Why Terbinafine is Preferred Over Azoles for Dermatophyte Infections
Terbinafine should be considered first-line treatment for dermatophyte onychomycosis and other dermatophyte infections due to its superior fungicidal activity, higher cure rates, and lower relapse rates compared to azole antifungals. 1
Superior In Vitro and In Vivo Activity
Terbinafine demonstrates true fungicidal activity against dermatophytes, with a minimum inhibitory concentration (MIC) of approximately 0.004 µg/mL that equals its minimal fungicidal concentration (MFC), making it the most active antidermatophyte agent available. 1
Itraconazole (the primary azole comparator) has 10-fold higher MIC and MFC values than terbinafine, indicating significantly weaker antifungal potency against dermatophytes. 1
Terbinafine has particularly potent fungicidal effects against Trichophyton rubrum and T. mentagrophytes, the most common causative organisms in dermatophyte infections. 1
Clinical Efficacy: The Evidence
Onychomycosis Treatment Outcomes
In the landmark L.I.ON. study, terbinafine achieved approximately double the cure rates of itraconazole: mycological cure rates were 76% vs 38% after 12 weeks and 81% vs 49% after 16 weeks at 72-week follow-up. 2
Complete cure rates in dermatophyte toenail onychomycosis were 55% with terbinafine versus 26% with pulsed itraconazole in a large multicenter randomized trial of 508 patients. 1
Long-Term Effectiveness
At 5-year follow-up in the L.I.ON. Icelandic Extension study, terbinafine maintained superior outcomes: mycological cure without retreatment was 46% versus 13% for itraconazole. 1, 2
Relapse rates were significantly lower with terbinafine: mycological relapse occurred in 23% versus 53% with itraconazole, and clinical relapse in 21% versus 48%. 1, 2
Mechanism of Action Advantage
Terbinafine inhibits squalene epoxidase, blocking ergosterol biosynthesis and causing toxic accumulation of intracellular squalene, resulting in both fungistatic (ergosterol depletion) and fungicidal (squalene accumulation) effects. 1, 3
Azoles are primarily fungistatic rather than fungicidal, which contributes to their lower cure rates and higher relapse rates in dermatophyte infections. 1
Practical Treatment Considerations
Dosing and Duration
Terbinafine requires shorter treatment duration: 250 mg daily for 6 weeks (fingernails) or 12-16 weeks (toenails). 1
Itraconazole requires either 12 weeks continuous therapy or pulse therapy (400 mg daily for 1 week per month for 2-3 pulses), which may be less convenient. 1
Drug Interactions
Terbinafine has minimal drug-drug interactions, with only potentially significant interaction involving cytochrome P450 2D6 substrates. 1
Itraconazole has extensive drug interactions including enhanced toxicity with warfarin, antihistamines, antipsychotics, anxiolytics, digoxin, cisapride, ciclosporin, and simvastatin. 1
Safety Profile
Both agents are generally well tolerated, with comparable overall safety profiles in comparative trials. 2
Common terbinafine side effects are mild: gastrointestinal disturbances (49%) and dermatological events (23%) such as rash or pruritus, with serious adverse events occurring in only 0.04% of patients. 1
Important caveat: Taste disturbance occurs in approximately 1:400 patients and can rarely be permanent—patients must be warned of this risk. 1
Both agents are contraindicated in active or chronic liver disease and require baseline liver function monitoring in high-risk patients. 1, 3
When Azoles May Be Preferred
For Candida onychomycosis, itraconazole is superior as terbinafine has only fungistatic activity against Candida species while azoles demonstrate better anti-Candida efficacy. 1
When terbinafine is contraindicated (active liver disease, severe kidney disease, lupus erythematosus, porphyria), itraconazole becomes the next best alternative. 1, 3