What is the first line of treatment for a patient with Onychomycosis (fungal infection of the nail)?

First-Line Treatment for Onychomycosis

Oral terbinafine 250 mg daily for 12 weeks (toenails) or 6 weeks (fingernails) is the first-line treatment for dermatophyte onychomycosis, with superior efficacy compared to all other oral agents. 1, 2, 3

Diagnostic Confirmation Required Before Treatment

• Always obtain laboratory confirmation (KOH preparation, fungal culture, or nail biopsy) before initiating any systemic therapy, as incorrect diagnosis is the most common cause of treatment failure 4, 3
• This step is critical because onychomycosis can mimic other nail disorders, and systemic antifungals require prolonged treatment with potential adverse effects 5, 6

First-Line Systemic Treatment: Terbinafine

Terbinafine is recommended as first-line by both the British Association of Dermatologists and American College of Dermatology due to:

• Superior mycological cure rates (>80% for dermatophyte infections) 7
• Fungicidal mechanism (inhibits squalene epoxidase, directly killing dermatophytes) 2
• Shorter treatment duration compared to alternatives 1, 2
• Better cost-effectiveness profile 2, 8

Terbinafine Dosing Regimen

• Adults: 250 mg once daily for 12 weeks for toenails, 6 weeks for fingernails 1, 2, 3
• Pediatric patients (weight-based): 1, 2
  • <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

Monitoring Requirements for Terbinafine

• Baseline liver function tests and complete blood count are recommended, particularly in patients with history of hepatotoxicity or hematological abnormalities 1, 4
• Monitor for common adverse effects: headache, taste disturbance, gastrointestinal upset 1, 8
• Important caveat: Terbinafine can exacerbate psoriasis and cause subacute lupus-like syndrome 1, 2

Alternative First-Line: Itraconazole

Itraconazole is an acceptable alternative first-line agent when terbinafine is contraindicated or not tolerated, with two dosing options: 1, 2, 9

Itraconazole Dosing Options

• Pulse therapy (preferred): 400 mg daily (200 mg twice daily) for 1 week per month 2, 9
  • 2 pulses (2 months total) for fingernails
  • 3 pulses (3 months total) for toenails
• Continuous therapy: 200 mg daily for 12 weeks 9, 4

Critical Itraconazole Considerations

• Must be taken with food and acidic beverages for optimal absorption 2, 9
• Contraindicated in heart failure due to negative inotropic effects 2, 9
• Extensive drug interactions, particularly with statins (can increase statin levels significantly) 9
• Baseline liver function tests required, with ongoing monitoring if therapy exceeds 1 month or with concomitant hepatotoxic drugs 2, 9

When to Choose Itraconazole Over Terbinafine

Itraconazole should be selected as first-line in these specific scenarios:

• Candida onychomycosis: Itraconazole has 92% cure rate vs. only 40% with terbinafine 2
• Nondermatophyte molds (Scopulariopsis, Aspergillus, Fusarium): Itraconazole has broader antimicrobial coverage with 88% cure rates 2
• Terbinafine has low activity against these organisms despite excellent dermatophyte efficacy 2

Second-Line Systemic Options

Fluconazole

• Consider when both terbinafine and itraconazole are contraindicated or not tolerated 1, 2
• Dosing: 150-450 mg once weekly for at least 6 months for toenails 2, 9, 4
• Advantages: Fewer drug interactions with statins compared to itraconazole, particularly important in elderly patients 9
• Disadvantage: Less effective than terbinafine or itraconazole for dermatophyte infections 2

Griseofulvin

• Not recommended as first-line due to poor efficacy (only 30-40% mycological cure), long treatment duration (12-18 months for toenails), and high relapse rates 2, 9, 7
• Only consider when other agents are unavailable or contraindicated 2

Topical Therapy: Limited Role

Topical antifungals should only be used as monotherapy for: 2, 4

• Superficial white onychomycosis
• Very early distal lateral subungual onychomycosis
• When systemic therapy is contraindicated

Topical Options

• Amorolfine 5% nail lacquer: Apply once or twice weekly for 6-12 months, approximately 50% effective when infection limited to distal nail 2, 9
• Efinaconazole 10% solution: Mycological cure rates approaching 50%, complete cure in 15% after 48 weeks 9, 5
• Ciclopirox 8% nail lacquer: 34% mycological cure vs. 10% placebo, but only 8% clinical cure 9, 5

Combination Therapy for Enhanced Efficacy

Consider combining systemic and topical therapy to: 9

• Improve cure rates through antimicrobial synergy
• Provide wider antifungal spectrum
• Suppress resistant mutants
• Particularly useful in severe cases or treatment failures

Special Population Considerations

Diabetic Patients

• Terbinafine is preferred due to lower risk of drug interactions and hypoglycemia 2
• Treatment is particularly important as onychomycosis is a significant predictor for foot ulcers in diabetics 2

Immunosuppressed Patients

• Terbinafine and fluconazole are preferred due to lower risk of interactions with antiretrovirals compared to itraconazole/ketoconazole 2, 4

Elderly Patients

• Fluconazole may be preferred over itraconazole due to fewer drug interactions with commonly used medications (statins, cardiac drugs) and contraindication of itraconazole in heart failure 9

Adjunctive Measures to Improve Outcomes

Mechanical Debridement

• Nail trimming and debridement used concurrently with pharmacologic therapy improve treatment response 6
• Consider mechanical removal of dermatophytoma before or during antifungal therapy, as this is a common cause of treatment failure 4

Footwear Decontamination

• Decontaminate or replace contaminated footwear to eliminate fungal reservoirs 9
• Place naphthalene mothballs in shoes and seal in plastic bags for minimum 3 days 9
• Apply antifungal powders inside shoes regularly 9

Prevention of Recurrence

Onychomycosis has high recurrence rates of 40-70%, requiring preventive strategies: 2, 4

• Wear protective footwear in public places 2, 6
• Use absorbent and antifungal powders in shoes 2
• Keep nails short and clean 2, 4
• Avoid sharing nail clippers 2
• Consider prophylactic amorolfine application 2

Common Pitfalls to Avoid

• Never initiate systemic therapy without laboratory confirmation - this is the most common cause of treatment failure 4, 3
• Do not use terbinafine as first-line for Candida or nondermatophyte mold infections - it has poor activity against these organisms 2
• Avoid itraconazole in patients with heart failure - it is absolutely contraindicated 2, 9
• Monitor for drug interactions with itraconazole, especially with statins, which can lead to rhabdomyolysis 9
• Ensure adequate treatment duration - premature discontinuation leads to relapse 1