Version July 2025
General dosing:
Treatment: Preterm and term neonates: IV, Oral: Initial: 25 mg/kg on day 1, followed by 12 mg/kg/dose once daily (Ref). Note: For candidiasis, the manufacturer's labeling recommends lower dosing for neonates with GA <30 weeks; refer to indication-specific dosing.
Candidiasis, prophylaxis: Limited data available; optimal dose uncertain.
Early prophylaxis ( initiation in the first 5 days of life): Note: Recommended for use in NICUs with high rates (>10%) of invasive candidiasis.
Birth weight <1 kg: IV, Oral: 3 to 6 mg/kg/dose twice weekly for up to 6 weeks or until IV access is no longer required; usually initiated within 72 hours of birth (Ref). NICU-specific Candida sp. susceptibility patterns/minimum inhibitory concentration (MIC) distributions may be considered when selecting the dose; 3 mg/kg/dose is likely to be effective when local Candida isolate MICs are ≤2 mg/L; 6 mg/kg/dose is necessary when MICs are >2 mg/L or are unknown (Ref); when MICs are low within a NICU, 3 mg/kg is likely as efficacious as 6 mg/kg (Ref).
Late prophylaxis: Note: May be considered in patients ≥8 days PNA who are at high risk of invasive candidiasis and receiving broad-spectrum antibiotics, particularly in the setting of gastrointestinal disease; dosing is based on pharmacokinetic modeling and has not been evaluated prospectively (Ref).
Preterm and term neonates: IV, Oral:
|
Gestational Age |
Postnatal Age |
Dose |
|---|---|---|
|
23 to <30 weeks |
8 to <42 days |
6 mg/kg/dose every 72 hours |
|
≥42 days |
6 mg/kg/dose every 48 hours | |
|
30 to 40 weeks |
8 to <42 days |
6 mg/kg/dose every 48 hours |
Candidiasis, systemic (including Candidemia and invasive candidiasis), treatment: Note: Alternative treatment for patients who have not received fluconazole prophylaxis.
Preterm and term neonates: IV, Oral: 25 mg/kg on day 1, followed by 12 mg/kg/dose once daily (Ref). Note: Following the initial load, the manufacturer’s labeling recommends neonates with GA <30 weeks receive 9 mg/kg/dose once daily until 3 months postnatal age, based on pharmacokinetic simulations, to target an AUC24 of 400 to 800 mg*h/L (Ref).
Candidiasis, CNS, step-down therapy: Preterm and term neonates: IV, Oral: 12 mg/kg/dose once daily until all signs, symptoms, and CSF and radiological abnormalities have resolved (Ref).
Candidiasis, ECMO patients: Limited data available; dosing based on a pharmacokinetic study of pediatric patients (including neonates):
Prophylaxis: IV: Preterm and term neonates: 12 mg/kg on day 1, followed by 6 mg/kg/dose once daily (Ref).
Treatment: Preterm and term neonates: IV: 35 mg/kg on day 1, followed by 12 mg/kg/dose once daily (Ref). Note: Following the initial load, the manufacturer's labeling recommends neonates with GA <30 weeks receive 9 mg/kg/dose once daily until 3 months postnatal age, based on pharmacokinetic simulations, to target an AUC24 of 400 to 800 mg*h/L (Ref).
Coccidioidomycosis: Limited data available; optimal dose has not been established.
Preterm and term neonates: IV, Oral: 6 to 12 mg/kg/dose once daily. Treatment duration for confirmed infection depends on site and severity of infection and clinical response (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing: Altered Kidney Function: Neonatal: There are no specific neonatal dosage adjustments provided in the manufacturer's labeling; some experts have suggested the following indication-specific dosing based on pharmacokinetic studies (Ref):
Candidiasis, prophylaxis:
Early prophylaxis: Note: Dosing based on usual dose of 6 mg/kg/dose twice weekly.
Preterm neonates: GA 23 to 29 weeks, PNA ≥3 days, and SCr 1.3 to 2 mg/dL: IV, Oral: 6 mg/kg/dose once weekly; resume 6 mg/kg/dose twice weekly when SCr is ≤1 mg/dL (Ref).
Late prophylaxis: Note: Dosing based on usual dose of 6 mg/kg/dose every 48 to 72 hours.
Preterm and term neonates: PNA ≥8 days with SCr ≥1.3 mg/dL: 6 mg/kg/dose once weekly; resume standard late prophylaxis dose for GA and PNA when SCr is ≤1 mg/dL (Ref).
General dosing: Infants, Children, and Adolescents: IV, Oral: 6 to 12 mg/kg/dose once daily; usual maximum dose: 800 mg/dose (Ref); refer to indication-specific dosing.
Candida infection, 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 (including Candidemia and invasive candidiasis), treatment:
Infants, Children, and Adolescents: IV, Oral: 25 mg/kg (maximum dose: 800 mg/dose) on day 1, followed by 12 mg/kg/dose once daily (maximum dose: 400 mg/dose; may consider up to 600 mg in patients with HIV); continue treatment for ≥14 days after documented clearance, resolution of symptoms, and resolution of neutropenia if present (Ref).
Candidiasis, CNS, step-down therapy:
Infants, Children, and Adolescents: Oral, IV: 25 mg/kg on day 1, followed by 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:
Infants, Children, and Adolescents: Oral, IV: 25 mg/kg once, followed by 12 mg/kg/dose once daily for at least 4 to 6 weeks until examination indicates resolution; maximum dose: 800 mg/dose. Use in combination with intravitreal injection of voriconazole or amphotericin B deoxycholate when vitritis or macular involvement is present (Ref).
Candidiasis, esophageal:
Treatment: Infants, Children, and Adolescents:
High dose: Oral, IV: 6 to 12 mg/kg/dose once daily for 14 to 21 days; maximum dose: 400 mg/dose; a higher maximum dose (600 mg/dose) has been recommended for infants and children with HIV (Ref). Note: An initial loading dose of 25 mg/kg has also been suggested (Ref). High-dose regimen is recommended for infants and children with HIV (Ref).
