Brand name: Diflucan
Drug class: Azoles
VA class: AM700
Chemical name: α-(2,4-Difluorophenyl)-α-(1H-1,2,4-triazole-1-ylmethyl)-1H-1,2,4-triazole-1-ethanol
CAS number: 86386-73-4

Medically reviewed by Drugs.com on Sep 23, 2024. Written by ASHP.

Introduction

Antifungal; azole (triazole derivative).

Uses for Fluconazole

Blastomycosis

Alternative for treatment of blastomycosis^{† [off-label]} caused by Blastomyces dermatitidis.

Drugs of choice are IV amphotericin B and oral itraconazole; oral fluconazole is an alternative, but may be less effective and should be used only when drugs of choice are contraindicated or cannot be used.

Do not use oral azoles for initial treatment of CNS blastomycosis. Treatment failures or relapses reported when an oral azole (e.g., ketoconazole) was used in treatment of cutaneous or pulmonary blastomycosis in patients who had asymptomatic or subclinical CNS involvement at the time of initial diagnosis.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of blastomycosis.

Candidemia and Disseminated Candida Infections

Treatment of candidemia, disseminated candidiasis (e.g., disseminated hepatosplenic infections), and other serious Candida infections, including urinary tract infections (cystitis, pyelonephritis, fungus balls), peritonitis, meningitis, osteoarticular infections (osteomyelitis, septic arthritis), intravascular infections (endocarditis, implantable cardiac device infections), pneumonia, endophthalmitis, and neonatal candidiasis^{† [off-label]} (including CNS infections).

A drug of choice for many Candida infections. However, fluconazole-resistant C. albicans are being isolated with increasing frequency from patients who received prior fluconazole therapy (especially HIV-infected patients), and some Candida infections (e.g., candidemia) are increasingly caused by strains intrinsically resistant to fluconazole (e.g., C. krusei) or likely to have resistance or reduced susceptibility to the drug (e.g., C. glabrata).

When choosing antifungals for treatment of candidemia or invasive Candida infections, take into consideration any history of recent exposure to azole or echinocandin antifungals or intolerance to antifungals, local and/or institutional epidemiologic data regarding prevalence of the various Candida strains and their patterns of resistance, severity of illness, relevant comorbidities, presence and duration of neutropenia or immunosuppression, and evidence of involvement of the CNS, cardiac valves, and/or visceral organs.

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis^{† [off-label]} in nonneutropenic patients in intensive care units (ICUs), IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial therapy; IV or oral fluconazole is an acceptable alternative for initial therapy in selected patients, including those who are not critically ill and unlikely to have infections caused by fluconazole-resistant Candida. IV amphotericin B recommended if echinocandin- and azole-resistant Candida suspected and is an alternative when echinocandins and fluconazole have been ineffective or cannot be used. Consider transition from the echinocandin to fluconazole (usually within 5–7 days) in clinically stable patients if strain susceptible to fluconazole (e.g., C. albicans) and initial treatment resulted in negative repeat blood cultures.

For treatment of candidemia in neutropenic patients, IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) or, alternatively, amphotericin B for initial therapy. Fluconazole is an alternative for initial therapy in those who are not critically ill and have had no prior exposure to azole antifungals; also can be used for step-down therapy in clinically stable patients who have fluconazole-susceptible isolates and negative repeat blood cultures.

For treatment of disseminated candidiasis in neonates^{† [off-label]} (neonatal candidiasis), IV amphotericin B usually drug of choice. IDSA states fluconazole is a reasonable alternative in those who have not been receiving fluconazole prophylaxis; AAP states fluconazole can be considered for follow-up (step-down) therapy after initial response to IV amphotericin B. Fluconazole also has been used for prophylaxis to reduce the incidence of invasive candidiasis in low birthweight neonates^{† [off-label]} at high risk. (See Prevention of Candidiasis in Transplant Recipients, Cancer Patients, or Other Patients at High Risk under Uses.)

For treatment of CNS candidiasis, IDSA recommends initial treatment with IV amphotericin B (with or without oral flucytosine) and follow-up treatment with fluconazole.

Antifungal treatment not recommended in patients with asymptomatic candiduria, unless there is high risk of disseminated candidiasis (e.g., neutropenic patients, low birthweight infants [<1.5 kg], patients who will undergo urologic manipulations). Fluconazole is the drug of choice for treatment of symptomatic candiduria (cystitis, pyelonephritis, fungus balls) caused by fluconazole-susceptible Candida; IV amphotericin B and/or flucytosine is recommended when fluconazole-resistant Candida (e.g., C. glabrata, C. krusei) are likely.

For treatment of osteoarticular infections (e.g., osteomyelitis, septic arthritis) caused by Candida, IDSA recommends initial treatment with fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole. If septic arthritis involved a prosthetic device and the device cannot be removed, long-term suppressive or maintenance therapy (secondary prophylaxis)^† with fluconazole recommended if isolate is susceptible.

For treatment of endocarditis (native or prosthetic valve) or implantable cardiac device infections caused by Candida, IDSA recommends initial treatment with IV amphotericin B (with or without flucytosine) or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole. If isolate is susceptible, long-term suppressive or maintenance therapy (secondary prophylaxis)^† with fluconazole recommended to prevent recurrence in those with native valve endocarditis who cannot undergo valve replacement and in those with prosthetic valve endocarditis.

For treatment of chorioretinitis (with or without vitritis) caused by Candida, IDSA recommends fluconazole or voriconazole when isolates are susceptible and amphotericin B (with or without oral flucytosine) when isolates are resistant to fluconazole and voriconazole; intravitreal amphotericin B or voriconazole may also be indicated.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of candidemia and disseminated candida infections.

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis in immunocompromised adults with HIV infection, malignancy, or other serious underlying disease. A drug of choice.

For mild oropharyngeal candidiasis, IDSA recommends topical treatment with clotrimazole lozenges or miconazole buccal tablets; nystatin (oral suspension or tablets) is an alternative. For moderate to severe oropharyngeal candidiasis, IDSA recommends oral fluconazole. For fluconazole-refractory oropharyngeal candidiasis, IDSA recommends itraconazole oral solution or posaconazole oral suspension; oral voriconazole or amphotericin B oral suspension (not commercially available in US) recommended as alternatives. Other alternatives for refractory oropharyngeal candidiasis are IV echinocandins (anidulafungin, caspofungin, micafungin) or IV amphotericin B.

For HIV-infected adults and adolescents with oropharyngeal candidiasis, CDC, NIH, and IDSA recommend oral fluconazole as the preferred drug of choice for initial episodes; if topical therapy used (e.g., mild to moderate episodes), drugs of choice are clotrimazole lozenges or miconazole buccal tablets. Alternatives for systemic treatment are itraconazole oral solution or posaconazole oral suspension; nystatin oral suspension is an alternative for topical treatment. For fluconazole-refractory infections in HIV-infected adults and adolescents, posaconazole oral suspension is preferred; itraconazole oral solution is an alternative.

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis)^† to prevent relapse or recurrence not usually recommended in patients adequately treated for oropharyngeal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of oropharyngeal candidiasis may benefit from secondary prophylaxis with oral fluconazole; however, consider potential for development of azole resistance.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of oropharyngeal candidiasis.

Esophageal Candidiasis

Treatment of esophageal candidiasis. A drug of choice.

Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).

IDSA recommends oral fluconazole as the preferred drug of choice for treatment of esophageal candidiasis; if oral therapy not tolerated, IV fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) recommended. For fluconazole-refractory esophageal candidiasis, IDSA recommends itraconazole oral solution or IV or oral voriconazole; alternatives are an IV echinocandin (anidulafungin, caspofungin, micafungin) or IV amphotericin B. IDSA states oral posaconazole (oral suspension or delayed-release tablets) is another possible alternative for treatment of fluconazole-refractory esophageal candidiasis.

