What are the treatment options for onychomycosis (toe nail fungus)?

Treatment of Toenail Fungus (Onychomycosis)

Oral terbinafine 250 mg daily for 12-16 weeks is the first-line treatment for toenail onychomycosis, as it demonstrates superior efficacy compared to all other antifungal agents with cure rates of 70-80%. 1, 2

Confirm Diagnosis Before Treatment

• Obtain nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) to confirm onychomycosis before initiating any antifungal therapy 2, 3
• Treatment should never be commenced without mycological confirmation 1

Treatment Algorithm Based on Disease Severity

For Moderate-to-Severe Disease (Multiple Nails, >80% Nail Involvement, or Lunula Involvement)

Oral systemic therapy is required:

• Terbinafine 250 mg daily for 12-16 weeks is the preferred first-line agent 1

  • Obtain baseline liver function tests and complete blood count before starting treatment 1
  • Terbinafine is generally preferred over itraconazole due to superior efficacy 1
  • Common adverse effects include headache, taste disturbance, and gastrointestinal upset 1
  • Can aggravate psoriasis and cause subacute lupus-like syndrome 1
  • Contraindicated in hepatic or renal impairment 1

• Itraconazole as alternative first-line option 1

  • Pulse therapy: 400 mg daily for 1 week per month, repeated for 3 pulses (3 months total) 1
  • Continuous therapy: 200 mg daily for 12 weeks 1
  • Must be taken with food for optimal absorption 1
  • Monitor hepatic function tests in patients with pre-existing abnormalities or receiving therapy >1 month 1
  • Contraindicated in heart failure and hepatotoxicity 1

• Fluconazole as second-line alternative if terbinafine or itraconazole are contraindicated or not tolerated 1

  • Dosing: 150-450 mg per week for at least 6 months for toenail infections 1
  • Perform baseline liver function tests and full blood count 1

For Mild-to-Moderate Disease (<80% Nail Involvement, No Lunula Involvement, Distal/Superficial Disease)

Topical therapy options:

• Efinaconazole 10% solution is the most effective topical agent 4

  • Applied daily for 48 weeks 4
  • Achieves complete cure in 3.5 times more patients than vehicle (high-quality evidence) 4
  • Slightly higher risk of adverse events (dermatitis, vesicles) compared to vehicle 4

• Tavaborole 5% solution 4

  • Applied daily for 48 weeks 4
  • Probably more effective than vehicle for complete cure (moderate-quality evidence) 4
  • Higher risk of application site reactions 4

• Ciclopirox 8% lacquer 1, 5

  • Applied once daily for up to 48 weeks 1, 5
  • Must be used as component of comprehensive management program including monthly removal of infected nail by healthcare professional 5
  • Only for mild-to-moderate onychomycosis without lunula involvement 5
  • May be more effective than vehicle but has lower cure rates than efinaconazole 1, 4

• Amorolfine 5% lacquer (available in Europe) 1

  • Applied once or twice weekly for 6-12 months 1
  • Adverse effects are rare (local burning, pruritus, erythema) 1

Special Populations

Diabetic Patients

• Oral terbinafine is the preferred first-line agent due to low risk of drug interactions and hypoglycemia 6
• Standard dosing: 250 mg daily for 12 weeks 6
• Onychomycosis affects up to one-third of diabetic patients and is a significant predictor for foot ulcer development 6
• Assess for potential drug interactions with diabetes medications 6

Children (Age 1-12 Years)

• Terbinafine is first-line and generally preferred over itraconazole 1

  • Weight-based dosing: 62.5 mg daily if <20 kg, 125 mg daily for 20-40 kg, 250 mg daily for >40 kg 1
  • Duration: 6 weeks for fingernails, 12 weeks for toenails 1
  • Baseline liver function tests and complete blood count required (unlicensed for children) 1

• Itraconazole as alternative first-line 1

  • Pulse therapy: 5 mg/kg daily for 1 week per month, 3 pulses for toenails 1

Combination Therapy

• Recommended when response to topical monotherapy alone is likely to be poor 1
• Consider combining oral and topical agents for improved efficacy 1

Critical Pitfalls to Avoid

• Inadequate treatment duration: Toenail infections require 12-16 weeks of oral therapy or up to 48 weeks of topical therapy 1, 6
• Not addressing nail debridement: Monthly removal of infected nail material by healthcare professional improves outcomes, especially with topical therapy 5
• Expecting immediate results: Complete nail regrowth may take up to 18 months due to slow toenail growth 6
• Ignoring treatment failure causes: If treatment fails, consider subungual dermatophytoma (tightly packed fungal mass), poor compliance, poor absorption, or immunosuppression 1
• Not counseling on recurrence prevention: Patients must wear protective footwear in public areas, use antifungal powders in shoes, keep nails short, and avoid sharing nail clippers 1

Treatment Failure Management

• If first-line oral therapy fails, consider partial nail removal combined with systemic therapy to cover regrowth period 1
• Cure rates approaching 100% can be achieved with complete nail avulsion prior to treatment, though this is not necessary in most cases 1
• Recurrence rates are high; long-term preventive measures are essential 3, 7

Monitoring Requirements

• Terbinafine: Baseline liver function tests and complete blood count; monitor if history of hepatotoxicity or hematological abnormalities 1
• Itraconazole: Monitor hepatic function tests in patients with pre-existing abnormalities, continuous therapy >1 month, or concomitant hepatotoxic drug use 1
• Fluconazole: Baseline liver function tests and full blood count; monitor in high-dose or prolonged therapy 1

Treatments with Insufficient Evidence

• 1064-nm Nd:YAG laser: Very low-quality evidence for effectiveness; we are uncertain if it differs from no treatment 4
• Laser treatment is FDA-approved only for temporary increases in clear nail, with suboptimal clinical results 3