Low dose: Oral, IV: 6 mg/kg on day 1 (usual maximum dose: 200 mg/dose), followed by 3 to 6 mg/kg/dose once daily (usual maximum dose: 100 mg/dose) for at least 3 weeks, including at least 2 weeks following resolution of symptoms (Ref); in adolescents, up to 400 mg/day may be needed (Ref).
Suppressive therapy (secondary prophylaxis): Note: Not typically recommended, but can be considered if experiencing frequent severe recurrent infection (Ref).
Patients with HIV:
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:
Treatment:
Infants and Children: Oral: 6 mg/kg on day 1, then 3 to 6 mg/kg/dose once daily for a total of 7 to 14 days; maximum dose: 200 mg/dose (Ref); higher doses up to 12 mg/kg/dose may be recommended for patients with HIV; maximum dose: 400 mg/dose (Ref).
Adolescents: Oral: 6 mg/kg on day 1, then 3 to 6 mg/kg/dose once daily for a total of 7 to 14 days; maximum dose: 200 mg/dose (Ref).
Suppressive therapy (secondary prophylaxis): Note: Not typically recommended, but can be considered if experiencing frequent severe recurrent infection (Ref).
Patients with HIV:
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 mg once daily or three times weekly (Ref).
Candidiasis, peritoneal dialysis–related infections:
Peritonitis: Infants, Children, and Adolescents:
Treatment: IV, Oral: 6 mg/kg/dose every 24 to 48 hours; maximum dose: 400 mg/dose (Ref).
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 (Ref).
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 (Ref).
Candidiasis, vulvovaginal:
Uncomplicated infection: Adolescents: Oral: 150 mg as a single dose (Ref).
Severe infection:
Patients without HIV: Adolescents: Oral: 150 mg every 72 hours for 2 to 3 doses (Ref).
Patients with HIV: Adolescents: Oral: 100 to 200 mg once daily for ≥7 days (Ref).
Recurrent infection:
Patients without HIV: Adolescents: Oral: Initial: 100 to 200 mg every 72 hours for 3 doses (ie, on days 1, 4, and 7); followed by maintenance of 100 to 200 mg once weekly for 6 months (Ref).
Patients with HIV: Adolescents:
Fluconazole monotherapy: Oral: 100 to 200 mg once daily for ≥7 days (Ref).
Combination regimen with ibrexafungerp: Oral: 150 mg every 72 hours for 3 doses (ie, on days 1, 4, and 7), followed by ibrexafungerp (Ref).
Suppressive therapy (secondary prophylaxis): Note: Not typically recommended, but can be considered if experiencing frequent or severe recurrent infection; if used, reasonable to discontinue if CD4 count increased to >200 cells/mm3 following initiation of antiretroviral therapy (Ref).
Patients with HIV: Adolescents: Oral: 150 mg once weekly (Ref).
Coccidioidomycosis:
Primary prophylaxis: Note: Not recommended routinely; yearly or twice-yearly serological testing should be considered in patients with HIV who live in endemic areas. Primary prophylaxis/preemptive therapy may be considered in patients with CD4 count <250 cells/mm3 with new positive Coccidioides IgM or IgG and no signs or symptoms consistent with infection (Ref).
Patients with HIV: Adolescents: Oral: 400 mg once daily; discontinue when CD4 cell count is ≥250 cells/mm3 and patient has achieved virologic suppression on antiretroviral therapy (Ref).
Mild to moderate non-meningeal infection (eg, focal pneumonia):
Infants, Children, and Adolescents: IV, Oral: 6 to 12 mg/kg/dose once daily; maximum dose: 400 mg/dose. Duration typically ≥3 to 6 months and depends on clinical response, immune response, and in patients with HIV, virologic suppression (Ref). Note: An initial loading dose of 25 mg/kg has also been suggested (Ref).
Severe illness (diffuse pulmonary or disseminated non-meningitic disease):
Note: May be used as initial therapy if unable to use amphotericin or as step-down therapy; some experts recommend initiating at the same time as amphotericin B and continuing once amphotericin B is stopped (Ref).
Patients with HIV:
Infants and Children: IV, Oral: 12 mg/kg/dose once daily; maximum dose: 800 mg/dose. Treatment is continued for a total of ≥1 year based on clinical and serological response, followed by secondary prophylaxis (Ref).
Adolescents: Oral: 400 mg once daily. May consider discontinuation after ≥1 year based on clinical and serological response (Ref).
Meningeal infection:
Infants and Children: IV, Oral: 12 mg/kg/dose once daily; maximum dose: 800 mg/dose, followed by lifelong secondary prophylaxis (Ref). Note: An initial loading dose of 25 mg/kg has also been suggested (Ref).
Adolescents: Oral: 800 to 1,200 mg once daily; recommended duration is lifelong even in patients with immune reconstitution (Ref).
Suppressive therapy (secondary prophylaxis): Note: Duration is lifelong for immunocompromised patients with meningitis or disseminated disease; prophylaxis may also be considered after treatment of milder disease if CD4 remains <250 cells/mm3 or <15% (Ref).
Patients with HIV: Infants and Children: Oral: 6 mg/kg/dose once daily; maximum dose: 400 mg/dose (Ref).
Cryptococcal infection:
Mild to moderate localized infection including pneumonia (not CNS):
Patients without HIV: 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).
Patients with HIV:
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 6 to 12 months, depending on symptom resolution (Ref).
CNS infection, severe pulmonary infection, or disseminated infection:
Induction therapy: Patients with HIV (alternative agent):
Infants and Children: IV: 12 mg/kg on day 1, then 10 to 12 mg/kg/dose once daily as part of an appropriate combination regimen for ≥14 days; maximum dose: 800 mg/dose (Ref).
Adolescents: IV, Oral: 800 to 1,200 mg once daily for 2 weeks as part of an appropriate combination regimen. For CNS disease, if cerebrospinal fluid (CSF) cultures remain positive in a clinically stable patient after 2 weeks of induction therapy, may use 1,200 mg once daily for an additional 2 weeks, with or without flucytosine (Ref).