For HIV-infected adults and adolescents with esophageal candidiasis, CDC, NIH, and IDSA recommend oral or IV fluconazole or itraconazole oral solution. Alternatives include oral or IV voriconazole, an IV echinocandin (anidulafungin, caspofungin, micafungin), or IV amphotericin B. For refractory esophageal candidiasis, including fluconazole-refractory infections, in HIV-infected adults and adolescents, itraconazole oral solution or posaconazole oral suspension is recommended; alternatives are IV amphotericin B, an IV echinocandin (anidulafungin, caspofungin, micafungin), or oral or IV voriconazole.

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis)^† to prevent relapse or recurrence not usually recommended in patients adequately treated for oropharyngeal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of esophageal candidiasis may benefit from secondary prophylaxis with oral fluconazole or posaconazole oral suspension; however, consider potential for development of azole resistance.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of esophageal candidiasis.

Vulvovaginal Candidiasis

Treatment of uncomplicated vulvovaginal candidiasis or complicated vulvovaginal candidiasis^†.

For treatment of uncomplicated vulvovaginal candidiasis (mild to moderate, sporadic or infrequent, most likely caused by C. albicans, occurring in immunocompetent women) in nonpregnant women, CDC and others recommend a topical (intravaginal) azole antifungal (e.g., butoconazole, clotrimazole, miconazole, terconazole, tioconazole) given in appropriate single-dose or short-course (1–3 days) regimen or, alternatively, single-dose regimen of oral fluconazole. Single-dose oral fluconazole offers some advantages over topical agents (e.g., ensures compliance, may reduce or eliminate concurrent rectal infections that can be source of reinfection).

For treatment of recurrent vulvovaginal candidiasis (usually defined as ≥4 episodes of symptomatic vulvovaginal candidiasis within a year), each individual episode caused by C. albicans may respond to a short-course regimen of intravaginal azole or oral fluconazole. To maintain clinical and mycologic control, some experts recommend a longer duration of initial therapy (e.g., 7–14 days of intravaginal azole antifungal or 3-dose regimen of oral fluconazole) to attempt mycologic remission before initiating a maintenance antifungal regimen. Women with recurrent infections who are symptomatic and remain culture-positive despite maintenance antifungal therapy should be managed in consultation with a specialist.

Vulvovaginal candidiasis frequently occurs during pregnancy. CDC states use topical (intravaginal) azole antifungals (not oral fluconazole) for treatment of vulvovaginal candidiasis during pregnancy. (See Pregnancy under Cautions.)

Consult current CDC guidelines available at [Web], current IDSA clinical practice guidelines available at [Web], and current CDC, NIH, and IDSA clinical practice guidelines on prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of vulvovaginal candidiasis.

Coccidioidomycosis

Treatment and prevention of coccidioidomycosis^† caused by Coccidioides immitis or C. posadasii. A drug of choice.

Used for treatment of coccidioidal pulmonary infections, meningitis, and disseminated (extrapulmonary) infections involving soft tissue or bone and joint.

Antifungal treatment may not be necessary for mild, uncomplicated coccidioidal pneumonia since such infections may resolve spontaneously; treatment recommended for patients with more severe or rapidly progressing infections, those with chronic pulmonary or disseminated infections, and immunocompromised or debilitated individuals (e.g., HIV-infected individuals, organ transplant recipients, those receiving immunosuppressive therapy, those with diabetes or cardiopulmonary disease).

IDSA and others recommend an oral azole (fluconazole or itraconazole) for initial treatment of symptomatic pulmonary coccidioidomycosis and chronic fibrocavitary or disseminated (extrapulmonary) coccidioidomycosis. IV amphotericin B recommended as an alternative and is preferred for initial treatment of severely ill patients who have hypoxia or rapidly progressing disease, for immunocompromised individuals, or when azole antifungals have been ineffective or cannot be used (e.g., pregnant women).

For HIV-infected adults and adolescents with clinically mild coccidioidomycosis (e.g., focal pneumonia), CDC, NIH, and IDSA recommend oral fluconazole or oral itraconazole for initial treatment; although data are limited, oral voriconazole or posaconazole oral suspension are alternatives if there is no response to fluconazole or itraconazole.

For HIV-infected adults and adolescents with diffuse pulmonary infections or extrathoracic disseminated coccidioidomycosis (nonmeningeal), CDC, NIH, and IDSA recommend initial therapy with IV amphotericin B followed by an oral azole (e.g., fluconazole). Alternatively, some experts recommend initial therapy with IV amphotericin B used in conjunction with an oral azole (e.g., fluconazole) followed by an oral azole alone.

For treatment of diffuse pulmonary or disseminated coccidioidomycosis in HIV-infected infants and children, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B followed by oral fluconazole or oral itraconazole. In those with severe disseminated disease, some experts recommend initial therapy with IV amphotericin B used in conjunction with an oral azole (e.g., fluconazole) followed by an oral azole alone. Use of fluconazole or itraconazole alone may be sufficient for treatment of mild coccidioidomycosis in HIV-infected infants and children with only mild disease (e.g., focal pneumonia) and also can be considered an alternative for those with stable pulmonary or disseminated coccidioidomycosis (nonmeningeal).

For treatment of coccidioidal meningitis in HIV-infected adults, adolescents, and children and other individuals, fluconazole (with or without intrathecal amphotericin B) is considered the regimen of choice. Consultation with an expert is recommended.

In HIV-infected adults and adolescents who live in areas in the US where coccidioidomycosis is endemic (e.g., lower San Joaquin Valley in California, much of Arizona, southern regions of Utah, Nevada, and New Mexico, western Texas), CDC, NIH, and IDSA recommend annual serologic testing for the disease. Those with newly positive IgM or IgG serologic tests and CD4⁺ T-cell counts <250/mm³ should receive oral fluconazole for primary prophylaxis against coccidioidomycosis^† (preemptive antifungal therapy) since they are at increased risk of developing active coccidioidomycosis. Primary prophylaxis against coccidioidomycosis is not recommended in other HIV-infected adults or adolescents or in HIV-infected infants and children.

HIV-infected adults, adolescents, or children who have been adequately treated for coccidioidomycosis should receive long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent recurrence or relapse^†. CDC, NIH, and IDSA recommend oral fluconazole or oral itraconazole for secondary prophylaxis of coccidioidomycosis in HIV-infected individuals.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines on prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of coccidioidomycosis.

Cryptococcosis

Treatment of meningitis caused by Cryptococcus neoformans. Also used for treatment of pulmonary cryptococcosis^†, cryptococcemia^†, and disseminated cryptococcal infections^†.

For treatment of cryptococcal meningitis in HIV-infected adults, adolescents, and children, CDC, NIH, IDSA, and others state that the preferred regimen is initial (induction) therapy with IV amphotericin B given in conjunction with oral flucytosine for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then follow-up (consolidation) therapy with oral fluconazole administered for at least 8 weeks.

Alternative regimens for treatment of cryptococcal meningitis in HIV-infected adults, adolescents, and children who cannot receive the preferred regimen are induction and consolidation therapy with IV amphotericin B alone; induction therapy with IV amphotericin B given in conjunction with oral fluconazole, then consolidation therapy with oral fluconazole; induction and consolidation therapy with oral or IV fluconazole used in conjunction with oral flucytosine, then consolidation therapy with oral fluconazole; or induction and consolidation therapy with oral fluconazole alone. These alternative regimens may be less effective and are recommended only in patients who cannot tolerate or have not responded to the preferred regimen.

For treatment of cryptococcal CNS infections in organ transplant recipients, IDSA recommends induction therapy with IV amphotericin B given in conjunction with oral flucytosine for at least 2 weeks, then consolidation therapy with oral fluconazole given for 8 weeks. If induction regimen does not include flucytosine, continue for at least 4–6 weeks. For organ transplant recipients with mild to moderate pulmonary cryptococcosis (without diffuse pulmonary infiltrates) or with other mild to moderate cryptococcal infections not involving the CNS, IDSA recommends fluconazole given for 6–12 months.

