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

Management of Toenail Fungus (Onychomycosis)

For dermatophyte toenail onychomycosis, oral terbinafine 250 mg daily for 12-16 weeks is the first-line treatment and generally preferred over itraconazole due to superior efficacy. 1

Diagnostic Confirmation Required

Before initiating any systemic therapy, you must obtain laboratory confirmation through KOH preparation, fungal culture, or nail biopsy to confirm onychomycosis. 2 The most common cause of treatment failure is incorrect diagnosis made on clinical grounds alone. 1

First-Line Systemic Therapy for Adults

Terbinafine (Preferred)

• Dosing: 250 mg once daily for 12-16 weeks for toenails (6 weeks for fingernails) 1
• Monitoring: Obtain baseline liver function tests and complete blood count in patients with history of hepatotoxicity or hematological abnormalities 1
• Common adverse effects: Headache, taste disturbance, gastrointestinal upset; can aggravate psoriasis and cause subacute lupus-like syndrome 1
• Contraindications: Hepatic impairment, renal impairment 1

Itraconazole (Alternative First-Line)

• Continuous dosing: 200 mg daily for 12 weeks 1
• Pulse therapy: 400 mg daily for 1 week per month; three pulses recommended for toenails 1
• Administration: Take with food and acidic pH for optimal absorption 1
• Monitoring: Check hepatic function tests in patients with pre-existing abnormalities, those on continuous therapy >1 month, or with concomitant hepatotoxic drugs 1
• Contraindications: Heart failure, hepatotoxicity risk 1

Note: Pulse and continuous regimens for both terbinafine and itraconazole have similar efficacy and adverse event rates. 3 However, 24-week continuous terbinafine demonstrates the highest mycological cure rates. 3

Second-Line Systemic Therapy

Fluconazole

• Dosing: 150-450 mg per week for at least 6 months for toenails (3 months for fingernails) 1
• Use when: Patients cannot tolerate terbinafine or itraconazole 1
• Monitoring: Baseline liver function tests and full blood count; monitor LFTs in high-dose or prolonged therapy 1

Griseofulvin (Not Recommended)

• Lower efficacy and higher relapse rates compared to terbinafine and itraconazole 1
• Requires 12-18 months of treatment for toenails 1

Topical Therapy

Topical agents are only appropriate for superficial and distal onychomycosis, or when systemic therapy is contraindicated. 1 Systemic therapy is almost always more successful than topical treatment. 1

Available Topical Options

• Amorolfine 5% lacquer: Apply once or twice weekly for 6-12 months 1
• Ciclopirox 8% lacquer: Apply once daily for up to 48 weeks; requires monthly removal of unattached infected nail by healthcare professional 1, 4
• Tioconazole 28% solution: Apply twice daily for 6-12 months 1

Combination Therapy

Recommended if response to topical monotherapy is likely to be poor. 1 Do not combine ciclopirox with systemic antifungals as no studies have evaluated this approach. 4

Special Populations

Immunosuppressed Patients (HIV, Transplant)

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

Children (Ages 1-12 Years)

• Terbinafine (preferred): 62.5 mg daily if <20 kg; 125 mg daily for 20-40 kg; 250 mg daily for >40 kg; treat for 12 weeks for toenails 1
• Itraconazole: Pulse therapy 5 mg/kg/day for 1 week per month; three pulses for toenails 1
• Fluconazole (second-line): 3-6 mg/kg once weekly for 18-26 weeks for toenails 1

Critical Warnings

Hepatotoxicity Risk

Cases of liver failure leading to transplant or death have occurred with terbinafine. 2 Discontinue immediately if biochemical or clinical evidence of liver injury develops. 2 Warn patients to report persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools. 2

Sensory Disturbances

• Taste disturbance: Can be severe, prolonged (>1 year), or permanent; discontinue if occurs 2
• Smell disturbance: May be prolonged or permanent; discontinue if occurs 2

Treatment Failure Management

Common Causes of Failure

• Dermatophytoma: Dense white lesion of tightly packed hyphae beneath nail; resistant to antifungals without mechanical removal 1
• Nail thickness >2 mm, slow outgrowth, severe onycholysis also contribute to failure 1
• Incorrect diagnosis (most common in UK) 1

Management Approach

If dermatophytoma is present, mechanical intervention is necessary to remove the lesion before or during antifungal therapy. 1 Consider partial nail removal for individual nails likely to fail. 1

Recurrence Prevention

Recurrence rates are 40-70%. 1 Up to 18 months is required for complete nail plate outgrowth. 1

Patient Counseling

• 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
• Do not share toenail clippers 1
• Discard old, moldy footwear or treat with naphthalene mothballs in sealed plastic bag for minimum 3 days 1
• Treat all infected family members simultaneously 1

Not Recommended

• Surgical avulsion followed by topical therapy: Disappointing results in randomized controlled trials 1
• Photodynamic therapy: Insufficient evidence (cure rates 36-44%) 1
• Laser therapy: Promising but recommendations cannot be made at this stage 1