Consolidation therapy:
Patients without HIV: 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/day (Ref).
Patients with HIV:
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: Oral: 800 mg once daily for ≥8 weeks. Dose may be reduced to 400 mg once daily in clinically stable patients once CSF cultures are sterile and antiretroviral therapy has been initiated (Ref).
Suppressive therapy (secondary prophylaxis):
Patients without HIV: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for 6 to 12 months; maximum dose: 200 mg/dose (Ref).
Patients with HIV: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for ≥12 months; maximum dose: 200 mg/dose (Ref).
Histoplasmosis: Patients with HIV (alternative agent):
Pulmonary, acute primary disease:
Infants and Children: Oral: 3 to 6 mg/kg/dose once daily; maximum dose: 200 mg/dose (Ref).
Adolescents: Oral: 800 mg once daily (Ref).
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 (Ref).
Adolescents: Oral: 800 mg once daily (Ref).
Suppressive therapy (secondary prophylaxis):
Infants and Children: Oral: 3 to 6 mg/kg/dose once daily for ≥12 months; maximum dose: 200 mg/dose (Ref).
Adolescents: Oral: 400 mg once daily for ≥12 months (Ref).
Tinea capitis (scalp ringworm) (alternative agent): Limited data available:
Daily regimen: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for 3 to 6 weeks; maximum dose: 400 mg/dose. Some patients may require longer or shorter durations based on clinical response (Ref).
Weekly regimen: Children and Adolescents: Oral: 6 to 8 mg/kg/dose once weekly. Maximum dose has not been established; 150 to 300 mg once weekly has been recommended in adults with other tinea infections. Duration of therapy is until clinical resolution, typically 6 to 12 weeks, although durations up to 16 weeks may be necessary, particularly for disease caused by Microsporum canis (Ref).
Tinea corporis (ringworm), tinea cruris (jock itch), and tinea pedis (athlete's foot) (alternative agent): Limited data available: Note: Oral therapy should be reserved for disease that does not respond to topical therapy or for extensive/severe infection (Ref).
Children and Adolescents: Oral: 6 mg/kg/dose once weekly for 2 to 6 weeks until clinical resolution; maximum dose: 150 mg/dose (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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).
There are no dosage adjustments provided in manufacturer's labeling; use with caution.
(For additional information see "Fluconazole: Drug information")
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): Note: Reserve for patients unable to tolerate itraconazole (Ref).
Oral: 400 to 800 mg once daily for 6 to 12 months (Ref).
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:
Initial therapy (alternative agent):
Note: For use in patients without neutropenia who are not critically ill and not at high risk of fluconazole-resistant isolate. For use in patients with neutropenia who are not critically ill and have had no prior azole exposure (Ref); some experts reserve for patients with neutropenia 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 infection, native or prosthetic valve endocarditis, or device infection (eg, implantable cardiac defibrillator, pacemaker, ventricular assist device [VAD]):
Step-down therapy (for patients who are clinically stable and have responded to initial therapy with negative repeat cultures): IV, Oral: 400 to 800 mg (or 6 to 12 mg/kg) once daily (IDSA [Pappas 2016]).
Duration: For device infection without endocarditis, ≥4 weeks after device removal (4 weeks for generator pocket infections and ≥6 weeks after device removal for wire infections). If VAD cannot be removed, continue chronic suppressive therapy for as long as the VAD remains in place with fluconazole 400 to 800 mg (or 6 to 12 mg/kg) once daily. For endocarditis, ≥6 weeks after valve replacement surgery, with longer duration for perivalvular abscesses or other complications; long-term suppressive therapy is recommended for prosthetic valve endocarditis or if valve cannot be replaced (Ref).
CNS: Step-down therapy: 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).
Endophthalmitis, endogenous (with or without vitritis): 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 patients who are immunocompromised (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).
Hepatosplenic, chronic disseminated: 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).
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 confirmed susceptibility (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 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 patients who are immunocompromised (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):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, treatment (peritoneal dialysis): Oral (preferred), IV: 200 mg on day 1, then 100 to 200 mg once daily; continue for 2 to 4 weeks after catheter removal (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 a patient who is immunocompetent: Oral: 150 mg as a single dose (Ref). Note: For patients with persistent symptoms, some experts recommend a second dose of 150 mg administered 72 hours after the first dose (Ref).
Severe infection or infection in a patient who is immunocompromised: Oral: 150 mg every 72 hours for 2 or 3 doses (Ref).
Recurrent infection:
Fluconazole monotherapy: Oral: 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); some experts prefer 150 mg for all doses (Ref) and some suggest longer induction dosing of 150 mg every 72 hours for 10 to 14 days (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:
H igh-risk patients in the ICU 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).
Patients with hematologic malignancy (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).
Peritonitis, secondary prevention (peritoneal dialysis):
Note: To prevent development of fungal peritonitis in patients on peritoneal dialysis who require antibiotics (Ref).
Oral: 200 mg every other day or 100 mg once daily for the duration of antibiotic therapy; may extend fluconazole duration for an additional 3 days after the last dose of an aminoglycoside or an additional 7 days after the last dose of vancomycin (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 (off-label use):
Note: Initial parenteral antifungal therapy with amphotericin B is warranted for severe disease (Ref).
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 (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). Duration is lifelong because of the high relapse rate (Ref).
Pneumonia, primary infection: Note: Reserve for patients with or at risk for severe disease (eg, extensive pulmonary involvement, patients who are immunocompromised) (Ref):
Oral: Usual dose: 400 mg once daily; IDSA guidelines state that some experts recommend 800 mg once daily. For severe disease, use in combination with initial therapy with amphotericin B. Duration is typically 3 to 6 months, but can vary depending on comorbid conditions, severity of disease, and response to therapy (Ref).
