Medication Guide App

Fluconazole

Pronunciation

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
Brands: Diflucan

Introduction

Antifungal; azole (triazole derivative).1 5 51 68 84 124

Uses for Fluconazole

Aspergillosis

Has been used in the treatment of pneumonia or other respiratory tract infections caused by Aspergillus fumigatus, A. niger, or A. terreus,3 37 64 124 138 139 but has produced variable results and low efficacy rates.3 37 64 124 138 139

IDSA considers voriconazole the drug of choice for primary treatment of invasive pulmonary aspergillosis in most patients and IV amphotericin B the preferred alternative.423 436 For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends amphotericin B, caspofungin, micafungin, posaconazole, or itraconazole.423 IDSA states that fluconazole is not considered active against invasive aspergillosis.423

Blastomycosis

Treatment of blastomycosis caused by Blastomyces dermatitidis.146 286 287 288 289 290 291 436

Drugs of choice are IV amphotericin B and oral itraconazole.289 290 292 296 315 316 424 436 Although oral fluconazole and oral ketoconazole are considered alternatives,436 424 these drugs may be less effective and should be used only when the drugs of choice are contraindicated or cannot be used.436 424

Azole antifungals should not be relied on for initial treatment of CNS blastomycosis.424 Treatment failures have been reported when an oral antifungal (e.g., ketoconazole) was used in the treatment of cutaneous or pulmonary blastomycosis in patients who had asymptomatic or subclinical CNS involvement at the time of initial diagnosis.293 294

IDSA states that long-term suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole may be required to prevent relapse or recurrence of blastomycosis in immunocompromised patients and in other patients who experience relapse despite appropriate therapy.424 Such prophylaxis is not addressed in current CDC, NIH, and IDSA guidelines for prevention of opportunistic infections in individuals infected with HIV.440 441

Candidemia and Disseminated Candida Infections

Treatment of candidemia,1 124 322 324 331 394 410 411 425 436 disseminated candidiasis,1 330 333 334 and other serious Candida infections, including urinary tract infections (symptomatic cystitis, pyelonephritis, fungus balls),1 37 49 61 64 94 425 436 peritonitis,1 36 47 61 64 68 94 436 meningitis,407 409 425 osteomyelitis or septic arthritis,425 endophthalmitis,425 cardiovascular infections,1 37 64 94 405 425 or pneumonia.1 37 64 94

A drug of choice for many Candida infections.326 425 436 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).267 425

Choice of an antifungal for treatment of candidemia or invasive Candida infections should take into consideration any history of recent exposure to azole 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.425

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in nonneutropenic patients, IDSA recommends fluconazole or an echinocandin (caspofungin, micafungin, anidulafungin) for initial therapy;425 amphotericin B is an alternative when these drugs have been ineffective or cannot be used because of intolerance or resistance.425 Initial therapy with an echinocandin is preferred in patients with moderately severe to severe infections and for those who recently received an azole antifungal or are likely to be infected with C. glabrata or C. krusei;425 consider transition from the echinocandin to fluconazole in clinically stable patients if strains susceptible to fluconazole (e.g., C. albicans) are likely.425 Fluconazole is the drug of choice for treatment of infections caused by C. parapsilosis in these patients.425

For treatment of candidemia in neutropenic patients, IDSA recommends an echinocandin (caspofungin, micafungin, anidulafungin) or amphotericin B for initial therapy;425 fluconazole is a reasonable alternative in those who are less critically ill or have not recently received an azole;425 voriconazole can be used as an alternative when broader antifungal coverage is required.425 An echinocandin, amphotericin B, or voriconazole is recommended for C. krusei infections.425 An echinocandin is preferred for C. glabrata infections;425 fluconazole or amphotericin B is preferred for C. parapsilosis infections.425 For infections known to be caused by C. krusei, an echinocandin, amphotericin B, or voriconazole is recommended.425 For initial empiric treatment of suspected invasive candidiasis in neutropenic patients, amphotericin B, caspofungin, or IV voriconazole is recommended;425 alternatives are fluconazole or itraconazole.425

Although IV amphotericin B usually is the drug of choice for treatment of disseminated candidiasis in neonates (neonatal candidiasis),146 425 IDSA states that fluconazole is a reasonable alternative.425 Fluconazole also has been used for prophylaxis to reduce the incidence of invasive candidiasis in low birthweight neonates at high risk.425 471 472 473 474 475 (See Prevention of Fungal Infections 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.425

Antifungal treatment not usually indicated in patients with asymptomatic candiduria, unless there is a high risk of disseminated candidiasis (e.g., neutropenic patients, low birthweight infants, patients who will undergo urologic manipulations).425 Fluconazole is the drug of choice for treatment of symptomatic cystitis, pyelonephritis, or fungus balls likely to be caused by fluconazole-susceptible Candida;425 IV amphotericin B and/or flucytosine is recommended when fluconazole-resistant Candida (e.g., C. glabrata, C. krusei) are likely.425

For treatment of endophthalmitis caused by Candida, IDSA states that IV amphotericin B used in conjunction with flucytosine is the regimen of choice in patients with advancing lesions or lesions threatening the macula;425 fluconazole is an acceptable alternative for less severe endophthalmitis.425

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis in immunocompromised adults with HIV infection, malignancy, or other serious underlying disease.39 40 41 92 95 124 335 336 337 400 402 404 406 425 425 436 440 441 A drug of choice.337 425 436 440 441

IDSA recommends topical treatment with clotrimazole lozenges or nystatin oral suspension for mild oropharyngeal candidiasis;425 oral fluconazole is recommended for moderate to severe disease.425 For refractory oropharyngeal candidiasis, including fluconazole-refractory infections, itraconazole oral solution, oral posaconazole, or oral voriconazole is recommended.425 An IV echinocandin (caspofungin, micafungin, anidulafungin) or IV amphotericin B also are recommended as alternatives for refractory infections.425

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For treatment of oropharyngeal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral fluconazole as the preferred drug of choice for initial episodes;440 other drugs of choice are clotrimazole lozenges or nystatin oral suspension.440 Alternatives for initial episodes are itraconazole oral solution or oral posaconazole.440 For fluconazole-refractory infections in HIV-infected adults and adolescents, itraconazole oral solution or oral posaconazole is preferred;440 alternatives include IV amphotericin B, an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.440

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence is not usually recommended in patients adequately treated for oropharyngeal candidiasis, patients with frequent or severe recurrences, including HIV-infected adults, adolescents, or children, may benefit from secondary prophylaxis with oral fluconazole or oral posaconazole; however, consider the potential for azole resistance.425 440 441 Patients with fluconazole-refractory esophageal candidiasis who responded to treatment with an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.440

Esophageal Candidiasis

Treatment of esophageal candidiasis.1 44 173 401 403 404 425 436 440 441

Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).425 440

IDSA recommends oral fluconazole as the preferred drug of choice for treatment of esophageal candidiasis;425 if oral therapy is not tolerated, IV fluconazole, IV amphotericin B, or an IV echinocandin (caspofungin, micafungin, anidulafungin) is recommended.425 For fluconazole-refractory infections, preferred alternatives are itraconazole oral solution, oral posaconazole, or oral or IV voriconazole;425 other alternatives are an IV echinocandin or IV amphotericin B.425

For treatment of esophageal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral or IV fluconazole as the preferred drug of choice and itraconazole oral solution as a preferred alternative.440 Other alternatives include an IV echinocandin (caspofungin, micafungin, anidulafungin), oral or IV voriconazole, oral posaconazole, or IV amphotericin B.440 For refractory esophageal candidiasis, including fluconazole-refractory infections, in HIV-infected adults and adolescents, itraconazole oral solution or oral posaconazole is preferred;440 alternatives include IV amphotericin B, an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.440

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence is not usually recommended in patients adequately treated for oropharyngeal candidiasis, patients with frequent or severe recurrences, including HIV-infected adults, adolescents, or children, may benefit from secondary prophylaxis with oral fluconazole or itraconazole oral solution; however, consider the potential for azole resistance.425 440 441 Patients with fluconazole-refractory oropharyngeal candidiasis who responded to an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.440

Vulvovaginal Candidiasis

Treatment of uncomplicated vulvovaginal candidiasis or complicated vulvovaginal candidiasis.1 45 66 129 147 148 197 198 201 203 204 205 206 209 210 399 436 440 443 444

For treatment of uncomplicated vulvovaginal candidiasis (mild to moderate, sporadic or infrequent, most likely caused by C. albicans, occurring in immunocompetent women), CDC and others recommend an intravaginal azole antifungal (e.g., butoconazole, clotrimazole, miconazole, terconazole, tioconazole) or, alternatively, a single dose of oral fluconazole.348 349 350 352 436 440 443 444 Single-dose oral fluconazole regimen offers some advantages over topical agents45 46 51 116 195 197 198 (e.g., ensures compliance, may reduce or eliminate concurrent rectal infections that can be source of reinfection).45 46 66 195 196

For treatment of recurrent vulvovaginal candidiasis (usually defined as 4 or more episodes of symptomatic vulvovaginal candidiasis in a year), each individual episode caused by C. albicans may respond to a short course of intravaginal azole antifungal or oral fluconazole.443 To maintain clinical and mycologic control, some experts recommend a longer duration of initial therapy to attempt mycologic remission before initiating a maintenance antifungal regimen.443

Coccidioidomycosis

Treatment and prevention of coccidioidomycosis caused by Coccidioides immitis or C. posadasii.54 97 115 125 146 220 298 299 300 426 436 440 441 464 465 466 A drug of choice.146 426 436 440 441 464

Used for treatment of coccidioidal pulmonary infections, meningitis, and disseminated (extrapulmonary) infections involving soft tissue or bone and joint.54 97 115 125 146 220 298 299 300 426 440 441 464 465 466

Antifungal treatment may not be necessary for mild, uncomplicated coccidioidal pneumonia since such infections may resolve spontaneously;146 426 treatment is 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).146 426 440 441

For initial treatment of symptomatic pulmonary coccidioidomycosis and chronic fibrocavitary or disseminated (extrapulmonary) coccidioidomycosis, IDSA states that an oral azole (fluconazole or itraconazole) usually is recommended.426 IV amphotericin B is 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 cannot be used (e.g., pregnant women).146 426

For treatment of clinically mild coccidioidomycosis (e.g., focal pneumonia or a positive coccidioidal serologic test alone) in HIV-infected adults or adolescents, CDC, NIH, and IDSA recommend oral fluconazole or oral itraconazole.440 For treatment of diffuse pulmonary infections or extrathoracic disseminated coccidioidomycosis (nonmeningeal) in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend initial therapy with IV amphotericin B followed by oral azole therapy.440 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.440

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.441 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.441 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).441

For treatment of coccidioidal meningitis in HIV-infected adults, adolescents, or children or for other individuals, fluconazole (with or without intrathecal amphotericin B) is considered the regimen of choice.146 426 440 441 Consultation with an expert is recommended.146 440 441

In HIV-infected adults and adolescents who live in areas where coccidioidomycosis is endemic, CDC, NIH, and IDSA recommend primary prophylaxis against coccidioidomycosis in those who have positive IgM or IgG serologic tests and CD4+ T-cell counts <250/mm3 since these individuals may be at increased risk for development of active infections.440 Oral fluconazole or oral itraconazole should be used for primary prophylaxis against coccidioidomycosis in these HIV-infected adults and adolescents.440 Primary prophylaxis against coccidioidomycosis is not recommended in HIV-infected infants and children.441

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.440 441 CDC, NIH, and IDSA recommend oral fluconazole or oral itraconazole for secondary prophylaxis of coccidioidomycosis in HIV-infected individuals.440 441

Long-term (life-long) suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or oral itraconazole also is necessary in any individual treated for coccidioidal meningitis.146 426 465

Cryptococcosis

Treatment of meningitis caused by Cryptococcus neoformans.1 28 29 30 31 32 33 93 118 146 303 304 305 306 310 311 427 436 440 441 Also used for treatment of pulmonary cryptococcosis, cryptococcemia, and disseminated cryptococcal infections.57 135 136 309 427

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 (conventional formulation) 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.146 427 436 440 441 A lipid formulation of amphotericin B (e.g., amphotericin B lipid complex, amphotericin B liposomal) could be substituted for conventional amphotericin B in this preferred regimen in patients who have or are predisposed to renal dysfunction.427 440 441

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 conventional IV amphotericin B or a lipid formulation of IV amphotericin B (e.g., amphotericin B lipid complex, amphotericin B liposomal) given for 4–6 weeks; induction therapy with conventional IV amphotericin B given in conjunction with oral fluconazole for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral fluconazole administered for at least 8 weeks;146 427 440 441 induction and consolidation therapy with oral or IV fluconazole used in conjunction with oral flucytosine for 4–6 weeks;146 427 440 441 or induction and consolidation therapy with oral fluconazole given for 10–12 weeks.427 These alternative regimens may be less effective and are recommended only in patients who cannot tolerate or have not responded to the preferred regimen.427 440 441

For treatment of cryptococcal CNS infections in organ transplant recipients, IDSA recommends induction therapy with IV amphotericin B liposomal or amphotericin B lipid complex given in conjunction with oral flucytosine for at least 2 weeks, then consolidation therapy with oral fluconazole given for 8 weeks.427 If induction regimen does not include flucytosine, continue for at least 4–6 weeks.427 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.427

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 (conventional formulation) 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.427 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.427

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.427 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.427 Severe pulmonary infections, cryptococcemia, and disseminated infections in immunocompetent or immunosuppressed individuals should be treated using regimens recommended for cryptococcal meningitis.427

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.427 440 441 CDC, NIH, and IDSA recommend oral fluconazole as the drug of choice for secondary prophylaxis of cryptococcosis in HIV-infected individuals;427 440 441 oral itraconazole is considered an alternative in those who cannot tolerate fluconazole, but may be less effective than fluconazole.427 440 441 Conventional 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.427

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.427

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.427 IDSA states that single, small cryptococcoma may be treated with oral fluconazole; induction therapy with a regimen of amphotericin B (conventional formulation) and flucytosine given for 4–6 weeks, followed by consolidation therapy with fluconazole given for 6–18 months, should be considered for very large or multiple cryptococcomas caused by C. gattii.427 Regimens that include amphotericin B (conventional or liposomal formulations), flucytosine, and fluconazole have been effective in a few patients with CNS infections known to be caused by C. gattii.450 451 480 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).449 450 (See Actions and Spectrum.)

Histoplasmosis

Treatment of histoplasmosis caused by Histoplasma capsulatum.312 313 315 436 Considered an alternative, not a drug of first choice.315 316 428 436

IV amphotericin B and oral itraconazole are the drugs of choice for treatment of histoplasmosis.146 315 316 428 436 440 441 Fluconazole is considered an alternative,315 316 428 436 but generally should be used only in patients who cannot tolerate the drugs of choice.436 Fluconazole has been used successfully in some patients, but may be less effective than itraconazole; fluconazole-resistant H. capsulatum have developed in some HIV-infected patients who failed to respond to the drug.428

Sporotrichosis

Treatment of lymphocutaneous and cutaneous sporotrichosis caused by Sporothrix schenckii.146 429 436 Considered an alternative, not a drug of first choice.146 429 436

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.146 429 436 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.146 429 436

Although fluconazole can be used as an alternative for treatment of cutaneous and lymphocutaneous sporotrichosis,429 436 it may be less effective than itraconazole146 429 and should be used only if patient cannot tolerate itraconazole or other alternatives (oral terbinafine, oral potassium iodide, local hyperthermia).429

Do not use for treatment of pulmonary, osteoarticular, or meningeal sporotrichosis.429

Dermatophytoses

Treatment of certain dermatophytoses (e.g., tinea capitis,146 375 376 377 379 454 477 478 tinea corporis,146 373 374 378 478 tinea cruris,373 374 378 478 tinea pedis146 374 436 478 ) 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.146 380 381 382 383 384 386 478 Tinea capitis and tinea barbae generally are treated using an oral antifungal.146 372 381 385 387 478

While topical antifungals usually are effective for treatment of uncomplicated tinea manuum and tinea pedis,146 381 382 384 386 419 478 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.381 384 386 419 478

Onychomycosis

Treatment of onychomycosis of toenails or fingernails.140 176 417 420 421 436 455 458 476 479

Drug of choice for treatment of onychomycosis usually is oral terbinafine or oral itraconazole.436 455 456 457 458 477 478 Oral fluconazole is an alternative, especially in those who cannot tolerate the drugs of choice,436 455 458 but may be less effective.140 176 420 421 455 477 479 Concomitant use of oral and topical antifungals may be more effective in some patients.458 477 478 479

Pityriasis (Tinea) Versicolor

Oral fluconazole has been used in the treatment of pityriasis (tinea) versicolor caused by Malassezia furfur (Pityrosporum orbiculare or P. ovale).146 459 460 461 462 477 478

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%).146 459 463 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.459 460 463 477 478

Prevention of Fungal Infections 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.1 110 124 157 158 159 160 161 179 184 186 188 189 340 341 342 422 425 436 452 Also used to prevent Candida infections in high-risk patients undergoing urologic procedures425 and for prevention of invasive candidiasis in high-risk patients in intensive care units (ICUs)425 and in low birthweight neonates at high risk.425 471 472 473 474 475

CDC, IDSA, and American Society of Blood and Marrow Transplantation (ASBMT) recommend antifungal prophylaxis with fluconazole in adults, adolescents, and children undergoing allogeneic HSCT.422 425 452 Although recipients of autologous HSCT have a lower risk for invasive fungal infections, these experts also recommend fluconazole prophylaxis in autologous HSCT recipients who have underlying hematologic malignancies (e.g., lymphoma, leukemia), have or will have prolonged neutropenia and mucosal damage from intense conditioning regimens or graft manipulation, or have recently received fludarabine or cladribine.425 452 Alternatively, IDSA states that posaconazole or micafungin can be used in HSCT recipients with neutropenia at risk for candidiasis.425

For postoperative antifungal prophylaxis in recipients of solid organ transplants at high risk for invasive candidiasis (i.e., liver, pancreas, or small bowel transplant recipients), IDSA recommends fluconazole or IV amphotericin B.425 Risk of invasive candidiasis after other solid organ transplants (e.g., kidney, heart) appears to be too low to warrant routine antifungal prophylaxis.425

For primary prophylaxis of candidiasis in individuals with chemotherapy-induced neutropenia at risk for such infections, IDSA recommends fluconazole, posaconazole, or caspofungin.425

IDSA states that fluconazole prophylaxis can be considered for high-risk patients in ICUs that are known to have a high incidence of invasive candidiasis.425 Although there is some evidence that antifungal prophylaxis may decrease the incidence of invasive candidiasis in such patients, a survival benefit has not been demonstrated.425

Has been used for prophylaxis of invasive candidiasis in low birthweight neonates at high risk.425 471 472 473 474 475 Although such prophylaxis is controversial since there are concerns about emergence of resistant fungi or increased colonization with fluconazole-resistant Candida,471 472 there is some evidence that fluconazole prophylaxis can prevent colonization and reduce the incidence of invasive candidiasis.471 472 473 474 475 AAP and IDSA state that use of fluconazole prophylaxis can be considered for very low birthweight neonates (<1 kg) in nurseries that have very high rates of neonatal invasive candidiasis.146 425

Empiric Therapy in Febrile Neutropenic Patients

Empiric therapy of presumed fungal infections in febrile neutropenic patients who have not responded to empiric treatment with broad-spectrum antibacterial agents.422 453

Amphotericin B generally has been the drug of choice for empiric antifungal treatment in patients who remain febrile and neutropenic despite 5–7 days of empiric treatment with an appropriate broad-spectrum antibacterial agent.422 453 Fluconazole is an alternative if infection with Aspergillus or fluconazole-resistant Candida (e.g., C. glabrata, C. krusei) is unlikely.422

Do not use for empiric antifungal therapy in patients who received the drug for prophylaxis or in patients with symptoms of sinusitis or pulmonary infection (i.e., high probability of Aspergillus infection).422

Fluconazole Dosage and Administration

Administration

Administer orally or by IV infusion.1

Since absorption from the GI tract is rapid and almost complete,1 2 51 61 67 68 IV route generally is reserved for patients who do not tolerate or are unable to take the drug orally.116 117

