What are the treatment options for a patient with onychomycosis (fungal infection of the nail)?

Treatment of Onychomycosis

First-Line Recommendation

Oral terbinafine is the preferred first-line treatment for onychomycosis due to its superior efficacy, fungicidal properties, and favorable cost-effectiveness profile. 1, 2

Systemic (Oral) Therapy

Systemic therapy is almost always more successful than topical treatment and should be the primary approach for most cases of onychomycosis. 3

Terbinafine (First-Line)

• Terbinafine is FDA-approved for onychomycosis of toenails and fingernails caused by dermatophytes and works by inhibiting squalene epoxidase, which is directly fungicidal 1, 2
• Standard dosing: 250 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) 1
• Particularly preferred in diabetic patients due to lower risk of drug interactions and hypoglycemia 1
• Baseline liver function tests and complete blood count should be obtained before starting treatment 4
• Common adverse effects include headache, taste disturbance, and gastrointestinal upset 4
• Monitor for drug-drug interactions with tricyclic antidepressants, SSRIs, atypical antipsychotics, beta blockers, and tamoxifen 5

Itraconazole (Second-Line)

• Effective alternative administered as pulse therapy: 200 mg twice daily for 1 week per month 1
• Two pulses for fingernails, three pulses for toenails 1
• Should be taken with food and acidic pH for optimal absorption 4
• Contraindicated in heart failure and hepatotoxicity 4

Griseofulvin (Third-Line)

• Now considered third-line due to poor cure rates (30-40%), high relapse rates, and lengthy treatment duration of 6-18 months 1
• Weakly fungistatic with lower efficacy than newer agents 3

Topical Therapy

Topical therapy should only be used for superficial white onychomycosis (SWO), very early distal lateral subungual onychomycosis (DLSO) with <80% nail plate involvement without lunula involvement, or when systemic therapy is contraindicated. 3, 6

FDA-Approved Topical Agents

Efinaconazole 10% Solution

• Applied once daily for 48 weeks 6
• Achieves mycological cure rates approaching 50% and complete cure in 15% of patients 6
• Most effective topical option currently available 6

Ciclopirox 8% Nail Lacquer

• FDA-approved as a component of comprehensive management including monthly removal of unattached infected nails by a healthcare professional 7
• Applied once daily for up to 48 weeks on toenails 6
• Achieves 34% mycological cure versus 10% with placebo 6
• Indicated only for mild to moderate onychomycosis without lunula involvement 7
• Side effects include periungual and nail fold erythema 6

Amorolfine 5% Nail Lacquer

• Applied once or twice weekly for 6-12 months 6
• Effective in approximately 50% of cases when infection is limited to the distal portion of the nail 3, 6
• Comparable efficacy to efinaconazole but less convenient dosing 6

Tavaborole 5% Solution

• Applied once daily 5
• Less effective than oral agents but fewer adverse effects and drug interactions 5

Important Topical Therapy Limitations

• The nail plate acts as a significant barrier, with drug concentration dropping 1000-fold from outer to inner nail surface 6
• Clinical improvement does not equal mycological cure, with cure rates often 30% lower than apparent clinical improvement 6
• Mycological cure rates are about 30% better than clinical cure rates, with clinical cure rates often below 50% 3

Combination Therapy

Combination of topical and systemic therapy is recommended when response to topical monotherapy is likely to be poor. 6

• Ciclopirox combined with oral terbinafine achieves 66.7% mycological cure in moderate-to-severe cases 6
• Nail trimming and debridement used concurrently with pharmacologic therapy improve treatment response 5
• Partial nail avulsion aids topical therapy in DLSO for more effective treatment 8

Special Populations

Diabetic Patients

• Terbinafine is the preferred treatment due to lower risk of drug interactions and hypoglycemia 1
• Onychomycosis is a significant predictor for foot ulcers in diabetics, making treatment particularly important 1

Immunosuppressed Patients

• Terbinafine and fluconazole are preferred due to lower risk of interactions with antiretrovirals 1

Pediatric Patients

• Oral terbinafine is first-line: 62.5 mg daily if <20 kg, 125 mg daily if 20-40 kg, for 12 weeks for toenails 4
• Alternative: pulse itraconazole 5 mg/kg/day for 1 week every month for 3 months (toenails) 1, 4
• Baseline liver function tests and complete blood count required 4

Critical Management Points

Diagnostic Confirmation

• Appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm diagnosis before initiating treatment 2
• Confirmatory testing is essential because therapy is lengthy and can cause adverse effects 5

Treatment Duration and Expectations

• Treatment duration is prolonged: minimum 12 weeks for toenails with systemic therapy 4
• Up to 18 months may be required for complete nail clearance 4
• Successful eradication of fungus does not always render nails completely normal if they were dystrophic prior to infection 3

Prevention of Recurrence

• Onychomycosis has high recurrence rates (40-70%), necessitating preventive strategies 1
• Wear protective footwear in public facilities 1
• Use absorbent and antifungal powders in shoes 1
• Keep nails short 1
• Avoid sharing nail clippers 1
• Treat all infected family members simultaneously 4
• Disinfect shoes and socks 5

Common Pitfalls to Avoid

• Do not use salicylic acid or methyl undecenoate preparations as there are no published studies on their efficacy 3
• Concomitant use of topical ciclopirox and systemic antifungals is not recommended per FDA labeling 7
• Do not rely on clinical appearance alone—mycological cure is the primary endpoint 3
• Do not use topical therapy alone for extensive nail involvement (>80% of nail plate) or lunula involvement 6, 7