What are the treatment options for onychomycosis?

Treatment for Onychomycosis

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

Confirm Diagnosis Before Treatment

• Never initiate treatment without mycological confirmation through KOH preparation, fungal culture, or nail biopsy 3, 2
• Starting treatment based on clinical appearance alone is the most common cause of treatment failure 4
• Dermatophytes (primarily Trichophyton rubrum) cause the majority of cases, but Candida and non-dermatophyte molds require different treatment approaches 1, 4

Treatment Algorithm by Causative Organism

For Dermatophyte Onychomycosis (Most Cases)

First-line: Terbinafine

• Dosing: 250 mg once daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 3
• Efficacy: Mycological cure rates of 76-81% and complete cure rates approximately twice as high as itraconazole 5
• Monitoring: Obtain baseline liver function tests (ALT, AST) and complete blood count, especially in patients with history of hepatotoxicity or hematological abnormalities 1, 4
• Advantages: Fungicidal (not just fungistatic), superior efficacy to all alternatives, low drug interaction potential, and detected in nail within 1 week with persistence for 30 weeks after treatment completion 1, 5

Second-line: Itraconazole

• Dosing: Pulse therapy of 200 mg twice daily (400 mg/day) for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 1
• Alternative continuous dosing: 200 mg daily for 12 weeks 1
• Efficacy: Mycological cure 38-49% and complete cure approximately half that of terbinafine 5
• Monitoring: Check liver function tests at baseline and in patients receiving continuous therapy >1 month or with concomitant hepatotoxic drugs 1
• Critical contraindication: Heart failure due to negative inotropic effects 1
• Drug interactions: Avoid with statins, antiretrovirals, and multiple other medications 2, 4

Third-line: Fluconazole

• Dosing: 150-450 mg weekly for 3 months (fingernails) or at least 6 months (toenails) 1
• Use only when: Terbinafine and itraconazole are contraindicated or not tolerated 1

Avoid: Griseofulvin

• Lower efficacy (30-40% mycological cure), higher relapse rates, and requires 12-18 months of treatment for toenails 1
• No longer recommended as first-line due to availability of superior alternatives 1

For Candida Onychomycosis

First-line: Itraconazole

• Dosing: 400 mg daily for 1 week per month, repeated for 2 months (fingernails) or 3-4 pulses (toenails) 4
• Itraconazole is most effective when nail plate is invaded by Candida species 4
• Azoles are specifically advocated for Candida infections 1

Topical Therapy: Limited Role

Topical agents are inferior to systemic therapy except for very distal infection or superficial white onychomycosis 2, 4

Amorolfine 5% lacquer

• Apply once or twice weekly for 6-12 months 1
• Useful for superficial and distal onychomycosis 1
• Adverse effects rare: local burning, pruritus, erythema 1

Ciclopirox 8% lacquer

• Apply once daily for up to 48 weeks 1, 6
• FDA-approved only for mild-to-moderate onychomycosis without lunula involvement in immunocompetent patients 6
• Mycological cure 34% vs 10% placebo, but clinical cure only 8% vs 1% placebo 1
• Do not use concomitantly with systemic antifungals—no studies support this combination 6

Combination topical + systemic therapy

• Consider when response to systemic monotherapy alone is likely to be poor 1
• May provide antimicrobial synergy and improved cure rates 1

Special Populations

Diabetic Patients

• Terbinafine is strongly preferred over itraconazole due to low risk of drug interactions and no hypoglycemia risk 1, 2
• Onychomycosis is a significant predictor of foot ulcers and cellulitis in diabetics 1, 4
• Itraconazole contraindicated if congestive heart failure present (common comorbidity in diabetics) 1

Pediatric Patients (Age 1-12 Years)

• Both terbinafine and itraconazole are first-line options with higher cure rates than adults 1
• Terbinafine dosing: 62.5 mg/day if <20 kg, 125 mg/day for 20-40 kg, 250 mg/day if >40 kg, for 6 weeks (fingernails) or 12 weeks (toenails) 1, 4
• Itraconazole pulse therapy: 5 mg/kg/day for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 1
• Baseline liver function tests and complete blood count recommended as terbinafine is unlicensed in children 1
• Griseofulvin is second-line only if terbinafine and itraconazole contraindicated 1

Immunocompromised Patients

• Terbinafine preferred over itraconazole due to lower risk of drug interactions with antiretrovirals and immunosuppressive medications 4
• Prevalence of onychomycosis in HIV-positive patients is approximately 30% 1
• Griseofulvin is least effective in HIV-positive patients and should be avoided 4

Treatment Duration and Follow-up

• Reevaluate patients 3-6 months after initiating treatment 4
• Minimum follow-up period should be 48 weeks from treatment start to allow detection of relapse 2
• Nail terbinafine concentrations persist for at least 30 weeks after treatment completion 5
• Relapse rates: 23% with terbinafine vs 53% with itraconazole at 5-year follow-up 5

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

Common causes of failure:

• Poor adherence to treatment 4
• Poor drug absorption 4
• Dermatophytoma (compact subungual mass of fungi preventing drug penetration) 4
• Immunosuppression or dermatophyte resistance 4

Strategies for failure:

• Consider partial nail removal if dermatophytoma present 4
• Switch to alternative agent: if terbinafine failed, try itraconazole or vice versa 4
• Ensure mycological confirmation was obtained initially—incorrect diagnosis is the most common cause of failure 4

Prevention of Recurrence (25% Relapse Rate)

• Apply absorbent antifungal powder inside shoes regularly 2
• Spray terbinafine solution into shoes periodically 2
• Wear protective footwear in communal bathing facilities, gyms, and hotel rooms 4
• Keep nails short, wear cotton socks, avoid sharing toenail clippers, and discard old footwear 4

Critical Pitfalls to Avoid

• Starting treatment without mycological confirmation leads to unnecessary therapy for non-fungal nail dystrophies (psoriasis, lichen planus, trauma) 2, 4
• Inadequate treatment duration results in higher relapse rates—complete the full course even if nails appear improved 2
• Ignoring drug interactions: Itraconazole interacts with statins, antiretrovirals, and is contraindicated in heart failure 2, 4
• Expecting complete clinical normalization: Nails may have pre-existing dystrophy from trauma or non-fungal disease even with mycological cure 4
• Using pulse terbinafine regimens: Recent evidence shows continuous daily dosing (250 mg/day) achieves 76.67% cure vs only 26.67% with pulse dosing 7