In adults and children who do not have HIV infection and are not transplant recipients, the preferred regimen for treatment of cryptococcal meningitis is induction therapy with IV amphotericin B given in conjunction with oral flucytosine for at least 4 weeks (a 2-week induction period can be considered in those who are immunocompetent, are without uncontrolled underlying disease, and are at low risk for therapeutic failure), then consolidation therapy with oral fluconazole administered for an additional 8 weeks or longer. IDSA states that data are insufficient to date to recommend fluconazole used alone or in conjunction with flucytosine for induction therapy in non-HIV-infected individuals.

For treatment of mild to moderate pulmonary cryptococcosis (nonmeningeal) in immunocompetent or immunosuppressed adults or children, IDSA states that the regimen of choice is oral fluconazole given for 6–12 months. A regimen of oral fluconazole given for 6–12 months also can be considered for treatment of nonmeningeal, nonpulmonary cryptococcosis in immunocompetent individuals if the infection occurs at a single site and fungemia is not present. Severe pulmonary infections, cryptococcemia, and disseminated infections in immunocompetent or immunosuppressed individuals should be treated using regimens recommended for cryptococcal meningitis.

HIV-infected adults, adolescents, and children who have been adequately treated for cryptococcal meningitis should receive long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent recurrence or relapse^†. CDC, NIH, and IDSA recommend oral fluconazole as the drug of choice for secondary prophylaxis of cryptococcosis in HIV-infected individuals; although oral itraconazole suggested as an alternative in those who cannot tolerate fluconazole, it may be less effective than fluconazole. IV amphotericin B can be used for secondary prophylaxis if necessary in individuals who cannot receive azole antifungals, but is less effective and not generally recommended.

Long-term suppressive or maintenance therapy (secondary prophylaxis)^† with oral fluconazole also recommended in non-HIV-infected adults and children who have been adequately treated for cryptococcal meningitis, including organ transplant recipients who have been adequately treated for CNS cryptococcosis.

Although data are limited, IDSA states that recommendations for treatment of CNS, pulmonary, or disseminated infections caused by Cryptococcus gattii and recommendations for secondary prophylaxis of C. gattii infections are the same as recommendations for C. neoformans infections. Consider that there is some in vitro evidence that fluconazole may be less active against C. gattii than some other azole antifungals (e.g., itraconazole, posaconazole, voriconazole). (See Actions and Spectrum.)

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines on prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of cryptococcosis.

Histoplasmosis

Alternative for treatment of histoplasmosis^† caused by Histoplasma capsulatum.

IDSA and others recommend IV amphotericin B or oral itraconazole for treatment of histoplasmosis. IV amphotericin B preferred for initial treatment of severe, life-threatening histoplasmosis, especially in immunocompromised patients. Other azole antifungals (fluconazole, ketoconazole, posaconazole, voriconazole) considered second-line alternatives to itraconazole.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines on prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of histoplasmosis.

Sporotrichosis

Alternative for treatment of lymphocutaneous and cutaneous sporotrichosis^† caused by Sporothrix schenckii.

IV amphotericin B is the drug of choice for initial treatment of severe, life-threatening sporotrichosis and whenever sporotrichosis is disseminated or has CNS involvement. Oral itraconazole is the drug of choice for treatment of cutaneous, lymphocutaneous, or mild pulmonary or osteoarticular sporotrichosis and for follow-up treatment of severe infections after a response has been obtained with IV amphotericin B.

Although fluconazole can be used as an alternative for treatment of cutaneous and lymphocutaneous sporotrichosis, it may be less effective than itraconazole and should be used only if patient cannot tolerate itraconazole or other alternatives (oral terbinafine, oral potassium iodide, local hyperthermia).

Do not use for treatment of pulmonary, osteoarticular, or meningeal sporotrichosis.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of sporotrichosis.

Dermatophytoses

Treatment of certain dermatophytoses^† (e.g., tinea capitis, tinea corporis, tinea cruris, tinea pedis ) caused by Epidermophyton, Microsporum, or Trichophyton.

Tinea corporis and tinea cruris generally can be effectively treated using a topical antifungal; an oral antifungal may be necessary if the disease is extensive, dermatophyte folliculitis is present, the infection does not respond to topical therapy, or the patient is immunocompromised or has a coexisting disease. Tinea capitis and tinea barbae generally are treated using an oral antifungal.

While topical antifungals usually are effective for treatment of uncomplicated tinea manuum and tinea pedis, an oral antifungal usually is necessary for treatment of severe, chronic, or recalcitrant tinea pedis and for treatment of chronic moccasin-type (dry-type) tinea pedis.

Onychomycosis

Treatment of onychomycosis of toenails^† or fingernails.

Onychomycosis generally treated using an oral antifungal (e.g., terbinafine, itraconazole, fluconazole) and adjunctive physical modalities (nail trimming, aggressive debridement, nail avulsion) with or without a topical antifungal.

Oral fluconazole may be less effective than oral terbinafine or oral itraconazole.

Pityriasis (Tinea) Versicolor

Treatment of pityriasis (tinea) versicolor^† caused by Malassezia furfur (Pityrosporum orbiculare or P. ovale).

Pityriasis (tinea) versicolor generally can be treated topically with an azole antifungal (e.g., clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole), an allylamine antifungal (e.g., naftifine, terbinafine), ciclopirox olamine, or certain other topical therapies (e.g., selenium sulfide 2.5%). An oral antifungal (e.g., fluconazole, itraconazole, ketoconazole) may be indicated, with or without a topical agent, in patients who have extensive or severe infections or who fail to respond to or have frequent relapses with topical therapy.

Prevention of Candidiasis in Transplant Recipients, Cancer Patients, or Other Patients at High Risk

Prevention of Candida infections in patients at high risk, including those undergoing bone marrow transplantation (BMT), hematopoietic stem cell transplantation (HSCT)^†, or solid organ transplantation^† and neutropenic patients undergoing chemotherapy and radiation therapy^†. Also used to prevent Candida infections in high-risk patients undergoing urologic procedures^† and for prevention of invasive candidiasis in high-risk patients in intensive care units (ICUs)^† and in low birthweight neonates^† at high risk.

For primary prophylaxis to prevent Candida infections in neutropenic patients when risk of invasive candida infection is substantial (e.g., allogeneic HSCT recipients, patients with acute leukemia undergoing intensive remission-induction or salvage-induction chemotherapy), IDSA recommends an azole antifungal (fluconazole, itraconazole, posaconazole, voriconazole) or IV echinocandin (caspofungin or micafungin). If primary prophylaxis is used to prevent invasive candida infection in high-risk adults in ICUs, IDSA recommends fluconazole as drug of choice and IV echinocandins (anidulafungin, caspofungin, micafungin) as alternatives.

Has been used for prophylaxis of invasive candidiasis in low birthweight neonates^† at high risk. Although such prophylaxis is controversial since there are concerns about emergence of resistant fungi or increased colonization with fluconazole-resistant Candida, there is some evidence that fluconazole prophylaxis can prevent colonization and reduce the incidence of invasive candidiasis. IDSA and AAP state that use of fluconazole prophylaxis can be considered for very low birthweight neonates (<1 kg) in nurseries that have high rates of neonatal invasive candidiasis.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on prevention of fungal infections in immunocompromised patients.

Fluconazole Dosage and Administration

Administration

Administer orally or by IV infusion.

Since absorption from the GI tract is rapid and almost complete, IV route generally is reserved for patients who do not tolerate or are unable to take the drug orally.

Oral Administration

Administer orally without regard to meals.

Reconstitution

Reconstitute powder for oral suspension at time of dispensing by adding 24 mL of distilled or purified water to container containing 0.35 or 1.4 g of the drug to provide a suspension containing 50 or 200 mg/5 mL, respectively. Shake bottle vigorously to suspend the powder.

Shake suspension well just prior to administration of each dose.

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Fluconazole solutions may be administered by IV infusion without further dilution.

Fluconazole solutions in plastic containers should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration from the secondary container is complete.

Rate of Administration

IV infusions should be administered at a rate ≤200 mg/hour.

Dosage

Oral and IV dosage are identical.

