What is the best topical treatment for onychomycosis?

Best Topical Treatment for Onychomycosis

Amorolfine 5% nail lacquer is the best topical treatment for onychomycosis, with approximately 50% efficacy in distal fingernail and toenail infections and superior cure rates compared to other topical options. 1

Topical Treatment Options and Efficacy

Amorolfine 5% Nail Lacquer

• Mechanism: Belongs to morpholine group; inhibits delta 14 reductase and delta 8/7 isomerase enzymes in ergosterol biosynthesis
• Application: Once or twice weekly for 6-12 months (once-weekly is as effective as twice-weekly)
• Efficacy: ~50% effective in distal fingernail and toenail onychomycosis
• Persistence: Remains in nail for 14 days after treatment completion
• Side effects: Rare - limited to local burning, pruritus, and erythema
• Additional benefit: Effective as prophylactic treatment for recurrence 1

Ciclopirox 8% Nail Lacquer

• Mechanism: Hydroxypyridone derivative inhibiting metal-dependent enzymatic processes
• Application: Once daily for up to 48 weeks (24 weeks for fingernails, 48 weeks for toenails)
• Efficacy: Lower than amorolfine (34% mycological cure vs. 10% with placebo; clinical cure of only 8% vs. 1% with placebo)
• Side effects: Periungual and nail fold erythema
• FDA indication: Indicated for mild to moderate onychomycosis without lunula involvement, due to Trichophyton rubrum 1, 2

Efinaconazole 10% Solution

• Mechanism: Triazole antifungal agent
• Application: Once daily for 48 weeks
• Efficacy: Mycological cure rates approaching 50%, complete cure in 15% of patients
• Comparison: More recent agent with better efficacy than ciclopirox 1

Tioconazole 28% Solution

• Mechanism: Imidazole antifungal
• Efficacy: Only 22% mycological and clinical cure in studies
• Side effects: Allergic contact dermatitis not uncommon, nausea and rashes in 8-15% of patients
• Contraindications: Pregnancy; manufacturers caution against men fathering a child for 6 months after therapy 1

Treatment Algorithm for Topical Therapy

1. First-line topical therapy: Amorolfine 5% nail lacquer

   • Apply once weekly for 6-12 months
   • Remove diseased areas of nail by gentle filing before application
   • Most effective topical option with ~50% efficacy

2. Alternative if amorolfine unavailable: Efinaconazole 10% solution

   • Apply once daily for 48 weeks
   • Comparable mycological cure rates to amorolfine

3. Second alternative: Ciclopirox 8% nail lacquer

   • Apply once daily for 24 weeks (fingernails) or 48 weeks (toenails)
   • Less effective than amorolfine but FDA-approved in US

4. Last resort topical option: Tioconazole 28% solution

   • Lowest efficacy among topical options (22%)
   • Higher rate of side effects

Important Clinical Considerations

• Limited indications for topical monotherapy:

  • Superficial white onychomycosis (except transverse/striate infections)
  • Early distal lateral subungual onychomycosis when <80% of nail plate affected
  • No involvement of the lunula
  • Cases where systemic antifungals are contraindicated 1

• Clinical vs. mycological cure: Important to note that clinical improvement with topical antifungals may not equal mycological cure, which has invariably lower rates (often by 30%) 1

• Comparative studies: A randomized controlled trial comparing ciclopirox 8% with amorolfine 5% found amorolfine to be superior (treatment success: 26.7% for amorolfine vs. 58.3% for a newer ciclopirox formulation) 3

• Nail preparation: Always remove as much diseased nail as possible by gentle filing before applying topical treatments to improve penetration 1

Pitfalls and Caveats

1. Barrier to penetration: The hard keratin and compact structure of the dorsal nail plate significantly impedes topical drug diffusion. Drug concentration can drop by 1000 times from outer to inner surface 1

2. Treatment duration: Topical treatments require long treatment periods (6-12 months) and patient adherence is crucial for success

3. Systemic options may be needed: For extensive disease (>80% nail involvement), lunula involvement, or dermatophyte infections, oral antifungals like terbinafine may be more appropriate 1

4. Realistic expectations: Discuss with patients that complete cure rates with topical therapy are modest, and recurrence is common

5. Proper application technique: Ensure patients understand the importance of nail preparation and correct application frequency to maximize efficacy