Pneumonia, symptomatic chronic cavitary and/or cavitary disease in patients who are immunocompromised: 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 (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:
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: 1.2 g once daily in combination with flucytosine for ≥2 weeks (Ref). Note: Some experts use 800 mg once daily in combination with flucytosine (Ref).
If flucytosine and amphotericin B are unavailable or not tolerated: Oral: 1.2 g once daily as monotherapy for ≥2 weeks. Note: Efficacy is decreased with fluconazole monotherapy (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).
Patients without HIV:
Induction (alternative regimens):
If flucytosine is unavailable or not tolerated: Oral: 800 mg to 1.2 g 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. Note: Fluconazole monotherapy for induction is generally not recommended (Ref).
Consolidation: Oral: 400 to 800 mg once daily for 8 weeks (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 (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).
Tinea infection (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 (pityriasis 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.
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). Note: For treatment or prevention of peritoneal dialysis-associated infection, dosage adjustments have already been incorporated to the indication-specific dosing in the adult dosing field.
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.
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Liver impairment prior to treatment initiation:
Initial or dose adjustment in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (Ref).
Liver impairment developing in patient already receiving fluconazole:
Chronic disease progression (eg, outpatient):
Baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (Ref).
Acute worsening of liver function (eg, requiring hospitalization):
Baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (Ref). If fluconazole-induced liver injury is suspected, usually resolves without intervention. If intervention is required, liver injury is generally reversible within ~2 weeks after dose reduction or discontinuation but may recur upon rechallenge (Ref).
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 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 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).
Azole antifungals, including fluconazole, may cause hepatotoxicity (ranging from mild and asymptomatic increased serum transaminases to hepatic failure) (Ref). Hepatotoxicity may also occur as part of drug rash eosinophilia with systemic symptoms (DRESS) (Ref). Fluconazole-induced liver injury usually resolves without intervention. If intervention is required, liver injury is generally reversible within ~2 weeks after dose reduction or discontinuation but may recur upon rechallenge (Ref). Fatal cases have been reported (Ref).
Onset: Varied; most cases of hepatotoxicity due to azoles occur within the first month of therapy (but may occur at any time) (Ref).
Risk factors:
• Longer treatment duration (Ref)
• Preexisting liver disease (Ref)
• Concurrent hepatotoxic agents and/or drug interactions (Ref)
• Kidney impairment (Ref)
• HIV infection (Ref)
• Older age (Ref)
• Cross-reactivity among oral azole antifungals has not been consistently reported in patients with histories of hepatotoxicity (Ref)
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 (Ref)
Dermatologic: Acute generalized exanthematous pustulosis (Ref), alopecia (Ref), diaphoresis, exfoliative dermatitis, fixed drug eruption (Ref), Stevens-Johnson syndrome (Ref), Sweet syndrome (Ref), toxic epidermal necrolysis (Ref)
Endocrine & metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia
Gastrointestinal: Xerostomia
Hematologic & oncologic: Agranulocytosis (Ref), leukopenia, neutropenia, thrombocytopenia (Ref)
Hepatic: Cholestatic hepatitis (Ref), hepatic failure (Ref), hepatitis (mixed) (Ref), hepatocellular hepatitis (Ref), hepatotoxicity (Ref), increased serum transaminases (Ref)
Hypersensitivity: Anaphylaxis (Ref), angioedema, drug reaction with eosinophilia and systemic symptoms (Ref)
Nervous system: Asthenia, drowsiness, fatigue, insomnia, malaise, paresthesia, seizure, tremor, vertigo
Neuromuscular & skeletal: Myalgia
Miscellaneous: Fever
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).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Use fluconazole prophylaxis with caution in preterm neonates weighing <750 grams; per the manufacturer's labeling, a higher incidence of spontaneous intestinal perforation was reported in patients receiving fluconazole compared to placebo (N=361). However, no statistically significant difference was found between the 2 groups (fluconazole: 9%, placebo: 5%; p=0.22) after the allocations were adjudicated by neonatologists blinded to group assignment (Benjamin 2014).
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 [DSC]); 400 mg (200 mL [DSC])
Solution, Intravenous [preservative free]:
Generic: 100 mg/50 mL in NaCl 0.9% (50 mL); 200 mg/100 mL in NaCl 0.9% (100 mL); 400 mg (200 mL); 400 mg/200 mL in NaCl 0.9% (200 mL)
Suspension Reconstituted, Oral:
Diflucan: 10 mg/mL (35 mL [DSC]); 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 [DSC], 200 mg [contains fd&c red #40(allura red ac)aluminum lake]
Generic: 50 mg, 100 mg, 150 mg, 200 mg
Yes
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 - $0.22
400 mg/200 mL 0.9% (per mL): $0.03 - $0.12
Suspension (reconstituted) (Diflucan Oral)
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)
100 mg (per each): $1.36
200 mg (per each): $75.11
Tablets (Fluconazole Oral)
50 mg (per each): $5.57 - $5.60
100 mg (per each): $8.75 - $8.80
150 mg (per each): $13.59 - $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.
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
Dosing equivalency suggested by the Canadian manufacturer's labeling:
Pediatric patients 3 mg/kg = Adults 100 mg
Pediatric patients 6 mg/kg = Adults 200 mg
Pediatric patients 12 mg/kg = Adults 400 mg
The following feeding tube recommendations are based upon the best available evidence and clinical expertise. Senior editor panel: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Oral: Administer without regard to meals.
Oral suspension (commercially available): Shake well before use. Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).
Administration via feeding tube:
Gastric (eg, NG, G-tube) or post-pyloric tubes (eg, J-tube): Shake suspension well prior to drawing up dose for dilution. Dilute dose with at least an equivalent volume of purified water immediately prior to administration to reduce osmolality and viscosity (Ref); further dilution may be necessary for post-pyloric administration (Ref). Draw up diluted suspension into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some undiluted formulations have been reported to have osmolalities of ~2,000 to ~2,200 mOsm/kg (Ref); oral suspensions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during fluconazole administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Tablet:
Administration via feeding tube:
Gastric (eg, NG, G-tube) or post-pyloric tubes (eg, J-tube): Crush tablet(s) into a fine powder and disperse in at least 10 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
General guidance: Hold enteral nutrition during fluconazole administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
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 have been described in pediatric patients:
Neonatal: Loading doses (25 mg/kg) have been infused over 2 hours (Ref); doses ranging from 6 to 12 mg/kg/dose have been infused over 1 to 2 hours including extremely low birth weight neonates (Ref); a dose of 3 mg/kg/dose may be infused over 30 minutes (Ref).
