What is the recommended dosage and treatment duration of itraconazole for various fungal infections?

Itraconazole Pharmacology: Dosing and Duration for Fungal Infections

Itraconazole dosing varies significantly by infection type and severity, with most systemic infections requiring 200 mg once or twice daily for 6-12 months, though therapeutic drug monitoring is essential to ensure adequate exposure with target trough levels of 1-2 mcg/mL for invasive infections and >0.5 mcg/mL for prophylaxis. 1

Dosing by Infection Type

Mucocutaneous Candidiasis

Oropharyngeal candidiasis:

• 200 mg once daily for 7-14 days (1-7 days in children) for uncomplicated disease 1
• For fluconazole-refractory esophageal disease: 200 mg once daily for up to 28 days 2

Esophageal candidiasis:

• 200 mg once daily for 14-21 days until clinical improvement 1

Blastomycosis

Mild to moderate pulmonary or disseminated disease:

• 200 mg three times daily for 3 days (loading dose), then 200 mg once or twice daily for 6-12 months 1, 2

Moderately severe to severe disease:

• Initial amphotericin B (lipid formulation 3-5 mg/kg/day or deoxycholate 0.7-1 mg/kg/day) for 1-2 weeks until improvement 1, 2
• Step-down to itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily for total duration of 6-12 months 1, 2

Osteoarticular blastomycosis:

• Same dosing as above but minimum total duration of 12 months 1, 2

Invasive Aspergillosis

Empirical, pre-emptive, or documented infection:

• Itraconazole is listed as an alternative agent (not first-line) 1
• Continue treatment until resolution or stabilization of all clinical and radiographic manifestations 1

Chronic cavitary pulmonary aspergillosis:

• Itraconazole is a first-line oral option 1

Critical Pharmacokinetic Considerations

Formulation-Specific Administration

Capsule formulation:

• Must be taken with a full meal to enhance absorption by 43% in fasted patients 1

Solution formulation:

• Give 1 hour before or 1 hour after meals due to 43% increase in bioavailability when fasting 1

SUBA-itraconazole:

• Enhanced bioavailability formulation allowing lower dosing while achieving similar serum concentrations 1
• FDA-approved for blastomycosis, histoplasmosis, and aspergillosis 1

Therapeutic Drug Monitoring (TDM)

Target trough concentrations:

• Prophylaxis: >0.5 mcg/mL 1
• Active invasive infection: 1-2 mcg/mL 1
• Upper safety limit: 5 mcg/mL (increased mortality observed above this level) 1
• Some sources suggest upper limit of 17 mcg/mL by bioassay, though data are limited 1

Timing of TDM:

• Measure serum levels after at least 2 weeks of therapy to ensure adequate drug exposure 1, 2
• Breakthrough infections occur at concentrations <0.5 mcg/mL 1

Drug Interactions

Critical warning: Itraconazole is a potent cytochrome P450 3A4 inhibitor, creating substantial risk for drug interactions that can result in subtherapeutic effects or toxicity 1, 3

Common pitfall: When treating CNS aspergillosis, beware of interactions between anticonvulsant therapy and azole antifungals 1

Special Populations

Immunocompromised Patients

Initial therapy:

• Amphotericin B (lipid formulation 3-5 mg/kg/day or deoxycholate 0.7-1 mg/kg/day) for 1-2 weeks until improvement 1
• Step-down to itraconazole 200 mg three times daily for 3 days, then twice daily 1

Maintenance therapy:

• Lifelong suppressive therapy may be required if immunosuppression cannot be reversed 2

CNS Infections

Blastomycosis with CNS involvement:

• Amphotericin B (lipid formulation 5 mg/kg/day) for 4-6 weeks 1
• Step-down options include itraconazole 200 mg 2-3 times daily for at least 12 months and until resolution of CSF abnormalities 1, 2

Tolerability Profile

• Generally well-tolerated at doses up to 400 mg/day 3, 4
• Most common adverse effects: gastrointestinal disturbances, dizziness, headache 4
• Serious toxicity is rare; only 29% of patients experience any side effects 5
• Treatment discontinuation due to toxicity occurs in <2% of patients 5
• Hypokalemia has been reported rarely 6

Efficacy Data

Blastomycosis: 90% success rate overall; 95% success for patients treated >2 months 5

Histoplasmosis: 81% success rate overall; 86% success for patients treated >2 months (chronic cavitary disease has lower response) 5

Aspergillosis: 71% response rate in invasive pulmonary aspergillosis (15 of 18 patients cured in one series) 6