Itraconazole Dosing for a 10-Month-Old Infant
For a 10-month-old baby, itraconazole oral suspension should be dosed at 5 mg/kg/day divided into two doses for prophylaxis or superficial infections, or 10 mg/kg/day divided into two doses for systemic/invasive fungal infections, with mandatory therapeutic drug monitoring after 2 weeks of therapy. 1, 2, 3
Age-Specific Dosing Considerations
Standard Dosing by Infection Severity
- Superficial fungal infections (e.g., cutaneous infections, mucosal candidiasis): 5 mg/kg/day of oral suspension divided into two doses 2, 3, 4
- Systemic/invasive fungal infections: 10 mg/kg/day divided into two doses, with a loading dose of 10 mg/kg/day in two divided doses on day 1 1, 2, 3
Critical Pharmacokinetic Issues in Infants
- Infants under 2 years require close monitoring because they demonstrate lower peak concentrations and drug exposure (AUC) compared to older children, particularly after the first dose 4
- The accumulation factor from day 1 to day 14 ranges from 3.3 to 8.6 for itraconazole in young infants, meaning therapeutic levels build gradually over the first 2 weeks 4
- Despite lower initial levels, by day 14 of therapy, infants 6 months to 2 years achieve comparable drug exposure to older children when dosed at 5 mg/kg/day 4
Mandatory Therapeutic Drug Monitoring
Serum itraconazole trough levels must be measured after at least 2 weeks of therapy to ensure adequate drug exposure. 1, 5, 6
Target Trough Concentrations
- Prophylaxis: >0.5 mcg/mL (>500 ng/mL) 6
- Active invasive infection: 1-2 mcg/mL (1000-2000 ng/mL) 6
- Samples should be drawn as trough levels at steady state (immediately before the next dose) 7
Common Pitfall
- In children ≤12 years, 71.4% require doses above the standard 5 mg/kg/day recommendation to achieve therapeutic levels 7
- For a 10-month-old with invasive infection not responding to standard dosing, consider increasing to 10 mg/kg/day based on subtherapeutic levels 7, 3
Formulation Requirements
- Use only itraconazole oral solution (cyclodextrin formulation) in infants 2, 4
- Capsules should NOT be used interchangeably with oral solution and are generally ineffective for esophageal disease 2
- The oral solution provides superior bioavailability in young children compared to capsules 4
Treatment Duration by Indication
- Cutaneous/superficial infections: 6-12 months 2, 8
- Systemic/disseminated infections: At least 12 months 2, 3
- Prophylaxis in high-risk patients (e.g., post-transplant): Continue until immune recovery or discontinuation of immunosuppression 1
Safety Profile in Infants
Itraconazole is safe and well-tolerated in infants at doses of 5-10 mg/kg/day. 3, 4
Adverse Events
- Gastrointestinal symptoms occur in approximately 15% of pediatric courses 7
- Hepatotoxicity occurs in approximately 6.5% of cases, with mild transient asymptomatic liver enzyme elevations (less than twice upper limit of normal) in 3.4% of monitored children 7, 8
- Cutaneous eruptions are rare (1.2% incidence) 8
- Neither gastrointestinal symptoms nor hepatotoxicity correlate with elevated trough levels 7
Monitoring Requirements
- Baseline liver function tests before initiating therapy 7
- Monitor liver enzymes periodically during treatment, especially in the first 2-3 months 7, 8
Critical Drug Interactions
- Exercise extreme caution with concomitant immunosuppressants (cyclosporine, tacrolimus, sirolimus) as itraconazole inhibits cytochrome P450 3A4, potentially increasing immunosuppressant levels 1, 9
- Significant interactions occur with protease inhibitors and non-nucleoside reverse transcriptase inhibitors 2
When to Use Alternative Therapy
- For severe or life-threatening invasive fungal infections, initiate with amphotericin B (lipid formulation 3-5 mg/kg/day or deoxycholate 0.7-1 mg/kg/day) for 1-2 weeks until clinical improvement, then step down to itraconazole 1, 5, 2
- Liposomal amphotericin B is not approved in infants <1 month of age 1