Oral Administration

Administer orally without regard to meals.1

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.1 Shake bottle vigorously to suspend the powder.1

Shake suspension well just prior to administration of each dose.1

IV Infusion

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

Fluconazole solutions may be administered by IV infusion without further dilution.1

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.1

Rate of Administration

IV infusions should be administered at a rate ≤200 mg/hour.1

Dosage

Oral and IV dosage are identical.1

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.1

Pediatric Patients

General Pediatric Dosage
Treatment of Fungal Infections
Oral or IV

3–12 mg/kg once daily.1 146

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.1

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.1

Candida Infections
Treatment of Disseminated or Invasive Candida Infections
Oral or IV

6–12 mg/kg daily.1 146

Meningitis or septicemia in neonates and infants ≤3 months of age: 5–6 mg/kg once daily has been used.394 409 410 An initial loading dose of 10 mg/kg followed by 5 mg/kg once daily has been used for Candida septicemia.392 394

Treatment of Neonatal Candidiasis
Oral or IV

12 mg/kg daily for at least 3 weeks has been recommended by IDSA as an alternative to IV amphotericin B.425

Treatment of Oropharyngeal Candidiasis
Oral or IV

6 mg/kg on the first day, then 3 mg/kg once daily.1 146 To decrease likelihood of relapse, manufacturer states treatment usually should be continued for at least 2 weeks.1

HIV-infected infants and children: 3–6 mg/kg (up to 400 mg) once daily for 7–14 days.441

HIV-infected adolescents: 100 mg once daily for 7–14 days.440

Treatment of Esophageal Candidiasis
Oral or IV

6 mg/kg on the first day, then 3 mg/kg once daily.1 146 Dosage may be increased up to 12 mg/kg daily if necessary, based on response and condition of the patient.1 Manufacturer states treatment usually should be continued for at least 3 weeks and for at least 2 weeks after symptoms resolve.1

HIV-infected infants and children: 6 mg/kg on the first day, then 3–6 mg/kg (up to 400 mg) once daily for 14–21 days.441

HIV-infected adolescents: 100 mg (up to 400 mg) once daily for 14–21 days.440

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.441

HIV-infected adolescents with frequent or severe recurrences: 100–200 mg once daily.440

Limited data are available regarding the safety of discontinuing secondary prophylaxis against oropharyngeal or esophageal candidiasis in HIV-infected individuals.440 441 In HIV-infected infants and children, consideration can be given to discontinuing secondary prophylaxis against oropharyngeal or esophageal candidiasis when CD4+ T-cell count or percentage increases to CDC immunologic category 2 or 1.441 Consideration can be given to discontinuing such prophylaxis in HIV-infected adolescents when CD4+ T-cell counts increase to 200/mm3 in response to antiretroviral therapy.440

Coccidioidomycosis
Treatment of Coccidioidomycosis (Nonmeningeal)
Oral or IV

HIV-infected infants and children with mild coccidioidomycosis (e.g., focal pneumonia): 5–6 mg/kg twice daily (up to 800 mg daily).441

HIV-infected infants and children with diffuse pulmonary or disseminated coccidioidomycosis: 5–6 mg/kg twice daily (up to 800 mg daily).441 Usually used in conjunction with IV amphotericin B or as follow-up after an initial regimen of IV amphotericin B.441

HIV-infected adolescents with mild coccidioidomycosis (e.g., focal pneumonia or positive coccidioidal serologic test alone): 400 mg once daily.440

HIV-infected adolescents with severe coccidioidomycosis (e.g., diffuse pulmonary infection): 400 mg once daily.440 Usually used in conjunction with IV amphotericin B or as follow-up after an initial regimen of IV amphotericin B.440

Treatment of Coccidioidal Meningitis
Oral or IV

HIV-infected infants and children with coccidioidal meningitis: 5–6 mg/kg twice daily (up to 800 mg daily).441 Dosage up to 12 mg/kg daily has been used.441

HIV-infected adolescents with meningeal coccidioidomycosis: 400–800 mg daily.440

Consultation with an expert experienced in treating coccidioidal meningitis is recommended.146 440

Primary Prophylaxis to Prevent First Episode of Coccidioidomycosis
Oral

HIV-infected adolescents living in areas endemic for coccidioidomycosis who have positive IgM or IgG serologic test and CD4+ T-cell count <250/mm3: 400 mg once daily.440

Consider discontinuing primary prophylaxis against coccidioidomycosis if CD4+ T-cell count is >250/mm3 for 6 months.440 Reinitiate primary prophylaxis if CD4+ T-cell count decreases to <250/mm3.440

Prevention of Recurrence (Secondary Prophylaxis) of Coccidioidomycosis
Oral

HIV-infected infants and children: 6 mg/kg (up to 400 mg) once daily.441

HIV-infected adolescents: 400 mg once daily.440

Initiate secondary prophylaxis after primary infection has been adequately treated.440 441

HIV-infected infants and children: Continue life-long, secondary prophylaxis against coccidioidomycosis, regardless of antiretroviral therapy or immune reconstitution.441

HIV-infected adolescents with history of focal coccidioidal pneumonia who responded to antifungal treatment, are receiving antiretroviral therapy, and have CD4+ T-cell counts >250/mm3: Consider discontinuing secondary prophylaxis against coccidioidomycosis after 12 months, but continue monitoring for recurrence (e.g., serial chest radiographs, coccidioidal serology).440

HIV-infected adolescents with history of diffuse pulmonary or disseminated coccidioidomycosis or history of coccidioidal meningitis: Continue life-long secondary prophylaxis against coccidioidomycosis, regardless of antiretroviral therapy or immune reconstitution.440

Cryptococcosis
Treatment of Cryptococcal Meningitis
Oral or IV

Manufacturer recommends 12 mg/kg on the first day, then 6 mg/kg once daily.1 Dosage may be increased to 12 mg/kg daily if necessary based on condition of the patient and response to the drug.1 Continue for 10–12 weeks after CSF culture are negative.1

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 day 1 and then 6–12 mg/kg daily (up to 800 mg daily) given for at least 8 weeks.427 441 Some clinicians recommend fluconazole dosage of 10–12 mg/kg daily for consolidation therapy.427

HIV-infected infants and children who cannot receive amphotericin B: Induction therapy with oral or IV fluconazole 12 mg/kg on day 1 and then 6–12 mg/kg daily (up to 800 mg daily) and oral flucytosine (100 mg/kg daily in 4 divided doses) given for at least 2 weeks, then consolidation therapy with oral or IV fluconazole 6–12 mg/kg daily (up to 800 mg daily) given for at least 8 weeks.441

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.440

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.440

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.440

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 day 1, then 6–12 mg/kg daily (up to 600 mg daily).427 441

HIV-infected infants and children with disseminated or severe pulmonary cryptococcosis without CNS involvement who cannot receive amphotericin B: 12 mg/kg on day 1, then 6–12 mg/kg daily (up to 600 mg daily).441

Duration of treatment depends on clinical response and site and severity of infection.441 A duration of 6–12 months has been recommended.427

Prevention of Recurrence (Secondary Prophylaxis) of Cryptococcosis
Oral

HIV-infected infants and children: 6 mg/kg (up to 200 mg) once daily.427 441

HIV-infected adolescents: 200 mg once daily.440

Initiate secondary prophylaxis after primary infection has been adequately treated.440 441

HIV-infected infants and children with history of cryptococcal meningitis usually should receive life-long suppressive therapy to prevent recurrence.441 Consideration can be given to discontinuing secondary prophylaxis in HIV-infected children ≥6 years of age who are asymptomatic for cryptococcosis, have received secondary prophylaxis for ≥6 months, have been receiving antiretroviral therapy for ≥6 months, and have had CD4+ T-cell counts ≥200/mm3 for ≥6 months.441 Reinitiate secondary prophylaxis against cryptococcosis if CD4+ T-cell count decreases to <200/mm3.441

HIV-infected adolescents with history of cryptococcal meningitis usually should receive life-long secondary prophylaxis to prevent recurrence.440 Some experts state that consideration can be given to discontinuing secondary prophylaxis in HIV-infected adolescents who are asymptomatic for cryptococcosis and have had increases in CD4+ T-cell counts in response to antiretroviral therapy according to recommendations for adults.440

Dermatophytoses
Tinea Capitis
Oral

3–6 mg/kg daily for 2–6 weeks has been effective in children 1.5–16 years of age.375 377 379

Tinea Corporis or Tinea Cruris
Oral

Some clinicians recommend 150 mg once weekly for 2–6 weeks.476

Tinea Manuum or Tinea Pedis
Oral

Some clinicians recommend 150 mg once weekly for 4–6 weeks.476

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.458 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.476

Prevention of Fungal Infections 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).452

Adolescents >13 years of age: 400 mg once daily.452

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/mm3.452

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.425 471 472 473 474 475 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 very high incidence of Candida infections.425 If such prophylaxis is used, monitor for antifungal resistance, toxicity, and neurodevelopmental outcomes.425

Adults

Blastomycosis
Treatment of Blastomycosis
Oral

Mild to moderate pulmonary or mild to moderate disseminated blastomycosis (without CNS involvement): 400–800 mg daily.424

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.424

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.1

Urinary tract infections or peritonitis: Manufacturer states that 50–200 mg daily has been used.1

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.425

Chronic disseminated candidiasis (hepatosplenic) in clinically stable patients: 400 mg (6 mg/kg) daily.425 Severely ill patients should receive IV amphotericin B initially for 1–2 weeks, then fluconazole 400 mg (6 mg/kg) daily.425 Continue antifungal treatment until calcification occurs or lesions resolve (usually weeks to months); continue through periods of immunosuppression.425

CNS candidiasis: Initial regimen of IV amphotericin B given with or without flucytosine for several weeks, then follow-up therapy with fluconazole 400–800 mg (6–12 mg/kg) daily.425 Continue antifungal treatment until signs and symptoms, CSF abnormalities, and radiologic abnormalities resolve.425 In patients who cannot receive amphotericin B, fluconazole may be used alone in a dosage of 400–800 mg (6–12 mg/kg) daily.425

Treatment of Candida Urinary Tract Infections
Oral or IV

Urinary tract infections caused by fluconazole-susceptible Candida: 200 mg (3 mg/kg) daily for 2 weeks for treatment of symptomatic cystitis or 200–400 mg (3–6 mg/kg) daily for 2 weeks for treatment of pyelonephritis.425 For treatment of urinary fungus balls, 200–400 mg (3–6 mg/kg) daily until symptoms have resolved and urine cultures are negative for Candida.425

Treatment of Candida Endophthalmitis
Oral or IV

>;Candida endophthalmitis that is less severe (i.e., without advancing lesions or lesions threatening the macula): 12 mg/kg on day 1, then 6–12 mg/kg daily for at least 4–6 weeks.425

Treatment of Oropharyngeal Candidiasis
Oral or IV

200 mg on first day, then 100 or 200 mg once daily.1 64 68 118 436 To decrease likelihood of relapse, manufacturer states treatment usually should be continued for at least 2 weeks.1

HIV-infected adults: 100 mg once daily for 7–14 days.440

Treatment of Esophageal Candidiasis
Oral or IV

200 mg on first day, then 100 or 200 mg once daily.1 64 68 118 436 Up to 400 mg once daily may be used depending on the patient’s response.1 Manufacturer states treatment usually should be continued for at least 3 weeks and for at least 2 weeks after symptoms resolve.1

IDSA recommends 200–400 mg (3–6 mg/kg) daily for 14–21 days.425

HIV-infected adults: 100 mg (up to 400 mg) once daily for 14–21 days.440

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

HIV-infected adults with frequent or severe recurrences of oropharyngeal candidiasis: 100 mg 3 times weekly.425 440

HIV-infected adults with frequent or severe recurrences of esophageal candidiasis: 100–200 mg once daily.440 Alternatively, 100–200 mg 3 times weekly.425

Limited data are available regarding the safety of discontinuing secondary prophylaxis against oropharyngeal or esophageal candidiasis in HIV-infected individuals.440 Consideration can be given to discontinuing such prophylaxis in HIV-infected adults when the CD4+ T-cell count increases to 200/mm3 in response to antiretroviral therapy.440

Treatment of Vulvovaginal Candidiasis
Oral

Uncomplicated infections in nonpregnant women: Single 150-mg dose.1 436 443 444

Severe vulvovaginal candidiasis (extensive vulvar erythema, edema, excoriation, and fissure formation) in nonpregnant women: CDC recommends 2-dose regimen (two 150-mg doses given 3 days apart).443

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,443 then maintenance regimen of 100, 150, or 200 mg once weekly for 6 months to prevent recurrence.443

HIV-infected women with uncomplicated vulvovaginal candidiasis: Single 150-mg dose.440

HIV-infected women with severe or recurrent vulvovaginal candidiasis: 150 mg once every 72 hours for 2–3 doses.440 In those with frequent or severe recurrences, consider 150 mg once weekly for prevention of recurrence (secondary prophylaxis).440

Coccidioidomycosis
Treatment of Coccidioidomycosis (Nonmeningeal)
Oral or IV

400–800 mg daily.426 436

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.426 Duration of treatment usually 3–6 months for uncomplicated pneumonia;426 total duration of treatment usually at least 1 year for diffuse pneumonia and chronic progressive fibrocavitary pneumonia.426

HIV-infected adults with mild coccidioidomycosis (e.g., focal pneumonia, positive coccidioidal serologic test alone): 400 mg once daily.440

HIV-infected adults with severe coccidioidomycosis (e.g., diffuse pulmonary infection): 400 mg once daily.440 Usually used as follow-up after an initial regimen of IV amphotericin B or in conjunction with IV amphotericin B.440

Treatment of Coccidioidal Meningitis
Oral or IV

HIV-infected adults or other adults: 400–800 mg once daily.298 300 315 426 436 440 465 Concomitant intracisternal, intraventricular, or intrathecal amphotericin B therapy has been used in some patients.97 426

Consultation with an expert experienced in treating coccidioidal meningitis is recommended.146 440

Primary Prophylaxis to Prevent First Episode of Coccidioidomycosis
Oral

HIV-infected adults living in areas endemic for coccidioidomycosis who have positive IgM or IgG serologic test and CD4+ T-cell count <250/mm3: 400 mg once daily.440

Consider discontinuing primary prophylaxis against coccidioidomycosis if CD4+ T-cell count is >250/mm3 for 6 months.440 Reinitiate primary prophylaxis if CD4+ T-cell count decreases to <250/mm3.440

Prevention of Recurrence (Secondary Prophylaxis) of Coccidioidomycosis
Oral

HIV-infected adults: 400 mg once daily.440

Initiate secondary prophylaxis after primary infection has been adequately treated.440

HIV-infected adults with history of focal coccidioidal pneumonia who responded to antifungal treatment, are receiving antiretroviral therapy, and have CD4+ T-cell counts >250/mm3: Consider discontinuing secondary prophylaxis against coccidioidomycosis after 12 months, but continue monitoring for recurrence (e.g., serial chest radiographs, coccidioidal serology).440

HIV-infected adults with history of diffuse pulmonary or disseminated coccidioidomycosis or history of coccidioidal meningitis: Continue life-long secondary prophylaxis against coccidioidomycosis, regardless of antiretroviral therapy or immune reconstitution.440

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.1 Some evidence suggests that the 400-mg dosage is more effective than lower dosage.93 116 117

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.427 440

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.440 Some experts state that higher fluconazole dosage (800 mg daily) is preferred for induction and consolidation therapy when this regimen is used.427

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.440 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.427

HIV-infected adults who cannot receive amphotericin B or flucytosine: ≥800 mg daily given for 10–12 weeks is recommended.427 IDSA states that a dosage ≥1.2 g daily is preferred when fluconazole monotherapy is used;427 dosage as high as 2 g daily has been used, but may be associated with toxicity.427 High dosage should be given in divided doses to minimize GI toxicity.427

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.427 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.427

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.427

Immunocompetent adults with nonpulmonary cryptococcosis at a single site: 400 mg (6 mg/kg) daily for 6–12 months.427

Immunocompetent or immunocompromised adults with severe pulmonary cryptococcosis, cryptococcemia, or disseminated cryptococcosis: Use regimens recommended for adults with cryptococcal meningitis.427

Cryptococcosis in Organ Transplant Recipients
Oral or IV

CNS disease: Induction therapy with IV amphotericin B liposomal or IV amphotericin B lipid complex 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.427

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.427

Prevention of Recurrence (Secondary Prophylaxis) of Cryptococcosis
Oral

HIV-infected or other adults adequately treated for cryptococcal meningitis: 200 mg once daily.427 440

Organ transplant recipients adequately treated for CNS cryptococcosis: 200–400 mg daily for 6–12 months.427

Initiate secondary prophylaxis after primary infection has been adequately treated.440

IDSA states consider discontinuing secondary prophylaxis against cryptococcosis in HIV-infected adults who have received at least 1 year of antifungal treatment, are receiving antiretroviral therapy, have had undetectable or low plasma HIV RNA levels for at least 3 months, and have CD4+ T-cell counts >100/mm3.427 If secondary prophylaxis against cryptococcosis is discontinued, follow patient closely and perform serial cryptococcal serum antigen tests.427 Reinitiate secondary prophylaxis if CD4+ T-cell count decreases to <100/mm3 and/or serum cryptococcal antigen titer increases.427

Other experts state consider discontinuing secondary prophylaxis against cryptococcosis in HIV-infected adults and adolescents who are asymptomatic for cryptococcosis, are receiving antiretroviral therapy, and have had CD4+ T-cell counts ≥200/mm3 for ≥6 months.440 These experts state reinitiate secondary prophylaxis against cryptococcosis in HIV-infected adults, adolescents, or children if CD4+ T-cell count decreases to <200/mm3.440 441 Some experts recommend that a lumbar puncture be performed to determine whether the CSF is culture negative and antigen negative before discontinuing secondary prophylaxis, even in asymptomatic individuals.440

Histoplasmosis
Treatment of Histoplasmosis
Oral or IV

400–800 mg once daily.315 316 428 436 Alternatively, 800 mg daily has been given for 12 weeks for induction therapy, followed by 400 mg daily.428

Sporotrichosis
Lymphocutaneous and Cutaneous Sporotrichosis
Oral

400–800 mg once daily.429 436 Use only when other drugs cannot be used.429

Dermatophytoses
Tinea Corporis, Tinea Cruris, or Tinea Pedis
Oral

150 mg once weekly for 2–6 weeks has been effective.373 374 378

Tinea pedis: Some clinicians recommend 150 mg once weekly for 1–4 weeks.436

Onychomycosis
Oral

100–450 mg once weekly for 3–12 months has been used.140 176 417 420 421 455 479 Some clinicians recommend 150–300 mg once weekly for 3–6 months for fingernail infections or for 6–12 months for toenail infections.436 Efficacy may be low, even with the higher dosages.479

Pityriasis (Tinea) Versicolor
Oral

A single 400-mg dose has been used.146 461 462 Alternatively, 150 mg has been given once weekly for 2 or 4 weeks460 462 or 300 mg has been given once weekly for 2 weeks.459

Prevention of Fungal Infections in Transplant Recipients, Cancer Patients, or Other Patients at High Risk
Bone Marrow Transplant (BMT) Recipients
Oral or IV

400 mg once daily.1 157 340

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/mm3.1

Hematologic Stem Cell Transplant (HSCT) Recipients
Oral or IV

400 mg (6 mg/kg) once daily.422 425 452

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/mm3.422 452

Solid Organ Transplant Recipients
Oral or IV

Postoperative prophylaxis in liver, pancreas, or small bowel transplant recipients: 200–400 mg (3–6 mg/kg) once daily for at least 7–14 days.425

Patients with Chemotherapy-induced Neutropenia
Oral or IV

400 mg (6 mg/kg) once daily.425

Initiate during induction chemotherapy and continue for the duration of neutropenia.425

High-risk Patients Undergoing Urologic Procedures
Oral or IV

200–400 mg (3–6 mg/kg) daily for several days before and after the procedure.425

High-risk Patients in Intensive Care Units (ICUs)
Oral or IV

High-risk patients in ICUs with known high incidence of invasive candidiasis: 400 mg (6 mg/kg) once daily.425

Empiric Therapy in Febrile Neutropenic Patients
Oral or IV

Initial dose of 400 mg, then 5 mg/kg daily (up to 400 mg daily) has been used until neutropenia resolved.453

If no fungal infection occurs, discontinue when neutropenia resolves.422 In those with prolonged neutropenia, IDSA suggests that empiric antifungal therapy may be discontinued after 2 weeks if patient is clinically well and no discernible lesions are found by clinical evaluation, chest radiographs, or abdominal CT scans.422 If patient appears ill or is at high risk, consider continuing empiric antifungal treatment throughout the neutropenic episode.422

Prescribing Limits

Pediatric Patients

Treatment of Fungal Infections
Oral or IV

Maximum of 600 mg daily.1

Special Populations

Renal Impairment

Treatment of Fungal Infections
Oral or IV

Dosage must be modified in response to the degree of impairment and should be based on the patient’s measured or estimated Clcr.1 124

Manufacturer recommends that adults with impaired renal function receive an initial loading dose of 50–400 mg (based on the type of infection being treated), then patients with Clcr >50 mL/minute should receive 100% of the usual daily dose and those with Clcr ≤50 mL/minute should receive 50% of the usual daily dose.1

Patients who are undergoing regular dialysis should receive 100% of the usual daily dose after each dialysis period.1

These dosage recommendations are based on pharmacokinetics following multiple doses; further dosage adjustments may be necessary depending on patient condition.1

Modification of the single-dose regimen of oral fluconazole for treatment of vulvovaginal candidiasis is unnecessary in impaired renal function.1

Pharmacokinetics not studied in children with impaired renal function; recommendations for dosage reduction in such children should parallel those recommended for adults.1

Geriatric Patients

Adjust dosage based on Clcr.1 (See Renal Impairment under Dosage.)

