Is ketoconazole (an antifungal medication) safe to use in a 5-year-old pediatric patient with a suspected fungal infection?

Ketoconazole Should NOT Be Used Systemically in a 5-Year-Old Child

Systemic ketoconazole is contraindicated in pediatric patients, including 5-year-olds, due to serious risks of hepatotoxicity, adrenal suppression, and dangerous drug interactions that outweigh any potential benefits. 1

Regulatory Warnings Against Systemic Ketoconazole

• Both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have issued explicit warnings against systemic ketoconazole use due to risks of hepatic toxicities, adrenal suppression, and drug interactions. 1

• The 2020 Journal of Clinical Oncology guidelines specifically excluded ketoconazole from their systematic review of antifungal prophylaxis in pediatric cancer patients based on these regulatory safety warnings. 1

• Post-marketing surveillance revealed that symptomatic drug-induced hepatitis occurs in approximately 1 in 12,000 patients, along with effects on testosterone and cortisol synthesis. 2

Safe Alternatives for Systemic Fungal Infections in 5-Year-Olds

For invasive candidiasis or systemic fungal infections in a 5-year-old, fluconazole is the first-line agent at 8-12 mg/kg once daily. 3

• For children younger than 13 years requiring mold-active coverage, an echinocandin, voriconazole, or itraconazole should be used based on efficacy and adverse effect profiles. 1

• Voriconazole can be dosed at 9 mg/kg twice daily orally with therapeutic drug monitoring to maintain trough levels ≥1 mg/L. 3

Limited Safe Use: Topical Ketoconazole Only

Ketoconazole shampoo remains safe for topical use in pediatric scalp fungal infections when left on for 3-5 minutes before rinsing. 4

• For cutaneous candidiasis in children, clotrimazole 1% cream applied 2-3 times daily for 7-14 days is preferred over any ketoconazole formulation. 4

• Prophylactic ketoconazole solution wash has shown effectiveness in preventing fungal infection recurrence (4% recurrence rate vs 60% without prophylaxis at 6 months), but this applies only to topical use. 5

Clinical Decision Algorithm for a 5-Year-Old with Suspected Fungal Infection

1. Identify infection type and location:

   • Superficial/cutaneous → Use topical clotrimazole or nystatin 6, 4
   • Scalp dermatophyte → Use ketoconazole shampoo (topical only) 4
   • Invasive candidiasis → Use fluconazole 8-12 mg/kg daily 3
   • Suspected mold infection → Use echinocandin, voriconazole, or itraconazole 1, 3

2. Never consider systemic ketoconazole regardless of infection severity or location 1

3. For refractory superficial infections: Use oral fluconazole 3-6 mg/kg daily for 7 days or itraconazole solution 2.5 mg/kg twice daily (for children ≥5 years). 6, 4

Critical Safety Considerations

• The hepatotoxicity risk with systemic ketoconazole increases with treatment duration (median 276 days in treatment studies showed 5.6% elevated liver enzymes). 7

• All azole antifungals have significant drug interactions with immunosuppressants requiring careful medication reconciliation, but ketoconazole's risk-benefit profile makes it uniquely unsuitable. 3, 8

• Newer oral antifungals have similar or greater efficacy with substantially less risk, making ketoconazole obsolete for systemic use. 8