A 35-year-old woman presents with onycholysis, subungual hyperkeratosis, and discoloration of the toenails for 8 months. Fungal culture confirms Trichophyton rubrum. What is the preferred systemic antifungal regimen for tinea unguium (onychomycosis)?

## Tinea Unguium (Onychomycosis): Systemic Antifungal Choice ### Clinical Context Tinea unguium (onychomycosis) is a chronic fungal infection of the toenails or fingernails, most commonly caused by dermatophytes (T. rubrum, T. mentagrophytes). It presents with discoloration, thickening, and crumbling of the nail plate. Systemic therapy is mandatory because topical agents cannot penetrate the nail plate adequately. ### Drug of Choice: Terbinafine **Key Point:** Terbinafine 250 mg once daily for 12 weeks is the gold standard systemic antifungal for dermatophyte-induced onychomycosis. **High-Yield:** Terbinafine achieves high concentrations in the nail plate (via sebaceous gland secretion and transungual diffusion), resulting in the highest cure rates (70–90%) among all systemic antifungals for dermatophyte onychomycosis. ### Comparison of Systemic Antifungals for Onychomycosis | Parameter | Terbinafine | Itraconazole (Pulse) | Griseofulvin | Fluconazole | |-----------|-------------|----------------------|--------------|-------------| | **Duration** | 12 weeks continuous | 3 months (1 week/month) | 12 weeks | 12 weeks | | **Dosing** | Once daily | Twice daily (pulse) | Twice daily | Once weekly | | **Nail penetration** | Excellent | Good | Poor | Moderate | | **Cure rate (dermatophytes)** | 70–90% | 60–70% | 40–50% | 50–60% | | **Hepatotoxicity risk** | Low | Moderate | Low | Low | | **Drug interactions** | Moderate | High (CYP3A4 inhibitor) | High | High | | **Cost** | Moderate | High | Low | Moderate | **Clinical Pearl:** Terbinafine's superior nail penetration and fungicidal activity make it the preferred choice for dermatophyte onychomycosis. Itraconazole pulse therapy is reserved for azole-resistant cases or when terbinafine is contraindicated. ### Why Continuous Therapy > Pulse Therapy for Terbinafine - Terbinafine's fungicidal action and excellent nail penetration allow continuous dosing to be more effective than pulse therapy - Itraconazole, being fungistatic, benefits from pulse therapy (drug accumulation during pulse weeks) - Terbinafine does not require pulse dosing because it achieves adequate nail concentrations with continuous daily dosing **Mnemonic:** **TERBINAFINE for TOENAILS** — Terbinafine Terminates Tinea unguium (12 weeks, continuous). ### Treatment Monitoring - Clinical cure typically takes 3–6 months after completing therapy (nail must grow out) - Mycological cure (negative culture) is the endpoint - Relapse rate is 10–15% even with adequate therapy due to reinfection [cite:KD Tripathi 8e Ch 57; Harrison 21e Ch 211]