Pediatric: Doses up to 8 to 10 mg/kg were infused over 2 hours (Ref).
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.
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Oral suspension (commercially available):
Gastric (eg, NG, G-tube ) or post-pyloric (eg, J-tube) tubes: Shake suspension well prior to drawing up dose for dilution. Dilute dose with at least an equivalent volume of purified water immediately prior to administration to reduce osmolality and viscosity; some experts recommend diluting in a volume of purified water that is 3 times the fluconazole suspension volume (eg, 10 mL fluconazole suspension diluted in 30 mL of purified water). Draw up diluted suspension into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some undiluted formulations have been reported to have osmolalities of ~2,000 to ~2,200 mOsm/kg (Ref); oral suspensions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during fluconazole administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 30 mL) and restart enteral nutrition (Ref).
Oral tablet:
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Crush tablet(s) into a fine powder and disperse in at least 10 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
General guidance: Hold enteral nutrition during fluconazole administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 30 mL) and restart enteral nutrition (Ref).
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Tablet: Store at <30°C (86°F).
Powder for oral suspension: Store dry powder at <30°C (86°F). Following reconstitution, store at 5°C to 30°C (41°F to 86°F). Discard unused portion after 2 weeks. Do not freeze.
Injection: Store in overwrap at 20°C to 25°C (68°F to 77°F) (Note: Some products may also be stored at additional temperature ranges; refer to product labeling). Do not freeze. Do not unwrap unit until ready for use.
Treatment of systemic candidiasis (FDA approved in all ages); treatment of cryptococcal meningitis (FDA approved in all ages); treatment of esophageal and oropharyngeal candidiasis (FDA approved in ages ≥6 months and adults); treatment of Candida vaginal and urinary tract infections and peritonitis (FDA approved in adults); prophylaxis of candidiasis in bone marrow transplant recipients (FDA approved in adults); has also been used for treatment of coccidioidomycosis and histoplasmosis, as well as prophylaxis and treatment of peritonitis and treatment of exit-site and tunnel infections in patients with peritoneal dialysis catheters.
Fluconazole may be confused with flecainide, FLUoxetine, furosemide, itraconazole, voriconazole
Diflucan may be confused with diclofenac, Diprivan, disulfiram
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]
Inhibits CYP2C19 (Strong), CYP2C9 (Moderate), CYP3A4 (Moderate);
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase 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
Abrocitinib: Fluconazole may increase serum concentration of Abrocitinib. Risk X: Avoid
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase 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
Acrivastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acrivastine. Risk C: Monitor
ALfentanil: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Alfuzosin. Risk C: Monitor
Alitretinoin (Systemic): CYP2C9 Inhibitors (Moderate) may increase 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 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 increase QTc-prolonging effects of Amiodarone. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor
Amitriptyline: May increase QTc-prolonging effects of Fluconazole. Fluconazole may increase serum concentration of Amitriptyline. Risk C: Monitor
Amitriptylinoxide: May increase QTc-prolonging effects of Fluconazole. Fluconazole may increase active metabolite exposure of Amitriptylinoxide. Fluconazole may increase serum concentration of Amitriptylinoxide. Risk C: Monitor
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of AmLODIPine. Risk C: Monitor
Apixaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Apixaban. Risk C: Monitor
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Aprepitant. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase 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
Atazanavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atazanavir. Risk C: Monitor
Atogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atogepant. Risk C: Monitor
Atorvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atorvastatin. Risk C: Monitor
Avacopan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avacopan. Risk C: Monitor
Avanafil: CYP3A4 Inhibitors (Moderate) may increase 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 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 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 serum concentration of Axitinib. Risk C: Monitor
Barnidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Barnidipine. Risk C: Monitor
Belzutifan: CYP2C19 Inhibitors (Strong) may increase serum concentration of Belzutifan. Risk C: Monitor
Benidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benidipine. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Blonanserin. Risk C: Monitor
Bortezomib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bortezomib. Risk C: Monitor
Bosentan: Fluconazole may increase serum concentration of Bosentan. Risk X: Avoid
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bosutinib. Risk X: Avoid
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase 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
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Brivaracetam. Risk C: Monitor
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Budesonide (Topical). Risk X: Avoid
Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of BusPIRone. Risk C: Monitor
Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cabozantinib. Risk C: Monitor
Cannabis: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Risk C: Monitor
Cannabis: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor
Capivasertib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider Therapy Modification
CarBAMazepine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of CarBAMazepine. Risk C: Monitor
Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Cariprazine. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a moderate CYP3A4 inhibitor or cariprazine, as well as cariprazine indication. See full mono for details. Some non-US labels contraindicate this combination. Risk D: Consider Therapy Modification
Carisoprodol: CYP2C19 Inhibitors (Strong) may increase serum concentration of Carisoprodol. CYP2C19 Inhibitors (Strong) may decrease active metabolite exposure of Carisoprodol. Risk C: Monitor
Carvedilol: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor
Celecoxib: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Celecoxib. Risk C: Monitor
Ceritinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Ceritinib. Ceritinib may increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase 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 increase QTc-prolonging effects of Cisapride. Fluconazole may increase serum concentration of Cisapride. Risk X: Avoid
Citalopram: Fluconazole may increase QTc-prolonging effects of Citalopram. Fluconazole may increase 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 serum concentration of Clindamycin (Systemic). Risk C: Monitor
CloBAZam: CYP2C19 Inhibitors (Strong) may increase active metabolite exposure of CloBAZam. CYP2C19 Inhibitors (Strong) may increase serum concentration of CloBAZam. Risk C: Monitor
Clopidogrel: CYP2C19 Inhibitors (Strong) may decrease active metabolite exposure 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 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 active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider Therapy Modification
Conivaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Conivaptan. Risk C: Monitor
Copanlisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Copanlisib. Risk C: Monitor
Crizotinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Crizotinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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
