daily as an alternative to itraconazole. 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 count of more than 150 cells/mm3 on antiretroviral therapy for at least 6 months. Resume secondary prophylaxis if the CD4 count decreases below 150 cells/mm3. Guidelines recommend secondary prophylaxis for patients with severe disseminated or CNS infection after completing at least 12 months of therapy and relapse despite appropriate initial therapy.[34362]

    Adolescents

    400 mg PO once daily as an alternative to itraconazole. 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 count of more than 150 cells/mm3 on antiretroviral therapy for at least 6 months. Resume secondary prophylaxis if the CD4 count decreases below 150 cells/mm3. Guidelines recommend secondary prophylaxis for patients with severe disseminated or CNS infection after completing at least 12 months of therapy and relapse despite appropriate initial therapy.[34362]

    For primary talaromycosis prophylaxis† in HIV-infected patients.
    For primary talaromycosis prophylaxis in HIV-infected patients residing in endemic areas†.
    Oral dosage
    Adults

    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.

    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
    Adults

    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.

    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
    Adults

    200 mg PO once daily for 6 weeks. Alternatively for L. major, 400 mg PO once daily for 6 weeks.[63762]

    Infants, Children, and Adolescents

    5 mg/kg/dose PO once daily (Max: 200 mg/day).[64603] [64604] [64605] [64606] [64607] Higher doses (8 mg/kg/day) may be needed for incomplete clinical response.[64606]

    For the treatment of skin and skin structure infections† caused by Candida sp..
    Oral dosage
    Adults

    100 to 400 mg PO once daily in febrile, immunosuppressed patients as an alternative to an echinocandin or amphotericin B.[57437]

    Intravenous dosage
    Adults

    800 mg IV once, then 400 mg IV once daily in febrile, immunosuppressed patients as an alternative to an echinocandin or amphotericin B.[57437]

    For the treatment of cutaneous or lymphocutaneous sporotrichosis†.
    Oral dosage
    Adults

    400 to 800 mg PO once daily for 2 to 4 weeks after all lesions have resolved, usually for a total of 3 to 6 months in patients who cannot tolerate other agents.[50784]

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    400 mg/day PO/IV is FDA-approved; however, up to 1,200 mg/day PO/IV has been used off-label.

    Geriatric

    400 mg/day PO/IV is FDA-approved; however, up to 1,200 mg/day PO/IV has been used off-label.

    Adolescents

    12 mg/kg/day (Max: 600 mg/day) PO/IV is FDA-approved; however, up to 1,200 mg/day PO/IV has been used off-label.

    Children

    12 mg/kg/day (Max: 600 mg/day) PO/IV is FDA-approved; however, up to 800 mg/day PO/IV has been used off-label.

    Infants

    6 to 12 months: 12 mg/kg/day PO/IV.
    1 to 5 months: Safety and efficacy have not been established; however, up to 12 mg/kg/day PO/IV has been used off-label.

    Neonates

    Safety and efficacy have not been established; however, 25 mg/kg PO/IV loading dose, then up to 12 mg/kg/day PO/IV has been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    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.[28674]
     
    Adults [28674] [32569] [60686]
    CrCl more than 50 mL/minute: No dosage adjustment needed.
    CrCl 50 mL/minute or less: Administer usual loading dose, then reduce maintenance dose by 50%.
     
    Infants, Children, and Adolescents [28674] [32569] [60686]
    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.
     
    Neonates† [53038]
    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.
     
    Intermittent hemodialysis
    NOTE: A 3-hour hemodialysis session decreases plasma concentrations by approximately 50%.[28674] [32569] [60686]
     
    Adults and Pediatric patients (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.[28674] [60686]
     
    Adults (alternative)†
    200 to 400 mg IV or PO every 48 to 72 hours or 100 to 200 mg IV or PO every 24 hours.[42303]
     
    Pediatric patients (alternative)†
    Administer usual loading dose, then reduce maintenance dose by 50% and administer every 48 hours (after dialysis).[32569]
     
    Peritoneal dialysis†
    Adults
    Administer usual loading dose, then reduce maintenance dose by 50%.[32569]
     
    Pediatric patients
    Administer usual loading dose, then reduce maintenance dose by 50% and administer every 48 hours.[32569]
     
    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.[42303]
     
    Adults
    200 to 400 mg IV or PO every 24 hours has generally been suggested for CRRT.[32569] Specific recommendations for patients receiving CVVH, CVVHD, or CVVHD include the following:
    CVVH: 400 to 800 mg IV or PO loading dose, then 200 to 400 mg IV or PO every 24 hours.[34038] [42303]
    CVVHD or CVVHDF: 400 mg to 800 mg IV or PO every 24 hours. If the dialysate flow rate is 2 L/hour or more and/or if treating relatively resistant organisms, 800 mg IV or PO every 24 hours.[34038] [42303]
     
    Pediatric patients
    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.[32569] 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 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 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.[65397]
     
    Adults
    800 mg IV loading dose, then 400 mg IV every 12 hours or pre- and post-PIRRT achieved at least a 90% probability of pharmacodynamic target attainment for C. albicans for an 8- to 10-hour PIRRT session. Dosing was studied using 4 different PIRRT setting simulations over 8 to 10 hours/day in a Monte Carlo simulation study using population pharmacokinetic data.[65424]
     
    Pediatric patients
    Fluconazole dosing data are not available in pediatric patients receiving hybrid hemodialysis. Based on adult data, dosage adjustments may be necessary.[65424]

    ADMINISTRATION

    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.

    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.

    STORAGE

    Generic:
    - Avoid excessive heat (above 104 degrees F)
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from freezing
    - Store between 68 to 86 degrees F
    - Store in moisture barrier overwrap until time of use
    Diflucan:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    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, people 65 years and older, 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.

    Hepatic disease

    Fluconazole can be hepatotoxic and should be used with caution in patients with preexisting hepatic disease. The related azole, ketoconazole, also has been associated with hepatotoxicity. Liver-function tests should be monitored. If signs and symptoms of hepatotoxicity develop, fluconazole therapy should be stopped.

    Renal failure, renal impairment

    Approximately 60 to 80% of fluconazole is renally excreted. Dose reduction or extension of the dosing interval is indicated in patients with renal impairment or renal failure.

