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Fluconazole: Drug information

Fluconazole: Drug information
(For additional information see "Fluconazole: Patient drug information" and see "Fluconazole: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Diflucan
Brand Names: Canada
  • ACT Fluconazole;
  • APO-Fluconazole;
  • Diflucan;
  • Fluconazole SDZ;
  • MYLAN-Fluconazole;
  • PMS-Fluconazole;
  • PRO-Fluconazole;
  • TARO-Fluconazole;
  • TEVA-Fluconazole
Pharmacologic Category
  • Antifungal Agent, Azole Derivative;
  • Antifungal Agent, Oral;
  • Antifungal Agent, Parenteral
Dosing: Adult
Blastomycosis

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 (Ref).

Pulmonary disease (alternative agent if unable to tolerate itraconazole): Oral: 400 to 800 mg once daily for 6 to 12 months (Ref).

Candidiasis, treatment

Candidiasis, treatment: Note: Consider weight-based dosing for patients <50 kg or >90 kg (Ref). 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 (Ref).

Candidemia (neutropenic and non-neutropenic patients):

Initial therapy (alternative agent):

Note: For use in non-neutropenic patients that are not critically ill and not at high risk of fluconazole-resistant isolate. For use in neutropenic patients that are not critically ill and have had no prior azole exposure (Ref); some experts reserve for neutropenic patients who cannot be treated with other agents and whose ANC is >500 and increasing (Ref).

IV, Oral: Loading dose of 800 mg (or 12 mg/kg) on day 1, then 400 mg (or 6 mg/kg) once daily; if fluconazole-susceptible Candida glabrata isolated, transition to 800 mg (or 12 mg/kg) once daily (Ref).

Step-down therapy:

Isolates other than C. glabrata: Oral: 400 mg (or 6 mg/kg) once daily (Ref).

Isolates of C. glabrata (if fluconazole-susceptible or susceptible dose-dependent): Oral: 800 mg (or 12 mg/kg) once daily (Ref).

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 (Ref).

Cardiac device infection (eg, implantable cardiac defibrillator, pacemaker, ventricular assist device [VAD]): Step-down therapy: IV, Oral: 400 to 800 mg (or 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 (or 6 to 12 mg/kg) once daily should be used (Ref).

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

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

Endocarditis, native or prosthetic valve: Step-down therapy (fluconazole-susceptible isolates): IV, Oral: 400 to 800 mg (or 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 (or 6 to 12 mg/kg) once daily should be used (Ref).

Endophthalmitis, endogenous (with or without vitritis) (fluconazole-susceptible isolates): IV, Oral: Loading dose of 800 mg (or 12 mg/kg) on day 1, then 400 to 800 mg (or 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 (Ref).

Esophageal, treatment: IV, Oral: 400 mg (or 6 mg/kg) on day 1, then 200 to 400 mg (or 3 to 6 mg/kg) once daily for 14 to 21 days (Ref). Some experts increase to 800 mg once daily for those with C. albicans infection who do not respond after 1 week (Ref).

Esophageal, chronic suppression for recurrent infection:

Note: Suppressive therapy is usually unnecessary. Reserve for immunocompromised patients (eg, with HIV and low CD4 count) who have multiple recurrent infections (Ref).

Oral: 100 to 200 mg once daily (Ref). Some experts suggest 100 to 200 mg 3 times weekly (Ref); however, resistance may be a potential concern (Ref). May discontinue once immune reconstitution occurs (Ref).

Intertrigo, refractory to topical therapy (off-label use): Oral: 150 mg once weekly for 4 weeks (Ref).

Intra-abdominal infection, acute, including peritonitis and/or abscess (alternative agent):

Note: For empiric therapy, reserve as an alternative to an echinocandin if no previous azole exposure, noncritically ill, and not at high risk of fluconazole-resistant isolate (Ref). Step-down therapy (after patient has responded to initial therapy [eg, echinocandin]) with fluconazole is recommended in stable patients with a fluconazole-susceptible isolate (Ref).

IV, Oral: 800 mg (or 12 mg/kg) on day 1, then 400 mg (or 6 mg/kg) once daily. Total antifungal duration is ≥14 days based on source control and clinical response (Ref).

Oropharyngeal:

Note: Reserve use for moderate to severe disease, poor response to topical treatment, or recurrent infection (Ref).

IV, Oral: 200 mg on day 1, then 100 to 200 mg once daily for 7 to 14 days (Ref); some experts increase to 400 mg once daily for those who do not initially respond (Ref).

Oropharyngeal, chronic suppression for recurrent infection:

Note: Suppressive therapy is usually unnecessary. Reserve for immunocompromised patients (eg, with HIV and low CD4 count) who have multiple recurrent infections (Ref).

Oral: 100 mg once daily (Ref). Some experts suggest 100 mg 3 times weekly (Ref); however, resistance may be a potential concern (Ref). May discontinue once immune reconstitution occurs (Ref).