CycloPHOSphamide: Fluconazole may increase adverse/toxic effects of CycloPHOSphamide. Specifically, serum bilirubin and serum creatinine may be increased. Fluconazole may increase serum concentration of CycloPHOSphamide. Risk C: Monitor
CycloSPORINE (Systemic): Fluconazole may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
Dabigatran Etexilate: Fluconazole may increase anticoagulant effects of Dabigatran Etexilate. Risk C: Monitor
Dabrafenib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Dabrafenib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Darifenacin. Risk C: Monitor
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure 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
Deuruxolitinib: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Deuruxolitinib. Risk X: Avoid
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
Dexlansoprazole: CYP2C19 Inhibitors (Strong) may increase serum concentration of Dexlansoprazole. Risk C: Monitor
DiazePAM: CYP2C19 Inhibitors (Strong) may increase serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Dichlorphenamide: Antifungal Agents (Azole Derivatives, Systemic) may increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Diclofenac (Systemic): CYP2C9 Inhibitors (Moderate) may increase serum concentration of Diclofenac (Systemic). Risk C: Monitor
Dienogest: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dienogest. Risk C: Monitor
DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DilTIAZem. Risk C: Monitor
DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOCEtaxel. Risk C: Monitor
Domperidone: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Domperidone. Risk X: Avoid
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroNABinol: CYP2C9 Inhibitors (Moderate) may increase serum concentration of DroNABinol. Risk C: Monitor
DroNABinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DroNABinol. Risk C: Monitor
Dronedarone: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Dronedarone. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 serum concentration of Ebastine. Risk C: Monitor
Elacestrant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elacestrant. Risk X: Avoid
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eletriptan. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider Therapy Modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase 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 increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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
Ensartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Entrectinib. Risk X: Avoid
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor
Erlotinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Erlotinib. Risk C: Monitor
Erythromycin (Systemic): Fluconazole may increase QTc-prolonging effects of Erythromycin (Systemic). Fluconazole may increase serum concentration of Erythromycin (Systemic). Risk X: Avoid
Escitalopram: May increase QTc-prolonging effects of Fluconazole. Fluconazole may increase serum concentration of Escitalopram. Risk C: Monitor
Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eszopiclone. Risk C: Monitor
Etizolam: CYP2C19 Inhibitors (Strong) may increase serum concentration of Etizolam. Risk C: Monitor
Etrasimod: Fluconazole may increase serum concentration of Etrasimod. Risk X: Avoid
Etravirine: CYP2C19 Inhibitors (Strong) may increase serum concentration of Etravirine. Risk C: Monitor
Everolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Everolimus. Risk C: Monitor
Fedratinib: Fluconazole may increase serum concentration of Fedratinib. Risk C: Monitor
Felodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Felodipine. Risk C: Monitor
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase 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 increase QTc-prolonging effects of Fexinidazole. Fexinidazole may decrease serum concentration of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Specifically, concentrations of crizotinib, nilotinib, and ribociclib may be decreased. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may decrease active metabolite exposure of Fexinidazole. Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Also monitor for reduced efficacy of fexinidazole, crizotinib, nilotinib, and ribociclib. Risk D: Consider Therapy Modification
Finerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase 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
Fluorouracil Products: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects 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
Flurbiprofen (Systemic): CYP2C9 Inhibitors (Moderate) may increase serum concentration of Flurbiprofen (Systemic). Risk C: Monitor
Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Nasal). Risk C: Monitor
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor
Fluvastatin: CYP2C9 Inhibitors (Moderate) may increase 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. Avoid coadministration of fluvastatin extended-release tablets with moderate CYP2C9 inhibitors. Risk D: Consider Therapy Modification
Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosaprepitant. Risk X: Avoid
Fosphenytoin-Phenytoin: CYP2C19 Inhibitors (Strong) may increase serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor
Gepirone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider Therapy Modification
Gepotidacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepotidacin. Risk C: Monitor
Glasdegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Glasdegib. Risk C: Monitor
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase 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 increase QTc-prolonging effects 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
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of HYDROcodone. Risk C: Monitor
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Ibuprofen. Risk C: Monitor
Ifosfamide: CYP3A4 Inhibitors (Moderate) may increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Iloperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Iloperidone. Risk C: Monitor
Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Irinotecan Products. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. Risk C: Monitor
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor
Isradipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Isradipine. Risk C: Monitor
Itraconazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Itraconazole. Risk C: Monitor
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase 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 increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 serum concentration of Ixabepilone. Risk C: Monitor
Lansoprazole: CYP2C19 Inhibitors (Strong) may increase serum concentration of Lansoprazole. Risk C: Monitor
Lapatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lefamulin. Management: Monitor for lefamulin adverse effects during coadministration of lefamulin tablets with moderate CYP3A4 inhibitors. Risk C: Monitor
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lemborexant. Risk X: Avoid
Leniolisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Leniolisib. Risk C: Monitor
Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lercanidipine. Risk C: Monitor
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levamlodipine. Risk C: Monitor
Levoketoconazole: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Levoketoconazole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Levoketoconazole. Risk X: Avoid
Levomethadone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomethadone. Risk C: Monitor
Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomilnacipran. Risk C: Monitor
Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lidocaine (Systemic). CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lomitapide. Risk X: Avoid
Lonafarnib: May increase QTc-prolonging effects 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
Lopinavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lopinavir. Risk C: Monitor
Lorlatinib: Fluconazole may increase 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 serum concentration of Lornoxicam. Risk C: Monitor
Losartan: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Losartan. CYP2C9 Inhibitors (Moderate) may decrease active metabolite exposure of Losartan. Risk C: Monitor
Lovastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lovastatin. Risk C: Monitor