    Pregnancy

    Avoid the use of fluconazole during pregnancy except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the potential benefit outweighs the possible risk to the fetus. No adequate and well-controlled studies have been conducted in pregnant women; however, a few case reports have described a pattern of distinct congenital anomalies in infants born to women exposed to high dose fluconazole (400 to 800 mg/day) during the first trimester.[28674] The features observed in fluconazole-exposed infants included brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease. The nature of these birth defects suggests that the teratogenic effect may occur early in the first trimester.[26025] Additionally, retrospective epidemiological studies suggest a potential association between the use of low-dose fluconazole (i.e., 150 mg) and increased risk of birth defects and spontaneous abortions.[60495] [60789] Data from the National Birth Defects Prevention Study found an association between maternal exposure to low-dose fluconazole in the first trimester and both cleft lip with cleft palate and d-transposition of the great arteries. Of the 43,247 mothers analyzed, 44 case mothers and 6 control mothers were identified. The majority of cases (n =36/50; 72%) reported taking fluconazole for vaginal candidiasis and almost all (n = 49/50) reported taking fluconazole for a short duration. Six exposed infants had cleft lip with cleft palate, 4 had an atrial septal defect, and each of the following defects had 3 exposed cases: hypospadias, tetralogy of Fallot, d-transposition of the great arteries, and pulmonary valve stenosis. Fluconazole use was associated with a significant risk for cleft lip with cleft palate (OR 5.53; 95% CI, 1.68 to 18.24) and d-transposition of the great arteries (OR 7.56; 95% CI, 1.22 to 35.45). The increases for the other conditions were not statistically significant.[60789] A large population-based cohort study of U.S. Medicaid data found oral fluconazole use during the first trimester to be associated with musculoskeletal malformations but not with oral clefts or conotruncal malformations. This cohort included 1,969,954 pregnancies, with 37,650 pregnancies exposed to oral fluconazole and 82,090 exposed to topical azoles during the first trimester. The unadjusted relative risk for musculoskeletal malformations with fluconazole vs. unexposed pregnancies was 1.37 (95% CI, 1.19 to 1.58). When comparing oral fluconazole with topical azoles, the unadjusted relative risk for musculoskeletal malformations was 1.4 (95% CI, 1.17 to 1.67). A subanalysis found a 30% increase in risk for musculoskeletal malformations for cumulative fluconazole doses of 150 to 450 mg and an almost 2-fold increase in risk for cumulative doses more than 450 mg. Malformations were defined as deformities of the skull/face/jaw, feet, and/or spine.[65469] A nationwide Danish cohort study also found an association between maternal exposure to oral fluconazole, including doses used to treat vaginal candidiasis, during gestational weeks 7 through 22 and spontaneous abortions. Specifically, 147 spontaneous abortions were reported among 3,315 fluconazole-treated women, as compared to 563 spontaneous abortions among the 13,246 unexposed matched control pregnancies. Of these 147 spontaneous abortions, 132 were reported in pregnancies exposed to a fluconazole dose of 150 to 300 mg (n = 2,986 fluconazole-treated women). These data indicate a statistically significant increase in risk for spontaneous abortion with maternal exposure to fluconazole during gestational weeks 7 through 22 (HR, 1.48; 95% CI, 1.23 to 1.77).[60495] Topical antifungals, administered for a longer duration in persistent or recurrent infections, are recommended for the treatment of vaginal candidiasis during pregnancy.[60741] Guidelines for the prevention of opportunistic infections in HIV patients recommend that oral azole antifungals, including fluconazole, not be started during pregnancy and that these agents should be discontinued in HIV-positive women who become pregnant.[34362] If fluconazole is administered during pregnancy, or if a patient becomes pregnant while taking fluconazole, advise the patient of the potential hazard to the infant.[28674]

    Breast-feeding

    Use caution when fluconazole is administered to a breast-feeding woman.[28674] Previous American Academy of Pediatrics (AAP) recommendations considered fluconazole as usually compatible with breast-feeding.[27500] Fluconazole is distributed in human breast milk at concentrations similar to those in the plasma. A case report found breast milk to plasma ratios of 0.46, 0.85, 0.85, and 0.83 at 2, 5, 24, and 48 hours after a single 150 mg dose of fluconazole.[46093] Experts have estimated, based on limited data of concentrations in breast milk, that an exclusively breast-fed infant whose mother was receiving fluconazole 200 mg daily would receive a maximum dose of 0.6 mg/kg/day. This is equivalent to 60% of the recommended dose for thrush in newborns younger than 2 weeks of age and 20% of the recommended dose for older newborns and infants.[46094] Another study determined the daily infant fluconazole dose from breast milk (assuming mean milk consumption of 150 mL/kg/day) based on the mean peak milk concentration (2.61 mcg/mL [range: 1.57 to 3.65 mcg/mL] at 5.2 hours post-dose) to be 0.39 mg/kg/day, which is approximately 13% of the recommended pediatric dose for oropharyngeal candidiasis.[28674] Fluconazole has been used successfully to treat mastitis due to yeast resistant to other therapies in breast-feeding mothers.[46095] [46096]

    Azole antifungals hypersensitivity

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

    Neonates

    Fluconazole is approved for all pediatric populations. The safety of fluconazole has been studied in children ages 1 day to 17 years; however, experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. Several studies have shown fluconazole to be effective in treating oropharyngeal candidiasis in children 6 months to 13 years. Fluconazole has also been shown effective in treating serious systemic fungal infections and for suppression of cryptococcal meningitis; there is no information regarding the efficacy of fluconazole for primary treatment of cryptococcal meningitis in children. Pharmacokinetic studies in children have established dose proportionality between children and adults.

    Geriatric

    Controlled clinical trials of fluconazole did not include sufficient numbers of geriatric patients (65 years of age and older) to evaluate whether they respond differently from younger adults in each indication. Other reported clinical experience has not identified differences in responses between older adult and younger adult patients. Since fluconazole is primarily cleared renally and geriatric patients are more likely to have decreased renal function, care should be taken to adjust dose based on creatinine clearance. It may also be useful to monitor renal function. Systemic fluconazole can prolong the QT interval. Geriatric patients may be at increased risk for QT prolongation and for serious drug-drug interactions that may increase the risk QT prolongation risk or may increase the risk for other serious side effects. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, systemic azole antifungals should be used in the lowest possible dose for the shortest possible duration, particularly in patients receiving other medications known to interact with these medications. Increased monitoring may be required to identify and minimize the toxicity of warfarin, phenytoin, theophylline, or sulfonylureas when an azole antifungal is co-administered; other medications such as rifampin and cimetidine may decrease the therapeutic effect of the antifungal. Some drug-drug combinations may be contraindicated. OBRA guidelines caution that azole antifungals may cause hepatotoxicity, headaches, and GI distress.

    Driving or operating machinery

    Fluconazole may rarely cause dizziness or seizures. Patients should use caution when driving or operating machinery until they are aware of the effects of the drug.

    Serious rash

    Serious rash, including exfoliative skin disorders such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients receiving treatment with fluconazole. According to the manufacturer, 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, immediately discontinue use of the drug. However, if a rash develops on a patient being treated for a deep seated fungal infection, the patients should be closely monitored, and the drug discontinued if the lesion progresses.

    Contraception requirements, reproductive risk

    Fluconazole may be associated with reproductive risk. Discuss contraception requirements with the patient. Consider effective contraceptive measures for women of child-bearing potential who are receiving high dose fluconazole (i.e., 400 to 800 mg/day), and continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose.