Cautions for Fluconazole

Contraindications

  • Hypersensitivity to fluconazole or any ingredient in the formulation.1

  • Concomitant use with drugs that are known to prolong the QT interval and are metabolized by CYP3A4 (e.g., astemizole, cisapride, pimozide, quinidine).1 (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.1 124 216 253 254 255 256 257 A clear relationship between these hepatic effects and daily dosage, duration of therapy, gender, or age has not been demonstrated.1

While hepatotoxicity usually has been reversible, fatalities have occurred,1 124 216 254 255 256 257 principally in patients with serious underlying disease (e.g., AIDS, malignancy) who were receiving other drugs concomitantly.1 124 216 253 254 255 256 257

Mild, transient increases (1.5–3 times ULN) in serum concentrations of AST,19 28 39 64 68 94 ALT,19 28 39 62 64 68 94 96 alkaline phosphatase,28 37 44 64 68 γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGTP),37 64 68 and bilirubin19 68 have been reported.15 19 28 32 37 39 44 65 68 94 149

In most reported cases, concentrations returned to pretreatment levels either during or after fluconazole therapy and were not associated with hepatotoxicity.15 68 94 However, higher increases in serum transaminase concentrations (≥8 times the ULN), which required discontinuance of the drug, also have occurred.1 28 32 65 68

If abnormal liver function test results occur, monitor patient for the development of more severe hepatic injury.1

If signs and symptoms consistent with liver disease develop, discontinue fluconazole.1

Dermatologic Reactions

Rash1 28 32 62 64 65 94 142 (including diffuse rash accompanied by eosinophilia)94 and pruritus28 62 163 have been reported.1 94

Exfoliative skin disorders have been reported rarely in patients with serious underlying disease (principally AIDS or malignancy);1 124 142 fatalities have been reported.1

Stevens-Johnson syndrome,1 93 150 which can be fatal,1 also has been reported.

If rash develops, monitor closely; discontinue fluconazole if lesions progress.1 124

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.1 258 492 493 494 495 (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.1 492

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis (including angioedema, face edema, and pruritus) has been reported rarely.1 163 Angioedema and anaphylactic reactions have been reported rarely in women who received a single oral dose for treatment of vulvovaginal candidiasis.1

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.1

General Precautions

Cardiovascular Effects

Prolonged QT interval reported with some azoles, including fluconazole.1 448 Torsades de pointes reported rarely.1 448

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).1 448

Use with caution in patients with potentially proarrhythmic conditions and risk factors for QT prolongation.1 448

Selection and Use of Antifungals

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.1

Superinfection with nonsusceptible fungi (e.g., C. krusei) may occur;1 alternative antifungal therapy may be required.1

CNS Effects

Dizziness or seizures may occur occasionally and should be considered in patients who drive or operate machines.1

Fructose or Galactose Intolerance

Diflucan powder for oral suspension contains sucrose; do not use in patients with hereditary fructose, glucose-galactose malabsorption, and sucrase-isomaltase deficiency.1

Diflucan capsules (not commercially available in the US) contain lactose; do not use in patients with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.1

Glycerol Content

Diflucan syrup (not commercially available in the US) contains glycerol, which may cause headache, stomach upset, and diarrhea.1

Specific Populations

Pregnancy

Category C when used as a single 150-mg oral dose for treatment of vulvovaginal candidiasis.1 CDC recommends use of topical (intravaginal) azoles (not oral fluconazole) for treatment of vulvovaginal candidiasis during pregnancy.443

Category D when used for all other indications (e.g., treatment of oropharyngeal or esophageal candidiasis, cryptococcal meningitis, prevention of Candida infections).1 IDSA states avoid use of fluconazole for treatment of serious fungal infections (e.g., blastomycosis, candidiasis, histoplasmosis, coccidioidomycosis, cryptococcosis) during pregnancy.424 425 426 427 428

If used during pregnancy or if patient becomes pregnant while receiving fluconazole, inform patient of potential hazard to the fetus.1 (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Distributed into milk at concentrations similar to those achieved in plasma.1 261 Use with caution in nursing women.1

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).1 391 392 394 408 409 410

Adverse effects in children generally have been similar to those in adults.1 393 395

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.1 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.1

Insufficient experience in controlled clinical studies in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 Other clinical experience has not revealed age-related differences in response.1

Substantially eliminated by kidneys; assess renal function periodically since geriatric patients more likely to have decreased renal function.1 Adjust dosage based on Clcr.1 (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Use with caution.1

Renal Impairment

Plasma concentrations are higher and half-life prolonged.1 37 57 67 105 Use with caution;1 dosage adjustments required based on degree of renal impairment.1 124 (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.1 19 28 32 39 62 64 65 68 94 95 96

Interactions for Fluconazole

Drugs Metabolized by Hepatic Microsomal Enzymes

Fluconazole is a potent inhibitor of CYP2C9 and a moderate inhibitor of CYP3A4.1 Because fluconazole has a long half-life, the enzyme-inhibiting effects of the drug persist for 4–5 days following discontinuance.1 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.1

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.1

Specific Drugs

Drug

Interaction

Comments

Amphotericin B

In vitro evidence of antagonism against Candida or Aspergillus fumigatus231 232

Use concomitantly with caution and close monitoring,1 232 235 236 especially in immunocompromised patients232 235 236

Antacids (aluminum- or magnesium-containing)

No clinically important effect on fluconazole pharmacokinetics1 61 249

Anticoagulants, oral (warfarin)

Possible increased PT;1 48 61 91 251 bleeding events (bruising, epistaxis, GI bleeding, hematuria, melena) reported1

Monitor PT or other appropriate tests closely if used with warfarin; reduce anticoagulant dosage if necessary1 61 62 68 91 251

Anticonvulsants (carbamazepine, phenytoin)

Carbamazepine: Increased carbamazepine concentrations and increased risk of toxicity1 370

Phenytoin: Increased phenytoin concentrations and AUC and increased risk of toxicity;1 25 61 124 141 fluconazole pharmacokinetics not affected141

Carbamazepine: Use concomitantly with caution and close monitoring;1 carbamazepine dosage based on carbamazepine concentrations and clinical effect may be necessary1

Phenytoin: Use concomitantly with caution and close monitoring;1 carefully monitor phenytoin concentrations;1 61 141 adjust phenytoin dosage as needed whenever fluconazole is initiated or discontinued61 91 141

Antidepressants, tricyclics (amitriptyline, nortriptyline)

Possible increased tricyclic antidepressant concentrations and increased risk of CNS toxicity1 367

Use concomitantly with caution and close monitoring;1 consider monitoring S-amitriptyline and/or 5-nortriptyline concentrations when concomitant therapy is initiated and after 1 week of concomitant therapy;1 adjust antidepressant dosage if needed1

Antidiabetic agents, sulfonylureas (glipizide, glyburide, tolbutamide)

Increased plasma concentrations and AUCs of the antidiabetic agent; symptoms of hypoglycemia reported1 61 91

Monitor blood glucose and observe patient for signs and symptoms of hypoglycemia; adjust dosage of antidiabetic agent as necessary1 61 91

Antihistamines (astemizole, terfenadine)

Possible pharmacokinetic interaction and potential for serious or life-threatening reactions (e.g., cardiac arrhythmias, prolonged QT interval)164 165 166 167 168 169 171 172 174 175 347

Concomitant administration of terfenadine and fluconazole (≥400) is contraindicated; monitor closely if lower fluconazole dosages used1

Antimycobacterial agents (rifabutin, rifampin)

Rifabutin: Substantially increased rifabutin concentrations and AUC;241 possible increased risk of adverse effects (e.g., uveitis)241 242 243

Rifampin: Increased rifampin concentrations;1 91 244 decreased fluconazole AUC and possible decreased fluconazole efficacy1 91 244 245

Rifabutin: Use concomitantly with caution and close monitoring1

Rifampin: Use concomitantly with caution and close monitoring;1 consider increasing fluconazole dosage1

Antiretrovirals, HIV protease inhibitors (PIs)

Atazanavir (with low-dose ritonavir): No clinically important effects on pharmacokinetics of atazanavir or fluconazole200 446

Indinavir: No clinically important effects on pharmacokinetics of indinavir or fluconazole368

Lopinavir/ritonavir: Clinically important interactions not expected433

Ritonavir: No clinically important effects on ritonavir pharmacokinetics;432 minor increase in ritonavir concentrations and AUC248 432

Saquinavir: Increased saquinavir concentrations and AUC;1 200 481 data not available regarding ritonavir-boosted saquinavir200

Ritonavir-boosted tipranavir: Increased tipranavir peak plasma concentrations and AUC;200 445 no change in fluconazole pharmacokinetics445

Indinavir: Dosage adjustment not needed368

Ritonavir: Dosage adjustment not needed432

Saquinavir: Use concomitantly with caution and close monitoring;1 saquinavir dosage adjustment may be necessary1

Ritonavir-boosted tipranavir: Dosage adjustments not needed;445 fluconazole dosage >200 mg daily not recommended;200 445 if high-dose fluconazole is indicated, consider alternative antiretroviral200

Antiretrovirals, nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Delavirdine: No clinically important effects on delavirdine or fluconazole pharmacokinetics389 434

Efavirenz: No clinically important effects on efavirenz or fluconazole pharmacokinetics200 371

Etravirine: Substantially increased etravirine concentrations and AUC;200 447 no change in fluconazole concentrations447

Nevirapine: Increased nevirapine concentrations;200 435 no effect on fluconazole concentrations;435 possible increased risk of hepatotoxicity200

Rilpivirine: Possible increased rilpivirine concentrations226

Delavirdine: Dosage adjustments not needed389

Efavirenz: Dosage adjustments not needed371

Etravirine: Dosage adjustments not needed for either drug;200 447 use caution because of limited safety data regarding increased etravirine concentrations447

Nevirapine: Use concomitantly with caution;435 monitor closely for nevirapine-associated adverse effects200 435 or use alternative antiretroviral200

Rilpivirine: Dosage adjustments of rilpivirine not needed;226 monitor for breakthrough fungal infections226

Antiretrovirals, nucleoside reverse transcriptase inhibitors (NRTIs)

Didanosine: No clinically important effects on didanosine or fluconazole pharmacokinetics218

Stavudine: Pharmacokinetic interactions unlikely438

Zidovudine: Increased zidovudine concentrations and AUC1 217

Zidovudine: Use concomitantly with caution and close monitoring;1 217 monitor for zidovudine-associated adverse effects;1 217 consider reducing zidovudine dosage1

Benzodiazepines (midazolam, triazolam)

Midazolam: Increased midazolam peak plasma concentrations and AUC and possible prolonged sedative effects reported with oral or IV fluconazole;1 369 482 483 no effect on fluconazole concentrations or AUC482

Triazolam: Increased peak plasma triazolam concentrations and AUC; prolonged triazolam half-life1

Short-acting benzodiazepines metabolized by CYP: Use concomitantly with caution and close monitoring1 ; monitor for manifestations of benzodiazepine toxicity;1 consider decreasing benzodiazepine dosage as needed1 369

Calcium-channel blocking agents (amlodipine, felodipine, isradipine, nifedipine)

Possible increased systemic exposure to calcium-channel blocking agents metabolized by CYP3A41

Use concomitantly with caution and close monitoring;1 monitor frequently for adverse events1

Cisapride

Increased cisapride concentrations and increased risk of adverse effects (e.g., cardiac effects);1 prolonged QT interval and torsades de pointes reported1

Concomitant use contraindicated1

Corticosteroids

Prednisone: Acute adrenal cortex insufficiency reported when 3-month fluconazole regimen was discontinued in liver transplant patient receiving prednisone1

Prednisone: Use concomitantly with caution and close monitoring;1 if used concomitantly for prolonged periods of time, carefully monitor for adrenal cortex insufficiency when fluconazole is discontinued1

Cyclophosphamide

Increased serum bilirubin and serum creatinine1

Use concomitantly with caution and close monitoring;1 consider the risks of increased serum bilirubin and serum creatinine1

Diuretics, thiazides

Increased fluconazole concentrations and AUC1 124

Use concomitantly with caution and close monitoring;1 fluconazole dosage adjustment probably not necessary1

Estrogens/progestins

Possible increased AUCs of ethinyl estradiol, levonorgestrel, and norethindrone1 18 61 68 439

Fluconazole dosage of 50–200 mg daily unlikely to interfere with oral contraceptive efficacy1 439

Flucytosine

In vitro evidence of synergistic, additive, or indifferent antifungal effects against C. neoformans; no evidence of antagonism239

Histamine H2-receptor antagonists (cimetidine)

Decreased fluconazole concentrations and AUC1 61 68 91

Not considered clinically important61 68 91

HMG-CoA reductase inhibitors (statins)

Increased risk of myopathy and rhabdomyolysis when used concomitantly with statins metabolized by CYP3A4 (atorvastatin, simvastatin) or 2C9 (fluvastatin)1

Fluvastatin: Prolonged fluvastatin half-life and increased fluvastatin AUC and peak plasma concentrations486

Pravastatin: No clinically important effects on pravastatin pharmacokinetics486

If concomitant therapy necessary, monitor CK and monitor for symptoms of myopathy and rhabdomyolysis;1 if substantial increase in CK occurs or myopathy/rhabdomyolysis is diagnosed or suspected, discontinue statin1

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Cyclosporine: Increased cyclosporine concentrations and AUC,1 22 23 24 61 68 91 especially in renal transplant recipients22 23 24 68

Tacrolimus: Increased serum tacrolimus concentrations with oral tacrolimus;1 clinically important interaction not observed with IV tacrolimus;1 increased tacrolimus concentrations have been associated with nephrotoxicity1

Sirolimus: Increased sirolimus concentrations1

Cyclosporine: Use concomitantly with caution and close monitoring;1 closely monitor cyclosporine concentrations and serum creatinine;1 22 23 adjust dosage accordingly22 23

Tacrolimus: Use concomitantly with caution and close monitoring;1 decrease tacrolimus dosage based on tacrolimus concentrations1

Sirolimus: Use concomitantly with caution and close monitoring;1 adjust sirolimus dosage based on sirolimus concentrations and clinical effects1

Losartan

Decreased AUC and peak plasma concentrations of the active losartan metabolite1 487

Use concomitantly with caution and close monitoring;1 consider possibility of decreased losartan therapeutic effect;487 closely monitor BP1

Macrolides

Azithromycin: No clinically important pharmacokinetic interactions1

Erythromycin: Possible increased risk of prolonged QT interval, torsades de pointes, and subsequent sudden cardiac death1

Erythromycin: Avoid concomitant use1

Nonsteroidal anti-inflammatory agents (NSAIAs)

Celecoxib: Increased celecoxib AUC and peak plasma concentrations1

Flurbiprofen: Increased flurbiprofen AUC and peak plasma concentrations1

Ibuprofen: Increased AUC and peak plasma concentrations of pharmacologically active S-isomer of ibuprofen1 484

Other NSAIAs metabolized by CYP2C9 (e.g., diclofenac, meloxicam, naproxen): Possible increased NSAIA exposure1

Celecoxib: Use concomitantly with caution and close monitoring;1 reduction of celecoxib dosage by 50% may be necessary1

Other NSAIAs metabolized by CYP2C9: Use concomitantly with caution and close monitoring;1 frequently monitor for NSAIA-associated adverse events;1 NSAIA dosage adjustment may be necessary484

Opiate agonists (alfentanil, fentanyl, methadone)

Alfentanil: Reduced alfentanil clearance and volume of distribution and prolonged alfentanil half-life1 485

Fentanyl: Substantially delayed elimination of fentanyl;1 490 elevated fentanyl concentrations may lead to respiratory depression;1 fatality possibly related to fentanyl intoxication reported in patient receiving fentanyl and fluconazole1 489

Methadone: Increased methadone concentrations and AUC488

Alfentanil: Use concomitantly with caution and close monitoring; alfentanil dosage adjustment may be necessary1

Fentanyl: Use concomitantly with caution and close monitoring1

Methadone: Use concomitantly with caution and close monitoring; methadone dosage adjustment may be necessary1

Pimozide

Possible increased pimozide concentrations; potential for QT interval prolongation1

Concomitant use contraindicated1

Theophylline

Increased theophylline concentrations and AUC1

Use concomitantly with caution and close monitoring; carefully monitor theophylline concentrations1

Tretinoin

Pseudotumor cerebri reported in patient receiving tretinoin (all-trans-retinoic acid) and fluconazole; CNS effects resolved when fluconazole discontinued1

Use concomitantly with caution and close monitoring; consider possibility of adverse CNS effects1

Vinca alkaloids (vinblastine, vincristine)

Possible increased vinca alkaloid concentrations with possible neurotoxicity1

Use concomitantly with caution and close monitoring1

Voriconazole

Increased voriconazole peak plasma concentrations and AUC;1 dosage adjustments of voriconazole or fluconazole do not overcome this pharmacokinetic interaction1

Avoid concomitant use; if voriconazole used sequentially after fluconazole, monitor patient closely for voriconazole-associated adverse events, particularly during first 24 hours after last fluconazole dose1

Fluconazole Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics are similar following IV or oral administration.1 61 105

Rapidly and almost completely absorbed from GI tract;1 2 51 61 67 68 peak plasma concentrations attained within 1–2 hours.1 68 99 105

Oral bioavailability ≥90% in healthy, fasting adults.1 61 68 105 124 131

Oral bioavailability in HIV-infected adults appears to be similar to that reported for healthy adults.219 223

Unlike some imidazoles (e.g., ketoconazole), GI absorption of fluconazole does not appear to be affected by gastric pH.1 16 61 68 91 124 249 250

Oral suspensions are bioequivalent to tablets.1

Food

Administration with a high-fat meal does not affect fluconazole peak plasma concentrations or AUC compared with administration in the fasting state.1

Distribution

Extent

Widely distributed into body tissues and fluids following oral or IV administration.1 61 62 64 76 102 103 105

Concentrations attained in urine and skin may be 10 times higher than concurrent plasma concentrations.1 105

Concentrations attained in saliva,1 61 105 sputum,1 13 61 105 nails,1 blister fluid,1 105 blister skin,1 105 and vaginal tissue1 are approximately equal to concurrent plasma concentrations.1 13 61 99 105

Unlike some azoles (e.g., itraconazole, ketoconazole), fluconazole readily distributes into CSF following oral or IV administration;1 2 3 14 15 29 30 36 54 61 62 102 105 CSF concentrations may be 50–94% of concurrent plasma concentrations, regardless of the degree of meningeal inflammation.1 2 3 14 15 29 30 54 61 62 67 102 105

Crosses the placenta in rats; not known whether crosses the placenta in humans.117

Distributed into human milk in concentrations similar to those attained in plasma.1 261

