What is the recommended dose of itraconazole for an adult patient with a fungal infection, considering factors such as type and severity of infection, and potential Impaired renal function?

Itraconazole Dosing for Fungal Infections

For most systemic fungal infections in adults with normal renal function, itraconazole 200 mg twice daily is the standard dose, with a loading dose of 200 mg three times daily for 3 days recommended for severe infections. 1, 2

Standard Dosing by Infection Type

Blastomycosis

• Mild to moderate pulmonary or disseminated disease: 200 mg once or twice daily for 6-12 months 2
• Moderately severe to severe disease: Start with amphotericin B for 1-2 weeks, then itraconazole 200 mg three times daily for 3 days (loading), followed by 200 mg twice daily to complete 6-12 months total 1, 2
• Osteoarticular blastomycosis: Minimum 12 months total treatment duration 2
• Immunosuppressed patients: After initial amphotericin B and response, use 200 mg three times daily for 3 days, then twice daily for at least 12 months 1

Cryptococcosis (Non-Meningeal)

• Alternative therapy: 200 mg twice daily orally 1
• Used primarily when fluconazole is not appropriate or available 1

Fluconazole-Refractory Esophageal Candidiasis

• Itraconazole solution: 200 mg once daily for up to 28 days 2

CNS Infections

• Minimum 12 months duration and continue until CSF abnormalities resolve 2

Critical Renal Function Considerations

Renal impairment does NOT require dose adjustment for itraconazole itself, as less than 1% is renally excreted. 3

• Mild renal impairment (CrCl 50-79 mL/min): No dose adjustment needed 3
• Moderate renal impairment (CrCl 20-49 mL/min): Exposure decreased by ~30%, but no specific dose adjustment recommended 3
• Severe renal impairment (CrCl <20 mL/min): Exposure decreased by ~40%, but no specific dose adjustment recommended 3
• Hemodialysis and peritoneal dialysis have no effect on itraconazole clearance 3

Formulation-Specific Absorption Requirements

Capsules MUST be taken with food to enhance absorption; oral solution should be taken on an empty stomach for optimal bioavailability. 2, 3

• Oral solution has 30% higher bioavailability when taken fasting compared to fed state 3
• Oral solution provides greater drug exposure than capsules at the same dose 3
• Peak concentrations occur at 2.5 hours with oral solution 3

Mandatory Therapeutic Drug Monitoring

Serum itraconazole levels MUST be checked after at least 2 weeks of therapy to ensure adequate drug exposure. 1, 2

• Target trough concentration: >250 ng/mL for systemic infections 3
• Treatment failures are associated with levels <2.5 mcg/mL 4
• Mean trough levels should be above 5 mcg/mL for severe infections 4
• Wide interpatient variability exists (up to 98% coefficient of variation) 3

High-Dose Regimens for Refractory Disease

For severe mycoses with prior treatment failures, doses up to 600 mg daily have been used, though this approaches the upper limit of acceptable long-term dosing 4:

• Six of eight patients without AIDS showed improvement on 600 mg daily 4
• One patient progressed after dose reduction from 600 mg to 400 mg daily 4
• Significant adverse effects at 600 mg/day include hypokalemia, hypertension, and potential adrenal insufficiency 4

Special Population Considerations

Hepatic Impairment

• No dose adjustment recommended despite 47% reduction in Cmax and doubled half-life in cirrhotic patients 3
• Overall AUC exposure remains similar to healthy subjects 3
• Monitor closely for drug accumulation with prolonged use 3

Immunosuppressed Patients

• Lifelong suppressive therapy with 200 mg daily may be required if immunosuppression cannot be reversed 1, 2
• Also indicated for patients who relapse despite appropriate therapy 1

Pediatric Patients

• 10 mg/kg per day (maximum 400 mg daily) for children with blastomycosis 1
• Serum level monitoring is essential, as children <16 years with cystic fibrosis had difficulty achieving therapeutic levels 3

Critical Drug Interaction Warning

Itraconazole is a potent CYP3A4 inhibitor with extensive drug-drug interactions that must be screened before prescribing. 2, 3, 5

• 99.8% protein bound, primarily to albumin 3
• Significant interactions with immunosuppressants, statins, calcium channel blockers, and many other medications 5

Common Pitfalls to Avoid

• Do not use capsule formulation without food - absorption will be inadequate 2, 3
• Do not skip therapeutic drug monitoring - treatment failures are common with subtherapeutic levels 1, 2, 4
• Do not assume renal dosing is needed - unlike many antifungals, itraconazole does not require renal dose adjustment 3
• Do not use in cystic fibrosis patients without close monitoring - this population has particularly poor and variable absorption 3
• Do not continue therapy without response - if levels are adequate and no response occurs, switch to alternative therapy 3