    ADVERSE REACTIONS

    Severe

    toxic epidermal necrolysis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    renal failure / Delayed / Incidence not known
    teratogenesis / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 1.0-1.0
    QT prolongation / Rapid / Incidence not known
    jaundice / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known
    anemia / Delayed / Incidence not known

    Mild

    headache / Early / 1.9-13.0
    nausea / Early / 2.3-7.0
    abdominal pain / Early / 1.7-6.0
    vomiting / Early / 1.7-5.4
    diarrhea / Early / 1.5-3.0
    rash / Early / 1.8-1.8
    dysgeusia / Early / 1.0-1.0
    dyspepsia / Early / 1.0-1.0
    dizziness / Early / 1.0-1.0
    xerostomia / Early / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    insomnia / Early / Incidence not known
    tremor / Early / Incidence not known
    vertigo / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    drowsiness / Early / Incidence not known
    malaise / Early / Incidence not known
    asthenia / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    myalgia / Early / Incidence not known
    fever / Early / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Minor) During concomitant administration with fluconazole, the clearance of zidovudine may be reduced. Although the clinical significance of this interaction has not been established, patients receiving fluconazole with zidovudine should be closely monitored for zidovudine-induced adverse effects, especially hematologic toxicity. Zidovudine dosage reduction may be considered.
    Abarelix: (Major) Separately both fluconazole and abarelix have been associated with QT prolongation. If fluconazole and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation and torsade de pointes.
    Abemaciclib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with fluconazole is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
    Abrocitinib: (Major) Avoid coadministration of abrocitinib with fluconazole as the combined exposure of abrocitinib and its 2 active metabolites may be increased, which may increase the risk for adverse reactions. Abrocitinib is a substrate of CYP2C19 and CYP2C9; fluconazole is a strong inhibitor of CYP2C19 and a moderate CYP2C9 inhibitor.
    Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with fluconazole. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; fluconazole is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
    Acetaminophen; Caffeine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with fluconazole may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Fluconazole is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
    Acetaminophen; Caffeine; Pyrilamine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4.
    Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of fluconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like fluconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If fluconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of fluconazole is necessary. If fluconazole is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like fluconazole can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If fluconazole is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Acetohexamide: (Moderate) Fluconazole should be used cautiously with oral sulfonylureas because blood glucose response may be altered in diabetic patients. In some cases, dosage adjustment of the sulfonylurea may be necessary.
    Alfentanil: (Moderate) Fluconazole may decrease the systemic clearance of alfentanil. Prolonged duration of opiate action, increased sedation, respiratory depression or other opiate side effects may occur. Close monitoring of patients is warranted.
    Alfuzosin: (Contraindicated) Due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP), coadministration of fluconazole with drugs that both prolong the QT interval and are CYP3A4 substrates, such as alfuzosin, is contraindicated. Fluconazole has been associated with QT prolongation and rare cases of TdP. Additonally, fluconazole is an inhibitor of CYP3A4. Coadministration may result in elevated plasma concentrations of alfuzosin, causing an increased risk for adverse events, such as QT prolongation.
    Aliskiren; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
    Alprazolam: (Major) Avoid coadministration of alprazolam and fluconazole due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with fluconazole, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased alprazolam exposure by 1.6- to 1.98-fold.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
    Amiodarone: (Contraindicated) Avoid concomitant use of amiodarone and fluconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase amiodarone exposure and the risk for other amiodarone-related adverse effects; amiodarone is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
    Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with fluconazole. Amisulpride causes dose- and concentration- dependent QT prolongation. Fluconazole has been associated with QT prolongation and rare cases of TdP.
    Amitriptyline: (Minor) Fluconazole should be administered together with TCAs with caution. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, fluconazole has been reported to increase the effects of amitriptyline, likely via inhibition of the hepatic microsomal CYP2C19 or CYP3A4 isoenzymes. In at least one case, the interaction resulted in an increased incidence of TCA-related side effects, like dizziness and syncope. Monitor for an increased response to amitriptyline if fluconazole is coadministered.
    Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
    Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with fluconazole is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a CYP3A substrate; fluconazole is a CYP3A inhibitor. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
    Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
    Amlodipine; Celecoxib: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure. (Moderate) The dose of celecoxib may need to be reduced in patients receiving fluconazole. Fluconazole significantly inhibits the metabolism of celecoxib via CYP2C9. Fluconazole at 200 mg per day resulted in a two-fold increase in celecoxib plasma concentration after a single 200 mg dose of celecoxib.
    Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
    Amlodipine; Valsartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with fluconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
    Amobarbital: (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Be alert for lack of efficacy of fluconazole in concurrent use.
    Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Coadministration is contraindicated. Fluconazole has been associated with QT prolongation and clarithromycin has been specifically established to have a causal association with QT prolongation and torsade de pointes (TdP). Additionally, fluconazole is an inhibitor of CYP3A4 and clarithromycin is a known inhibitor and substrate of CYP3A4. In healthy volunteers, the coadministration of clarithromycin (500 mg orally twice daily) with fluconazole (200 mg once daily) led to increases in clarithromycin mean steady-state Cmin (33%) and AUC (18%); however, mean steady-state concentrations of 14-OH clarithromycin were not affected. The changes appeared to be of minor consequence in healthy subjects. The potential for a more significant interaction between fluconazole and clarithromycin might exist at higher dosages of either drug; caution is advised in such circumstances but should not normally alter therapy. Fluconazole is usually considered a less potent inhibitor of CYP3A4 than other azole-family systemic antifungal agents (e.g., ketoconazole, itraconazole), especially at dosages of < 200 mg/day. Azithromycin can be considered as an alternative macrolide antimicrobial if appropriate for the clinical circumstance, due to its lack of metabolism via CYP3A4.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
    Amphotericin B lipid complex (ABLC): (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
    Amphotericin B liposomal (LAmB): (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
    Amphotericin B: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include fluconazole.
    Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with fluconazole since concurrent use may increase the risk of QT prolongation. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
    Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of fluconazole with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant. After administration, fosaprepitant is rapidly converted to aprepitant. Fluconazole is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur.
    Aripiprazole: (Contraindicated) Avoid use of aripiprazole with fluconazole unless the benefit outweighs the risk of QT prolongation or other side effects. Conflicting recommendations are available from the manufacturers of the drugs. According to the manufacturer of fluconazole, coadministration of drugs known to prolong the QT interval and which are CYP3A4 substrates, such as aripiprazole, is contraindicated in patients receiving fluconazole. Metabolism of aripiprazole occurs mainly through CYP3A4 and CYP2D6. Both fluconazole and aripiprazole have been associated with QT prolongation. The manufacturers of aripiprazole products do not contraindicate use of fluconazole, but do recommend dosage adjustments of oral aripiprazole when used with CYP3A4 inhibitors such as fluconazole. Manufacturers of aripiprazole injections recommend adjustments when a potent CYP3A4 inhibitor will be used for more than 14 days. See the manufacturer prescribing information for detailed recommendations.
