What is the best antifungal for the treatment of onychomycosis of the toenail?

Terbinafine is the First-Line Treatment for Toenail Onychomycosis

Oral terbinafine 250 mg daily for 12 weeks is the most effective treatment for onychomycosis of the toenail due to its superior efficacy and safety profile compared to other antifungals. 1, 2

Treatment Algorithm for Toenail Onychomycosis

First-Line Treatment:

• Terbinafine 250 mg daily
  • Duration: 12 weeks for toenails (6 weeks for fingernails)
  • Expected cure rates: 70-80% for toenails, 80-90% for fingernails 1, 2
  • Mechanism: Fungicidal action through inhibition of squalene epoxidase, depleting ergosterol and accumulating toxic squalene 1

Second-Line Treatment (if terbinafine is contraindicated or fails):

• Itraconazole
  • Option 1: 200 mg daily for 12 weeks continuously
  • Option 2: Pulse therapy - 400 mg daily for 1 week per month for 3 months
  • Less effective than terbinafine with mycological cure rates of only 38-49% vs. 76-81% for terbinafine 3

Third-Line Treatment:

• Fluconazole
  • 450 mg once weekly for at least 6 months
  • Lower efficacy than both terbinafine and itraconazole 1, 2
  • Consider when other options aren't tolerated

Evidence Supporting Terbinafine as First Choice

Terbinafine is superior to other antifungals for treating dermatophyte onychomycosis based on:

1. Superior efficacy: Multiple studies demonstrate higher cure rates with terbinafine compared to itraconazole, fluconazole, and griseofulvin 1, 3

2. Long-term effectiveness: The L.I.ON. Icelandic Extension study showed significantly lower relapse rates with terbinafine (23%) compared to itraconazole (53%) at 5-year follow-up 3

3. Continuous vs. pulse dosing: Continuous dosing of terbinafine (250 mg daily for 12 weeks) shows superior clinical cure rates (76.67%) compared to pulse dosing (26.67%) 4

4. Safety profile: Terbinafine has fewer drug interactions compared to azoles, making it particularly suitable for patients on multiple medications 1, 2

5. Cost-effectiveness: Terbinafine is more cost-effective than griseofulvin, fluconazole, or itraconazole 5

Special Populations

• Diabetic patients: Terbinafine is preferred due to lower risk of drug interactions and no contraindication in cardiac disease 1, 2

• Immunosuppressed patients: Terbinafine or fluconazole is preferred over itraconazole due to fewer interactions with antiretrovirals 1, 2

• Pediatric patients: Terbinafine dosing based on weight:

  • <20 kg: 62.5 mg daily
  • 20-40 kg: 125 mg daily

  • 40 kg: 250 mg daily

  • Duration: 6 weeks for fingernails, 12 weeks for toenails 1

Monitoring and Precautions

• Obtain baseline liver function tests and complete blood count before starting terbinafine, especially in patients with history of hepatotoxicity 2, 6

• Common adverse effects include headache (12-13%), diarrhea (6%), rash (6%), dyspepsia (4%), taste disturbance (3%), and nausea (3%) 6

• Serious but rare adverse effects include liver failure, severe taste/smell disturbance, depressive symptoms, severe neutropenia, and serious skin reactions 6

Management of Treatment Failure

If treatment fails despite appropriate therapy, consider:

1. Poor compliance
2. Poor drug absorption
3. Immunosuppression
4. Dermatophyte resistance
5. Subungual dermatophytoma preventing drug penetration

Options for management of treatment failure:

• Partial nail removal plus antifungal therapy
• Alternative antifungal drug
• Complete nail avulsion combined with antifungal therapy 1

Important Caveats

• Always confirm diagnosis with appropriate nail specimens (KOH preparation, fungal culture, or nail biopsy) before initiating treatment 6

• For Candida onychomycosis, itraconazole may be more effective than terbinafine 1

• For non-dermatophyte mold infections, treatment should be guided by in vitro susceptibility testing 1

• Topical therapy alone (amorolfine 5% lacquer, ciclopirox 8% lacquer) should only be considered for superficial white onychomycosis or very early distal lateral subungual onychomycosis with <80% nail involvement 2