Use of loading dose that is twice the daily dosage generally is recommended on the first day of treatment; this results in fluconazole plasma concentrations on the second day of treatment that are close to steady-state concentrations.

Pediatric Patients

General Pediatric Dosage

Treatment of Fungal Infections

Oral or IV

3–12 mg/kg once daily.

Dosage of 3, 6, or 12 mg/kg daily in pediatric patients is equivalent to dosage of 100, 200, or 400 mg daily, respectively, in adults.

Premature neonates (gestational age 26–29 weeks): Based on available pharmacokinetic data, manufacturer recommends that the usual pediatric dosage be given once every 72 hours during the first 2 weeks of life; after 2 weeks of age, give usual pediatric dosage once daily.

Candida Infections

Treatment of Disseminated or Invasive Candida Infections

Oral or IV

6–12 mg/kg daily.

Meningitis or septicemia in neonates and infants ≤3 months of age^†: 5–6 mg/kg once daily has been used. An initial loading dose of 10 mg/kg followed by 5 mg/kg once daily has been used for Candida septicemia.

Treatment of Neonatal Candidiasis†

Oral or IV

12 mg/kg daily for at least 3 weeks has been recommended by IDSA and AAP as an alternative to IV amphotericin B.

Treatment of Oropharyngeal Candidiasis

Oral or IV

6 mg/kg on the first day, then 3 mg/kg once daily. To decrease likelihood of relapse, manufacturer states treatment usually should be continued for at least 2 weeks.

HIV-infected infants and children: 6–12 mg/kg (up to 400 mg) once daily for 7–14 days.

HIV-infected adolescents: 100 mg once daily for 7–14 days.

Treatment of Esophageal Candidiasis

Oral or IV

6 mg/kg on the first day, then 3 mg/kg once daily. Dosage may be increased up to 12 mg/kg daily if necessary, based on response and condition of the patient. Manufacturer states treatment usually should be continued for at least 3 weeks and for at least 2 weeks after symptoms resolve.

HIV-infected infants and children: 6–12 mg/kg (up to 600 mg) once daily for at least 3 weeks and for at least 2 weeks after symptoms resolve.

HIV-infected adolescents: 100 mg (up to 400 mg) daily for 14–21 days.

Prevention of Recurrence (Secondary Prophylaxis) of Oropharyngeal or Esophageal Candidiasis†

Oral

HIV-infected infants and children with frequent or severe recurrences: 3–6 mg/kg (up to 200 mg) once daily.

HIV-infected adolescents with frequent or severe recurrences of oropharyngeal candidiasis: 100 mg once daily or 3 times weekly.

HIV-infected adolescents with frequent or severe recurrences of esophageal candidiasis: 100–200 mg once daily.

HIV-infected infants and children: Consider discontinuing secondary prophylaxis against oropharyngeal or esophageal candidiasis if CD4⁺ T-cell count or percentage increases to CDC immunologic category 2 or 1.

HIV-infected adolescents: Consider discontinuing secondary prophylaxis against oropharyngeal or esophageal candidiasis if CD4⁺ T-cell count increases to >200/mm³ in response to antiretroviral therapy.

Coccidioidomycosis†

Treatment of Coccidioidomycosis (Nonmeningeal)†

Oral or IV

HIV-infected infants and children with mild to moderate coccidioidomycosis (e.g., focal pneumonia): 6–12 mg/kg (up to 400 mg) once daily.

HIV-infected infants and children with diffuse pulmonary or disseminated coccidioidomycosis (nonmeningeal) who cannot receive amphotericin B: 12 mg/kg (up to 800 mg) once daily.

HIV-infected adolescents with mild coccidioidomycosis (e.g., focal pneumonia): 400 mg once daily.

HIV-infected adolescents with severe coccidioidomycosis (e.g., diffuse pulmonary infection): 400 mg once daily. Usually used in conjunction with IV amphotericin B or as follow-up after an initial regimen of IV amphotericin B.

Treatment of Coccidioidal Meningitis†

Oral or IV

HIV-infected infants and children: 12 mg (up to 800 mg) once daily.

HIV-infected adolescents: 400–800 mg daily.

Consultation with an expert experienced in treating coccidioidal meningitis is recommended.

Primary Prophylaxis to Prevent First Episode of Coccidioidomycosis†

Oral

HIV-infected adolescents living in areas endemic for coccidioidomycosis who have newly positive IgM or IgG serologic test and CD4⁺ T-cell count <250/mm³: 400 mg once daily.

Prevention of Recurrence (Secondary Prophylaxis) of Coccidioidomycosis†

Oral

HIV-infected infants and children: 6 mg/kg (up to 400 mg) once daily.

HIV-infected adolescents: 400 mg once daily.

Initiate secondary prophylaxis after primary infection has been adequately treated.

HIV-infected infants and children: Continue life-long, secondary prophylaxis against coccidioidomycosis, regardless of antiretroviral therapy or immune reconstitution.

HIV-infected adolescents who were treated for focal coccidioidal pneumonia and are receiving antiretroviral therapy: Consider discontinuing secondary prophylaxis against coccidioidomycosis after 12 months if CD4⁺ T-cell count ≥250/mm³, but continue monitoring for recurrence (e.g., serial chest radiographs, coccidioidal serology).

HIV-infected adolescents who were treated for diffuse pulmonary or disseminated coccidioidomycosis or coccidioidal meningitis: Life-long secondary prophylaxis against coccidioidomycosis usually required.

Cryptococcosis

Treatment of Cryptococcal Meningitis

Oral or IV

Manufacturer recommends 12 mg/kg on the first day, then 6 mg/kg once daily. Dosage may be increased to 12 mg/kg daily if necessary based on condition of the patient and response to the drug. Continue for 10–12 weeks after CSF cultures are negative.

HIV-infected infants and children: Induction therapy with IV amphotericin B and oral flucytosine given for at least 2 weeks, then consolidation therapy with oral or IV fluconazole 12 mg/kg on first day, then 10–12 mg/kg (up to 800 mg) once daily for at least 8 weeks.

HIV-infected infants and children who cannot receive amphotericin B: Induction therapy with oral or IV fluconazole 12 mg/kg on first day, then 10–12 mg/kg (up to 800 mg) once daily given in conjunction with oral flucytosine (25 mg/kg 4 times daily) for at least 2 weeks, then consolidation therapy with oral or IV fluconazole 10–12 mg/kg (up to 800 mg) once daily for at least 8 weeks.

HIV-infected adolescents: Induction therapy with IV amphotericin B and oral flucytosine given for at least 2 weeks, then consolidation therapy with oral or IV fluconazole 400 mg (6 mg/kg) daily given for at least 8 weeks.

HIV-infected adolescents who cannot receive flucytosine: Induction therapy with IV amphotericin B and oral or IV fluconazole 400 mg daily given for at least 2 weeks, then consolidation therapy with fluconazole 400 mg daily given for at least 8 weeks.

HIV-infected adolescents who cannot receive amphotericin B: Induction therapy with oral or IV fluconazole 400–800 mg daily and oral flucytosine given for at least 4–6 weeks, then consolidation therapy with oral fluconazole 400 mg daily given for at least 8 weeks.

Treatment of Cryptococcal Infections (Nonmeningeal)†

Oral or IV

HIV-infected infants and children with localized cryptococcosis without CNS involvement (e.g., isolated pulmonary disease): 12 mg/kg on first day, then 6–12 mg/kg (up to 600 mg) once daily.

HIV-infected infants and children with disseminated or severe pulmonary cryptococcosis without CNS involvement who cannot receive amphotericin B: 12 mg/kg on first day, then 6–12 mg/kg (up to 600 mg) once daily.

Duration of treatment depends on clinical response and site and severity of infection. A duration of 6–12 months has been recommended.

Prevention of Recurrence (Secondary Prophylaxis) of Cryptococcosis†

Oral

HIV-infected infants and children: 6 mg/kg (up to 200 mg) once daily.

HIV-infected adolescents: 200 mg once daily.

Initiate secondary prophylaxis after primary infection has been adequately treated and continue for at least 1 year.

