Fluconazole

Pharmacologic Category

Antifungal Agent, Azole Derivative; Antifungal Agent, Oral; Antifungal Agent, Parenteral

Dosing: Adult

Blastomycosis (off-label use):

CNS disease (alternative agent): Step-down therapy: Oral: 800 mg once daily for ≥12 months and until resolution of cerebrospinal (CSF) abnormalities (Bradsher 2020; IDSA [Chapman 2008]).

Pulmonary disease (alternative agent if unable to tolerate itraconazole): Oral: 400 to 800 mg once daily for 6 to 12 months (IDSA [Chapman 2008]; Pappas 1997).

Candidiasis, treatment: Note: Consider weight-based dosing for patients <50 kg or >90 kg (Rex 1994; Rex 2003). A maximum dose has not been established, but based on a small number of patients, doses up to 1.6 g/day appear to be well tolerated (Anaissie 1995).

Candidemia (neutropenic and non-neutropenic patients):

Initial therapy (alternative to echinocandin if no previous azole exposure, noncritically ill, and not at high risk of fluconazole-resistant isolate): IV, Oral: Loading dose of 800 mg (12 mg/kg) on day 1, then 400 mg (6 mg/kg) once daily; if fluconazole-susceptible Candida glabrata isolated, transition to 800 mg (12 mg/kg) once daily (IDSA [Pappas 2016]).

Step-down therapy:

Isolates other than C. glabrata: Oral: 400 mg (6 mg/kg) once daily (IDSA [Pappas 2016]).

Isolates of C. glabrata (if fluconazole-susceptible or susceptible dose-dependent): Oral: 800 mg (12 mg/kg) once daily (IDSA [Pappas 2016]; Kauffman 2020a).

Duration: Continue for ≥14 days after first negative blood culture and resolution of signs/symptoms (longer duration required in patients with metastatic complications); step-down therapy to oral fluconazole (eg, after initial therapy with an echinocandin) is recommended after 5 to 7 days in stable patients with negative repeat cultures and fluconazole-susceptible isolates (IDSA [Pappas 2016]; Kauffman 2020a).

Candidiasis, invasive (empiric therapy) and/or critically ill non-neutropenic patients in the ICU at risk of invasive candidiasis with fever and unidentified etiology (alternative to echinocandin if not critically ill and unlikely to be colonized with a fluconazole-resistant isolate): IV, Oral: Loading dose of 800 mg (12 mg/kg) on day 1, then 400 mg (6 mg/kg) once daily; continue for ≥14 days in patients with clinical improvement. Consider discontinuing after 4 to 5 days in patients with no clinical response and no evidence of invasive candidiasis (IDSA [Pappas 2016]; Kauffman 2020a).

Cardiac device infection (eg, implantable cardiac defibrillator, pacemaker, ventricular assist device [VAD]): Step-down therapy: IV, Oral: 400 to 800 mg (6 to 12 mg/kg) once daily for 4 to 6 weeks after device removal (4 weeks for infections limited to generator pockets and ≥6 weeks for infections involving wires). Note: If VAD cannot be removed, chronic suppressive therapy with fluconazole 400 to 800 mg (6 to 12 mg/kg) once daily should be used (IDSA [Pappas 2016]).

Chronic, disseminated (hepatosplenic): Step-down therapy: Oral: 400 mg (6 mg/kg) once daily; continue until lesion resolution (usually several months) and through periods of immunosuppression (IDSA [Pappas 2016]).

CNS: Step-down therapy (fluconazole-susceptible isolates): IV, Oral: 400 to 800 mg (6 to 12 mg/kg) once daily; continue until signs/symptoms and CSF/radiologic abnormalities have resolved (IDSA [Pappas 2016]; IDSA [Tunkel 2017]).

Endocarditis, native or prosthetic valve: Step-down therapy (fluconazole-susceptible isolates): IV, Oral: 400 to 800 mg (6 to 12 mg/kg) once daily for ≥6 weeks after valve replacement surgery (longer durations recommended in patients with perivalvular abscesses or other complications). Note: In patients who cannot undergo valve replacement surgery or with prosthetic valve endocarditis, chronic suppressive therapy with fluconazole 400 to 800 mg (6 to 12 mg/kg) once daily should be used (IDSA [Pappas 2016]).

Endophthalmitis, endogenous (with or without vitritis) (fluconazole-susceptible isolates): IV, Oral: Loading dose of 800 mg (12 mg/kg) on day 1, then 400 to 800 mg (6 to 12 mg/kg) once daily for ≥4 to 6 weeks and until examination indicates resolution (longer duration may be needed for patients with vitritis); for patients with vitritis or macular involvement, intravitreal antifungal therapy is also recommended (IDSA [Pappas 2016]; Kauffman 2020b).

Esophageal: IV, Oral: Loading dose of 400 mg (6 mg/kg) on day 1, then 200 to 400 mg (3 to 6 mg/kg) once daily for 14 to 21 days; for patients with HIV with recurrent infections who have not attained immune reconstitution on antiretroviral therapy, chronic suppressive therapy of 100 to 200 mg 3 times weekly may be used (Goldman 2005; IDSA [Pappas 2016]; Kauffman 2018).

Intertrigo, refractory to topical therapy (off-label use): Oral: 150 mg once weekly for 4 weeks (Brodell 2018; Nozickova 1998; Stengel 1994).

Intra-abdominal infections (alternative to echinocandin if no previous azole exposure, noncritically ill, and not at high risk of fluconazole-resistant isolate): IV, Oral: Loading dose of 800 mg (12 mg/kg) on day 1, then 400 mg (6 mg/kg) once daily; duration is for ≥2 weeks and until all signs of infection have resolved. Step-down therapy (after patient has responded to initial therapy [eg, echinocandin]) with fluconazole is recommended in stable patients with a fluconazole-susceptible isolate (IDSA [Pappas 2016]; Kauffman 2020c).

Oropharyngeal: IV, Oral: Loading dose of 200 mg on day 1, then 100 to 200 mg once daily for 7 to 14 days; recommended for patients unresponsive to topical therapy or those with moderate to severe infection, recurrent infection, or risk for esophageal candidiasis (eg, patients with HIV with CD4 counts <100 cells/mm3). In patients with recurrent infection, chronic suppressive therapy (100 mg 3 times weekly) may be considered, but is usually unnecessary (IDSA [Pappas 2016]; Kauffman 2018).

Osteoarticular (osteomyelitis or septic arthritis) (fluconazole-susceptible isolates): Initial or step-down therapy: IV, Oral: 400 mg (6 mg/kg) once daily. Duration for osteomyelitis is 6 to 12 months and for septic arthritis is 6 weeks. Course may include 2 weeks of initial treatment with a lipid formulation of amphotericin B or an echinocandin. For prosthetic joints that cannot be removed, chronic suppressive therapy with fluconazole 400 mg (6 mg/kg) once daily is recommended (IDSA [Pappas 2016]).

Peritonitis, associated with peritoneal dialysis: Note: Use for empiric treatment if no prior azole exposure or for directed therapy against fluconazole-susceptible isolates (Glickman 2019):

IV, Oral: 200 mg on day 1, then 100 to 200 mg once daily for 2 to 4 weeks (Chen 2004; Glickman 2019; ISPD [Li 2016]; Wang 2000).

Thrombophlebitis, suppurative: Initial or step-down therapy: IV, Oral: 400 to 800 mg (6 to 12 mg/kg) once daily for ≥2 weeks after candidemia (if present) has cleared (IDSA [Pappas 2016]).

Urinary tract infection:

Candiduria (asymptomatic):

Patients with neutropenia: Treat as if patient has candidemia (Georgiadou 2013; IDSA [Pappas 2016]).

Patients undergoing a urologic procedure: Oral: 400 mg (6 mg/kg) once daily several days before and after the procedure (IDSA [Pappas 2016]).

Cystitis (symptomatic): Oral: 200 mg (3 mg/kg) once daily for 2 weeks (IDSA [Pappas 2016]).

Pyelonephritis: Oral: 200 to 400 mg (3 to 6 mg/kg) once daily for 2 weeks (IDSA [Pappas 2016]).

Urinary tract infection associated with fungus balls: Oral: 200 to 400 mg (3 to 6 mg/kg) once daily; concomitant amphotericin B deoxycholate irrigation via nephrostomy tubes, if present, is also recommended, along with surgical management (IDSA [Pappas 2016]).

Vaginal/Vulvovaginal:

Uncomplicated: Oral: 150 mg as a single dose (IDSA [Pappas 2016]; manufacturer's labeling).

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

Recurrent: Oral: 150 mg every 72 hours for 10 to 14 days, followed by 150 mg once weekly for 6 months (IDSA [Pappas 2016]; Sobel 2004) or 100 mg, 150 mg, or 200 mg every 72 hours for 3 doses, then 100 mg, 150 mg, or 200 mg once weekly for 6 months (CDC [Workowski 2015]).

Candidiasis, prophylaxis:

Hematologic malignancy patients (off-label use) or hematopoietic cell transplant (HCT) recipients who do not warrant mold-active prophylaxis (off-label use): Oral: 400 mg once daily. Duration is at least until resolution of neutropenia and/or through day 75 in allogeneic HCT recipients (ASBMT [Tomblyn 2009]; ASCO/IDSA [Taplitz 2018]; Glasmacher 2006; Wingard 2019).

ICU patients (high risk) in units with a high rate (>5%) of invasive candidiasis (off-label use): Oral, IV: Loading dose of 800 mg (12 mg/kg) once on day 1, then 400 mg (6 mg/kg) once daily (IDSA [Pappas 2016]). Note: Some experts do not routinely use prophylaxis in this setting (Kauffman 2020a).

Peritoneal dialysis-associated infection (concurrently treated with antibacterials), prevention of secondary fungal infection: Oral: 200 mg every other day or 100 mg once daily (Burkart 2018; Glickman 2019; Restrepo 2010).

Solid organ transplant recipients (selected patients at high-risk for Candida infection) (off-label use): Oral, IV: 400 mg (6 mg/kg) given perioperatively and continued once daily postoperatively; indications and duration vary among transplant centers (ASHP/IDSA/SIS/SHEA [Bratzler 2013]; Fishman 2020; Winston 2002).

Coccidioidomycosis, treatment (off-label use):

Bone and/or joint infection: Initial or step-down therapy: Oral: 800 mg once daily for ≥3 years; in some cases, lifelong treatment is needed; duration depends on severity and host immunocompetence (IDSA [Galgiani 2016]).

Meningitis: Oral: 400 mg to 1.2 g once daily, depending on severity (IDSA [Galgiani 2016]); some experts favor a starting dose of ≥800 mg once daily (AST-IDCOP [Miller 2019]; Blair 2020). Continue lifelong as there is a high relapse rate when the dose is decreased or treatment is discontinued (HHS [OI adult 2020]; IDSA [Galgiani 2016]).

Pneumonia, primary infection: Note: Only for patients with significantly debilitating illness, extensive pulmonary involvement, concurrent diabetes, frailty due to age or comorbidities, or HIV (HHS [OI adult 2020]; IDSA [Galgiani 2016]):

Oral: Usual dose: 400 mg once daily; IDSA guidelines state that some experts recommend 800 mg once daily. Duration of therapy is 3 to 6 months for immunocompetent patients; immunocompromised patients require a longer duration of therapy (sometimes lifelong) (HHS [adult OI 2020]; IDSA [Galgiani 2016]).

