What is the appropriate terbinafine regimen, monitoring, and contraindications for treating a healthy adult with confirmed toenail onychomycosis?

Terbinafine for Toenail Onychomycosis

Terbinafine 250 mg once daily for 12 weeks is the first-line treatment for confirmed dermatophyte toenail onychomycosis in healthy adults, with baseline liver function tests and complete blood count required before initiation. 1, 2, 3, 4

Standard Dosing Regimen

• Terbinafine 250 mg orally once daily for 12 weeks is the evidence-based regimen for toenail onychomycosis, achieving mycologic cure rates of 70–80% 2, 3, 4
• For severe infections with extensive nail involvement, extend treatment to 16 weeks 2, 3
• The drug can be taken with or without food, as absorption is unaffected 3
• Optimal clinical effect appears months after treatment cessation due to the time required for healthy nail outgrowth 4
• Terbinafine persists in nails for 6 months post-treatment due to its long half-life and lipophilic properties, providing continued fungicidal activity 2, 3

Pre-Treatment Requirements

Mandatory baseline testing includes: 1, 2, 3, 4

• Mycological confirmation (KOH preparation, fungal culture, or nail biopsy) to confirm dermatophyte infection—only 50% of nail dystrophies are fungal 2, 4
• Liver function tests (ALT and AST) 1, 2, 3, 4
• Complete blood count 1, 2, 3

The FDA label explicitly requires nail specimens for laboratory confirmation before initiating treatment 4. This step is critical because terbinafine has markedly inferior efficacy against Candida onychomycosis (40% cure rate) compared to dermatophytes (70–80%), making organism identification essential 2.

Monitoring During Treatment

For Low-Risk Patients (No Liver Disease History)

• No routine repeat LFTs are required during the standard 12-week toenail treatment course unless clinical symptoms develop 1
• Baseline normal liver tests in patients without risk factors do not require periodic monitoring for treatment ≤12 weeks 1

For High-Risk Patients

High-risk features include: 1

• History of hepatitis or liver disease
• Heavy alcohol consumption
• Concurrent hepatotoxic medications
• Pre-existing abnormal liver enzymes

For these patients, implement intensive monitoring: 1

• Weekly LFTs for the first 2 weeks
• Every 2 weeks for the first 2 months of therapy
• If baseline AST/ALT is <2× upper limit of normal (ULN), repeat at 2 weeks; if decreased, further testing only if symptoms develop 1
• If baseline AST/ALT ≥2× ULN, monitor weekly for 2 weeks, then every 2 weeks until normalization 1

Immediate Discontinuation Criteria

Stop terbinafine immediately if: 1, 4

• AST/ALT ≥5× ULN
• Rising bilirubin during treatment
• Symptoms of hepatotoxicity: persistent nausea, vomiting, right upper abdominal pain, jaundice, dark urine, pale stools, unexplained fatigue 1, 4
• Progressive skin rash (Stevens-Johnson syndrome or toxic epidermal necrolysis risk) 1, 3

The FDA label warns that liver failure leading to transplant or death has occurred with terbinafine, though rarely 4.

Absolute Contraindications

• Active or chronic liver disease 1, 3, 4
• Renal impairment with creatinine clearance ≤50 mL/min—terbinafine is primarily renally cleared and explicitly contraindicated, not dose-adjustable 1
• History of allergic reaction to oral terbinafine (anaphylaxis risk) 4
• Lupus erythematosus 3

Common Adverse Effects

• Gastrointestinal disturbances (49% of reported side effects): nausea, diarrhea, abdominal pain 1, 5
• Dermatological events (23%): rash, pruritus, urticaria 1
• Taste disturbance (≈1 in 400 patients)—can be severe, prolonged (>1 year), or permanent; discontinue if occurs 1, 4
• Smell disturbance—may be prolonged or permanent 4
• Headache 1, 3
• Transient lymphocyte count decreases 4

Rare but serious: Stevens-Johnson syndrome, toxic epidermal necrolysis, subacute lupus-like syndrome, psoriasis aggravation 1, 3

Drug Interactions

Terbinafine has minimal drug interactions compared to azole antifungals, making it safer for patients on multiple medications 2, 3. The only clinically significant interactions involve: 1, 3

• Rifampicin (decreases terbinafine levels)
• Cimetidine (increases terbinafine levels)
• CYP2D6-metabolized drugs (certain antidepressants, beta-blockers, antiarrhythmics)—monitor but rarely requires dose adjustment

Notably, terbinafine can be safely used with corticosteroids without dose adjustment 3.

Why Terbinafine is First-Line

• Superior efficacy: The landmark L.I.ON. study demonstrated mycologic cure rates of 76% (12 weeks) and 81% (16 weeks) with terbinafine versus 38% and 49% with itraconazole at 72 weeks 5
• Lower relapse rates: 5-year follow-up showed 23% mycologic relapse with terbinafine versus 53% with itraconazole 5
• Fungicidal activity against dermatophytes with very low minimum inhibitory concentrations (0.004 μg/mL) 2, 5
• Shorter treatment duration than alternatives 5, 6
• Fewer drug interactions than azoles 3, 5
• Better cost-effectiveness than itraconazole, fluconazole, or griseofulvin 5, 6

Alternative Agents (When Terbinafine is Contraindicated)

Second-Line: Itraconazole

• Continuous dosing: 200 mg daily for 12 weeks 2
• Pulse dosing: 400 mg daily (200 mg twice daily) for 1 week per month × 3 cycles 2
• Must be taken with food and acidic beverages for absorption 2
• Contraindicated in heart failure (negative inotropic effects) 2
• Requires baseline and periodic hepatic monitoring 2
• Multiple drug interactions with warfarin, digoxin, ciclosporin, statins 2

Third-Line: Fluconazole

• Dosing: 150–450 mg once weekly for minimum 6 months 2
• Requires baseline LFTs and CBC, with monitoring during prolonged therapy 2
• Fewer drug interactions than itraconazole but less effective than terbinafine 2

Topical Therapy (Adjunct or Mild Disease)

• Amorolfine 5% lacquer: once or twice weekly for 6–12 months 2
• Ciclopirox 8% lacquer: once daily for up to 48 weeks 2
• Combination topical + systemic therapy enhances cure rates 2

Reinfection Prevention

• Decontaminate or discard old footwear 2
• Place naphthalene mothballs in shoes, seal in plastic bags for minimum 3 days 2
• Apply antifungal powders inside shoes regularly 2
• Keep nails short and clean 2
• Wear cotton absorbent socks 2

Follow-Up and Treatment Failure

• Monitor for at least 48 weeks (preferably 72 weeks) from treatment start to detect relapse 2
• Assess both clinical improvement and mycological cure (negative microscopy and culture) 2
• If treatment fails after 3–6 months, repeat mycological testing and consider: 2, 3
  • Immediate resumption of terbinafine (no waiting period required) if dermatophyte confirmed 3
  • Switch to itraconazole if second terbinafine course fails 3
  • Evaluate for subungual dermatophytoma (may require mechanical debridement) 2
  • Confirm patient adherence 2

Even with optimal therapy, a consistent 20–30% failure rate occurs with terbinafine 2.