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

Treatment of Onychomycosis (Nail Fungus)

Oral terbinafine 250 mg daily is the first-line treatment for nail fungus, taken for 6 weeks for fingernails or 12 weeks for toenails, due to its superior efficacy, fungicidal properties, and cost-effectiveness compared to all other options. 1, 2, 3

Systemic (Oral) Treatment Options

First-Line: Terbinafine

• Terbinafine is the preferred oral agent recommended by the American College of Dermatology for dermatophyte onychomycosis 1, 2
• Dosing: 250 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) 4, 3
• Mechanism: Inhibits squalene epoxidase, causing direct fungicidal activity against dermatophytes 1, 2
• Common side effects: Headache, taste disturbance, gastrointestinal upset; can aggravate psoriasis and cause subacute lupus-like syndrome 4
• Monitoring required: Baseline liver function tests and complete blood count before starting treatment 4

Alternative First-Line: Itraconazole

• Use itraconazole when terbinafine is contraindicated or for Candida infections (where it has 92% cure rate vs. 40% with terbinafine) 1
• Dosing: 200 mg twice daily for 1 week per month (pulse therapy); 2 pulses for fingernails, 3 pulses for toenails 4, 1
• Critical administration detail: Must be taken with food and requires acidic pH for optimal absorption 4, 1
• Contraindication: Heart failure, hepatotoxicity 4
• Monitoring: Hepatic function tests recommended with pre-existing abnormalities, continuous therapy >1 month, or concomitant hepatotoxic drugs 4

Second-Line: Fluconazole

• Consider only when both terbinafine and itraconazole are contraindicated or not tolerated 4
• Dosing: 150-450 mg per week for 3 months (fingernails) or at least 6 months (toenails) 4
• Monitoring: Baseline liver function tests and full blood count; monitor LFTs with high-dose or prolonged therapy 4

Third-Line: Griseofulvin

• Griseofulvin is now relegated to third-line status due to poor mycological cure rates (30-40%), high relapse rates, and lengthy treatment duration 1, 2
• Dosing: 500-1000 mg daily for 6-9 months (fingernails) or 12-18 months (toenails) 4
• Must be taken with fatty food to increase absorption 4

Topical Treatment Options

When to Use Topical Therapy Alone

Topical antifungals should only be used as monotherapy in three specific scenarios: 4, 2

• Superficial white onychomycosis (SWO) affecting only the nail surface
• Very early distal lateral subungual onychomycosis (DLSO) with <80% nail plate involvement and no lunula involvement
• When systemic antifungals are contraindicated

Amorolfine 5% Nail Lacquer

• Apply once or twice weekly for 6-12 months after filing away diseased nail 4
• Efficacy: Approximately 50% effective for distal fingernail and toenail onychomycosis 4, 1
• Important caveat: Clinical improvement does not equal mycological cure—cure rates are typically 30% lower than clinical improvement rates 4
• Side effects are rare: local burning, pruritus, erythema 4

Ciclopirox 8% Nail Lacquer

• Apply once daily for up to 48 weeks (24 weeks for fingernails, 48 weeks for toenails) 4, 5
• FDA-approved only for mild to moderate onychomycosis without lunula involvement 5
• Efficacy is lower than amorolfine: 5.5-8.5% complete cure rate vs. 0.9% with placebo 5
• Must be used with monthly removal of infected nail by healthcare professional 5
• Do not combine with systemic antifungals—no studies support this combination and it is not recommended 5

Special Populations

Diabetic Patients

• Terbinafine is the preferred treatment due to lower risk of drug interactions and hypoglycemia 1, 2
• Critical consideration: Onychomycosis is a significant predictor for foot ulcers in diabetics, making treatment particularly important 4, 1, 2

Immunosuppressed Patients

• Use terbinafine or fluconazole due to lower risk of interactions with antiretrovirals 1, 2

Pediatric Patients (Ages 1-12 Years)

First-line options are terbinafine or itraconazole, with higher cure rates (88-100%) than adults: 4, 1

Terbinafine Dosing (Weight-Based):

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

• 40 kg: 250 mg daily

• Duration: 6 weeks (fingernails), 12 weeks (toenails) 4, 1

Itraconazole Pulse Therapy:

• 5 mg/kg/day for 1 week per month
• 2 pulses (fingernails), 3 pulses (toenails) 4, 1

Non-Dermatophyte Molds (Scopulariopsis, Aspergillus)

• Itraconazole is the preferred treatment with 88% cure rates for Scopulariopsis 1
• Standard regimen: 200-400 mg daily for 1 week per month for 3 months 4, 1
• Terbinafine has low activity against non-dermatophyte molds despite effectiveness against dermatophytes 1

Candida Infections

• Itraconazole is first-line with 92% cure rate 1
• Fluconazole is an alternative: 50 mg daily or 300 mg weekly 1

Combination Therapy

Combining topical and systemic antifungals improves outcomes when response to topical monotherapy alone would be poor: 4, 6

• Provides antimicrobial synergy and wider antifungal spectrum 4
• Increases cure rates and suppresses resistant mutants 4
• Specific recommendation: Use systemic terbinafine plus topical therapy for severe onychomycosis 7

Prevention of Recurrence

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

• Wear protective footwear in public facilities (pools, gyms, showers) 1, 2
• Use absorbent and antifungal powders in shoes 1, 2
• Keep nails short 1, 2
• Avoid sharing nail clippers 1, 2
• Amorolfine can be used prophylactically to prevent recurrence 4

Common Pitfalls to Avoid

• Do not start treatment without laboratory confirmation (KOH preparation, fungal culture, or nail biopsy) 3
• Do not use topical therapy alone for extensive disease (>80% nail involvement or lunula involvement) 4
• Do not combine ciclopirox with systemic antifungals—this is not recommended 5
• Do not assume clinical improvement equals mycological cure—fungal eradication rates are typically 30% lower than clinical improvement 4
• Do not use griseofulvin as first-line therapy due to poor efficacy and long treatment duration 1, 2