What is the recommended first‑line therapy for toenail onychomycosis in an adult with normal hepatic function, including drug choice, dosage, duration, monitoring, and adjunct measures?

Toenail Onychomycosis: First-Line Treatment

Terbinafine 250 mg once daily for 12 weeks is the first-line treatment for toenail onychomycosis caused by dermatophytes in adults with normal liver function. 1, 2, 3

Drug Selection and Rationale

• Terbinafine is superior to all alternatives with mycological cure rates of 76-81% compared to itraconazole (38-49%), fluconazole, and griseofulvin (30-40%) 4, 5
• The British Association of Dermatologists designates terbinafine as Grade A recommendation (highest level of evidence) and explicitly states it is "generally preferred over itraconazole" 1, 2
• Terbinafine demonstrates lower relapse rates (21-23%) versus itraconazole (48-53%) at 5-year follow-up 4

Dosing and Duration

• Standard regimen: 250 mg orally once daily for 12 weeks 1, 2, 3
• Can be taken with or without food (absorption unaffected) 2
• For severe cases, extend to 16 weeks 1, 2
• Fingernail infections require only 6 weeks 1, 3

Why 12 Weeks Works

• Terbinafine persists in the nail for 6 months after treatment cessation due to its lipophilic properties and long half-life 2
• Optimal clinical effect appears months after mycological cure as healthy nail grows out 3
• Studies show 12-week treatment achieves 82% complete cure at 24 weeks and 71% at 48 weeks 6

Pre-Treatment Requirements

Mandatory before prescribing: 1, 2, 3

• Mycological confirmation (KOH preparation, fungal culture, or nail biopsy) to confirm dermatophyte infection
• Baseline liver function tests (ALT and AST)
• Complete blood count

Why Confirmation Matters

• Terbinafine is highly effective for dermatophytes but significantly less effective for Candida species 1
• For Candida onychomycosis, itraconazole is superior with 92% cure rates versus terbinafine's 40-60% 1

Monitoring During Treatment

For low-risk patients with normal baseline labs: 2, 7

• No routine repeat liver function tests needed during the standard 12-week course
• Monitor only if clinical symptoms develop (nausea, fatigue, right upper quadrant pain, jaundice, dark urine)

For high-risk patients, monitor liver function tests if: 1, 7

• History of hepatitis or liver disease
• Heavy alcohol consumption
• Concomitant hepatotoxic medications
• Treatment extends beyond 1 month

Absolute Contraindications

• Active or chronic liver disease 2, 7, 3
• Renal impairment (creatinine clearance ≤50 mL/min) 7
• History of allergic reaction to terbinafine 3
• Lupus erythematosus 2

Common Adverse Effects

• Gastrointestinal disturbances (49% of reported side effects): nausea, diarrhea, abdominal pain 7, 8
• Headache 1, 7
• Taste disturbance (can be permanent in rare cases) 1, 7, 3
• Dermatological reactions (23%): rash, pruritus, urticaria 7

Serious but Rare Warnings

• Hepatotoxicity: Discontinue immediately if liver enzyme elevation or symptoms develop 7, 3
• Stevens-Johnson syndrome and toxic epidermal necrolysis 7
• Severe neutropenia (reversible upon discontinuation) 3
• Permanent taste or smell loss 3

Drug Interaction Advantages

• Terbinafine has minimal drug-drug interactions compared to azole antifungals (itraconazole, fluconazole) 2, 7
• Only significant interaction: drugs metabolized by cytochrome P450 2D6 (certain antidepressants, beta-blockers, antiarrhythmics) 2, 7
• Safe to use with corticosteroids 8

Adjunct Measures

Topical therapy can be added for combination treatment if: 1

• Response to systemic monotherapy likely to be poor
• Extensive nail involvement
• Patient preference for enhanced efficacy

Options: 1

• Amorolfine 5% lacquer applied once or twice weekly
• Ciclopirox 8% lacquer applied once daily

Re-evaluation and Treatment Failure

• Re-evaluate at 3-6 months after starting treatment 2
• If disease persists at 3-6 months, immediately resume treatment without waiting 2
• Repeat baseline labs (liver function tests and complete blood count) before restarting 2
• If second terbinafine course fails, switch to itraconazole 200 mg daily for 12 weeks or pulse therapy (400 mg daily for 1 week per month for 3 cycles) 2

Alternative Agents (When Terbinafine Contraindicated)

Itraconazole: 1

• 200 mg daily for 12 weeks continuously, OR
• Pulse therapy: 400 mg daily for 1 week per month (3 pulses for toenails)
• Requires monitoring if continuous therapy exceeds 1 month
• More drug interactions than terbinafine

Fluconazole: 1

• 150-450 mg weekly for at least 6 months
• Useful if terbinafine and itraconazole not tolerated
• Lower efficacy than terbinafine

Topical monotherapy (if systemic therapy contraindicated): 1, 8

• Amorolfine 5% lacquer once or twice weekly for 6-12 months
• Ciclopirox 8% lacquer once daily for up to 48 weeks
• Limited efficacy for severe disease

Critical Clinical Pitfalls

• Never prescribe without mycological confirmation – clinical appearance alone is insufficient 3
• Do not use terbinafine for Candida onychomycosis – itraconazole is superior 1
• Avoid in renal impairment – this is an absolute contraindication, not a dose-adjustment scenario 7
• Warn patients about permanent taste/smell loss risk before prescribing 3
• Instruct patients to stop immediately and report if they develop persistent nausea, fatigue, right upper quadrant pain, jaundice, or dark urine 3