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Sporanox

Pronunciation

Generic Name: Itraconazole
Class: Azoles
VA Class: AM700
Chemical Name: 4 - [4 - [4 - [4 - [[2 - (2,4 - dichlorophenyl) - 2 - (1H - 1,2,4 - triazol - 1 - ylmethyl) - 1,3 - dioxolan - 4 - l]methoxy]phenyl] - 1 - piperazinyl]phenyl] - 2,4 - dihydro - 2 - (1 - methylpropyl) - 3H - 1,2,4 - triazol - 3 - one
CAS Number: 84625-61-6

Warning(s)

  • Itraconazole capsules should not be used for treatment of onychomycosis in patients with evidence of ventricular dysfunction, including CHF or history of CHF.1

  • Discontinue itraconazole if signs or symptoms of CHF occur.1 IV itraconazole (no longer commercially available in the US) caused negative inotropic effects in healthy individuals and in dogs.1 48

  • Concomitant use with cisapride (currently commercially available in the US only under a limited-access protocol), pimozide, quinidine, dofetilide, or levomethadyl (no longer commercially available in the US) is contraindicated.1 48 Itraconazole is a potent inhibitor of CYP3A4 isoenzymes and may increase plasma concentrations of drugs metabolized by CYP3A4.1 48 Serious cardiovascular events, including QT prolongation, torsades de pointes, ventricular tachycardia, cardiac arrest, and/or sudden death have occurred in patients using cisapride, pimozide, levomethadyl, or quinidine concomitantly with itraconazole and/or other CYP3A4 inhibitors.1 48 (See Interactions.)

Introduction

Antifungal; azole (triazole derivative).1 3 37 48

Uses for Sporanox

Aspergillosis

Treatment of invasive aspergillosis.1 66 423 Considered an alternative, not a drug of choice.1 423 436

Treatment of pulmonary and extrapulmonary aspergillosis in patients intolerant of, or whose disease is refractory to, IV amphotericin B.1 66

IDSA considers voriconazole the drug of choice for primary treatment of invasive aspergillosis in most patients and IV amphotericin B the preferred alternative.423 For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends amphotericin B, caspofungin, micafungin, posaconazole, or itraconazole.423 For empiric or preemptive therapy of presumed aspergillosis, IDSA recommends amphotericin B, caspofungin, itraconazole, or voriconazole.423

Not considered a drug of choice or preferred alternative for treatment of invasive aspergillosis in HIV-infected individuals.440 441 For treatment of invasive aspergillosis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend voriconazole as the drug of choice;440 voriconazole also considered the drug of choice for treatment of invasive aspergillosis in HIV-infected children.441 Because the drugs have similar mechanisms of action and cross-resistance may occur, itraconazole not recommended for treatment of aspergillosis refractory to voriconazole.441

For primary prophylaxis of aspergillosis in immunocompromised individuals at high risk of invasive disease (i.e., neutropenic patients with acute myelogenous leukemia [AML] or myelodysplastic syndrome [MDS], hematopoietic stem cell transplant [HSCT] recipients with graft-versus-host disease [GVHD]), IDSA considers posaconazole the drug of choice;423 alternatives are itraconazole or micafungin.423

Blastomycosis

Treatment of pulmonary and extrapulmonary blastomycosis caused by Blastomyces dermatitidis.1 36 49 50 51 52 53 54 59 62 63 424 436

Drugs of choice are oral itraconazole or IV amphotericin B.36 49 50 51 52 436

IV amphotericin B is preferred for initial treatment of severe blastomycosis, especially infections involving the CNS51 52 55 56 50 51 52 53 54 61 424 436 and for initial treatment of presumptive blastomycosis in immunocompromised patients, including HIV-infected individuals.50 55 61 424

Itraconazole is the drug of choice for treatment of nonmeningeal, non-life-threatening blastomycosis, including mild to moderate pulmonary blastomycosis or mild to moderate disseminated blastomycosis (without CNS involvement), and also is recommended for follow-up therapy in patients with more severe infections after an initial response has been obtained with IV amphotericin B.36 61 62 63 424 436

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 the initial diagnosis.57 58

IDSA states that long-term suppressive or maintenance therapy (secondary prophylaxis) with 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 Other Invasive Candida Infections

Not a drug of choice or preferred alternative for treatment of candidemia or other invasive Candida infections.425 436 Fluconazole or voriconazole usually are recommended when an azole antifungal is used for treatment of candidemia.425 436

Has been used and is recommended as an alternative for initial empiric treatment of suspected invasive candidiasis in neutropenic patients.425 IV amphotericin B, caspofungin, or voriconazole are drugs of choice in these patients;425 alternatives are fluconazole or itraconazole.425 Do not use an azole antifungal for empiric treatment in patients who previously received an azole for prophylaxis.425

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis.48 425

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

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

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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 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.48 425

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 (caspofungin, micafungin, anidulafungin) 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 the 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 esophageal 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 Itraconazole is not included in current recommendations for secondary prophylaxis of esophageal candidiasis.425 440

Vulvovaginal Candidiasis

Has been used for treatment of uncomplicated vulvovaginal candidiasis.436

Vulvovaginal candidiasis is usually treated with an intravaginal azole antifungal (e.g., butoconazole, clotrimazole, miconazole, terconazole, tioconazole) or a single-dose oral fluconazole regimen.425 436 443 444 Although some clinicians suggest that oral itraconazole or oral ketoconazole can be used as alternatives for treatment of vulvovaginal candidiasis,436 fluconazole is the only oral antifungal included in CDC recommendations for treatment of uncomplicated or complicated vulvovaginal candidiasis.443

Chromomycosis

Has been used for treatment of chromomycosis (chromoblastomycosis) caused by various dematiaceous fungi (e.g., Cladosporium, Exophiala, Fonsecaea, Phialophora).43 60 71 72 73

Coccidioidomycosis

Treatment and prevention of coccidioidomycosis caused by Coccidioides immitis or C. posadasii.36 56 60 426 436 440 441 A drug of choice.426 436 440

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

For initial treatment of symptomatic pulmonary coccidioidomycosis and chronic fibrocavitary or disseminated (extrapulmonary) coccidioidomycosis, IDSA states than 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).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 coccidioidomycosis or extrathoracic disseminated (nonmeningeal) coccidioidomycosis 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 (nonmeningeal) coccidioidomycosis.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 the regimen of choice.426 440 441 Itraconazole may be an alternative to fluconazole in adults and adolescents.440 Consultation with an expert is recommended.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 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.426

Cryptococcosis

Has been used for treatment of cryptococcosis.36 49 68 427 436 440 441 Not a drug of choice or preferred alternative.427 440 441

For treatment of cryptococcal meningitis in HIV-infected adults, adolescents, and children, CDC, NIH, and IDSA state that the preferred regimen is initial (induction) therapy with IV amphotericin B given in conjunction with oral flucytosine, then follow-up (consolidation) therapy with oral fluconazole.427 440 441 Although data are limited and use of the drug is discouraged, IDSA and others state that itraconazole can be considered an alternative for induction and consolidation therapy if all other alternative regimens have failed or are not available.427 440 441

For treatment of mild to moderate pulmonary cryptococcosis in immunocompetent individuals, the regimen of choice is oral fluconazole.427 Although data are limited, IDSA states that itraconazole, voriconazole, and posaconazole are acceptable alternatives in immunocompetent individuals if fluconazole is unavailable or contraindicated.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 cryptococcus 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

Although data are limited, IDSA states that recommendations for treatment of CNS 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

Histoplasmosis

Treatment of histoplasmosis caused by Histoplasma capsulatum, including chronic cavitary pulmonary disease and disseminated nonmeningeal disease.48 428 436 440 441

Drugs of choice for treatment of histoplasmosis are IV amphotericin B and oral itraconazole.36 49 55 59 60 61 65 428 436 440 441 IV amphotericin B is preferred for initial treatment of severe, life-threatening histoplasmosis, especially in immunocompromised patients such as those with HIV infection.36 42 44 45 49 55 56 60 61 64 65 428 436 440 441 Oral itraconazole generally is used for initial treatment of less severe disease (e.g., mild to moderate acute pulmonary histoplasmosis, chronic cavitary pulmonary histoplasmosis) and as follow-up treatment of severe infections after a response has been obtained with IV amphotericin B.36 49 56 59 61 65 428 436 440 441

