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

Treatment of Onychomycosis

First-Line Treatment for Dermatophyte Onychomycosis

Oral terbinafine 250 mg once daily is the recommended first-line treatment for dermatophyte onychomycosis (the most common cause), 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, 3, 4

Why Terbinafine is Superior

• Terbinafine demonstrates superior efficacy compared to itraconazole and fluconazole for dermatophyte infections both in vitro and in vivo. 1, 3, 5, 6
• The drug has fungicidal (not just fungistatic) activity against dermatophytes, allowing for shorter treatment duration. 2, 7
• Terbinafine has minimal drug interactions and does not cause hypoglycemia, making it particularly suitable for diabetic patients and those on multiple medications. 1, 2, 3
• Meta-analysis of 18 randomized controlled trials shows mycological cure rates of 76% ± 3%. 6

Critical Pre-Treatment Requirements

Never initiate treatment without mycological confirmation through KOH preparation, fungal culture, or nail biopsy—this is the most common cause of treatment failure. 3, 4, 8

Baseline Monitoring

• Obtain liver function tests (ALT and AST) and complete blood count before starting terbinafine, especially in patients with history of alcohol consumption, hepatitis, or liver disease. 1, 3
• Common adverse effects include gastrointestinal disturbances (49% of reported side effects), dermatological reactions (23%), headache, and taste disturbance. 1, 2
• Rare but serious: hepatotoxicity, subacute lupus-like syndrome, and psoriasis aggravation. 1, 2

Treatment Algorithm Based on Causative Organism

For Candida Onychomycosis

Itraconazole is the first-line treatment when Candida invades the nail plate, given as pulse therapy: 400 mg daily for 1 week per month, repeated for 2 months for fingernails and 3-4 pulses for toenails. 1, 3

• Itraconazole demonstrates cure rates of 92% for Candida onychomycosis when given as pulse therapy (400 mg per day for 1 week each month) for 4 months. 1
• Alternative: Fluconazole 50 mg daily or 300 mg weekly for minimum 4 weeks (fingernails) or 12 weeks (toenails). 1
• Terbinafine is less effective for Candida and requires prolonged treatment (48 weeks) to achieve cure rates of 70-85%. 1
• Itraconazole is more cost-effective and associated with greater compliance due to shorter treatment duration. 1

For Nondermatophyte Molds

• Itraconazole has broader antimicrobial coverage than terbinafine for nondermatophyte molds, particularly Aspergillus. 1
• Scopulariopsis shows wide MIC ranges for nearly all antifungals; clinical efficacy does not always correlate with in vitro activity. 1
• Fusarium and Acremonium demonstrate reduced susceptibility to nearly all antifungal drugs tested. 1

Special Population Considerations

Diabetic Patients

Terbinafine is the preferred agent in diabetics due to low risk of drug interactions and no hypoglycemia risk. 1, 2, 3

• Onychomycosis is a significant predictor for development of foot ulcers in diabetes. 1, 3
• Itraconazole is contraindicated in congestive heart failure due to negative inotropic effects, and cardiac disease prevalence is higher in diabetics. 1

Immunocompromised Patients

Terbinafine is preferred over itraconazole in immunocompromised patients due to lower risk of drug interactions with antiretrovirals and immunosuppressive medications. 3

• Prevalence of onychomycosis in HIV-positive patients is approximately 30%. 1
• Griseofulvin should be avoided in HIV-positive patients as it is the least effective oral antifungal in this population. 3

Pediatric Patients (Age 1-12 Years)

Both terbinafine and itraconazole are first-line options for children, with higher cure rates (94-100%) than adults due to faster nail growth. 1, 3

Terbinafine Dosing by Weight:

• <20 kg: 62.5 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 3
• 20-40 kg: 125 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 3
• >40 kg: 250 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 3

Itraconazole Pulse Therapy:

• 5 mg/kg per day for 1 week per month: 2 pulses for fingernails, 3 pulses for toenails 1
• One study demonstrated 94% clinical cure rate with no relapse for 1-4.25 years after therapy. 1

Topical Therapy Limitations

Topical treatment is inferior to systemic therapy except in very limited cases of distal or superficial white onychomycosis without matrix involvement. 3, 8

When to Consider Topical Therapy:

• Mild-to-moderate infections without lunula involvement 1, 8
• Patients with contraindications to systemic therapy 1, 8
• As adjunct to systemic therapy for antimicrobial synergy 1

Topical Options:

• Amorolfine 5% lacquer: Apply once or twice weekly for 6-12 months 1, 3
• Ciclopirox 8% lacquer: Apply once daily for up to 48 weeks, achieving complete cure in only 5.5-8.5% of patients 1, 8
• Ciclopirox requires monthly removal of unattached infected nail by healthcare professional. 8

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

Common Causes:

• Incorrect diagnosis without mycological confirmation 3
• Poor adherence to treatment 3
• Poor drug absorption 3
• Dermatophytoma (compact subungual mass of fungi preventing drug penetration) 3
• Immunosuppression or dermatophyte resistance 3

Strategies for Failure:

• Consider partial nail removal in cases of dermatophytoma. 3
• Switch antifungal agents: If terbinafine failed, switch to itraconazole or vice versa. 3
• Re-confirm diagnosis with repeat mycological testing. 3

Follow-Up and Realistic Expectations

• Reevaluate patients 3-6 months after initiating treatment. 3
• Do not expect complete clinical normalization even with mycological cure—nails may have pre-existing dystrophy from trauma or non-fungal disease. 3
• Continuous terbinafine regimen (250 mg daily for 12 weeks) demonstrates significantly greater efficacy (76.67%) compared to pulse regimen (250 mg twice daily for 1 week every 4 weeks) at 26.67%. 9

Prevention of Recurrence

• Wear protective footwear in communal bathing facilities, gyms, and hotel rooms to avoid re-exposure to T. rubrum. 3
• Apply absorbent antifungal powders, wear cotton socks, keep nails short, avoid sharing toenail clippers, and discard old footwear. 3
• Thoroughly dry between toes after bathing, change socks daily, and periodically clean footwear. 2

Second-Line and Alternative Agents

Itraconazole (for dermatophytes when terbinafine contraindicated):

• 200 mg twice daily (400 mg/day) for 1 week per month: 2 pulses for fingernails, 3 pulses for toenails 3
• Contraindicated in heart failure and requires monitoring for drug interactions. 1
• Must be taken with food and acidic pH for optimal absorption. 1

Fluconazole (second-line alternative):

• 150-450 mg per week for 3 months (fingernails) or at least 6 months (toenails) 1
• Pediatric dosing: 3-6 mg/kg once weekly for 12-16 weeks (fingernails) or 18-26 weeks (toenails) 1

Griseofulvin (not recommended):

• Lower efficacy (30-40% mycological cure) and higher relapse rates compared to terbinafine and itraconazole. 1, 3
• Requires 6-9 months for fingernails and 12-18 months for toenails. 1