What is the efficacy of efinaconazole, tavaborole, oral terbinafine (Lamisil), tolnaftate, urea, and lactic acid compared to topical terbinafine and ketoconazole (Nizoral)/ibuprofen in dimethyl sulfoxide (DMSO) for treating onychomycosis (nail fungus)?

Treatment Efficacy for Onychomycosis (Nail Fungus)

Oral terbinafine is the most effective treatment for onychomycosis with mycological cure rates of 70-80% for toenail infections and 80-90% for fingernail infections, significantly outperforming all other treatment options. 1

First-Line Treatment: Oral Terbinafine

Oral terbinafine is clearly the treatment of choice for onychomycosis based on the highest quality evidence:

• Dosage: 250mg once daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 2
• Mechanism: Inhibits ergosterol biosynthesis via squalene epoxidase inhibition, causing both fungistatic and fungicidal effects 2
• Efficacy:
  • 73-94% mycological cure rate (high-quality evidence) 1
  • Clinical studies show superior efficacy compared to itraconazole, fluconazole, and griseofulvin 3
  • Long-term studies demonstrate significantly lower relapse rates (23%) compared to other treatments (53% for itraconazole) 3

Topical Treatment Options (Second-Line)

When oral terbinafine is contraindicated, topical options can be considered, though they are less effective:

• Efinaconazole 10% solution:

  • Mycological cure rates of approximately 50% 1
  • Better penetration than older topical agents 4
  • Requires longer treatment duration

• Tavaborole 5%:

  • Lower efficacy than oral agents but fewer adverse effects and drug interactions 4
  • May be appropriate for mild to moderate cases

• Ciclopirox 8% lacquer:

  • Mycological cure rates of 34% 1
  • Less effective than newer topical agents

• Amorolfine 5% nail lacquer:

  • Approximately 50% efficacy in distal nail infections 1

• Topical terbinafine:

  • Less effective than oral formulation due to limited nail penetration

Alternative Oral Treatments

When terbinafine is not suitable:

• Itraconazole:

  • 200mg daily for 12 weeks 1
  • 45.8% mycological cure rate at 48 weeks (moderate-quality evidence) 1
  • Higher relapse rates than terbinafine 3
  • Requires liver function monitoring for treatment durations >1 month 1

• Fluconazole:

  • 150-450mg once weekly for at least 6 months 1
  • Lower efficacy than terbinafine 1
  • Useful when patients cannot tolerate terbinafine or itraconazole

Treatment Selection Algorithm

1. Confirm diagnosis through microscopic examination with potassium hydroxide (KOH), mycological culture, or nail biopsy 1
2. Assess severity and patient factors:
   • For moderate to severe infections: Oral terbinafine (first choice)
   • For mild to moderate infections or when oral therapy is contraindicated: Consider topical options
   • For patients with liver disease: Avoid oral terbinafine, consider topical options
   • For patients on multiple medications: Check for drug interactions, especially with itraconazole

Important Considerations and Caveats

• Treatment duration: Complete clinical improvement may take months after mycological cure due to the time required for healthy nail outgrowth 2
• Relapse prevention: Maintain short and clean nails, dry feet well after bathing, wear cotton socks and change them daily, apply antifungal powders to shoes and feet 1
• Monitoring: For oral terbinafine, baseline liver function tests are recommended 2
• Common pitfalls to avoid:
  • Not confirming diagnosis before treatment initiation
  • Inadequate treatment duration
  • Unrealistic expectations about speed of improvement
  • Not addressing predisposing factors 1

Special Populations

• Diabetic patients: Terbinafine is preferred due to lower risk of drug interactions 1
• Immunosuppressed patients: Consider topical options when systemic therapy is contraindicated 1
• Pediatric patients: Terbinafine dosing based on weight 1

Oral terbinafine remains the gold standard for treating onychomycosis, with significantly higher cure rates and lower relapse rates than all other available treatments.