How to treat onychomycosis (fungal infection of the toenails)?

Treatment of Onychomycosis (Fungal Toenail Infection)

For dermatophyte toenail onychomycosis, oral terbinafine 250 mg daily for 12-16 weeks is the first-line treatment, achieving superior cure rates (70-80%) compared to all other oral antifungals. 1

Confirm Diagnosis Before Treatment

• Never initiate systemic antifungal therapy without mycological confirmation through positive culture, direct microscopy (KOH), or histological examination 1
• Dermatophytes (primarily Trichophyton rubrum) cause the vast majority of cases 1, 2
• Yeasts and non-dermatophyte molds require careful interpretation—they are often secondary colonizers or saprophytes in previously damaged nails 1

Treatment Algorithm by Organism Type

Dermatophyte Infections (Most Common)

First-Line: Terbinafine

• Terbinafine 250 mg daily for 12-16 weeks for toenails (6 weeks for fingernails) 1
• Superior to itraconazole both in vitro and in vivo 1
• Achieves 70-80% cure rates for toenails 1, 3
• High-quality evidence shows 4.53 times higher mycological cure rate versus placebo 3
• Baseline liver function tests and complete blood count recommended 1
• Common adverse effects: headache, taste disturbance, gastrointestinal upset; can aggravate psoriasis 1

Second-Line: Itraconazole

• Pulse therapy: 400 mg daily for 1 week per month × 3 pulses for toenails (2 pulses for fingernails) 1
• Alternative: 200 mg daily continuously for 12 weeks 1
• Take with food for optimal absorption (requires acidic pH) 1
• Monitor hepatic function in patients with pre-existing abnormalities or on hepatotoxic drugs 1
• Contraindicated in heart failure due to negative inotropic effects 1

Third-Line: Fluconazole

• 150-450 mg weekly for at least 6 months for toenails (3 months for fingernails) 1
• Use when terbinafine or itraconazole are contraindicated or not tolerated 1

Candida Infections

First-Line: Itraconazole

• Pulse therapy: 400 mg daily for 1 week per month × 3-4 pulses for toenails (2 pulses for fingernails) 1
• Alternative: 200 mg daily for minimum 12 weeks for toenails 1
• Achieves 92% cure rates versus 40% with terbinafine pulse therapy 1
• Itraconazole is the most effective agent when nail plate is invaded by Candida 1

Second-Line: Fluconazole

• 50 mg daily or 300 mg weekly for minimum 12 weeks for toenails 1
• Equally effective as itraconazole for Candida onychomycosis 1

Terbinafine for Candida

• Requires longer treatment: 48 weeks at 250 mg daily achieves 70-85% cure for C. albicans and C. parapsilosis 1
• Only effective with extended duration; not recommended as first-line 1

Non-Dermatophyte Molds

Itraconazole is preferred due to broader antimicrobial coverage 1, 4

• Effective against Scopulariopsis brevicaulis (4/4 mycological cure) and Aspergillus species (5/6 mycological cure) 4
• Use standard pulse regimen: 400 mg daily for 1 week per month, with additional pulses as needed 4
• Terbinafine shows poor efficacy against most non-dermatophyte molds 4

Topical Therapy

Topical monotherapy is limited to specific scenarios only:

• Superficial white onychomycosis 1
• Early distal lateral subungual onychomycosis with <80% nail plate involvement, no lunula involvement, and no longitudinal streaks 1
• When systemic antifungals are contraindicated 1

Topical Options:

• Amorolfine 5% lacquer: Apply once or twice weekly for 6-12 months after filing diseased nail; achieves ~50% efficacy 1
• Ciclopirox 8% lacquer: Apply daily for up to 48 weeks; achieves 34% mycological cure versus 10% placebo, but only 8% clinical cure 1, 5
• Efinaconazole 10%: Daily application achieves ~50% mycological cure and 15% complete cure after 48 weeks 1

Critical limitation: Mycological cure rates are typically 30% lower than clinical improvement rates with topical agents 1

Combination Therapy

Recommended when response to topical monotherapy alone is likely to be poor 1

• Combining topical (amorolfine or ciclopirox) with systemic antifungals provides antimicrobial synergy and improved cure rates 1

Special Populations

Diabetic Patients

• Terbinafine is preferred due to low risk of drug interactions and no hypoglycemia risk 1
• Onychomycosis is a significant predictor for diabetic foot ulcers 1
• Itraconazole contraindicated if congestive heart failure present 1

Immunosuppressed Patients (HIV, Transplant)

• Terbinafine is preferred due to increased risk of itraconazole/ketoconazole interactions with antiretrovirals 1
• Griseofulvin is least effective in HIV patients 1

Children

• Terbinafine: 62.5 mg daily if <20 kg, 125 mg daily for 20-40 kg, 250 mg daily if >40 kg; treat for 6 weeks (fingernails) or 12 weeks (toenails) 1
• Itraconazole pulse therapy: 5 mg/kg daily for 1 week per month × 2 pulses (fingernails) or 3 pulses (toenails) 1
• Higher cure rates and faster response than adults 1
• Griseofulvin is the only licensed agent for children but no longer first-line due to low efficacy 1

Treatment Failure Management

Consistent 20-30% failure rate occurs even with optimal terbinafine therapy 1

Evaluate for:

• Poor compliance 1
• Poor drug absorption 1
• Immunosuppression 1
• Subungual dermatophytoma (tightly packed fungal mass preventing drug penetration) 1

For treatment failure:

• Consider partial nail removal combined with systemic therapy to cover regrowth period 1
• Switch to alternative oral antifungal 1
• Complete nail avulsion achieves near 100% cure rates but is rarely necessary 1

Critical Pitfalls to Avoid

• Never combine ciclopirox topical solution with systemic antifungals for onychomycosis—no studies have determined if ciclopirox reduces systemic agent effectiveness 5
• Do not use griseofulvin as first-line—it has only 30-40% cure rates, requires 12-18 months of treatment, and is inferior to newer agents 1
• Do not treat yeast or non-dermatophyte mold cultures as primary pathogens without careful clinical correlation—they are often secondary colonizers 1
• Topical therapy alone is inferior to systemic therapy except in very limited circumstances 1