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

Treatment of Toenail Fungus (Onychomycosis)

For moderate-to-severe toenail onychomycosis, oral terbinafine 250 mg daily for 12-16 weeks is the first-line treatment, achieving 70-80% cure rates and demonstrating superior efficacy compared to other systemic antifungals. 1

Confirming the Diagnosis Before Treatment

• Never initiate treatment without mycological confirmation through KOH preparation, fungal culture, or nail biopsy 1, 2
• Dermatophytes (primarily Trichophyton rubrum) cause 80% of toenail infections 1
• Look specifically for: distal nail involvement, percentage of nail plate affected (<80% vs >80%), presence of longitudinal streaks, and lunula involvement—these determine treatment selection 1

Systemic Treatment Algorithm (First-Line for Most Cases)

Oral Terbinafine (Preferred)

• Dosing: 250 mg daily for 12-16 weeks for toenails (6 weeks for fingernails) 1
• Efficacy: 70-80% cure rate for toenails, superior to itraconazole both in vitro and in vivo 1
• Monitoring: Baseline liver function tests and complete blood count required; monitor in patients with history of hepatotoxicity 1
• Common adverse effects: Headache, taste disturbance, gastrointestinal upset 1
• Critical caveat: Can aggravate psoriasis and cause subacute lupus-like syndrome 1

Oral Itraconazole (Second-Line)

• Dosing options: Either 200 mg daily for 12 weeks continuously, OR pulse therapy with 400 mg daily for 1 week per month (3 pulses for toenails) 1
• Efficacy: 70-85% success rate, but consistently inferior to terbinafine 1, 3
• Administration: Must be taken with food and acidic pH for optimal absorption 1
• Contraindications: Heart failure, hepatotoxicity 1
• Monitoring: Hepatic function tests required in patients with pre-existing abnormalities, continuous therapy >1 month, or concomitant hepatotoxic drugs 1

Oral Fluconazole (Third-Line Alternative)

• Dosing: 150-450 mg per week for at least 6 months for toenail infections 1
• Use when: Patients cannot tolerate terbinafine or itraconazole 1
• Monitoring: Baseline liver function tests and full blood count; monitor in high-dose or prolonged therapy 1

Griseofulvin (Rarely Used)

• Dosing: 500-1000 mg daily for 12-18 months for toenails 1
• Major limitation: Lower efficacy and higher relapse rates compared to terbinafine and itraconazole 1
• Administration: Must be taken with fatty food to increase absorption 1

Topical Treatment (Limited Role)

Topical monotherapy is ONLY appropriate for: superficial white onychomycosis, early distal infection with <80% nail plate involvement, no lunula involvement, or when systemic therapy is contraindicated 1, 4

Efinaconazole 10% Solution (Most Effective Topical)

• Application: Once daily for 48 weeks 4
• Efficacy: Mycological cure rates approaching 50%, complete cure in 15% 4
• Evidence quality: High-quality evidence shows it is more effective than vehicle for complete cure (RR 3.54) and clinical cure (RR 3.07) 5
• Adverse events: Slightly higher risk (RR 1.10), including dermatitis and vesicles 5

Tavaborole 5% Solution

• Application: Once daily for 48 weeks 6
• Efficacy: Moderate-quality evidence shows probable effectiveness for complete cure (RR 7.40) and improved mycological cure (RR 3.40) 5
• Adverse events: Probably higher risk (RR 3.82), mainly application site reactions 5

Amorolfine 5% Lacquer

• Application: Once or twice weekly for 6-12 months 1, 4
• Efficacy: Approximately 50% effectiveness in distal toenail onychomycosis 1, 4
• Adverse effects: Rare—local burning, pruritus, erythema 1
• Important note: Once-weekly application is as effective as twice-weekly 1

Ciclopirox 8% Lacquer

• Application: Once daily for up to 48 weeks 1, 4, 7
• Efficacy: 34% mycological cure vs 10% placebo; only 8% clinical cure vs 1% placebo 1, 4
• FDA indication: Only for mild-to-moderate onychomycosis without lunula involvement, as component of comprehensive management including monthly nail debridement 7
• Lower efficacy: No head-to-head trials with amorolfine, but cure rates are usually lower with ciclopirox 1

Critical Limitation of All Topical Treatments

• The nail plate acts as a massive barrier: drug concentration drops 1000-fold from outer to inner nail surface 1, 4
• Clinical improvement ≠ mycological cure: apparent clinical improvement often exceeds actual mycological cure by 30% 1, 4
• Overall assessment: Complete cure rates with topical treatments are relatively low 5

Combination Therapy

• Recommended when: response to topical monotherapy alone is likely to be poor 1
• Combining systemic and topical treatments may improve efficacy, though specific evidence is limited 1

Device-Based Treatments (Laser)

1064-nm Nd:YAG Laser

• Evidence quality: Very low-quality evidence for adverse events; low-quality evidence shows there may be little or no difference in mycological cure at 52 weeks (RR 1.04) 5
• FDA approval: Only for temporary increases in clear nail, but clinical results are suboptimal 8
• Current recommendation: Insufficient evidence to support routine use 5

Treatment Failure Management

When treatment fails despite adequate therapy (20-30% failure rate even with terbinafine) 1:

1. Exclude obvious causes: poor compliance, poor absorption, immunosuppression, dermatophyte resistance, zero nail growth 1
2. Consider dermatophytoma: tightly packed fungal mass prevents drug penetration 1
3. Management approach: Partial nail removal (avulsion) prior to restarting systemic therapy can achieve cure rates close to 100% 1
4. Alternative strategy: Switch to different systemic agent or combine nail removal with antifungal therapy covering the regrowth period 1

Prevention of Recurrence

• Always wear protective footwear in public bathing facilities, gyms, hotel rooms to avoid re-exposure 1
• Apply antifungal powders (miconazole, clotrimazole, tolnaftate) in shoes and on feet 1
• Wear cotton, absorbent socks 1
• Keep nails as short as possible; avoid sharing nail clippers 1
• Shoe decontamination: Discard old footwear or place naphthalene mothballs in shoes within sealed plastic bag for minimum 3 days, or spray terbinafine solution periodically 1
• Treat all infected family members simultaneously 1
• Prophylactic amorolfine has been found effective for preventing recurrence 1

Special Populations

Children (Age 1-12 Years)

• Terbinafine (preferred): Weight-based dosing—62.5 mg daily if <20 kg, 125 mg daily for 20-40 kg, 250 mg daily for >40 kg; 12 weeks for toenails 1
• Itraconazole: Pulse therapy 5 mg/kg/day for 1 week per month; 3 pulses for toenails 1
• Note: Terbinafine is unlicensed for children; baseline monitoring required 1

Candidal Onychomycosis

• Most yeast infections can be treated topically, particularly with paronychia 1
• For nail plate invasion: Itraconazole 400 mg daily for 1 week per month, 3-4 pulses for toenails 1
• Apply broad-spectrum, colorless, non-sensitizing antiseptics to proximal nail until cuticle integrity restored (may take several months) 1