Osteoarticular (osteomyelitis or septic arthritis) (fluconazole-susceptible isolates): Initial or step-down therapy: IV, Oral: 400 mg (or 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 (or 6 mg/kg) once daily is recommended (Ref).

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

IV, Oral: 200 mg on day 1, then 100 to 200 mg once daily for 2 to 4 weeks (Ref).

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

Urinary tract infection:

Candiduria (asymptomatic):

Patients with neutropenia: Treat as if patient has candidemia (Ref).

Patients undergoing a urologic procedure: Oral: 400 mg (or 6 mg/kg) once daily several days before and after the procedure (Ref).

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

Pyelonephritis: Oral: 200 to 400 mg (or 3 to 6 mg/kg) once daily for 2 weeks (Ref).

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

Vulvovaginal: Note: Not recommended for infection due to C. glabrata or C. krusei (Ref).

Mild or moderate infection in immunocompetent patient: Oral: 150 mg as a single dose (Ref).

Severe infection or infection in immunocompromised patient: Oral: 150 mg every 72 hours for 2 or 3 doses (Ref).

Recurrent infection:

Fluconazole monotherapy: Oral: 150 mg every 72 hours for 10 to 14 days, followed by 150 mg once weekly for 6 months (Ref) 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 (Ref).

Combination therapy with oteseconazole: Oral:

Days 1 to 7: Fluconazole 150 mg as a single dose on days 1, 4, and 7 (Ref).

Days 14 to 20: Oteseconazole 150 mg once daily (Ref).

Starting on day 28: Oteseconazole 150 once weekly for 11 weeks (Ref).

Candidiasis, prophylaxis

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 (Ref).

ICU patients (high risk) in units with a high rate (>5%) of invasive candidiasis (off-label use): Oral, IV: Loading dose of 800 mg (or 12 mg/kg) once on day 1, then 400 mg (or 6 mg/kg) once daily (Ref).

Peritoneal dialysis-associated infection (concurrently treated with antibacterials), prevention of secondary fungal infection: Oral: 200 mg every other day or 100 mg once daily (Ref).

Solid organ transplant recipients (selected patients at high-risk for Candida infection) (off-label use): Oral, IV: 400 mg (or 6 mg/kg) given perioperatively and continued once daily postoperatively; indications and duration vary among transplant centers (Ref).

Coccidioidomycosis, treatment

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 (Ref).

Meningitis: Oral: 400 mg to 1.2 g once daily, depending on severity (Ref); some experts favor a starting dose of ≥800 mg once daily (Ref). Continue lifelong as there is a high relapse rate when the dose is decreased or treatment is discontinued (Ref).

Pneumonia, primary infection: Note: Only for patients with significantly debilitating illness, extensive pulmonary involvement, concurrent diabetes, frailty due to age or comorbidities, or HIV (Ref):

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) (Ref).

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 (Ref).

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 (Ref).

Coccidioidomycosis, prophylaxis

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 (Ref).

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 (Ref); some experts favor 400 mg once daily (Ref).

Seropositive patients in endemic areas: Oral: 400 mg once daily for 6 to 12 months following transplantation (Ref); some experts favor 400 mg once daily for 12 months posttransplantation followed by 200 mg once daily for the duration of immunosuppressive therapy (Ref).

Cryptococcal meningitis

Cryptococcal meningitis:

Patients with HIV:

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

Resource-rich settings, alternative regimens:

If flucytosine is unavailable or not tolerated: Oral: 800 mg to 1.2 g once daily in combination with amphotericin B (lipid formulation preferred) for ≥2 weeks (Ref).

If amphotericin B is unavailable or not tolerated: Oral: 800 mg to 1.2 g once daily in combination with flucytosine for ≥2 weeks (Ref).

If flucytosine and amphotericin B are unavailable or not tolerated: Oral: 1.2 g once daily as monotherapy for ≥2 weeks (Ref).

Resource-limited settings:

Oral: 1.2 g once daily for 2 weeks in combination with flucytosine and a single dose of liposomal amphotericin B (preferred regimen) (Ref).

If liposomal amphotericin B is not available: Oral: 1.2 g once daily for 1 week, started after completion of 1 week of amphotericin B deoxycholate in combination with flucytosine (Ref).

If no amphotericin B formulation is available: Oral: 1.2 g once daily in combination with flucytosine for 2 weeks (Ref).

If flucytosine is unavailable: Oral: 1.2 g once daily in combination with liposomal amphotericin B or amphotericin B deoxycholate for 2 weeks (Ref).

Consolidation: Oral: 800 mg once daily for ≥8 weeks; may consider reducing dose to 400 mg once daily in patients who are treated with amphotericin B and flucytosine induction regimen, have negative CSF cultures after 2 weeks of induction therapy, and are initiated on antiretroviral therapy (Ref).

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 (Ref).

HIV-uninfected patients:

Induction (alternative regimens):

If flucytosine is unavailable or not tolerated: Oral: 800 mg once daily in combination with amphotericin B for 2 weeks (Ref).