HIV-infected infants and children: Consider discontinuing secondary prophylaxis against cryptococcosis in those ≥6 years of age who are asymptomatic for cryptococcosis, have received such prophylaxis for ≥1 year, are receiving antiretroviral therapy, have had undetectable or low plasma HIV RNA levels for ≥3 months, and have CD4⁺ T-cell counts ≥100/mm³. Reinitiate secondary prophylaxis against cryptococcosis if CD4⁺ T-cell count decreases to <100/mm³.

HIV-infected adolescents: Consider discontinuing secondary prophylaxis against cryptococcosis in those who are asymptomatic for cryptococcosis, have received such prophylaxis for ≥1 year, are receiving antiretroviral therapy, have had undetectable or low plasma HIV RNA levels for ≥3 months, and have CD4⁺ T-cell counts ≥100/mm³. Reinitiate secondary prophylaxis against cryptococcosis if CD4⁺ T-cell count decreases to <100/mm³.

Histoplasmosis

Treatment of Less Severe Histoplasmosis†

Oral

HIV-infected infants and children: 3–6 mg/kg (up to 200 mg) once daily for acute primary pulmonary histoplasmosis.

HIV-infected adolescents: 800 mg daily.

Prevention of Recurrence (Secondary Prophylaxis) of Histoplasmosis†

Oral

HIV-infected infants and children: 3–6 mg/kg (up to 200 mg) once daily for at least 1 year.

HIV-infected adolescents: 400 mg daily.

Consider discontinuing secondary prophylaxis against histoplasmosis in HIV-infected infants, children, or adolescents who have received such prophylaxis for ≥1 year, have negative fungal blood cultures and serum histoplasma antigen levels <2 ng/mL, have been receiving antiretroviral therapy for ≥6 months, and have CD4⁺ T-cell percentage >15% (CD4⁺ T-cell counts ≥150/mm³ in those ≥6 years of age).

Reinitiate secondary prophylaxis against histoplasmosis if parameters for discontinuing such prophylaxis are not met.

Dermatophytoses†

Tinea Capitis†

Oral

3–6 mg/kg daily for 2–6 weeks has been effective in children 1.5–16 years of age. AAP recommends 6 mg/kg daily for 3–6 weeks.

Tinea Corporis† or Tinea Cruris†

Oral

Some clinicians recommend 150 mg once weekly for 2–6 weeks.

Tinea Manuum† or Tinea Pedis†

Oral

Some clinicians recommend 150 mg once weekly for 4–6 weeks.

Onychomycosis†

Oral

Some clinicians recommend 3–6 mg/kg once weekly for 12–16 weeks for fingernail infections or 3–6 mg/kg once weekly for 18–26 weeks for toenail infections. Others recommend 150 mg once weekly for 4–6 months for fingernail infections or 150 mg once weekly for 9–12 months for toenail infections.

Prevention of Candidiasis in Transplant Recipients, Cancer Patients, or Other Patients at High Risk

Hematopoietic Stem Cell Transplant (HSCT) Recipients†

Oral or IV

Children 6 months to 13 years of age: 3–6 mg/kg daily (maximum 600 mg daily).

Adolescents >13 years of age: 400 mg once daily.

Initiate prophylaxis on the day of HSCT transplantation (i.e., day 0) and continue until engraftment occurs (i.e., approximately 30 days after HSCT) or until 7 days after neutrophil count is >1000/mm³.

Low Birthweight Neonates†

Oral or IV

Various dosage regimens have been used for prophylaxis to reduce the incidence of invasive candidiasis in low birthweight neonates^† at high risk. If such prophylaxis is used, monitor for antifungal resistance, toxicity, and neurodevelopmental outcomes.

IDSA states that a dosage of 3 or 6 mg/kg twice weekly reduces the rate of invasive candidiasis in premature neonates in nurseries with a high incidence of Candida infections.

Low birthweight neonates (<1 kg) at high risk: AAP recommends an initial dose of 3 mg/kg IV during first 48–72 hours after birth, followed by 3 mg/kg IV twice weekly for 4–6 weeks or until IV access no longer required for care.

Adults

Blastomycosis†

Treatment of Blastomycosis†

Oral

Mild to moderate pulmonary or mild to moderate disseminated blastomycosis (without CNS involvement): 400–800 mg daily.

CNS blastomycosis: Initial regimen of IV amphotericin B given for 4–6 weeks, followed by fluconazole 800 mg daily for at least 12 months and until CSF abnormalities resolve.

Candida Infections

Treatment of Disseminated or Invasive Candida Infections

Oral or IV

Candidemia, disseminated candidiasis, or pneumonia: Manufacturer states that 400 mg daily has been used.

Urinary tract infections or peritonitis: Manufacturer states that 50–200 mg daily has been used.

Candidemia in nonneutropenic or neutropenic adults: Loading dose of 800 mg (12 mg/kg) on first day, then 400 mg (6 mg/kg) daily continued for 2 weeks after documented clearance of Candida from the bloodstream, resolution of candidemia symptoms, and resolution of neutropenia.

Chronic disseminated candidiasis (hepatosplenic) in clinically stable patients: 400 mg (6 mg/kg) daily. Severely ill patients should receive IV amphotericin B initially for several weeks, then fluconazole 400 mg (6 mg/kg) daily. Continue antifungal treatment until lesions resolve (usually several months); continue through periods of immunosuppression.

CNS candidiasis: Initial regimen of IV amphotericin B (with or without oral flucytosine) given for several weeks, then follow-up therapy with fluconazole 400–800 mg (6–12 mg/kg) daily. Continue antifungal treatment until signs and symptoms, CSF abnormalities, and radiologic abnormalities resolve.

Treatment of Candida Urinary Tract Infections

Oral or IV

Symptomatic cystitis caused by fluconazole-susceptible Candida: 200 mg (3 mg/kg) daily for 2 weeks.

Pyelonephritis caused by fluconazole-susceptible Candida: 200–400 mg (3–6 mg/kg) daily for 2 weeks.

Treatment of Candida Osteoarticular Infections

Oral or IV

Osteomyelitis: 400 mg (6 mg/kg) daily for 6–12 months.

Septic arthritis: 400 mg (6 mg/kg) daily for 6 weeks.

Secondary prophylaxis for prevention of recurrence if septic arthritis involved a prosthetic device that cannot be removed: 400 mg (6 mg/kg) daily.

Treatment of Candida Intravascular Infections

Oral or IV

Endocarditis (native or prosthetic valve) or implantable cardiac device: Initial regimen of IV amphotericin B (with or without oral flucytosine), then follow-up therapy with fluconazole 400–800 mg (6–12 mg/kg) daily. Continue antifungal treatment for at least 6 weeks after valve replacement.

Secondary prophylaxis for prevention of recurrence in those with native valve endocarditis who cannot undergo valve replacement or in those with prosthetic valve endocarditis: 400–800 mg (6–12 mg/kg) daily.

Treatment of Candida Endophthalmitis

Oral or IV

Chorioretinitis (with or without vitritis): Loading dose of 800 mg (12 mg/kg) on first day, then 400–800 mg (6–12 mg/kg) daily for at least 4–6 weeks. Intravitreal amphotericin B or voriconazole may also be indicated if there is macular involvement.

Treatment of Oropharyngeal Candidiasis

Oral or IV

200 mg on first day, then 100 or 200 mg once daily. To decrease likelihood of relapse, manufacturer states treatment usually should be continued for at least 2 weeks.

Moderate or severe oropharyngeal candidiasis: IDSA recommends 100–200 mg daily for 7–14 days.

HIV-infected adults: 100 mg daily for 7–14 days.

Treatment of Esophageal Candidiasis

Oral or IV

200 mg on first day, then 100 or 200 mg once daily. Up to 400 mg once daily may be used depending on the patient’s response. Manufacturer states treatment usually should be continued for at least 3 weeks and for at least 2 weeks after symptoms resolve.

IDSA recommends 200–400 mg (3–6 mg/kg) daily for 14–21 days.

HIV-infected adults: 100 mg (up to 400 mg) daily for 14–21 days.