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Lurasidone. Management: Reduce the lurasidone dose by half when initiating therapy with a moderate CYP3A4 inhibitor. If initiating lurasidone in a patient already receiving a moderate CYP3A4 inhibitor, start lurasidone at 20 mg/day with a max dose of 80 mg/day. Risk D: Consider Therapy Modification
Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, reduce the lurbinectedin dose by 50%. Risk D: Consider Therapy Modification
Macitentan: Fluconazole may increase serum concentration of Macitentan. Risk X: Avoid
Manidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Manidipine. Risk C: Monitor
Maraviroc: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Maraviroc. Risk C: Monitor
Mavacamten: CYP2C19 Inhibitors (Strong) may increase serum concentration of Mavacamten. Risk X: Avoid
Mavorixafor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mavorixafor. Risk C: Monitor
Meloxicam: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Meloxicam. Risk C: Monitor
Meperidine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Meperidine. Risk C: Monitor
Methadone: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 serum concentration of MethylPREDNISolone. Risk C: Monitor
Methysergide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Methysergide. Risk X: Avoid
Midazolam: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of MiFEPRIStone. Risk C: Monitor
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mirodenafil. Risk C: Monitor
Mitapivat: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Mizolastine. Risk X: Avoid
Mobocertinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Mobocertinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Mobocertinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase active metabolite exposure 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 serum concentration of Moclobemide. Risk C: Monitor
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naldemedine. Risk C: Monitor
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nalfurafine. Risk C: Monitor
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Nateglinide. Risk C: Monitor
Nelfinavir: CYP2C19 Inhibitors (Strong) may increase serum concentration of Nelfinavir. Risk C: Monitor
Neratinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Neratinib. Risk C: Monitor
Nevirapine: Fluconazole may increase serum concentration of Nevirapine. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine (Topical). Risk C: Monitor
NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NiMODipine. Risk C: Monitor
Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nisoldipine. Risk X: Avoid
Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nitrendipine. Risk C: Monitor
Olaparib: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olmutinib. Risk C: Monitor
Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider Therapy Modification
Omeprazole: CYP2C19 Inhibitors (Strong) may increase serum concentration of Omeprazole. Risk C: Monitor
Ondansetron: May increase QTc-prolonging effects 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
Ospemifene: Fluconazole may increase serum concentration of Ospemifene. Risk X: Avoid
OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pacritinib. Risk C: Monitor
Palbociclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palbociclib. Risk C: Monitor
Palovarotene: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider Therapy Modification
Panobinostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Panobinostat. Risk C: Monitor
Parecoxib: CYP2C9 Inhibitors (Moderate) may increase 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 increase QTc-prolonging effects of PAZOPanib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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
Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase 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 increase QTc-prolonging effects 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
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider Therapy Modification
PHENobarbital: CYP2C19 Inhibitors (Strong) may increase serum concentration of PHENobarbital. Risk C: Monitor
Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pimavanserin. Risk C: Monitor
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease metabolism of Pimecrolimus. Risk C: Monitor
Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Piperaquine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Pirtobrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pirtobrutinib. Risk C: Monitor
PONATinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of PONATinib. Risk C: Monitor
Pralsetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Prazepam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Prazepam. Risk C: Monitor
Praziquantel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Praziquantel. Risk C: Monitor
Primidone: CYP2C19 Inhibitors (Strong) may increase active metabolite exposure of Primidone. Specifically, concentrations of phenobarbital may be increased. Risk C: Monitor
Proguanil: CYP2C19 Inhibitors (Strong) may increase serum concentration of Proguanil. CYP2C19 Inhibitors (Strong) may decrease active metabolite exposure of Proguanil. Risk C: Monitor
QT-prolonging Antidepressants (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects 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
QT-prolonging Class IA Antiarrhythmics (Highest Risk): Fluconazole may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
QT-prolonging Class III Antiarrhythmics (Highest Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 increase QTc-prolonging effects 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
QT-prolonging Kinase Inhibitors (Highest Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Risk C: Monitor
QT-prolonging Miscellaneous Agents (Highest Risk): Fluconazole may increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Miscellaneous Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Fluconazole may increase QTc-prolonging effects 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
QT-prolonging Quinolone Antibiotics (Moderate Risk): May increase QTc-prolonging effects 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
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
QUEtiapine: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QUEtiapine. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of QUEtiapine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and other quetiapine toxicities. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor
QuiNIDine: Fluconazole may increase QTc-prolonging effects of QuiNIDine. Fluconazole may increase serum concentration of QuiNIDine. Risk X: Avoid
Ramelteon: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Ramelteon. Risk C: Monitor
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Red Yeast Rice. Risk C: Monitor
Regorafenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Regorafenib. Risk C: Monitor
Repotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Repotrectinib. Risk X: Avoid
Revumenib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Revumenib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Revumenib. 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
Rifabutin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rifabutin. Risk C: Monitor
RifAMPin: May decrease serum concentration of Fluconazole. Fluconazole may increase 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 serum concentration of Fluconazole. Risk C: Monitor
Rimegepant: CYP3A4 Inhibitors (Moderate) may increase 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 increase QTc-prolonging effects 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
Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase 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
Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rupatadine. Risk C: Monitor
Ruxolitinib (Systemic): Fluconazole may increase 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 and Oral [Non-Absorbable]) may decrease therapeutic effects of Saccharomyces boulardii. Risk X: Avoid
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Salmeterol. Risk C: Monitor
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SAXagliptin. Risk C: Monitor