Pneumonia, symptomatic chronic cavitary and/or cavitary disease in immunocompromised patients: Oral: 400 mg once daily for ≥12 months. In patients with ruptured cavities, the duration may be shorter, but depends upon the postoperative course (IDSA [Galgiani 2016]; Jaroszewski 2020).

Soft tissue infection (not associated with bone infection): Oral: 400 mg once daily; some experts give up to 800 mg once daily; duration is for ≥6 to 12 months (IDSA [Galgiani 2016]).

Coccidioidomycosis, prophylaxis (off-label use):

Patients with HIV: Note: Primary prophylaxis is not recommended; yearly or twice-yearly serologic testing should be performed in patients living in endemic areas.

Patients with a CD4 count <250 cells/mm3 who have a new positive serology: Oral: 400 mg once daily until antiretroviral therapy has fully suppressed HIV replication and the CD4 count is ≥250 cells/mm3 (HHS [OI adult 2020]).

Solid organ transplant recipients:

Seronegative patients in endemic areas (regardless of clinical history of coccidioidomycosis): Oral: 200 mg once daily for 6 to 12 months following transplantation (AST-IDCOP [Miller 2019]; IDSA [Galgiani 2016]); some experts favor 400 mg once daily (Ampel 2020).

Seropositive patients in endemic areas: Oral: 400 mg once daily for 6 to 12 months following transplantation (AST-IDCOP [Miller 2019]; IDSA [Galgiani 2016]); some experts favor 400 mg once daily for 12 months posttransplantation followed by 200 mg once daily for the duration of immunosuppressive therapy (Ampel 2020).

Cryptococcal meningitis: Note: Treatment involves induction, consolidation, and maintenance phases of therapy.

Patients with HIV:

Induction: Oral:

Resource-rich settings, alternative regimens:

If flucytosine is unavailable or not tolerated: 800 mg once daily in combination with amphotericin B (lipid formulation preferred) for ≥2 weeks (HHS [OI adult 2020]); or

If amphotericin B is unavailable or not tolerated: 800 mg to 1.2 g once daily in combination with flucytosine for ≥2 weeks (IDSA [Perfect 2010]; Molloy 2018; Nussbaum 2010); or

If flucytosine and amphotericin B are unavailable or not tolerated: 1.2 g once daily as monotherapy for ≥2 weeks (HHS [OI adult 2020]).

Resource-limited settings:

Amphotericin B deoxycholate in combination with flucytosine for 1 week followed by fluconazole 1.2 g once daily for 1 week (preferred regimen) (WHO 2018); or

If IV therapy is difficult to administer: 1.2 g once daily as a 2-week induction regimen in combination with flucytosine for 2 weeks (WHO 2018); or

If flucytosine is unavailable: 1.2 g once daily in combination with amphotericin B deoxycholate for 2 weeks (WHO 2018).

Note: Induction therapy should be continued beyond the durations listed above if clinical improvement is not observed and/or if CSF cultures remain positive (Cox 2018).

Consolidation: Oral: 400 mg once daily for ≥8 weeks following induction with the preferred regimen of amphotericin B and flucytosine (HHS [OI adult 2020]; IDSA [Perfect 2010]); patients receiving any other induction regimen should receive 800 mg once daily for ≥8 weeks (Cox 2018; IDSA [Perfect 2010]; WHO 2018).

Maintenance (suppression): Oral: 200 mg once daily for ≥12 months; may discontinue if completed induction, consolidation, and ≥12 months of maintenance therapy, patient remains asymptomatic, and CD4 count has been ≥100 cells/mm3 for ≥3 months and HIV RNA is suppressed in response to effective antiretroviral therapy (HHS [OI adult 2020]).

HIV-uninfected patients:

Induction (alternative regimens): Oral:

If flucytosine is unavailable or not tolerated: 800 mg once daily in combination with amphotericin B for 2 weeks (Cox 2020a); or

If amphotericin B is unavailable or not tolerated: 800 mg to 1.2 g once daily in combination with flucytosine for 2 to 10 weeks, depending on severity and response to therapy (Cox 2020a); or

If amphotericin B and flucytosine are unavailable or not tolerated: 1.2 g once daily as monotherapy for ≥10 weeks (Cox 2020a).

Consolidation: Oral: 400 to 800 mg once daily for 8 weeks (800 mg once daily preferred for patients who receive a 2-week induction course) (AST-IDCOP [Baddley 2019]; Cox 2020a; IDSA [Perfect 2010]).

Maintenance (suppression): Oral: 200 to 400 mg once daily for 6 to 12 months (AST-IDCOP [Baddley 2019]; IDSA [Perfect 2010]). A longer duration may be warranted for patients receiving very high doses of immunosuppression (eg, high-dose steroids or biologic agents [eg, alemtuzumab]) or with radiographic evidence of cryptococcoma (AST-IDCOP [Baddley 2019]; Cox 2020a).

Cryptococcosis, pulmonary infection (off-label use):

Mild to moderate symptoms (if severe pneumonia, treat like CNS infection): Immunocompetent or immunocompromised patients without diffuse pulmonary infiltrates or disseminated infection: Oral: 400 mg once daily for 6 to 12 months (AST-IDCOP [Baddley 2019]; Cox 2020b; IDSA [Perfect 2010]); for patients with HIV, some experts recommend a duration of 12 months (HHS [OI adult 2020]). Chronic suppressive therapy may be warranted for patients with ongoing immunosuppression (AST-IDCOP [Baddley 2019]; Cox 2020b; HHS [OI adult 2020]).

Tinea:

Tinea corporis or cruris: Oral: 150 to 200 mg once weekly for 2 to 4 weeks (Goldstein 2020; Kotogyan 1996; Montero-Gei 1992; Stary 1998).

Tinea pedis: Oral: 150 mg once weekly for 2 to 6 weeks (Gupta 2008; Kotogyan 1996; Montero-Gei 1992).

Tinea versicolor: Oral: 300 mg once weekly for 2 weeks (Karakas 2005).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Renal function estimated using the Cockcroft-Gault formula.

No adjustment for vaginal candidiasis single-dose therapy.

For multiple dosing, administer 100% of the indication-specific loading/initial dose recommended in the adult dosing section, then adjust daily doses as follows: IV, Oral (Berl 1995; manufacturer's labeling):

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl ≤50 mL/minute: Reduce dose by 50%.

Hemodialysis, intermittent (thrice weekly): IV, Oral: Dialyzable (33% to 38% with low-flux dialyzers [Oono 1992; Toon 1990]): No dosage adjustment necessary for indication-specific loading/initial or maintenance dose recommended in the adult dosing section; however, only administer maintenance doses 3 times/week (on dialysis days) after the hemodialysis session (Berl 1995).

Peritoneal dialysis:

IV, Oral: Initial: Administer 100% of the indication-specific loading/initial dose recommended in the adult dosing section; reduce maintenance doses by 50% (Cousin 2003; expert opinion).

CRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour), unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: IV, Oral:

If the usual recommended dose is 200 mg once daily, administer 400 mg once daily (expert opinion; see note regarding increased clearance in patients receiving renal replacement therapy below).

If the usual recommended dose is 400 mg once daily, administer an 800 mg loading dose, followed by maintenance doses of 800 mg/day in 1 to 2 divided doses (Bergner 2006; Kishino 2001; Muhl 2000; Patel 2011).

If the usual recommended dose is 800 mg once daily, administer a 1.2 g loading dose, followed by maintenance doses of 1.2 g/day in 1 to 2 divided doses (expert opinion; see note regarding increased clearance in patients receiving renal replacement therapy below).

Note: Fluconazole undergoes substantial tubular reabsorption in patients with normal kidney function. Because this reabsorption is absent in anuric patients receiving renal replacement therapy, total fluconazole clearance during CRRT with rates of 1,500 to 3,000 mL/hour is 1.5 to 2.3 times that reported in healthy volunteers (Bergner 2006; Kishino 2001; Muhl 2000; Patel 2011; Valtonen 1997).

PIRRT (eg, sustained, low-efficiency diafiltration): Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

PIRRT (effluent flow rate 4 to 5 L/hour, 8- to 10-hour session given every day):

IV, Oral:

Loading dose:

Administer 100% of the recommended indication-specific loading dose recommended in the adult dosing section.

Maintenance dose: Note: Optimal dose not well established. Select dose based on pathogen, minimum inhibitory concentration, immunocompromised state, and disease severity.

400 mg once (Sinnollareddy 2015; expert opinion) or twice daily (Gharibian 2016).

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

General dosing, susceptible infection: Infants, Children, and Adolescents: IV, Oral: Initial: 6 to 12 mg/kg/dose, followed by 3 to 12 mg/kg/dose once daily; duration and dosage depends on severity of infection; the manufacturer suggests limiting dose to 600 mg/dose.

Candida infections, prophylaxis:

Oncology patients at high risk of invasive candidiasis (eg, AML, recurrent ALL, myelodysplastic syndrome [MDS], HSCT recipients): Limited data available: Infants, Children, and Adolescents: IV, Oral: 6 to 12 mg/kg/dose once daily; maximum dose: 400 mg/dose; duration dependent upon type of transplant and/or chemotherapy, consult institution-specific protocols (ESCMID [Hope 2012]; Science 2014).

Surgical prophylaxis, high-risk patients undergoing liver, pancreas, kidney, or pancreas-kidney transplantation: Infants, Children, and Adolescents: IV: 6 mg/kg as a single dose 60 minutes before procedure; maximum dose: 400 mg/dose; time of initiation and duration varies with transplant type, consult institution-specific protocols (ASHP/IDSA [Bratzler 2013]).

Candidiasis, systemic (including Candidemia and invasive candidiasis), treatment: Infants, Children, and Adolescents: IV, Oral: 12 mg/kg/dose once daily; maximum dose: 800 mg/dose; continue treatment for 14 days after documented clearance and resolution of symptoms (ESCMID [Hope 2012]; IDSA [Pappas 2016]; Red Book [AAP 2018]).

Candidiasis, chronic, disseminated (hepatosplenic), step-down therapy: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily following several weeks of initial therapy with an amphotericin B lipid formulation or an echinocandin; treatment should continue until lesion resolution (usually several months); maximum dose: 400 mg/dose (IDSA [Pappas 2016]).

Candidiasis, CNS candidiasis, step-down therapy: Infants, Children, and Adolescents: Oral, IV: 12 mg/kg/dose once daily following initial therapy with liposomal amphotericin B (with or without flucytosine); maximum dose: 800 mg/dose; treatment should continue until all signs, symptoms, and CSF and radiological abnormalities have resolved (IDSA [Pappas 2016]; IDSA [Tunkel 2017]; Red Book [AAP 2018]).

Candidiasis, endophthalmitis, treatment: Oral, IV: Infants, Children, and Adolescents: 12 mg/kg/dose on day 1 followed by 6 to 12 mg/kg/dose once daily for at least 4 to 6 weeks until examination indicates resolution; maximum dose 800 mg/dose. Note: Use in combination with intravitreal injection of voriconazole or amphotericin B deoxycholate when vitritis or macular involvement is present (IDSA [Pappas 2016]).

Candidiasis, esophageal, treatment:

Non-HIV-exposed/-positive: Infants, Children, and Adolescents: IV, Oral: 6 mg/kg/dose once daily for 14 to 21 days. Note: Usual adult dose is 200 to 400 mg/day (IDSA [Pappas 2016]; Red Book [AAP 2018]).