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

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

Consolidation: Oral: 400 to 800 mg once daily for 8 weeks (some experts prefer 800 mg once daily for patients who receive a 2-week induction course) (Ref).

Maintenance (suppression): Oral: 200 to 400 mg once daily for 6 to 12 months (Ref). 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 (Ref).

Cryptococcosis, pulmonary infection

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 (Ref); for patients with HIV, some experts recommend 400 to 800 mg once daily for 10 weeks, followed by 200 mg once daily for a total of 6 months in combination with effective antiretroviral therapy (Ref). Chronic suppressive therapy may be warranted for patients with ongoing immunosuppression (Ref).

Onychomycosis

Onychomycosis (alternative agent) (off-label use):

Note: For patients unable to use preferred agents (Ref).

Oral: 150 to 450 mg once weekly. Usual duration of therapy: 3 months (fingernail) or 6 to 12 months (toenail) (Ref).

Tinea infections

Tinea infections (alternative agent) (off-label use): Note: For disease that is extensive or refractory to topical therapy (Ref).

Tinea corporis/tinea cruris: Oral: 150 to 200 mg once weekly for 2 to 4 weeks (Ref).

Tinea pedis/tinea manuum: Oral: 150 mg once weekly for 2 to 6 weeks (Ref).

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

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

Dosing: Kidney 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.

Altered kidney function: 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 (Ref):

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 (Ref):

Three-times-weekly (postdialysis) dosing: 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 dialysis session (Ref).

Note: The manufacturer's labeling recommends that in addition to 100% of the dose given after dialysis on dialysis days, patients should also receive a reduced dose according to their creatinine clearance on nondialysis days; however, this appears unnecessary, as fluconazole concentrations decrease only minimally during the interdialytic period (Ref).

Once-daily dosing (may be considered when a more convenient dosing regimen is preferred [eg, hospitalized patients]): Administer 100% of the indication-specific loading/initial dose recommended in the adult dosing section, then reduce maintenance dose by 50% and administer once daily; when scheduled dose falls on a dialysis day, administer after dialysis (Ref).

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% (Ref).

CRRT: 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 (Ref) (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 (Ref).

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 (Ref) (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 (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): 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 (Ref) or twice daily (Ref).

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

(For additional information see "Fluconazole: Pediatric drug information")

General dosing, susceptible infection: Infants, Children, and Adolescents: IV, Oral: Initial: 6 to 12 mg/kg/dose on day 1, 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; however, higher maximum doses have been used; see specific indications.

Candida infections, prophylaxis

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 (Ref).

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 (Ref).

Candidiasis, systemic, treatment

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, resolution of symptoms, and resolution of neutropenia if present (Ref). An initial loading dose of 25 mg/kg has also been suggested (Ref).

Candidiasis, CNS candidiasis, step-down therapy

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 (Ref).

Candidiasis, endophthalmitis, treatment

Candidiasis, endophthalmitis, treatment: Infants, Children, and Adolescents: Oral, IV: 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 (Ref). An initial loading dose of 25 mg/kg has also been suggested (Ref).

Candidiasis, esophageal

Candidiasis, esophageal:

Treatment:

Infants and Children: Oral, IV: 6 to 12 mg/kg/dose once daily for 14 to 21 days (Ref); maximum dose: 600 mg/dose (Ref). Note: An initial loading dose of 25 mg/kg has also been suggested (Ref).

Adolescents: Oral, IV: 6 to 12 mg/kg/dose once daily for 14 to 21 days (Ref); usual adult dose: 400 mg/dose (Ref). Note: An initial loading dose of 25 mg/kg has also been suggested (Ref).

Suppressive therapy (secondary prophylaxis): Patients with HIV: Note: Not typically recommended, but can be considered if experiencing frequent severe recurrent infection (Ref).

Infants and Children: Oral: 6 to 12 mg/kg/dose three times weekly; maximum dose: 600 mg/dose. If daily administration is required, maximum dose is 200 mg/dose (Ref).

Adolescents: Oral: 100 to 200 mg once daily (Ref).

Candidiasis, oropharyngeal

Candidiasis, oropharyngeal:

Treatment:

Infants and Children: Oral: 6 to 12 mg/kg/dose once daily for 7 to 14 days (Ref); maximum dose: 400 mg/dose (Ref).

Adolescents: Oral: 6 mg/kg/dose once daily for 7 to 14 days (Ref); usual adult dose: 100 to 200 mg/dose (Ref).

Suppressive therapy (secondary prophylaxis): Patients with HIV: Note: Not typically recommended, but can be considered if experiencing frequent severe recurrent infection (Ref).

Infants and Children: Oral: 6 to 12 mg/kg/dose three times weekly; maximum dose: 600 mg/dose. If daily administration is required, maximum dose is 200 mg/dose (Ref).

Adolescents: Oral: 100 to 200 mg once daily or three times weekly (Ref).