For treatment of moderately severe to severe acute pulmonary histoplasmosis or progressive disseminated histoplasmosis in HIV-infected adults and adolescents and other adults, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B and follow-up treatment with oral itraconazole.428 440

For treatment of progressive disseminated histoplasmosis in children, IDSA states that IV amphotericin B or an initial regimen of IV amphotericin B and follow-up treatment with oral itraconazole can be used.428 For treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected infants and children, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B and follow-up treatment with oral itraconazole.441 Although oral itraconazole may be used alone for treatment of mild to moderate disseminated histoplasmosis in children, including HIV-infected infants and children, it is not recommended for more severe infections.428 441

HIV-infected adults or adolescents with CD4+ T-cell counts <150/mm3 who are at high risk because they reside in areas where histoplasmosis is highly endemic should receive primary prophylaxis against initial episodes of histoplasmosis.428 436 440 Itraconazole is the drug of choice for primary prophylaxis against histoplasmosis in these HIV-infected adults and adolescents.428 436 440 Primary prophylaxis against histoplasmosis is not recommended in HIV-infected children.441

HIV-infected adults, adolescents, or children and other immunosuppressed individuals who have been adequately treated for histoplasmosis should receive long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent recurrence or relapse.428 440 441 Itraconazole is the drug of choice for secondary prophylaxis against histoplasmosis.428 440

Microsporidiosis

Treatment of microsporidiosis.135 136 440 442

Has been effective in a few cases of keratoconjunctivitis or sinusitis caused by Encephalitozoon.135 136 Regimen of choice for ocular microsporidiosis is fumagillin (not commercially available in the US) used in conjunction with albendazole.440 441 442

Alternative for disseminated microsporidiosis, especially infections caused by Trachipleistophora or Anncaliia;440 442 used in conjunction with albendazole.440 442 Albendazole usually is the drug of choice for intestinal or disseminated microsporidiosis (except infections caused by Enterocytozoon bienuesi or Vittaforma corneae).440 441 442

Onychomycosis

Treatment of onychomycosis of the toenails (with or without fingernail involvement) and onychomycosis of the fingernails caused by dermatophytes (tinea unguium).1 132 133 436

Paracoccidioidomycosis

Treatment of paracoccidioidomycosis (South American blastomycosis) caused by Paracoccidioides brasiliensis.36 43 56 436

IV amphotericin B is the drug of choice for initial treatment of severe paracoccidioidomycosis.436 Oral itraconazole is the drug of choice for treatment of less severe or localized paracoccidioidomycosis and for follow-up in more severe infections after initial treatment with IV amphotericin B.56 60

Penicilliosis

Treatment of penicilliosis caused by Penicillium marneffei.115 116 117 119 440

For treatment of severe or disseminated P. marneffei infections, including in HIV-infected adults or adolescents, an initial regimen of IV amphotericin B followed by oral itraconazole is recommended.115 116 119 440 Oral itraconazole can be used alone for treatment of mild infections.440

Chronic suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole is recommended to prevent relapse of penicilliosis in HIV-infected adults or adolescents who respond to an initial treatment regimen of IV amphoterin B and/or oral itraconazole.116 117 440

Sporotrichosis

Treatment of sporotrichosis caused by Sporothrix schenckii.43 49 55 56 61 67 429 436

IV amphotericin B is the drug of choice for initial treatment of severe, life-threatening sporotrichosis and sporotrichosis that is disseminated or has CNS involvement.56 60 61 67 429 436 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.43 56 60 61 67 429 436

Zygomycosis

Treatment of GI basidiobolomycosis, a zygomycosis caused by Basidiobolus ranarum.38 104 105 106 107

Has been effective in a few patients for the treatment of subcutaneous basidiobolomycosis.124 125

GI basidiobolomycosis has been successfully treated with oral itraconazole after partial surgical resection of the GI tract; unclear whether a clinical response would have been obtained if itraconazole had been used alone without surgical intervention.38 105

Empiric Therapy in Febrile Neutropenic Patients

Has been used for empiric therapy of presumed fungal infections in febrile neutropenic patients.48 93 425

Sporanox Dosage and Administration

Administration

Administer orally.1 3 30 36 37 38 48

Has been administered by IV infusion,76 but an IV preparation is no longer commercially available in the US.

Oral Administration

Oral bioavailability varies depending on whether the drug is administered as capsules or the oral solution; these preparations should not be used interchangeably.1 48

The possibility that GI absorption may be decreased in patients with hypochlorhydria (e.g., HIV-infected individuals) should be considered.1 10 (See Absorption under Pharmacokinetics.)

Capsules

The capsules should be administered with a full meal to ensure maximal absorption of the drug.1

Capsules should not be used for treatment of oropharyngeal or esophageal candidiasis;425 440 441 efficacy not established,1 may be less effective than oral solution for these infections.425 440 441

If capsules are given in a dosage >200 mg daily, daily dosage should be divided into 2 doses.1

Oral Solution

The oral solution should be administered without food to ensure maximal absorption of the drug.48

For treatment of oropharyngeal or esophageal candidiasis, the recommended dosage of itraconazole oral solution should be vigorously swished in the mouth (10 mL at a time) for several seconds and then swallowed.48

Manufacturer states that data are limited to date regarding the safety of long-term use of itraconazole oral solution (i.e., >6 months).48

Dosage

Because of differences in oral bioavailability, itraconazole capsules and oral solution should not be used interchangeably.1 48

Only the oral solution (not capsules) is indicated for treatment of oropharyngeal or esophageal candidiasis.48

To ensure adequate plasma concentrations of itraconazole (especially in patients with life-threatening fungal infections), IDSA and others recommend that itraconazole plasma concentrations be determined, usually after 2 weeks of therapy.423 424 425 428 429

Pediatric Patients

Blastomycosis
Treatment of Blastomycosis
Oral

Mild to moderate blastomycosis: IDSA recommends 10 mg/kg daily (up to 400 mg daily) for 6–12 months.424

Moderately severe to severe blastomycosis: IDSA recommends an initial regimen of IV amphotericin B given for 1–2 weeks, followed by itraconazole 10 mg/kg daily (up to 400 mg daily) for a total treatment duration of 12 months.424

Candida Infections
Treatment of Oropharyngeal Candidiasis
Oral

HIV-infected infants and children (oral solution): 2.5 mg/kg twice daily (up to 200 mg daily) for 7–14 days.441

HIV-infected infants and children with fluconazole-refractory infections (oral solution): 2.5 mg/kg twice daily (up to 200–400 mg daily) for 7–14 days.441

HIV-infected adolescents (oral solution): 200 mg daily for 7–14 days.440 Same dosage can be used for fluconazole-refractory infections.440

Prevention of Recurrence (Secondary Prophylaxis) of Oropharyngeal Candidiasis
Oral

HIV-infected adolescents (oral solution): 200 mg daily.440

Secondary prophylaxis not usually recommended; use only if patient has frequent or severe recurrences.440 Consider discontinuing secondary prophylaxis if CD4+ T-cell count increases to ≥200/mm3 in response to antiretroviral therapy.440

Treatment of Esophageal Candidiasis
Oral

HIV-infected infants and children (oral solution): 2.5 mg/kg twice daily or 5 mg/kg once daily for 14–21 days.441

HIV-infected adolescents (oral solution): 200 mg daily for 14–21 days.440

Treatment of Vulvovaginal Candidiasis
Oral

HIV-infected adolescents (oral solution): 200 mg daily for 3–7 days.440

Coccidioidomycosis
Treatment of Coccidioidomycosis (Nonmeningeal)
Oral

HIV-infected infants and children with mild coccidioidomycosis (e.g., focal pneumonia): 5–10 mg/kg twice daily for 3 days, then 2–5 mg/kg twice daily.441

HIV-infected infants and children with diffuse pulmonary or disseminated coccidioidomycosis: Initial regimen of IV amphotericin B given until a response is obtained, followed by itraconazole 5–10 mg/kg twice daily for 3 days, then 2–5 mg/kg twice daily (up to 400 mg daily).441

