What are the treatment options for onychomycosis (toe nail fungus)?

Treatment of Toenail Fungus (Onychomycosis)

Oral terbinafine 250 mg daily for 12-16 weeks is the first-line treatment for toenail onychomycosis caused by dermatophytes, as it demonstrates superior efficacy compared to all other systemic and topical options. 1, 2

Confirm the Diagnosis First

• Do not initiate treatment without mycological confirmation through KOH preparation, fungal culture, or nail biopsy, as many nail conditions mimic onychomycosis 1, 2
• Dermatophytes (especially Trichophyton rubrum) cause the vast majority of cases 1
• Yeasts and non-dermatophyte molds require careful interpretation—they are often secondary infections or saprophytes in previously damaged nails 1

Systemic Treatment (Moderate to Severe Disease)

First-Line: Oral Terbinafine

• Terbinafine 250 mg daily for 12-16 weeks for toenails (6 weeks for fingernails) is superior to itraconazole both in vitro and in vivo 1
• Expected cure rates: 70-80% for toenails, 80-90% for fingernails 1
• Obtain baseline liver function tests and complete blood count in patients with history of hepatotoxicity or hematological abnormalities 1
• Common adverse effects include headache, taste disturbance, and gastrointestinal upset; can aggravate psoriasis and cause subacute lupus-like syndrome 1
• Preferred in diabetics due to low risk of drug interactions and no hypoglycemia risk 1

Second-Line: Itraconazole

• Itraconazole pulse therapy: 400 mg daily for 1 week per month—three pulses for toenails, two pulses for fingernails 1
• Alternative: 200 mg daily continuously for 12 weeks 1
• Contraindicated in heart failure due to negative inotropic effects 1
• Take with food and acidic pH for optimal absorption 1
• Monitor hepatic function tests in patients with pre-existing abnormalities, those on continuous therapy >1 month, or with concomitant hepatotoxic drugs 1
• Most effective for Candida onychomycosis when nail plate is invaded 1

Third-Line: Fluconazole

• Fluconazole 150-450 mg weekly for at least 6 months for toenails (3 months for fingernails) 1
• Useful alternative when terbinafine or itraconazole are not tolerated 1
• Perform baseline liver function tests and complete blood count; monitor with high-dose or prolonged therapy 1

Avoid: Griseofulvin

• Lower efficacy and higher relapse rates compared to terbinafine and itraconazole 1
• Requires 12-18 months of treatment for toenails at 500-1000 mg daily 1
• No longer recommended as first-line treatment 1

Topical Treatment (Mild to Moderate Disease)

Topical therapy should be reserved for superficial white onychomycosis, early distal lateral subungual onychomycosis affecting <80% of nail plate without lunula involvement, or when systemic antifungals are contraindicated. 3

FDA-Approved Topical Agents

Efinaconazole 10% Solution (Most Effective Topical)

• Applied once daily for 48 weeks 4
• Achieves complete cure in approximately 15-18% of patients (versus 3-5% with vehicle) 4
• Mycological cure rates approach 50% 3, 4
• Slightly higher risk of adverse events (dermatitis, vesicles) compared to vehicle (RR 1.10) 4

Tavaborole 5% Solution

• Applied once daily for 48 weeks 4
• Complete cure rates approximately 6-9% (versus 1% with vehicle) 4
• Mycological cure rates around 31-35% 4
• Higher risk of application site reactions (RR 3.82) 4

Ciclopirox 8% Lacquer

• Applied once daily for up to 48 weeks 1, 5
• Only indicated for mild to moderate onychomycosis without lunula involvement as part of comprehensive management including monthly removal of infected nail by healthcare professional 5
• Achieves 34% mycological cure versus 10% with placebo 3, 5
• Complete cure rates only 5.5-8.5% 5
• Rare adverse effects: periungual and nail fold erythema 1
• Concomitant use with systemic antifungals is not recommended per FDA labeling 5

Amorolfine 5% Lacquer (Not FDA-Approved in US, Available in Europe)

• Applied once or twice weekly for 6-12 months 1, 3
• Approximately 50% effectiveness in distal onychomycosis 3
• Comparable efficacy to efinaconazole but less convenient dosing 3
• Rare adverse effects: local burning, pruritus, erythema 1