Candidiasis, peritoneal dialysis-related infections

Candidiasis, peritoneal dialysis-related infections (Ref):

Peritonitis: Infants, Children, and Adolescents:

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: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose every 24 to 48 hours; maximum dose: 400 mg/dose.

Candidiasis, vulvovaginal infection

Candidiasis, vulvovaginal infection:

Uncomplicated infections, treatment (independent of HIV status): Adolescents: Oral: 150 mg as a single dose (Ref).

Severe infections, treatment:

Non-HIV-exposed/-infected: Adolescents: Oral: 150 mg every 72 hours for 2 to 3 doses (Ref).

HIV-exposed/-infected: Adolescents: Oral: 100 to 200 mg once daily for ≥7 days; may follow with chronic suppressive therapy of 150 mg once weekly (Ref).

Recurrent infection, treatment:

Non HIV-exposed/-infected: 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 (Ref).

HIV-exposed/-infected: Adolescents: Oral: 100 to 200 mg once daily for ≥ 7 days; may follow with chronic suppressive therapy of 150 mg once weekly (Ref).

Coccidioidomycosis, HIV-exposed/-infected

Coccidioidomycosis, HIV-exposed/-infected (Ref):

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

Cryptococcal infection:

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

Non HIV-exposed/-infected: 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 (Ref).

HIV-exposed/-infected:

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 (Ref).

Adolescents: Oral: 400 mg daily for 12 months (Ref).

CNS, severe pulmonary or disseminate infection, treatment:

Induction therapy: HIV-exposed/-infected (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 (Ref).

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 (Ref).

Consolidation:

Non-HIV-exposed/-infected: 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 (Ref).

HIV-exposed/-infected:

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 (Ref).

Adolescents: IV, Oral: 400 mg once daily for ≥8 weeks (Ref).

Secondary prophylaxis/chronic suppressive maintenance therapy:

Non-HIV-exposed/-infected: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for 6 to 12 months; maximum dose: 200 mg/dose (Ref).

HIV-exposed/-infected: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for ≥12 months; maximum dose: 200 mg/dose (Ref).

Histoplasmosis

Histoplasmosis: HIV-exposed/-infected patients, alternative therapy (Ref):

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: Kidney Impairment: Pediatric

Note: Dosing is based on pharmacokinetic parameters, limited pediatric studies, adult studies, and expert opinion (Ref).

Altered kidney function:

Infants, Children, and Adolescents (Ref): Note: In critically ill patients with altered kidney function, consider monitoring serum concentrations if available (Ref).

CrCl ≥50 mL/minute/1.73 m2: IV, Oral: Administer the usual indication-specific dose every 24 hours.

CrCl <50 mL/minute/1.73 m2: IV, Oral: Administer the usual indication-specific dose every 48 hours or administer 100% of the usual indication-specific dose or loading dose initially, followed by 50% of the usual indication-specific dose every 24 hours.

Note: No dosage adjustment necessary for single-dose therapy for vaginal candidiasis (Ref).

Hemodialysis, intermittent:

Note: Based on adult information, fluconazole is dialyzable (33% to 38% with low-flux dialyzers (Ref) or approximately 50% after a 3-hour session (Ref).

Infants, Children, and Adolescents: IV/Oral:

Dialysis days: Administer the usual indication-specific dose after each dialysis session (Ref). Note: The manufacturer's labeling recommends that in addition to 100% of the dose given after dialysis on dialysis days, patients should also receive a reduced dose according to their creatinine clearance on nondialysis days; however, based on adult data, this appears unnecessary, as fluconazole concentrations decrease only minimally during the interdialytic period (Ref).

Peritoneal dialysis:

Infants, Children, and Adolescents: IV, Oral: Administer 50% of the usual indication-specific dose every 24 to 48 hours (Ref).

CRRT:

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Flow rates vary widely in pediatric patients. Appropriate dosing requires consideration of drug penetration to site of infection, severity of illness, and consideration of loading dose. Close monitoring of response and adverse reactions due to drug accumulation is important. Due to limited data and patient variability, monitor serum concentrations if available (target AUC24/MIC 50 to 100 or trough concentrations 10 to 15 mg/L [for MICs up to 4 mg/L] in critical illness) (Ref)­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­.

CVVH/CVVHD/CVVHDF: Children and Adolescents: IV, Oral: Loading dose: 6 to 12 mg/kg once, followed by 6 to 12 mg/kg/dose (as appropriate for patient-specific indication) every 24 hours; maximum dose: 800 mg/dose. For some indications, a higher initial loading dose may be appropriate (Ref).

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 in adults receiving CRRT with rates of 1,500 to 3,000 mL/hour is 1.5 to 2.3 times that reported in healthy volunteers (Ref). In one case report in an adolescent receiving CVVH with a high flow rate (4,090 mL/hour), the patient required double the initial dosage (to 20 mg/kg/day) to achieve pharmacodynamic targets (Ref).

Dosing: Hepatic Impairment: Pediatric

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

Dosing: Older Adult

Refer to adult dosing.