HIV-infected adolescents with mild coccidioidomycosis (e.g., focal pneumonia or positive coccidioidal serologic test alone): 200 mg 3 times daily for 3 days, then 200 mg twice daily.440

Treatment of Coccidioidal Meningitis
Oral

HIV-infected adolescents with meningeal coccidioidomycosis: 200 mg 3 times daily for 3 days, then 200 mg twice daily.440

Consultation with an expert experienced in treating coccidioidal meningitis is recommended.441

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: 200 mg twice daily.440

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

Prevention of Recurrence (Secondary Prophylaxis) of Coccidioidomycosis
Oral

HIV-infected infants and children: 2–5 mg/kg (up to 200 mg) twice daily.441

HIV-infected adolescents: 200 mg twice 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 Cryptococcosis
Oral

HIV-infected infants and children with CNS cryptococcosis: Initial (induction) regimen of IV amphotericin B given for at least 2 weeks, then follow-up (consolidation) regimen of itraconazole 200 mg 3 times daily for 3 days, then 5–10 mg/kg (maximum 200 mg) once or twice daily for at least 8 weeks.441

HIV-infected adolescents with CNS cryptococcosis: Initial (induction) regimen of IV amphotericin B given for at least 2 weeks, then follow-up (consolidation) regimen of itraconazole 200 mg twice daily for 8 weeks or until CD4+ T-cell count is ≥200/mm3 for at least 6 months as the result of antiretroviral therapy.440

Some clinicians suggest the oral solution may be preferred (instead of capsules) for treatment of cryptococcosis.427

Prevention of Recurrence (Secondary Prophylaxis) of Cryptococcosis
Oral

HIV-infected infants and children (oral solution): 5 mg/kg (up to 200 mg) daily.441

HIV-infected adolescents: 200 mg daily.440

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

HIV-infected infants and children with a history of cryptococcosis 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 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 a history of cryptococcosis 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, are receiving antiretroviral therapy, and have CD4+ T-cell counts ≥200/mm3 for >6 months.440 Reinitiate secondary prophylaxis against cryptococcosis if CD4+ T-cell count decreases to <200/mm3.440

Histoplasmosis
Treatment of Histoplasmosis
Oral

Acute pulmonary histoplasmosis: IDSA recommends 5–10 mg/kg daily (up to 400 mg daily) given in 2 divided doses.428

Progressive disseminated histoplasmosis: IDSA recommends initial regimen of IV amphotericin B given for 2–4 weeks, followed by itraconazole 5–10 mg/kg daily (up to 400 mg daily) given in 2 divided doses for a total duration of 3 months.428 A longer duration may be necessary in children with severe disease or with immunosuppression or primary immunodeficiency syndromes.428

HIV-infected infants and children with mild disseminated histoplasmosis (oral solution): 2–5 mg/kg (up to 200 mg) 3 times daily for 3 days, then 2–5 mg/kg (up to 200 mg) twice daily for 12 months.441

HIV-infected infants and children with moderately severe to severe disseminated histoplasmosis: Initial regimen of IV amphotericin B given for at least 1–2 weeks, followed by itraconazole (oral solution) 2–5 mg/kg (up to 200 mg) 3 times daily for 3 days, then 2–5 mg/kg (up to 200 mg) twice daily for 12 months.441

HIV-infected infants and children with CNS histoplasmosis: Initial regimen of IV amphotericin B given for 4–6 weeks, followed by itraconazole (oral solution) 2–5 mg/kg (up to 200 mg) 3 times daily for 3 days, then 2–5 mg/kg (up to 200 mg) twice daily for at least 12 months and until CSF abnormalities resolve and histoplasmal antigen is undetectable.441

HIV-infected adolescents with less severe disseminated histoplasmosis: 200 mg 3 times daily for 3 days, then 200 mg twice daily for at least 12 months.440

HIV-infected adolescents with moderately severe to severe disseminated histoplasmosis: Initial regimen of IV amphotericin B given for at least 2 weeks or until a response is obtained, followed by itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for a total duration of at least 12 months and until histoplasmal antigen is undetectable.441

HIV-infected adolescents with CNS histoplasmosis: Initial regimen of IV amphotericin B given for 4–6 weeks or until a response is obtained, followed by itraconazole 200 mg 2 or 3 times daily for at least 12 months and until CSF abnormalities resolve and histoplasmal antigen is undetectable.441

Some clinicians suggest the oral solution may be preferred (instead of capsules) for treatment of histoplasmosis.428 440

Primary Prophylaxis to Prevent First Episode of Histoplasmosis
Oral

HIV-infected adolescents with CD4+ T-cell counts ≤150/mm3 who are at high risk because they reside in areas where histoplasma is highly endemic: 200 mg daily.440

Consider discontinuing primary prophylaxis in HIV-infected adolescents receiving antiretroviral therapy if CD4+ T-cell count >150/mm3 for 6 months.440 Reinitiate primary prophylaxis if CD4+ T-cell count decreases to ≤150/mm3.440

Prevention of Recurrence (Secondary Prophylaxis) of Histoplasmosis
Oral

HIV-infected infants and children and other immunosuppressed children and children who experience relapse after adequate treatment (oral solution): 5 mg/kg daily (up to 200 mg daily).428 441

HIV-infected adolescents: 200 mg daily.440

Initiate secondary prophylaxis after primary infection has been adequately treated.428 440 441

HIV-infected infants and children with a history of histoplasmosis 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 have negative Histoplasma blood cultures, have serum Histoplasma antigen <2 ng/mL, have received itraconazole for ≥12 months, have been receiving antiretroviral therapy for ≥6 months, and have CD4+ T-cell counts ≥150/mm3.441 Reinitiate secondary prophylaxis against histoplasmosis if CD4+ T-cell count decreases to <150/mm3.441

HIV-infected adolescents with a history of histoplasmosis should receive life-long suppressive therapy to prevent recurrence.440 Consideration can be given to discontinuing secondary prophylaxis in HIV-infected adolescents who have negative Histoplasma blood cultures, have serum Histoplasma antigen <2 ng/mL, have received itraconazole for ≥12 months, have been receiving antiretroviral therapy for ≥6 months, and have CD4+ T-cell counts ≥150/mm3.440 Reinitiate secondary prophylaxis against histoplasmosis if CD4+ T-cell count decreases to <150/mm3.440

Penicilliosis
Treatment of Penicilliosis
Oral

HIV-infected adolescents with mild penicilliosis: 400 mg daily for 8 weeks.440

HIV-infected adolescents with severe penicilliosis: Initial regimen of IV amphotericin B given for 2 weeks, followed by itraconazole 400 mg daily for 10 weeks.440

Prevention of Recurrence (Secondary Prophylaxis) of Penicilliosis
Oral

HIV-infected adolescents: 200 mg daily.440

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

Limited data indicate secondary prophylaxis may be discontinued in HIV-infected adolescents who are receiving antiretroviral therapy and have CD4+ T-cell counts >100/mm3 for ≥6 months.440 Reinitiate secondary prophylaxis against penicilliosis if CD4+ T-cell count decreases to <100/mm3.440

Sporotrichosis
Treatment of Sporotrichosis
Oral

Cutaneous or lymphocutaneous sporotrichosis: IDSA recommends 6–10 mg/kg daily (up to 400 mg daily).429 Continue for 2–4 weeks after all lesions have resolved; usual duration is 3–6 months.429

Disseminated sporotrichosis: IDSA recommends initial regimen of IV amphotericin B given until a response is obtained, followed by itraconazole 6–10 mg/kg daily (up to 400 mg daily) for a total duration of at least 12 months.429

Some clinicians suggest the oral solution may be preferred (instead of capsules) for treatment of sporotrichosis.429

Adults

General Adult Dosage
Treatment of Serious, Life-threatening Systemic Fungal Infections
Oral

Capsules: Manufacturer recommends initial loading dosage of 200 mg 3 times daily (600 mg daily) for the first 3 days, then 200–400 mg daily thereafter.1