    Armodafinil: (Moderate) Armodafinil is partially metabolized by CYP3A4/5 isoenzymes. Interactions with potent inhibitors of CYP3A4 such as fluconazole are possible. However, because armodafinil is itself an inducer of the CYP3A4 isoenzyme, drug interactions due to CYP3A4 inhibition by other medications may be complex and difficult to predict. Observation of the patient for increased effects from armodafinil may be needed.
    Arsenic Trioxide: (Major) Concurrent use of arsenic trioxide and fluconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, fluconazole should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Fluconazole has also been associated with QT prolongation and rare cases of TdP.
    Artemether; Lumefantrine: (Contraindicated) Concomitant administration of fluconazole and lumefantrine is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as lumefantrine. Coadministration of fluconazole with lumefantrine may result in elevated plasma concentrations of lumefantrine, causing an increased risk for adverse events, such as QT prolongation. (Contraindicated) The concomitant administration of fluconazole and artemether is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as artemether. Coadministration of fluconazole with artemether may result in elevated plasma concentrations of artemether as well.
    Asenapine: (Contraindicated) Due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP), coadministration of fluconazole with drugs that both prolong the QT interval and are CYP3A4 substrates, such as asenapine, is contraindicated. Fluconazole has been associated with QT prolongation and rare cases of TdP. Additonally, fluconazole is an inhibitor of CYP3A4. Coadministration may result in elevated plasma concentrations of asenapine, causing an increased risk for adverse events such as QT prolongation.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined. (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Be alert for lack of efficacy of fluconazole in concurrent use.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4. (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined. (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Be alert for lack of efficacy of fluconazole in concurrent use.
    Aspirin, ASA; Caffeine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4.
    Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of fluconazole is necessary. If fluconazole is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like fluconazole can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If fluconazole is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with fluconazole as there is a potential for elevated cobicistat concentrations. Fluconazole is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4.
    Atomoxetine: (Moderate) Concomitant use of atomoxetine and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with fluconazole is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a CYP3A substrate; fluconazole is a CYP3A inhibitor.
    Atorvastatin; Ezetimibe: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with fluconazole is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a CYP3A substrate; fluconazole is a CYP3A inhibitor.
    Avanafil: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving fluconazole. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
    Avapritinib: (Major) Avoid coadministration of avapritinib with fluconazole due to the risk of increased avapritinib-related adverse reactions. If concurrent use is unavoidable, reduce the starting dose of avapritinib from 300 mg PO once daily to 100 mg PO once daily in patients with gastrointestinal stromal tumor or from 200 mg PO once daily to 50 mg PO once daily in patients with advanced systemic mastocytosis. Avapritinib is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration of avapritinib 300 mg PO once daily with fluconazole is predicted to increase the AUC of avapritinib by 210% at steady-state.
    Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), reduce the starting dose of avatrombopag to 20 mg PO 3 times weekly when used concomitantly with fluconazole. In patients starting fluconazole while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A4 substrate, and dual moderate or strong inhibitors such as fluconazole increase avatrombopag exposure, increasing the risk of avatrombopag toxicity.
    Azithromycin: (Major) Concomitant use of azithromycin and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Barbiturates: (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Be alert for lack of efficacy of fluconazole in concurrent use.
    Bedaquiline: (Major) Caution is advised when administering bedaquiline concurrently with fluconazole due to the risk for increased bedaquiline concentrations and a potential for QT prolongation. Fluconazole may inhibit the CYP3A4 metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions. Furthermore, since both drugs are associated with QT prolongation, coadministration may result in additive prolongation of the QT interval and torsade de pointes (TdP). Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of fluconazole with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and fluconazole is a CYP2C19 inhibitor.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
    Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with fluconazole may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of fluconazole in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Fluconazole is an inhibitor of CYP3A4.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
    Bortezomib: (Minor) Fluconazole inhibits CYP3A4 and may increase the exposure to bortezomib and increase the risk for toxicity; however, bortezomib is also metabolized by other CYP isoenzymes. Therefore, the clinical significance of concurrent administration of bortezomib with fluconazole is not known.
    Bosentan: (Major) Coadministration of fluconazole with bosentan is not recommended due to the potential for large increases in bosentan exposure. Fluconazole is a CYP3A4 and CYP2C9 inhibitor; bosentan is metabolized by both CYP3A4 and CYP2C9.
    Bosutinib: (Major) Avoid concomitant use of bosutinib and fluconazole; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor.
    Brigatinib: (Major) Avoid coadministration of brigatinib with fluconazole if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 40% without breaking tablets (i.e., from 180 mg to 120 mg; from 120 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of fluconazole, resume the brigatinib dose that was tolerated prior to initiation of fluconazole. Brigatinib is a CYP3A4 substrate; fluconazole is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase the AUC of brigatinib by approximately 40%.
    Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of fluconazole. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; fluconazole is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
    Budesonide: (Moderate) Avoid coadministration of oral budesonide with fluconazole due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
    Budesonide; Formoterol: (Moderate) Avoid coadministration of oral budesonide with fluconazole due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Avoid coadministration of oral budesonide with fluconazole due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
    Bupivacaine Liposomal: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
    Bupivacaine: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
    Bupivacaine; Epinephrine: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
    Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and fluconazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; fluconazole inhibits CYP3A4. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
    Bupivacaine; Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with fluconazole is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and fluconazole is a moderate CYP2C9 inhibitor. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
    Buprenorphine: (Contraindicated) Avoid concomitant use of fluconazole and buprenorphine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Additionally, concomitant use can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when fluconazole is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping fluconazole, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If fluconazole is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A and fluconazole is a CYP3A inhibitor.
    Buprenorphine; Naloxone: (Contraindicated) Avoid concomitant use of fluconazole and buprenorphine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Additionally, concomitant use can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when fluconazole is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping fluconazole, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If fluconazole is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A and fluconazole is a CYP3A inhibitor.
    Butabarbital: (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Be alert for lack of efficacy of fluconazole in concurrent use.
    Butalbital; Acetaminophen: (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Be alert for lack of efficacy of fluconazole in concurrent use.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined. (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Be alert for lack of efficacy of fluconazole in concurrent use.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4. (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined. (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Be alert for lack of efficacy of fluconazole in concurrent use.
