Is ketoconazole (antifungal medication) cream approved for use in pediatric patients?

Ketoconazole Cream for Pediatric Use: FDA Approval Status

Ketoconazole cream is NOT FDA-approved for use in children, as the drug label explicitly states "Safety and effectiveness in children have not been established." 1

Critical Distinction: Systemic vs. Topical Ketoconazole

Systemic Ketoconazole is Contraindicated

• Both the FDA and European Medicines Agency have issued explicit warnings against systemic ketoconazole use in all patients, including children, due to risks of hepatic toxicities, adrenal suppression, and drug interactions. 2, 3
• The American Society of Clinical Oncology specifically excluded systemic ketoconazole from their 2020 pediatric antifungal prophylaxis guidelines based on these regulatory safety warnings. 2, 3

Topical Ketoconazole Cream: Lack of Pediatric Approval

• The FDA drug label for ketoconazole cream 2% clearly states that "Safety and effectiveness in children have not been established." 1
• Despite this lack of formal approval, ketoconazole cream has been studied and used off-label in pediatric populations for specific conditions. 4, 5, 6

Clinical Evidence for Off-Label Pediatric Use

Seborrheic Dermatitis

• Ketoconazole 2% foam has been studied in patients aged ≥12 years for seborrheic dermatitis, showing efficacy and safety comparable to vehicle and cream formulations. 4
• A comparative study in infants (2 weeks to 2 years) with infantile seborrheic dermatitis found ketoconazole 2% cream as effective as hydrocortisone 1% cream, with all lesions clearing by two weeks. 6

Systemic Absorption Concerns

• A study in infants aged 1-5 months with extensive seborrheic dermatitis (>50% body surface area) found minimal systemic absorption after ketoconazole 2% cream application, with plasma levels (0.018-0.133 μg/mL) far below those seen with oral administration (4-9 μg/mL). 5
• This suggests systemic dose-dependent side effects are unlikely with topical use, though careful monitoring remains necessary. 5

Recommended Alternatives for Pediatric Fungal Infections

For Superficial/Cutaneous Infections

• Topical clotrimazole 1% cream applied 2-3 times daily for 7-14 days is the recommended first-line treatment for superficial fungal infections in children. 7

For Scalp Fungal Infections

• Ketoconazole shampoo (topical application only) may be used for scalp dermatophyte infections, leaving on for 3-5 minutes before rinsing. 3, 8

For Systemic/Invasive Fungal Infections

• Fluconazole 8-12 mg/kg once daily is first-line systemic treatment for invasive or mucosal candidiasis in pediatric patients. 7, 3
• For children <13 years requiring mold-active coverage, use an echinocandin, voriconazole, or itraconazole based on efficacy and adverse effect profiles. 2, 3

Clinical Decision Algorithm

When considering antifungal therapy in a pediatric patient:

1. Identify infection type and location:

   • Superficial/cutaneous → Use topical clotrimazole or nystatin 7, 3
   • Scalp dermatophyte → Consider ketoconazole shampoo (topical only) 3, 8
   • Invasive candidiasis → Use fluconazole 8-12 mg/kg daily 7, 3
   • Suspected mold infection → Use echinocandin, voriconazole, or itraconazole 2, 3

2. Never use systemic ketoconazole regardless of infection severity or location. 2, 3

3. If considering ketoconazole cream off-label for superficial infections, recognize this is not FDA-approved in children and safer alternatives (clotrimazole) exist. 7, 1

Key Caveats

• The FDA label's statement about lack of established safety and effectiveness in children does not mean the medication is dangerous, but rather that formal pediatric approval studies were not completed. 1
• Off-label use has been documented in clinical studies, particularly for infantile seborrheic dermatitis, with favorable safety profiles. 5, 6
• However, given the availability of FDA-approved alternatives like clotrimazole for most superficial fungal infections, these should be prioritized over ketoconazole cream in pediatric patients. 7