Usually continued for 3 months and until clinical parameters and laboratory tests indicate that the active fungal infection has subsided.1 An inadequate period of treatment can result in recurrence of active infection.1

Aspergillosis
Treatment of Pulmonary or Extrapulmonary Aspergillosis
Oral

Capsules: 200–400 mg daily.1 12 30 31 32 33 34 37 39

Invasive Aspergillosis
Oral

IDSA and others recommend 200 mg 3 times daily for 3 days, then 200 mg twice daily.423 436

Empiric or Preemptive Therapy of Presumed Aspergillosis
Oral

IDSA recommends 200 mg twice daily.423

Primary Prophylaxis to Prevent Aspergillosis
Oral

Immunocompromised individuals at high risk of invasive aspergillosis: IDSA recommends 200 mg twice daily.423

Blastomycosis
Treatment of Pulmonary or Extrapulmonary Blastomycosis
Oral

Capsules: Manufacturer recommends 200 mg once daily.1 If there is evidence of progression or no apparent improvement, increase dosage in 100-mg increments daily up to a maximum dosage of 400 mg daily.1 Usual duration is 6–12 months.37

Mild to moderate pulmonary or mild to moderate disseminated blastomycosis (without CNS involvement): IDSA recommends 200 mg 3 times daily for 3 days, then 200 mg once or twice daily for 6–12 months.424

Moderately severe to severe pulmonary blastomycosis (without CNS involvement): IDSA recommends an initial regimen of IV amphotericin B given for 1–2 weeks or until a response is obtained, followed by itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for a total treatment duration of 6–12 months.424

Moderately severe to severe disseminated blastomycosis (without CNS involvement): IDSA recommends an initial regimen of IV amphotericin B given for 1–2 weeks or until a response is obtained, followed by itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for a total treatment duration of at least 12 months.424

CNS blastomycosis: IDSA recommends an initial regimen of IV amphotericin B given for 4–6 weeks, followed by itraconazole 200 mg 2 or 3 times daily for at least 12 months and until CSF abnormalities resolve.424

Prevention of Recurrence (Secondary Prophylaxis) of Blastomycosis
Oral

Immunocompromised adults: IDSA recommends 200 mg daily.424

Life-long secondary prophylaxis may be necessary if immunosuppression cannot be reversed.424 In HIV-infected adults, consider discontinuing secondary prophylaxis after at least 12 months if patient is receiving antiretroviral therapy and CD4+ T-cell count is >150/mm3 for at least 6 months.424

Candida Infections
Treatment of Oropharyngeal Candidiasis
Oral

Oral solution: Manufacturer recommends 200 mg (20 mL) daily for 1–2 weeks.48 425 Clinical signs and symptoms generally resolve within several days.48

Retreatment in patients who failed to respond to or are refractory to oral fluconazole: Manufacturer recommends 100 mg (10 mL) twice daily.48 A response to itraconazole in these patients generally is evident within 2–4 weeks; relapse may be expected shortly after the drug is discontinued.48

HIV-infected adults (oral solution): 200 mg daily for 7–14 days.440

Prevention of Recurrence (Secondary Prophylaxis) of Oropharyngeal Candidiasis
Oral

HIV-infected adults (oral solution): 200 mg daily.440

Secondary prophylaxis not usually recommended; use only if patient has frequent or severe recurrences.440 Consider discontinuing secondary prophylaxis if CD4+ T-cell count increases to ≥200/mm3 in response to antiretroviral therapy.440

Treatment of Esophageal Candidiasis
Oral

Oral solution: Manufacturer recommends 100 mg (10 mL) daily;48 depending on patient response, up to 200 mg (20 mL) daily may be given.48 Manufacturer states usual duration is at least 3 weeks; continue for 2 weeks after symptoms resolve.48

HIV-infected adults and other adults (oral solution): 200 mg daily for 14–21 days.425 440

Treatment of Vulvovaginal Candidiasis
Oral

200 mg twice daily for 1 day recommended by some clinicians.436

HIV-infected adults (oral solution): 200 mg daily for 3–7 days.440

Empiric Treatment of Suspected Candidiasis in Neutropenic Patients
Oral

IDSA recommends 200 mg twice daily.425 Do not use in patients who previously received prophylaxis with an azole antifungal.425

Coccidioidomycosis
Treatment of Coccidioidomycosis (Nonmeningeal)
Oral

200 mg 2 or 3 times daily.426 436

HIV-infected adults with mild coccidioidomycosis (e.g., focal pneumonia or positive coccidioidal serologic test alone): 200 mg 3 times daily for 3 days, then 200 mg twice daily.440 Uncomplicated coccidioidal pneumonia usually treated for 3–6 months.426

Treatment of Coccidioidal Meningitis
Oral

HIV-infected adults with meningeal coccidioidomycosis: 200 mg 3 times daily for 3 days, then 200 mg twice daily.440

Consultation with an expert experienced in treating coccidioidal meningitis is recommended.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: 200 mg twice daily.440

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

Prevention of Recurrence (Secondary Prophylaxis) of Coccidioidomycosis
Oral

HIV-infected adults: 200 mg twice daily.440

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

HIV-infected adults with history of focal coccidioidal pneumonia who 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 Cryptococcosis
Oral

Immunocompetent adults with mild to moderate pulmonary (nonmeningeal) cryptococcosis: 200 mg twice daily for 6–12 months.427

HIV-infected adults with cryptococcal meningitis: Initial (induction) regimen of IV amphotericin B given for at least 2 weeks, then follow-up (consolidation) regimen of itraconazole 200 mg twice daily for 8 weeks or until CD4+ T-cell count is ≥200/mm3 for at least 6 months as the result of antiretroviral therapy.440

HIV-infected adults with cryptococcal meningoencephalitis: IDSA states itraconazole 200 mg twice daily given for 10–12 weeks can be considered as an alternative for both induction and consolidation therapy, although use of this regimen is discouraged and should be used only when all other alternative regimens have failed or are not available.427

Some clinicians suggest the oral solution may be preferred (instead of capsules) for treatment of cryptococcosis.427

Prevention of Recurrence (Secondary Prophylaxis) of Cryptococcosis
Oral

HIV-infected adults: 200 mg once or twice daily.427 440 Some evidence that the twice-daily regimen is more effective for secondary prophylaxis than the once-daily regimen.427

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

IDSA states that consideration can be given to discontinuing secondary prophylaxis 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, the patient should be followed closely and serial cryptococcal serum antigen tests performed.427 Reinitiate secondary prophylaxis against cryptococcosis if CD4+ T-cell count decreases to <100/mm3 and/or serum cryptococcal antigen titer increases.427

Other experts state that HIV-infected adults with a history of cryptococcosis generally should receive life-long suppressive therapy to prevent recurrence unless immune reconstitution occurs in response to antiretroviral therapy.440 These experts state that consideration can be given to discontinuing secondary prophylaxis in HIV-infected adults who are asymptomatic for cryptococcosis, are receiving antiretroviral therapy, and have CD4+ T-cell counts ≥200/mm3 for >6 months.440 Reinitiate secondary prophylaxis against cryptococcosis if CD4+ T-cell count decreases to <200/mm3.440

Histoplasmosis
Treatment of Histoplasmosis
Oral

Chronic cavitary pulmonary histoplasmosis or disseminated, nonmeningeal histoplasmosis (capsules): Manufacturer recommends 200 mg once daily.1 If there is evidence of progression or no apparent improvement, increase dosage in 100-mg increments daily up to a maximum dosage of 400 mg daily.1 Usual duration is at least 12 months.37

Mild to moderate acute pulmonary histoplasmosis when treatment is considered necessary (i.e., symptomatic for >1 month): IDSA recommends 200 mg 3 times daily for 3 days, then 200 mg once or twice daily for 6–12 weeks.428

Moderately severe to severe acute pulmonary histoplasmosis: IDSA recommends an initial regimen of IV amphotericin B given for 1–2 weeks, followed by itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for a total treatment duration of 12 weeks.428

Chronic cavitary pulmonary histoplasmosis: IDSA recommends 200 mg 3 times daily for 3 days, then 200 mg once or twice daily for at least 1 year.428 Because of relapse risk, some clinicians prefer a duration of 18–24 months.428

