A 28-year-old woman with tinea unguium (onychomycosis) affecting 3 toenails for 6 months presents for treatment. Which drug is the preferred first-line oral agent?

Explanation

## First-Line Treatment of Tinea Unguium (Onychomycosis) **Key Point:** Terbinafine is the gold-standard first-line oral antifungal for dermatophyte-induced onychomycosis because it achieves the highest cure rates (80–90%), shortest treatment duration, and best nail penetration among all systemic agents. ### Why Terbinafine Dominates in Nail Disease **High-Yield:** Terbinafine concentrates in nail keratin and achieves fungicidal levels in nail tissue for weeks after discontinuation, allowing for shorter treatment courses (12 weeks for toenails vs. 6 weeks for fingernails). ### Comparative Efficacy in Onychomycosis | Agent | Cure Rate | Duration (Toenail) | Mechanism | Nail Penetration | |-------|-----------|-------------------|-----------|------------------| | **Terbinafine** | 80–90% | 12 weeks | Fungicidal | Excellent | | **Itraconazole** | 60–70% | 12 weeks (pulse) | Fungistatic | Moderate | | **Griseofulvin** | 40–60% | 12–18 months | Fungistatic | Poor | | **Ketoconazole** | <50% | Not recommended | Fungistatic | Poor | **Clinical Pearl:** Terbinafine 250 mg once daily for 12 weeks achieves mycological cure in ~80% of patients with dermatophyte onychomycosis. Clinical cure (normal nail appearance) may take 6–12 months after mycological cure due to slow nail growth. ### Mechanism of Terbinafine's Superiority 1. **Fungicidal action**: Kills dermatophytes; others are fungistatic 2. **Lipophilic**: Concentrates in sebum and nail keratin 3. **Persistent levels**: Remains in nail tissue for weeks after stopping, allowing shorter courses 4. **Rapid onset**: Begins eradicating infection within days 5. **No food interaction**: Can be taken without regard to meals ### Treatment Algorithm for Onychomycosis ```mermaid flowchart TD A[Suspected onychomycosis]:::outcome --> B{Confirm with KOH/culture}:::decision B -->|Dermatophyte confirmed| C{Number of nails affected?}:::decision C -->|1-2 nails, <50% involvement| D[Topical terbinafine or amorolfine]:::action C -->|≥3 nails or >50% involvement| E[Oral terbinafine indicated]:::action E --> F[250 mg once daily]:::action F --> G{Fingernails or toenails?}:::decision G -->|Fingernails| H[6 weeks]:::action G -->|Toenails| I[12 weeks]:::action H --> J[Mycological cure in 6-8 weeks]:::outcome I --> K[Mycological cure in 12-16 weeks]:::outcome ``` **Mnemonic:** **TERBINAFINE = NAIL KILLER** — **T**erbinafine **E**xcels at **R**eaching **B**oth **I**nfected **N**ails, **A**chieving **F**ungicidal **I**njury, **N**ail **E**radication. ### Why Itraconazole is Second-Line Itraconazole (200 mg twice daily) can be used as pulse therapy (1 week per month for 3 months) but: - Cure rates are 60–70% (lower than terbinafine) - Requires food for absorption (lipophilic) - More drug interactions (CYP3A4 inhibitor) - Fungistatic, not fungicidal **Warning:** Griseofulvin and ketoconazole are now obsolete for onychomycosis. Griseofulvin requires 12–18 months of therapy with poor nail penetration; ketoconazole has hepatotoxicity concerns and <50% efficacy. Do not select these in modern NEET PG exams.