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.1 2 3 12 51 62 67 78 84 105 124

Elimination

Elimination Route

Eliminated principally by renal excretion.1 2

Approximately 60–80% of a single oral or IV dose excreted in urine unchanged;1 2 3 12 51 61 68 105 117 about 11% is excreted in urine as metabolites.1 51 61 105

Small amounts excreted in feces.68

Removed by hemodialysis.1 37

Removed by peritoneal dialysis.47

Half-life

Adults with normal renal function: Approximately 30 hours (range: 20–50 hours).1 2 3 12 13 14 61 62 67 68 78 105

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.1

Neonates: Decreases over time, averaging 88 hours after the first dose and 55 hours after the fifth dose (day 13).259

Special Populations

Elimination half-life not affected by impaired hepatic function.117

In impaired renal function, plasma concentrations are higher and half-life prolonged;1 37 57 67 105 elimination half-life is inversely proportional to Clcr.1

Renal clearance may be lower in geriatric patients than in younger adults,1 124 apparently because of decreased kidney function in this age group.1

Stability

Storage

Oral

Tablets

<30°C.1

For Suspension

<30°C.1

Following reconstitution, store between 5–30°C;1 protect from freezing.1 Discard unused oral suspension 2 weeks after reconstitution.1

Parenteral

Injection for IV Infusion

Glass bottles: 5–30°C;1 protect from freezing.1

Viaflex plastic containers: 5–25°C (may be exposed to temperatures up to 40°C); protect from freezing.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Ringer’s injection, lactated

Drug Compatibility
Admixture CompatibilityHID

Compatible

Acyclovir sodium

Amikacin sulfate

Amphotericin B

Cefazolin sodium

Ceftazidime

Ciprofloxacin

Clindamycin phosphate

Gentamicin sulfate

Heparin sodium

Meropenem

Metronidazole

Morphine sulfate

Potassium chloride

Ranitidine HCl with ondansetron HCl

Theophylline

Incompatible

Co-trimoxazole

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Aldesleukin

Allopurinol sodium

Amifostine

Amikacin sulfate

Aminophylline

Amiodarone HCl

Ampicillin sodium–sulbactam sodium

Anidulafungin

Aztreonam

Benztropine mesylate

Bivalirudin

Caspofungin acetate

Cefazolin sodium

Cefepime HCl

Cefotetan disodium

Cefoxitin sodium

Ceftaroline fosamil

Chlorpromazine HCl

Cisatracurium besylate

Daptomycin

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Diltiazem HCl

Dimenhydrinate

Diphenhydramine HCl

Dobutamine HCl

Docetaxel

Dopamine HCl

Doripenem

Doxorubicin HCl liposome injection

Droperidol

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Filgrastim

Fludarabine phosphate

Foscarnet sodium

Gallium nitrate

Ganciclovir sodium

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Immune globulin intravenous

Leucovorin calcium

Linezolid

Lorazepam

Melphalan HCl

Meperidine HCl

Meropenem

Metoclopramide HCl

Metronidazole

Midazolam HCl

Morphine sulfate

Nafcillin sodium

Nitroglycerin

Ondansetron HCl

Oxacillin sodium

Paclitaxel

Pancuronium bromide

Pemetrexed disodium

Penicillin G potassium

Phenytoin sodium

Piperacillin sodium–tazobactam sodium

Prochlorperazine edisylate

Promethazine HCl

Propofol

Quinupristin-dalfopristin

Ranitidine HCl

Remifentanil HCl

Sargramostim

Tacrolimus

Telavancin HCl

Teniposide

Theophylline

Thiotepa

Ticarcillin disodium–clavulanate potassium

Tigecycline

Tobramycin sulfate

Vancomycin HCl

Vasopressin

Vecuronium bromide

Vinorelbine tartrate

Zidovudine

Incompatible

Amphotericin B

Amphotericin B cholesteryl sulfate complex

Ampicillin sodium

Calcium gluconate

Cefotaxime sodium

Ceftriaxone sodium

Cefuroxime sodium

Chloramphenicol sodium succinate

Clindamycin phosphate

Co-trimoxazole

Diazepam

Digoxin

Furosemide

Haloperidol lactate

Hydroxyzine HCl

Imipenem–cilastatin sodium

Pentamidine isethionate

Variable

Ceftazidime

Actions and Spectrum

  • Triazole-derivative azole antifungal.2 3 5 28 51 61 67 68 76 78 84 124

  • Usually fungistatic in action.1 51 75 268

  • 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).2 51 61 76 79 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.1 2 3 51 61 76 79 84

  • Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes.1 3 51 78 87 88 Inactive against bacteria.117

  • Candida: Active in vitro and in vivo against C. albicans,1 5 49 51 89 102 359 360 363 365 C. dubliniensis,1 390 C. guilliermondii,1 365 C. kefyr,1 C. parapsilosis,1 359 362 363 365 C. lusitaniae,1 386 and C. tropicalis.1 103 359 362 363 C. krusei are intrinsically resistant to fluconazole and many strains of C. glabrata also are resistant or have reduced susceptibility to the drug.1 267 275 343 346 359 360 362 363 365

  • Other fungi: Active against Blastomyces dermatitidis,358 Coccidioides immitis,1 467 C. posadasii,467 468 Cryptococcus neoformans,1 7 30 51 55 102 107 359 and Histoplasma capsulatum.8 9 51 100 May be active in vitro against some strains of C. gattii,449 450 but there is in vitro evidence that fluconazole may be less active against C. gattii than some other azoles (e.g., itraconazole, posaconazole, voriconazole).449

  • Fluconazole generally is inactive against Aspergillus in vitro.51 101 Inactive against Malassezia pachydermatis11 and Scopulariopsis, including S. acremonium and S. brevicaulis.366 Although a few strains of Penicillium marneffei may be inhibited in vitro by fluconazole concentrations,469 470 most strains tested are resistant to the drug.470

  • Candida and C. neoformans with decreased in susceptibility to fluconazole have been reported.265 266 267 272 273 275 282 343 346 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.265 266 267 269 271 276 278 284 285

  • Fluconazole-resistant fungi also may be cross-resistant to other azole antifungals (e.g., itraconazole, ketoconazole, posaconazole, voriconazole).5 6 67 87 102 103 104 178 269 275 277 278 279 346

Advice to Patients

  • Importance of completing full course of therapy.1 An inadequate period of treatment may lead to recurrence of active infection.1

  • When driving or operating machinery, patients receiving fluconazole should take into account that dizziness or seizures may occur occasionally.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

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

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

Fluconazole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For suspension

50 mg/5 mL*

Diflucan

Pfizer

Fluconazole for Oral Suspension

200 mg/5 mL

Diflucan

Pfizer

Fluconazole for Oral Suspension

Tablets

50 mg*

Diflucan

Pfizer

Fluconazole Tablets

100 mg*

Diflucan

Pfizer

Fluconazole Tablets

150 mg*

Diflucan

Pfizer

Fluconazole Tablets

200 mg*

Diflucan

Pfizer

Fluconazole Tablets

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

Fluconazole in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion only

2 mg/mL (200 or 400 mg) in 5.6% Dextrose*

Diflucan in Iso-osmotic Dextrose Injection (in Viaflex Plus [Baxter])

Pfizer

Fluconazole in Iso-osmotic Dextrose Injection

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

Fluconazole in Sodium Chloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion only

2 mg/mL (200 or 400 mg) in 0.9% Sodium Chloride*

Diflucan in Iso-osmotic Sodium Chloride Injection (in glass and Viaflex Plus [Baxter])

Pfizer

Fluconazole in Iso-osmotic Sodium Chloride Injection

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Diflucan 10MG/ML Suspension (PFIZER U.S.): 35/$59.99 or 105/$176.38

Diflucan 100MG Tablets (PFIZER U.S.): 30/$433.98 or 60/$856.95

Diflucan 150MG Tablets (PFIZER U.S.): 1/$33.59 or 3/$76.62

Diflucan 200MG Tablets (PFIZER U.S.): 4/$98.69 or 20/$456.70

Diflucan 40MG/ML Suspension (PFIZER U.S.): 35/$190.99 or 105/$565.95

Diflucan 50MG Tablets (PFIZER U.S.): 15/$136.49 or 45/$367.49

Fluconazole 10MG/ML Suspension (ROXANE): 35/$27.99 or 105/$69.97

Fluconazole 100MG Tablets (IVAX PHARMACEUTICALS): 15/$54.99 or 45/$157.96

Fluconazole 150MG Tablets (IVAX PHARMACEUTICALS): 12/$49.99 or 24/$75.97

Fluconazole 200MG Tablets (IVAX PHARMACEUTICALS): 4/$39.99 or 20/$165.97

Fluconazole 40MG/ML Suspension (GREENSTONE): 35/$109.98 or 105/$295.92

Fluconazole 50MG Tablets (IVAX PHARMACEUTICALS): 15/$49.99 or 45/$139.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 9, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Pfizer. Diflucan (fluconazole) tablets, injection - for intravenous infusion only, and oral suspension prescribing information. New York, NY; 2011 May.

2. Saag MS, Dismukes WE. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother. 1988; 32:1-8. [IDIS 243869] [PubMed 2831809]

3. Dismukes WE. Azole antifungal drugs: old and new. Ann Intern Med. 1988; 109:177-9. [IDIS 244739] [PubMed 2839058]

4. Aberg JA, Price RW, Heeren DM et al. A pilot study of the discontinuation of antifungal therapy for disseminated cryptococcal disease in patients with acquired immunodeficiency syndrome, following immunologic response to antiretroviral therapy. J Infect Dis. 2002; 185:1179-82. [IDIS 479822] [PubMed 11930330]

5. Rogers TE, Galgiani JN. Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo. Antimicrob Agents Chemother. 1986; 30:418-22. [PubMed 3022641]

6. Warnock DW, Burcke J, Cope NJ et al. Fluconazole resistance in Candida glabrata. Lancet. 1988; 2:1310. [IDIS 248387] [PubMed 2904031]

7. de Fernandez EP, Patino MM, Graybill JR et al. Treatment of cryptococcal meningitis in mice with fluconazole. J Antimicrob Chemother. 1986; 18:261-70. [PubMed 3019986]

8. Graybill JR, Palou E, Ahrens J. Treatment of murine histoplasmosis with UK 49,858 (fluconazole). Am Rev Respir Dis. 1986; 134:768-70. [PubMed 3021035]

9. Kobayashi GS, Travis S, Medoff G. Comparison of the in vitro and in vivo activity of the bis-triazole derivative UK 49,858 with that of amphotericin B against Histoplasma capsulatum. Antimicrob Agents Chemother. 1986; 29:660-2. [IDIS 215027] [PubMed 3010852]

10. Odds FC, Cheesman SL, Abbott AB. Suppression of ATP in Candida albicans by imidazole and derivative antifungal agents. J Med Vet Med. 1985; 23:415-24.

11. Mickelsen PA, Viano-Paulson MC, Stevens DA et al. Clinical and microbiological features of infection with Malassezia pachydermatis in high-risk infants. J Infect Dis. 1988; 157:1163-8. [IDIS 244275] [PubMed 3373021]

12. Humphrey MJ, Jevons S, Tarbit MH. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother. 1985; 28:648-53. [IDIS 208216] [PubMed 3004323]

13. Ebden P, Neill P, Farrow PR. Sputum levels of fluconazole in humans. Antimicrob Agents Chemother. 1989; 33:963-4. [IDIS 255728] [PubMed 2548443]

14. Foulds G, Brennan DR, Wajszczuk C et al. Fluconazole penetration into cerebrospinal fluid in humans. J Clin Pharmacol. 1988; 28:363-6. [IDIS 241029] [PubMed 2839557]

15. Tucker RM, Williams PL, Arathoon EG et al. Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. Antimicrob Agents Chemother. 1988; 32:369-73. [IDIS 263640] [PubMed 2835002]

16. Drew RH, Perfect JR, Gallis HA. Use of fluconazole in a patient with documented malabsorption of ketoconazole. Clin Pharm. 1988; 7:622-3. [IDIS 244560] [PubMed 2844468]

17. Hanger DP, Jevons S, Shaw JTB. Fluconazole and testosterone: in vivo and in vitro studies. Antimicrob Agents Chemother. 1988; 32:646-8. [IDIS 242907] [PubMed 2840013]

18. Devenport MH, Crook D, Wynn V et al. Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives. Br J Clin Pharmacol. 1989; 27:851-9. [IDIS 257536] [PubMed 2547410]

19. Holmes J, Clements D. Jaundice in HIV positive haemophiliac. Lancet. 1989; 1:1027. [IDIS 254713] [PubMed 2565508]

20. Purba HS, Back DJ. Effect of fluconazole (UK-49,858) on antipyrine metabolism. Br J Clin Pharmacol. 1986; 21:603P.

21. Ehninger G, Jaschonek K, Schuler U et al. Interaction of fluconazole with cyclosporin. Lancet. 1989; 2:104-5. [IDIS 257180] [PubMed 2567846]

22. Sugar AM, Saunders C, Idelson BA et al. Interaction of fluconazole and cyclosporine. Ann Intern Med. 1989; 110:844. [IDIS 254579] [PubMed 2540690]

23. Collignon P, Hurley B. Interaction between fluconazole and cyclosporin. Lancet. 1989; 2:867-8. [IDIS 259605] [PubMed 2571795]

24. Collignon P, Hurley B, Mitchell D. Interaction of fluconazole with cyclosporin. Lancet. 1989; 1:1262. [IDIS 255579] [PubMed 2566800]

25. Mitchell AS, Holland JT. Fluconazole and phenytoin: a predictable interaction. BMJ. 1989; 298:1315. [IDIS 254589] [PubMed 2544241]

26. Kidd D, Ranaghan EA, Morris TCM. Hypokalaemia in patients with acute myeloid leukaemia after treatment with fluconazole. Lancet. 1989; 1:1017.

27. Anon. Cryptococcosis and AIDS. Lancet. 1988; 1:1434-6. [PubMed 2898587]

28. Sugar AM, Saunders C. Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome. Am J Med. 1988; 85:481-9. [IDIS 247330] [PubMed 2845779]

29. Dupont B, Drouhet E. Cryptococcal meningitis and fluconazole. Ann Intern Med. 1987; 106:778. [IDIS 229441] [PubMed 3032037]

30. Byrne WR, Wajszczuk CP. Cryptococcal meningitis in the acquired immunodeficiency syndrome (AIDS): successful treatment with fluconazole after failure of amphotericin B. Ann Intern Med. 1988; 108:384-5. [IDIS 239620] [PubMed 2829678]

31. Esposito R, Foppa CU, Antinori S. Fluconazole for cryptococcal meningitis. Ann Intern Med. 1989; 110:170. [IDIS 250518] [PubMed 2535777]

32. Stern JJ, Hartman BJ, Sharkey P et al. Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients. Am J Med. 1988; 85: 477-80. [IDIS 247329] [PubMed 2845778]

33. Tozzi V, Bordi E, Galgani S et al. Fluconazole treatment of cryptococcosis in patients with acquired immunodeficiency syndrome. Am J Med. 1989; 87:353. [IDIS 258429] [PubMed 2549790]

34. Larsen RA, Bozzette S, McCutchan A et al. Persistent Cryptococcus neoformans infection of the prostate after successful treatment of meningitis. Ann Intern Med. 1989; 111:125-8. [IDIS 257101] [PubMed 2545124]

35. Glatt AE, Chirgwin K, Landesman SH. Treatment of infections associated with human immunodeficiency virus. N Engl J Med. 1988; 318:1439-48. [IDIS 241931] [PubMed 3285211]

36. Denning DW, Stevens DA. New drugs for systemic fungal infections: greater choices means more difficult clinical decisions. BMJ. 1989; 299:407-8. [IDIS 258168] [PubMed 2506994]

37. Van’t Wout JW, Mattie H, van Furth R. A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections. J Antimicrob Chemother. 1988; 21:665-72. [PubMed 2839447]

38. Kirk AJB, Gould FK, Freeman R et al. Fluconazole and candidosis. Lancet. 1989; 1:339. [IDIS 251084] [PubMed 2563504]

39. De Wit S, Weerts D, Goossens H et al. Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. Lancet. 1989; 1:746-8. [IDIS 253561] [PubMed 2564563]

40. Budtz-Jorgensen E, Holmstrup P, Krogh P. Fluconazole in the treatment of Candida-associated denture stomatitis. Antimicrob Agents Chemother. 1988; 32:1859-63. [IDIS 249133] [PubMed 2854455]

41. Chave JP, Cajot A, Bille J et al. Single-dose therapy for oral candidiasis with fluconazole in HIV-infected adults: a pilot study. J Infect Dis. 1989; 159:806-7. [IDIS 253821] [PubMed 2538523]

42. Anon. Oral candidosis in HIV infection. Lancet. 1989; 2:1491-2. [PubMed 2574773]

43. Hay RJ, Clayton YM. Fluconazole in the management of patients with chronic mucocutaneous candidosis. Br J Dermatol. 1988; 119:683-5. [IDIS 249223] [PubMed 2849978]

44. Hendel L, Svejgaard E, Walsoe I et al. Esophageal candidosis in progressive systemic sclerosis: occurrence, significance, and treatment with fluconazole. Scand J Gastroenterol. 1988; 23:1182-6. [IDIS 251915] [PubMed 2854911]

45. Osinusi BO, Rotowa NA. Fluconazole as single-dose treatment of vulvo-vaginal candidosis. Curr Ther Res. 1988; 32:1014-8.

46. Adetoro OO. Vulvo-vaginal candidosis in african women: efficacy and safety of a single oral dose of fluconazole. Curr Ther Res. 1989; 46:768-73.

47. Levine J, Bernard DB, Idelson BA et al. Fungal peritonitis complicating continuous ambulatory peritoneal dialysis: successful treatment with fluconazole, a new orally active antifungal agent. Br J Med. 1989; 86:825-7.

48. Isalska BJ, Stanbridge TN. Fluconazole in the treatment of candidal prosthetic valve endocarditis. BMJ. 1988; 297:178-9. [IDIS 244287] [PubMed 2841997]

49. Dave J, Hickey MM, Wilkins EGL. Fluconazole in renal candidosis. Lancet. 1989; 1:163-4.

50. Kerridge D. Mode of action of clinically important antifungal drugs. Advanc Microb Physiol. 1986; 27:1-72.

51. Fromtling RA. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev. 1988; 1:187-217. [PubMed 3069196]

52. Conti DJ, Tolkoff-Rubin NE, Baker GP et al. Successful treatment of invasive fungal infection with fluconazole in organ transplant recipients. Transplantation. 1989; 47:692-5.

53. Arndt CA, Walsh TJ, McCully CL et al. Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. J Infect Dis. 1988; 157: 178-80. [PubMed 2826606]

54. Classen DC, Burke JP, Smith CB. Treatment of coccidioidal meningitis with fluconazole. J Infect Dis. 1988; 158:903-4. [IDIS 263622] [PubMed 2844925]

55. Perfect JR, Wright KA, Hobbs MM et al. Treatment of experimental cryptococcal meningitis and disseminated candidiasis with SCH39304. Antimicrob Agents Chemother. 1989; 33:1735-40. [PubMed 2556078]

56. Fisher MA, Shen SH, Haddad J et al. Comparison of in vivo activity of fluconazole with that of amphotericin B against Candida tropicalis, Candida glabrata, and Candida krusei. Antimicrob Agents Chemother. 1989; 33:1443-6. [PubMed 2554797]

57. Shuttleworth D, Philpot CM, Knight AG. Cutaneous cryptococcosis: treatment with oral fluconazole. Br J Dermatol. 1989; 120:683-7. [IDIS 263647] [PubMed 2547419]

58. Restrepo BI, Ahrens J, Graybill JR. Efficacy of SCH39304 in murine cryptococcosis. Antimicrob Agents Chemother. 1989; 33:1242-6. [PubMed 2552903]

59. Fisher MA, Lee PG, Tarry WF. Fluconazole (UK-49,858) treatment of candidiasis in normal and diabetic rats. Antimicrob Agents Chemother. 1989; 33:1042-5. [PubMed 2551214]

60. Troke PF, Andrews RJ, Brammer KW et al. Efficacy of UK-49,858 (fluconazole) against Candida albicans experimental infections in mice. Antimicrob Agents Chemother. 1985; 28:815-8. [PubMed 3002246]

61. Jacobson CE (Roerig, New York, NY): Personal communication; 1989 Feb 28.

62. Mau S, Salamone FR, Muller RJ et al. Trimetrexate, ganciclovir, foscarnet and fluconazole: investigational drugs used in the management of AIDS. Hosp Pharm. 1989; 24:209-15.

