What are the treatment options for onychomycosis?

Treatment of Onychomycosis

First-Line Treatment Recommendation

Oral terbinafine 250 mg once daily is the first-line treatment for dermatophyte onychomycosis: 6 weeks for fingernails and 12 weeks for toenails, achieving mycological cure rates of 80-90% for fingernails and 70-80% for toenails. 1, 2, 3

Diagnostic Confirmation Required Before Treatment

• Never initiate treatment without mycological confirmation through KOH microscopy and fungal culture. 1
• The most common cause of treatment failure is incorrect diagnosis made on clinical grounds alone. 4
• Appropriate nail specimens (KOH preparation, fungal culture, or nail biopsy) must confirm the diagnosis before starting therapy. 3

Treatment Algorithm by Clinical Presentation

Limited Disease (<50% nail involvement, no matrix involvement)

• Topical monotherapy with amorolfine nail lacquer or FDA-approved agents (efinaconazole 10%, tavaborole 5%, or ciclopirox 8%) is appropriate. 5, 6
• Ciclopirox 8% topical solution is FDA-approved as part of a comprehensive management program including monthly removal of unattached infected nail by a healthcare professional. 7
• Topical therapy alone achieves significantly lower cure rates than systemic therapy and should only be used in superficial white onychomycosis, very early distal lateral subungual onychomycosis, or when systemic therapy is contraindicated. 4, 1

Moderate to Severe Disease (>50% nail involvement or matrix involvement)

• Oral terbinafine 250 mg daily remains the gold standard: 6 weeks for fingernails, 12 weeks for toenails. 1, 2
• Terbinafine is superior to itraconazole both in vitro and in vivo for dermatophyte infections. 1, 2
• Mycological cure rates consistently exceed clinical cure rates by approximately 30%, with clinical cure rates often below 50%. 4

Combination Therapy Indications

• When dermatophytoma (compact subungual fungal mass) is present, topical agents cannot penetrate adequately and oral therapy with or without mechanical debridement is required. 1, 5
• Combination therapy increases antifungal spectrum, fungicidal activity, and safety profiles. 5
• Consider partial nail removal in cases of dermatophytoma to allow drug penetration. 1

Treatment Selection by Causative Organism

Dermatophyte Onychomycosis (Majority of Cases)

• Terbinafine 250 mg daily is the agent of choice. 1, 2
• Alternative: Itraconazole 200 mg daily for 12 weeks continuously, or pulse therapy 400 mg daily for 1 week per month for 2 pulses (fingernails) or 3-4 pulses (toenails). 2

Candida Onychomycosis

• Itraconazole is the most effective agent when Candida invades the nail plate: 400 mg daily for 1 week per month, repeated for 2 months for fingernails and 3-4 pulses for toenails. 1

Special Population Considerations

Diabetic Patients

• Terbinafine is the agent of choice due to low risk of drug interactions and hypoglycemia. 1
• Onychomycosis is a significant predictor of foot ulcers and cellulitis in diabetic patients, making treatment particularly important to prevent serious complications. 4, 1

Immunocompromised Patients (HIV, Transplant Recipients)

• Terbinafine is preferred over itraconazole due to lower risk of drug interactions with antiretrovirals and immunosuppressive medications. 4, 1
• Griseofulvin is the least effective oral antifungal in HIV-positive patients and should be avoided. 4

Pediatric Patients

• Terbinafine dosing by weight: 62.5 mg/day for <20 kg, 125 mg/day for 20-40 kg, and 250 mg/day for >40 kg, for 6 weeks (fingernails) or 12 weeks (toenails). 1
• Cure rates are higher in pediatric populations than adults. 1

Elderly Patients

• Treatment is particularly important as onychomycosis can lead to cellulitis and further compromise limbs in those with diabetes or peripheral vascular disease. 4

Pre-Treatment Monitoring

• Obtain baseline liver function tests (ALT and AST) before starting terbinafine, especially in patients with history of excessive alcohol consumption, hepatitis, or other liver diseases. 1, 2
• Active or chronic liver disease is a contraindication to terbinafine. 2

Management of Treatment Failure (20-30% of Cases)

Common Causes of Failure

• Poor adherence to treatment regimen. 1
• Poor drug absorption. 1
• Immunosuppression. 1, 2
• Dermatophyte resistance. 1
• Presence of dermatophytoma preventing drug penetration. 1

Strategies for Treatment Failure

• Consider partial nail removal if dermatophytoma is present. 1
• Switch to alternative agent: if terbinafine failed, use itraconazole, or vice versa. 1
• Re-evaluate compliance and absorption issues. 1, 2

Follow-Up and Monitoring

• Re-evaluate patients 3-6 months after initiating treatment. 1, 2
• Up to 18 months is required for complete toenail plate outgrowth due to slow nail growth. 4
• Monitor for side effects including gastrointestinal complaints, taste disturbance, and skin reactions. 2

Prevention of Recurrence

• Always wear protective footwear in communal bathing facilities, gyms, and hotel rooms to avoid re-exposure to T. rubrum. 4
• Apply absorbent antifungal powders (miconazole, clotrimazole, or tolnaftate) in shoes and on feet. 4
• Wear cotton, absorbent socks. 4
• Keep nails as short as possible. 4
• Avoid sharing toenail clippers with family members. 4
• Discard old, moldy footwear or treat with naphthalene mothballs in enclosed plastic bags. 4

Common Pitfalls to Avoid

• Do not treat based on clinical appearance alone without mycological confirmation—this is the most common cause of treatment failure. 4, 1
• Do not use topical therapy alone when dermatophytoma, significant onycholysis, or spikes are present, as drug transport is suboptimal. 5
• Do not expect complete clinical normalization even with mycological cure, as nails may have pre-existing dystrophy from trauma or non-fungal disease. 4
• Do not use concomitant topical ciclopirox with systemic antifungals, as no studies have determined safety or efficacy of this combination. 7