HIV-exposed/-positive:

Infants and Children: IV, Oral: 6 to 12 mg/kg/dose once daily for 14 days following symptom resolution (minimum duration: 21 days); maximum dose: 600 mg/dose (HHS [OI pediatric 2018]).

Adolescents: IV, Oral: 100 to 400 mg once daily for 14 to 21 days; may follow with chronic suppressive therapy of 100 to 200 mg once daily for patients with frequent or severe recurrences (HHS [OI adult 2018]).

Candidiasis, oropharyngeal:

Non-HIV-exposed/-positive: Infants, Children, and Adolescents: IV, Oral: 6 mg/kg/dose on day 1 followed by 3 to 6 mg/kg/dose once daily for 7 to 14 days (IDSA [Pappas 2016]; Red Book [AAP 2018]). Note: Usual adult dose is 100 to 200 mg/day.

HIV-exposed/-positive:

Treatment:

Infants and Children: IV, Oral: 6 to 12 mg/kg/dose once daily for 7 to 14 days; maximum dose: 400 mg/dose (HHS [OI pediatric 2018]).

Adolescents: Oral: 100 mg once daily for 7 to 14 days; may follow with chronic suppressive therapy of 100 mg once daily or 3 times weekly for patients with frequent or severe recurrences (HHS [OI adult 2018]).

Secondary prophylaxis, recurrent severe: Infants and Children: Oral: 3 to 6 mg/kg/dose once daily; maximum dose: 200 mg/dose (HHS [OI pediatric 2018]).

Candidiasis, peritoneal dialysis-related infections (ISPD [Warady 2012]):

Peritonitis:

Treatment: Intraperitoneal, IV, Oral: 6 to 12 mg/kg/dose every 24 to 48 hours; maximum dose: 400 mg/dose.

Prophylaxis for high-risk situations (eg, during antibiotic therapy or PEG placement): IV, Oral: 3 to 6 mg/kg/dose every 24 to 48 hours; maximum dose: 200 mg/dose.

Exit-site or tunnel infection, treatment: Oral: 6 mg/kg/dose every 24 to 48 hours; maximum dose: 400 mg/dose.

Candidiasis, vulvovaginal infection:

Uncomplicated infections, treatment (independent of HIV status): Adolescents: Oral: 150 mg as a single dose (CDC [Workowski 2015]; HHS [OI adult 2018]).

Severe infections, treatment:

Non-HIV-exposed/-positive: Adolescents: Oral: 150 mg every 72 hours for 2 to 3 doses (CDC [Workowski 2015]; IDSA [Pappas 2016]).

HIV-exposed/-positive: Adolescents: Oral: 100 to 200 mg once daily for ≥7 days; may follow with chronic suppressive therapy of 150 mg once weekly (HHS [OI adult 2018]).

Recurrent infection, treatment:

Non HIV-exposed/-positive: Adolescents: Oral: Initial: 100 to 200 mg every 72 hours for 3 doses; followed by maintenance of 100 to 200 mg once weekly for 6 months (CDC [Workowski 2015]; IDSA [Pappas 2016]).

HIV-exposed/-positive: Adolescents: Oral: 100 to 200 mg once daily for ≥ 7 days; may follow with chronic suppressive therapy of 150 mg once weekly (HHS [OI adult 2018]).

Coccidioidomycosis (HIV-exposed/-positive) (HHS [OI adult 2018]; HHS [OI pediatric 2018]):

Mild to moderate non-meningeal infection (eg, focal pneumonia):

Infants and Children: IV, Oral: 6 to 12 mg/kg/dose once daily; maximum dose: 400 mg/dose.

Adolescents: Oral: 400 mg once daily for ≥6 months.

Severe illness (diffuse pulmonary or disseminated non-meningitic disease) initial therapy if unable to use amphotericin or as step-down therapy: Infants and Children: IV, Oral: 12 mg/kg/dose once daily; maximum dose: 800 mg/dose for a total of 1 year of treatment followed by secondary prophylaxis.

Meningeal infection:

Infants and Children: IV, Oral: 12 mg/kg/dose once daily; maximum dose: 800 mg/dose, followed by lifelong secondary prophylaxis.

Adolescents: IV, Oral: 400 to 800 mg once daily, followed by lifelong suppressive therapy.

Secondary prophylaxis/chromic suppressive therapy: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily; maximum dose: 400 mg/dose.

Cryptococcal infection:

Mild to moderate localized infection including pneumonia (not CNS), treatment:

Non HIV-exposed/-positive: Infants, Children, and Adolescents: Oral: 6 to 12 mg/kg/dose once daily for 6 to 12 months. Usual adult dose is 400 mg/dose (IDSA [Perfect 2010]).

HIV-exposed/-positive:

Infants and Children: IV, Oral: 12 mg/kg on day 1, then 6 to 12 mg/kg/dose once daily; maximum dose: 600 mg/dose; duration depends on severity and clinical response (HHS [OI pediatric 2018].

Adolescents: Oral: 400 mg daily for 12 months (HHS [OI adult 2018]).

CNS, severe pulmonary or disseminate infection, treatment:

Induction therapy: HIV-exposed/-positive (not first-line therapy):

Infants and Children: IV: 12 mg/kg on day 1, then 10 to 12 mg/kg/dose once daily in combination with amphotericin B or flucytosine for ≥14 days; maximum dose: 800 mg/dose (HHS [OI pediatric 2018]).

Adolescents: IV, Oral: 400 to 800 mg once daily in combination with flucytosine for ≥14 days or 800 mg once daily in combination with amphotericin for ≥14 days or 1,200 mg once daily as monotherapy for at least 2 weeks (HHS [OI adult 2018]).

Consolidation:

Non-HIV-exposed/-positive: Infants, Children, and Adolescents: IV, Oral: 10 to 12 mg/kg/day once daily or in divided doses twice daily for 8 weeks; maximum dose: 800 mg/dose (IDSA [Perfect 2010]; Red Book [AAP 2018]).

HIV-exposed/-positive:

Infants and Children: IV, Oral: 12 mg/kg on day 1, then 10 to 12 mg/kg/day once daily for ≥8 weeks; maximum daily dose: 800 mg/dose (HHS [OI pediatric 2018]).

Adolescents: IV, Oral: 400 mg once daily for ≥8 weeks (HHS [OI adult 2018]).

Secondary prophylaxis/chronic suppressive maintenance therapy:

Non-HIV-exposed/-positive: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for 6 to 12 months; maximum dose: 200 mg/dose (IDSA [Perfect 2010]).

HIV-exposed/-positive: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for ≥12 months; maximum dose: 200 mg/dose (HHS [OI adult 2018]; HHS [OI pediatric 2018]).

Histoplasmosis: HIV-exposed/-positive patients, alternative therapy (HHS [OI adult 2018]; HHS [OI pediatric 2018]):

Pulmonary, acute primary disease: Infants and Children: Oral: 3 to 6 mg/kg/dose once daily; maximum dose: 200 mg/dose.

Disseminated disease, mild to moderate:

Infants and Children: IV, Oral: 5 to 6 mg/kg/dose twice daily for 12 months; maximum dose: 300 mg/dose.

Adolescents: Oral: 800 mg once daily.

Secondary prophylaxis/chronic suppressive therapy:

Infants and Children: Oral: 3 to 6 mg/kg/dose once daily for ≥12 months; maximum dose: 200 mg/dose.

Adolescents: Oral: 400 mg once daily for ≥12 months.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

Altered kidney function: Note: Kidney function estimated using the Schwartz equation.

Single-dose therapy: Adolescents: Oral: No adjustment required for vaginal candidiasis single-dose therapy.

Multiple-dose therapy: Infants, Children, and Adolescents: IV, Oral: Administer 100% of the indication-specific loading/initial dose recommended in the dosing section, then adjust daily doses as follows:

CrCl >50 mL/minute/1.73 m2: No adjustment necessary.

CrCl ≤50 mL/minute/1.73 m2: Reduce dose by 50%.

Hemodialysis, intermittent: Note: Based on adult information, fluconazole is dialyzable (33% to 38% with low-flux dialyzers [Oono 1992; Toon 1990]) or approximately 50% after a 3-hour session (manufacturer labeling).

Infants, Children, and Adolescents: IV, Oral: Dialysis days: No dosage adjustment necessary for indication-specific loading/initial or maintenance dose recommended in the dosing section; administer dose after hemodialysis.

Peritoneal dialysis: Infants, Children, and Adolescents: IV, Oral: Administer 50% of recommended dose every 48 hours (Aronoff 2007).

Continuous renal replacement therapy (CRRT) (Veltri 2004): Limited data available: Children and Adolescents: IV, Oral:

<1,500 mL/m2/hour (<25 mL/m2/minute):

Loading dose: Usual dose: 6 to 10 mg/kg/dose once.

Maintenance dose: 3 to 12 mg/kg/dose once daily depending on indication.

≥1,500 mL/m2/hour (≥25 mL/m2/minute):

Loading dose: Usual dose: 6 to 10 mg/kg/dose once.

Maintenance dose: 6 to 12 mg/kg/dose once daily depending on indication.

Prolonged intermittent renal replacement therapy (PIRRT) (eg, sustained, low-efficiency diafiltration): There are no pediatric-specific recommendations for dosing in patients receiving PIRRT; based on adult experience, dose adjustment may be necessary.

Dosing: Hepatic Impairment: Pediatric

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

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

Treatment of candidiasis (esophageal, oropharyngeal, peritoneal, urinary tract, vaginal); systemic candida infections (eg, candidemia, disseminated candidiasis, pneumonia); and cryptococcal meningitis; and antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

​BlastomycosisLevel of Evidence [C, G]

Data from a randomized, multicenter, open-label study comparing fluconazole 400 mg versus 800 mg suggest that the use of fluconazole at each of these doses is effective for the treatment of non-life-threatening blastomycosis Ref.

Based on the IDSA clinical practice guidelines for the management of blastomycosis, fluconazole is an effective and recommended agent for consolidation treatment of CNS disease and an effective and recommended alternative agent for treatment of pulmonary disease.

​Candida intertrigoLevel of Evidence [B]

Data from case reports and a multicenter, randomized, double-blind, double-dummy trial support the use of fluconazole for the treatment of candida intertrigo refractory to topical therapy Ref.

​Candidiasis, empiric therapy (non-neutropenic patients in the ICU)Level of Evidence [G]

Based on the IDSA clinical practice guideline for the management of candidiasis, fluconazole is an effective and recommended alternative agent for empiric therapy of suspected invasive candidiasis in non-neutropenic patients in the ICU. It should not be used for patients with previous azole exposure or those colonized with azole-resistant Candida spp.

​Candidiasis, prophylaxis in high-risk ICU patients (in units with high incidence of invasive candidiasis)Level of Evidence [G]

Based on the IDSA clinical practice guideline for the management of candidiasis, fluconazole may be considered for prophylaxis against invasive candidiasis in high-risk patients in adult ICUs with a high rate of invasive candidiasis (>5%).

​Candidiasis, prophylaxis in hematologic malignancy patientsLevel of Evidence [B, G]

Data from an open-label, randomized trial support the use of fluconazole for the prevention of invasive fungal infection in patients with hematologic malignancy during neutropenia Ref.