Mild to moderate disseminated histoplasmosis: IDSA recommends 200 mg 3 times daily for 3 days, then 200 mg twice daily for at least 1 year.428

Moderately severe to severe progressive disseminated histoplasmosis: IDSA recommends an initial regimen of IV amphotericin B given for 1–2 weeks, followed by itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for a total treatment duration of at least 12 months.428

Histoplasmosis with symptomatic mediastinal granuloma or with complications (pericarditis, rheumatologic syndromes, symptomatic mediastinal lymphadenitis) that require treatment with corticosteroids: 200 mg 3 times daily for 3 days, then 200 mg once or twice daily for 6–12 weeks.428

HIV-infected adults with less severe disseminated histoplasmosis: 200 mg 3 times daily for 3 days, then 200 mg twice daily for at least 12 months.440

HIV-infected adults with moderately severe to severe disseminated histoplasmosis: Initial regimen of IV amphotericin B given for at least 2 weeks or until a response is obtained, then follow-up regimen of itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for a total duration of at least 12 months and until histoplasmal antigen is undetectable.441

CNS histoplasmosis in HIV-infected adults or other adults: Initial regimen of IV amphotericin B given for 4–6 weeks or until a response is obtained, then follow-up regimen of itraconazole 200 mg 2 or 3 times daily for at least 12 months and until CSF abnormalities resolve and histoplasmal antigen is undetectable.441

Some clinicians suggest the oral solution may be preferred (instead of capsules) for treatment of histoplasmosis.428

Primary Prophylaxis to Prevent First Episode of Histoplasmosis
Oral

Immunosuppressed adults: IDSA recommends 200 mg daily.428

HIV-infected adults with CD4+ T-cell counts ≤150/mm3 who are at high risk because they live in areas where histoplasmosis is endemic: 200 mg daily.428 440

Consider discontinuing primary prophylaxis against histoplasmosis in HIV-infected adults receiving antiretroviral therapy if CD4+ T-cell count is >150/mm3 for 6 months.440 Reinitiate primary prophylaxis against histoplasmosis if CD4+ T-cell count decreases to ≤150/mm3.440

Prevention of Recurrence (Secondary Prophylaxis) of Histoplasmosis
Oral

HIV-infected adults and other immunosuppressed adults: 200 mg daily.428 440

Initiate secondary prophylaxis after primary infection has been adequately treated.428 440

HIV-infected adults with a history of histoplasmosis should receive life-long suppressive therapy to prevent recurrence.440 Consideration can be given to discontinuing secondary prophylaxis in HIV-infected adults who have negative Histoplasma blood cultures, have serum Histoplasma antigen <2 ng/mL, have received itraconazole for ≥12 months, have been receiving antiretroviral therapy for ≥6 months, and have CD4+ T-cell counts ≥150/mm3.440 Reinitiate secondary prophylaxis against histoplasmosis if CD4+ T-cell count decreases to <150/mm3.440

Microsporidiosis
Oral

Keratoconjunctivitis and sinusitis caused by Encephalitozoon: 200 mg daily for 8 weeks has been used.135

Disseminated microsporidiosis caused by Trachipleistophora or Anncaliia: 400 mg daily in conjunction with albendazole has been recommended.440

Onychomycosis
Onychomycosis of the Fingernails (Without Toenail Involvement)
Oral

Capsules: Manufacturer recommends a pulse-dosing regimen of 200 mg twice daily during the first week, no itraconazole during weeks 2–4, then 200 mg twice daily during the fifth week.48

Onychomycosis of the Toenails (With or Without Fingernail Involvement)
Oral

Capsules: Manufacturer recommends 200 mg once daily for 12 consecutive weeks.1

Capsules: a pulse-dosing regimen of 400 mg once daily for one week each month for 3 months also has been effective.75

Penicilliosis
Treatment of Penicilliosis
Oral

HIV-infected adults with mild penicilliosis: 400 mg daily for 8 weeks.440

HIV-infected adults with severe or disseminated penicilliosis: Initial regimen of IV amphotericin B given for 2 weeks, followed by itraconazole 400 mg daily for 10 weeks.440

Prevention of Recurrence (Secondary Prophylaxis) of Penicilliosis
Oral

HIV-infected adults: 200 mg daily.440

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

Limited data indicate secondary prophylaxis may be discontinued in HIV-infected adults who are receiving antiretroviral therapy and have CD4+ T-cell counts >100/mm3 for ≥6 months.440 Reinitiate secondary prophylaxis against penicilliosis if CD4+ T-cell count decreases to <100/mm3.440

Sporotrichosis
Treatment of Sporotrichosis
Oral

Cutaneous or lymphocutaneous sporotrichosis: IDSA and others recommend 200 mg once daily.429 436 If a response is not obtained, increase dosage to 200 mg twice daily.429 Continue for 2–4 weeks after all lesions have resolved;429 usual duration is 3–6 months.429 436

Osteoarticular sporotrichosis: IDSA recommends 200 mg twice daily for at least 12 months.429 If itraconazole is used after a response has been obtained with an initial regimen of IV amphotericin B, continue itraconazole for a total treatment duration of at least 12 months.429

Mild pulmonary sporotrichosis: IDSA recommends 200 mg twice daily for at least 12 months.429

Severe or life-threatening pulmonary or disseminated sporotrichosis: IDSA recommends initial regimen of IV amphotericin B given until a response is obtained, followed by itraconazole 200 mg twice daily continued for a total treatment duration of at least 12 months.429

Meningeal sporotrichosis: IDSA recommends initial regimen of IV amphotericin B given for at least 4–6 weeks and until a response is obtained, followed by itraconazole 200 mg twice daily continued for a total treatment duration of at least 12 months.429

Some clinicians suggest the oral solution may be preferred (instead of capsules) for treatment of sporotrichosis.429

Empiric Therapy in Febrile Neutropenic Patients
IV, then Oral

Initially, 200 mg IV twice daily for 4 doses, then 200 mg IV once daily for up to 14 days (IV preparation no longer commercially available in the US).48 76 93 After 14 days, switch to itraconazole oral solution in a dosage of 200 mg (20 mL) twice daily until clinically important neutropenia has resolved.48 76 93 Safety and efficacy of itraconazole administered for >28 days for this indication are not known.48 76

Oral

Empiric therapy in chemotherapy-induced neutropenia: IDSA recommends 200 mg twice daily.425

Special Populations

Hepatic Impairment

Use caution; only limited data available.1 48 (See Hepatic Impairment under Cautions.)

Renal Impairment

Use caution; only limited data available.1 48 (See Renal Impairment under Cautions.)

Cautions for Sporanox

Contraindications

  • Hypersensitivity to itraconazole or any ingredient in the formulation.1 48

  • Concomitant use with certain drugs metabolized by CYP3A4 isoenzymes (e.g., cisapride, lovastatin, midazolam, pimozide, quinidine, dofetilide, simvastatin, triazolam).1 (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Hepatotoxicity

Serious hepatotoxicity, including liver failure and death, has occurred rarely and has been reported in patients with or without preexisting liver disease or a serious underlying medical condition.1 48 Some cases occurred within the first week of itraconazole therapy.48

Mild transient increases in serum liver enzyme concentrations may occur.1 16 17 19 28 36 Increased serum hepatic enzymes (greater than twice the ULN) that required temporary or permanent discontinuance of the drug has occurred in patients receiving itraconazole capsules for treatment of onychomycosis of the toenails (using a 12-week continuous dosing regimen).1

Should not be used in patients with increased serum hepatic enzymes, active liver disease, or a history of liver toxicity with other drugs unless the potential benefits exceed the risks.1 48

Monitor serum hepatic enzyme concentrations in any patient with preexisting hepatic impairment and in those who have experienced liver toxicity with other drugs.1 48 In addition, consider monitoring serum hepatic enzymes in all patients receiving itraconazole.1 48

Itraconazole should be discontinued immediately and the risks and benefits of continuing therapy with the drug reassessed if signs and symptoms consistent with liver disease develop.1 48

