What is the treatment for onychomycosis?

Treatment of Onychomycosis

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

First-Line Systemic Treatment

Terbinafine is the preferred agent because it inhibits squalene epoxidase, depleting ergosterol and accumulating squalene, which directly kills dermatophytes rather than just inhibiting their growth. 1, 3 The American Academy of Dermatology endorses this as first-line therapy based on the highest quality evidence. 1, 2

• Dosing: 250 mg orally once daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 3, 4
• FDA-approved indication: Treatment of onychomycosis of toenail or fingernail due to dermatophytes, with confirmation via KOH preparation, fungal culture, or nail biopsy required before initiating treatment 4
• Common side effects: Headache, taste disturbance, gastrointestinal upset; can aggravate psoriasis and cause lupus-like syndrome 3
• Contraindication: Hepatic impairment 3

Alternative First-Line Systemic Treatment

Itraconazole pulse therapy is an effective alternative when terbinafine is contraindicated or for specific organisms (see below). 1, 2, 3

• Dosing: 200 mg twice daily for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 1, 3
• Absorption: Better with food and acidic pH 1, 3
• Contraindications: Heart failure (negative inotropic effect) and hepatotoxicity 3

Organism-Specific Treatment Considerations

The choice between terbinafine and itraconazole depends on the causative organism:

• Dermatophytes (T. rubrum): Terbinafine is superior 1, 2, 3
• Candida species: Itraconazole is preferred, with 92% cure rate versus 40% with pulse terbinafine 1; azoles are specifically advocated for Candida infections 5
• Nondermatophyte molds (Scopulariopsis, Aspergillus, Fusarium, Acremonium): Itraconazole is the treatment of choice due to broader antimicrobial coverage, with 88% cure rates for Scopulariopsis 1; terbinafine has low activity against these organisms 1

Topical Treatments

Topical therapy should only be used for superficial white onychomycosis, very early distal lateral subungual onychomycosis, or when systemic therapy is contraindicated. 1, 2, 3

• Amorolfine 5% nail lacquer: Approximately 50% effective when infection is limited to the distal portion of the nail 1, 2, 3
• Ciclopirox 8% nail lacquer: FDA-approved as part of a comprehensive management program for mild to moderate onychomycosis without lunula involvement, with 34% mycological cure versus 10% with placebo 3, 6; requires monthly removal of unattached infected nail by a healthcare professional 6
• Efinaconazole 10% and tavaborole 5%: FDA-approved topical options with favorable safety profiles for mild to moderate disease 7, 8

Critical caveat: Concomitant use of topical and systemic antifungal agents is not recommended per FDA labeling, as no studies have determined whether topical agents reduce systemic effectiveness. 6

Special Population Considerations

Diabetic Patients

Terbinafine is the preferred agent due to lower risk of drug interactions and hypoglycemia. 5, 1, 2, 3

• Onychomycosis is a significant predictor for foot ulcers in diabetics, making treatment particularly important 5, 1, 2
• Itraconazole is contraindicated in congestive heart failure, which has increased prevalence in diabetics 5

Immunosuppressed Patients (HIV, Transplant Recipients)

Terbinafine and fluconazole are preferred due to lower risk of interactions with antiretrovirals. 5, 1, 2, 3

• Most cases are due to T. rubrum 5, 3
• Avoid itraconazole and ketoconazole due to significant drug interactions with antiretrovirals 5

Pediatric Patients

Pulse itraconazole therapy is recommended: 5 mg/kg/day for 1 week every month for 2 months (fingernails) or 3 months (toenails). 5, 1, 2

Terbinafine dosing (alternative option):

• <20 kg: 62.5 mg/day
• 20-40 kg: 125 mg/day

• 40 kg: 250 mg/day 5, 1, 2

• Duration: 6 weeks for fingernails, 12 weeks for toenails 5

Pediatric cure rates are higher (88-100%) than adults, with faster response to treatment. 5, 1

Fluconazole alternative: 3-6 mg/kg once weekly for 12-16 weeks (fingernails) or 18-26 weeks (toenails) 5

Griseofulvin is no longer recommended as first-line treatment due to long duration and low efficacy. 5

Second-Line Treatment

Griseofulvin is now relegated to third-line status with only 30-40% mycological cure rates and high relapse rates. 1, 2, 3

• Duration: 6-9 months for fingernails, 12-18 months for toenails 3
• Only indicated when other agents are unavailable or contraindicated 1, 3

Adjunctive Measures

Nail debridement and trimming used concurrently with pharmacologic therapy improve treatment response. 8

• Monthly removal of unattached infected nail by a healthcare professional is required when using ciclopirox 6
• Mechanical intervention may be necessary to remove dermatophytomas within the nail plate or nail bed 5

Emerging Therapies (Insufficient Evidence for Routine Use)

• Photodynamic therapy: 44.3% cure rate at 12 months, but evidence remains limited 5, 1, 2
• Laser therapy (1064nm Nd:YAG, near infrared diode 870/930nm): Promising results but insufficient evidence for strong recommendations 5, 9, 7
• Surgical avulsion followed by topical therapy: Disappointing results in randomized controlled trials, not currently recommended 5

Prevention of Recurrence

Onychomycosis has 40-70% recurrence rates, necessitating preventive strategies:

• Wear protective footwear in public facilities 1, 2, 3
• Use absorbent and antifungal powders in shoes 1, 2, 3
• Keep nails short 1, 2
• Avoid sharing nail clippers 1, 2, 3
• Promptly treat tinea pedis infections 10
• Consider discarding contaminated footwear or treating with naphthalene mothballs 3

Common Pitfalls

• Starting treatment without mycological confirmation: Always obtain KOH preparation, fungal culture, or nail biopsy before initiating therapy 4, 7, 8
• Using topical therapy for moderate-severe disease: Topical agents have significantly lower cure rates than oral therapy and should be reserved for mild disease or contraindications to systemic treatment 1, 2, 3, 8
• Inadequate treatment duration: Treatment failure occurs in 25-40% of patients, often due to poor compliance with lengthy regimens 3
• Drug interactions with terbinafine: Monitor patients taking tricyclic antidepressants, SSRIs, atypical antipsychotics, beta blockers, or tamoxifen 8