63. Viscoli C, Castagnola E, Corsini M et al. Fluconazole therapy in an underweight infant. Eur J Clin Microbiol Infect Dis. 1989; 8:925-6. [PubMed 2556276]

64. Ikemoto H. A clinical study of fluconazole for the treatment of deep mycoses. Diagn Microbiol Infect Dis. 1989; 12:239S-47S. [PubMed 2556241]

65. Jones PD, Marriott D, Speed BR. Efficacy of fluconazole in cryptococcal meningitis. Diagn Microbiol Infect Dis. 1989; 12:235S-8S. [PubMed 2556240]

66. Brammer KW. Treatment of vaginal candidiasis with a single oral dose of fluconazole. Eur J Clin Microbiol Infect Dis. 1988; 7:364-7. [PubMed 2842157]

67. Warnock DW. Itraconazole and fluconazole: new drugs for deep fungal infection. J Antimicrob Chemother. 1989; 24:275-80. [PubMed 2553654]

68. Washton H. Review of fluconazole: a new triazole antifungal agent. Diagn Microbiol Infect Dis. 1989; 12:229S-33S. [PubMed 2556239]

69. Dismukes WE. Cryptococcal meningitis in patients with AIDS. J Infect Dis. 1988; 157:624-8. [IDIS 239669] [PubMed 3279135]

70. Dismukes WE, Cloud G, Gallis HA et al. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med. 1987; 317:334-41. [IDIS 232272] [PubMed 3299095]

71. Zuger A, Louie E, Holzman RS et al. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1986; 104:234-40. [IDIS 213659] [PubMed 3946951]

72. Zuger A, Schuster M, Simberkoff S et al. Maintenance amphotericin B for cryptococcal meningitis in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1988; 109:592-3. [IDIS 246239] [PubMed 3421567]

73. Kovacs JA, Kovacs AA, Polis M et al. Cryptococcosis in the acquired immunodeficiency syndrome. Ann Intern Med. 1985; 103:533-8. [IDIS 205103] [PubMed 3898951]

74. Savani DV, Perfect JR, Cobo M et al. Penetration of new azole compounds into the eye and efficacy in experimental Candida endophthalmitis. Antimicrob Agents Chemother. 1987; 31:6-10. [PubMed 3032091]

75. Roilides E, Walsh TJ, Rubin M et al. Effects of antifungal agents on the function of human neutrophils in vitro. Antimicrob Agents Chemother. 1990; 34: 196-201.

76. Lavrijsen KL, Van Houdt JM, Van Dyck DM et al. Induction potential of fluconazole toward drug-metabolizing enzymes in rats. Antimicrob Agents Chemother. 1990; 34:402-8. [PubMed 2334152]

77. Schulman JA, Peyman G, Fiscella R et al. Toxicity of intravitreal injection of fluconazole in the rabbit. Can J Ophthalmol. 1987; 22:304-6. [PubMed 2827871]

78. Walsh TJ, Pizzo A. Treatment of systemic fungal infections: recent progress and current problems. Eur J Clin Microbiol Infect Dis. 1988; 7:460-75. [PubMed 2846299]

79. Watson PF, Rose ME, Ellis SW et al. Defective sterol C56 desaturation and azole resistance: a new hypothesis for the mode of action of azole antifungals. Biochem Biophys Res Commun. 1989; 164:1170-5. [PubMed 2556119]

80. Odds FC, Abbott AB, Pye G et al. Improved method for estimation of azole antifungal inhibitory concentrations against Candida species, based on azole/antibiotic interactions. J Med Vet Mycol. 1986; 24:305-11. [PubMed 3746584]

81. Kruger HU, Schuler U, Zimmerman R et al. Absence of significant interaction of fluconazole with cyclosporin. J Antimicrob Chemother. 1989; 24:781-6. [PubMed 2557319]

83. Jakab K, Kelemen E, Prinz G et al. Amphotericin-resistant invasive hepatosplenic candidiasis controlled by fluconazole. Lancet. 1990; 1:473-4.

84. Richardson K, Cooper K, Marriott MS et al. Discovery of fluconazole, a novel antifungal agent. Clin Infect Dis. 1990; 12(Suppl 3):S267-1.

85. La Delfa I, Zhu QM, Mo Z et al. Fluconazole is a potent inhibitor of antipyrine metabolism in vivo in mice. Drug Metab Dispos. 1989; 17:49-53. [PubMed 2566469]

86. Back DJ, Tjia JF, Karbwang J et al. In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinolines. Br J Clin Pharmacol. 1988; 26:23-9. [PubMed 3203057]

87. Galgiani JN. Susceptibility of Candida albicans and other yeasts to fluconazole: relation between in vitro and in vivo studies. Clin Infect Dis. 1990; 12(Suppl 3):S272-5.

88. Troke PF, Andrews RJ, Pye GW et al. Fluconazole and other azoles: translation of in vitro activity to in vivo and clinical efficacy. Clin Infect Dis. 1990; 12(Suppl 3):S276-80.

89. Longman LP, Hibbert SA, Martin MV. Efficacy of fluconazole in prophylaxis and treatment of experimental Candida endocarditis. Clin Infect Dis. 1990; 12(Suppl 3):S294-8.

90. Stevens DA, Brummer E, McEwen JG et al. Comparison of fluconazole and ketoconazole in experimental murine blastomycosis. Clin Infect Dis. 1990; 12(Suppl 3):S304-6.

91. Lazar JD, Wilner KD. Drug interactions with fluconazole. Clin Infect Dis. 1990; 12(Suppl 3): S327-33.

92. Hay RJ. Overview of studies of fluconazole in oropharyngeal candidiasis. Clin Infect Dis. 1990; 12(Suppl 3):S334-7.

93. Sugar AM, Stern JJ, Dupont B. Overview: treatment of cryptococcal meningitis. Clin Infect Dis. 1990; 12(Suppl 3):S338-48.

94. Robinson PA, Knirsch AK, Joseph JA. Fluconazole for life-threatening fungal infections in patients who cannot be treated with conventional antifungal agents. Clin Infect Dis. 1990; 12(Suppl 3):S349-63.

95. Meunier F, Aoun M, Gerard M. Therapy for oropharyngeal candidiasis in the immunocompromised host: a randomized double-blind study of fluconazole vs. ketoconazole. Clin Infect Dis. 1990; 12(Suppl 3):S364-8.

96. Samonis G, Rolston K, Karl C et al. Prophylaxis of oropharyngeal candidiasis with fluconazole. Clin Infect Dis. 1990; 12(Suppl 3):S369-73.

97. Tucker RM, Galgiani JN, Denning DW et al. Treatment of coccidioidal meningitis with fluconazole. Clin Infect Dis. 1990; 12(Suppl 3):S380-9.

98. Galgiani JN. Antifungal susceptibility tests. Antimicrob Agents Chemother. 1987; 31:1867-70. [IDIS 253318] [PubMed 3326524]

99. Houang ET, Chappatte OP, Byrne D et al. Fluconazole levels in plasma and vaginal secretions of patients after a 150-milligram single oral dose and rate of eradication of infection in vaginal candidiasis. Antimicrob Agents Chemother. 1990; 34:909-10. [IDIS 266004] [PubMed 2360828]

100. Kobayashi GS, Travis SJ, Medoff G. Comparison of fluconazole with amphotericin B in treatment of histoplasmosis in normal and immunosuppressed mice. Clin Infect Dis. 1990; 12(Suppl 3):S291-3.

101. Patterson TF, Miniter P, Andriole VT. Efficacy of fluconazole in experimental invasive aspergillosis. Clin Infect Dis. 1990; 12:(Suppl 3):S281-5.

102. Perfect JR, Savani DV, Durack DT. Comparison of itraconazole and fluconazole in treatment of cryptococcal meningitis and candida pyelonephritis in rabbits. Antimicrob Agents Chemother. 1986; 29: 579-83. [PubMed 3010846]

103. Hughes CE, Bennett RL, Tuna IC et al. Activities of fluconazole (UK 49,858) and ketoconazole against ketoconazole-susceptible and -resistant Candida albicans. Antimicrob Agents Chemother. 1988; 32:209-12. [PubMed 2834995]

104. Smith KJ, Warnock DW, Kennedy CT et al. Azole resistance in Candida albicans. J Med Vet Mycol. 1986; 24:133-44. [PubMed 3014106]

105. Brammer KW, Farrow PR, Faulkner JK. Pharmacokinetics and tissue penetration of fluconazole in humans. Clin Infect Dis. 1990; 12(Suppl 3):S318-26.

106. Richardson K, Brammer KW, Marriott MS et al. Activity of UK-49,858, a bis-triazole derivative, against experimental infections with Candida albicans and Trichophyton mentagrophytes. Antimicrob Agents Chemother. 1985; 27:832-5. [PubMed 2990328]

107. Kobayashi GS, Travis SJ, Rinaldi MG et al. In vitro and in vivo activities of Sch 39304, fluconazole, and amphotericin B against Histoplasma capsulatum. Antimicrob Agents Chemother. 1990; 34:524-8. [PubMed 2344160]

108. Fierer J, Kirkland T, Finley F. Comparison of fluconazole and SDZ89-485 for therapy of experimental murine coccidioidomyces. Antimicrob Agents Chemother. 1990; 34:13-6. [PubMed 2327748]

109. Kobayashi GS, Travis SJ, Medoff G. Comparison of fluconazole and amphotericin B in treating histoplasmosis in immunosuppressed mice. Antimicrob Agents Chemother. 1987; 31:2005-6. [PubMed 2830843]

110. Milliken ST, Powles RL. Antifungal prophylaxis in bone marrow transplantation. Clin Infect Dis. 1990; 12(Suppl 3):S374-9.

111. Meunier F. Prevention of mycoses in immunocompromised patients. Rev Infect Dis. 1987; 9:408-16. [IDIS 228176] [PubMed 3296106]

112. Baily G. Weekly fluconazole for preventing mucosal candidiasis in HIV infection. Ann Intern Med. 1997; 127:1131. [IDIS 397025] [PubMed 9412323]

113. Ortho Pharmaceutical Corporation. Terazol (terconazole 0.4% cream/80 mg suppositories) clinical monograph. Raritan, NJ; 1988 Jun.

115. Ampel NM, Wieden MA, Galgiani JN. Coccidioidomycosis: clinical update. Rev Infect Dis. 1989; 11:897-911. [PubMed 2690287]

116. Reviewers’ comments (personal observations).

117. Roerig, New York, NY: Personal communication.

118. Anon. Fluconazole. Med Lett Drugs Ther. 1990; 32:50-2. [PubMed 2185400]

120. Martino P, Meloni G, Cassone A. Candidal endocarditis and treatment with fluconazole and granulocyte-macrophage colony-stimulating factor. Ann Intern Med. 1990; 112:966-7. [IDIS 267346] [PubMed 2187396]

121. Grant SM, Clissold SP. Itraconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses. Drugs. 1989; 37:310-44. [PubMed 2540949]

122. Lyman CA, Sugar AM, Diamond RD. Comparative activities of UK-49,858 and amphotericin B against Blastomyces dermatitidis infections in mice. Antimicrob Agents Chemother. 1986; 29:161-2. [PubMed 3015001]

124. Grant SM, Clissold SP. Fluconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses. Drugs. 1990; 39:877-916. [PubMed 2196167]

125. Catanzaro A, Fierer J, Friedman PJ. Fluconazole in the treatment of persistent coccidioidomycosis. Chest. 1990; 97:666-9. [IDIS 299319] [PubMed 2306969]

126. Bodey GP, Samonis G, Rolston K. Prophylaxis of candidiasis in cancer patients. Semin Oncol. 1990; 17(3 Suppl 6):24-8. [PubMed 2191444]

127. Odds FC, Webster CE. Effects of azole antifungals in vitro on host/parasite interactions relevant to Candida infections. J Antimicrob Chemother. 1988; 22:473-81. [PubMed 2849601]

128. Senior DS, Shaw JTB. In vitro effects of fluconazole (UK-49,858) and ketoconazole on mouse lymphocyte proliferation and on Candida blastospore destruction by human polymorphonuclear leukocytes. Int J Immunopharmacol. 1988; 10:169-73. [PubMed 2836326]

129. Kutzer E, Oittner R, Leodolter S et al. A comparison of fluconazole and ketoconazole in the oral treatment of vaginal candidiasis; report of a double-blind multicentre trial. Eur J Obstet Gynecol Reprod Biol. 1988; 29:305-13. [PubMed 2852609]

131. Shiba K, Saito A, Miyahara T. Pharmacokinetics evaluation of fluconazole in healthy volunteers. Jpn J Antibiot. 1989; 42:17-30. [PubMed 2540363]

133. Oka S, Tokitsu M, Mori H et al. Clinical evaluation of fluconazole. Jpn J Antibiot. 1989; 42:31-9. [PubMed 2540365]

134. Ikemoto H, Watanabe K, Mori T et al. Clinical study of fluconazole on deep-seated fungal infections. Jpn J Antibiot. 1989; 42:63-116. [PubMed 2540369]

135. Lee Y, Shiota T, Ikeda S et al. Clinical efficacy of fluconazole in the patient with pulmonary mycosis. Jpn J Antibiot. 1989; 42:138-43. [PubMed 2540359]

136. Nakashima M. The clinical study of fluconazole against pulmonary mycosis: effects of fluconazole on pulmonary cryptococcosis and aspergillosis and its pharmacokinetics in patients. Jpn J Antibiot. 1989; 42:127-37. [PubMed 2540358]

137. Yagi S, Watanabe M, Nakajima M et al. A clinical evaluation of fluconazole in the treatment of deep mycosis. Jpn J Antibiot. 1989; 42:144-52. [PubMed 2540360]

138. Graybill JR. New antifungal agents. Eur J Clin Microbiol Infect Dis. 1989; 8:402-12. [PubMed 2546775]

139. Yagi S, Nakajima M, Umeki S. A case of pulmonary aspergillosis treated successfully by transbronchial infusion of fluconazole. Nippon Kyobu Rinsho. 1989; 48:564-9.

140. Arca E, Tastan HB, Akar A et al. An open, randomized, comparative study of oral fluconazole, itraconazole and terbinafine therapy in onychomycosis. J Dermatolog Treat. 2002; 13:3-9. [PubMed 12006131]

141. Blum RA, Wilton JH, Hilligoss DM et al. Effect of fluconazole on the disposition of phenytoin. Clin Pharmacol Ther. 1991; 49:420-5. [IDIS 281229] [PubMed 2015731]

142. National Institute of Allergy and Infectious Diseases, Division of AIDS. A note to physicians: important information on results of a controlled clinical trial of fluconazole vs. amphotericin B for suppression of cryptococcal meningitis. Bethesda, MD: 1990 Apr 30.

143. Bozzette SA, Larsen RA, Chiu J et al. Fluconazole treatment of persistent Cryptococcus neoformans prostatic infection in AIDS. Ann Intern Med. 1991; 115:285-6. [IDIS 284358] [PubMed 1854112]

144. Bozzette SA, Larsen RA, Chiu J et al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. N Engl J Med. 1991; 324:580-4. [IDIS 278071] [PubMed 1992319]

145. Larsen RA, Leal MAE, Chan LS. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS: a randomized trial. Ann Intern Med. 1990; 113:183-7. [IDIS 268747] [PubMed 2197908]

146. American Academy of Pediatrics. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

147. Stein GE, Christensen S, Mummaw N. Comparative study of fluconazole and clotrimazole in the treatment of vulvovaginal candidiasis. DICP. 1991; 25:582-5. [IDIS 281935] [PubMed 1877264]

148. Osser S, Haglund A, Westrom L. Treatment of candidal vaginitis: a prospective randomized investigator-blind multicenter study comparing topically applied econazole with oral fluconazole. Acta Obstet Gynecol Scand. 1991; 70:73-8. [PubMed 1858500]

149. Viscoli C, Castagnola E, Fioredda F et al. Fluconazole in the treatment of candidiasis in immunocompromised children. Antimicrob Agents Chemother. 1991; 35:365-7. [IDIS 278273] [PubMed 2024968]

150. Gussenhoven MJE, Haak A, Peereboom-Wynia JDR et al. Stevens-Johnson syndrome after fluconazole. Lancet. 1991; 338:120.

151. Collazos J, Egurbide MV, Atucha K et al. Persistence of Cryptococcus neoformans in the prostate: failure of fluconazole despite high doses. J Infect Dis. 1991; 164:435. [IDIS 286646] [PubMed 1856498]

152. Saag MS, Powderly WG, Cloud GA et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. N Engl J Med. 1992; 326:83-9. [IDIS 289749] [PubMed 1727236]

153. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired imunodeficiency syndrome. N Engl J Med. 1992; 326:793-8.

154. Wingard JR, Merz WG, Rinaldi MG et al. Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med. 1992; 325:1274-7.

155. Persons DA, Laughlin M, Tanner D et al. Fluconazole and Candida krusei fungemia. N Engl J Med. 1992; 325:1315.

157. Goodman JL, Winston DJ, Greenfield RA et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992; 326:845-51. [IDIS 293032] [PubMed 1542320]

158. Metlay LA. Prophylactic fluconazole and marrow transplantation. N Engl J Med. 1992; 327:644. [IDIS 300875] [PubMed 1640962]

159. Scholten SL, Nettleman MD, Sarrazin EF. Prophylactic fluconazole and marrow transplantation. N Engl J Med. 1992; 327:644. [IDIS 300876] [PubMed 1640963]

160. Denning DW. Prophylactic fluconazole and marrow transplantation. N Engl J Med. 1992; 327:645. [IDIS 300877] [PubMed 1640964]

161. Goodman JL, Greenfield R, Buell D. Prophylactic fluconazole and marrow transplantation. N Engl J Med. 1992; 327:645.

162. Garrelts JC, Briceland LL, Goldman MP et al. Fluconazole: a position statement by the society of infectious diseases pharmacists. Ann Pharmacotherapy. 1992; 26:809-11.

163. Neuhaus G, Pavic N, Pletscher M. Anaphylactic reaction after oral fluconazole. BMJ. 1991; 302:1341. [IDIS 282083] [PubMed 2059703]

164. Marion Merrell Dow Seldane (terfenadine) tablets prescribing information. Kansas City, MO: 1992 Sep.

165. Marion Merrell Dow, Kansas City, MO: Personal communication.

166. Cruzan S (US Food and Drug Administration). HHS News. Press release No. P92-22. 1992 Jul 7.

167. Marion Merrell Dow. Dear health care professional letter regarding appropriate use of Seldane. Kansas City, MO: July 7, 1992.

168. Zimmerman M, Duruz H, Guinand O et al. Torsades de pointes after treatment with terfenadine and ketoconazole. Eur Heart J. 1992; 13:1002-3. [PubMed 1644069]

169. Mathews DR, McNutt B, Okerholm R et al. Torsades de pointes occurring in association with terfenadine use. JAMA. 1991; 266:2375-6. [IDIS 287469] [PubMed 1920744]

170. Cortese L, Bjornson DC. Potential interaction between terfenadine and macrolide antibiotics. Clin Pharm. 1992; 11:675. [IDIS 299287] [PubMed 1511540]

171. Mathews DR, McNutt B, Okerholm R. Torsades de pointes occurring in association with terfenadine use. JAMA. 1991; 266:2375-6. [IDIS 287469] [PubMed 1920744]

172. Eller MG, Okerholm RA. Pharmacokinetic interaction between terfenadine and ketoconazole. Clin Pharmacol Ther. 1991; 49:130.

173. Laine L, Dretler RH, Conteas CN et al. Fluconazole compared with ketoconazole for the treatment of candida esophagitis in AIDS: a randomized trial. Ann Intern Med. 1992; 117:655-60. [IDIS 303496] [PubMed 1308663]

174. Janssen Pharmaceutica. Hismanal (astemizole) tablets prescribing information. Titusville, NJ; 1998 Feb.

175. Janssen Pharmaceutical Products, L.P.. Nizoral (ketoconazole) tablets prescribing information. Titusville, NJ; 2002 Feb.