    Cabotegravir; Rilpivirine: (Contraindicated) Concurrent use of fluconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Fluconazole is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of rilpivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for adverse events, such as QT prolongation. Additionally, fluconazole has been associated with prolongation of the QT interval; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine.
    Caffeine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
    Caffeine; Sodium Benzoate: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
    Carbamazepine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of fluconazole; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and fluconazole is a CYP3A inhibitor.
    Carvedilol: (Moderate) Monitor for signs of bradycardia or heart block if coadministration of carvedilol with fluconazole is necessary. Carvedilol is a CYP2C9 substrate and fluconazole is a CYP2C9 inhibitor. Concomitant use may enhance the beta-blocking properties of carvedilol resulting in further slowing of the heart rate or cardiac conduction.
    Celecoxib: (Moderate) The dose of celecoxib may need to be reduced in patients receiving fluconazole. Fluconazole significantly inhibits the metabolism of celecoxib via CYP2C9. Fluconazole at 200 mg per day resulted in a two-fold increase in celecoxib plasma concentration after a single 200 mg dose of celecoxib.
    Celecoxib; Tramadol: (Moderate) The dose of celecoxib may need to be reduced in patients receiving fluconazole. Fluconazole significantly inhibits the metabolism of celecoxib via CYP2C9. Fluconazole at 200 mg per day resulted in a two-fold increase in celecoxib plasma concentration after a single 200 mg dose of celecoxib.
    Ceritinib: (Contraindicated) The concurrent use of fluconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as ceritinib, is contraindicated. Fluconazole has been associated with QT prolongation and concentration-dependent QT prolongation has been reported with ceritinib.
    Chlordiazepoxide; Amitriptyline: (Minor) Fluconazole should be administered together with TCAs with caution. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, fluconazole has been reported to increase the effects of amitriptyline, likely via inhibition of the hepatic microsomal CYP2C19 or CYP3A4 isoenzymes. In at least one case, the interaction resulted in an increased incidence of TCA-related side effects, like dizziness and syncope. Monitor for an increased response to amitriptyline if fluconazole is coadministered.
    Chloroquine: (Major) Avoid coadministration of chloroquine with fluconazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Fluconazole has been associated with QT prolongation and rare cases of TdP.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with fluconazole may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Fluconazole is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of fluconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like fluconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If fluconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Fluconazole is an inhibitor of CYP2C9, which is the isoenzyme responsible for the metabolism of ibuprofen. Thus, increased plasma concentrations of ibuprofen are possible. If fluconazole is administered concurrently with ibuprofen, monitor for NSAID-related side-effects such as fluid retention, GI irritation, or renal dysfunction and adjust the ibuprofen dose, if needed. Among 12 healthy males, the mean systemic exposure of S-(+)-ibuprofen after a single dose of 400 mg of racemic ibuprofen was 67.4 +/- 16.2 mcg x hour/mL. In contrast, the mean systemic exposure was 122 +/- 32 mcg x hour/mL when ibuprofen was given 1 hour after the second fluconazole dose; fluconazole 400 mg was given on day 1 and 200 mg was given on day 2. In addition to increased systemic exposure, the maximum concentration and half-life of S-(+)-ibuprofen were all statistically significantly greater in the presence of fluconazole. Increased S-(+)-ibuprofen concentrations leads to increased inhibition of both COX-1 and COX-2, and impaired ibuprofen metabolism due to mutations in the CYP2C9 gene increases the risk of acute gastrointestinal bleeding.
    Chlorpromazine: (Major) Concurrent use of chlorpromazine and fluconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Fluconazole has been associated with QT prolongation and rare cases of TdP. Phenothiazines have also been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Chlorpropamide: (Moderate) Fluconazole should be used cautiously with oral sulfonylureas because blood glucose response may be altered in diabetic patients. In some cases, dosage adjustment of the sulfonylurea may be necessary.
    Cilostazol: (Major) Decrease cilostazol dose to one half of the recommended dosage when coadministered with fluconazole. Coadministration may increase cilostazol serum concentrations and increase the risk for adverse reactions. Cilostazol is extensively metabolized by hepatic isoenzyme CYP3A4; fluconazole is a moderate inhibitor of CYP3A4.
    Cimetidine: (Minor) Fluconazole 100 mg was administered as a single oral dose alone and 2 hours after a single dose of cimetidine 400 mg to healthy volunteers (n = 6); after administration of cimetidine, there was a mean decrease in fluconazole AUC of 13% and Cmax decreased by 19%. However, the administration of cimetidine 600 to 900 mg IV over 4 hours (from 1 hour before to 3 hours after a single oral dose of fluconazole 200 mg) did not affect the bioavailability or pharmacokinetics of fluconazole in healthy volunteers (n = 24).
    Cinacalcet: (Major) Cinacalcet is metabolized primarily by the CYP3A4 isoenzyme. Subjects being treated with 200 mg ketoconazole twice daily for 7 days received a single 90 mg cinacalcet dose on day 5 of therapy. The AUC and Cmax for cinacalcet increased 2.3 to 2.2 times, respectively, compared to 90 mg cinacalcet given alone. Therefore, caution is recommended when co-administering cinacalcet with other CYP3A4 enzyme inhibitors. These agents may include fluconazole. If a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor during cinacalcet therapy, the manufacturer recommends that dosage adjustment may be needed with close monitoring of PTH and serum calcium concentrations.
    Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Cisapride: (Contraindicated) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). Because of the potential for TdP, use of cisapride with fluconazole is contraindicated.
    Citalopram: (Contraindicated) Due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP), coadministration of fluconazole with drugs that both prolong the QT interval and are CYP3A4 substrates, such as citalopram, is contraindicated. Fluconazole has been associated with QT prolongation and rare cases of TdP. Additonally, fluconazole is an inhibitor of CYP3A4. Coadministration may result in elevated plasma concentrations of citalopram, causing an increased risk for adverse events such as QT prolongation.
    Clarithromycin: (Contraindicated) Coadministration is contraindicated. Fluconazole has been associated with QT prolongation and clarithromycin has been specifically established to have a causal association with QT prolongation and torsade de pointes (TdP). Additionally, fluconazole is an inhibitor of CYP3A4 and clarithromycin is a known inhibitor and substrate of CYP3A4. In healthy volunteers, the coadministration of clarithromycin (500 mg orally twice daily) with fluconazole (200 mg once daily) led to increases in clarithromycin mean steady-state Cmin (33%) and AUC (18%); however, mean steady-state concentrations of 14-OH clarithromycin were not affected. The changes appeared to be of minor consequence in healthy subjects. The potential for a more significant interaction between fluconazole and clarithromycin might exist at higher dosages of either drug; caution is advised in such circumstances but should not normally alter therapy. Fluconazole is usually considered a less potent inhibitor of CYP3A4 than other azole-family systemic antifungal agents (e.g., ketoconazole, itraconazole), especially at dosages of < 200 mg/day. Azithromycin can be considered as an alternative macrolide antimicrobial if appropriate for the clinical circumstance, due to its lack of metabolism via CYP3A4.
    Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of fluconazole. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and fluconazole is a potent inhibitor of CYP2C19. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
    Clofazimine: (Moderate) Concomitant use of clofazimine and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Clomipramine: (Minor) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). Tricyclic antidepressants have been associated with a possible risk of QT prolongation. Fluconazole should be administered together with TCAs with caution.
    Clonazepam: (Moderate) Monitor for increased sedation and respiratory depression if clonazepam is coadministered with fluconazole; adjust the dose of clonazepam if necessary. The systemic exposure of clonazepam may be increased resulting in an increase in treatment-related adverse reactions. Clonazepam is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
    Clopidogrel: (Moderate) Monitor for reduced clopidogrel efficacy during concomitant use of fluconazole. Clopidogrel is primarily metabolized to its active metabolite by CYP2C19; fluconazole is a potent CYP2C19 inhibitor.
