What is the best treatment for onychomycosis (fungal nail infection)?

Best Treatment for Onychomycosis

Terbinafine 250 mg daily is the best first-line treatment for dermatophyte onychomycosis, given for 6 weeks for fingernails and 12 weeks for toenails, as it demonstrates superior efficacy compared to all other oral antifungals with similar safety profiles. 1

Treatment Algorithm by Causative Organism

Dermatophyte Onychomycosis (Most Common)

First-line: Terbinafine

• Dosing: 250 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 2
• Efficacy: Achieves 70-80% cure rates for toenails and 80-90% for fingernails 1
• Evidence: Multiple comparative trials demonstrate terbinafine achieves complete cure in 55% vs 26% for itraconazole at 72 weeks, with mycological cure maintained in 46% vs 13% at 5-year follow-up 1
• Monitoring: Baseline liver function tests and complete blood count recommended 1
• Common adverse effects: Headache, taste disturbance, gastrointestinal upset 1

Second-line: Itraconazole

• Dosing options: Either 200 mg daily for 12 weeks continuously OR pulse therapy 400 mg daily for 1 week per month (2 pulses for fingernails, 3 pulses for toenails) 1
• Administration: Must be taken with food and acidic beverages for optimal absorption 1, 3
• Efficacy: Clinical cure rates of 14-26% with mycological cure of 54% 1
• Monitoring: Hepatic function tests required, especially with continuous therapy >1 month or concomitant hepatotoxic drugs 1
• Drug interactions: Contraindicated in heart failure; caution with statins as itraconazole increases statin levels 1, 3

Third-line: Fluconazole (off-label)

• Dosing: 150-450 mg weekly for 6+ months (toenails) or 3 months (fingernails) 1
• Use when: Patient cannot tolerate terbinafine or itraconazole 1
• Advantage: Fewer drug interactions than itraconazole, once-weekly dosing improves compliance 1

Candida Onychomycosis

First-line: Itraconazole

• Dosing: 200 mg daily OR pulse therapy 400 mg daily for 1 week per month (2 months for fingernails, 3-4 months for toenails) 1
• Rationale: Shorter treatment duration than terbinafine, more cost-effective, better compliance 1

Alternative: Fluconazole

• Dosing: 50 mg daily OR 300 mg weekly for minimum 4 weeks (fingernails) or 12 weeks (toenails) 1
• Use when: Contraindications to itraconazole exist 1

Terbinafine for Candida: Requires extended therapy (48 weeks) with lower efficacy; not recommended as first-line 1

Nondermatophyte Mould Onychomycosis

Preferred: Itraconazole

• Dosing: Standard 3-month pulse therapy (200-400 mg daily for 1 week per month) 1
• Efficacy: 88% cure rate for Scopulariopsis and Aspergillus infections 1
• Rationale: Broader antimicrobial coverage despite terbinafine showing lowest in vitro activity against nondermatophyte moulds 1

Special Populations

Diabetic Patients

• Preferred: Terbinafine over itraconazole 1
• Rationale: Lower risk of drug interactions, no hypoglycemia risk, itraconazole contraindicated in heart failure (more prevalent in diabetics) 1
• Clinical significance: Onychomycosis is a significant predictor for diabetic foot ulcers 1

Pediatric Patients

Both terbinafine and itraconazole are first-line options with higher cure rates than adults 1

• Terbinafine dosing: Weight-based for 6 weeks (fingernails) or 12 weeks (toenails):

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

  • 40 kg: 250 mg daily 1

• Itraconazole pulse therapy: 5 mg/kg daily for 1 week per month (2 months for fingernails, 3 months for toenails) 1

• Clinical cure rates: 100% with itraconazole, 88-94% with terbinafine in pediatric studies 1

Immunosuppressed Patients

• Preferred: Terbinafine 1
• Rationale: Increased risk of itraconazole and ketoconazole interactions with antiretrovirals 1

Topical Therapy

Topical agents are inferior to systemic therapy except for very distal infection or superficial white onychomycosis 1

When to Consider Topical Therapy

• Mild to moderate disease without lunula involvement 1, 4
• Contraindications to systemic therapy 1
• Adjunct to systemic therapy for improved cure rates 1

Topical Options

• Amorolfine 5% lacquer: Once or twice weekly for 6-12 months 1
• Ciclopirox 8% lacquer: Daily for up to 48 weeks; achieves 5.5-8.5% complete cure rates 1, 4
• Efinaconazole 10% solution: FDA-approved with fewer adverse effects than oral agents 5, 6
• Tavaborole 5% solution: FDA-approved alternative 5, 6

Critical Management Principles

Pre-Treatment Requirements

Never initiate treatment without mycological confirmation 1

• Obtain KOH preparation, fungal culture, or nail biopsy before starting therapy 1, 2
• Culture interpretation: Yeasts often represent secondary infection; nondermatophyte moulds may be saprophytic in damaged nails 1

Adjunctive Measures That Improve Outcomes

• Monthly nail debridement by healthcare professional during treatment 4, 5
• Mechanical removal of dermatophytoma before antifungal therapy 3
• Nail trimming concurrent with pharmacologic therapy 5

Expected Treatment Failure Rates

• Consistent 20-30% failure rate occurs even with optimal terbinafine therapy 1
• Common causes: Poor compliance, poor absorption, reinfection 1
• Management of failure: Consider alternative drug or nail removal with therapy covering regrowth period 1

Follow-up and Monitoring

• Minimum follow-up: 48 weeks from treatment start, preferably 72 weeks 1, 3
• Rationale: Allows identification of superior drug and detection of relapse 1
• Re-evaluation: 3-6 months after treatment initiation; continue if disease persists 1

Prevention of Recurrence (25% Relapse Rate)

• Footwear management: Discard or decontaminate old shoes with naphthalene mothballs 3
• Regular antifungal powder application inside shoes 3
• Periodic terbinafine solution spraying into shoes 3
• Hygiene measures: Keep nails short and clean, wear cotton socks, avoid sharing nail clippers, avoid barefoot walking in public places 3, 5

Common Pitfalls to Avoid

• Starting treatment without mycological confirmation leads to unnecessary therapy for non-fungal nail dystrophies 1
• Inadequate treatment duration results in higher relapse rates 1
• Ignoring drug interactions: Particularly itraconazole with statins, antiretrovirals, and in heart failure patients 1, 3
• Using griseofulvin: No longer recommended due to long treatment duration (12-18 months) and low efficacy 1
• Expecting 100% cure rates: Even optimal therapy has 20-30% failure rates 1