In a healthy adult with uncomplicated dermatophyte onychomycosis and no significant drug‑interaction concerns, what are the advantages and disadvantages of itraconazole versus terbinafine?

Terbinafine vs Itraconazole for Dermatophyte Onychomycosis

Terbinafine is superior to itraconazole for dermatophyte onychomycosis and should be your first-line choice in healthy adults without contraindications. 1, 2

Efficacy Comparison

Terbinafine demonstrates approximately twice the cure rates of itraconazole:

• Mycologic cure: Terbinafine achieves 76-81% vs itraconazole 38-49% at 72 weeks 2
• Complete cure: Terbinafine 52% vs itraconazole 32% 2
• Long-term durability: At 5-year follow-up, terbinafine maintained 46% mycologic cure vs itraconazole 13%, with lower relapse rates (23% vs 53%) 2
• Mechanism advantage: Terbinafine is fungicidal against dermatophytes with very low MICs (0.004 μg/mL), while itraconazole is fungistatic 3, 2

Treatment Duration

Terbinafine requires continuous daily dosing but for a defined period:

• Toenails: 250 mg daily for 12 weeks (up to 16 weeks for severe cases) 1, 3
• Fingernails: 250 mg daily for 6 weeks 1, 3

Itraconazole offers pulse dosing flexibility:

• 200 mg twice daily for 1 week per month for 3-4 pulses 1, 2
• Alternative: 200 mg daily continuously for 12 weeks 1

Drug Interaction Profile

Terbinafine has minimal drug interactions—a major clinical advantage:

• Only significant interaction is with CYP2D6-metabolized drugs (certain antidepressants, beta-blockers, antiarrhythmics) 1, 3
• Does not affect warfarin, oral contraceptives, or most common medications 2

Itraconazole has extensive drug interactions:

• Inhibits CYP3A4, affecting statins, calcium channel blockers, immunosuppressants, many other drugs 1
• Requires careful medication review before prescribing 1

Safety and Monitoring

Both require baseline liver function tests and complete blood count 1, 4

Terbinafine adverse effects (generally mild):

• Gastrointestinal disturbances: 49% of reported side effects (nausea, diarrhea) 4
• Dermatological events: 23% (rash, pruritus) 4
• Taste disturbance (rarely permanent—counsel patients) 1, 4
• Hepatotoxicity: rare but serious; contraindicated in active/chronic liver disease 1, 4
• Can aggravate psoriasis and cause subacute lupus-like syndrome 1

Itraconazole adverse effects:

• Headache and gastrointestinal upset 1
• Hepatotoxicity risk similar to terbinafine 1
• Requires monitoring in patients with hepatic impairment 1

Ongoing monitoring:

• For terbinafine: repeat LFTs only if treatment exceeds 1 month or symptoms develop 4
• For itraconazole: similar hepatic monitoring required 1

Contraindications

Terbinafine contraindications:

• Active or chronic liver disease 1, 4
• Renal impairment (primarily cleared by kidneys) 4
• Lupus erythematosus 3

Itraconazole contraindications:

• Hepatic impairment 1
• Heart failure (negative inotropic effects) 1

Special Clinical Scenarios

When itraconazole may be preferred:

• Candida onychomycosis: Itraconazole and voriconazole are most active against yeast species, while terbinafine has limited efficacy 1
• Patients on CYP2D6-metabolized drugs: If terbinafine interaction is problematic 3
• Patient preference for pulse dosing: Some patients prefer intermittent therapy 1

When terbinafine is clearly superior:

• Dermatophyte infections: Terbinafine is fungicidal with superior cure rates 1, 2
• Patients on multiple medications: Minimal drug interactions 3, 2
• Cost-effectiveness: Higher cure rates translate to better cost-effectiveness despite continuous dosing 2

Practical Prescribing Algorithm

1. Confirm dermatophyte infection with culture before starting therapy 1
2. Obtain baseline LFTs and CBC 1, 4
3. Review medication list for CYP2D6 substrates (terbinafine) or CYP3A4 substrates (itraconazole) 1, 3
4. Screen for contraindications: liver disease, renal impairment, heart failure 1, 4
5. First-line choice: Terbinafine 250 mg daily for 12 weeks (toenails) or 6 weeks (fingernails) 1, 2
6. Second-line choice: Itraconazole if terbinafine contraindicated, not tolerated, or Candida infection 1

Common Pitfalls

• Don't use terbinafine for Candida onychomycosis—it has poor efficacy against yeasts 1
• Don't skip baseline testing—hepatotoxicity, though rare, can be serious 1, 4
• Don't assume treatment failure at 3 months—terbinafine persists in nails for 6 months post-treatment; evaluate at 3-6 months 3, 5
• Don't ignore drug interactions with itraconazole—review all medications carefully 1
• Counsel about permanent taste disturbance risk with terbinafine before starting 4, 6