    Clozapine: (Contraindicated) Due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP), coadministration of fluconazole with drugs that both prolong the QT interval and are CYP3A4 substrates, like clozapine, is contraindicated. Fluconazole has been associated with QT prolongation and rare cases of TdP. Additonally, fluconazole is an inhibitor of CYP3A4. Coadministration may result in elevated plasma concentrations of clozapine, causing an increased risk for adverse events such as QT prolongation.
    Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with fluconazole as there is a potential for elevated cobicistat concentrations. Fluconazole is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic fluconazole therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of fluconazole is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of fluconazole, resume cobimetinib at the previous dose. Use an alternative to fluconazole in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a CYP3A substrate in vitro, and fluconazole is a moderate inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
    Codeine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4. (Moderate) Concomitant use of promethazine and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with fluconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of fluconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If fluconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Fluconazole is a moderate inhibitor of CYP3A4. (Moderate) Concomitant use of promethazine and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and fluconazole in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Fluconazole can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like fluconazole in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Crizotinib: (Contraindicated) The concurrent use of fluconazole with crizotinib is contraindicated due to the risk of QT prolongation; increased crizotinib exposure may also occur. Both fluconazole and crizotinib have been associated with QT prolongation; fluconazole has also been associated with rare cases of torsade de pointes (TdP). Additionally, fluconazole is a moderate inhibitor of CYP3A4 and crizotinib is a CYP3A4 substrate. Fluconazole is contraindicated for coadministration with drugs that are associated with QT prolongation and are also CYP3A4 substrates.
    Cyclosporine: (Major) Fluconazole inhibits the CYP3A4 metabolism of cyclosporine, resulting in significant increases in cyclosporine plasma concentrations. If these drugs are used together, monitor serum creatinine and cyclosporine concentrations, and adjust cyclosporine dosage accordingly. Renal transplant patients stabilized on cyclosporine for at least 6 months and on a stable cyclosporine dose for at least 6 weeks received fluconazole 200 mg PO daily for 14 days. Cyclosporine AUC, Cmax, Cmin were increased by 92%, 60%, and 157%, respectively. In addition, the apparent cyclosporine clearance decreased by 45%.
    Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with fluconazole, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
    Daridorexant: (Major) Limit the daridorexant dose to 25 mg if coadministered with fluconazole. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Concomitant use of another moderate CYP3A inhibitor increased daridorexant overall exposure 2.4-fold.
    Darifenacin: (Moderate) Fluconazole, an inhibitor of CYP3A4, may decrease the metabolism of darifenacin and increase serum concentrations. Patients should be monitored for increased anticholinergic effects if these drugs are used concomitantly; dosage adjustments of darifenacin may be necessary.
    Darunavir: (Moderate) Caution is warranted when darunavir is administered with fluconazole as there is a potential for elevated concentrations of darunavir. Fluconazole is a CYP3A4 inhibitor, while darunavir is a CYP3A4 substrate.
    Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with fluconazole as there is a potential for elevated cobicistat concentrations. Fluconazole is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when darunavir is administered with fluconazole as there is a potential for elevated concentrations of darunavir. Fluconazole is a CYP3A4 inhibitor, while darunavir is a CYP3A4 substrate.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with fluconazole as there is a potential for elevated cobicistat concentrations. Fluconazole is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when darunavir is administered with fluconazole as there is a potential for elevated concentrations of darunavir. Fluconazole is a CYP3A4 inhibitor, while darunavir is a CYP3A4 substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid concurrent administration of fluconazole with dasabuvir; ombitasvir; paritaprevir; ritonavir due to an increased risk of QT prolongation. Although therapy with dasabuvir; ombitasvir; paritaprevir; ritonavir did not prolong the QTc interval to a clinical relevant extent in healthy subjects, ritonavir has been associated with concentration-dependent QT prolongation in other trials. Concurrent use of fluconazole with other agents known to prolong the QT interval and which are metabolized by CYP3A4 is contraindicated. Fluconazole is an inhibitor of the hepatic isoenzyme CYP3A4; ritonavir, paritaprevir, and dasabuvir (minor) are metabolized by this enzyme. (Moderate) Caution is warranted with the use of fluconazole and ritonavir as ritonavir serum concentrations may be increased resulting in increased treatment-related adverse effects. Fluconazole is a moderate CYP3A4 inhibitor, while ritonavir is a substrate of CYP3A4.
    Dasatinib: (Contraindicated) Coadministration of fluconazole and dasatinib is contraindicated due to the potential for QT prolongation. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as dasatinib. Coadministration of fluconazole with dasatinib may result in elevated plasma concentrations of dasatinib, causing an increased risk for adverse events, such as QT prolongation.
    Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with fluconazole. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; fluconazole is a moderate inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
    Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving fluconazole as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
    Desflurane: (Major) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with fluconazole include the halogenated anesthetics Halogenated anesthetics can prolong the QT interval and have been associated with QT prolongation and rare cases of torsades de pointes (TdP).
    Desipramine: (Minor) Fluconazole should be administered together with TCAs with caution. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, fluconazole inhibits CYP2C19 and CYP3A4; both CYP2C19 and CYP3A4 are partially involved in the metabolism of TCAs. Fluconazole has been reported to increase the effects of amitriptyline. In at least one case, the interaction resulted in an increased incidence of TCA-related side effects, such as dizziness and syncope. In another case, QT-prolongation and TdP occurred. Desipramine may be affected by this potential interaction, but specific data are lacking.
    Desogestrel; Ethinyl Estradiol: (Minor) CYP3A4 inhibitors such as fluconazole may increase plasma hormone concentrations of ethinyl estradiol. Fluconazole tablets, administered concomitantly with oral contraceptives containing ethinyl estradiol have resulted in an overall mean increase in ethinyl estradiol compared to placebo. However, in some patients there are decreases up to 47% of ethinyl estradiol concentrations. The available data indicate that the decreases in some individual ethinyl estradiol AUC values with fluconazole treatment are likely due to random variation. While there is evidence that fluconazole can inhibit the metabolism of ethinyl estradiol, there is no evidence that fluconazole is a net inducer of ethinyl estradiol metabolism. The clinical significance of these effects is unknown.
    Deutetrabenazine: (Moderate) Use fluconazole with caution in combination with deutetrabenazine. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dextromethorphan; Quinidine: (Contraindicated) The concomitant administration of fluconazole and quinidine is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as quinidine. Coadministration of fluconazole with quinidine may result in elevated plasma concentrations of quinidine, causing an increased risk for adverse events, such as QT prolongation.
    Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with fluconazole is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP2C19 and CYP3A substrate and fluconazole is a CYP2C19 and CYP3A inhibitor.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and fluconazole together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dichlorphenamide dose or discontinuing dichlorphenamide therapy.
    Diclofenac: (Moderate) Monitor for diclofenac toxicity if coadministered with fluconazole; a diclofenac dosage adjustment may be necessary. Concurrent use may increase diclofenac exposure. Diclofenac is a CYP2C9 substrate and fluconazole is a CYP2C9 inhibitor.
    Diclofenac; Misoprostol: (Moderate) Monitor for diclofenac toxicity if coadministered with fluconazole; a diclofenac dosage adjustment may be necessary. Concurrent use may increase diclofenac exposure. Diclofenac is a CYP2C9 substrate and fluconazole is a CYP2C9 inhibitor.
    Dienogest; Estradiol valerate: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives. (Minor) Estradiol valerate and dienogest are both substrates of CYP3A4. Certain azole antifungals, including fluconazole, itraconazole, ketonconazole, miconazole (systemic formulation only), posaconazole, and voriconazole, are CYP3A4 inhibitors and therefore may inhibit the metabolism of dienogest; estradiol valerate, possibly leading to increased serum concentrations. In a pharmacokinetic study evaluating the effect of ketoconazole on dienogest and estradiol, co-administration with ketoconazole increased the AUC at steady-state for dienogest and estradiol by 2.86 and 1.57-fold, respectively. There was also a 1.94 and 1.65-fold increase of Cmax at steady-state for dienogest and estradiol when co-administered with ketoconazole.