Based on the American Society of Clinical Oncology (ASCO) and the IDSA clinical practice guidelines for antimicrobial prophylaxis for adult patients with cancer-related immunosuppression, fluconazole is recommended for prophylaxis for patients with hematologic malignancy who do not require mold-active prophylaxis.

​Candidiasis, prophylaxis in solid organ transplant recipientsLevel of Evidence [G]

Based on the American Society of Health-System Pharmacists (ASHP), IDSA, Surgical Infection Society (SIS), and Society for Healthcare Epidemiology of America (SHEA) guidelines for antimicrobial prophylaxis in surgery and the American Society of Transplantation Infectious Diseases Community of Practice guidelines for Candida infections in solid organ transplantation, fluconazole is recommended for surgical prophylaxis (perioperative) in select high-risk solid organ transplant patients.

​CoccidioidomycosisLevel of Evidence [G]

Based on the IDSA clinical practice guideline for the treatment of coccidioidomycosis and the US Department of Health and Human Services (HHS) guidelines for prevention and treatment of opportunistic infections in adults and adolescents with HIV, fluconazole is an effective and recommended agent in the treatment of coccidioidomycosis as well as in the prophylaxis (initial or chronic suppressive therapy) of coccidioidomycosis in patients with HIV and solid organ transplant recipients undergoing transplantation in endemic areas and/or from infected donors.

​Cryptococcosis, pulmonary infectionLevel of Evidence [G]

Based on the IDSA clinical practice guidelines for management of cryptococcal disease, fluconazole is effective and recommended for the treatment of cryptococcal pneumonia Ref.

​TineaLevel of Evidence [C]

Data from multiple noncomparative trials suggest that the use of fluconazole is effective for the treatment of tinea corporis or cruris tinea pedis Ref. In addition, data from one noncomparative trial suggest that the use of fluconazole is effective for the treatment of tinea versicolor Ref.

Level of Evidence Definitions

​Level of Evidence Scale

Clinical Practice Guidelines

Blastomycosis:

IDSA, “Management of Blastomycosis,” June 2008

Candidiasis:

IDSA, "Management of Candidiasis," 2016

Coccidioidomycosis:

IDSA, "Treatment of Coccidioidomycosis," 2016.

Cryptococcosis:

IDSA, "Management of Cryptococcal Disease,” February 2010

Infective Endocarditis:

AHA, “Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications,” October 2015

AHA, “Infective endocarditis in Childhood: 2015 Update,” October 2015

British Society for Antimicrobial Chemotherapy (BSAC), "Guidelines for the Diagnosis and Antibiotic Treatment of Endocarditis in Adults," 2012

Leishmaniasis:

IDSA/ASTMH, "Diagnosis and Treatment of Leishmaniasis," December 2016

Meningitis and Ventriculitis, Healthcare-Associated:

IDSA, "Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis," February 2017.

Oncology:

C17 Canadian Children’s Cancer and Blood Disorders, "Guideline for Primary Antifungal Prophylaxis for Pediatric Patients with Cancer or Hematopoietic Stem Cell Transplant Recipients," February 2014

Opportunistic Infection:

HHS, Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV

Sexually Transmitted Disease:

CDC, “Sexually Transmitted Diseases Treatment Guidelines,” June 2015

Skin and Soft-tissue Infection:

IDSA, “Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections,” June 2014

Surgical Prophylaxis:

ASHP, “Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery,” February 2013

Administration: IV

Do not use if cloudy or precipitated. Infuse over ~1 to 2 hours; do not exceed 200 mg/hour.

Administration: Injectable Detail

Premixed solutions: pH: 4 to 8 (sodium chloride diluent); 3.5 to 6.5 (dextrose diluent)

Administration: Oral

May be administered without regard to meals.

Administration: Pediatric

Oral: Administer without regard to meals; shake suspension well before use

Parenteral: Do not use if cloudy or precipitated. Administered by IV infusion over approximately 1 to 2 hours at a rate not to exceed 200 mg/hour. The following infusion times were described in pediatric clinical trials:

Neonatal: Loading doses (25 mg/kg) have been infused over 2 hours (Piper 2011; Watt 2012); doses ranging from 3 to 12 mg/kg/dose have been infused over 1 hour including ELBWs (Momper 2016; Piper 2011; Watt 2012)

Pediatric: Doses up to 8 to 10 mg/kg were infused over 2 hours (Driessen 1996; Lee 1992)

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 3]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.

NIOSH recommends single gloving for administration of intact tablets or capsules. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration. For IV compounding, double gloves, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) are recommended. Double gloving and a gown are required during IV administration (NIOSH 2016). Premixed solutions may be excluded from some hazardous drug handling requirements. Assess risk to determine appropriate containment strategy (USP-NF 2017).

Storage/Stability

Tablet: Store at <30°C (86°F).

Powder for oral suspension: Store dry powder at <30°C (86°F). Following reconstitution, store at 5°C to 30°C (41°F to 86°F). Discard unused portion after 2 weeks. Do not freeze.

Injection: Store injection in glass at 5°C to 30°C (41°F to 86°F). Store injection in plastic flexible containers with overwrap at 20°C to 25°C (68°F to 77°F). Do not freeze. Do not unwrap unit until ready for use.

Preparation for Administration: Pediatric

Oral: Reconstitute powder for oral suspension with appropriate amount of water as specified on the bottle. Shake vigorously until suspended.

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat fungal infections.

• It is used to prevent fungal infections.

• This drug is used to treat vaginal yeast infections.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Nausea

• Vomiting

• Dizziness

• Abdominal pain

• Diarrhea

• Change in taste

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss.

• Fast heartbeat

• Abnormal heartbeat

• Passing out

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

​International issues:

Contraindications

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

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: Cases of QTc prolongation and torsade de pointes associated with fluconazole use have been reported (usually high dose or in combination with agents known to prolong the QT interval); use caution in patients with concomitant medications or conditions which are arrhythmogenic.

• CNS effects: May occasionally cause dizziness or seizures; use caution driving or operating machinery.

• Hepatotoxicity: Serious (and sometimes fatal) hepatic toxicity (eg, hepatitis, cholestasis, fulminant hepatic failure) has been observed. Monitor patients who develop abnormal liver function tests for the development of more severe hepatic injury; discontinue fluconazole if signs and symptoms consistent with liver disease develop.

• Hypersensitivity reactions: Anaphylaxis has been reported rarely; use with caution in patients with hypersensitivity to other azoles.

• Skin reactions: Rare exfoliative skin disorders have been observed; fatal outcomes have been reported in patients with serious concomitant diseases. Monitor patients with deep seated fungal infections closely for rash development and discontinue if lesions progress. In patients with superficial fungal infections who develop a rash attributable to fluconazole, treatment should also be discontinued.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with preexisting hepatic impairment; monitor liver function closely and discontinue if symptoms consistent with liver disease develop.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be necessary.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

• Sucrose: Oral suspension contains sucrose; avoid use in patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Has not been specifically studied in the elderly.

Reproductive Considerations

The manufacturer recommends females of childbearing potential taking higher doses (≥400 mg/day) use effective contraception during therapy and for ~1 week after the final fluconazole dose.

Pregnancy Considerations

Following exposure during the first trimester, malformations have been noted in humans when maternal fluconazole was used in higher doses (≥400 mg/day). Abnormalities reported include brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease. Fetal outcomes following exposure to lower doses is less clear and additional study is needed to confirm an association between maternal use of low dose fluconazole and an increased risk of birth defects. However, epidemiological studies of fluconazole ≤150 mg as a single dose or repeated doses in the first trimester suggest a potential risk of spontaneous abortion and malformations (Liu 2020; Zhang 2019; Zhu 2020).

Oral fluconazole for the treatment of vaginal candidiasis is not recommended during pregnancy. Topical therapy for oral or vaginal candidiasis is recommended in pregnant women whenever possible (HHS [OI adult 2020]; Workowski [CDC 2015]). Fluconazole is not the treatment of choice for invasive candidiasis in pregnant women (IDSA [Pappas 2016]). Fluconazole may be used for the treatment of cryptococcosis or coccidioidomycosis after the first trimester if otherwise appropriate (IDSA [Galgiani 2016]; IDSA [Perfect 2010]; Pastick 2020). Systemic fluconazole is not preferred for the treatment of blastomycosis in pregnant women (IDSA Chapman 2008]).

Breast-Feeding Considerations

Fluconazole is present in breast milk.

The relative infant dose (RID) of fluconazole is 5% to 21% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 3 to 12 mg/kg/day.

In general, breastfeeding is considered acceptable when the RID is <10%; when an RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000).

The RID of fluconazole was calculated using a milk concentration of 4.1 mcg/mL, providing an estimated daily infant dose via breast milk of 0.62 mg/kg/day. This milk concentration was obtained following maternal administration of oral fluconazole 200 mg daily for 18 days; the apparent elimination half-life of fluconazole in breast milk was 26.9 hours (Schilling 1993). In another study, peak breast milk concentrations following a single oral dose of fluconazole 150 mg to 10 lactating women, 5 days' to 19 months' postpartum, were reported as 1.57 to 3.65 mcg/mL

Serious adverse events in breastfeeding infants have not been reported following maternal use of fluconazole for nipple or breast candidiasis (Bodley 1997; Chetwynd 2002; Moorhead 2011); flushed cheeks, GI upset, loose stools, mucous feces, and somnolence have been reported in breastfed infants (Moorhead 2011).

Although the manufacturer recommends that caution be exercised when administering fluconazole to breastfeeding women, existing recommendations state that fluconazole is considered compatible with breastfeeding when used in usual recommended doses (WHO 2002). Treatment of breastfeeding women with nipple or breast candidiasis with oral fluconazole is common, especially in persistent or recurring infections (Brent 2001). Untreated candida nipple or breast infections may be painful for the mother and can contribute to premature weaning (Brent 2001). The amount of fluconazole contained in the breast milk is not sufficient to treat mucocutaneous candidiasis in the infant (Force 1995; Schilling 1993); concurrent treatment of both the breastfeeding infant and mother may be required (Chetwynd 2002).