Cardiac Effects

CHF, peripheral edema, and pulmonary edema have been reported in immunocompromised or immunocompetent patients receiving itraconazole for treatment of systemic fungal infections and also have been reported in immunocompetent patients receiving oral itraconazole capsules for treatment of onychomycosis.1 48

Heart failure reported more frequently in those receiving itraconazole dosage of 400 mg daily, but has been reported in those receiving lower dosage.1 48

Manufacturer states itraconazole capsules should not be used for treatment of onychomycosis in patients with evidence of ventricular dysfunction, such as CHF or history of CHF, and should not be used for other indications in patients with evidence of ventricular dysfunction, unless benefits clearly outweigh risks.1 Discontinued itraconazole oral capsules in patients who develop CHF while receiving the drug.1

Manufacturer states itraconazole oral solution should not be used for treatment of systemic fungal infections in patients with evidence of ventricular dysfunction, such as CHF or history of CHF, except for treatment of life-threatening or other serious infections when benefits clearly outweigh risks.48 If CHF occurs during therapy with itraconazole oral solution, carefully monitor patient and evaluate therapeutic options (including possible discontinuance of the drug).48

Clinicians should carefully review the risks and benefits of itraconazole therapy in patients with risk factors for CHF (e.g., those with cardiac disease such as ischemic and valvular disease, clinically important pulmonary disease such as chronic obstructive pulmonary disease, or renal failure and other edematous disorders).1 48 If itraconazole is considered necessary in patients with risk factors for CHF, they should be informed of the signs and symptoms of CHF and carefully monitored during therapy.1 48

Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients receiving cisapride, pimozide, levomethadyl (no longer commercially available in the US), or quinidine concomitantly with itraconazole or other CYP3A4 inhibitors.1 48 (See Interactions.)

Warnings Related to Oral Solution

Safety and efficacy of itraconazole oral solution has been established only for treatment of oropharyngeal and esophageal candidiasis; the oral solution should not be used interchangeably with the capsules for treatment of other fungal infections.48

Oral solution not evaluated for treatment of oropharyngeal and/or esophageal candidiasis in severely neutropenic patients.48 Oral solution not recommended for initial treatment in patients at immediate risk of systemic candidiasis.48

Variable itraconazole concentrations reported in cystic fibrosis patients receiving the oral solution.48 If oral solution is used in cystic fibrosis patients and an adequate response is not obtained, consider using alternative therapy.48 (See Pediatric Use under Cautions.)

Oral solution contains hydroxypropyl-β-cyclodextrin (HP-β-CD) as an excipient.48 HP-β-CD has produced pancreatic adenocarcinomas in rat carcinogenicity studies, but similar effects were not observed in a mouse carcinogenicity study.48 The clinical relevance of this finding is not known.48

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and Stevens-Johnson syndrome reported rarely.1 48

Cross-hypersensitivity

Although information concerning cross-sensitivity between itraconazole and other triazole or imidazole antifungals is not available, manufacturer states that itraconazole should be used with caution in individuals hypersensitive to other azoles.1

General Precautions

Neuropathy

Although a causal relationship has not been established, neuropathy (including peripheral neuropathy) has occurred rarely in patients receiving itraconazole.1 48

Discontinue itraconazole if neuropathy occurs that may be attributable to the drug.1

Otic Effects

Transient or permanent hearing loss reported in patients receiving itraconazole.1 48 In some reported cases, patient was also receiving quinidine, a drug that is contraindicated during itraconazole therapy.1 48 (See Specific Drugs under Interactions.)

Hearing loss usually resolves when itraconazole is discontinued, but persists in some patients.1 48

If hearing loss occurs, discontinue itraconazole.1 48

Superinfection

Overgrowth of nonsusceptible fungi may occur.1 These patients may require alternative antifungal therapy.1

Selection and Use of Antifungals for Onychomycosis

Prior to administration of itraconazole, appropriate nail specimens for microbiologic studies (e.g., potassium hydroxide [KOH] preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis.1

When selecting an antifungal for treatment of onychomycosis, consider reported adverse effects and risk of serious effects, possibility of drug interactions, need for prolonged therapy, cost, and risk of relapse.132 133

Toenail infections generally require more prolonged antifungal therapy than fingernail infections.1 132 133

Specific Populations

Pregnancy

Category C.1 48

Although causal relationship not established, congenital abnormalities (skeletal, genitourinary tract, cardiovascular, ophthalmic) and chromosomal and multiple malformations have been reported during postmarketing experience when the drug was used in pregnant women.1 48

Do not use for treatment of onychomycosis in pregnant women or women contemplating pregnancy.1

Lactation

Distributed into human milk.1 48 Weigh expected benefits against potential risks to the infant.1 48

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1 49

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 14 48

Has been recommended by IDSA and others for treatment of some fungal infections (e.g., blastomycosis, oropharyngeal candidiasis, coccidioidomycosis, histoplasmosis, sporotrichosis) in children, including HIV-infected infants, children, and adolescents.424 428 429 441

The manufacturer states that a limited number of patients 3–16 years of age with systemic nonmeningeal fungal infections have received itraconazole capsules in a dosage of 100 mg daily1 14 48 and a limited number of pediatric patients 6 months to 12 years of age requiring systemic antifungal therapy have received itraconazole oral solution in a dosage of 5 mg/kg once daily for 2 weeks without any unusual adverse effects.48

Data from a pharmacokinetic study evaluating itraconazole oral solution in patients with cystic fibrosis indicate that itraconazole concentrations are variable in such patients and trough concentrations attained in children <16 years of age are lower than those attained in patients 16–28 years of age.48 Consider using alternative therapy if the oral solution is used in cystic fibrosis patients and an adequate response is not obtained.48

Long-term effects of itraconazole therapy on bone growth in children not known.1 48 Data from rat studies indicate that itraconazole induces bone defects, including decreased bone plate activity, thinning of the zona compacta of large bones, and increased bone fragility.1 48 Bone toxicity observed in animals has not been reported to date in adults receiving itraconazole.1 48

Geriatric Use

Use caution in geriatric patients.1 48

Transient or permanent hearing loss reported in geriatric patients receiving itraconazole.1 48 In some reported cases, patient was also receiving quinidine, a drug that is contraindicated during itraconazole therapy.1 48 (See Specific Drugs under Interactions.)

Hepatic Impairment

Use caution; only limited data available on use in patients with hepatic impairment.1 48 Prolonged half-life in patients with cirrhosis.1 48 (See Pharmacokinetics.) This prolonged half-life in cirrhotic patients should be considered when deciding to initiate concomitant therapy with drugs that are metabolized by CYP3A4.1 48 (See Interactions.)

Use of itraconazole in patients with increased serum hepatic enzymes, active liver disease, or a history of liver toxicity with other drugs is strongly discouraged unless there is a serious or life-threatening situation when potential benefits outweigh risks.1 48

Monitor serum hepatic enzyme concentrations in patients with preexisting hepatic impairment and in those who have experienced liver toxicity with other drugs.1 48

Renal Impairment

Use caution; only limited data available on use in patients with renal impairment.1 48

Wide interindividual variations in AUC reported in patients with renal impairment.1 48 (See Absorption: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

GI effects (nausea, vomiting, diarrhea, abdominal pain, anorexia); rash and pruritus; CNS effects (headache, dizziness); hypokalemia.1 10 16 17 18 19 28 36 37 48

Interactions for Sporanox

Metabolized by CYP3A.1

Itraconazole and its major metabolite, hydroxyitraconazole, inhibit CYP3A4.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A with possible alteration in metabolism of itraconazole and/or the other drug.1

Specific Drugs

Drug

Interaction

Comments

Alfentanil

Possible increased alfentanil concentrations1 48

Amphotericin B

Possible antagonism1 48

Clinical importance unclear1 48

Antacids

Possible decreased absorption of itraconazole1

Administer antacids at least 1 hour before or 2 hours after itraconazole capsules1

Antiarrhythmic agents (digoxin, disopyramide, quinidine, dofetilide)

Increased concentrations of the antiarrhythmic agent and increased risk of serious adverse cardiovascular effects;1 48 life-threatening cardiac dysrhythmias and/or sudden death have occurred1 48

Dofetilide, quinidine: Concomitant use contraindicated1 48

Disopyramide: Use caution1 48

Anticoagulants, oral (warfarin)

