What is the treatment for fungal nail infection?

Treatment for Fungal Nail Infection

Oral terbinafine 250 mg once daily is the first-line treatment for fungal nail infections, given for 6 weeks for fingernails and 12 weeks for toenails, achieving mycological cure rates of 70-80% for toenails and 80-90% for fingernails. 1, 2

Confirm Diagnosis Before Treatment

• Never initiate treatment without mycological confirmation through KOH microscopy and fungal culture. 2
• The most common cause of treatment failure is incorrect diagnosis made on clinical grounds alone. 2
• Dermatophytes (primarily Trichophyton rubrum) are the causative organisms in most cases. 2, 3

Treatment Algorithm by Causative Organism

For Dermatophyte Onychomycosis (Most Common)

First-Line: Terbinafine

• Dosing: 250 mg orally once daily 1, 2, 4
  • Fingernails: 6 weeks of treatment 1, 2, 4
  • Toenails: 12 weeks of treatment 1, 2, 4
• Efficacy: Terbinafine is superior to itraconazole both in vitro (10-fold lower MIC) and in clinical outcomes. 1, 2
• Mechanism: Fungicidal action through squalene epoxidase inhibition, causing ergosterol depletion and toxic squalene accumulation. 1
• Persistence: Remains in nail tissue for 6 months after treatment completion, allowing continued antifungal effect. 1

Second-Line: Itraconazole (if terbinafine contraindicated)

• Continuous regimen: 200 mg daily for 12 weeks 1
• Pulse regimen: 400 mg daily for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 1
• Less effective than terbinafine for dermatophytes (MIC 10 times higher). 1

For Candida Onychomycosis (When Nail Plate Invaded)

First-Line: Itraconazole

• Itraconazole is the most effective agent when Candida invades the nail plate. 1, 2
• Pulse regimen: 400 mg daily for 1 week per month—2 pulses for fingernails, 3-4 pulses for toenails 2
• Terbinafine has lower fungistatic activity against Candida species compared to azoles, though 16 weeks of terbinafine (250 mg/day) achieved 60% cure in Candida nail infections. 1, 5

For Yeast Paronychia (Without Nail Plate Invasion)

• Topical imidazole lotion alternating with antibacterial lotion applied to proximal nail fold 1
• Continue until cuticle integrity is restored (may require several months) 1

Pre-Treatment Monitoring

• Obtain baseline liver function tests (ALT and AST) before starting terbinafine, especially in patients with history of excessive alcohol consumption, hepatitis, or other liver disease. 1, 2, 6, 4
• Terbinafine is contraindicated in active or chronic liver disease. 6, 4

Special Populations

Diabetic Patients

• Terbinafine is the agent of choice due to low risk of drug interactions and hypoglycemia. 2
• Onychomycosis is a significant predictor of foot ulcers and cellulitis in diabetic patients, making treatment particularly important. 2

Immunocompromised Patients

• Prefer terbinafine over itraconazole due to lower risk of drug interactions with antiretrovirals and immunosuppressive medications. 2
• Griseofulvin should be avoided as it is the least effective oral antifungal in HIV-positive patients. 2

Pediatric Patients

• Terbinafine dosing: 62.5 mg/day for <20 kg, 125 mg/day for 20-40 kg, 250 mg/day for >40 kg 2
• Duration: 6 weeks for fingernails, 12 weeks for toenails 2
• Cure rates are higher in children than adults. 2
• Griseofulvin (10 mg/kg/day) is the only licensed antifungal for children with onychomycosis but has poor cure rates (30-40%) and is no longer first-line. 1

Common Adverse Effects and Monitoring

• Most common side effects: Gastrointestinal symptoms (49%)—nausea, diarrhea, taste disturbance; dermatological events (23%)—rash, pruritus, urticaria 1
• Serious adverse events: Incidence of 0.04%, including rare Stevens-Johnson syndrome and toxic epidermal necrolysis 1
• Hepatotoxicity: Rare but serious; advise patients to immediately report persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools. 1, 4
• Taste/smell disturbance and depressive symptoms: Discontinue terbinafine if these occur. 4
• Monitor liver enzymes during first month of treatment, particularly with terbinafine. 5

Drug Interactions

Terbinafine

• Plasma concentrations reduced by rifampicin, increased by cimetidine 1
• Minimal drug interactions compared to azoles 1, 2

Itraconazole

• Significant interactions: Enhanced toxicity with warfarin, terfenadine, astemizole, sertindole, midazolam, digoxin, cisapride, ciclosporin, simvastatin 1
• Monitoring of liver function required for treatment durations longer than 1 month 1

Management of Treatment Failure (20-30% of Cases)

Common causes of failure: 2

• Poor adherence to treatment
• Poor drug absorption
• Immunosuppression
• Dermatophyte resistance
• Subungual dermatophytoma (compact fungal mass preventing drug penetration)

Strategies for therapeutic failure: 2

• Re-evaluate 3-6 months after treatment initiation 2, 6
• Consider partial nail removal in cases of dermatophytoma 2
• Switch to alternative agent: if terbinafine failed, use itraconazole (or vice versa) 2

Topical Treatment Limitations

• Topical therapy is inferior to systemic treatment except in very limited cases of distal or superficial white onychomycosis. 2
• Topical options include amorolfine and ciclopirox, but cure rates are substantially lower than oral therapy. 1, 3
• Consider topical treatment only for mild to moderate infection without nail matrix involvement. 2

Setting Realistic Expectations

• Optimal clinical effect occurs months after mycological cure due to time required for healthy nail outgrowth. 4
• Mean time to overall success: approximately 10 months for toenails, 4 months for fingernails 4
• Do not expect complete clinical normalization even with mycological cure, as nails may have pre-existing dystrophy from trauma or non-fungal disease. 2
• Clinical relapse rate is approximately 15% at one year after completing therapy. 4

Prevention of Recurrence

• Wear protective footwear in communal bathing facilities, gyms, and hotel rooms 2
• Apply absorbent antifungal powders, wear cotton socks, keep nails short 2
• Avoid sharing toenail clippers and discard old footwear 2

Critical Pitfalls to Avoid

• Do not treat based on clinical appearance alone—this is the most common cause of treatment failure. 2
• Do not use griseofulvin as first-line therapy; it has poor cure rates (30-40%), requires 12-18 months of treatment for toenails, and is inferior to terbinafine and itraconazole. 1
• Advise patients to minimize exposure to natural and artificial sunlight (tanning beds, UVA/B treatment) while using terbinafine due to photosensitivity risk. 4