Important Topical Therapy Limitations

• Clinical improvement does not equal mycological cure—cure rates are often 30% lower than apparent clinical improvement 3
• The nail plate acts as a significant barrier, with drug concentration dropping 1000-fold from outer to inner nail surface 3
• Topical monotherapy is inferior to systemic therapy in all but very limited cases 1

Combination Therapy

Combination of topical and systemic treatment is recommended when response to topical monotherapy is likely to be poor 1

• Ciclopirox combined with oral terbinafine achieves 66.7% mycological cure in moderate-to-severe cases 3
• Combination provides antimicrobial synergy, wider antifungal spectrum, increased cure rates, and suppression of resistant mutants 1
• However, FDA labeling for ciclopirox specifically states concomitant use with systemic antifungals is not recommended 5—this creates a clinical dilemma where guidelines support combination but drug labeling does not

Special Populations

Diabetic Patients

• Terbinafine is the oral antifungal of choice due to low drug interaction risk and no hypoglycemia 1
• Onychomycosis is a significant predictor for foot ulcer development in diabetes 1
• Itraconazole should be avoided due to increased cardiac disease prevalence in diabetics 1

Immunosuppressed Patients (HIV, Transplant)

• Terbinafine is preferred due to increased risk of drug interactions between itraconazole/ketoconazole and antiretrovirals 1
• Griseofulvin is least effective in HIV patients 1

Pediatric Patients (Ages 1-12)

• Terbinafine is first-line and generally preferred over itraconazole 1
• Dosing by weight: 62.5 mg daily if <20 kg, 125 mg daily for 20-40 kg, 250 mg daily if >40 kg 1
• Duration: 6 weeks for fingernails, 12 weeks for toenails 1
• Pulse itraconazole alternative: 5 mg/kg daily for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 1
• Higher cure rates and faster response than adults 1

Device-Based Treatments

Laser Therapy (1064-nm Nd:YAG)

• Evidence is insufficient—we are uncertain if laser treatment differs from no treatment or sham treatment for mycological cure 4
• FDA-approved only for temporary increase in clear nail, not for cure 6
• Clinical results are suboptimal 6
• Larger randomized trials needed 7

Adjunctive Measures Critical for Success

Nail Debridement

• Monthly removal of unattached, infected nail by healthcare professional improves treatment response 1, 5, 7
• Dermatophytoma (dense white lesion of tightly packed hyphae beneath nail) can be resistant to antifungal treatment without prior removal 1
• Partial nail avulsion indicated when subungual dermatophytoma present 1

Prevention of Reinfection

• Always wear protective footwear in public bathing facilities, gyms, hotel rooms 1
• Apply antifungal powders (miconazole, clotrimazole, tolnaftate) in shoes and on feet 1
• Wear cotton, absorbent socks 1
• Keep nails as short as possible 1
• Discard old, moldy footwear or treat with naphthalene mothballs in sealed plastic bag for 3 days 1
• Treat all infected family members simultaneously 1
• Disinfect shoes and socks regularly 7

Common Pitfalls and Treatment Failure

Reasons for 20-30% Consistent Failure Rate

• Poor compliance 1
• Poor drug absorption 1
• Immunosuppression 1
• Zero nail growth 1
• Subungual dermatophytoma preventing drug penetration 1
• Nail thickness >2 mm, severe onycholysis 1
• Reinfection versus relapse—distinguish between incomplete cure (relapse) and new infection (reinfection) 1

When to Consider Alternative Approaches

• If first-line treatment fails, carefully evaluate reasons for failure 1
• Consider alternative drug or nail removal combined with therapy during regrowth period 1
• Cure rates approaching 100% can be achieved if all affected nails are avulsed under ring block prior to treatment, though this is neither feasible nor necessary in most cases 1

Treatment Duration and Follow-Up

• Toenails require up to 18 months for complete nail plate regrowth 1
• Follow-up period of at least 48 weeks (preferably 72 weeks) from treatment start needed to assess efficacy and identify relapse 1
• Therapeutic success depends on newly grown-out nail plate being fungus-free 1
• Recurrence rate is approximately 25% despite successful treatment 7