Lexicomp Pregnancy & Lactation, In-Depth

• Fluconazole

Briggs' Drugs in Pregnancy & Lactation

• Fluconazole

Adverse Reactions

>10%: Central nervous system: Headache (adults: 2% to 13%)

1% to 10%:

Central nervous system: Dizziness (adults: 1%)

Dermatologic: Skin rash (adults: 2%)

Gastrointestinal: Nausea (adults: 4% to 7%; children and adolescents: 2%), abdominal pain (2% to 6%), vomiting (2% to 5%), diarrhea (2% to 3%), dysgeusia (adults: 1%), dyspepsia (adults: 1%)

Frequency not defined: Hepatic: Fulminant hepatitis, hepatitis, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum transaminases, jaundice

<1%, postmarketing, and/or case reports: Acute generalized exanthematous pustulosis, agranulocytosis, alopecia, anaphylaxis, angioedema, asthenia, cholestasis, diaphoresis, DRESS syndrome, drowsiness, exfoliative dermatitis, fatigue, fever, fixed drug eruption, hepatic failure, hepatotoxicity, hypercholesterolemia, hypertriglyceridemia, hypokalemia, insomnia, leukopenia, malaise, myalgia, neutropenia, paresthesia, prolonged QT interval on ECG, seizure, Stevens-Johnson syndrome, thrombocytopenia, torsades de pointes, toxic epidermal necrolysis, tremor, vertigo, xerostomia

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Azole Antifungal Allergy

Metabolism/Transport Effects

Inhibits CYP2C19 (strong), CYP2C9 (moderate), CYP3A4 (moderate)

Drug Interactions Open Interactions

Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor therapy

Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider therapy modification

Alfentanil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification

Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alfuzosin. Risk C: Monitor therapy

Alitretinoin (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with moderate CYP2C9 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a moderate CYP2C9 inhibitor. Risk D: Consider therapy modification

Amiodarone: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Amiodarone. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy

Amitriptyline: May enhance the QTc-prolonging effect of Fluconazole. Fluconazole may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy

AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy

Amphotericin B: Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy

Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Risk C: Monitor therapy

Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Risk X: Avoid combination

ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy

Astemizole: Fluconazole may enhance the QTc-prolonging effect of Astemizole. Fluconazole may increase the serum concentration of Astemizole. Risk X: Avoid combination

Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination

AtorvaSTATin: Fluconazole may increase the serum concentration of AtorvaSTATin. Risk C: Monitor therapy

Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider therapy modification

Avapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose from 300 mg once daily to 100 mg once daily. Risk D: Consider therapy modification

Avatrombopag: Fluconazole may increase the serum concentration of Avatrombopag. Management: For chronic immune thrombocytopenia, reduce initial avatrombopag dose to 20 mg 3 tiems per week. No dosage reduction needed for patients with chronic liver disease-associated thrombocytopenia using altrombopag prior to a procedure. Risk D: Consider therapy modification

Axitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Axitinib. Risk C: Monitor therapy

Barnidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Barnidipine. Risk C: Monitor therapy

Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy

Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Risk C: Monitor therapy

Bortezomib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy

Bosentan: Fluconazole may increase the serum concentration of Bosentan. Risk X: Avoid combination

Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Risk X: Avoid combination

Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor therapy

Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification

Brivaracetam: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Brivaracetam. Risk C: Monitor therapy

Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modification

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor therapy

Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification

Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Risk X: Avoid combination

Busulfan: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Busulfan. Isavuconazonium considerations are addressed in separate monographs. Risk C: Monitor therapy

Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy

Calcium Channel Blockers: Fluconazole may increase the serum concentration of Calcium Channel Blockers. Exceptions: Clevidipine. Risk C: Monitor therapy

Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol. Risk C: Monitor therapy

Cannabidiol: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. Risk C: Monitor therapy

Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Risk C: Monitor therapy

Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy

CarBAMazepine: Fluconazole may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Carisoprodol: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inhibitors (Strong) may increase the serum concentration of Carisoprodol. Risk C: Monitor therapy

Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy

Celecoxib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Celecoxib. Risk C: Monitor therapy

Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Ceritinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Ceritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4. Risk D: Consider therapy modification

Cilostazol: CYP2C19 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Cilostazol. CYP2C19 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving strong inhibitors of CYP2C19. Monitor clinical response to cilostazol closely. Risk D: Consider therapy modification

Cisapride: Fluconazole may enhance the QTc-prolonging effect of Cisapride. Fluconazole may increase the serum concentration of Cisapride. Risk X: Avoid combination

Citalopram: Fluconazole may enhance the QTc-prolonging effect of Citalopram. Fluconazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with fluconazole, which is a strong CYP2C19 inhibitor. Patients using this combination should be monitored closely for citalopram toxicities, including serotonin syndrome and QT prolongation. Risk D: Consider therapy modification

CloBAZam: CYP2C19 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Strong) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy

Clopidogrel: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a strong CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Risk D: Consider therapy modification

Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider therapy modification

Codeine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy

Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See interaction monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification

Copanlisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Copanlisib. Risk C: Monitor therapy

Crizotinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Crizotinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Crizotinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

CycloSPORINE (Systemic): Fluconazole may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Substrates (High risk with Inhibitors): CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Exceptions: Alitretinoin (Systemic); Bromperidol; Copanlisib; Erdafitinib; Praziquantel; Ripretinib; Trabectedin; Vinorelbine. Risk C: Monitor therapy

Dabigatran Etexilate: Fluconazole may enhance the anticoagulant effect of Dabigatran Etexilate. Risk C: Monitor therapy

Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider therapy modification

Darifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Darifenacin. Risk C: Monitor therapy

Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

DexAMETHasone (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy

Dexlansoprazole: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Dexlansoprazole. Risk C: Monitor therapy

DiazePAM: CYP2C19 Inhibitors (Strong) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy

Dichlorphenamide: Antifungal Agents (Azole Derivatives, Systemic) may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy

Diclofenac (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Diclofenac (Systemic). Risk C: Monitor therapy

Domperidone: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Domperidone. Risk X: Avoid combination

DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Risk D: Consider therapy modification

Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Risk C: Monitor therapy

Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Risk C: Monitor therapy

Dronedarone: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Dronedarone. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Dronedarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided. Risk D: Consider therapy modification

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, two elexacaftor/tezacaftor/ivacaftor (100 mg/50 mg/75 mg) tablets should be given in the morning, every other day. Ivacaftor (150 mg) should be given in the morning, every other day on alternate days. Risk D: Consider therapy modification

Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Use in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors is contraindicated. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Risk D: Consider therapy modification

Encorafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and moderate CYP3A4 inhibitors when possible. If combined, decrease the encorafenib dose from 450 mg to 225 mg; 300 mg to 150 mg; and 225 mg or 150 mg to 75 mg. Resume prior dose once inhibitor discontinued for 3 to 5 half-lives. Risk D: Consider therapy modification

Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and moderate CYP3A4 inhibitors when possible. If combined, decrease encorafenib dose from 450 mg to 225 mg; 300 mg to 150 mg; and 225 mg or 150 mg to 75 mg. Monitor closely for QT interval prolongation. Risk D: Consider therapy modification

Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Entrectinib. Risk X: Avoid combination

Eplerenone: Fluconazole may increase the serum concentration of Eplerenone. Management: Reduce the starting dose of eplerenone to 25 mg/day if combined with fluconazole; monitor patients closely for increased eplerenone effects. Risk D: Consider therapy modification

Erdafitinib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and moderate CYP2C9 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modification

Erythromycin (Systemic): Fluconazole may enhance the QTc-prolonging effect of Erythromycin (Systemic). Fluconazole may increase the serum concentration of Erythromycin (Systemic). Risk X: Avoid combination

Estrogen Derivatives: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Etizolam: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Etizolam. Risk C: Monitor therapy

Etravirine: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Etravirine. Risk C: Monitor therapy

Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Risk C: Monitor therapy

Fedratinib: Fluconazole may increase the serum concentration of Fedratinib. Risk X: Avoid combination

FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider therapy modification

Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid combination

Flurbiprofen (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Flurbiprofen (Systemic). Risk C: Monitor therapy

Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor therapy

Fluvastatin: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Fluvastatin. Management: Fluvastatin should be used at the lowest effective dose and should not exceed 20 mg twice daily when combined with moderate CYP2C9 inhibitors. Monitor patients closely for increased fluvastatin toxicities when combined. Risk D: Consider therapy modification

Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination

Fosphenytoin-Phenytoin: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification

Haloperidol: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy

Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider therapy modification

Ibuprofen: Fluconazole may increase the serum concentration of Ibuprofen. Risk C: Monitor therapy

Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy

Imatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib. Risk C: Monitor therapy

Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Risk X: Avoid combination

Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider therapy modification

Ivosidenib: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Ivosidenib. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Lansoprazole: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Lansoprazole. Risk C: Monitor therapy

Lapatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lapatinib. Risk C: Monitor therapy

Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy

Lefamulin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lefamulin. Management: Monitor for lefamulin adverse effects during coadministration of lefamulin tablets with moderate CYP3A4 inhibitors. Risk C: Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lemborexant. Risk X: Avoid combination

Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lercanidipine. Risk C: Monitor therapy

Lesinurad: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Lesinurad. Risk C: Monitor therapy

Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy

Levomethadone: Fluconazole may increase the serum concentration of Levomethadone. Risk C: Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Risk X: Avoid combination

Lorlatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lorlatinib. Risk C: Monitor therapy

Lornoxicam: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Lornoxicam. Risk C: Monitor therapy

Losartan: CYP2C9 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Losartan. CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Losartan. Risk C: Monitor therapy

Lovastatin: Fluconazole may increase the serum concentration of Lovastatin. Risk C: Monitor therapy

Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Risk X: Avoid combination

Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Risk D: Consider therapy modification

Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Risk D: Consider therapy modification

Macitentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Macitentan. Risk C: Monitor therapy

Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Risk C: Monitor therapy

Meloxicam: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Meloxicam. Risk C: Monitor therapy

Meperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine. Risk C: Monitor therapy

Methadone: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy

Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Risk C: Monitor therapy

Mizolastine: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Mizolastine. Risk X: Avoid combination

Moclobemide: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Moclobemide. Risk C: Monitor therapy

Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy

Nalmefene: Fluconazole may increase the serum concentration of Nalmefene. Risk C: Monitor therapy

Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider therapy modification

Nateglinide: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Nateglinide. Risk C: Monitor therapy

Nelfinavir: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Nelfinavir. Risk C: Monitor therapy

Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Risk C: Monitor therapy

Nevirapine: Fluconazole may increase the serum concentration of Nevirapine. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider therapy modification

Oliceridine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy

Omeprazole: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Omeprazole. Risk C: Monitor therapy

Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Ospemifene: Fluconazole may increase the serum concentration of Ospemifene. Risk X: Avoid combination

OxyCODONE: CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy

Parecoxib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Management: Use the lowest effective dose of parecoxib and consider a dose reduction in patients taking moderate CYP2C9 inhibitors. Risk D: Consider therapy modification

PAZOPanib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PAZOPanib. Risk C: Monitor therapy

Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with moderate CYP3A4 inhibitors if possible. If combined, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily. Risk D: Consider therapy modification

Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Proguanil: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Proguanil. CYP2C19 Inhibitors (Strong) may increase the serum concentration of Proguanil. Risk C: Monitor therapy

QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Exceptions: Citalopram. Risk C: Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Pimozide; QUEtiapine. Risk C: Monitor therapy

QT-prolonging Class IA Antiarrhythmics (Highest Risk): Fluconazole may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: QuiNIDine. Risk D: Consider therapy modification

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Dronedarone. Risk D: Consider therapy modification

QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Ivosidenib; Selpercatinib. Risk D: Consider therapy modification

QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Exceptions: Encorafenib; Entrectinib. Risk C: Monitor therapy

QT-prolonging Miscellaneous Agents (Highest Risk): Fluconazole may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluconazole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Astemizole; Cisapride; Terfenadine. Risk D: Consider therapy modification

QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone. Risk C: Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Fluconazole may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Crizotinib; Erythromycin (Systemic). Risk C: Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Fluconazole may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Voriconazole. Risk C: Monitor therapy

QUEtiapine: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QUEtiapine. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QUEtiapine. Management: Monitor for increased quetiapine toxicities including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QuiNIDine: Fluconazole may enhance the QTc-prolonging effect of QuiNIDine. Fluconazole may increase the serum concentration of QuiNIDine. Risk X: Avoid combination

Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy

Ramelteon: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy

Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider therapy modification

Red Yeast Rice: Fluconazole may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Risk C: Monitor therapy

Rifamycin Derivatives: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Avoid these combinations when possible. Voriconazole and isavuconazonium are considered contraindicated. Risk D: Consider therapy modification

Rimegepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rimegepant. Management: Avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Risk C: Monitor therapy