Possible increased warfarin concentrations1 48

Monitor PT or other appropriate tests closely if used with warfarin; reduce anticoagulant dosage if necessary1 48

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Possible increased concentrations of carbamazepine; 1 48 possible decreased itraconazole concentrations1 48

Monitor anticonvulsant concentrations if possible; adjust dosage as needed when itraconazole is initiated or discontinued1 48

Antidiabetic agents, sulfonylureas

Increased plasma concentrations of the antidiabetic agent; symptoms of hypoglycemia reported1 48

Monitor blood glucose and observe patient for signs and symptoms of hypoglycemia; adjust dosage of antidiabetic agent as necessary1 48

Antihistamines (astemizole, terfenadine)

Pharmacokinetic interaction and potential for serious or life-threatening reactions (e.g., cardiac arrhythmias) with astemizole or terfenadine (drugs no longer commercially available in the US)22 23 27 37

Concomitant use contraindicated27 74

Antimycobacterials (isoniazid, rifabutin, rifampin)

Possible increased concentrations of rifabutin, rifampin, or isoniazid; possible decreased itraconazole concentrations1 48

Concomitant use with isoniazid, rifabutin, or rifampin not recommended1 48

Antineoplastic agents (busulfan, docetaxel, vinca alkaloids)

Possible increased concentrations of busulfan, docetaxel, or vinca alkaloids1 48

Monitor antineoplastic agent concentrations if possible; adjust dosage as needed when itraconazole is initiated or discontinued1 48

Antiretrovirals, HIV entry inhibitors

Maraviroc: Possible increased maraviroc concentrations431

Maraviroc: Consider reducing maraviroc dosage to 150 mg twice daily431

Antiretroviral agents, HIV protease inhibitors (PIs)

Possible pharmacokinetic interactions if itraconazole used in patients receiving PIs (e.g., atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir, tipranavir), especially if ritonavir-boosted PI regimens are used;431 concomitant use may result in altered serum concentrations of the PIs and/or the antifungal431

If used in patients receiving ritonavir-boosted atazanavir, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, or ritonavir-boosted tipranavir, consider monitoring itraconazole concentrations to guide dosage adjustments of the antifungal; high itraconazole dosage (>200 mg daily) not recommended unless plasma concentrations of the antifungal are used to guide dosage431

Indinavir (without low-dose ritonavir): Some experts recommend indinavir dosage of 600 mg every 8 hours and state that itraconazole dosage should not exceed 200 mg twice daily431

Ritonavir-boosted indinavir: Appropriate dosage of indinavir: (with low-dose ritonavir) not established for patients receiving concomitant itraconazole; high itraconazole dosage (>200 mg daily) is not recommended unless plasma concentrations of the antifungal are used to guide dosage431

Lopinavir/ritonavir: Consider not exceeding itraconazole dosage of 200 mg daily or consider monitoring itraconazole plasma concentrations431

Ritonavir-boosted saquinavir: Consider monitoring itraconazole plasma concentrations;431 appropriate dosage for concomitant use not established, but decreased itraconazole dosage may be warranted431

Antiretroviral agents, nonnucleoside reverse transcriptase agents (NNRTIs)

Efavirenz: Decreased plasma concentrations and AUC of itraconazole and its major metabolite, hydroxyitraconazole;129 431 efavirenz concentrations not affected129

Etravirine: Possible decreased itraconazole concentrations and increased etravirine concentrations131 431

Nevirapine: Possible decreased itraconazole concentrations and increased nevirapine concentrations130 431

Efavirenz: Manufacturer of efavirenz states consider an alternative antifungal in patients receiving efavirenz;129 some experts state monitor itraconazole plasma concentrations and consider that antifungal dosage may need to be adjusted431

Efavirenz: Manufacturer of efavirenz states consider an alternative antifungal in patients receiving efavirenz;129 some experts state monitor itraconazole plasma concentrations and consider that antifungal dosage may need to be adjusted431

Nevirapine: Concomitant use not recommended;1 48 130 some experts state that if itraconazole and nevirapine are used concomitantly, consider monitoring plasma concentrations of both drugs431

Antiretroviral agents, nucleoside reverse transcriptase inhibitors (NRTIs)

Zidovudine: No evidence of pharmacokinetic interaction1

Benzodiazepines (alprazolam, diazepam, midazolam, triazolam)

Increased plasma concentrations of benzodiazepines; possible prolonged sedative and hypnotic effects of the drugs1 48

Concomitant use with oral midazolam or triazolam is contraindicated1 48

If parenteral midazolam used concomitantly with itraconazole, closely monitor patient and use special precaution.1 48

Buspirone

Possible increased buspirone concentrations1 48

Monitor buspirone concentrations if possible; adjust dosage as needed when itraconazole is initiated or discontinued1 48

Calcium-channel blocking agents (nifedipine, nisoldipine, felodipine, verapamil)

Possible increased concentrations of calcium-channel blocking agents (e.g., nifedipine, felodipine, verapamil); possible additive negative inotropic effects;1 48 edema reported when dihydropyridines (nifedipine, felodipine) used with itraconazole1 48

Nisoldipine: Concomitant use results in a clinically important increase in nisoldipine concentrations that cannot be managed by dosage reduction1 48

Use concomitantly with caution; dosage adjustment of calcium-channel blocking agent may be necessary1 48

Nisoldipine: Concomitant use contraindicated1 48

Carbamazepine

Possible increased carbamazepine concentrations and decreased itraconazole concentrations128

Cilostazol

Possible increased cilostazol concentrations1 48

Cisapride

Increased cisapride concentrations and increased risk of adverse effects (e.g., cardiac effects)1 47 48

Concomitant use contraindicated1 48

Corticosteroids (budesonide, dexamethasone, fluticasone, methyprednisolone)

Possible increased corticosteroid concentrations1 48

Eletriptan

Possible increased eletriptan concentrations1 48

Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)

Possible increased concentrations of ergot alkaloid and risk of ergotism (i.e., risk for venospasm potentially leading to cerebral ischemia and/or ischemia of the extremities)1 48

Concomitant use contraindicated1 48

Fentanyl

Possible increased fentanyl concentrations and increased potential for fatal respiratory depression1 48

Halofantrine (not commercially available in the US)

Possible increased halofantrine concentrations and increased risk of prolonged QT interval1 48

Use concomitantly with caution1 48

Histamine H2-receptor antagonists (cimetidine)

Possible decreased itraconazole concentrations1 48

When used in patients taking a histamine H2-receptor antagonist, administer oral itraconazole with a cola beverage to increase oral absorption1 48

HMG-CoA reductase inhibitors (statins)

Decreased clearance and increased concentrations of some HMG-CoA reductase inhibitors with potential for increased risk of myopathy (including rhabdomyolysis)1 48

Concomitant use with lovastatin or simvastatin contraindicated1 48

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Possible increased concentrations of cyclosporine, sirolimus, tacrolimus1 48

Monitor immunosuppressive agent concentrations if possible; adjust dosage as needed when itraconazole is initiated or discontinued1 48

Macrolides (clarithromycin, erythromycin)

Possible increased itraconazole concentrations1 48

Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil)

Increased concentrations of the PDE5 inhibitor and increased risk of PDE5 inhibitor-associated adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)109 110 111

Sildenafil: Consider initial sildenafil dose of 25 mg in patients receiving itraconazole109

Tadalafil: Patients receiving itraconazole should receive no more than 10 mg of tadalafil once every 72 hours;110 if a once-daily tadalafil regimen is used, those receiving itraconazole should receive no more than 2.5 mg of tadalafil once daily110

Vardenafil: Patients receiving itraconazole dosage of 400 mg daily should receive no more than a single 2.5-mg dose of vardenafil in a 24-hour period; those receiving itraconazole 200 mg daily should receive no more than a single 5-mg dose of vardenafil in a 24-hour period111

Pimozide

Increased pimozide concentrations; life-threatening cardiac dysrhythmias and/or sudden death reported1 48

Concomitant use contraindicated1 48

Proton-pump inhibitors (omeprazole)

