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

Treatment for Toenail Fungus (Onychomycosis)

Terbinafine 250 mg daily for 12 weeks is the first-line treatment for toenail onychomycosis caused by dermatophytes, offering superior cure rates, fungicidal action, and better cost-effectiveness compared to all alternatives. 1, 2, 3, 4, 5

First-Line Oral Therapy: Terbinafine

Terbinafine is the gold standard for dermatophyte toenail infections based on multiple high-quality guidelines and FDA approval. 1, 2, 3, 4

Dosing and Mechanism

• Toenails: 250 mg once daily for 12 weeks 5
• Fingernails: 250 mg once daily for 6 weeks 5
• Works by inhibiting squalene epoxidase, causing fungal cell death through ergosterol depletion and toxic squalene accumulation 1
• Truly fungicidal with minimal inhibitory concentration equal to minimal fungicidal concentration 1

Efficacy

• Mycological cure rate: 70-82% 6, 7
• Complete cure rate: 38-59% 6, 7
• Significantly superior to itraconazole for dermatophyte infections (evidence grade A-I) 1
• Clinical improvement continues for months after treatment completion as healthy nail grows out 5

Monitoring and Precautions

• Obtain baseline liver function tests before starting treatment 5
• Monitor periodically during therapy, especially if treatment exceeds 6 weeks 5
• Discontinue immediately if liver enzyme elevation occurs or if patient develops persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools 5
• Contraindicated in patients with chronic or active liver disease 5

Common Adverse Effects

• Taste disturbance (1 in 400 patients) - can be severe, prolonged, or permanent 1, 5
• Headache, gastrointestinal upset 4
• Can aggravate psoriasis or cause lupus-like syndrome 4
• Smell disturbance - may be permanent 5
• Depressive symptoms have been reported 5

Alternative First-Line: Itraconazole

Use itraconazole when terbinafine is contraindicated or for Candida/nondermatophyte mold infections. 1, 2, 3

Dosing Options

• Continuous therapy: 200 mg once daily for 12 weeks 1
• Pulse therapy (preferred): 200 mg twice daily for 1 week per month - three pulses for toenails, two pulses for fingernails 1, 2, 3
• Take with food and acidic beverages to enhance absorption 3

Efficacy

• Mycological cure: 54% for continuous therapy 6
• Less effective than terbinafine for dermatophytes (evidence grade A-I) 1
• Superior for Candida infections: 92% cure rate versus 40% with terbinafine 3
• Excellent for nondermatophyte molds (Scopulariopsis, Aspergillus, Fusarium): 88% cure rate 3, 8

Monitoring and Drug Interactions

• Requires liver function monitoring for treatment exceeding 1 month 1
• Contraindicated in heart failure 1
• Major drug interactions: warfarin, terfenadine, astemizole, sertindole, midazolam, digoxin, cisapride, ciclosporin, simvastatin 1

Topical Therapy: Limited Role

Topical treatments should only be used for superficial white onychomycosis, very early distal lateral subungual onychomycosis, or when systemic therapy is contraindicated. 1, 2, 3

Amorolfine 5% Nail Lacquer

• Apply to affected nails after filing 4
• Efficacy: approximately 50% when infection is limited to distal nail 1, 2, 4
• Side effects: local burning, pruritus, erythema 4

Ciclopirox 8% Nail Lacquer

• FDA-approved for mild to moderate onychomycosis without lunula involvement 9
• Requires monthly removal of unattached infected nail by healthcare professional 9
• Mycological cure: 34% versus 10% with placebo 4, 9
• Apply daily for up to 48 weeks 9
• Not recommended with concurrent systemic antifungals 9

Third-Line: Griseofulvin (Not Recommended)

Griseofulvin is no longer the treatment of choice due to poor cure rates and lengthy treatment duration. 1, 2, 3

• Mycological cure rate: only 30-40% 3, 4
• Requires 12-18 months for toenails 3, 4
• High relapse rates 1
• Only indicated when terbinafine and azoles are unavailable or contraindicated 3, 4
• Licensed for children (only antifungal with this indication) 1

Special Populations

Diabetic Patients

Terbinafine is preferred due to lower risk of drug interactions and hypoglycemia. 2, 3, 4

• Onychomycosis is a significant predictor for foot ulcers in diabetics 2, 3
• Treatment is particularly important in this population 2, 3

Immunosuppressed Patients

Terbinafine and fluconazole are preferred due to lower risk of interactions with antiretrovirals. 2, 3, 4

Pediatric Patients

• Pulse itraconazole: 5 mg/kg/day for 1 week per month - 2 months for fingernails, 3 months for toenails 2, 3
• Terbinafine dosing by weight: 62.5 mg/day if <20 kg, 125 mg/day for 20-40 kg, 250 mg/day if >40 kg 2, 3
• Pediatric cure rates with terbinafine: 88-100% 3

Treatment Failure and Prevention

Common Causes of Treatment Failure

• Dermatophytoma (dense white lesion) - requires mechanical removal before antifungal therapy 1, 4
• Nail thickness >2 mm 1
• Severe onycholysis 1
• Slow nail outgrowth 1
• Poor compliance with lengthy regimens 4

Prevention of Recurrence (40-70% recurrence rate)

• Wear protective footwear in public facilities (gyms, pools, hotel rooms) 1, 4
• Apply absorbent and antifungal powders (miconazole, clotrimazole, tolnaftate) in shoes and on feet 1, 4
• Wear cotton, absorbent socks 1
• Keep nails as short as possible 1, 4
• Never share nail clippers 1, 4
• Discard contaminated footwear or treat with naphthalene mothballs in sealed plastic bag for 3 days 1
• Treat all infected family members simultaneously 1

Emerging Therapies

Newer Azoles (Not FDA-Approved for Onychomycosis)

• Fosravuconazole: 100 mg/day × 12 weeks - 59.4% complete cure, 82% mycological cure 6
• Posaconazole: 200 mg/day × 24 weeks - 54.1% complete cure, 70.3% mycological cure 6
• Oteseconazole: 300 mg/day × 2 weeks loading, then 300 mg/week × 10 weeks - 45% complete cure, 70% mycological cure 6

Laser Therapy

• 1064nm Nd:YAG lasers showing promising results 10
• Insufficient evidence for strong recommendations at this time 1

Photodynamic Therapy

• Cure rates: 44.3% at 12 months, declining to 36.6% at 18 months 1, 2
• Cannot be recommended based on limited evidence (strength of recommendation D, level of evidence 3) 1

Critical Pitfall to Avoid

Always confirm diagnosis with KOH preparation, fungal culture, or nail biopsy before initiating treatment - clinical appearance alone is insufficient. 5 Many nail dystrophies mimic onychomycosis, and unsuccessful treatment of misdiagnosed cases leads to unnecessary medication exposure and cost.