    Dihydroergotamine: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and fluconazole is a moderate CYP3A inhibitor.
    Diltiazem: (Moderate) Monitor blood pressure and heart rate if coadministration of diltiazem with fluconazole is necessary. Concurrent use may result in elevated diltiazem concentrations. Diltiazem is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
    Diphenhydramine; Ibuprofen: (Moderate) Fluconazole is an inhibitor of CYP2C9, which is the isoenzyme responsible for the metabolism of ibuprofen. Thus, increased plasma concentrations of ibuprofen are possible. If fluconazole is administered concurrently with ibuprofen, monitor for NSAID-related side-effects such as fluid retention, GI irritation, or renal dysfunction and adjust the ibuprofen dose, if needed. Among 12 healthy males, the mean systemic exposure of S-(+)-ibuprofen after a single dose of 400 mg of racemic ibuprofen was 67.4 +/- 16.2 mcg x hour/mL. In contrast, the mean systemic exposure was 122 +/- 32 mcg x hour/mL when ibuprofen was given 1 hour after the second fluconazole dose; fluconazole 400 mg was given on day 1 and 200 mg was given on day 2. In addition to increased systemic exposure, the maximum concentration and half-life of S-(+)-ibuprofen were all statistically significantly greater in the presence of fluconazole. Increased S-(+)-ibuprofen concentrations leads to increased inhibition of both COX-1 and COX-2, and impaired ibuprofen metabolism due to mutations in the CYP2C9 gene increases the risk of acute gastrointestinal bleeding.
    Disopyramide: (Contraindicated) The concomitant administration of fluconazole and disopyramide is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as disopyramide. Coadministration of fluconazole with disopyramide may result in elevated plasma concentrations of disopyramide, causing an increased risk for adverse events, such as QT prolongation.
    Docetaxel: (Minor) Docetaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit the CYP3A enzymes, such as fluconazole, can significantly reduce the metabolism of docetaxel. Use docetaxel cautiously when administered concurrently with inhibitors of CYP3A enzymes.
    Dofetilide: (Contraindicated) Coadministration of dofetilide and fluconazole is contraindicated as concurrent use may increase the risk of QT prolongation and torsade de pointes (TdP). Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Fluconazole has been associated with QT prolongation and rare cases of TdP. Additionally, fluconazole is also an inhibitor of CYP3A4, which could increase dofetilide exposure, further increasing the risk of cardiac events.
    Dolasetron: (Moderate) Administer dolasetron with caution in combination with fluconazole as concurrent use may increase the risk of QT prolongation. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Contraindicated) Concurrent use of fluconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Fluconazole is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of rilpivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for adverse events, such as QT prolongation. Additionally, fluconazole has been associated with prolongation of the QT interval; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine.
    Donepezil: (Moderate) Use donepezil with caution in combination with fluconazole as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Fluconazole has been associated with QT prolongation and rare cases of TdP.
    Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with fluconazole as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Fluconazole has been associated with QT prolongation and rare cases of TdP.
    Doxepin: (Minor) Use fluconazole and tricyclic antidepressants (TCAs) with caution. Fluconazole is associated with QT prolongation. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, fluconazole inhibits CYP2C19, CYP2C9, and CYP3A4; these enzymes are involved in the metabolism of some TCAs. Doxepin is primarily metabolized by CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9. In at least one case, a TCA interaction resulted in an increased incidence of TCA-related side effects, such as dizziness and syncope. In another case involving amitriptyline, QT-prolongation and torsade de pointes occurred. Concurrent administration of doxepin and fluconazole may result in increased doxepin plasma concentrations and subsequent adverse reactions.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as fluconazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Doxorubicin Liposomal: (Major) Avoid coadministration of fluconazole with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Fluconazole is a moderate CYP3A4 inhibitor, and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
    Doxorubicin: (Major) Avoid coadministration of fluconazole with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Fluconazole is a moderate CYP3A4 inhibitor, and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with fluconazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; fluconazole is a moderate inhibitor of both enzymes.
    Dronedarone: (Contraindicated) Concurrent use of dronedarone and fluconazole is contraindicated. Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Contraindicated) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). The concurrent use of fluconazole and other drugs that prolong the QT and are CYP3A4 substrates is contraindicated due to the risk of life-threatening arrhythmias such as TdP. Coadministration of fluconazole with drugs that are CYP3A4 substrates may result in an elevated plasma concentration of the interacting drug, causing an increased risk for adverse events, such as QT prolongation. Drugs that prolong QT and are substrates for CYP3A4 that are contraindicated with fluconazole include droperidol.
    Drospirenone; Estradiol: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
    Drospirenone; Ethinyl Estradiol: (Minor) CYP3A4 inhibitors such as fluconazole may increase plasma hormone concentrations of ethinyl estradiol. Fluconazole tablets, administered concomitantly with oral contraceptives containing ethinyl estradiol have resulted in an overall mean increase in ethinyl estradiol compared to placebo. However, in some patients there are decreases up to 47% of ethinyl estradiol concentrations. The available data indicate that the decreases in some individual ethinyl estradiol AUC values with fluconazole treatment are likely due to random variation. While there is evidence that fluconazole can inhibit the metabolism of ethinyl estradiol, there is no evidence that fluconazole is a net inducer of ethinyl estradiol metabolism. The clinical significance of these effects is unknown.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) CYP3A4 inhibitors such as fluconazole may increase plasma hormone concentrations of ethinyl estradiol. Fluconazole tablets, administered concomitantly with oral contraceptives containing ethinyl estradiol have resulted in an overall mean increase in ethinyl estradiol compared to placebo. However, in some patients there are decreases up to 47% of ethinyl estradiol concentrations. The available data indicate that the decreases in some individual ethinyl estradiol AUC values with fluconazole treatment are likely due to random variation. While there is evidence that fluconazole can inhibit the metabolism of ethinyl estradiol, there is no evidence that fluconazole is a net inducer of ethinyl estradiol metabolism. The clinical significance of these effects is unknown.
    Dutasteride: (Moderate) Dutasteride is metabolized by the CYP3A4/5 hepatic enzyme. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors including fluconazole.
    Dutasteride; Tamsulosin: (Moderate) Dutasteride is metabolized by the CYP3A4/5 hepatic enzyme. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors including fluconazole. (Moderate) Use caution if coadministration of fluconazole with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
    Duvelisib: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with fluconazole. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; fluconazole is a moderate CYP3A inhibitor.
    Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with flucanazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with flucanazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with flucanazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
    Elagolix; Estradiol; Norethindrone acetate: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
    Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with fluconazole may cause the plasma concentrations of elbasvir and grazoprevir to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Fluconazole is a moderate inhibitor of CYP3A; both elbasvir and grazoprevir are metabolized by CYP3A. If these drugs are used together, closely monitor for signs of hepatotoxicity.