Dosing: Obesity: Adult

The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):

Candidiasis, invasive: Note: For use in patients who are unlikely to be infected with a fluconazole-resistant isolate:

IV, Oral: Initial: Use actual body weight for weight-based dose calculations; loading dose of 12 mg/kg (maximum loading dose: 1.6 g) on day 1, followed by 6 mg/kg once daily (maximum dose [not well established]: 800 mg to 1.6 g); daily doses up to 1.6 g are well tolerated (Ref). Note: May omit loading doses in non–critically ill patients (Ref). Refer to "Dosing: Adults" for other indication-specific dosing.

Other fungal indications: Evidence currently does not exist for other indications in patients with obesity; however, the same dosing principles and use of actual body weight would apply (Ref).

Rationale for recommendations: There are limited pharmacokinetic data in patients with obesity (Ref). A pharmacokinetic study using Monte Carlo simulation evaluated both fixed and weight-based dosing of fluconazole aimed to achieve a target fAUC/minimum inhibitory concentration (MIC) of 25 and 100. This study suggests that a loading dose of 12 mg/kg (using actual body weight), followed by a maintenance dose of 6 mg/kg (using actual body weight), achieves fAUC/MIC targets regardless of BMI and patient weight (Ref).

Dosage Forms: US

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

Solution, Intravenous:

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

Solution, Intravenous [preservative free]:

Generic: 100 mg/50 mL in NaCl 0.9% (50 mL); 200 mg (100 mL [DSC]); 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 [DSC], 100 mg, 150 mg, 200 mg [contains fd&c red #40(allura red ac)aluminum lake]

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

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Solution, Intravenous:

Diflucan: 2-0.9 MG/ML-% (100 mL)

Generic: 2-0.9 MG/ML-% (100 mL)

Suspension Reconstituted, Oral:

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

Tablet, Oral:

Generic: 50 mg, 100 mg, 200 mg

Administration: Adult

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

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 (Ref); doses ranging from 3 to 12 mg/kg/dose have been infused over 1 to 2 hours including extremely low birth weight neonates (Ref).

Pediatric: Doses up to 8 to 10 mg/kg were infused over 2 hours (Ref).

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).

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

Use: Off-Label: Adult

Blastomycosis; Candida intertrigo; Candidiasis, empiric therapy (non-neutropenic patients in the ICU); Candidiasis, prophylaxis in high-risk ICU patients (in units with high incidence of invasive candidiasis); Candidiasis, prophylaxis in hematologic malignancy patients; Candidiasis, prophylaxis in solid organ transplant recipients; Coccidioidomycosis; Cryptococcosis, pulmonary infection; Onychomycosis; Tinea infections

Medication Safety Issues
Sound-alike/look-alike issues:

Fluconazole may be confused with flecainide, FLUoxetine, furosemide, itraconazole, voriconazole

Diflucan may be confused with diclofenac, Diprivan, disulfiram

International issues:

Canesten (oral capsules) [Great Britain] may be confused with Canesten brand name for clotrimazole (various dosage forms) [multiple international markets]; Cenestin brand name estrogens (conjugated A/synthetic) [US, Canada]

Adverse Reactions (Significant): Considerations
Cardiovascular effects

Dysrhythmias: Azole antifungals, including fluconazole, have been associated with prolonged QT interval on ECG, which may lead to torsades de pointes (TdP) or polymorphic ventricular arrhythmias. Numerous probable cases of TdP have been reported with fluconazole in patients with additional risk factors (Ref). Drug-drug interactions commonly play a role in risk related to cardiac effects with fluconazole either by an additive pharmacodynamic effect, reducing the clearance of fluconazole, or by lowering potassium and/or magnesium concentrations (Ref).

Vascular: Another rare cardiac effect with fluconazole is hypersensitivity coronary syndrome (ie, allergic angina or Kounis syndrome) (Ref).

Mechanism:

Dysrhythmias: One proposed mechanism is that azole antifungals may block the IKr channel (Ref). Another possible mechanism is depression of rapidly activating delayed rectifier potassium channels (Ref).

Vascular: Kounis syndrome is thought to be caused by an allergen mediated-IgE and mast cell activation and degranulation causing histamine release (Ref).

Onset:

Dysrhythmias: Rapid; QT prolongation occurred within the first 24 hours to a couple of days after initiation, dependent on drug-drug interactions (Ref).

Vascular: Kounis syndrome may occur immediately after the first dose (Ref).

Risk factors:

Drug-induced QTc prolongation/TdP (in general):

• Females (Ref)

• Age >65 years (Ref)

• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)

• Genetic defects of cardiac ion channels (Ref)

• History of drug-induced TdP (Ref)

• Congenital long QT syndrome (Ref)

• Longer baseline QTc interval (eg, >450 msec) or lengthening of the QTc by ≥60 msec (Ref)

• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)

• Bradycardia (Ref)

• Hepatic impairment (Ref)

• Kidney impairment (Ref)

• Diuretic use (Ref)

• Sepsis (Ref)

• Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref)

Dermatologic reactions

Dermatologic reactions are usually mild and include maculopapular skin rash (Ref), fixed drug eruption (FDE) (Ref), alopecia (Ref) and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) (Ref). Rare reports of severe cutaneous adverse reactions (SCARs) include Stevens-Johnson syndrome (SJS) (Ref), toxic epidermal necrolysis (TEN) (Ref), drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref), and acute generalized exanthematous pustulosis (AGEP) (Ref). Other cutaneous reactions include Sweet’s syndrome (Ref).

