What is the recommended treatment for a patient with onychomycosis (fungal infection of the nail)?

Onychomycosis Treatment

Oral terbinafine 250 mg daily is the first-line treatment for onychomycosis: 6 weeks for fingernails and 12 weeks for toenails, with the highest level of evidence (strength A, level 1+) and superior efficacy compared to all other options. 1, 2, 3

Diagnostic Confirmation Required Before Treatment

• Always confirm the diagnosis with mycological examination (KOH preparation, fungal culture, or nail biopsy) before initiating any treatment — the most common cause of treatment failure is incorrect diagnosis made on clinical grounds alone. 1, 2, 3

Treatment Algorithm by Disease Severity

For Limited Disease (Topical Therapy Appropriate)

Use topical therapy ONLY when ALL of the following criteria are met: 1, 2, 4

• Superficial white onychomycosis (SWO), OR
• Very early distal lateral subungual onychomycosis (DLSO) with <80% nail plate involvement AND no lunula involvement, OR
• Systemic therapy is contraindicated

Topical options (in order of preference): 2, 5

• Amorolfine 5% nail lacquer applied once or twice weekly for 6-12 months (approximately 50% effectiveness) 2, 5
• Efinaconazole 10% solution applied once daily for 48 weeks (mycological cure approaching 50%, complete cure 15%) 5
• Ciclopirox 8% nail lacquer applied daily for up to 48 weeks (34% mycological cure vs 10% placebo) 2, 5, 4

For Most Other Cases (Oral Therapy Required)

Any infection beyond the limited criteria above requires oral therapy. 1, 2

First-Line: Terbinafine

• Terbinafine 250 mg once daily 1, 2, 3
  • 6 weeks for fingernails
  • 12 weeks for toenails
• Most effective against dermatophytes (which cause the majority of cases) 6, 7, 8
• High-quality evidence shows terbinafine achieves 6-fold higher clinical cure rates versus placebo (RR 6.00,95% CI 3.96-9.08) 8
• Minimal drug interactions (does not inhibit CYP3A4) 6

Second-Line: Itraconazole

• Pulse itraconazole 200 mg twice daily for 1 week per month 1, 2
  • 2 pulses (2 months) for fingernails
  • 3 pulses (3 months) for toenails
• Particularly effective for Candida onychomycosis 1, 2
• Moderate-quality evidence shows terbinafine is probably more effective than azoles for both clinical cure (RR 0.82,95% CI 0.72-0.95) and mycological cure (RR 0.77,95% CI 0.68-0.88) 8
• Caution: Multiple drug interactions via CYP3A4 metabolism 6, 9

Special Population Considerations

Diabetic Patients

• Terbinafine is strongly preferred over itraconazole due to low risk of drug interactions and hypoglycemia 1
• Onychomycosis is a significant predictor for foot ulcer development in diabetes 1
• Itraconazole is contraindicated in congestive heart failure (increased prevalence in diabetics) 1

Immunosuppressed Patients (HIV, Transplant Recipients)

• Terbinafine or fluconazole are preferred over itraconazole due to reduced drug interactions with antiretrovirals and immunosuppressants 1
• Prevalence of onychomycosis approaches 30% in HIV-positive patients 1

Pediatric Patients

• Pulse itraconazole 5 mg/kg/day for 1 week per month: 2 months for fingernails, 3 months for toenails 1
• Daily terbinafine (weight-based): 6 weeks for fingernails, 12 weeks for toenails 1
  • <20 kg: 62.5 mg/day
  • 20-40 kg: 125 mg/day

  • 40 kg: 250 mg/day

• Pediatric cure rates are higher than adults (88-100% in studies) 1

Combination Therapy

• Consider combining topical and oral therapy for improved outcomes, particularly in moderate-to-severe cases 2, 5
• Ciclopirox combined with oral terbinafine achieved 66.7% mycological cure in moderate-to-severe cases 5
• Combination provides antimicrobial synergy, wider antifungal spectrum, and increased cure rates 1

Common Pitfalls to Avoid

• Treatment failure rates of 20-30% occur even with the most effective agents — set realistic expectations 2
• Recurrence rates are high (40-70%) — counsel patients on preventive strategies including treating tinea pedis and avoiding reinfection sources 1, 2
• Do not use topical therapy for extensive disease — this results in predictable failure 2
• Dermatophytomas (dense white lesions beneath the nail) are resistant to antifungal treatment without prior mechanical removal 1
• Clinical improvement does not equal mycological cure — cure rates are often 30% lower than apparent clinical improvement with topical antifungals 5
• Itraconazole has significant drug interactions — carefully review medication lists before prescribing 1, 6
• Up to 18 months is required for complete toenail regrowth — therapeutic success depends on the newly grown-out nail being fungus-free 1

Adverse Events

• Terbinafine: Gastrointestinal symptoms, infections, headache, taste disturbances (no significant difference in risk vs placebo, RR 1.13) 8
• Azoles: Headache, flu-like symptoms, nausea (slightly more events but probably not significant, RR 1.04) 8
• Both agents are generally well tolerated with moderate-quality evidence of safety 8