Possible decreased itraconazole concentrations1 48

Trimetrexate

Possible increased trimetrexate concentrations1 48

Monitor trimetrexate concentrations if possible; adjust dosage as needed when itraconazole is initiated or discontinued1 48

Sporanox Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability varies depending on whether the drug is administered as capsules or the oral solution; these preparations are not bioequivalent.1 48

When administered under optimum conditions for GI absorption (oral solution under fasting conditions or oral capsules with food), the oral solution is more bioavailable than capsules.48

When a single 200-mg dose is given as capsules (with a meal), peak plasma concentrations usually attained within 5 hours and average 302 ng/mL.1 48 When a single 200-mg dose of itraconazole is given as the oral solution (without food), peak plasma concentrations usually attained within 2.2 hours and average 544 ng/mL.48

Food

When itraconazole capsules are used, bioavailability is maximal when administered with food.1 Food decreases the rate of absorption, but increases peak plasma concentrations and AUC of the oral capsules.1

When itraconazole oral solution is used, bioavailability is maximal when administered under fasting conditions.48 Food decreases the rate and extent of absorption of the oral solution.48

Special Populations

In cirrhotic patients who received a single 100-mg itraconazole capsule, mean peak plasma concentrations were 47% lower, but overall exposure (based on AUC) was similar to that in healthy individuals.1 48 Data not available regarding long-tem use in such patients.1 48

Single-dose study in uremic patients (mean Clcr 13 mL/minute per 1.73 m2) indicates AUC is slightly decreased compared with healthy individuals.1 48 Wide interindividual variation in AUC reported in uremic patients and in patients undergoing hemodialysis or CAPD.1 48

Oral absorption of itraconazole is impaired when gastric acid production is decreased.1 In fasting individuals with relative or absolute achlorhydria (e.g., HIV-infected individuals, those receiving a histamine H2-receptor antagonist), peak plasma concentrations and AUC are increased when itraconazole oral capsules are administered with a cola beverage compared with administration with water.1

In patients with cystic fibrosis receiving itraconazole oral solution (2.5 mg/kg twice daily for 14 days), itraconazole concentrations were variable and trough concentrations attained in children <16 years of age were lower than those in patients 16–28 years of age.48

Distribution

Extent

Itraconazole is highly lipophilic and is distributed into nail matrix, bed, and plate following oral administration, persisting in these tissues for several months after discontinuance of the drug.132 133

Distributed into human milk.1 48

Plasma Protein Binding

Itraconazole is 99.8% and hydroxyitraconazole is 99.5% bound to plasma proteins.1 48

Elimination

Metabolism

Metabolized principally in the liver by CYP3A4 isoenzyme to several metabolites.1 48 Hydroxyitraconazole, the major metabolite, has antifungal activity.1 48

Saturable metabolism may occur with multiple dosing.1 48

Elimination Route

Approximately 40% of a dose is eliminated in urine as inactive metabolites, <0.03% is eliminated in urine as unchanged drug, and 3–18% is eliminated in feces as unchanged drug.1 48

Itraconazole not appreciably removed by hemodialysis or peritoneal dialysis.1 48

Half-life

Adults receiving oral capsules (200 mg twice daily with a meal): Half-life of itraconazole is 64 hours and half-life of hydroxyitraconazole is 56 hours at steady state.1

Adults receiving oral solution (200 mg daily without food): Half-life of itraconazole is 39.7 hours and half-life of hydroxyitraconazole is 27.3 hours at steady state.48

Special Populations

Children 6 months to 12 years of age receiving oral solution (5 mg/kg once daily): Half-life of itraconazole is 35.8 hours and half-life of hydroxyitraconazole is 17.7 hours at steady state.48

In cirrhotic patients who received a single 100-mg itraconazole dose as capsules, the elimination half-life was 37 hours (compared with 16 hours following a single dose in healthy individuals).1 48 Data not available regarding long-tem use in such patients.1 48

Stability

Storage

Oral

Capsules

15–25°C; protect from light and moisture.1

Solution

≤25°C; do not freeze.48

Actions and Spectrum

  • Triazole-derivative azole antifungal.1 2 3 36 37 48

  • Both itraconazole and its major metabolite, hydroxyitraconazole, have antifungal activity.1 48

  • Usually fungistatic in action.1 48

  • 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).1 48 Inhibits cytochrome P-450 14-α-desmethylase in susceptible fungi, which leads to accumulation of C-14 methylated sterols (e.g., lanosterol) and decreased concentrations of ergosterol.1 48

  • Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes.1 2 3 12 36

  • Candida: Active in vitro and in vivo against C. albicans,1 C. guilliermondii,85 C. krusei,1 84 85 C. parapsilosis,82 84 85 and C. tropicalis.82 84 Some strains of C. lusitaniae are inhibited in vitro by itraconazole.80 81 85

  • Dermatophytes: Active against Epidermophyton,133 Microsporum,133 Trichophyton mentagrophytes,1 and T. rubrum.1

  • Other fungi: Active against Aspergillus (including A. flavus,1 122 A. fumigatus,1 122 A. niger,122 and A. terreus),122 Blastomyces dermatitidis,78 Coccidioides immitis,1 Cryptococcus neoformans,1 82 C. gattii,121 Histoplasma capsulatum,1 H. duboisii,1 Paracoccidioides brasiliensis,1 Penicillium marneffei,118 120 and Sporothrix schenckii.1 94 105 Some zygomycetes, including some strains of Rhizopus,127 Mucor,126 127 Absidia,126 127 Rhizomucor,126 127 Cunninghamella,126 and Apophysomyces elegans,126 are inhibited in vitro by itraconazole. The drug has some activity against Basidiobolus ranarum.104 123

  • Itraconazole is not active against Fusarium,1 48 Scedosporium,1 48 or Scopulariopsis,1 48 including S. acremonium and S. brevicaulis.86

  • Strains of fungi resistant to itraconazole have been isolated in vitro and from patients who received prolonged therapy with the drug.1 48 Itraconazole-resistant fungi may be cross-resistant to other azole antifungals (e.g., fluconazole, ketoconazole).5 48

Advice to Patients

  • Advise patients that only the oral solution should be used for treatment of oropharyngeal or esophageal candidiasis; the oral solution and capsules are not interchangeable.1 48

  • When using itraconazole capsules, importance of taking with a full meal.1

  • When using itraconazole oral solution, importance of taking without food (if possible) to maximize absorption.48 Importance of vigorously swishing solution in the mouth for several seconds before swallowing.48

  • Instruct patients to immediately discontinue itraconazole and contact their clinician if any signs or symptoms of liver dysfunction occur (e.g., unusual fatigue, dark urine, pale stool, anorexia, nausea, vomiting, jaundice) so that appropriate laboratory testing can be performed.1 48

  • Inform patients, especially those with risk factors for CHF (e.g., those with cardiac disease such as ischemic and valvular disease, clinically important pulmonary disease such as chronic obstructive pulmonary disease, or renal failure and other edematous disorders) about the signs and symptoms of CHF and importance of immediately discontinuing itraconazole and contacting their clinician if any of these symptoms occur.1 48

  • Inform patients that hearing loss can occur; hearing loss usually resolves when itraconazole is discontinued, but persists in some patients.1 48 Importance of discontinuing itraconazole and contacting clinician if any symptoms of hearing loss occur.1 48

  • Inform patient that HP-β-CD, an excipient present in the oral solution, has been associated with pancreatic adenocarcinoma in rats but that clinical relevance to humans in unknown.48

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

Itraconazole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

100 mg*

Itraconazole Capsules

Sporanox

Ortho-McNeil-Janssen

Solution

50 mg/5 mL

Sporanox

Centocor Ortho Biotech

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.

Itraconazole 100MG Capsules (PATRIOT PHARMACEUTICALS LLC): 28/$239.97 or 84/$669.98

Itraconazole 100MG Capsules (PATRIOT PHARMACEUTICALS LLC): 30/$251.98 or 90/$691.99

Sporanox 10MG/ML Solution (JANSSEN PRODUCTS): 150/$217.99 or 450/$632.00

Sporanox 100MG Capsules (JANSSEN): 30/$439.99 or 90/$1,230.01

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2011. 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.

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