Mechanism: Non–dose-related; immunologic. Maculopapular eruptions, FDE, SDRIFE, and SCARs are T-cell-mediated (Ref).

Onset: Delayed hypersensitivity reactions: Varied. Maculopapular rash usually occurs 5 to 21 days after start of therapy (Ref), although can occur after 1 dose, especially in previously sensitized patients (Ref). FDE lesions can develop within 15 minutes to 2 days after drug administration (Ref). SCARs usually occur 1 to 8 weeks after initiation (Ref); reexposure may lead to more rapid onset (usually within 1 to 4 days) (Ref).

Risk factors:

• Cross-reactivity: Cross-reactivity among oral azole antifungals has not been consistently reported. Possible cross-reactivity between fluconazole and itraconazole has been suggested (Ref). However, lack of cross-reactivity has been documented between fluconazole and itraconazole, as well as between fluconazole and ketoconazole (Ref). In addition, no cross-reactivity was noted between fluconazole and voriconazole (Ref).

Hepatotoxicity

Azole antifungals, including fluconazole, may cause hepatotoxicity (ranging from mild and asymptomatic liver abnormalities to hepatic failure) (Ref). From a 2010 meta-analysis, fluconazole users had increased serum transaminases that did not require discontinuation (Ref). Hepatotoxicity may also occur as part of drug rash eosinophilia with systemic symptoms (DRESS) (Ref). Fluconazole liver injury is usually hepatocellular hepatitis, but may present as cholestatic hepatitis or hepatitis (mixed) (Ref). Most cases of hepatotoxicity are self-limited; although, recovery may take up to 3 to 4 months (Ref).

Mechanism: Not well known; possible mechanisms include mitochondrial dysfunction, idiosyncratic, and immunologic (Ref).

Onset: Varied; most cases occur within 1 to 2 months of initiation (Ref).

Risk factors:

• Fluconazole-induced liver injury has been reported as both dose- and non–dose-dependent (Ref)

• Preexisting liver disease (Ref)

• Concurrent hepatotoxic agents and drug interactions (Ref)

• Kidney impairment (Ref)

• HIV (Ref)

• Cross-reactivity among oral azole antifungals has not been consistently reported in patients with histories of hepatotoxicity (Ref)

• Acute liver injury is less common with fluconazole than other azoles (voriconazole, posaconazole) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

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

1% to 10%:

Dermatologic: Skin rash (adults: 2%)

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

Nervous system: Dizziness (adults: 1%)

Frequency not defined: Hepatic: Increased serum alkaline phosphatase

Postmarketing:

Cardiovascular: Prolonged QT interval on ECG, torsades de pointes (Poluzzi 2010)

Dermatologic: Acute generalized exanthematous pustulosis (Alsadhan 2002; Di Lernia 2015), alopecia (Pappas 1995), diaphoresis, exfoliative dermatitis, Stevens-Johnson syndrome (Craythorne 2009, Monastirli 2008), Sweet’s syndrome (Adler 2018), toxic epidermal necrolysis (George 2012, Islam 2014)

Endocrine & metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia

Gastrointestinal: Xerostomia

Hematologic & oncologic: Agranulocytosis (Murakami 1992), leukopenia, neutropenia, thrombocytopenia (Murakami 1992)

Hepatic: Cholestatic hepatitis (Joseph 2019), hepatic failure (Gayam 2018), hepatitis (mixed) (Joseph 2019), hepatocellular hepatitis (Joseph 2019), hepatotoxicity (Kyriakidis 2017, Song 2005), increased serum transaminases (Wang 2010)

Hypersensitivity: Anaphylaxis (Neuhaus 1991), angioedema, fixed drug eruption (Nakai 2013, Quint 2019)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Benjamin Lash 2016, Su 2003)

Nervous system: Drowsiness, fatigue, insomnia, malaise, paresthesia, seizure, vertigo

Neuromuscular & skeletal: Asthenia, myalgia, tremor

Miscellaneous: Fever

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 with CYP3A4 substrates, which may lead to QTc prolongation (eg, erythromycin, pimozide, quinidine).

Warnings/Precautions

Concerns related to adverse effects:

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

Disease-related concerns:

• 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.