176. Havu V, Heikkila H, Kuokkanen K et al. A double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil) with fluconazole (Diflucan) in the treatment of onychomycosis. Br J Dermatol. 2000; 142:97-102. [IDIS 444260] [PubMed 10651701]

177. Honig PK, Wortham DC, Zamani K et al. The effect of fluconazole on the steady-state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in man. Clin Pharmacol Ther. 1993; 53:630-6. [IDIS 317107] [PubMed 8513654]

178. Vanden Bossche H, Marichal P, Odds FC et al. Characterization of an azole-resistant Candida glabrata isolate. Antimicrob Agents Chemother. 1992; 36:2602-10. [PubMed 1482129]

179. Walsh TJ, Lee JW. Prevention of invasive fungal infections in patients with neoplastic diseases. Clin Infect Dis. 1993; 17(Suppl 2):S468-80. [IDIS 323669] [PubMed 8274613]

180. Swerdloff JN, Filler SG, Edwards JE Jr. Severe candidal infections in neutropenic patients. Clin Infect Dis. 1993; 17(Suppl 2):S457-67. [IDIS 323668] [PubMed 8274612]

182. Wingard JR. The use of fluconazole prophylaxis in patients with chemotherapy-induced neutropenia. Leuk Lymphoma. 1992; 8:353-9. [PubMed 1290959]

183. Rozenberg-Arska M, Dekker AW, Branger J et al. A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia. J Antimicrob Chemother. 1991; 27:369-76. [PubMed 2037541]

184. Chandrasekar PH, Gatny CM. Effect of fluconazole prophylaxis on fever and use of amphotericin in neutropenic cancer patients. Chemotherapy. 1994; 40:136-43. [IDIS 325732] [PubMed 8131635]

185. Winston DJ, Chandrasekar PH, Lazarus HM et al. Fluconazole prophylaxis of fungal infections in patients with acute leukemia: results of a randomized placebo-controlled, double-blind, multicenter trial. Ann Intern Med. 1993; 118:495-503. [IDIS 311491] [PubMed 8442620]

186. Reents S, Goodwin SD, Singh V. Antifungal prophylaxis in immunocompromised hosts. Ann Pharmacother. 1993; 27:53-60. [IDIS 307670] [PubMed 8431623]

187. Pizzo PA, Walsh TJ. Fungal infections in the pediatric cancer patient. Semin Oncol. 1990; 17(Suppl 6):6-9. [PubMed 2191445]

188. Quabeck K, Muller KD, Beelen DW et al. Prophylaxis and treatment of fungal infections with fluconazole in bone marrow transplant patients. Mycoses. 1992; 35:221-4. [PubMed 1291872]

189. Denning DW, Donnelly JP, Hellreigel KP et al. Antifungal prophylaxis during neutropenia or allogeneic bone marrow transplantation: what is the state of the art? Chemotherapy. 1992; 38(Suppl 1):43-9. (IDIS 297490)

190. Rowe JM, Ciobanu N, Ascensao J et al. Recommended guidelines for the management of autologous and allogeneic bone marrow transplantation: a report from the Eastern Cooperative Oncology Group (ECOG). Ann Intern Med. 1994; 120:143-58. [IDIS 323859] [PubMed 8256974]

191. Perfect JR. Antifungal prophylaxis: to prevent or not. Am J Med. 1993; 94:233-4. [PubMed 8452146]

192. Herzog RE, Ansmann EB. Treatment of vaginal candidosis with fluconazole. Mycoses. 1989; 32:204-8. [PubMed 2547160]

193. Inman W, Pearce G, Wilton L. Safety of fluconazole in the treatment of vaginal candidiasis: a prescription-event monitoring study, with special reference to the outcome of pregnancy. Eur J Clin Pharmacol. 1994; 46:115-8. [IDIS 328445] [PubMed 8039528]

194. Doering PL, Santiago TM. Drugs for treatment of vulvovaginal candidiasis: comparative efficacy of agents and regimens. DICP. 1990; 24:1078-83. [IDIS 274670] [PubMed 2275233]

195. Patel HS, Peters MD II, Smith CL. Is there a role for fluconazole in the treatment of vulvovaginal candidiasis? Ann Pharmacother. 1992; 26:350-3. (IDIS 293102)

196. Anon. Fluconazole and itraconazole for vulvo-vaginal candidosis. Drug Ther Bull. 1990; 28:7-8. [PubMed 1966679]

197. Phillips RJM, Watson SA, McKay FF. An open multicentre study of the efficacy and safety of a single dose of fluconazole 150 mg in the treatment of vaginal candidiasis in general practice. Br J Clin Pract. 1990; 44:219-22. [IDIS 269168] [PubMed 2206814]

198. Otubu JAM, Imade GE, Sagay AS et al. Efficacy of single-dose oral fluconazole in the treatment of vulvovaginal candidiasis. Curr Ther Res. 1990; 48:632-7.

199. Sobel JD. Fluconazole maintenance therapy in recurrent vulvovaginal candidiasis. Int J Gynecol Obstet. 1992; 37(Suppl 1):17-24.

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (DHHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (January 10, 2011). Updates available at DHHS AIDS Information (AIDSinfo) website.

201. de los Reyes C, Edelman DE, De Bruin MF. Clinical experience with single-dose fluconazole in vaginal candidiasis: a review of the worldwide database. Int J Gynecol Obstet. 1992; 37(Suppl):9-15.

202. Dellenbach P. Penetration of fluconazole into vaginal tissues and secretions. In: Richardson RG, ed. Fluconazole and its role in vaginal candidiasis. Royal Society of Medicine Services International Congress and Symposium Series No. 160. London: Royal Society of Medicine Services Ltd; 1989:19-22.

203. Andersen GM, Barrat J, Bergan T et al. A comparison of single-dose oral fluconazole with 3-day intravaginal clotrimazole in the treatment of vaginal candidiasis: report of an international multicentre trial. Br J Obstet Gynaecol. 1989; 96:226-32. [PubMed 2539186]

204. Adetoro OO. Comparative trial of a single oral dose of fluconazole (150 mg) and a single intravaginal tablet of clotrimazole (500 mg) in the treatment of vaginal candidiasis. Curr Ther Res. 1990; 48:275-81.

205. Boag FC, Houang ET, Westrom R et al. Comparison of vaginal flora after treatment with a clotrimazole 500 mg vaginal pessary or a fluconazole 150 mg capsule for vaginal candidosis. Genitourin Med. 1991; 67:232-4. [PubMed 2071126]

206. Timonen H. Shorter treatment for vaginal candidosis: comparison between single-dose oral fluconazole and three-day treatment with local miconazole. Mycoses. 1992; 317-20.

207. Bodey GP, Samonis G, Rolston K. Prophylaxis of candidiasis in cancer patients. Semin Oncol. 1990; 17(Suppl 6):24-8. [PubMed 2191444]

209. Rees T, Phillips R. Multicenter comparison of one-day oral therapy with fluconazole or itraconazole in vaginal candidiasis. Int J Gynecol Obstet. 1992; 37(Suppl):33-8.

210. van Heusden AM, Merkus HMWM, Corbeij RSACM et al. Single-dose oral fluconazole versus single-dose topical miconazole for the treatment of acute vulvovaginal candidosis. Acta Obstet Gynecol Scand. 1990; 69:417-22. [PubMed 2270767]

211. Slavin MB, Benrubi GI, Parker R et al. Single dose oral fluconazole vs intravaginal terconazole in treatment of candida vaginitis: comparison and pilot study. J Florida Med Assoc. 1992; 79:693-6.

213. Morgan JM, Carmichael AJ. Fixed drug eruption with fluconazole. BMJ. 1994; 308:454. [IDIS 326200] [PubMed 8124179]

215. Baxter. Baxter premix medications. Round Lake, IL; 1994 Feb 21.

216. Anon. Oral fluconazole for vaginal candidiasis. Med Lett Drugs Ther. 1994; 36:81-2. [PubMed 8072449]

217. Sahai J, Gallicano K, Pakuts A et al. Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus. J Infect Dis. 1994; 169:1103-7. [IDIS 329297] [PubMed 8169401]

218. Bruzzese VL, Gillum JG, Israel DS et al. Effect of fluconazole on pharmacokinetics of 2’,3’-dideoxyinosine in persons seropositive for human immunodeficiency virus. Antimicrob Agents Chemother. 1995; 39:1050-3. [IDIS 346311] [PubMed 7625787]

219. Tett S, Moore S, Ray J. Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection. Antimicrob Agents Chemother. 1995; 39:1835-41. [IDIS 352193] [PubMed 7486928]

220. American Thoracic Society. Fungal infection in HIV-infected persons. Am J Respir Crit Care Med. 1995; 152:816-22. [IDIS 352046] [PubMed 7633749]

223. DeMuria D, Forrest A, Rich J et al. Pharmacokinetics and bioavailability of fluconazole in patients with AIDS. Antimicrob Agents Chemother. 1993; 37:2187-92. [IDIS 320616] [PubMed 8257143]

224. Yeates RA, Ruhnke M, Pfaff G et al. The pharmacokinetics of fluconazole after a single intravenous dose in AIDS patients. Br J Clin Pharmacol. 1994; 38:77-9. [IDIS 333380] [PubMed 7946940]

225. Pinner RW, Hajjeh RA, Powderly WG. Prospects for preventing cryptococcosis in persons infected with human immunodeficiency virus. Clin Infect Dis. 1995; 21(Suppl 1):S103-7.

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

227. Reef SE, Mayer KH. Opportunistic candidal infections in patient infected with human immunodeficiency virus: prevention and priorities. Clin Infect Dis. 1995; 21(Suppl 1):S99-102. [IDIS 352670] [PubMed 8547520]

228. Powderly WG, Finkelstein DM, Feinberg J et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. N Engl J Med. 1995; 332:700-5. [IDIS 343579] [PubMed 7854376]

229. Quagliarello VJ, Viscoli C, Horwitz R. Primary prevention of cryptococcal meningitis by fluconazole in HIV-infected patients. Lancet. 1995; 345:548-52. [IDIS 343545] [PubMed 7776774]

230. Clumeck N. Primary prophylaxis against opportunistic infections in patients with AIDS. N Engl J Med. 1995; 332:739-40. [IDIS 343582] [PubMed 7854383]

231. van Ettenn EWM, van de Rhee NE, van Kampen KM et al. Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans. Antimicrob Agents Chemother. 1991; 35:2275-81. [PubMed 1804000]

232. Sugar AM. Use of amphotericin B with azole antifungal drugs: what are we doing? Antimicrob Agents Chemother. 1995; 39:1907-12.

233. Sanati H, Ramos CF, Bayer AS et al. Combination therapy with amphotericin B and fluconazole against invasive candidiasis in neutropenic-mouse and infective-endocarditis rabbit models. Antimicrob Agents Chemother. 1997; 41:1345-8. [PubMed 9174196]

234. Sugar A, Hitchcock CA, Troke PF et al. Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B. Antimicrob Agents Chemother. 1995; 39:598-601. [PubMed 7793858]

235. Bristol-Myers Squibb. Fugizone (amphotericin B) injection, powder, lyophilized, for solution prescribing information. Princeton, NJ; 2009 Apr.

236. Astellas. AmBisome (amphotericin B) liposome for injection prescribing information. Deerfield, IL; 2008 Oct.

237. Walsh TJ, Peter J, McGough DA et al. Activities of amphotericin B and antifungal azoles alone and in combination against Pseudallescheria boydii. Antimicrob Agents Chemother. 1995; 39:1361-4. [IDIS 348687] [PubMed 7574531]

238. Allendoerfer R, Marquis AJ, Rinnaldi MG et al. Combined therapy with fluconazole and flucytosine in murine cryptococcal meningitis. Antimicrob Agents Chemother. 1991; 35:726-9. [PubMed 2069378]

239. Nguyen MH, Barchiesi F, McGough DA et al. In vitro evaluation of combination of fluconazole and flucytosine against Cryptococcus neoformans var neoformans. Antimicrob Agents Chemother. 1995; 39:1691-5. [IDIS 352190] [PubMed 7486902]

240. Martin E, Maier F, Bhakdi S. Antagonistic effects of fluconazole and 5-fluorocytosine on candidacidal action of amphotericin B in human serum. Antimicrob Agents Chemother. 1994; 38:1331-8. [PubMed 8092834]

241. Trapnell CB, Narag PK, Li R et al. Increased plasma rifabutin levels with concomitant fluconazole therapy in HIV-infected patients. Ann Intern Med. 1996; 124:573-6. [IDIS 361582] [PubMed 8597321]

242. Trapnell CB, Jamis-Dow C, Klecker RW et al. Metabolism of rifabutin and its 25- desacetyl metabolite, LM565, by human liver microsomes and recombinant human cytochrome P- 450 3A4: relevance to clinical interaction with fluconazole. Antimicrob Agents Chemother. 1997; 41:924-6. [PubMed 9145845]

243. Iatsimirskaia E, Tulebaev S, Storozhuk E et al. Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. Clin Pharmacol Ther. 1997; 61:554-62. [PubMed 9164417]

244. Peloquin CA, Nitta AT, Burman WJ et al. Low antituberculosis drug concentrations in patients with AIDS. Ann Pharmacother. 1996; 30:919-25. [IDIS 372121] [PubMed 8876848]

245. Coker RJ, Tomlinson DR, Parkin J et al. Interaction between fluconazole and rifampicin. Br Med J. 1990; 301:818.

246. Baciewicz AM, Baciewicz FA. Ketoconazole and fluconazole drug interactions. Arch Intern Med. 1993; 153:1970-6. [IDIS 319508] [PubMed 8357281]

248. Abbott Laboratories. Norvir (ritonavir) soft gelatin capsules and oral solution prescribing information. North Chicago, IL; 2010 Apr.

249. Thorpe JE, Baker N, Bromet-Petit M. Effect of oral antacid administration on the pharmacokinetics of oral fluconazole. Antimicrob Agents Chemother. 1990; 34:2032-3. [IDIS 281094] [PubMed 2291673]

250. Blum RA, D’Andrea DT, Florentino BM et al. Increased gastric pH and the bioavailability of fluconazole and ketoconazole. Ann Intern Med. 1991; 114:755-7. [IDIS 280193] [PubMed 2012358]

251. Crussell-Porter LL, Rindone JP, Ford MA et al. Low-dose fluconazole therapy potentiates the hypoprothrombinemic responses of warfarin sodium. Arch Intern Med. 1993; 153:102-4. [IDIS 308306] [PubMed 8422191]

252. Agarwal A. Fluconazole-induced thrombocytopenia. Ann Intern Med. 1990; 113:899. [IDIS 274426] [PubMed 2240909]

253. Franklin IM, Elias E, Hirsch C. Fluconazole-induced jaundice. Lancet. 1990; 336:565. [IDIS 270663] [PubMed 1975057]

254. Munoz P, Moreno S, Berenguer J et al. Fluconazole-related hepatotoxicity in patients with acquired immunodeficiency syndrome. Arch Intern Med. 1991; 151:1020-1. [IDIS 282026] [PubMed 2025128]

255. Jacobson A, Hanks DK, Ferrell LD. Fatal acute hepatic necrosis due to fluconazole. Am J Med. 1994; 96:188-90. [IDIS 326703] [PubMed 7677802]

256. Bronstein JA, Gros P, Hernandez E et al. Fatal acute hepatic necrosis due to dose- dependent fluconazole hepatotoxicity. Clin Infect Dis. 1997; 25:1266-7. [IDIS 397457] [PubMed 9402409]

257. Trujillo MA, Galgiani JN, Sampliner RE. Evaluation of hepatic injury arising during fluconazole therapy. Arch Intern Med. 1994; 154:102-4. [IDIS 323924] [PubMed 8267481]

258. Pursley TJ, Blomquist IK, Abraham J et al. Fluconazole-induced congenital anomalies in three infants. Clin Infect Dis. 1996; 22:336-40. [IDIS 363357] [PubMed 8838193]

259. Saxen H, Hoppu K, Pohjavuori M. Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life. Clin Pharmacol Ther. 1993; 54:269-77. [IDIS 320637] [PubMed 8375121]

260. Finley RW, Cleary JD, Goolsby J et al. Fluconazole penetration into the human prostate. Antimicrob Agents Chemother. 1995; 39:553-5. [IDIS 341980] [PubMed 7726532]

261. Force RW. Fluconazole concentrations in breast milk. Pediatr Infect Dis J. 1995; 14:235-6. [IDIS 343916] [PubMed 7761190]

262. National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard. NCCLS document M27-A. Wayne, PA: NCCLS; 1997 Jun.

263. Pfaller A, Rex JH, Rinaldi MG. Antifungal susceptibility testing: technical advances and potential clinical applications. Clin Infect Dis. 1997; 24:776-84. [IDIS 386039] [PubMed 9142769]

264. Rex JH, Pfaller MA, Galgiani JN et al. Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro—in vivo correlation data for fluconazole, itraconazole, and candida infections. Clin Infect Dis. 1997; 24:235-47. [IDIS 381120] [PubMed 9114154]

265. Martins MD, Lazano-Chiu M, Rex JH. Point prevalence of oropharyngeal carriage of fluconazole-resistant Candida in human immunodeficiency virus-infected patients. Clin Infect Dis. 1997;25:843-6.

266. Kelly SL, Lamb DC, Kelly DE et al. Resistance to fluconazole and amphotericin in Candida albicans from AIDS patients. Lancet. 1996; 348:1523-4. [IDIS 377911] [PubMed 8942815]

267. Nguyen MH, Peacock JE, Morris AJ et al. The changing face of candidemia: emergence of non-C. albicans species and antifungal resistance. Am J Med. 1996; 100:617-23. [IDIS 370428] [PubMed 8678081]

268. Klepser ME, Wolfe EJ, Jones RN et al. Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans. Antimicrob Agents Chemother. 1997; 41:1392-5. [IDIS 394224] [PubMed 9174207]

269. Maenza JR, Merz WG, Romagnoli MJ et al. Infection due to fluconazole-resistant Candida in patients with AIDS: prevalence and microbiology. Clin Infect Dis. 1997; 24:28-34. [IDIS 378941] [PubMed 8994752]

270. Sandven P, Nilsen K, Digranes A et al. Candida norvegensis: a fluconazole- resistant species. Antimicrob Agents Chemother. 1997; 41:1375-6. [IDIS 394221] [PubMed 9174202]

271. Marr KA, White TC, van Burik JAH et al. Development of fluconazole resistance in Candida albicans causing disseminated infection in a patient undergoing marrow transplantation. Clin Infect Dis. 1997; 25:908-10. [IDIS 395794] [PubMed 9356806]

272. Arenngou A, Porcar C, Mascaro J et al. Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1996; 23:1337-8. [IDIS 376923] [PubMed 8953097]

273. Venkateswarlu K, Taylor M, Manning NJ et al. Fluconazole tolerance in clinical isolates of Cryptococcus neoformans. Antimicrob Agents Chemother. 1997; 41:748-51. [IDIS 384385] [PubMed 9087482]

274. Calvet HM, Yeaman MR, Filler SG. Reversible fluconazole resistance in Candida albicans: a potential in vitro model. Antimicrob Agents Chemother. 1997; 41:535-9. [PubMed 9055988]

275. Hitchcock CA, Pye GW, Troke PF et al. Fluconazole resistance in Candida glabrata. Antimicrob Agents Chemother. 1993; 37:1962-5. [IDIS 319433] [PubMed 8239613]

276. Maenza JR, Keruly JC, Moore RD et al. Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients. J Infect Dis. 1996; 173:219-5. [IDIS 361388] [PubMed 8537662]

277. Tumbarello M, Bevilacqua N, Federico G et al. Fluconazole-resistant Candida parapsilosis fungemia in a patient with AIDS. Clin Infect Dis. 1996; 22:179-80. [IDIS 360701] [PubMed 8824996]

278. Denning DW. Can we prevent azole resistance in fungi? Lancet. 1995; 346:454- 5. Editorial.

279. Sanglard D, Kuchler K, Ischer F et al. Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob Agents Chemother. 1995; 39:2378-86. [IDIS 357538] [PubMed 8585712]

280. Hennequin C, Labenne M, Benkerrou M et al. Fluconazole-resistant Candida albicans in an immunocompetent child. Clin Infect Dis. 1994; 19:1179-80. [IDIS 341018] [PubMed 7888572]

281. Wingard JR. Infections due to resistant Candida species in patients with cancer who are receiving chemotherapy. Clin Infect Dis. 1994; 19(Suppl 1):S49-53. [IDIS 335129] [PubMed 7948571]

282. Paugam A, Dupouy-Camet J, Blannche P et al. Increased fluconazole resistance of Cryptococcus neoformans isolated from a patient with AIDS and recurrent meningitis. Clin Infect Dis. 1994; 19:975-6.