Prevention of Recurrence (Secondary Prophylaxis) of Oropharyngeal or Esophageal Candidiasis†

Oral

HIV-infected adults with frequent or severe recurrences of oropharyngeal candidiasis: 100 mg once daily or 3 times weekly.

HIV-infected adults with frequent or severe recurrences of esophageal candidiasis: 100–200 mg daily.

Consider discontinuing secondary prophylaxis against oropharyngeal or esophageal candidiasis in HIV-infected adults if CD4⁺ T-cell count increases to >200/mm³ in response to antiretroviral therapy.

Treatment of Vulvovaginal Candidiasis

Oral

Uncomplicated infections in nonpregnant women: Single 150-mg dose.

Recurrent vulvovaginal candidiasis^† caused by C. albicans in nonpregnant women: CDC recommends 100, 150, or 200 mg given every 3 days for 3 doses (i.e., days 1, 4, and 7) to achieve mycologic remission, then maintenance regimen of 100, 150, or 200 mg once weekly for 6 months to prevent recurrence. IDSA recommends maintenance regimen of 150 mg once weekly for 6 months.

Severe vulvovaginal candidiasis^† (extensive vulvar erythema, edema, excoriation, and fissure formation) in nonpregnant women: CDC recommends 2-dose regimen (two 150-mg doses given 72 hours [3 days] apart). IDSA recommends 150 mg once every 72 hours for a total of 2 or 3 doses.

HIV-infected nonpregnant women with uncomplicated or severe or recurrent vulvovaginal candidiasis^†: Use same regimens recommended for nonpregnant women without HIV infection.

Coccidioidomycosis†

Treatment of Coccidioidomycosis (Nonmeningeal)†

Oral or IV

400–800 mg daily.

Diffuse pneumonia or disseminated infections: Usually used in conjunction with IV amphotericin B or as follow-up after an initial regimen of IV amphotericin B. Duration of treatment usually 3–6 months for uncomplicated pneumonia; total duration of treatment usually at least 1 year for diffuse pneumonia and chronic progressive fibrocavitary pneumonia.

HIV-infected adults with mild coccidioidomycosis (e.g., focal pneumonia): 400 mg once daily.

HIV-infected adults with severe coccidioidomycosis (e.g., diffuse pulmonary infection): 400 mg once daily. Usually used as follow-up after an initial regimen of IV amphotericin B or in conjunction with IV amphotericin B.

Treatment of Coccidioidal Meningitis†

Oral or IV

HIV-infected adults or other adults: 400–800 mg daily. Concomitant intracisternal, intraventricular, or intrathecal amphotericin B therapy has been used in some patients.

Consultation with an expert experienced in treating coccidioidal meningitis is recommended.

Primary Prophylaxis to Prevent First Episode of Coccidioidomycosis†

Oral

HIV-infected adults living in areas endemic for coccidioidomycosis who have newly positive IgM or IgG serologic test and CD4⁺ T-cell count <250/mm³: 400 mg once daily.

Prevention of Recurrence (Secondary Prophylaxis) of Coccidioidomycosis†

Oral

HIV-infected adults: 400 mg once daily.

Initiate secondary prophylaxis after primary infection has been adequately treated.

HIV-infected adults who were treated for focal coccidioidal pneumonia and are receiving antiretroviral therapy: Consider discontinuing secondary prophylaxis against coccidioidomycosis after 12 months if CD4⁺ T-cell count ≥250/mm³, but continue monitoring for recurrence (e.g., serial chest radiographs, coccidioidal serology).

HIV-infected adults who were treated for diffuse pulmonary or disseminated coccidioidomycosis or coccidioidal meningitis: Life-long secondary prophylaxis against coccidioidomycosis usually required.

Cryptococcosis

Treatment of Cryptococcal Meningitis

Oral or IV

Manufacturer recommends 400 mg given as a single dose on first day, then 200-400 mg once daily. Some evidence suggests that the 400-mg dosage is more effective than lower dosage.

HIV-infected adults: Induction therapy with IV amphotericin B and oral flucytosine given for at least 2 weeks, then consolidation therapy with oral fluconazole 400 mg (6 mg/kg) daily given for at least 8 weeks.

HIV-infected adults who cannot receive flucytosine: Induction therapy with IV amphotericin B and oral or IV fluconazole 400 mg daily given for at least 2 weeks, then consolidation therapy with oral fluconazole 400 mg daily given for at least 8 weeks. Some experts state that higher fluconazole dosage (800 mg daily) is preferred for induction and consolidation therapy when this regimen is used.

HIV-infected adults who cannot receive amphotericin B: Induction therapy with oral or IV fluconazole 400–800 mg daily and oral flucytosine given for at least 4–6 weeks, then consolidation therapy with oral fluconazole 400 mg daily given for at least 8 weeks. Some experts recommend induction therapy using higher fluconazole dosage (preferably 1.2 g daily) and oral flucytosine given for 6 weeks, then consolidation therapy with fluconazole 400 mg daily.

HIV-infected adults who cannot receive amphotericin B or flucytosine: ≥800 mg daily given for 10–12 weeks is recommended. IDSA states that a dosage ≥1.2 g daily is preferred when fluconazole monotherapy is used; dosage as high as 2 g daily has been used, but may be associated with toxicity. High dosage should be given in divided doses to minimize GI toxicity.

Immunocompetent adults without HIV infection who are not transplant recipients: Induction therapy with IV amphotericin B and oral flucytosine given for at least 4 weeks, then consolidation therapy with oral fluconazole 400 mg daily given for at least 8 weeks. In those who are immunocompetent, are without uncontrolled underlying disease, and are at low risk for therapeutic failure, IDSA states that this induction regimen can be given for only 2 weeks, then consolidation therapy with oral fluconazole 800 mg (12 mg/kg) daily should be given for at least 8 weeks.

Treatment of Cryptococcosis (Nonmeningeal)†

Oral

Immunocompetent or immunocompromised adults with mild to moderate pulmonary cryptococcosis: 400 mg (6 mg/kg) daily for 6–12 months.

Immunocompetent adults with nonpulmonary cryptococcosis at a single site: 400 mg (6 mg/kg) daily for 6–12 months.

Immunocompetent or immunocompromised adults with severe pulmonary cryptococcosis, cryptococcemia, or disseminated cryptococcosis: Use regimens recommended for adults with cryptococcal meningitis.

Cryptococcosis in Organ Transplant Recipients†

Oral or IV

CNS disease: Induction therapy with IV amphotericin B and oral flucytosine given for at least 2 weeks, then consolidation therapy with oral fluconazole 400–800 mg (6–12 mg/kg) daily given for 8 weeks.

Mild to moderate pulmonary disease (without pulmonary infiltrates) or other mild to moderate non-CNS disease: 400 mg (6 mg/kg) daily for 6–12 months.

Prevention of Recurrence (Secondary Prophylaxis) of Cryptococcosis†

Oral

HIV-infected or other adults: 200 mg once daily.

Organ transplant recipients adequately treated for CNS cryptococcosis: 200–400 mg daily for 6–12 months.

Initiate secondary prophylaxis after primary infection has been adequately treated and continue for at least 1 year.

Consider discontinuing secondary prophylaxis against cryptococcosis in HIV-infected adults who are asymptomatic for cryptococcosis, have received such prophylaxis for ≥1 year, are receiving antiretroviral therapy, have had undetectable or low plasma HIV RNA levels for ≥3 months, and have CD4⁺ T-cell counts ≥100/mm³. Reinitiate secondary prophylaxis against cryptococcosis if CD4⁺ T-cell count decreases to <100/mm³.

Histoplasmosis†

Treatment of Histoplasmosis†

Oral or IV

400–800 mg once daily. Alternatively, 800 mg daily has been given for 12 weeks for induction therapy, followed by 400 mg daily.

HIV-infected adults with less severe disease: 800 mg daily.

Prevention of Recurrence (Secondary Prophylaxis) of Histoplasmosis†

Oral

HIV-infected adults: 400 mg daily.