Metabolism/Transport Effects

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

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

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

ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). 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

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

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

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

Avacopan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avacopan. 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 to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. 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 times 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

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

Benidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benidipine. 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

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

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

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

Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cariprazine. 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: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Ceritinib. Ceritinib 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 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: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. 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

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

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: Consider alternatives to this combination whenever possible. If such a combination must be used, 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

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

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

Cyclophosphamide: Fluconazole may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, serum bilirubin and serum creatinine may be increased. Fluconazole may increase the serum concentration of Cyclophosphamide. Risk C: Monitor therapy

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

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

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

Daridorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. 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

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

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

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

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

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

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

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. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. 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: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. 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

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

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

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

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

Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eszopiclone. 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

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

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: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Fexinidazole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QT prolongation may be at even higher risk. Also monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification

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

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

Fluorouracil Products: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. 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

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

Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Nasal). 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

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

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

Glasdegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Glasdegib. 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

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

Infigratinib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Infigratinib. Risk X: Avoid combination

Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Irinotecan Products. Risk C: Monitor therapy

Isavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor therapy

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

Itraconazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Itraconazole. 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

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

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

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

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

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

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

Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy

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

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

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

Lorlatinib: Fluconazole may increase the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with fluconazole whenever possible. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily. Risk D: Consider therapy modification

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

Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

Mavacamten: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Mavacamten. Risk X: Avoid combination

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 increased methadone toxicities (eg, respiratory depression, QTc interval prolongation). 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

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

Midazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider therapy modification

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

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

Mitapivat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider therapy modification

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

Mobocertinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Mobocertinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentrations of the active metabolite(s) of Mobocertinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Mobocertinib. Management: Avoid use of QT prolonging moderate CYP3A4 inhibitors with mobocertinib when possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider therapy modification

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

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

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

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

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

Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nitrendipine. 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

Olmutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. 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

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

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

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

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

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

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

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

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

Panobinostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Panobinostat. 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: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of PAZOPanib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of PAZOPanib. 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

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

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

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

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

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

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

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

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). 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. 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. 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. Risk D: Consider therapy modification

QT-Prolonging Inhalational Anesthetics (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 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. 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). 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. 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. 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. 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 (Highest Risk): May enhance the QTc-prolonging effect of Fluconazole. Management: Consider alternatives to this 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

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

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

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

RifAMPin: May decrease the serum concentration of Fluconazole. Fluconazole may increase the serum concentration of RifAMPin. Management: Consider increasing the dose of fluconazole when used concurrently with rifampin. When combined, monitor for both reduced clinical efficacy of fluconazole and increased rifampin toxicities. Risk D: Consider therapy modification

Rifapentine: May decrease the serum concentration of Fluconazole. Risk C: Monitor therapy

Rimegepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider therapy modification

RisperiDONE: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of RisperiDONE. 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

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

Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Risk C: Monitor therapy

Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy

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

Ruxolitinib (Systemic): Fluconazole may increase the serum concentration of Ruxolitinib (Systemic). Management: Avoid fluconazole doses over 200 mg/day in combination with ruxolitinib. Dose adjustments are required in some circumstances. See full interaction 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

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

Sildenafil: CYP3A4 Inhibitors (Moderate) 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: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Moderate) 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 (Conventional): Fluconazole may increase the serum concentration of Sirolimus (Conventional). 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

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of SUNItinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of SUNItinib. 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

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: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor therapy

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

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

Thiotepa: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Thiotepa. 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

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

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

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

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

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

Vitamin K Antagonists (eg, warfarin): Fluconazole may increase the serum concentration of Vitamin K Antagonists. Management: Consider alternatives when possible. If combined, 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

Voclosporin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

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

Reproductive Considerations

Based on human data, in utero exposure to high doses of fluconazole may cause fetal harm. According to the manufacturer, patients who may become pregnant and who are taking higher doses (≥400 mg/day) should use effective contraception during therapy and for ~1 week after the final fluconazole dose.

Pregnancy Considerations

Based on human data, in utero exposure to high doses of fluconazole may cause fetal harm. 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 (Budani 2021; Diflucan [fluconazole oral] prescribing information).

Oral fluconazole for the treatment of vaginal candidiasis is not recommended during pregnancy. Topical therapy for oral or vaginal candidiasis is recommended in pregnant patients (HHS [OI adult 2020]; Workowski [CDC 2021]). Secondary prophylaxis or chronic maintenance therapy using oral or IV fluconazole should not be initiated during pregnancy for esophageal, oropharyngeal, or vaginal candidiasis; fluconazole should be discontinued if pregnancy occurs during therapy (HHS [OI adult 2020]). Fluconazole is not the treatment of choice for invasive candidiasis in pregnant patients (IDSA [Pappas 2016]). Fluconazole may be used for the treatment of cryptococcosis or coccidioidomycosis after the first trimester if otherwise appropriate (HHS [OI adult 2020]; IDSA [Galgiani 2016]; Pastick 2020).

Breastfeeding Considerations

Fluconazole is present in breast milk.