Ruxolitinib: Fluconazole may increase the serum concentration of Ruxolitinib. Management: This combination should be avoided under some circumstances. See monograph for details. Risk D: Consider therapy modification

Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination

Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy

SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Risk C: Monitor therapy

Selpercatinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Selpercatinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120mg twice/day to 80mg twice/day, or from 160mg twice/day to 120mg twice/day. Monitor QT interval more closely for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification

Selumetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modification

Sildenafil: Fluconazole may increase the serum concentration of Sildenafil. Risk C: Monitor therapy

Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Risk C: Monitor therapy

Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Risk X: Avoid combination

Simvastatin: Fluconazole may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Siponimod: Fluconazole may increase the serum concentration of Siponimod. Risk X: Avoid combination

Sirolimus: Fluconazole may increase the serum concentration of Sirolimus. Management: Monitor for increased serum concentrations of sirolimus if combined with fluconazole. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider therapy modification

Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modification

Sulfonylureas: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

SUNItinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SUNItinib. Risk C: Monitor therapy

Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider therapy modification

Tacrolimus (Systemic): Fluconazole may increase the serum concentration of Tacrolimus (Systemic). Management: Monitor tacrolimus concentrations closely and adjust oral tacrolimus dose as necessary when concomitantly administered with fluconazole. Reduced doses of tacrolimus will likely be required. Risk D: Consider therapy modification

Tadalafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tadalafil. Risk C: Monitor therapy

Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy

Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider therapy modification

Telithromycin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Telithromycin. Risk C: Monitor therapy

Temsirolimus: Fluconazole may increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to fluconazole. Monitor sirolimus concentrations in all patients receiving fluconazole or any systemic azole antifungal. Risk D: Consider therapy modification

Terfenadine: Fluconazole may enhance the QTc-prolonging effect of Terfenadine. Fluconazole may increase the serum concentration of Terfenadine. Management: Concomitant use of fluconazole at doses of 400 mg/day or greater and terfenadine is contraindicated and should be avoided. If lower doses of fluconazole and terfenadine are combined, monitor patients for QT-prolongation. Risk D: Consider therapy modification

Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Specifically, concentrations of tetrahydrocannabinol may be increased. Risk C: Monitor therapy

Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider therapy modification

Theophylline Derivatives: Fluconazole may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy

Ticagrelor: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Risk C: Monitor therapy

Tipranavir: Fluconazole may increase the serum concentration of Tipranavir. Management: Limit fluconazole adult maximum dose to 200 mg/day in patients treated with tipranavir. Risk D: Consider therapy modification

Tofacitinib: Fluconazole may increase the serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with fluconazole. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider therapy modification

Tolterodine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy

Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider therapy modification

Torsemide: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Torsemide. Risk C: Monitor therapy

Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Risk C: Monitor therapy

Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Risk X: Avoid combination

Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Valbenazine. Risk C: Monitor therapy

Vardenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification

Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

Verapamil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Verapamil. Risk C: Monitor therapy

Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy

VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy

VinCRIStine: Fluconazole may increase the serum concentration of VinCRIStine. Risk C: Monitor therapy

VinCRIStine (Liposomal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine (Liposomal). Risk C: Monitor therapy

Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Fluconazole may increase the serum concentration of Vitamin K Antagonists. Management: Consider reducing the vitamin K antagonist dose by 10% to 20% if combined with fluconazole. Monitor for increased anticoagulant effects (ie, increased INR, bleeding) to guide further dose adjustments. Risk D: Consider therapy modification

Voriconazole: Fluconazole may enhance the QTc-prolonging effect of Voriconazole. Fluconazole may increase the serum concentration of Voriconazole. Risk X: Avoid combination

Voxelotor: Fluconazole may increase the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and fluconazole. If concomitant use is unavoidable, reduce the voxelotor dose to 1,000 mg once daily. Risk D: Consider therapy modification

Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modification

Zidovudine: Fluconazole may decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Risk C: Monitor therapy

Monitoring Parameters

Periodic liver function tests (AST, ALT, alkaline phosphatase) and renal function tests, potassium

Advanced Practitioners Physical Assessment/Monitoring

Assess results of cultures/sensitivity and patient's allergy history prior to beginning therapy. Obtain periodic liver function tests, renal function tests, and serum potassium. Obtain ECG (patients with concomitant medications or conditions that prolong the QT). Assess for hepatotoxicity (jaundice), skin disorders, and abdominal pain on a regular basis.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor for ECG changes. Monitor for signs and symptoms of hepatotoxicity (jaundice), skin disorders, and abdominal pain; instruct patient to report.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 100 mg/50 mL in NaCl 0.9% (50 mL [DSC]); 200 mg (100 mL); 200 mg/100 mL in NaCl 0.9% (100 mL); 400 mg (200 mL)

Solution, Intravenous [preservative free]:

Generic: 200 mg (100 mL); 200 mg/100 mL in NaCl 0.9% (100 mL); 400 mg (200 mL); 400 mg/200 mL in NaCl 0.9% (200 mL)

Suspension Reconstituted, Oral:

Diflucan: 10 mg/mL (35 mL); 40 mg/mL (35 mL) [orange flavor]

Generic: 10 mg/mL (35 mL); 40 mg/mL (35 mL)

Tablet, Oral:

Diflucan: 50 mg, 100 mg, 150 mg, 200 mg

Generic: 50 mg, 100 mg, 150 mg, 200 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Diflucan: 2 mg/mL (100 mL)

Generic: 2 mg/mL (50 mL, 100 mL, 200 mL)

Suspension Reconstituted, Oral:

Diflucan: 10 mg/mL (35 mL) [contains sodium benzoate]

Tablet, Oral:

Diflucan: 50 mg, 100 mg [contains fd&c red #40 aluminum lake]

Generic: 50 mg, 100 mg, 200 mg

Anatomic Therapeutic Chemical (ATC) Classification

• D01AC15
• J02AC01

Generic Available (US)

Yes

Pricing: US

Solution (Fluconazole in Sodium Chloride Intravenous)

200 mg/100 mL 0.9% (per mL): $0.05 - $0.58

400 mg/200 mL 0.9% (per mL): $0.03 - $0.42

Suspension (reconstituted) (Diflucan Oral)

10 mg/mL (per mL): $0.58

40 mg/mL (per mL): $0.95

Suspension (reconstituted) (Fluconazole Oral)

10 mg/mL (per mL): $0.99 - $1.03

40 mg/mL (per mL): $3.59 - $3.74

Tablets (Diflucan Oral)

50 mg (per each): $1.34

100 mg (per each): $1.34

150 mg (per each): $71.97

200 mg (per each): $74.00

Tablets (Fluconazole Oral)

50 mg (per each): $0.49 - $5.60

100 mg (per each): $8.75 - $8.80

150 mg (per each): $1.29 - $14.01

200 mg (per each): $14.32 - $14.40

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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

Pharmacodynamics/Kinetics

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

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

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

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

Protein binding, plasma: 11% to 12%

Bioavailability: Oral: >90%

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

Time to peak, serum: Oral: 1 to 2 hours

Excretion: Urine (80% as unchanged drug)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Pharmacokinetics are markedly affected; there is an inverse relationship between half-life and creatinine clearance.

Dental Use

Treatment of susceptible fungal infections in the oral cavity including candidiasis, oral thrush, and chronic mucocutaneous candidiasis treatment of esophageal and oropharyngeal candidiasis caused by Candida species; treatment of severe, chronic mucocutaneous candidiasis caused by Candida species

* See Uses in AHFS Essentials for additional information.

Local Anesthetic/Vasoconstrictor Precautions

Fluconazole is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.

Dental Health Professional Considerations

See Local Anesthetic/Vasoconstrictor Precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Abnormal taste.

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Candidiasis: Adults:

Usual dosage range: 200 to 400 mg/day; duration and dosage depends on severity of infection

Oropharyngeal (long-term suppression): 200 mg/day; chronic therapy is recommended in immunocompromised patients with history of oropharyngeal candidiasis (OPC)

Related Information

• Dosing Considerations for the Critically Ill Patient With Morbid Obesity
• Drug-Induced Prolongation of the QT Interval and Torsades de Pointes
• Relative Infant Dose
• Safe Handling of Hazardous Drugs

Index Terms

Diflucan

FDA Approval Date

January 29, 1990

References

<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.

Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319.[PubMed 11487763]

Aleck KA, Bartley DL. Multiple malformation syndrome following fluconazole use in pregnancy: report of an additional patient. Am J Med Genet. 1997;72(3):253-256.[PubMed 9332650]

American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018.

American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Ampel NM. Coccidioidomycosis in compromised hosts. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020.

Anaissie EJ, Kontoyiannis DP, Huls C, et al. Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections. J Infect Dis. 1995;172(2):599-602.[PubMed 7622915]

Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. doi: 10.1002/cpt.377.[PubMed 27060684]

Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.

Aslam S, Rotstein C; AST Infectious Disease Community of Practice. Candida infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13623. doi:10.1111/ctr.13623[PubMed 31155770]

Baddley JW, Forrest GN; AST Infectious Diseases Community of Practice. Cryptococcosis in solid organ transplantation-guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13543. doi:10.1111/ctr.13543[PubMed 30900315]

Bergner R, Hoffmann M, Riedel KD, et al. Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg. Nephrol Dial Transplant. 2006;21(4):1019-1023.[PubMed 16311263]

Berl T, Wilner KD, Gardner M, et al. Pharmacokinetics of fluconazole in renal failure. J Am Soc Nephrol. 1995;6(2):242-247.[PubMed 7579091]

Blair JE, Ampel NM. Coccidioidal meningitis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 24, 2020.

Bodley V, Powers D. Long-term treatment of a breastfeeding mother with fluconazole-resolved nipple pain caused by yeast: a case study. J Hum Lact.1997;13(4):307-311. doi: 10.1177/089033449701300416.[PubMed 9429366]

Bradley JS, Nelson JD, Barnett ED, Cantey JB, eds. Nelson's Pediatric Antimicrobial Therapy. 24th ed. American Academy of Pediatrics; 2018.

Bradsher RW. Treatment of blastomycosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020.

Bratzler DW, Dellinger EP, Olsen KM, et al; American Society of Health-System Pharmacists; Infectious Diseases Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. doi: 10.2146/ajhp120568.[PubMed 23327981]

Brent NB. Thrush in the breastfeeding dyad: results of a survey on diagnosis and treatment. Clin Pediatr (Phila). 2001;40(9):503-506. doi: 10.1177/000992280104000905.[PubMed 11583049]

Brodell RT, Dolohanty LB. Intertrigo. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 3, 2018.

Burkart JM, Bleyer A. Peritoneal catheter exit-site and tunnel infections in peritoneal dialysis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 11, 2018.

Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm.[PubMed 6810084]

Centers for Disease Control and Prevention (CDC). Guidelines for Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Adults and Adolescents. Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR-4):1-207.[PubMed 19357635]

Chapman SW, Dismukes WE, Proia LA, et al; Infectious Diseases Society of America. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(12):1801-1812.[PubMed 18462107]

Chen CM, Ho MW, Yu WL, Wang JH. Fungal peritonitis in peritoneal dialysis patients: effect of fluconazole treatment and use of the twin-bag disconnect system. J Microbiol Immunol Infect. 2004;37(2):115-120.[PubMed 15181494]

Chen SC, Korman TM, Slavin MA, et al; Australia and New Zealand Mycoses Interest Group (ANZMIG) Cryptococcus Study. Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii. Clin Infect Dis. 2013;57(4):543-551. doi: 10.1093/cid/cit341.[PubMed 23697747]

Chetwynd EM, Ives TJ, Payne PM, Edens-Bartholomew N. Fluconazole for postpartum candidal mastitis and infant thrush. J Hum Lact. 2002;18(2):168-171.[PubMed 15181494]

Coldiron BM, Manders SM. Persistent Candida intertrigo treated with fluconazole. Arch Dermatol. 1991;127(2):165-166.[PubMed 1990982]

Como JA and Dismukes WE, "Oral Azole Drugs as Systemic Antifungal Therapy," N Engl J Med, 1993, 330(4):263-72.

