Which is more effective for treating fungal infections of the skin, itraconazole or terbinafine?

Terbinafine is Superior for Most Fungal Skin Infections

For dermatophyte infections of the skin (tinea corporis, tinea cruris, tinea pedis), terbinafine is the preferred first-line treatment due to its superior fungicidal activity, higher cure rates, shorter treatment duration, and better safety profile compared to itraconazole. 1, 2

Evidence-Based Treatment Algorithm

First-Line: Terbinafine for Dermatophyte Infections

• 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 potent antidermatophyte agent available. 2

• Itraconazole has 10-fold higher MIC and MFC values than terbinafine, indicating significantly weaker antifungal potency against dermatophytes. 2

• Clinical efficacy rates of approximately 90% mycological cure and 80% overall cure have been achieved with oral terbinafine (250 mg/day) in cutaneous dermatophyte infections. 3

Dosing Regimen for Skin Infections

• Oral terbinafine 250 mg daily for 2-4 weeks is the standard regimen for fungal skin infections. 1

• For children, weight-based dosing applies: <20 kg receive 62.5 mg/day, 20-40 kg receive 125 mg/day, and >40 kg receive 250 mg/day for 2-4 weeks. 1

• Post-marketing surveillance of 454 patients showed that 2 weeks of terbinafine resulted in 97% good-to-excellent clinical efficacy, with 89% improvement in scaling, 83% in pruritus, and 81% in erythema. 4

When to Use Itraconazole Instead

Itraconazole should be reserved as second-line therapy or for specific clinical scenarios: 1, 5

• When terbinafine has failed or is contraindicated (active/chronic liver disease, severe kidney disease, lupus erythematosus, porphyria). 6

• For Microsporum species infections, where itraconazole may have comparable efficacy to terbinafine. 1

• When severe or progressive cutaneous reactions occur with terbinafine, itraconazole offers a different side effect profile. 5

• For Candida skin infections, where itraconazole is superior since terbinafine has only fungistatic activity against Candida species. 2

Itraconazole Dosing (When Used)

• Itraconazole 50-100 mg per day for 4 weeks, or 5 mg/kg per day for 2-4 weeks. 1

• Intermittent pulsed dosing regimens are effective and may be preferred for compliance. 1

Critical Safety Considerations

Terbinafine Safety Profile

• Adverse events occur in only 10.5% of patients, with gastrointestinal complaints (nausea, diarrhea) being most common. 2, 7

• Critical caveat: Taste disturbance occurs in approximately 1:400 patients and can rarely be permanent—patients must be warned of this risk before starting therapy. 2

• Rare but serious reactions include Stevens-Johnson syndrome, toxic epidermal necrolysis, and hepatotoxicity, particularly in patients with pre-existing liver disease. 6

• Minimal drug-drug interactions, with only potentially significant interaction involving cytochrome P450 2D6 substrates. 2

Itraconazole Safety Profile

• Extensive drug interactions including enhanced toxicity with warfarin, antihistamines (terfenadine, astemizole), antipsychotics, anxiolytics (midazolam), digoxin, cisapride, ciclosporin, and simvastatin. 1, 2

• Not licensed in the UK for children aged ≤12 years with tinea capitis. 1

• Decreased efficacy with concomitant H2 blockers, phenytoin, and rifampicin. 1

Comparative Efficacy Data

Head-to-Head Evidence

• A meta-analysis of published clinical trials revealed similar and high cure rates (>70%) for both agents in superficial fungal infections, but terbinafine demonstrated superior outcomes in dermatophyte-specific infections. 8

• In onychomycosis (which provides insight into dermatophyte treatment efficacy), complete cure rates were 55% with terbinafine versus 26% with pulsed itraconazole in a large multicenter randomized trial of 508 patients. 2

• At 5-year follow-up, mycological cure without retreatment was 46% versus 13% for itraconazole, with relapse rates significantly lower for terbinafine (23% versus 53%). 2

Common Pitfalls to Avoid

• Do not use topical therapy alone for tinea capitis or extensive skin infections—oral therapy is required for both clinical and mycological cure. 1

• Do not prescribe itraconazole to patients on multiple medications without checking for drug interactions, as its interaction profile is extensive. 1, 2

• Do not assume treatment failure without first considering lack of compliance, suboptimal drug absorption, or reinfection. 1

• Obtain baseline liver function tests for both agents in patients with hepatotoxicity history or risk factors. 2

• The endpoint of treatment is mycological rather than clinical cure—repeat mycology sampling is recommended until mycological clearance is achieved. 1

Emerging Resistance Considerations

• Recent reports suggest dermatophytes are developing resistance to terbinafine and traditional antifungals (itraconazole, fluconazole). 9

• When resistance to first-line agents occurs, newer generation azoles (voriconazole, posaconazole) may be considered off-label, but only after traditional agents have been thoroughly evaluated. 9

• Antifungal stewardship should be the top priority to prevent further resistance development. 9