Terbinafine for Fungal Nail Infections: Both Oral and Topical Formulations Available
Terbinafine is available in both oral and topical formulations, but oral terbinafine is the definitive first-line treatment for fungal nail infections (onychomycosis), while topical terbinafine formulations are under investigation and not yet standard therapy for this indication. 1
Oral Terbinafine: The Gold Standard
Oral terbinafine 250 mg daily represents the most effective treatment for dermatophyte onychomycosis, with the highest strength of recommendation (A) and level of evidence (1+) among all available antifungal agents. 1
Treatment Duration and Efficacy
- Fingernail infections: 6 weeks of continuous therapy 1
- Toenail infections: 12 weeks of continuous therapy 1, 2
- Mycological cure rates exceed 70-80% for dermatophyte infections 1, 3
- The drug persists in the nail for up to 6 months after treatment completion due to its lipophilic properties and long half-life 1
Mechanism and Pharmacology
Oral terbinafine works by inhibiting squalene epoxidase, which depletes ergosterol (fungistatic effect) and causes toxic squalene accumulation (fungicidal effect), making it the only oral fungicidal antimycotic currently available 1. More than 70% is absorbed orally, with 99% plasma protein binding and primarily renal clearance 1.
Superiority Over Alternatives
The British Association of Dermatologists guidelines clearly establish that terbinafine demonstrates superior efficacy compared to itraconazole, fluconazole, and griseofulvin in dermatophyte onychomycosis 1, 3. Specifically, mycological cure rates are approximately twice as high with terbinafine (76-81%) compared to itraconazole (38-49%) 3.
Topical Terbinafine: Limited Role in Nail Infections
New topical formulations of terbinafine are being investigated for onychomycosis, with early data showing promising results, but they currently carry only a strength of recommendation D with level of evidence 3. 1
Current Status
- Topical terbinafine is not the standard treatment for nail infections 1
- Research is ongoing into new topical formulations specifically designed for nail penetration 1
- Topical terbinafine 1% cream is highly effective (>80% mycological cure) for cutaneous dermatophyte infections like tinea pedis and tinea corporis, but this does not extend to nail infections 4, 5
Why Topical Fails for Nails
The nail plate's dense keratin structure prevents adequate penetration of standard topical formulations, making systemic therapy necessary for effective treatment of onychomycosis 1.
Safety Monitoring Requirements
Mandatory Baseline Testing
The British Association of Dermatologists recommends baseline liver function tests and complete blood count before initiating oral terbinafine, particularly in patients with 1, 6:
- History of heavy alcohol consumption
- Hepatitis
- Hematological abnormalities
- Children (as terbinafine is not licensed for pediatric onychomycosis)
Contraindications
Oral terbinafine is contraindicated in patients with active or chronic liver disease and those with renal impairment. 1, 6, 7
Common Adverse Effects
- Gastrointestinal symptoms (49%): nausea, diarrhea, taste disturbance 1, 7
- Dermatological events (23%): rash, pruritus, urticaria, eczema 1
- Serious adverse events occur in only 0.04% of patients 1
Rare but Serious Reactions
The FDA label warns of Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatotoxicity (particularly in pre-existing liver disease), and potentially permanent taste or smell disturbances 1, 6, 7.
Clinical Decision Algorithm
For confirmed dermatophyte onychomycosis:
- First choice: Oral terbinafine 250 mg daily (6 weeks for fingernails, 12 weeks for toenails) 1, 2
- Alternative if Candida suspected: Itraconazole (less effective for dermatophytes but better anti-Candida activity) 1, 2
- Topical therapy alone: Consider only for very mild cases or as adjunctive therapy with oral agents 1, 2
Critical pitfall: Do not use topical terbinafine as monotherapy for established nail infections—the evidence does not support this approach, and you will delay effective treatment 1.