    Eletriptan: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with fluconazole. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A, and fluconazole is a moderate CYP3A inhibitor. Coadministration of other moderate CYP3A inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Elexacaftor; tezacaftor; ivacaftor: (Major) Adjust the elexacaftor; tezacaftor; ivacaftor dosing schedule when coadministered with fluconazole; coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 2 elexacaftor; tezacaftor; ivacaftor combination tablets every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., elexacaftor/tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Elexacaftor, tezacaftor, and ivacaftor are CYP3A4 substrates (ivacaftor is a sensitive substrate); fluconazole is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. Simulation suggests a moderate inhibitor may increase elexacaftor and tezacaftor exposure by 2.3-fold and 2-fold, respectively. (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with fluconazole; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); fluconazole is a moderate CYP3A inhibitor. Coadministration of fluconazole increased ivacaftor exposure 3-fold. Simulation suggests fluconazole may increase tezacaftor exposure 2-fold. (Major) If fluconazole and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate. Coadministration with fluconazole, a moderate CYP3A inhibitor, increased ivacaftor exposure by 3-fold.
    Eliglustat: (Contraindicated) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of fluconazole and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of fluconazole and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both fluconazole and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and fluconazole can independently prolong the QT interval, and coadministration increases this risk. Fluconazole is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as fluconazole, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Although fluconazole's product labeling states that coadministration of other drugs that prolong the QT interval and are metabolized by CYP3A4 is contraindicated, the specific interaction between fluconazole and eliglustat was studied during clinical trials and supports eliglustat dosage reduction in EMs instead of contraindication.Physiology-based pharmacokinetic (PBPK) models suggest that fluconazole may increase the Cmax and AUC of eliglustat 2.8- and 3.2-fold, respectively, in EMs and 2.5- and 2.9-fold, respectively, in IMs. PBPK suggests fluconazole may increase the Cmax and AUC of eliglustat 2.4- and 3-fold, respectively, when administered with eliglustat 84 mg PO once daily in PMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a moderate 2D6 inhibitor and fluconazole (moderate 3A4 inhibitor) may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs.
    Elvitegravir: (Moderate) Caution is warranted when elvitegravir is administered with fluconazole as there is a potential for elevated elvitegravir concentrations. Fluconazole is a CYP3A4 and CYP2D6 inhibitor, while elvitegravir is a substrate of CYP3A4.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with fluconazole as there is a potential for elevated cobicistat concentrations. Fluconazole is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when elvitegravir is administered with fluconazole as there is a potential for elevated elvitegravir concentrations. Fluconazole is a CYP3A4 and CYP2D6 inhibitor, while elvitegravir is a substrate of CYP3A4.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with fluconazole as there is a potential for elevated cobicistat concentrations. Fluconazole is a CYP3A4 inhibitor, while cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when elvitegravir is administered with fluconazole as there is a potential for elevated elvitegravir concentrations. Fluconazole is a CYP3A4 and CYP2D6 inhibitor, while elvitegravir is a substrate of CYP3A4.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Concurrent use of fluconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Fluconazole is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of rilpivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for adverse events, such as QT prolongation. Additionally, fluconazole has been associated with prolongation of the QT interval; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent use of fluconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Fluconazole is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of rilpivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for adverse events, such as QT prolongation. Additionally, fluconazole has been associated with prolongation of the QT interval; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine.
    Enalapril; Felodipine: (Moderate) Fluconazole may decrease the clearance of calcium-channel blockers, including felodipine, via inhibition of CYP3A4 metabolism. Monitor blood pressure closely during concurrent use of these medications.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
    Encorafenib: (Contraindicated) The concurrent use of fluconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as encorafenib, is contraindicated. Fluconazole has been associated with QT prolongation.
    Entrectinib: (Major) Avoid coadministration of entrectinib with fluconazole due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If fluconazole is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of fluconazole. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; fluconazole is a moderate CYP3A4 inhibitor that has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
    Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Fluconazole is a CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
    Erdafitinib: (Major) Avoid coadministration of erdafitinib and fluconazole due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If fluconazole is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP2C9 substrate and fluconazole is a moderate CYP2C9 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 121% and 148%, respectively, when coadministered with fluconazole.
    Ergoloid Mesylates: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and fluconazole is a moderate CYP3A inhibitor.
    Ergonovine: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and fluconazole is a moderate CYP3A inhibitor.
    Ergot alkaloids: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and fluconazole is a moderate CYP3A inhibitor.
    Ergotamine: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and fluconazole is a moderate CYP3A inhibitor.
    Ergotamine; Caffeine: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined. (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and fluconazole is a moderate CYP3A inhibitor.
    Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include fluconazole.
    Erythromycin: (Major) Concomitant use of fluconazole and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Escitalopram: (Moderate) Concomitant use of fluconazole and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Esomeprazole: (Minor) Fluconazole may inhibit the CYP2C19 isoenzyme, leading to increased plasma levels of drugs that are substrates for the CYP2C19 isoenzyme, such as esomeprazole.
    Estazolam: (Moderate) In vitro studies with human liver microsomes indicate that the biotransformation of estazolam to the major circulating metabolite 4-hydroxy-estazolam is mediated by CYP3A. In theory, CYP3A4 inhibitors, such as fluconazole, may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity. The manufacturer suggests that estazolam be used only with caution and consideration of appropriate dosage reduction during coadministration.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
    Estradiol: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
    Estradiol; Levonorgestrel: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
    Estradiol; Norethindrone: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
    Estradiol; Norgestimate: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
    Estradiol; Progesterone: (Minor) As fluconazole inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives. (Minor) The metabolism of progesterone may be inhibited by fluconazole, an inhibitor of cytochrome P450 3A4 hepatic enzymes.
    Eszopiclone: (Moderate) A pharmacokinetic study of ketoconazole coadministered with eszopiclone resulted in an a 2.2-fold increase in eszopiclone AUC. Although fluconazole inhibits CYP3A4 to a lesser extent than ketoconazole, a clinically relevant interaction is possible, and dose adjustments of eszopiclone may be necessary. CYP3A4 is a primary metabolic pathway for eszopiclone, and increased systemic exposure to eszopiclone increases the risk of next-day psychomotor or memory impairment, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Ethinyl Estradiol: (Minor) CYP3A4 inhibitors such as fluconazole may increase plasma hormone concentrations of ethinyl estradiol. Fluconazole tablets, administered concomitantly with oral contraceptives containing ethinyl estradiol have resulted in an overall mean increase in ethinyl estradiol compared to placebo. However, in some patients there are decreases up to 47% of ethinyl estradiol concentrations. The available data indicate that the decreases in some individual ethinyl estradiol AUC values with fluconazole treatment are likely due to random variation. While there is evidence that fluconazole can inhibit the metabolism of ethinyl estradiol, there is no evidence that fluconazole is a net inducer of ethinyl estradiol metabolism. The clinical significance of these effects is unknown.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) CYP3A4 inhibitors such as fluconazole may increase plasma hormone concentrations of ethinyl estradiol. Fluconazole tablets, administered concomitantly with oral contraceptives containing ethinyl estradiol have resulted in an overall mean increase in ethinyl estradiol compared to placebo. However, in some patients there are decreases up to 47% of ethinyl estradiol concentrations. The available data indicate that the decreases in some individual ethinyl estradiol AUC values with fluconazole treatment are likely due to random variation. Wh