Information related to the presence of fluconazole in breast milk is available from multiple sources:

• A case report describes use of oral fluconazole 200 mg daily in a patient beginning 10 days prior to delivery and continuing postpartum. On day 18 of therapy (8 days after delivery), a total of 4 breast milk samples were obtained 30 minutes prior to and at intervals up to 10 hours after administration. Following the last dose (20 days after delivery), breast milk samples were obtained at 12-hour intervals, from 12 to 48 hours post administration. The peak breast milk concentration (4.1 mcg/mL) occurred at 2 hours after the maternal dose. The apparent elimination half-life of fluconazole in breast milk was 26.9 hours (r = 0.993); the apparent elimination half-life of fluconazole in maternal serum was 18.6 hours (Schilling 1993). Using a milk concentration of 4.1 mcg/mL, the estimated exposure to the breastfeeding infant would be 0.62 mg/kg/day (relative infant dose [RID] 5% to 10% based on a therapeutic infant dose of 6 to 12 mg/kg/day).

• In a second case report, a lactating female received oral fluconazole 150 mg as a single dose for the treatment of vulvovaginal candidiasis at 12 weeks' postpartum. The patient opted to withhold breastfeeding from her infant for 4 days following fluconazole administration but continued to maintain her milk supply. Breast milk concentrations of fluconazole were 2.93 mcg/mL 2 hours after the dose and decreased to 0.98 mcg/mL 48 hours after the dose (Force 1995).

• The manufacturer's labeling presents data from 10 breastfeeding women administered a single oral dose of fluconazole 150 mg, 5 days to 19 months postpartum. Peak breast milk concentrations were 1.57 to 3.65 mcg/mL 5.2 hours after the dose. Using a mean peak milk concentration of 2.61 mcg/mL, the estimated exposure to the breastfeeding infant was calculated to be 0.39 mg/kg/day (RID 13% based on a therapeutic infant dose of 3 mg/kg/day).

• In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).

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 patients, existing recommendations state that fluconazole is considered compatible with breastfeeding when used in usual recommended doses (WHO 2002).

Treatment of breastfeeding patients with nipple or breast candidiasis with oral fluconazole is common, especially in persistent or recurring infections. Untreated candida nipple or breast infections may be painful for the mother and can contribute to premature weaning (Brent 2001); however, treatment with oral fluconazole should be reserved only for resistant cases (ABM [Berens 2016]; Douglas 2021). 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).

Monitoring Parameters

Periodic LFTs (AST, ALT, alkaline phosphatase, especially in patients with preexisting liver disease) and renal function tests, potassium, rash; signs and symptoms of hepatic injury in patients with abnormal LFTs.

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

Pharmacokinetics

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)

Pharmacokinetics: Additional Considerations

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

Pricing: US

Solution (Fluconazole in Sodium Chloride Intravenous)

100 mg/50 mL 0.9% (per mL): $0.12

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): $0.96

Suspension (reconstituted) (Fluconazole Oral)

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

40 mg/mL (per mL): $3.59 - $3.73

Tablets (Diflucan Oral)

50 mg (per each): $1.36

100 mg (per each): $1.36

150 mg (per each): $73.05

200 mg (per each): $75.11

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.

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);
  • Beagyne (FR);
  • Biozole (MY);
  • Burnax (EC);
  • Canazole (BD);
  • Candid (BD);
  • Candifix (ES);
  • Candinil (LK);
  • Candivast (BH);
  • Canesoral (AU);
  • Canesten Oral (GB);
  • Cryptal (ID);
  • Damicol (AR);
  • Diflazole (IE);
  • Diflazon (UA, VN);
  • Diflucan (AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CL, CN, 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, VE, ZA, ZM);
  • Difluvid (MY, PH);
  • Difluzol (UA);
  • Difluzole (KR);
  • Difnazol (KR);
  • Dimycon (HR);
  • Dizole (AU);
  • Dofil (CR, DO, GT, HN, NI, PA, SV);
  • Duflucan (UA);
  • Dyzolor (PH);
  • Eapacon (ET);
  • Exomax (BH, HK, ZA);
  • FCZ Infusion (ID);
  • Flocan (KR);
  • FLU-D (TW);
  • Flucan (TR);
  • Flucand (BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);
  • Flucanol (IL, ZW);
  • Flucazol (AE, BR, CH, 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 (CZ, IN, LV, VN);
  • Fukole (MY, PH);
  • Fumay (TW);
  • Funa (TH);
  • Funazol (KR);
  • Funex (CO);
  • Fungata (DE);
  • Fungicon (ZW);
  • Fungostatin (GR);
  • Fungoz (ID);
  • Funzela (PH);
  • Funzol (JO, LB, QA, SA);
  • Fuzolan (ID);
  • Fuzolsel (VN);
  • Glonaz (PH);
  • Insep (ZA);
  • Jenfunga (EG);
  • Klevaflu (VN);
  • Kyrin (TH);
  • Medoflucon (CN, SG);
  • Mutum (AR, PE);
  • 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);
  • Reforce (PT);
  • Sixanol (PY, UY);
  • Solona (SE);
  • 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)


For country code abbreviations (show table)
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