What are the recommended oral and topical dosing regimens, treatment duration, liver function monitoring, contraindications, and alternative therapies for terbinafine in an adult with dermatophyte skin infection or onychomycosis?

Terbinafine Treatment for Dermatophyte Infections and Onychomycosis

Oral Dosing Regimens

For dermatophyte onychomycosis in adults, terbinafine 250 mg once daily is the first-line treatment, with 6 weeks for fingernails and 12 weeks for toenails (up to 16 weeks for severe cases). 1

• Toenail onychomycosis: 250 mg daily for 12 weeks (standard) or up to 16 weeks for severe infections 1
• Fingernail onychomycosis: 250 mg daily for 6 weeks 1
• Terbinafine can be taken with or without food, as absorption is unaffected 1
• The drug persists in nails for up to 30 weeks after treatment completion due to its lipophilic properties and long half-life, allowing continued fungicidal activity 1

Alternative Pulse Regimen

• A quarterly pulse regimen of 500 mg daily for 7 days every 3 months (totaling four treatments) has shown comparable effectiveness to continuous therapy in dermatophyte onychomycosis, potentially reducing side effects and drug interactions 2

Topical Therapy

Topical terbinafine is inferior to systemic therapy for onychomycosis except in very distal infections or superficial white onychomycosis. 3

• Topical 1% formulations applied once or twice daily for up to 2 weeks achieve >80% mycological cure in tinea pedis, tinea corporis/cruris, and cutaneous candidiasis 4
• For onychomycosis, topical alternatives include amorolfine 5% lacquer (once or twice weekly for 6-12 months) or ciclopirox 8% lacquer (daily for up to 48 weeks) 5

Pre-Treatment Requirements

Obtain mycological confirmation (microscopy and culture) before starting systemic therapy—this is mandatory. 3

Baseline Laboratory Testing

• Liver function tests (ALT and AST) are required before treatment initiation 1, 5
• Complete blood count is required before starting therapy 1, 5
• These tests are particularly important in patients with history of hepatitis, heavy alcohol use, or hematological abnormalities 1

Liver Function Monitoring During Treatment

Standard-Risk Patients (No Liver Disease History)

• For treatment ≤12 weeks with normal baseline LFTs, routine periodic monitoring is NOT required unless clinical symptoms develop 5
• Monitor only if treatment extends beyond one month or if the patient takes concomitant hepatotoxic medications 5, 6

High-Risk Patients

For patients with heavy alcohol use, prior liver disease, or concurrent hepatotoxic drugs:

• Weekly LFTs for the first 2 weeks, then every 2 weeks for the first 2 months of therapy 6
• If baseline AST/ALT is <2× upper limit of normal (ULN): repeat at 2 weeks; if decreased, further testing only if symptoms develop 6
• If baseline AST/ALT is ≥2× ULN: monitor weekly for 2 weeks, then every 2 weeks until normalized 6

When to Stop Treatment Immediately

Discontinue terbinafine immediately if: 6

• AST/ALT ≥5× ULN or rising bilirubin
• Jaundice or dark urine develops
• Persistent nausea, vomiting, or abdominal pain
• Unexplained fatigue or malaise
• Severe or progressive skin rash

Absolute Contraindications

Active or chronic liver disease is an absolute contraindication to terbinafine. 1, 5

• Lupus erythematosus (absolute contraindication) 1
• Renal impairment with creatinine clearance ≤50 mL/min (terbinafine is primarily cleared by kidneys) 5
• History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome with terbinafine 5, 6

Relative Contraindications

• Mild ALT elevation (1.25× ULN) does NOT preclude therapy but requires close monitoring 6
• Patients with controlled hepatitis B on antiviral therapy can receive terbinafine with heightened monitoring if transaminases are normal 5

Special Populations

Chronic Kidney Disease

For creatinine clearance ≤50 mL/min, terbinafine is contraindicated—use topical therapy instead. 5

• First choice: amorolfine 5% lacquer or ciclopirox 8% lacquer 5
• Second choice (if systemic therapy essential and hepatic function normal): itraconazole with dose adjustment 5

Alcohol Consumption

Patients should avoid alcohol during terbinafine therapy due to hepatotoxic potential. 6

• If alcohol abstinence is not possible, consider topical therapy alone 6
• Itraconazole is not a safer alternative, as it carries similar hepatotoxicity risk 6

Alternative Systemic Therapies

When Terbinafine Fails or Is Contraindicated

Itraconazole is the second-line alternative for dermatophyte onychomycosis. 3, 5

• Continuous regimen: 200 mg daily for 12 weeks 5
• Pulse regimen: 400 mg daily for 1 week per month for 3 cycles (fingernails) or 3-4 cycles (toenails) 3, 5
• Itraconazole is superior to terbinafine for Candida onychomycosis 3, 5

Third-Line Option

• Fluconazole 450 mg weekly for at least 6 months (less effective than terbinafine or itraconazole) 5

Why Terbinafine Is First-Line

Terbinafine is superior to itraconazole for dermatophyte onychomycosis with approximately twice the mycological cure rates (76% vs 38% at 12 weeks) and lower relapse rates (23% vs 53% at 5 years). 3, 7

• Fungicidal against dermatophytes with very low minimum inhibitory concentrations (0.004 μg/mL) 1
• Expected cure rates: 80-90% for fingernails, 70-80% for toenails 3
• Minimal drug-drug interactions compared to azole antifungals 1, 5
• The only significant interaction is with drugs metabolized by cytochrome P450 2D6 (certain antidepressants, beta-blockers, antiarrhythmics) 1

Common Adverse Effects

• Gastrointestinal disturbances (49% of reported side effects): nausea, diarrhea, abdominal pain 5
• Headache 5
• Taste disturbance (rarely permanent—counsel patients before starting) 5, 6
• Dermatological events (23%): rash, pruritus, urticaria 5
• Serious adverse events occur in only 0.04% of patients 1

Treatment Failure Management

If treatment fails after 3-6 months, immediately resume terbinafine without additional waiting period after confirming dermatophyte infection. 1

• Re-evaluate 3-6 months after initial treatment with mycological analysis and clinical examination 1
• Repeat baseline LFTs and CBC before resuming treatment 1
• Consider partial nail removal for subungual dermatophytoma (tightly packed fungal mass preventing drug penetration) 3
• If second terbinafine course fails, switch to itraconazole 1

Critical Pitfalls to Avoid

• Never start systemic therapy without mycological confirmation—this is the most common error 3
• Do not interpret yeast cultures as primary pathogens without careful clinical correlation (usually secondary infection) 3
• Do not interpret non-dermatophyte moulds as causative without confirming they are not saprophytic colonizers of previously damaged nails 3
• Terbinafine is highly effective against Trichophyton species but significantly less effective against Microsporum species—griseofulvin is superior for Microsporum infections 1