What oral antifungal agents are appropriate for treating a fungal skin rash?

Oral Antifungal Options for Fungal Skin Rash

First-Line Treatment Recommendation

For suspected Candida skin infections (intertrigo in skin folds, especially in obese/diabetic patients), fluconazole 200-400 mg daily for 7-14 days is the preferred first-line oral treatment. 1

For dermatophyte infections (scaly, ring-shaped lesions with central clearing), itraconazole is the most effective oral option based on the most recent high-quality evidence, followed by fluconazole, terbinafine, and griseofulvin. 2

Treatment Selection Algorithm

Step 1: Identify the Likely Organism

• Candida infections present as intertrigo in skin folds, particularly in obese or diabetic patients 1
• Dermatophyte infections present as scaly, ring-shaped lesions with central clearing 1
• Obtain KOH preparation or fungal culture when possible before initiating therapy 1

Step 2: Choose Appropriate Oral Agent

For Candida Infections:

• First-line: Fluconazole 200-400 mg daily for 7-14 days 1
• Fluconazole-refractory cases: Itraconazole solution 200 mg daily OR voriconazole 200 mg twice daily 1
• Important caveat: C. glabrata and C. krusei may be resistant to fluconazole; if these species are identified, alternative therapy is required 1

For Dermatophyte Infections:

Based on a 2020 randomized pragmatic trial in chronic/chronic relapsing dermatophytosis:

• First-line: Itraconazole 5 mg/kg per day (66% cure rate at 8 weeks, number needed to treat = 2) 2
• Second-line: Fluconazole 5 mg/kg per day (42% cure rate at 8 weeks, number needed to treat = 4) 2
• Third-line: Terbinafine 7.5 mg/kg per day (28% cure rate at 8 weeks, number needed to treat = 8) 2
• Last resort: Griseofulvin 10 mg/kg per day (14% cure rate at 8 weeks) 2

Treatment duration: 8 weeks or until cure 2

Important Monitoring and Safety Considerations

• Baseline liver function tests are recommended before starting fluconazole, with monitoring for signs of hepatotoxicity 1
• Baseline liver function tests and complete blood count are recommended for patients with history of heavy alcohol consumption, hepatitis, or hematological abnormalities when using terbinafine 3
• Terbinafine is not recommended in patients with active or chronic liver disease 3

Drug Interaction Warnings

Itraconazole:

• Enhanced toxicity with warfarin, certain antihistamines (terfenadine, astemizole), antipsychotics (sertindole), anxiolytics (midazolam), digoxin, cisapride, ciclosporin, and simvastatin 3
• Decreased efficacy with H2 blockers, phenytoin, and rifampicin 3

Terbinafine:

• Minimal drug-drug interactions; only potentially significant interaction is with drugs metabolized by cytochrome P450 2D6 isoenzyme 3

Critical Pitfalls to Avoid

• Do not use oral ketoconazole due to poor side-effect profile, especially hepatotoxicity risk (withdrawn from use in UK and Europe in 2013) 3
• Do not rely on griseofulvin for dermatophyte skin infections unless other drugs are unavailable or contraindicated, given its low efficacy (14% cure rate) 2
• All four oral antifungals show limited effectiveness in the current epidemic of altered dermatophytosis, particularly in India, with cure rates at 4 weeks being 8% or less 2
• High relapse rates occur after treatment completion regardless of which oral antifungal is used 2

When Oral Therapy is Indicated

• Extensive, severe, or resistant infections that have failed topical therapy 4
• Dermatophyte infections of the skin not adequately treated by topical therapy alone 5
• Oral therapy is not justified for minor or trivial dermatophyte infections that will respond to topical agents alone 5