What is the recommended treatment for onychomycosis (fungal infection of the nail) affecting up to 5 nails?

Treatment of Onychomycosis Affecting Up to 5 Nails

Oral terbinafine 250 mg once daily is the first-line treatment for dermatophyte onychomycosis: 6 weeks for fingernails and 12 weeks for toenails, achieving cure rates of 70-80% for toenails and 80-90% for fingernails. 1, 2

Diagnostic Confirmation Required Before Treatment

• Never initiate treatment without mycological confirmation through KOH preparation and fungal culture, as incorrect diagnosis is the most common cause of treatment failure 2, 3
• Dermatophytes (primarily Trichophyton rubrum) cause the majority of cases, but Candida and non-dermatophyte molds require different treatment approaches 2

Treatment Algorithm by Causative Organism

For Dermatophyte Onychomycosis (Most Common)

First-Line: Oral Terbinafine

• 250 mg once daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 2, 3
• Terbinafine is superior to itraconazole both in vitro and in vivo 2
• Continuous dosing is significantly more effective than pulse dosing (76.67% vs 26.67% clinical cure rate) 4
• The drug persists in nails for 6 months after treatment completion due to its long half-life 5

Second-Line: Itraconazole

• For patients who cannot tolerate terbinafine 1
• Pulse therapy: 400 mg daily (200 mg twice daily) for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 1, 2
• Alternative continuous dosing: 200 mg daily for 12 weeks 1
• Must be taken with food and acidic beverages for optimal absorption 1

For Candida Onychomycosis

• Itraconazole is first-line when Candida invades the nail plate 1, 2
• Pulse regimen: 400 mg daily for 1 week per month, minimum 4 weeks for fingernails and 12 weeks for toenails 1
• Itraconazole has superior cure rates compared to terbinafine for Candida infections (92% vs 40%) 1

Topical Therapy Options

Topical treatments are inferior to systemic therapy except in very limited cases of distal or superficial white onychomycosis 2

• Amorolfine 5% lacquer: once or twice weekly for 6-12 months 5, 1
• Ciclopirox 8% lacquer: once daily for up to 48 weeks on toenails, 24 weeks on fingernails 5, 1, 6
• Ciclopirox shows 34% mycological cure vs 10% with placebo, but clinical cure is only 8% vs 1% 5
• Efinaconazole 10% shows mycological cure rates approaching 50% and complete cure in 15% after 48 weeks 5
• Topical therapy may be considered as adjunct to systemic therapy or for mild cases without matrix involvement 1, 6

Pre-Treatment Monitoring

Before initiating terbinafine:

• Obtain baseline liver function tests (ALT and AST), especially in patients with history of excessive alcohol consumption, hepatitis, or other liver diseases 2, 7
• Obtain complete blood count in patients with history of heavy alcohol consumption, pre-existing hepatitis, hematological abnormalities, or in children 7

Before initiating itraconazole:

• Baseline liver function tests are required 1
• Monitor hepatic function tests when receiving continuous therapy for more than one month or with concomitant hepatotoxic drugs including statins 1

Special Population Considerations

Diabetic Patients:

• Terbinafine is the agent of choice due to low risk of drug interactions and no hypoglycemia risk 2
• Treatment is particularly important as onychomycosis is a significant predictor of foot ulcers and cellulitis in diabetics 2

Immunocompromised Patients:

• Terbinafine is preferred over itraconazole due to lower risk of drug interactions with antiretrovirals and immunosuppressive medications 2
• Prevalence of onychomycosis in HIV-positive patients is approximately 30% 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 pediatric population than adults 2
• Itraconazole pediatric pulse dosing: 5 mg/kg per day for 1 week every month, with 2 pulses for fingernails and 3 pulses for toenails, achieving 94% clinical cure rate 1

Important Drug Interactions and Contraindications

Itraconazole:

• Contraindicated in heart failure due to negative inotropic effects 1
• Contraindicated in hepatotoxicity or active liver disease 1
• Caution with statins as concurrent use may increase statin levels; temporary dose adjustment of rosuvastatin may be necessary 1
• Common adverse effects include headache and gastrointestinal upset 1

Terbinafine:

• Minimal drug-drug interactions compared to azole antifungals 7
• Potentially significant interaction with drugs metabolized by cytochrome P450 2D6 isoenzyme 7

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

Common causes of failure:

• Poor adherence to treatment, poor drug absorption, immunosuppression, and dermatophyte resistance 2
• Dermatophytoma subungual (compact mass of fungi preventing drug penetration) 2
• Thick nails may respond poorly and require nail debridement 1

Strategies for therapeutic failure:

• Consider partial nail removal in cases of dermatophytoma subungual 2
• Switch to alternative agent: if terbinafine was used, switch to itraconazole or vice versa 2
• Consider combination therapy with topical antifungals such as amorolfine or ciclopirox for enhanced efficacy 1

Follow-Up and Monitoring

• Reevaluate patients 3-6 months after initiating treatment 2, 7
• Monitor for at least 48 weeks from start of treatment to identify potential relapse 1
• Assessment should include both clinical improvement and mycological cure (negative microscopy and culture) 1
• Do not expect complete clinical normalization even with mycological cure, as nails may have pre-existing dystrophy from trauma or non-fungal disease 2

Prevention of Recurrence

• Discard old contaminated footwear if possible, or decontaminate shoes with naphthalene mothballs 1
• Apply antifungal powders inside shoes regularly and consider spraying terbinafine solution into shoes periodically 1
• Always wear protective footwear in communal bathing facilities, gyms, and hotel rooms 2
• Keep nails short and clean, wear cotton absorbent socks, use antifungal powders on feet, and avoid sharing nail clippers 1, 2

Critical Pitfalls to Avoid

• Do not treat based on clinical appearance alone without mycological confirmation—this is the most common cause of treatment failure 2
• Do not use pulse dosing for terbinafine, as continuous dosing is significantly superior 4
• Do not use griseofulvin as first-line treatment due to lower efficacy (30-40% mycological cure), long treatment duration (12-18 months for toenails), and higher relapse rates 5, 2
• Do not fail to monitor patients with risk factors more closely, such as those with heavy alcohol consumption, pre-existing hepatitis, or concomitant hepatotoxic drugs 7
• Concomitant use of ciclopirox 8% topical solution and systemic antifungal agents is not recommended, as no studies have determined whether ciclopirox might reduce the effectiveness of systemic agents 6