Cousin L, Berre ML, Launay-Vacher V, Izzedine H, Deray G. Dosing guidelines for fluconazole in patients with renal failure. Nephrol Dial Transplant. 2003;18(11):2227-2231.[PubMed 14551347]

Cox GM, Perfect JR. Cryptococcus neoformans meningoencephalitis in patients with HIV infection: treatment and prevention. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 17, 2018.

Cox GM, Perfect JR. Cryptococcus neoformans: treatment of meningoencephalitis and disseminated infection in HIV seronegative patients. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 7, 2020a.

Cox GM, Perfect JR. Cryptococcus neoformans infection outside the central nervous system. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020b.

Diflucan (fluconazole) [prescribing information]. New York, NY: Roerig, Division of Pfizer Inc; September 2020.

Diflucan (fluconazole in Dextrose injection and fluconazole in Sodium Chloride injection) [prescribing information]. New York, NY: Roerig, Division of Pfizer Inc; September 2020.

Driessen M, Ellis JB, Cooper PA, et al. Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pediatr Infect Dis J. 1996;15(12):1107-1112.[PubMed 8970221]

Egunsola O, Adefurin A, Fakis A, Jacqz-Aigrain E, Choonara I, Sammons H. Safety of fluconazole in paediatrics: a systematic review. Eur J Clin Pharmacol. 2013;69(6):1211-1221.[PubMed 23325436]

Eichenwald EC, ed. Cloherty and Stark's Manual of Neonatal Care. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2017.

Fishman JA, Alexander BD. Prophylaxis of infections in solid organ transplantation. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020.

Fluconazole injection (fluconazole in sodium chloride, IV infusion, USP) [prescribing information]. Deerfield, IL: Baxter Healthcare Corp; May 2018.

Fluconazole injection [prescribing information]. Eatontown, NJ: West-Ward Pharmaceutical Corp; December 2018.

Force RW. Fluconazole concentrations in breast milk. Pediatr Infect Dis J. 1995;14(3):235-236.[PubMed 7761190]

Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis. Clin Infect Dis. 2016;63(6):e112-e146. doi: 10.1093/cid/ciw360.[PubMed 27470238]

Georgiadou SP, Tarrand J, Sipsas NV, Kontoyiannia DP. Candiduria in haematologic malignancy patients without a urinary catheter: nothing more than a frailty marker? Mycoses. 2013;56(3):311-314 doi: 10.1111/myc.12024.[PubMed 23170870]

Gharibian KN, Mueller BA. Fluconazole dosing predictions in critically-ill patients receiving prolonged intermittent renal replacement therapy: a Monte Carlo simulation approach. Clin Nephrol. 2016;86(7):43-50. doi: 10.5414/CN108824.[PubMed 27251341]

Glasmacher A, Cornely O, Ullmann AJ, et al; Itraconazole Research Group of Germany. An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia. J Antimicrob Chemother. 2006;57(2):317-325.[PubMed 16339606]

Glickman JD, Cox GM, Kauffman CA. Fungal peritonitis in peritoneal dialysis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 2, 2019.

Goldman M, Cloud GA, Wade KD, et al. A randomized study of the use of fluconazole in continuous versus episodic therapy in patients with advanced HIV infection and a history of oropharyngeal candidiasis: AIDS Clinical Trials Group Study 323/Mycoses Study Group Study 40. Clin Infect Dis. 2005;41(10):1473-1480. doi:10.1086/497373[PubMed 16231260]

Goldstein AO, Goldstein BG. Dermatophyte (tinea) infections. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020.

Gould FK, Denning DW, Elliott TS, et al. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2012;67(2):269-89. doi: 10.1093/jac/dkr450.[PubMed 22086858]

Gupta AK, Cooper EA. Update in antifungal therapy of dermatophytosis. Mycopathologia. 2008;166(5-6):353-367. doi: 10.1007/s11046-008-9109-0.[PubMed 18478357]

Healy CM and Baker CJ, "Fluconazole Prophylaxis in the Neonatal Intensive Care Unit," Pediatr Infect Dis J, 2009, 28(1):49-52.[PubMed 19106754]

Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29(5):562-577. doi: 10.1592/phco.29.5.562.[PubMed 19397464]

HHS Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed April 30, 2020.

HHS Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America and the Pediatric Infectious Diseases Society. July 2018. Available at: https://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf.

Hope WW, Castagnola E, Groll AH, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clin Microbiol Infect. 2012;18 Suppl 7:38-52.[PubMed 23137136]

"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. doi: 10.1056/NEJM200007133430208.[PubMed 10891521]

Jaroszewski D, Blair JE, Ampel NM. Management of pulmonary sequelae and complications of coccidioidomycosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 7, 2020.

Jick SS. Pregnancy outcomes after maternal exposure to fluconazole. Pharmacotherapy. 1999;19(2):221-222.[PubMed 10030772]

Karakas M, Durdu M, Memişoğlu HR. Oral fluconazole in the treatment of tinea versicolor. J Dermatol. 2005;32(1):19-21.[PubMed 15841655]

Kauffman CA. Treatment of candidemia and invasive candidiasis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020a.

Kauffman CA, Durand ML. Treatment of endogenous endophthalmitis due to Candida species. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020b.

Kauffman CA. Treatment of oropharyngeal and esophageal candidiasis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 18, 2018.

Kauffman CA. Candida infections of the abdomen and thorax. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020c.

Kishino S, Koshinami Y, Hosoi T, et al. Effective fluconazole therapy for liver transplant recipients during continuous hemodiafiltration. Ther Drug Monit. 2001;23(1):4-8.[PubMed 11206042]

Kotogyan A, Harmanyeri Y, Tahsin Gunes A, et al. Efficacy and safety of oral fluconazole in the treatment of patients with tinea corporis, cruris or pedis or cutaneous candidosis: a multicentre, open, noncomparative study. Clin Drug Investig. 1996;12(2):59-66. doi: 10.2165/00044011-199612020-00001.[PubMed 24610666]

Lee J, Kim HS, Shin SH, et al. Efficacy and safety of fluconazole prophylaxis in extremely low birth weight infants: multicenter pre-post cohort study. BMC Pediatr. 2016;16:67.[PubMed 27184665]

Lee JM, Graciano AL, Dabrowski L, Kuzmic B, Tablizo MA. Coccidioidomycosis in infants: A retrospective case series. Pediatr Pulmonol. 2016;51(8):858-862.[PubMed 26829719]

Lee JW, Seibel NL, Amantea M, et al, "Safety and Pharmacokinetics of Fluconazole in Children With Neoplastic Diseases," J Pediatr, 1992, 120(6):987-93.[PubMed 1593362]

Leroux S, Jacqz-Aigrain E, Elie V, et al. Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial. Br J Clin Pharmacol. 2018;84(9):1989-1999.[PubMed 29744900]

Li PK, Szeto CC, Piraino B, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment [published correction appears in Perit Dial Int. 2018;38(4):313]. Perit Dial Int. 2016;36(5):481-508. doi: 10.3747/pdi.2016.00078.[PubMed 27282851]

Liu D, Zhang C, Wu L, Zhang L, Zhang L. Fetal outcomes after maternal exposure to oral antifungal agents during pregnancy: A systematic review and meta-analysis. Int J Gynaecol Obstet. 2020;148(1):6-13.[PubMed 31691277]

Malani PN, McNeil SA, Bradley SF, Kauffman CA. Candida albicans sternal wound infections: a chronic and recurrent complication of median sternotomy. Clin Infect Dis. 2002;35(11):1316-1320.[PubMed 12439793]

Miller R, Assi M; AST Infectious Diseases Community of Practice. Endemic fungal infections in solid organ transplant recipients-guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13553. doi: 10.1111/ctr.13553.[PubMed 30924967]

Molloy SF, Kanyama C, Heyderman RS, et al; ACTA Trial Study Team. Antifungal combinations for treatment of cryptococcal meningitis in Africa. N Engl J Med. 2018;378(11):1004-1017. doi: 10.1056/NEJMoa1710922.[PubMed 29539274]

Momper JD, Capparelli EV, Wade KC, et al. Population pharmacokinetics of fluconazole in premature infants with birth weights less than 750 grams. Antimicrob Agents Chemother. 2016;60(9):5539-5545.[PubMed 27401564]

Montero-Gei F, Perera A. Therapy with fluconazole for tinea corporis, tinea cruris, and tinea pedis. Clin Infect Dis. 1992;14(suppl 1):S77-S81.[PubMed 1562699]

Moorhead AM, Amir LH, O'Brien PW, Wong S. A prospective study of fluconazole treatment for breast and nipple thrush. Breastfeed Rev. 2011;19(3):25-29.[PubMed 22263374]

Muhl E, Martens T, Iven H, Rob P, Bruch HP. Influence of continuous veno-venous haemodiafiltration and continuous veno-venous haemofiltration on the pharmacokinetics of fluconazole. Eur J Clin Pharmacol. 2000;56(9-10):671-678.[PubMed 11214774]

Nenoff P, Krüger C, Paasch U, Ginter-Hanselmayer G. Mycology - an update part 3: Dermatomycoses: topical and systemic therapy. J Dtsch Dermatol Ges. 2015;13(5):387-410; quiz 411.[PubMed 25918080]

Nozickova M, Koudelkova V, Kulikova Z, Malina L, Urbanowski S, Silney W. A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidosis. Int J Dermatol. 1998;37(9):703-705.[PubMed 9762826]

Nussbaum JC, Jackson A, Namarika D, et al. Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: a randomized trial in Malawi. Clin Infect Dis. 2010;50(3):338-344. doi: 10.1086/649861.[PubMed 20038244]

Oono S, Tabei K, Tetsuka T, Asano Y. The pharmacokinetics of fluconazole during haemodialysis in uraemic patients. Eur J Clin Pharmacol. 1992;42(6):667-669.[PubMed 1623910]

Pappas PG, Bradsher RW, Kauffman CA, et al; The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Treatment of blastomycosis with higher doses of fluconazole. Clin Infect Dis. 1997;25(2):200-205.[PubMed 9332510]

Pappas PG, Kauffman CA, Andes D, et al; Infectious Diseases Society of America. Clinical practice guideline for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(5):503-535. doi: 10.1086/596757.[PubMed 19191635]

Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50. doi: 10.1093/cid/civ933.[PubMed 26679628]

Pastick KA, Nalintya E, Tugume L, et al. Cryptococcosis in pregnancy and the postpartum period: Case series and systematic review with recommendations for management. Med Mycol. 2020;58(3):282‐292. doi:10.1093/mmy/myz084[PubMed 31689712]

Patel K, Roberts JA, Lipman J, Tett SE, Deldot ME, Kirkpatrick CM. Population pharmacokinetics of fluconazole in critically ill patients receiving continuous venovenous hemodiafiltration: using Monte Carlo simulations to predict doses for specified pharmacodynamic targets. Antimicrob Agents Chemother. 2011;55(12):5868-5873. doi: 10.1128/AAC.00424-11.[PubMed 21930888]

Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of Cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(3):291-322. doi: 10.1086/649858.[PubMed 20047480]

Piper L, Smith PB, Hornik CP, et al, "Fluconazole Loading Dose Pharmacokinetics and Safety in Infants," Pediatr Infect Dis J, 2011, 30(5):375-8.[PubMed 21085048]

Restrepo C, Chacon J, Manjarres G. Fungal peritonitis in peritoneal dialysis patients: successful prophylaxis with fluconazole as demonstrated by prospective randomized control trial. Perit Dial Int. 2010;30(6):619-625. doi: 10.3747/pdi.2008.00189.[PubMed 20634438]

Rex JH, Bennett JE, Sugar AM; Candidemia Study Group and the National Institute. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med. 1994;331(20):1325-1330. doi: 10.1056/NEJM199411173312001.[PubMed 7935701]

Rex JH, Pappas PG, Karchmer AW, et al; National Institute of Allergy and Infectious Diseases Mycoses Study Group. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis. 2003;36(10):1221-1228.[PubMed 12746765]

Schilling CG, Seay RE, Larson TA, Meier KR. Excretion of fluconazole inhuman breast milk [abstract]. Pharmacotherapy, 1993;13(3):287.

