What is the recommended treatment for fungal nail infections?

Treatment of Fungal Nail Infections

Terbinafine 250 mg daily is the first-line treatment for dermatophyte onychomycosis: 6 weeks for fingernails and 12 weeks (up to 16 weeks) for toenails. 1, 2

Essential Pre-Treatment Requirements

Do not initiate treatment without mycological confirmation of infection through microscopy and culture. 1 This critical step prevents unnecessary treatment, as other conditions like psoriasis and nail trauma can mimic fungal infection. 3

First-Line Systemic Treatment: Terbinafine

Terbinafine is superior to all other antifungal agents for dermatophyte onychomycosis both in vitro and in vivo, making it the preferred first-line choice. 1

Dosing Regimen

• Fingernail infections: 250 mg daily for 6 weeks 1
• Toenail infections: 250 mg daily for 12-16 weeks 1, 2, 4
• Can be taken with or without food 5

Expected Outcomes

• Cure rates of 80-90% for fingernails and 70-80% for toenails 1
• Re-evaluate patients 3-6 months after treatment initiation 2
• Full nail regrowth may take up to 18 months for toenails 1

Mechanism and Superiority

Terbinafine inhibits squalene epoxidase, resulting in both fungistatic (ergosterol depletion) and fungicidal (squalene accumulation) effects. 1 Its minimum inhibitory concentration (MIC) is approximately 0.004 µg/mL, equivalent to its minimal fungicidal concentration, confirming true fungicidal activity. 1

Monitoring Requirements

• Baseline liver function tests (LFTs) and complete blood count are recommended 1, 2, 5
• More vigilant monitoring needed in patients with:
  • Pre-existing liver disease 2
  • Concomitant hepatotoxic medications 2
  • History of heavy alcohol consumption 2

Common Adverse Effects

• Headache, gastrointestinal upset, and taste disturbance 1, 4, 5
• Taste changes usually improve within weeks after stopping but may become permanent 5
• Can aggravate psoriasis and cause subacute lupus-like syndrome 1

Serious but Rare Adverse Effects

• Hepatotoxicity requiring liver transplant or causing death 5
• Stevens-Johnson syndrome and toxic epidermal necrolysis 4
• Depressive symptoms 5

Drug Interactions

Terbinafine has minimal drug interactions compared to azole antifungals, making it particularly useful in immunocompromised patients on multiple medications. 2, 6 The main concern is with drugs metabolized by cytochrome P450 2D6. 2

Second-Line Systemic Treatment: Itraconazole

Itraconazole is the next best alternative when terbinafine cannot be used. 1 It is less effective than terbinafine for dermatophytes but is the most effective agent for Candida nail infections. 1

Dosing Options

Two regimens are available:

• Continuous therapy: 200 mg daily for 12 weeks 1
• Pulse therapy: 400 mg daily for 1 week per month
  • 2 pulses (21 days apart) for fingernails 1
  • 3 pulses for toenails 1

Candida Onychomycosis

For Candida nail plate invasion, use the same pulse regimen: 400 mg daily for 1 week per month, repeated for 2 months (fingernails) or 3-4 pulses (toenails). 1

Important Considerations

• Must be taken with food and requires acidic pH for optimal absorption 1
• Contraindicated in heart failure 1
• Potent CYP3A4 inhibitor with significant drug interaction potential 6
• Monitor hepatic function in patients with pre-existing abnormalities or receiving continuous therapy >1 month 1

Third-Line Option: Fluconazole

Fluconazole may be useful when patients cannot tolerate terbinafine or itraconazole. 1, 4

• Dosing: 150-450 mg weekly for 3 months (fingernails) or at least 6 months (toenails) 1, 4
• Contraindicated in hepatic and renal impairment 1

Topical Treatments

Topical therapy is inferior to systemic treatment except in very distal infections or superficial white onychomycosis. 1

When to Consider Topical Treatment

• Mild cases with limited nail involvement 4
• As adjunctive therapy to systemic treatment 4
• Patients who cannot tolerate systemic therapy 4

Available Options

• Amorolfine nail lacquer: Applied once or twice weekly 4
• Ciclopirox 8% nail lacquer: Applied daily for up to 48 weeks; mycological cure rates approach 50% 4, 3
• Efinaconazole 10%: Applied daily; mycological cure rates approach 50% 4

Treatment of Yeast Infections

Most yeast infections associated with paronychia can be treated topically. 1

• Apply broad-spectrum, colorless, non-sensitizing antiseptics to the proximal nail 1
• Alternate imidazole lotion with antibacterial lotion 1
• Continue until cuticle integrity is restored (may take several months) 1

Managing Treatment Failure

Despite terbinafine being the most effective agent, a consistent 20-30% failure rate occurs. 1

Common Causes of Failure

• Poor compliance 1
• Presence of dermatophytoma (dense white lesion of tightly packed hyphae beneath the nail) 1
• Nail thickness >2 mm 1
• Severe onycholysis 1
• Slow nail outgrowth 1

Management of Dermatophytoma

Partial or complete nail removal is indicated before retreatment when dermatophytoma is present, as this tightly packed fungal mass prevents adequate drug penetration. 1 Cure rates approaching 100% can be achieved with nail avulsion under ring block prior to treatment. 1

Prevention of Recurrence

Recurrence is common due to ubiquitous environmental exposure to T. rubrum in public facilities. 1

Essential Preventive Measures

• Always wear protective footwear in public bathing facilities, gyms, and hotel rooms 1
• Apply absorbent antifungal powders (miconazole, clotrimazole, or tolnaftate) in shoes and on feet 1
• Wear cotton, absorbent socks 1
• Keep nails as short as possible 1
• Avoid sharing toenail clippers 1
• Discard old, moldy footwear or disinfect with naphthalene mothballs in sealed plastic bags for minimum 3 days 1
• Treat all infected family members simultaneously 1

Critical Pitfalls to Avoid

• Never treat without mycological confirmation - other conditions frequently mimic onychomycosis 1
• Do not use griseofulvin as first-line therapy - it has poor cure rates, high relapse rates, and requires prolonged treatment (often >1 year) 1, 7, 8
• Recognize that culture of yeasts and non-dermatophyte molds requires careful interpretation - yeasts are often secondary infections and non-dermatophyte molds are frequently saprophytic in previously damaged nails 1
• Do not expect immediate results - allow at least 48-72 weeks from treatment start to assess true efficacy and identify relapse 1
• Monitor for photosensitivity with terbinafine - advise patients to minimize exposure to natural and artificial sunlight 5