Oral Treatment for Nail Fungal Infections
Terbinafine 250 mg daily is the first-line oral treatment for fungal nail infections: 6 weeks for fingernails and 12 weeks for toenails. 1, 2, 3
Primary Treatment Recommendation
Terbinafine is superior to all other oral antifungals for dermatophyte onychomycosis (which causes 90-95% of nail infections) and should be your first choice. 1, 2, 4 The FDA-approved dosing is:
Expected outcomes with terbinafine include 70% mycological cure and 38% complete clinical cure in toenails, with higher rates (79% mycological cure, 59% complete cure) in fingernails. 3
Alternative Oral Agents
Itraconazole (Second-Line)
Use itraconazole when terbinafine is contraindicated or for Candida nail infections, where it is actually more effective than terbinafine. 1, 2
Dosing options:
- Continuous therapy: 200 mg daily for 12 weeks 1
- Pulse therapy: 400 mg daily for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 1, 5
Critical caveat: Itraconazole inhibits CYP3A4 and has significant drug interactions. 4 Avoid in patients taking multiple medications, particularly those on antiretrovirals, immunosuppressants, or medications metabolized by CYP3A4. 2
Fluconazole (Off-Label)
Fluconazole is not licensed for onychomycosis but can be used off-label at 150 mg weekly for at least 6 months. 4 It has fewer drug interactions than itraconazole but is less effective. 1
Griseofulvin (Third-Line, Rarely Used)
Griseofulvin should only be considered when newer agents are unavailable or contraindicated, as it has poor cure rates (30-40%), high relapse rates, and requires 6-18 months of treatment. 5, 6 Terbinafine is significantly more effective (RR 0.32 for clinical cure). 7
When Oral Therapy is Preferred
Systemic therapy is almost always more successful than topical treatment and should be used for: 1, 2
- Any distal lateral subungual onychomycosis (DLSO) beyond very early stages
- Total dystrophic onychomycosis
- Proximal subungual onychomycosis
- Infections involving >80% of nail plate
- Infections involving the lunula (nail matrix)
Special Populations
Diabetic Patients
Terbinafine is strongly preferred over itraconazole due to lower risk of drug interactions and hypoglycemia. 2, 5 Onychomycosis is a significant predictor for foot ulcers in diabetics, making treatment particularly important. 5
Immunosuppressed Patients
Terbinafine or fluconazole are preferred over itraconazole due to reduced drug interactions with antiretrovirals and immunosuppressants. 2, 5
Pediatric Patients
Dosing for children: 5
- Terbinafine: 62.5 mg/day if <20 kg, 125 mg/day for 20-40 kg, 250 mg/day if >40 kg
- Itraconazole pulse: 5 mg/kg/day for 1 week per month—2 months for fingernails, 3 months for toenails
Pediatric cure rates are higher than adults (88-100%). 2
Critical Pre-Treatment Requirements
Never initiate treatment without mycological confirmation—this is the most common cause of treatment failure. 1, 8, 2 Obtain:
- KOH preparation (direct microscopy), AND
- Fungal culture, OR
- Nail biopsy with histological examination 3
Clinical diagnosis alone is unreliable as psoriasis and other nail dystrophies mimic onychomycosis. 9
Common Pitfalls to Avoid
- Underdosing or insufficient treatment duration leads to predictable failure 2
- Using topical therapy for extensive disease results in poor outcomes 2
- Not checking for drug interactions, particularly with itraconazole in patients on multiple medications 2
- Treating without mycological confirmation—the single most common cause of treatment failure 1, 2
Adverse Effects Monitoring
Terbinafine
Common adverse events include gastrointestinal symptoms, infections, and headache, but there is no significant difference in overall adverse event risk compared to placebo. 7 Terbinafine inhibits CYP2D6, so monitor patients on tricyclic antidepressants, SSRIs, atypical antipsychotics, beta blockers, or tamoxifen. 4, 10
Itraconazole
Most common adverse events are headache, flu-like symptoms, and nausea. 7 Monitor liver enzymes if prolonged therapy is needed. 1
Expected Treatment Failure and Recurrence
Even with optimal therapy, expect 20-30% treatment failure rates. 1, 2 Recurrence rates are high (40-70%), requiring preventive strategies including avoiding barefoot walking in public facilities, disinfecting shoes, and keeping nails short. 2, 5, 10
Mean time to overall success is approximately 10 months for toenails and 4 months for fingernails. 3 Mycological cure rates are typically 30% better than clinical cure rates, as pre-existing nail dystrophy may not fully resolve. 1, 8