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
Brands: Sporanox

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  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 Itraconazole

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 CNS^{51 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

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}

Itraconazole 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) f