Consider discontinuing secondary prophylaxis against histoplasmosis in HIV-infected adults who have received such prophylaxis for ≥1 year, have negative fungal blood cultures and serum histoplasma antigen levels <2 ng/mL, have been receiving antiretroviral therapy for ≥6 months, and have CD4⁺ T-cell counts ≥150/mm³.

Reinitiate secondary prophylaxis against histoplasmosis if CD4⁺ T-cell count decreases to <150/mm³.

Sporotrichosis†

Lymphocutaneous and Cutaneous Sporotrichosis†

Oral

400–800 mg once daily. Use only when other drugs cannot be used.

Dermatophytoses†

Tinea Corporis†, Tinea Cruris†, or Tinea Pedis†

Oral

150 mg once weekly for 2–6 weeks has been effective.

Tinea corporis involving small, well-defined lesions: 250 mg once weekly for 2–4 weeks has been recommended.

Tinea pedis: 150–200 mg once weekly for 1–8 weeks has been recommended.

Onychomycosis†

Oral

100–450 mg once weekly for 2–12 months has been used. Some clinicians recommend 150–300 mg once weekly for 3–6 months for fingernail infections or for 6–12 months for toenail infections.

Pityriasis (Tinea) Versicolor†

Oral

A single 400-mg dose has been used. Alternatively, 150 mg has been given once weekly for 2 or 4 weeks or 300 mg has been given once weekly for 2 weeks.

Prevention of Candidiasis in Transplant Recipients, Cancer Patients, or Other Patients at High Risk

Bone Marrow Transplant (BMT) Recipients

Oral or IV

400 mg once daily.

In patients in whom severe granulocytopenia (neutrophil count <500/mm³) is anticipated, initiate several days before expected onset of neutropenia and continue for 7 days after neutrophil count is >1000/mm³.

Antifungal prophylaxis not usually recommended if anticipated duration of neutropenia is <7 days.

Hematologic Stem Cell Transplant (HSCT) Recipients†

Oral or IV

400 mg once daily.

Initiate on the day of HSCT transplantation (i.e., day 0) and continue until engraftment occurs (i.e., approximately 30 days after HSCT) or until 7 days after neutrophil count is >1000/mm³.

High-risk Patients in ICUs†

Oral or IV

High-risk patients in ICUs with known high incidence of invasive candidiasis: 400 mg (6 mg/kg) once daily.

Prescribing Limits

Pediatric Patients

Treatment of Fungal Infections

Oral or IV

Maximum of 600 mg daily.

Special Populations

Renal Impairment

Treatment of Fungal Infections

Oral or IV

Adults with impaired renal function receiving multiple doses: Adjust dosage in response to degree of impairment based on patient’s measured or estimated Cl_cr. Manufacturer recommends an initial loading dose of 50–400 mg (based on the type of infection being treated), then give 100% of the usual daily dose to those with Cl_cr >50 mL/minute and give 50% of the usual daily dose to those with Cl_cr ≤50 mL/minute. Further dosage adjustments may be necessary depending on patient condition.

Dialysis patients receiving multiple doses: Give 100% of the usual daily dose after each dialysis period; on days patient does not receive dialysis, give reduced dosage based on Cl_cr.

Adults with impaired renal function receiving single-dose regimen for treatment of vulvovaginal candidiasis: Modification of dosage not needed.

Children with impaired renal function: Pharmacokinetics not studied; make dosage adjustments similar to those recommended for adults.

Geriatric Patients

Adjust dosage based on Cl_cr. (See Renal Impairment under Dosage.)

Cautions for Fluconazole

Contraindications

• Hypersensitivity to fluconazole or any ingredient in the formulation.

• Concomitant use with drugs that are known to prolong the QT interval and are metabolized by CYP3A4 (e.g., astemizole, cisapride, pimozide, quinidine). (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Hepatotoxicity

Serious hepatic reactions (e.g., necrosis, clinical hepatitis, cholestasis, fulminant hepatic failure) have been reported rarely. A clear relationship between these hepatic effects and daily dosage, duration of therapy, gender, or age has not been demonstrated.

While hepatotoxicity usually has been reversible, fatalities have occurred, principally in patients with serious underlying disease (e.g., AIDS, malignancy) who were receiving other drugs concomitantly.

Mild, transient increases (1.5–3 times ULN) in serum concentrations of AST, ALT, alkaline phosphatase, γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGTP), and bilirubin have been reported.

In most reported cases, concentrations returned to pretreatment levels either during or after fluconazole therapy and were not associated with hepatotoxicity. However, higher increases in serum transaminase concentrations (≥8 times the ULN), which required discontinuance of the drug, also have occurred.

If abnormal liver function test results occur, monitor patient for the development of more severe hepatic injury.

If signs and symptoms consistent with liver disease develop, discontinue fluconazole.

Dermatologic Reactions

Rash (including diffuse rash accompanied by eosinophilia) and pruritus have been reported.

Exfoliative skin disorders have been reported rarely in patients with serious underlying disease (principally AIDS or malignancy); fatalities have been reported.

Stevens-Johnson syndrome, which can be fatal, also has been reported.

If rash develops in patient with deep-seated fungal infection, monitor closely and discontinue fluconazole if lesions progress.

If rash that may be attributable to fluconazole develops in patient with superficial fungal infection, discontinue the drug.

Fetal/Neonatal Morbidity

Rare and distinct pattern of birth defects (e.g., brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, congenital heart disease) observed in infants born to women who received high-dose fluconazole (400–800 mg daily) for serious, life-threatening fungal infections during most or all of first trimester. (See Pregnancy under Cautions.)

Available human data to date do not suggest increased risk of congenital anomalies when fluconazole used as a single 150-mg oral dose for treatment of vulvovaginal candidiasis in pregnant women. (See Pregnancy under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis (including angioedema, face edema, and pruritus) has been reported rarely. Angioedema and anaphylactic reactions have been reported rarely in women who received a single oral dose for treatment of vulvovaginal candidiasis.

Cross-hypersensitivity

Although information concerning cross-sensitivity between fluconazole and other triazole or imidazole antifungals is not available, manufacturer states that fluconazole should be used with caution in individuals hypersensitive to other azoles.

General Precautions

Cardiovascular Effects

Prolonged QT interval reported with some azoles, including fluconazole. Torsades de pointes reported rarely.

Most reported cases involved seriously ill patients with multiple confounding risk factors that may have contributed (e.g., structural heart disease, electrolyte abnormalities, concomitant drugs).

Use with caution in patients with potentially proarrhythmic conditions and risk factors for QT prolongation.

Selection and Use of Antifungals

Diflucan powder for oral suspension contains sucrose; do not use in patients with hereditary fructose, glucose-galactose malabsorption, and sucrase-isomaltase deficiency.

Prior to use of fluconazole, appropriate specimens for fungal culture and other relevant laboratory studies (serology, histopathology) should be obtained to isolate and identify causative organisms.

Superinfection with nonsusceptible fungi (e.g., C. krusei) may occur; alternative antifungal therapy may be required.

CNS Effects

Dizziness or seizures may occur occasionally and should be considered in patients who drive or operate machines.

Specific Populations

Pregnancy

FDA alerted clinicians in April 2016 that it is reviewing safety data regarding use of oral fluconazole during pregnancy and advised cautious prescribing of the drug until the review is completed.

Category C when used as a single 150-mg oral dose for treatment of vulvovaginal candidiasis. Classification based on data available to FDA at that time indicating single 150-mg oral dose not associated with increased risk of congenital anomalies. Data from a recent Danish study indicated increased risk of spontaneous abortion (i.e., miscarriage during gestational weeks 7 through 22) in pregnant women treated with oral fluconazole (most women received total cumulative dose of 150–300 mg) compared with matched control pregnancies not exposed to oral fluconazole. FDA is reviewing data from the Danish study and additional data; after completing the review, FDA will communicate its conclusions and updated recommendations regarding use of the single-dose 150-mg oral fluconazole regimen during pregnancy.

