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

Dosing by Infection Type and Severity

Systemic Mycoses

Blastomycosis:

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

Cryptococcosis:

• Non-meningeal disease: 200 mg twice daily as an alternative when fluconazole is not appropriate 1

Esophageal Candidiasis:

• Fluconazole-refractory disease: Itraconazole solution 200 mg once daily for up to 28 days 1

Superficial Fungal Infections

Dermatophyte infections (tinea corporis/cruris):

• 100 mg once daily for 15 days 2

Onychomycosis:

• Continuous therapy: 200 mg daily for 12 weeks 2
• Pulse therapy: 400 mg daily for 1 week per month (2 pulses for fingernails, 3 pulses for toenails) 2

Critical Administration Requirements

Capsule formulation MUST be taken with food to ensure adequate absorption - this is non-negotiable as bioavailability increases significantly with food intake. 2, 3 The oral solution has higher bioavailability and can be taken fasting, but absorption still increases by 30% with food. 3

Avoid concurrent use with:

• H2 blockers and proton pump inhibitors (significantly decrease absorption) 2
• Phenytoin and rifampicin (reduce efficacy) 2

Therapeutic Drug Monitoring

Serum itraconazole levels should be checked after at least 2 weeks of therapy to ensure adequate drug exposure, particularly for systemic infections. 1, 2 Target trough concentrations should exceed 250 ng/mL for optimal efficacy, though wide interpatient variability exists. 3

Special Population Considerations

Renal Impairment

No dose adjustment is necessary for renal impairment, including patients on hemodialysis or peritoneal dialysis. 3 Itraconazole is primarily metabolized hepatically, with less than 1% excreted unchanged in urine. 3 Dialysis does not affect the half-life or clearance of itraconazole. 3

Hepatic Impairment

Itraconazole is contraindicated in patients with active liver disease or hepatotoxicity. 2 In cirrhotic patients, the elimination half-life doubles (37 hours vs 16 hours), though overall AUC remains similar. 3 Monitor hepatic function tests in patients with pre-existing abnormal results. 2

Immunosuppressed Patients

Lifelong suppressive therapy with itraconazole 200 mg daily may be required if immunosuppression cannot be reversed. 1 For CNS infections, continue treatment for at least 12 months and until resolution of CSF abnormalities. 1

Important Safety Considerations

Heart failure is an absolute contraindication due to negative inotropic effects demonstrated in animal and human studies. 2, 3 Transient decreases in left ventricular ejection fraction have been documented. 3

Significant cytochrome P450 3A4 interactions occur - carefully review all concurrent medications before initiating therapy. 1, 2

High-dose therapy (600 mg/day) approaches the upper limits of acceptable long-term dosing and has been associated with reversible adrenal insufficiency, hypokalemia, hypertension, and rhabdomyolysis. 4 Standard doses of 200-400 mg/day are generally well-tolerated. 1

Management of Treatment Failure

If inadequate response occurs:

• First verify serum drug levels are adequate (>250 ng/mL) 3
• Confirm proper administration with food for capsules 2
• Consider increasing to 200 mg twice daily for refractory cases 2
• For continued failure, switch to alternative therapy such as terbinafine 250 mg daily 2