Science M, Robinson PD, MacDonald T, Rassekh SR, Dupuis LL, Sung L. Guideline for primary antifungal prophylaxis for pediatric patients with cancer or hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2014;61(3):393-400. doi: 10.1002/pbc.24847.[PubMed 24424789]

Sedlak T, Shufelt C, Iribarren C, Lyon LL, Bairey Merz CN. Oral contraceptive use and the ECG: evidence of an adverse QT effect on corrected QT interval. Ann Noninvasive Electrocardiol. 2013;18(4):389-398. doi: 10.1111/anec.12050.[PubMed 23879279]

Silveira FP, Kusne S; AST Infectious Diseases Community of Practice. Candida infections in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):220-227. doi: 10.1111/ajt.12114.[PubMed 23465015]

Singh N, Huprikar S, Burdette SD, Morris MI, Blair JE, Wheat LJ; American Society of Transplantation, Infectious Diseases Community of Practice, Donor-Derived Fungal Infection Working Group. Donor-derived fungal infections in organ transplant recipients: guidelines of the American Society of Transplantation, Infectious Diseases Community of Practice. Am J Transplant. 2012;12(9):2414-2428.[PubMed 22694672]

Sinnollareddy MG, Roberts MS, Lipman J, Robertson TA, Peake SL, Roberts JA. Pharmacokinetics of fluconazole in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration. Int J Antimicrob Agents. 2015;45(2):192-195. doi: 10.1016/j.ijantimicag.2014.08.013.[PubMed 25455854]

Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med. 2004;351(9):876-883. doi: 10.1056/NEJMoa033114.[PubMed 15329425]

Sobel JD. Candida vulvovaginitis: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 23, 2020.

Stary A, Sarnow E. Fluconazole in the treatment of tinea corporis and tinea cruris. Dermatology. 1998;196(2):237-241. doi: 10.1159/000017881.[PubMed 9568414]

Stengel F, Robles-Soto M, Galimberti R, Suchil P. Fluconazole versus ketoconazole in the treatment of dermatophytoses and cutaneous candidiasis. Int J Dermatol. 1994;33(10):726-729.[PubMed 8002145]

Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America [published online June 18, 2014]. Clin Infect Dis. 2014;59(2):e10-52. doi: 10.1093/cid/ciu296.[PubMed 24947530]

Taplitz RA, Kennedy EB, Bow EJ, et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update [published online ahead of print September 4, 2018]. J Clin Oncol. doi: 10.1200/JCO.18.00374.[PubMed 30179565]

Tomblyn M, Chiller T, Einsele H, et al; Center for International Blood and Marrow Research; National Marrow Donor Program; American Society of Blood and Marrow Transplantation; et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective [published correction appears in Biol Blood Marrow Transplant. 2010;16(2):294]. Biol Blood Marrow Transplant. 2009;15(10):1143-1238. doi: 10.1016/j.bbmt.2009.06.019.[PubMed 19747629]

Toon S, Ross CE, Gokal R, Rowland M. An assessment of the effects of impaired renal function and haemodialysis on the pharmacokinetics of fluconazole. Br J Clin Pharmacol. 1990;29(2):221-226.[PubMed 2306414]

Trotman RL, Williamson JC, Shoemaker DM, Salzer WL. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005;41(8):1159-1166. doi: 10.1086/444500.[PubMed 16163635]

Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017;64(6):e34-e65. doi: 10.1093/cid/ciw861.[PubMed 28203777]

US Department of Health and Human Services (HHS); Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.

Valtonen M, Tiula E, Neuvonen PJ. Effect of continuous venovenous haemofiltration and haemodiafiltration on the elimination of fluconazole in patients with acute renal failure. J Antimicrob Chemother. 1997;40(5):695-700.[PubMed 9421318]

Vas S, Oreopoulos DG. Infections in patients undergoing peritoneal dialysis. Infect Dis Clin North Am. 2001;15(3):743-774.[PubMed 11570140]

Veltri MA, Neu AM, Fivush BA, Parekh RS, Furth SL. Drug dosing during intermittent hemodialysis and continuous renal replacement therapy: special considerations in pediatric patients. Paediatr Drugs. 2004;6(1):45-65.[PubMed 14969569]

Wade KC, Benjamin DK Jr, Kaufman DA, et al, "Fluconazole Dosing for the Prevention or Treatment of Invasive Candidiasis in Young Infants," Pediatr Infect Dis J, 2009, 28(8):717-23.[PubMed 19593252]

Wang AY, Yu AW, Li PK, Leung CB, Lai KN, Lui SE. Factors predicting outcome of fungal peritonitis in peritoneal dialysis: analysis of a 9-year experience of fungal peritonitis in a single center. Am J Kidney Dis. 2000;36(6):1183-1192. doi: 10.1053/ajkd.2000.19833.[PubMed 11096043]

Warady BA, Bakkaloglu S, Newland J, et al. Consensus guideline for the prevention and treatment of catheter-related infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012. Peritoneal Dialysis International. 2012;32:s32-86.[PubMed 22851742]

Wassmann S, Nickenig G, Bohm M. Long QT syndrome and torsade de pointes in a patient receiving fluconazole. Ann Inter Med. 1999;131(10):797.[PubMed 10577320]

Watt KM, Benjamin DK Jr, Cheifetz IM, et al. Pharmacokinetics and safety of fluconazole in young infants supported with extracorporeal membrane oxygenation. Pediatr Infect Dis J. 2012;31(10):1042-1047.[PubMed 22627870]

Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(7):807-825.[PubMed 17806045]

Wingard JR. Prophylaxis of invasive fungal infection in adults with hematologic malignancies. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 9, 2019.

Winston DJ, Busuttil RW. Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients. Transplantation. 2002;74(5):688-695. doi: 10.1097/01.TP.0000019727.88291.F5.[PubMed 12352887]

World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the Eleventh WHO Model List of Essential Drugs. http://www.who.int/maternal_child_adolescent/documents/55732/en/. Published 2002.

World Health Organization (WHO). Guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents, and children. http://apps.who.int/iris/bitstream/handle/10665/260400/WHO-CDS-HIV-18.2-eng.pdf;sequence=1. Published 2018. Accessed October 16, 2018.

Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137.[PubMed 26042815 ]

Zhang Z, Zhang X, Zhou YY, Jiang CM, Jiang HY. The safety of oral fluconazole during the first trimester of pregnancy: a systematic review and meta-analysis. BJOG. 2019;126(13):1546-1552.[PubMed 31446677]

Zhu Y, Bateman BT, Gray KJ, et al. Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study. BMJ. 2020;369. doi:10.1136/bmj.m1494[PubMed 32434758]

Brand Names: International

Afungil (CR, DO, GT, HN, MX, NI, PA, SV); Apicon (BD); Asperlican (VN); Avezol (MY); Baten (DO, EC, GT, HN, PA, SV); Biozole (MY); Burnax (EC); Canazole (BD); Candid (BD); Candifix (ES); Candinil (LK); Candivast (BH); Candizole (BE); Canesoral (AU); Cryptal (ID); Diflazole (IE); Diflazon (UA, VN); Diflucan (AE, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CL, CR, CZ, DE, DK, DO, EE, EG, ES, ET, FI, GB, GH, GM, GN, GT, GY, HK, HN, HR, HU, ID, IE, IS, IT, JM, JO, JP, KE, KR, KW, LB, LR, LT, LU, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, PA, PE, PH, PL, PT, QA, RO, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SV, TH, TN, TR, TT, TW, TZ, UG, ZA, ZM); DiflucanOne (AU); Difluvid (MY, PH); Difluzol (UA); Difluzole (KR); Difnazol (KR); Dimycon (HR); Dizole One (AU); Dofil (CR, DO, GT, HN, NI, PA, SV); Duflucan (UA); Dyzolor (PH); Eapacon (ET); Exomax (BH, HK); FCZ Infusion (ID); Flocan (KR); FLU-D (TW); Flucand (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Flucanol (IL, ZW); Flucazol (AE, BR, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Flucazole (NZ); Flucogus (TW); Flucol (IE); Flucon (KR, MY); Flucona (KR); Flucona-Denk (TZ); Fluconal (BD); Fluconaz (PH); Flucoral (BH, ID); Flucoran (NZ); Flucoxan (MX); Flucozal (BR, LK, MT, PK); Flucozol (MY); Fludicon (HK); Fludizol (TH); Fluken (ZW); Flumax (KR); Flumyc (ZW); Flunazol (CY); Flunazole (TW); Flunco (TH); Fluxar (ID); Fluzin (KR); Fluzole (AU, LK); Fluzoral (TH); Forcan (IN, LV, VN); Fukole (MY, PH); Fumay (TW); Funa (TH); Funazol (KR); Funex (CO); Fungata (AT, DE); Fungicon (ZW); Fungostatin (GR); Fungoz (ID); Funzela (PH); Funzol (AE, HR, JO, LB, QA, SA); Fuzolan (ID); Fuzolsel (VN); Glonaz (PH); Jenfunga (EG); Klevaflu (VN); Kyrin (TH); Medoflucon (CN, SG); Mutum (AR, PE, VE); Mycocyst (BM, BS, BZ, GY, JM, SR, TT, UA); Mycomox (LV); Mycorest (SG); Mycosyst (HU); Mycozole (PH); Neoconal (KR); Nobzol-1 (CO); Nobzol-2 (CO); Odaft (MY, PH); Omastin (SG); Onecan (LK); Oneflu (KR); Oramax (AE, ET, KW, LB, QA, SA); Oxifungol (MX); Oxole (AU); Sixanol (PY, UY); Spirolac (PY); Stabilanol (ET, IL); Stalene (TH); Syscan (ET, IN); Tavor (EC); Tinazole (KR); Treflucan (AE, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Triconal (EG); Triflucan (FR, IL, TR); Trigal (BD); Uzol (TW); Zemyc (ID); Zocol (MY); Zoldicam (MX); Zoleshot (PH); Zolmed (VN)

Last Updated 10/14/20