Category D when used for all other indications (e.g., treatment of oropharyngeal or esophageal candidiasis, cryptococcal meningitis, prevention of Candida infections). Congenital abnormalities reported in infants born to women who received high-dose fluconazole (400–800 mg daily) for treatment of serious, life-threatening fungal infections during most or all of the first trimester.

CDC states use topical (intravaginal) azoles (not oral fluconazole) for treatment of vulvovaginal candidiasis during pregnancy.

Patients who are pregnant or actively trying to become pregnant should talk to their clinician about alternatives for treatment of vulvovaginal candidiasis.

IDSA states avoid use of fluconazole for treatment of serious fungal infections (e.g., blastomycosis^†, candidiasis, histoplasmosis^†, coccidioidomycosis^†, cryptococcosis) during pregnancy.

If used during pregnancy or if patient becomes pregnant while receiving fluconazole, inform patient of potential hazard to the fetus. (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Distributed into milk at concentrations similar to those achieved in plasma. Use with caution in nursing women.

Pediatric Use

Efficacy in children <6 months of age not established, but the drug has been used safely and effectively in neonates and children <6 months of age (including neonates as young as 1 day of age).

Adverse effects in children generally have been similar to those in adults.

Geriatric Use

Some evidence that rash, vomiting, and diarrhea occur more frequently in patients ≥65 years of age than in younger adults, but the discontinuance rate in geriatric patients has been similar to that in younger patients. There have been more reports of anemia and acute renal failure in geriatric patients than in those <65 years of age, but clinical importance unclear since there is a natural increase in reported incidence of these in geriatric individuals.

Insufficient experience in controlled clinical studies in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. Other clinical experience has not revealed age-related differences in response.

Substantially eliminated by kidneys; assess renal function periodically since geriatric patients more likely to have decreased renal function. Adjust dosage based on Cl_cr. (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Use with caution.

Renal Impairment

Use with caution; dosage adjustments required based on degree of renal impairment. Plasma concentrations are higher and half-life prolonged. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (nausea, vomiting, abdominal pain, diarrhea), rash, transient increases in liver enzymes and bilirubin.

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Fluconazole is a potent inhibitor of CYP2C9 and a moderate inhibitor of CYP3A4. Because fluconazole has a long half-life, the enzyme-inhibiting effects of the drug persist for 4–5 days following discontinuance. Concomitant use of fluconazole and drugs metabolized by CYP2C9 or 3A4 may result in increased plasma concentrations of the concomitant drug; use caution and monitor closely.

Drugs that Prolong the QT Interval

Concomitant use of fluconazole with drugs known to prolong the QT interval and that are metabolized by CYP3A4 is contraindicated.

Specific Drugs

Fluconazole Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics are similar following IV or oral administration.

Rapidly and almost completely absorbed from GI tract; peak plasma concentrations attained within 1–2 hours.

Oral bioavailability ≥90% in healthy, fasting adults.

Oral bioavailability in HIV-infected adults appears to be similar to that reported for healthy adults.

Unlike some imidazoles (e.g., ketoconazole), GI absorption of fluconazole does not appear to be affected by gastric pH.

Oral suspensions are bioequivalent to tablets.

Food

Administration with a high-fat meal does not affect fluconazole peak plasma concentrations or AUC compared with administration in the fasting state.

Distribution

Extent

Widely distributed into body tissues and fluids following oral or IV administration.

Concentrations attained in urine and skin may be 10 times higher than concurrent plasma concentrations.

Concentrations attained in saliva, sputum, nails, blister fluid, blister skin, and vaginal tissue are approximately equal to concurrent plasma concentrations.

Unlike some azoles (e.g., itraconazole, ketoconazole), fluconazole readily distributes into CSF following oral or IV administration; CSF concentrations may be 50–94% of concurrent plasma concentrations, regardless of the degree of meningeal inflammation.

Crosses the placenta in rats; not known whether crosses the placenta in humans.

Distributed into human milk in concentrations similar to those attained in plasma.

Plasma Protein Binding

Unlike some azoles (e.g., itraconazole, ketoconazole, miconazole), which are highly protein bound, fluconazole is only 11–12% bound to plasma proteins.

Elimination

Elimination Route

Eliminated principally by renal excretion.

Approximately 60–80% of a single oral or IV dose excreted in urine unchanged; about 11% is excreted in urine as metabolites.

Small amounts excreted in feces.

Removed by hemodialysis.

Removed by peritoneal dialysis.

Half-life

Adults with normal renal function: Approximately 30 hours (range: 20–50 hours).

Children: 19.5–25 hours following a single oral dose in those 9 months to 13 years of age and 15.2–17.6 hours following multiple IV doses in those 5–15 years of age.

Neonates: Decreases over time, averaging 88 hours after the first dose and 55 hours after the fifth dose (day 13).

Special Populations

Elimination half-life not affected by impaired hepatic function.

In impaired renal function, plasma concentrations are higher and half-life prolonged; elimination half-life is inversely proportional to Cl_cr.

Renal clearance may be lower in geriatric patients than in younger adults, apparently because of decreased kidney function in this age group.

Stability

Storage

Oral

Tablets

<30°C.

For Suspension

<30°C.

Following reconstitution, store between 5–30°C; protect from freezing. Discard unused oral suspension 2 weeks after reconstitution.

Parenteral

Injection for IV Infusion

Glass bottles: 5–30°C; protect from freezing.

Viaflex plastic containers: 5–25°C (may be exposed to temperatures up to 40°C); protect from freezing.

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

Actions and Spectrum

• Triazole-derivative azole antifungal.

• Presumably exerts its antifungal activity by altering cellular membranes resulting in increased membrane permeability, leakage of essential elements (e.g., amino acids, potassium), and impaired uptake of precursor molecules (e.g., purine and pyrimidine precursors to DNA). Inhibits CYP 14-α-desmethylase in susceptible fungi, which leads to accumulation of C-14 methylated sterols (e.g., lanosterol) and decreased concentrations of ergosterol.

• Usually fungistatic in action.

• Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes. Inactive against bacteria.

• Candida: Active in vitro and in vivo against C. albicans, C. dubliniensis, C. guilliermondii, C. kefyr, C. parapsilosis, C. lusitaniae, and C. tropicalis. C. krusei are intrinsically resistant to fluconazole and many strains of C. glabrata also are resistant or have reduced susceptibility to the drug. Some strains of C. duobushaemulonii inhibited in vitro by fluconazole; C. haemulonii and C. auris (often misidentified as C. haemulonii, C. famata, or Rhodotorula glutinis) generally resistant to fluconazole in vitro.

• Other fungi: Active against Blastomyces dermatitidis, Coccidioides immitis, C. posadasii, Cryptococcus neoformans, and Histoplasma capsulatum. May be active in vitro against some strains of C. gattii, but there is in vitro evidence that fluconazole may be less active against C. gattii than some other azoles (e.g., itraconazole, posaconazole, voriconazole).

• Fluconazole generally is inactive against Aspergillus in vitro. Inactive against Malassezia pachydermatis and Scopulariopsis, including S. acremonium and S. brevicaulis. Although a few strains of Penicillium marneffei may be inhibited in vitro by fluconazole concentrations, most strains tested are resistant to the drug.

• Candida and C. neoformans with decreased in susceptibility to fluconazole have been reported. Prolonged or intermittent use of oral fluconazole in immunocompromised patients has been suggested as a major contributing factor to emergence of fluconazole resistance in Candida.

• Fluconazole-resistant fungi also may be cross-resistant to other azole antifungals (e.g., itraconazole, ketoconazole, posaconazole, voriconazole).

Advice to Patients

• Importance of completing full course of therapy. An inadequate period of treatment may lead to recurrence of active infection.

• When driving or operating machinery, patients receiving fluconazole should take into account that dizziness or seizures may occur occasionally.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• Does fluconazole flush out yeast/discharge?
• How long does fluconazole take to work?
• Fluconazole - can you drink alcohol while using one dose of 150mg one time?
• What is the dose of fluconazole for tinea? Is it is indicated for tinea infections?
• I'm having a reaction after taking fluconazole, is this normal?

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