What is the recommended treatment for onychomycosis (nail fungus)?

Treatment of Onychomycosis (Nail Fungus)

Oral terbinafine 250 mg daily is the first-line treatment for nail fungus: 6 weeks for fingernails and 12 weeks for toenails. 1, 2, 3

Confirm the Diagnosis First

• Always obtain laboratory confirmation (KOH preparation, fungal culture, or nail biopsy) before starting treatment, as clinical diagnosis alone is the most common cause of treatment failure 4, 3
• Mycological cure rates mirror patient satisfaction more closely than clinical appearance scores, making organism eradication the primary treatment goal 5

Treatment Algorithm

For Most Cases: Oral Therapy

Terbinafine is superior to all alternatives due to its fungicidal mechanism (inhibits squalene epoxidase), highest cure rates, and favorable cost-effectiveness profile 1, 2

• Dosing: 250 mg once daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 4, 3
• Efficacy: Mycological cure rates exceed 80% for dermatophyte infections 6
• Mechanism: Directly fungicidal against dermatophytes by depleting ergosterol and accumulating toxic squalene 1

Itraconazole is the alternative first-line agent, particularly for Candida or nondermatophyte mold infections 1, 2

• Dosing: 200 mg twice daily for 1 week per month (pulse therapy): 2 pulses for fingernails, 3 pulses for toenails 1, 7
• Advantage: Broader antimicrobial coverage than terbinafine, with 92% cure rate for Candida infections versus 40% with terbinafine 1
• Important: Must be taken with food and acidic pH for optimal absorption 1

For Limited Disease Only: Topical Therapy

Topical treatment should only be used when ALL of the following criteria are met 5, 1, 4:

• Superficial white onychomycosis (SWO), OR
• Very early distal lateral subungual onychomycosis (DLSO) with <80% nail plate involvement and no lunula involvement, OR
• Systemic therapy is contraindicated

Topical options (in order of preference):

• Amorolfine 5% nail lacquer: ~50% effectiveness when infection is limited to distal nail 5, 1, 4
• Ciclopirox 8% nail lacquer: 34% mycological cure versus 10% with placebo 4, 8
• Avoid salicylic acid: No published efficacy studies exist and its use cannot be recommended 4

Critical caveat: Systemic therapy is almost always more successful than topical treatment, and using topical therapy for extensive disease results in predictable failure 5, 4

Special Populations

Diabetic Patients

• Terbinafine is strongly preferred over itraconazole due to lower risk of drug interactions and hypoglycemia 1, 2
• Treatment is particularly important as onychomycosis is a significant predictor for foot ulcers in diabetics 1, 2

Immunosuppressed Patients

• Terbinafine or fluconazole are preferred over itraconazole due to reduced drug interactions with antiretrovirals and immunosuppressants 1, 4

Pediatric Patients

• Pulse itraconazole: 5 mg/kg/day for 1 week per month for 2 months (fingernails) or 3 months (toenails) 1, 2
• Terbinafine (weight-based): 62.5 mg/day if <20 kg, 125 mg/day for 20-40 kg, 250 mg/day if >40 kg 1, 2
• Pediatric cure rates are higher (88-100%) than adults with terbinafine 1, 4

Candida or Nondermatophyte Mold Infections

• Itraconazole is the preferred treatment due to broader antimicrobial coverage 1
• For Scopulariopsis and Aspergillus: 88% cure rates with itraconazole 200-400 mg daily for 1 week per month for 3 months 1
• Terbinafine has low activity against nondermatophyte molds despite excellent dermatophyte efficacy 1

Monitoring and Safety

Baseline Testing

• Obtain liver function tests and complete blood count before initiating oral therapy 4
• Monitor liver function in patients with pre-existing abnormalities, those receiving continuous therapy >1 month, or those on concomitant hepatotoxic medications 4

Common Side Effects

Terbinafine: Headaches, taste disturbances, gastrointestinal disturbances; may exacerbate psoriasis or cause subacute lupus syndrome 4, 7

Itraconazole: Gastrointestinal distress, nausea, diarrhea, abdominal pain; contraindicated in heart failure 4, 7

Drug Interactions

• Itraconazole: Potent CYP3A4 inhibitor with significant drug interaction potential 9, 7
• Terbinafine: Inhibits CYP2D6 but has fewer interactions than itraconazole 9, 7
• Fluconazole: Inhibits CYP3A4, CYP2C9, and CYP2C19, but to a lesser degree than itraconazole 9

Second-Line and Avoided Treatments

Griseofulvin

• Now considered third-line due to poor cure rates (30-40%), high relapse rates, and lengthy treatment duration (6-18 months) 4, 2, 6
• Only indicated when other agents are unavailable or contraindicated 1

Fluconazole (Off-Label)

• Less effective than terbinafine or itraconazole for dermatophyte infections 4
• May be useful when other agents are contraindicated due to lower CYP450 inhibition 4, 10
• Typical dosing: 150 mg weekly for 9-18 months until abnormal nail grows out 7

Ketoconazole

• Cannot be prescribed for dermatophyte onychomycosis due to hepatotoxicity concerns 5

Prevention of Recurrence

Onychomycosis has high recurrence rates (40-70%), requiring preventive strategies 1, 4, 2:

• Wear protective footwear in communal bathing facilities 1, 2
• Use absorbent and antifungal powders in shoes 1, 2
• Keep nails short 1, 2
• Avoid sharing nail clippers 1, 2
• Consider prophylactic amorolfine nail lacquer 4

Common Pitfalls to Avoid

• Underdosing or insufficient treatment duration leads to poor outcomes and is a frequent cause of failure 4
• Not confirming diagnosis mycologically before treatment is the most common error 4
• Using topical therapy for extensive disease results in predictable failure 4
• Ignoring drug interactions in patients on multiple medications, particularly with itraconazole 4
• Treatment failure rates of 20-30% occur even with optimal agents, so realistic expectations should be set 4