283. While A, Goetz MB. Azole-resistant Candida albicans: report of two cases of resistance to fluconazole and review. Clin Infect Dis. 1994; 19:687-92. [IDIS 337497] [PubMed 7803633]

284. Sangeorzan JA, Bradley SF, He X et al. Epidemiology or oral candidiasis in HIV- infected patients: colonization, infection, treatment, and emergence of fluconazole resistance. Am J Med. 1994; 97:339-46. [IDIS 336788] [PubMed 7942935]

285. Sanguineeti A, Carmichael JK, Campbell K. Fluconazole-resistant Candida albicans after long-term suppressive therapy. Arch Intern Med. 1993; 153:1122-4. [PubMed 8481078]

286. Taillan B, Ferrari E, Cosnefroy JY et al. Favourable outcome of blastomycosis of the brain stem with fluconazole and flucytosine treatment. Ann Med. 1992; 24:71-2. [PubMed 1575964]

287. Pearson GJ, Chin TWF, Fong IW. Case report: treatment of blastomycosis with fluconazole. Am J Med Sci. 1992; 303:313-5. [IDIS 296161] [PubMed 1580320]

288. Pappas PG, Bradsher RW, Chapman SW et al. Treatment of blastomycosis with fluconazole: a pilot study. Clin Infect Dis. 1995; 20:267-71. [IDIS 343230] [PubMed 7742428]

289. Pappas PG, Bradsher RW, Kauffman CA et al. Treatment of blastomycosis with higher doses of fluconazole. Clin Infect Dis. 1997; 25:200-5. [IDIS 392203] [PubMed 9332510]

290. Pappas PG, Pottage JC, Powderly WG et al. Blastomycosis in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1992; 116:847-53. [IDIS 296295] [PubMed 1567099]

291. Bradsher RW. Therapy of blastomycosis. Semin Respir Infect. 1997; 12:263-7. [PubMed 9313298]

292. Chapman SW, Lin AC, Hendricks KA et al. Endemic blastomycosis in Mississippi: epidemiological and clinical studies. Semin Respir Infect. 1997; 12:219-28. [PubMed 9313293]

293. Yancey RW, Perlino CA, Kaufman L. Asymptomatic blastomycosis of the central nervous system with progression in patients given ketoconazole therapy: a report of two cases. J Infect Dis. 1991; 164:807-10. [IDIS 289561] [PubMed 1894941]

294. Pitrak DL, Anderson BR. Cerebral blastomycoma after ketoconazole therapy for respiratory tract blastomycosis. Am J Med. 1989; 86:713-4. [IDIS 255557] [PubMed 2729325]

295. Davies SF, Sarosi GA. Epidemiological and clinical features of pulmonary blastomycosis. Semin Respir Infect. 1997; 12:206-18. [PubMed 9313292]

296. Pappas PG. Blastomycosis in the immunocompromised patient. Semin Respir Infect. 1997; 12:243-51. [PubMed 9313296]

298. Galgiani JN, Catanzaro A, Cloud GA et al. Fluconazole therapy for coccidioidal meningitis. Ann Intern Med. 1993; 119:28-35. [IDIS 315934] [PubMed 8498760]

299. Catanzaro A, Galgiani JN, Levine BE et al. Fluconazole in the treatment of chronic pulmonary and nonmeningeal disseminated coccidioidomycosis. Am J Med. 1995; 98:249- 56. [IDIS 344105] [PubMed 7872341]

300. Perez JA, Johnson RH, Caldwell JW et al. Fluconazole therapy in coccidioidal meningitis maintained with intrathecal amphotericin B. Arch Intern Med. 1995; 155:1665- 8. [IDIS 352480] [PubMed 7618991]

302. Powderly WG. Recent advances in the management of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996; 22(Suppl 2):S119-23.

303. Dromer F, Mathoulin S, Dupont B et al. Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. Clin Infect Dis. 1996; 22(Suppl 2:S154-60. [IDIS 367022] [PubMed 8722844]

304. Berry AJ, Rinaldi G, Graybill JR. Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS. Antimicrob Agents Chemother. 1992; 36:690-2. [IDIS 292623] [PubMed 1622188]

305. Menichetti F, Fiorio M, Tosti A et al. High-dose fluconazole therapy for cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996; 22:838-40. [IDIS 363744] [PubMed 8722942]

306. Nightingale SD. Initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis with fluconazole. Arch Intern Med. 1995; 155:538-40. [IDIS 344098] [PubMed 7864710]

307. Van der Horst CM, Saag MS, Cloud GA et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl J Med. 1997; 337:15- 21. [IDIS 387972] [PubMed 9203426]

308. Singh N, Barnish MJ, Berman S et al. Low-dose fluconazole as primary prophylaxis for cryptococcal infection in AIDS patients with CD4 cell counts of ≤100/mm3: demonstration of efficacy in a prospective, multicenter trial. Clin Infect Dis. 1996; 23:1282-6. [IDIS 376910] [PubMed 8953072]

309. Coulter C, Benson SM, Whitby M. Fluconazole for cryptococcal cellulitis. Clin Infect Dis. 1993; 16:826-7. [IDIS 315630] [PubMed 8329516]

310. Larsen RA, Bozzette SA, Jones BE et al. Fluconazole combined with flucytosine for treatment of cryptococcal meningitis inn patients with AIDS. Clin Infect Dis. 1994; 19:741-5. [IDIS 337501] [PubMed 7803641]

311. Witt MD, Lewis RJ, Larsen RA et al. Identification of patients with acute AIDS- associated cryptococcal meningitis who can be effectively treated with fluconazole: the role of antifungal susceptibility testing. Clin Infect Dis. 1996; 22:322-8. [IDIS 363354] [PubMed 8838190]

312. Wheat J, MaWhinney S, Hafner R et al. Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. Am J Med. 1997; 103:223-32. [IDIS 395413] [PubMed 9316555]

313. Sharkey-Mathis PK, Velez J, Fetchick R et al. Histoplasmosis in the acquired immunodeficiency syndrome (AIDS): treatment with itraconazole and fluconazole. J Acquir Immune Defic Syndr. 1993; 6:809-19. [PubMed 8389850]

315. Kauffman CA. Role of azoles in antifungal therapy. Clin Infect Dis. 1996; 22(Suppl 2:S148-53. [IDIS 367021] [PubMed 8722843]

316. Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med. 1994; 330:263-72. [IDIS 324299] [PubMed 8272088]

317. Pepose JS, Holland G, Wilhelmus KR. Ocular infections & immunology. St. Louis, MO:Mosby—Year Book Inc; 1996:1048-61,1262-85.

318. Nomura J, Ruskin J. Failure of therapy with fluconazole for candidal endophthalmitis. Clin Infect Dis. 1993; 17:888-9. [IDIS 321797] [PubMed 8286632]

319. Akler ME, Vellend H, McNeely DM et al. Use of fluconazole in the treatment of candidal endophthalmitis. Clin Infect Dis. 1995; 20:657-64. [IDIS 345247] [PubMed 7756492]

321. Leu HS, Huang CT. Clearance of funguria with short-course antifungal regimens: a prospective randomized, controlled study. Clin Infect Dis. 1995; 20:1152-7. [IDIS 347157] [PubMed 7619991]

322. Fan-Havard P, O’Donovan C, Smith SM et al. Oral fluconazole versus amphotericin B bladder irrigation for treatment of candidal funguria. Clin Infect Dis. 1995; 21:960-5. [IDIS 355564] [PubMed 8645847]

323. Jacobs LG, Skidmore EA, Freeman K et al. Oral fluconazole compared with bladder irrigation with amphotericin B for treatment of fungal urinary tract infections in elderly patients. Clin Infect Dis. 1996; 22:30-5. [IDIS 360681] [PubMed 8824962]

324. Armstrong D. Treatment of opportunistic fungal infections. Clin Infect Dis. 1993; 16:1-9. [IDIS 307821] [PubMed 8448281]

326. Graybill JR. Editorial response: can we agree on the treatment of candidiasis? Clin Infect Dis. 1997; 25:60-2.

327. Anaissie EJ, Darouiche RO, Abi-Said D et al. Management of invasive candidal infections: results of a prospective, randomized multicenter study of fluconazole versus amphotericin B and review of the literature. Clin Infect Dis. 1996; 23:964-72. [IDIS 377538] [PubMed 8922787]

328. Soutar RL. Fluconazole or amphotericin for candidosis in neutropenic patients. Lancet. 1991; 337:181. [IDIS 276939] [PubMed 1670824]

329. Colville A, Wale MCJ. Fluconazole or amphotericin for candidaemia in non- neutropenic patients. Lancet. 1991; 337:1605-6. [IDIS 282588] [PubMed 1675729]

330. Anaissie E, Bodey GP, Kantarjiann H et al. Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy. Am J Med. 1991; 91:142-50. [IDIS 286567] [PubMed 1867240]

331. Rex JH, Bennett JE, Sugar AM et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med. 1994; 331:1325-30. [IDIS 338320] [PubMed 7935701]

332. Anaissie EJ, Vartivariann SE, Abi-Sai D et al. Fluconazole versus amphotericin B in the treatment of hematogenous candidiasis: a matched cohort study. Am J Med. 1996; 101:170-6. [IDIS 372409] [PubMed 8757357]

333. Kauffman CA, Bradley SF, Ross SC et al. Hepatosplenic candidiasis: successful treatment with fluconazole. Am J Med. 1991; 91:137-41. [IDIS 286566] [PubMed 1867239]

334. Flanery MT, Simmons DB, Saba H et al. Fluconazole in the treatment of hepatosplenic candidiasis. Arch Intern Med. 1992; 152:406-8. [IDIS 291571] [PubMed 1739374]

335. Koletar SL, Russell JA, Fass RJ et al. Comparison of oral fluconazole and clotrimazole troches as treatment of oral candidiasis in patients infected with human immunodeficiency virus. Antimicrob Agents Chemother. 1990; 34:2267-8. [IDIS 273726] [PubMed 2073120]

336. Pons V, Greenspan D, Lozada-Nur F et al. Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspension. Clin Infect Dis. 1997; 24:1204-7. [IDIS 388566] [PubMed 9195083]

337. Weinert M, Grimes RM, Lynch DP. Oral manifestations of HIV infection. Ann Intern Med. 1996; 125:485-96. [PubMed 8779462]

338. Schuman P, Capps L, Peng G et al. Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1997; 126:689-96. [IDIS 384255] [PubMed 9139554]

339. Manfredi R, Mastroianni A, Coronado OV et al. Fluconazole as prophylaxis against fungal infection in patients with advanced HIV infection. Arch Intern Med. 1997; 157:64- 9. [IDIS 380073] [PubMed 8996042]

340. Slavin MA, Osborne B, Adams R et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation—a prospective, randomized, double-blind study. J Infect Dis. 1995; 171:1545-52. [IDIS 348464] [PubMed 7769290]

341. Paya CV. Fungal infections in solid-organ transplantation. Clin Infect Dis. 1993; 16:677-88. [IDIS 314580] [PubMed 8507760]

342. Lumbreras C, Cuervas-Mons V, Jara P et al. Randomized trial of fluconazole versus nystatin for prophylaxis of Candida infection following liver transplantation. J Infect Dis. 1996; 174:583-8. [IDIS 374439] [PubMed 8769617]

343. Kung N, Fisher N, Gunson B et al. Fluconazole prophylaxis for high-risk liver transplant recipients. Lancet. 1995; 345:1234-6. [IDIS 350632] [PubMed 7739317]

344. Schaffner A, Schaffner M. Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. J Infect Dis. 1995; 172:1035-41. [IDIS 355091] [PubMed 7561177]

345. Menichetti F, Del Favero A, Martino P et al. Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B. Ann Intern Med. 1994; 120:913-8. [IDIS 330615] [PubMed 8172437]

346. Alexander BD, Perfect JR. Antifungal resistance trends towards the year 2000. Implications for therapy and new approaches. Drugs. 1997; 54:657-78. [PubMed 9360056]

347. Klausner MA. Dear doctor letter regarding important drug warning of Hismanal (astemizole). Titusville, NJ: Janssen Pharmaceutica; 1998 Feb.

348. Sobel JD. Vaginitis. N Engl J Med. 1997; 337:1896-903. [IDIS 401347] [PubMed 9407158]

349. Sobel JD, Faro S, Force RW et al. Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol. 1998; 178:203-11. [IDIS 402301] [PubMed 9500475]

350. Tobin MJ. Vulvovaginal candidiasis: topical vs. oral therapy. Am Fam Physician. 1995; 51:1715-24. [IDIS 348350] [PubMed 7754931]

352. Sobel JD. Controversial aspects in the management of vulvovaginal candidiasis. J Am Acad Dermatol. 1994; 31: S10-3. [IDIS 335764] [PubMed 8077494]

353. Sobel JD. Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin Infect Dis. 1992; 14(Suppl 1):S148-53.

354. Spinillo A, Capuzzo E, Gulminetti R et al. Prevalence of and risk factors for fungal vaginitis caused by non-albicans species. Am J Obstet Gynecol. 1997; 176: 138-41. [PubMed 9024104]

355. Chaim W. Fungal vaginitis caused by nonalbicans species. Am J Obstet Gynecol. 1997; 177: 485. [IDIS 393344] [PubMed 9290485]

356. Spinillo A, Capuzzo E. Fungal vaginitis caused by nonalbicans species. Am J Obstet Gynecol. 1997; 177: 485-6.

357. Redondo-Lopez V, Lynch M, Schmitt C et al. Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents. Obstet Gynecol. 1990; 76: 651-5.

358. Chapman SW, Rogers PD, Rinaldi MG et al. Susceptibilities of clinical and laboratory isolates of Blastomyces dermatitidis to ketoconazole, itraconazole, and fluconazole. Antimicrob Agents Chemother. 1998; 42:978-80. [IDIS 403759] [PubMed 9559827]

359. Hoban DJ, Zhanel GG, Karlowsky JA. In vitro susceptibilities of Candida and Cryptococcus neoformans isolates from blood cultures of neutropenic patients. Antimicrob Agents Chemother. 1999; 43:1463-4. [PubMed 10348771]

360. Pfaller MA, Messer SA, Hollis RJ et al. Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States. Diagn Microbiol Infect Dis. 1999; 33:217-22. [PubMed 10212747]

361. Cartledge JD, Midgley J, Gazzard BG. Non-albicans oral candidiasis in HIV-positive patients. J Antimicrob Chemother. 1999; 43:419-22. [IDIS 425880] [PubMed 10223601]

362. Martin-Mazuelos E, Gutierrez MJ, Aller AI et al. A comparative evaluation of Etest and broth microdilution methods for fluconazole and itraconazole susceptibility testing of Candida spp. J Antimicrob Chemother. 1999; 43:477-81. [IDIS 427715] [PubMed 10350375]

363. Canton E, Peman J, Carrillo-Munoz A et al. Fluconazole susceptibilities of bloodstream Candida sp. isolates as determined by National Committee for Clinical Laboratory Standards method M27-A and two other methods. J Clin Microbiol. 1999; 37:2197-200. [PubMed 10364585]

364. Nolte FS, Parkinson T, Falconer DJ et al. Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia. Antimicrob Agents Chemother. 1997; 44:196-9.

365. Law D, Moore CB, Denning DW. Activity of SCH 56592 compared with those of fluconazole and itraconazole against Candida spp. Antimicrob Agents Chemother. 1997; 41:2310-11. [PubMed 9333073]

366. Aguilar C, Pujol I, Guarro J. In vitro antifungal susceptibilities of Scopulariopsis isolates. Antimicrob Agents Chemother. 1999; 43:1520-2. [IDIS 426263] [PubMed 10348787]

367. Newberry DL, Bass SN, Mbanefo CO. A fluconazole/amitriptyline drug interaction in three male adults. Clin Infect Dis. 1997; 24:270-1. [IDIS 381126] [PubMed 9114163]

368. de Wit S, Debier M, de Smet M et al. Effect of fluconazole on indinavir pharmacokinetics in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1998; 42:223-7. [IDIS 403763] [PubMed 9527763]

369. Ahonen J, Olkkola KT, Takala A et al. Interaction between fluconazole and midazolam in intensive care patients. Acta Anaesthesiol Scand. 1999; 43:509-14. [PubMed 10341997]

370. Nair DR, Morris HH. Potential fluconazole-induced carbamazepine toxicity. Ann Pharmacother. 1999; 33:790-2. [IDIS 431849] [PubMed 10466905]

371. Bristol-Myers Squibb Company. Sustiva (efavirenz) capsules and tablets prescribing information. Princeton, NJ; 2010 Mar.

372. Abdel-Rahman, Nahata MC. Treatment of tinea capitis. Ann Pharmacother. 1997; 31:338-48. [IDIS 380840] [PubMed 9066943]

373. Faergemann J, Mork NJ, Haglund A et al. A multicentre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris. Br J Dermatol. 1997; 136:575-7. [IDIS 384787] [PubMed 9155961]

374. Nozickova M, Koudelkova V, Kulikova Z et al. A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidosis. Int J Dermatol. 1998; 37:701-8. [PubMed 9762825]

375. Gupta AK, Adam P, Hofstader SLR et al. Intermittent short duration therapy with fluconazole is effective for tinea capitis. Br J Dermatol. 1999; 141:304-6. [IDIS 432411] [PubMed 10468805]

376. Friedlander SF. The evolving role of itraconazole, fluconazole and terbinafine in the treatment of tinea capitis. Pediatr Infect Dis J. 1999; 18:205-10. [IDIS 423797] [PubMed 10048703]

377. Elewski BE. Treatment of tinea capitis: beyond griseofulvin. J Am Acad Dermatol. 1999; 40:S27-30.

378. Stary A, Sarnow E. Fluconazole in the treatment of tinea corporis and tinea cruris. Dermatology. 1998; 196:237-41. [PubMed 9568414]

379. Solomon BA, Collins R, Sharma R et al. Fluconazole for the treatment of tinea capitis in children. J Am Acad Dermatol. 1997; 37:274-5. [IDIS 391957] [PubMed 9270520]

380. Gupta AK, Einarson TR, Summerbell RC et al. An overview of topical antifungal therapy in dermatomycoses: a North American perspective. Drugs. 1998; 55:645-74. [PubMed 9585862]

381. Piérard GE, Arrese JE, Piérard-Franchimont C. Treatment and prophylaxis of tinea infections. Drugs. 1996; 52:209-24. [PubMed 8841739]

382. Lesher JL. Recent developments in antifungal therapy. Dermatol Clin. 1996; 14:163-9. [PubMed 8821170]

383. Hay RJ. Dermatophytosis and other superficial mycoses. In: Mandel GL, Douglas RG Jr, Bennett JE, eds. Principles and practices of infectious disease. 4th ed. New York: Churchill Livingston; 1995: 2375-86.

