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

Treatment of Onychomycosis (Nail Fungus)

Oral terbinafine 250 mg daily is the first-line treatment for nail fungus, taken for 6 weeks for fingernails or 12 weeks for toenails, due to its superior efficacy, fungicidal properties, and cost-effectiveness compared to all other options. 1, 2, 3

Systemic (Oral) Treatment Options

First-Line: Terbinafine

• Terbinafine is the preferred oral agent recommended by the American College of Dermatology for dermatophyte onychomycosis 1, 2
• Dosing: 250 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) 4, 3
• Mechanism: Inhibits squalene epoxidase, causing direct fungicidal activity against dermatophytes 1, 2
• Common side effects: Headache, taste disturbance, gastrointestinal upset; can aggravate psoriasis and cause subacute lupus-like syndrome 4
• Monitoring required: Baseline liver function tests and complete blood count before starting treatment 4

Alternative First-Line: Itraconazole

• Use itraconazole when terbinafine is contraindicated or for Candida infections (where it has 92% cure rate vs. 40% with terbinafine) 1
• Dosing: 200 mg twice daily for 1 week per month (pulse therapy); 2 pulses for fingernails, 3 pulses for toenails 4, 1
• Critical administration detail: Must be taken with food and requires acidic pH for optimal absorption 4, 1
• Contraindication: Heart failure, hepatotoxicity 4
• Monitoring: Hepatic function tests recommended with pre-existing abnormalities, continuous therapy >1 month, or concomitant hepatotoxic drugs 4

Second-Line: Fluconazole

• Consider only when both terbinafine and itraconazole are contraindicated or not tolerated 4
• Dosing: 150-450 mg per week for 3 months (fingernails) or at least 6 months (toenails) 4
• Monitoring: Baseline liver function tests and full blood count; monitor LFTs with high-dose or prolonged therapy 4

Third-Line: Griseofulvin

• Griseofulvin is now relegated to third-line status due to poor mycological cure rates (30-40%), high relapse rates, and lengthy treatment duration 1, 2
• Dosing: 500-1000 mg daily for 6-9 months (fingernails) or 12-18 months (toenails) 4
• Must be taken with fatty food to increase absorption 4

Topical Treatment Options

When to Use Topical Therapy Alone

Topical antifungals should only be used as monotherapy in three specific scenarios: 4, 2

• Superficial white onychomycosis (SWO) affecting only the nail surface
• Very early distal lateral subungual onychomycosis (DLSO) with <80% nail plate involvement and no lunula involvement
• When systemic antifungals are contraindicated

Amorolfine 5% Nail Lacquer

• Apply once or twice weekly for 6-12 months after filing away diseased nail 4
• Efficacy: Approximately 50% effective for distal fingernail and toenail onychomycosis 4, 1
• Important caveat: Clinical improvement does not equal mycological cure—cure rates are typically 30% lower than clinical improvement rates 4
• Side effects are rare: local burning, pruritus, erythema 4

Ciclopirox 8% Nail Lacquer

• Apply once daily for up to 48 weeks (fingernails: 24 weeks; toenails: 48 weeks) 4, 5
• FDA-approved only for mild to moderate onychomycosis without lunula involvement 5
• Efficacy is lower than amorolfine: 34% mycological cure vs. 10% placebo; only 5.5-8.5% complete cure rate 4, 5
• Must be used with monthly professional nail debridement by a healthcare provider competent in nail procedures 5
• Side effects: Periungual and nail fold erythema 4

Tioconazole 28% Solution

• Apply twice daily for 6-12 months 4
• Lower efficacy: Only 22% mycological and clinical cure in studies 4
• Significant risk: Allergic contact dermatitis is not uncommon 4
• Contraindicated in pregnancy 4

Special Populations

Diabetic Patients

• Terbinafine is the preferred treatment for diabetics due to lower risk of drug interactions and hypoglycemia 1, 2
• Critical importance: Onychomycosis is a significant predictor for foot ulcers in diabetics, making treatment essential 4, 1, 2
• Up to one-third of diabetics have onychomycosis due to impaired glycemic control, ischemia, neuropathy, and local immunosuppression 4

Immunosuppressed Patients

• Terbinafine and fluconazole are preferred due to lower risk of interactions with antiretrovirals 1, 2
• Avoid itraconazole due to extensive drug-drug interactions 1

Pediatric Patients (Ages 1-12 Years)

First-line options: 4, 1, 2

• Pulse itraconazole: 5 mg/kg/day for 1 week per month; 2 pulses for fingernails, 3 pulses for toenails
• Terbinafine (generally preferred): Weight-based dosing for 6 weeks (fingernails) or 12 weeks (toenails):
  • <20 kg: 62.5 mg daily
  • 20-40 kg: 125 mg daily

  • 40 kg: 250 mg daily

• Important note: Pediatric cure rates are higher (88-100%) than adults, with faster response to treatment 4, 1
• Fluconazole (second-line): 3-6 mg/kg once weekly for 12-16 weeks (fingernails) or 18-26 weeks (toenails) 4

Candida Infections

• Itraconazole is first-line for Candida onychomycosis with 92% cure rate 1
• Dosing: 200 mg daily or 400 mg daily pulse therapy for at least 4 weeks (fingernails) or 12 weeks (toenails) 1
• Fluconazole is an alternative: 50 mg daily or 300 mg weekly 1

Nondermatophyte Molds (Scopulariopsis, Aspergillus, Fusarium)

• Itraconazole is the preferred treatment due to broader antimicrobial coverage and 88% cure rate 1
• Standard regimen: 200-400 mg daily for 1 week per month for 3 months 1
• Terbinafine has low activity against nondermatophyte molds despite effectiveness against dermatophytes 1

Combination Therapy

Combining systemic and topical antifungals improves cure rates and provides antimicrobial synergy 4, 6

• Recommended when response to topical monotherapy alone would be poor 4
• Effective combinations: Terbinafine or itraconazole plus amorolfine or ciclopirox 4, 6
• Do not combine ciclopirox topical with systemic antifungals—no studies have determined safety/efficacy of this combination 5

Adjunctive Mechanical Treatments

• Monthly professional nail debridement (removal of unattached, infected nail) enhances treatment efficacy 4, 5
• Partial nail avulsion aids topical therapy in DLSO and partial subungual onychomycosis 7
• Chemical avulsion using keratinolysis formulas is painless but effective only in limited, early disease 7

Prevention of Recurrence

Onychomycosis has high recurrence rates of 40-70%, requiring preventive strategies: 1, 2

• Wear protective footwear in public facilities (pools, gyms, showers)
• Use absorbent and antifungal powders in shoes
• Keep nails short and properly trimmed
• Avoid sharing nail clippers or other nail care tools
• Amorolfine has been shown effective as prophylactic treatment for recurrence 4

Common Pitfalls to Avoid

• Do not start treatment without laboratory confirmation (KOH preparation, fungal culture, or nail biopsy) 3
• Do not use topical therapy alone for extensive disease (>80% nail involvement or lunula involvement) 4
• Do not expect rapid results—treatment requires 3-9 months minimum, and clinical improvement precedes mycological cure 7
• Do not assume clinical improvement equals cure—mycological cure rates are typically 30% lower than clinical improvement rates 4
• Do not use griseofulvin as first-line therapy given superior alternatives 1, 2