What is the recommended treatment for onychomycosis (fungal infection of the nails)?

Treatment of Onychomycosis

Terbinafine 250 mg daily is the first-line treatment for onychomycosis caused by dermatophytes, taken for 6 weeks for fingernails or 12 weeks for toenails, due to its superior efficacy, fungicidal properties, and favorable safety profile. 1, 2, 3

First-Line Oral Therapy

Terbinafine (Preferred)

• Terbinafine is recommended as first-line therapy by the American Academy of Dermatology and British Association of Dermatologists due to superior mycological cure rates compared to other agents 1, 4, 2
• Dosing: 250 mg once daily for 6 weeks (fingernails) or 12 weeks (toenails) 3
• Mechanism: Inhibits squalene epoxidase, causing ergosterol depletion and squalene accumulation, which is directly fungicidal against dermatophytes 1, 2
• Baseline liver function tests (ALT and AST) are required before initiating therapy 3
• Optimal clinical effect occurs months after treatment completion due to slow nail outgrowth 3

Itraconazole (Alternative First-Line)

• Use itraconazole for Candida onychomycosis or nondermatophyte molds, as it has broader antimicrobial coverage than terbinafine 4, 2
• Pulse dosing: 200 mg twice daily for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 5, 1, 4
• Itraconazole achieves 92% cure rate for Candida infections versus only 40% with terbinafine 4
• Contraindicated in congestive heart failure due to negative inotropic effects 5
• Better absorption with food and acidic pH 4, 2

Special Populations

Diabetic Patients

• Terbinafine is the preferred agent in diabetics due to lower risk of drug interactions and hypoglycemia 5, 1, 4
• Onychomycosis is a significant predictor for foot ulcer development in diabetics, making treatment particularly important 5, 1
• Itraconazole should be avoided given higher prevalence of cardiac disease in this population 5

Immunosuppressed Patients

• Terbinafine and fluconazole are preferred over itraconazole due to lower risk of interactions with antiretrovirals 5, 1, 4
• Most cases in immunosuppressed patients are caused by T. rubrum 5
• Griseofulvin is the least effective agent in HIV-positive patients 5

Pediatric Patients

• Pulse itraconazole: 5 mg/kg/day for 1 week per month—2 months for fingernails, 3 months for toenails 5, 1, 4
• Terbinafine dosing by weight: 62.5 mg/day if <20 kg, 125 mg/day for 20-40 kg, 250 mg/day if >40 kg 5, 1, 4
• Pediatric cure rates (88-100%) are higher than adults, with faster response to treatment 5, 4
• Fluconazole alternative: 3-6 mg/kg once weekly for 12-16 weeks (fingernails) or 18-26 weeks (toenails) 5

Topical Therapy

• Topical therapy should only be used for superficial white onychomycosis, very early distal lateral subungual onychomycosis, or when systemic therapy is contraindicated 1, 4, 2
• Amorolfine 5% nail lacquer: approximately 50% effective when infection is limited to distal nail 1, 4, 2
• Ciclopirox 8% nail lacquer: 34% mycological cure rate versus 10% with placebo 2
• Topical treatments are appropriate for mild-to-moderate infections in diabetics where drug interaction risk is high 5

Second-Line Agents

Griseofulvin

• Griseofulvin is no longer recommended as first-line therapy due to poor cure rates (30-40%), high relapse rates, and lengthy treatment duration (6-18 months) 5, 1, 4, 2
• Only indicated when other agents are unavailable or contraindicated 4, 2

Fluconazole (Off-Label)

• Not FDA-approved for onychomycosis but frequently used off-label with good efficacy 6
• Preferred for Candida infections as an alternative to itraconazole 4

Important Safety Considerations

Terbinafine Warnings

• Hepatotoxicity: Patients must immediately report persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools 3
• Taste/smell disturbances: May be prolonged or permanent; discontinue if occurs 3
• Depressive symptoms: Monitor for mood changes, worthlessness, sleep pattern changes, loss of energy 3
• Serious skin reactions: Discontinue immediately if hives, mouth sores, blistering, or facial swelling occur 3
• Lupus-like syndrome: Can aggravate existing lupus or cause new-onset disease 2, 3
• Photosensitivity: Minimize sun and artificial UV exposure during treatment 3

Diagnostic Confirmation

• Always obtain laboratory confirmation (KOH preparation, fungal culture, or nail biopsy) before initiating treatment 3, 6
• Confirmatory testing prevents unnecessary treatment of non-fungal nail conditions 6

Treatment Failure and Recurrence

• Recurrence rates are 40-70%, representing both treatment failure and reinfection 5, 4, 2
• Clinical relapse rate is approximately 15% at 6 months after achieving clinical cure 3
• Prevention strategies: wear protective footwear in public facilities, use antifungal powders in shoes, keep nails short, avoid sharing nail clippers, consider discarding contaminated footwear 4, 2

Emerging Therapies

• Photodynamic therapy and laser treatments (1064nm Nd:YAG) show promise but lack sufficient evidence for routine recommendation 5, 1, 7
• Surgical avulsion followed by topical therapy is not recommended based on disappointing randomized controlled trial results 5