384. Drake LA, Dincehart SM, Farmer ER et al. Guidelines of care for superficial mycotic infections of the skin: tinea corporis, tinea cruris, tinea faciei, tinea manuum, and tinea pedis. J Am Acad Dermatol. 1996; 34:282-6. [IDIS 363962] [PubMed 8642094]

385. Elewski B. Tinea capitis. Dermatol Clin. 1996; 14:23-31. [PubMed 8821154]

386. Crissey JT. Common dermatophyte infections: a simple diagnostic test and current management. Postgrad Med. 1998; 103:191-205. [IDIS 401902] [PubMed 9479316]

387. Drake LA, Dincehart SM, Farmer ER et al. Guidelines of care for superficial mycotic infections of the skin: tinea capitis and tinea barbae. J Am Acad Dermatol. 1996; 34:290-4. [IDIS 363964] [PubMed 8642096]

388. Favel A, Michel-Nguyen A, Chastin C et al. In-vitro susceptibility pattern of Candida lusitaniae and evaluating of the Etest method. J Antimicrob Chemother. 1997; 39:591-6. [IDIS 387158] [PubMed 9184357]

389. Borin MT, Cox SR, Herman BD et al. Effect of fluconazole on steady-state pharmacokinetics of delavirdine in human immunodeficiency virus-positive patients. Antimicrob Agents Chemother. 1997; 41:1892-7. [IDIS 393391] [PubMed 9303380]

390. Moran GP, Sullivan DJ, Henman MC et al. Antifungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole-resistant derivatives in vitro. Antimicrob Agents Chemother. 1997; 41:617-23. [IDIS 383166] [PubMed 9056003]

391. Schwarze R, Penk A, Pittrow L. Administration of fluconazole in children below 1 year of age. Mycoses. 1999; 42:3-16. [PubMed 10394841]

392. Wainer S, Cooper PA, Gouws H et al. Prospective study of fluconazole therapy in systemic neonatal fungal infection. Pediatr Infect Dis J. 1997; 16:763-7. [IDIS 391841] [PubMed 9271038]

393. Lee JW, Seibel NL, Amantea M et al. Safety and pharmacokinetics of fluconazole in children with neoplastic diseases. J Pediatr. 1992; 120:987-93. [IDIS 297901] [PubMed 1593362]

394. Driessen M, Ellis JB, Cooper PA et al. Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pediatr Infect Dis J. 1996; 15:1107-12. [IDIS 378160] [PubMed 8970221]

395. Novelli V, Holzel H. Safety and tolerability of fluconazole in children. Antimicrob Agents Chemother. 1999; 43:1955-60. [IDIS 433946] [PubMed 10428919]

396. Jick SS. Pregnancy outcomes after maternal exposure to fluconazole. Pharmacotherapy. 1999; 19:221-2. [IDIS 418873] [PubMed 10030772]

397. Sorensen HT, Nielsen GL, Olesen C et al. Risk of malformations and other outcomes in children exposed to fluconazole in utero. Br J Clin Pharmacol. 1999; 48:234-8. [IDIS 432038] [PubMed 10417502]

398. Pappas PG, Kauffman CA, Perfect J et al. Alopecia associated with fluconazole therapy. Ann Intern Med. 1995; 123:354-7. [IDIS 352959] [PubMed 7625624]

399. Sobel JD, Brooker D, Stein GE et al. Single oral dose fluconazole compared with conventional clotrimazole topical therapy of Candida vaginitis. Am J Obstet Gynecol. 1995; 172:1263-8. [IDIS 346294] [PubMed 7726267]

400. Phillips P, De Beule K, Frechette G et al. A double-blind comparison of itraconazole oral solution and fluconazole capsules for the treatment of oropharyngeal candidiasis in patients with AIDS. Clin Infect Dis. 1998; 26:1368-73. [IDIS 409160] [PubMed 9636865]

401. Wilcox CM, Darouiche RO, Laine L et al. A randomized, double-blind comparison of itraconazole oral solution and fluconazole tablets in the treatment of esophageal candidiasis. J Infect Dis. 1997; 176:227-32. [IDIS 389130] [PubMed 9207371]

402. Marints MD, Rex JH. Fluconazole suspension for oropharyngeal candidiasis unresponsive to tablets. Ann Intern Med. 1997; 126:332-3. [IDIS 380164] [PubMed 9036812]

403. Barbaro G, Barbarini G, Di Lorenzo G et al. Fluconazole vs itraconazole-flucytosine association in the treatment of esophageal candidiasis in AIDS patients: a double-blind, multicenter placebo-controlled study. Chest. 1996; 110:1507-14. [IDIS 378578] [PubMed 8989069]

404. Vazquez JA. Options for the management of mucosal candidiasis in patient with AIDS and HIV infection. Pharmacotherapy. 1999; 19:76-87. [IDIS 417512] [PubMed 9917080]

405. Turner DL, Johnson SA, Rule SA. Successful treatment of candidal osteomyelitis with fluconazole following failure with liposomal amphotericin. J Infect. 1999; 38:51-3. [IDIS 424621] [PubMed 10090510]

406. Blomgren J, Berggren U, Jontell M. Fluconazole versus nystatin in the treatment of oral candidosis. Acta Odontol Scand. 1998; 56:202-5. [PubMed 9765010]

407. Rodriquez-Arrondo F, Aguirrebengoa K, De Arce A et al. Candidal meningitis in HIV-infected patients: treatment of fluconazole. Scand J Infect Dis. 1998; 30:417-8. [PubMed 9817525]

408. Kamitsuka MD, Nugent NA, Conrad PD et al. Candida albicans brain abscesses in a premature infant treated with amphotericin B, flucytosine and fluconazole. Pediatr Infect Dis J. 1995; 14:329-41. [IDIS 345880] [PubMed 7603822]

409. Gurses N, Kalayci AG. Fluconazole monotherapy for candidal meningitis in a premature infant. Clin Infect Dis. 1996; 23:645-6. [IDIS 375096] [PubMed 8879800]

410. Huttova M, Hartmanova I, Kralinsky K et al. Candida fungemia in neonates treated with fluconazole: report of forty cases, including eight with meningitis. Pediatr Infect Dis J. 1998; 17:1012-5. [IDIS 417348] [PubMed 9849984]

411. Robinson LG, Jain L, Kourtis AP. Persistent candidemia in a premature infant treated with fluconazole. Pediatr Infect Dis J. 1999; 18:735-7. [IDIS 432101] [PubMed 10462351]

412. Rotstein C, Bow EJ, Laverdiere M et al. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. Clin Infect Dis. 1999; 28:331-40. [IDIS 420429] [PubMed 10064252]

413. Havlir DV, Dube MP, McCutchan JA et al. Prophylaxis with weekly versus daily fluconazole for fungal infections in patients with AIDS. Clin Infect Dis. 1998; 27:1369-75. [IDIS 418640] [PubMed 9868644]

414. Mylonakis E, Flanigan TP. Editorial response: antifungal prophylaxis with weekly fluconazole for patients with AIDS. Clin Infect Dis. 1998; 27:1376-8. [IDIS 418641] [PubMed 9868645]

415. Gripshover BM, Valdez H, Salata RA et al. Withdrawal of fluconazole suppressive therapy for thrush in patients responding to combination antiviral therapy including protease inhibitors. AIDS. 1998; 12:2513-4. [PubMed 9875599]

416. Saag MS, Cloud GA, Graybill JR et al. A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1999; 28:291-6. [IDIS 420425] [PubMed 10064246]

417. Scher RK, Breneman D, Rich P et al. Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail. J Am Acad Dermatol. 1998; 38:S77-86.

418. Ling MR, Swinyer LJ, Jarratt MT et al. Once-weekly fluconazole (450 mg) for 4, 6, or 99 months of treatment for distal subungual onychomycosis of the toenail. J Am Acad Dermatol. 1998; 38:S95-102.

419. Elewski BE, Hay RJ. Update on the management of onychomycosis: highlights of the third annual international summit on cutaneous antifungal therapy. Clin Infect Dis. 1996; 23:305-13. [IDIS 370227] [PubMed 8842269]

420. Trepanier EF, Amsden GW. Current issues in onychomycosis. Ann Pharmacother. 1998; 32:204-14. [IDIS 400373] [PubMed 9496407]

421. Niewerth M, Korting HC. Management of onychomycosis. Drugs. 1999; 58:38:283-96.

422. Hughes WT, Armstrong D, Bodey GP et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002; 34:730-51. [IDIS 479956] [PubMed 11850858]

423. Walsh TJ, Anaissie EJ, Denning DW et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008; 46:327-60. [PubMed 18177225]

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

425. Pappas PG, Kauffman CA, Andes D et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009; 48:503-35. [PubMed 19191635]

426. Galgiani JN, Ampel NM, Blair JE et al. Coccidioidomycosis. Clin Infect Dis. 2005; 41:1217-23. [PubMed 16206093]

427. Perfect JR, Dismukes WE, Dromer F et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010; 50:291-322. [PubMed 20047480]

428. Wheat LJ, Freifeld AG, Kleiman MB et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007; 45:807-25. [PubMed 17806045]

429. Kauffman CA, Bustamante B, Chapman SW et al. Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007; 45:1255-65. [PubMed 17968818]

430. Powderly WG, Mayer KH, Perfect JR. Diagnosis and treatment of oropharyngeal candidiasis in patients infected with HIV: a critical reassessment. AIDS Res Hum Retroviruses. 1999; 15:1405-12. [PubMed 10555102]

432. Cato A, Cao G, Hsu A et al. Evaluation of the effect of fluconazole on the pharmacokinetics of ritonavir. Drug Metab Dispos. 1997; 25:1104-6. [IDIS 393713] [PubMed 9311629]

433. Abbott Laboratories. Kaletra (lopinavir/ritonavir) tablet, film coated and solution prescribing information. North Chicago, IL; 2010 Jun.

434. Pfizer. Rescriptor (delavirdine mesylate) tablets prescribing information. New York, NY; 2008 May.

435. Boehringer Ingelheim. Viramune (nevirapine) tablets and oral suspension prescribing information. Ridgefield, CT; 2010 Jun.

436. . Antifungal drugs. Treat Guidel Med Lett. 2009; 7:95-102; quiz 103-4. [PubMed 19940816]

438. Piscitelli SC, Kelly G, Walker RE et al. A multiple drug interaction study of stavudine with agents for opportunistic infections in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1999; 43:647-50. [IDIS 424139] [PubMed 10049281]

439. Hilbert J, Messig M, Kuye O et al. Evaluation of interaction between fluconazole and oral contraceptive in healthy women. Obstet Gynecol. 2001; 98:218-23. [PubMed 11506836]

440. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58(RR-4):1-207; quiz CE1-4.

441. Mofenson LM, Brady MT, Danner SP et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009; 58(RR-11):1-166. [PubMed 19730409]

442. Anon. Drugs for parasitic infections. Treat Guidel Med Lett. 2010; 8 (suppl). From the Medical Letter website.

443. Workowski KA, Berman S, Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010; 59(RR-12):1-110.

444. Anon. Drugs for sexually transmitted infections. Treat Guidel Med Lett. 2010; 8:53-60. [PubMed 20585282]

445. Boehringer Ingelheim. Aptivus (tipranavir) capsules and oral suspension prescribing information. Ridgefield, CT; 2010 Apr.

446. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) prescribing information. Princeton, NJ; 2010 Apr.

447. Tibotec Therapeutics. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2010 Feb.

448. McMahon JH, Grayson ML. Torsades de pointes in a patient receiving fluconazole for cerebral cryptococcosis. Am J Health Syst Pharm. 2008; 65:619-23. [PubMed 18359968]

449. Gomez-Lopez A, Zaragoza O, Dos Anjos Martins M et al. In vitro susceptibility of Cryptococcus gattii clinical isolates. Clin Microbiol Infect. 2008; 14:727-30. [PubMed 18558948]

450. Okamoto K, Hatakeyama S, Itoyama S et al. Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007. Emerg Infect Dis. 2010; 16:1155-7. [PubMed 20587194]

451. Grosse P, Tintelnot K, Söllner O et al. Encephalomyelitis due to Cryptococcus neoformans var gattii presenting as spinal tumour: case report and review of the literature. J Neurol Neurosurg Psychiatry. 2001; 70:113-6. [PubMed 11118259]

452. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation. MMWR Recomm Rep. 2000; 49(RR-10):1-125.

453. Stemmer SM, Maor Y, Hardan I. Oral fluconazole for empiric treatment of prolonged fever in neutropenic patients: prospective study in 250 consecutive patients after stem cell transplantation. Am J Clin Oncol. 2004; 27:328-32. [PubMed 15289723]

454. González U, Seaton T, Bergus G et al. Systemic antifungal therapy for tinea capitis in children. Cochrane Database Syst Rev. 2007; :CD004685. [PubMed 17943825]

455. Brown SJ. Efficacy of fluconazole for the treatment of onychomycosis. Ann Pharmacother. 2009; 43:1684-91. [PubMed 19776299]

456. Roberts DT, Taylor WD, Boyle J et al. Guidelines for treatment of onychomycosis. Br J Dermatol. 2003; 148:402-10. [PubMed 12653730]

457. de Berker D. Clinical practice. Fungal nail disease. N Engl J Med. 2009; 360:2108-16. [PubMed 19439745]

458. Welsh O, Vera-Cabrera L, Welsh E. Onychomycosis. Clin Dermatol. 2010; 28:151-9. [PubMed 20347657]

459. Yazdanpanah MJ, Azizi H, Suizi B. Comparison between fluconazole and ketoconazole effectivity in the treatment of pityriasis versicolor. Mycoses. 2007; 50:311-3. [PubMed 17576325]

460. Farschian M, Yaghoobi R, Samadi K. Fluconazole versus ketoconazole in the treatment of tinea versicolor. J Dermatolog Treat. 2002; 13:73-6. [PubMed 12060505]

461. Partap R, Kaur I, Chakrabarti A et al. Single-dose fluconazole versus itraconazole in pityriasis versicolor. Dermatology. 2004; 208:55-9. [PubMed 14730238]

462. Bhogal CS, Singal A, Baruah MC. Comparative efficacy of ketoconazole and fluconazole in the treatment of pityriasis versicolor: a one year follow-up study. J Dermatol. 2001; 28:535-9. [PubMed 11732720]

463. Drake LA, Dincehart SM, Farmer ER et al. Guidelines of care for superficial mycotic infections of the skin: pityriasis (tinea) versicolor. J Am Acad Dermatol. 1996; 34:287-9. [IDIS 363963] [PubMed 8642095]

464. Fisher BT, Chiller TM, Prasad PA et al. Hospitalizations for coccidioidomycosis at forty-one children’s hospitals in the United States. Pediatr Infect Dis J. 2010; 29:243-7. [PubMed 19934792]

465. Drake KW, Adam RD. Coccidioidal meningitis and brain abscesses: analysis of 71 cases at a referral center. Neurology. 2009; 73:1780-6. [PubMed 19933980]

466. Burwell LA, Park BJ, Wannemuehler KA et al. Outcomes among inmates treated for coccidioidomycosis at a correctional institution during a community outbreak, Kern County, California, 2004. Clin Infect Dis. 2009; 49:e113-9. [PubMed 19886797]

467. Ramani R, Chaturvedi V. Antifungal susceptibility profiles of Coccidioides immitis and Coccidioides posadasii from endemic and non-endemic areas. Mycopathologia. 2007; 163:315-9. [PubMed 17484074]

468. Cordeiro RA, Brilhante RS, Rocha MF et al. In vitro activities of caspofungin, amphotericin B and azoles against Coccidioides posadasii strains from Northeast, Brazil. Mycopathologia. 2006; 161:21-6. [PubMed 16389480]

469. Sar B, Boy S, Keo C et al. In vitro antifungal-drug susceptibilities of mycelial and yeast forms of Penicillium marneffei isolates in Cambodia. J Clin Microbiol. 2006; 44:4208-10. [PubMed 16971649]

470. Imwidthaya P, Thipsuvan K, Chaiprasert A et al. Penicillium marneffei: types and drug susceptibility. Mycopathologia. 2001; 149:109-15. [PubMed 11307592]

471. Healy CM, Baker CJ. Fluconazole prophylaxis in the neonatal intensive care unit. Pediatr Infect Dis J. 2009; 28:49-52. [PubMed 19106754]

472. Aziz M, Patel AL, Losavio J et al. Efficacy of fluconazole prophylaxis for prevention of invasive fungal infection in extremely low birth weight infants. Pediatr Infect Dis J. 2010; 29:352-6. [PubMed 19934791]

473. Manzoni P, Stolfi I, Pugni L et al. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. N Engl J Med. 2007; 356:2483-95. [PubMed 17568029]

474. Reed BN, Caudle KE, Rogers PD. Fluconazole prophylaxis in high-risk neonates. Ann Pharmacother. 2010; 44:178-84. [PubMed 20040701]

475. Manzoni P, Mostert M, Jacqz-Aigrain E et al. The use of fluconazole in neonatal intensive care units. Arch Dis Child. 2009; 94:983-7. [PubMed 19723639]

476. Gupta AK, Cooper EA, Montero-Gei F. The use of fluconazole to treat superficial fungal infections in children. Dermatol Clin. 2003; 21:537-42. [PubMed 12956206]

477. Gupta AK, Ryder JE, Nicol K et al. Superficial fungal infections: an update on pityriasis versicolor, seborrheic dermatitis, tinea capitis, and onychomycosis. Clin Dermatol. 2003 Sep-Oct; 21:417-25.

478. Gupta AK, Cooper EA, Ryder JE et al. Optimal management of fungal infections of the skin, hair, and nails. Am J Clin Dermatol. 2004; 5:225-37. [PubMed 15301570]

479. Finch JJ, Warshaw EM. Toenail onychomycosis: current and future treatment options. Dermatol Ther. 2007 Jan-Feb; 20:31-46.

480. Galanis E, Hoang L, Kibsey P et al. Clinical presentation, diagnosis and management of Cryptococcus gattii cases: Lessons learned from British Columbia. Can J Infect Dis Med Microbiol. 2009; 20:23-8. [PubMed 20190892]

481. Koks CH, Crommentuyn KM, Hoetelmans RM et al. The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV-1-infected individuals. Br J Clin Pharmacol. 2001; 51:631-5. [PubMed 11422025]

482. Ahonen J, Olkkola KT, Neuvonen PJ. Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. Eur J Clin Pharmacol. 1997; 51:415-9. [PubMed 9049584]

483. Olkkola KT, Ahonen J, Neuvonen PJ. The effects of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Analg. 1996; 82:511-6. [PubMed 8623953]

484. Hynninen VV, Olkkola KT, Leino K et al. Effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of s-(+)- and R-(-)-Ibuprofen. Antimicrob Agents Chemother. 2006; 50:1967-72. [PubMed 16723553]

485. Palkama VJ, Isohanni MH, Neuvonen PJ et al. The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. Anesth Analg. 1998; 87:190-4. [PubMed 9661572]

486. Kantola T, Backman JT, Niemi M et al. Effect of fluconazole on plasma fluvastatin and pravastatin concentrations. Eur J Clin Pharmacol. 2000; 56:225-9. [PubMed 10952477]

487. Kaukonen KM, Olkkola KT, Neuvonen PJ. Fluconazole but not itraconazole decreases the metabolism of losartan to E-3174. Eur J Clin Pharmacol. 1998; 53:445-9. [PubMed 9551703]

488. Cobb MN, Desai J, Brown LS et al. The effect of fluconazole on the clinical pharmacokinetics of methadone. Clin Pharmacol Ther. 1998; 63:655-62. [PubMed 9663180]

489. Hallberg P, Martén L, Wadelius M. Possible fluconazole-fentanyl interaction-a case report. Eur J Clin Pharmacol. 2006; 62:491-2. [PubMed 16758267]

490. Saari TI, Laine K, Neuvonen M et al. Effect of voriconazole and fluconazole on the pharmacokinetics of intravenous fentanyl. Eur J Clin Pharmacol. 2008; 64:25-30. [PubMed 17987285]

491. Babalola CP, Kolade YT, Olaniyi AA et al. Effect of fluconazole on the pharmacokinetics of halofantrine in healthy volunteers. J Clin Pharm Ther. 2009; 34:677-82. [PubMed 20175801]

492. Food and Drug Administration. FDA Drug Safety Communication: Use of long-term, high-dose Diflucan (fluconazole) during pregnancy may be associated with birth defects in infants. Rockville, MD; 2011 Aug 3. From FDA website. Accessed 2011 Aug 9.

493. Lopez-Rangel E, Van Allen MI. Prenatal exposure to fluconazole: an identifiable dysmorphic phenotype. Birth Defects Res A Clin Mol Teratol. 2005; 73:919-23. [PubMed 16265639]

494. Lee BE, Feinberg M, Abraham JJ et al. Congenital malformations in an infant born to a woman treated with fluconazole. Pediatr Infect Dis J. 1992; 11:1062-4. [PubMed 1461702]

495. Aleck KA, Bartley DL. Multiple malformation syndrome following fluconazole use in pregnancy: report of an additional patient. Am J Med Genet. 1997; 72:253-6. [PubMed 9332650]

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:512-18.

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