Seladelpar: Inhibitors of CYP3A4 and CYP2C9 may increase serum concentration of Seladelpar. Risk C: Monitor
Selpercatinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Selpercatinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 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 increase QTc-prolonging effects of Sertindole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Sertindole. Risk X: Avoid
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sildenafil. Risk C: Monitor
Silodosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Silodosin. Risk C: Monitor
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Siponimod: Fluconazole may increase serum concentration of Siponimod. Risk X: Avoid
Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. 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 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 serum concentration of Solifenacin. Risk C: Monitor
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase 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
Sparsentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sparsentan. Risk C: Monitor
SUFentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SUFentanil. Risk C: Monitor
Sulfonylureas: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Sulfonylureas. Risk C: Monitor
SUNItinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of SUNItinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase 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
Suzetrigine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suzetrigine. Management: Reduce suzetrigine dose as follows: initiate with 100 mg for 1 dose; then 12 hours after first dose, give 50 mg every 12 hours for doses 2, 3, and 4; then 50 mg every 24 hours for dose 5 and thereafter. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): Fluconazole may increase 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 serum concentration of Tadalafil. Risk C: Monitor
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase 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
Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor
Tetrahydrocannabinol and Cannabidiol: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Specifically, concentrations of tetrahydrocannabinol may be increased. Risk C: Monitor
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Theophylline Derivatives. Risk C: Monitor
Thioridazine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Thiotepa: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Thiotepa. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Thiotepa. Risk C: Monitor
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ticagrelor. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor
Tilidine: CYP2C19 Inhibitors (Strong) may increase serum concentration of Tilidine. CYP2C19 Inhibitors (Strong) may increase active metabolite exposure of Tilidine. Risk C: Monitor
Tilidine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tilidine. Risk C: Monitor
Tipranavir: Fluconazole may increase 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 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 serum concentration of Tolterodine. Risk C: Monitor
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Torsemide. Risk C: Monitor
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Trabectedin. Risk C: Monitor
TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraZODone. Risk C: Monitor
Tretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tretinoin (Systemic). Risk C: Monitor
Triamcinolone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Udenafil. Risk C: Monitor
Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Valbenazine. Risk C: Monitor
Vamorolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vamorolone. Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Management: Age- and weight-specific dose reductions of vanzacaftor, tezacaftor, and deutivacaftor are recommended. Please see full Interact monograph or labeling for details. Risk D: Consider Therapy Modification
Vardenafil: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Verapamil. Risk C: Monitor
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vilazodone. Risk C: Monitor
VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinBLAStine. Risk C: Monitor
Vindesine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vindesine. Risk C: Monitor
Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Vinflunine. Risk C: Monitor
Vitamin K Antagonists: Fluconazole may increase 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 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 serum concentration of Vorapaxar. Risk C: Monitor
Voriconazole: Fluconazole may increase QTc-prolonging effects of Voriconazole. Fluconazole may increase serum concentration of Voriconazole. Risk X: Avoid
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Zopiclone. Risk C: Monitor
Zuranolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zuranolone. Risk C: Monitor
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.
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 (Diflucan [fluconazole oral] prescribing information; Liu 2020; Nyirjesy 2022; Zhang 2019; Zhu 2020).
Oral fluconazole for the treatment of vaginal candidiasis is not recommended during pregnancy. Topical therapy for oral or vaginal candidiasis is recommended in pregnant patients (HHS [OI adult] 2023; 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] 2023). 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] 2023; IDSA [Galgiani 2016]; Pastick 2020).
Periodic liver function (AST, ALT, alkaline phosphatase), renal function tests, serum potassium, CBC with differential and platelet count; conjugated bilirubin in neonates (Egunsola 2013)
Fluconazole concentration monitoring is not routinely recommended, and target concentrations are not well established; monitoring may be considered in certain scenarios (eg, concern for clinical failure or absorption issues [particularly in critical illness]; renal replacement therapy; drug-drug interactions; elevated MICs); evaluate results in context of clinical scenario (Downes 2020; John 2019; SIDP [McCreary 2023]; van der Elst 2014).
Timing of serum sampling:
AUC (preferred): To estimate AUC (at steady state), concentrations may be obtained at 1, 4, and 24 hours following administration (SIDP [McCreary 2023]).
Trough (alternative): Obtain trough concentration ~5 to 7 days after therapy is initiated or dose is adjusted; may be obtained sooner (eg, after 2 days) if a loading dose was administered (SIDP [McCreary 2023]; van der Elst 2014).
Recommended targets:
AUC24/MIC (preferred target): >25 to 100 (SIDP [McCreary 2023]; John 2019). Note: AUC24/MIC >100 has also been suggested in certain populations (eg, critical illness; liver transplant) (SIDP [McCreary 2023]; Pea 2014).
Systemic candidiasis: AUC24: 400 to 800 mg*h/L (manufacturer's labeling).
Trough concentration (alternative target): 10 to 15 mg/L (SIDP [McCreary 2023]). Note: This range has been suggested as a surrogate for AUC/MIC >100 based on an MIC value of 0.125 mg/L but has not been widely evaluated (SIDP [McCreary 2023]).
Interferes with fungal cytochrome P450 activity (lanosterol 14-α-demethylase), decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation
Absorption: Oral: Well absorbed; food does not affect extent of absorption.
Distribution: Widely throughout the body with good penetration into CSF, eye, peritoneal fluid, sputum, skin, and urine.
Vd:
Preterm and term neonates: ~1 L/kg (Hwang 2017).
Children ≥5 years and Adolescents ≤15 years: Mean range: 0.722 to 1.069 L/kg.
Adults: ~0.6 L/kg.
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:
Preterm neonates: GA 26 to 29 weeks:
<36 hours PNA: 73.6 hours.
~7 days PNA: 53.2 hours.
~13 days PNA: 46.4 hours.
Infants ≥9 months, Children, and Adolescents ≤13 years (single dose, oral): Mean range: 19.5 to 25 hours.
Children ≥5 years and Adolescents ≤15 years (multiple dose, IV): Mean range: 15.2 to 17.6 hours.
Adults: ~30 hours (range: 20 to 50 hours).
Older Adults ≥65 years: 46.2 hours.
Time to peak, serum: Oral: 1 to 2 hours.
Excretion: Urine (80% as unchanged drug).
Altered kidney function: Pharmacokinetics are markedly affected; there is an inverse relationship between half-life and creatinine clearance.
