For a healthy adult with confirmed dermatophyte onychomycosis, what is the recommended first‑line oral terbinafine regimen, baseline liver function testing, monitoring, contraindications, and alternative therapies?

Terbinafine for Onychomycosis

First-Line Oral Regimen

For confirmed dermatophyte onychomycosis in healthy adults, prescribe terbinafine 250 mg once daily for 6 weeks for fingernail infections and 12 weeks for toenail infections (extending to 16 weeks for severe toenail cases). 1, 2

• Terbinafine is designated as first-line therapy with strength of recommendation A and level of evidence 1+ by the British Association of Dermatologists, demonstrating superior efficacy over all alternatives. 1, 2

• The drug achieves mycological cure rates of 76–82% for toenails and 80–90% for fingernails, significantly outperforming itraconazole (complete cure 55% vs 26% at 72 weeks). 2, 3, 4

• Long-term data show sustained mycological cure of 46% with terbinafine versus only 13% with itraconazole at 5-year follow-up, with lower relapse rates (23% vs 53%). 5, 3

Pre-Treatment Requirements

Obtain baseline liver function tests (ALT, AST) and complete blood count before initiating therapy in all patients. 1, 2

• These laboratory tests are mandatory even in patients without known liver disease, as hepatotoxicity can occur de novo. 2

• Mycological confirmation through KOH preparation, fungal culture, or nail biopsy should be obtained to confirm dermatophyte infection before starting treatment. 2

Absolute Contraindications

Do not prescribe terbinafine in patients with active or chronic liver disease or lupus erythematosus. 1, 2

• These are absolute contraindications that preclude terbinafine use entirely. 1

Monitoring During Treatment

Routine monitoring of liver function during treatment is not required in patients with normal baseline values and no risk factors. 1

• However, monitor liver function tests if the patient has a history of hepatitis, heavy alcohol use, or develops symptoms suggestive of hepatotoxicity (nausea, jaundice, dark urine, right upper quadrant pain). 1

• Re-evaluate clinical response at 3–6 months after treatment initiation; if disease persists, consider additional treatment without waiting. 1, 2

• Continue follow-up for at least 48 weeks from treatment start to identify potential relapse. 5

Common Adverse Effects (Counseling Points)

• Gastrointestinal complaints (most common): nausea, diarrhea, abdominal pain occur in approximately 49% of reported side effects. 1

• Headache is frequently reported. 5, 1

• Taste disturbance (dysgeusia) can occur and may be permanent in rare cases. 5

• Dermatologic reactions: rash, pruritus, urticaria. 5

• Rare but serious: Stevens-Johnson syndrome, toxic epidermal necrolysis, subacute lupus-like syndrome, and psoriasis exacerbation have been reported. 5, 1

• The overall incidence of serious adverse events is only 0.04%. 1

Drug Interaction Profile

Terbinafine has minimal drug-drug interactions compared to azole antifungals, making it safer for patients on multiple medications. 1, 2

• The only potentially significant interaction involves drugs metabolized by cytochrome P450 2D6 (certain antidepressants, beta-blockers, antiarrhythmics). 1

• This favorable interaction profile is a key advantage over itraconazole and fluconazole. 1

Practical Administration

• Terbinafine can be taken with or without food, as absorption is not affected by food intake. 1

• The drug persists in nails for up to 6 months after treatment completion due to its long half-life and lipophilic properties, allowing continued fungicidal activity. 1

Alternative First-Line Therapy

If terbinafine is contraindicated or not tolerated, use itraconazole pulse therapy: 400 mg daily for 1 week per month for 2 pulses (fingernails) or 3 pulses (toenails). 5, 2

• Itraconazole must be taken with food and acidic beverages for optimal absorption. 5, 2

• Monitor hepatic function in patients with pre-existing liver abnormalities or when continuous therapy exceeds one month. 5

• Itraconazole is contraindicated in active liver disease. 2

Second-Line Options (When Both Terbinafine and Itraconazole Fail)

Fluconazole 450 mg once weekly for 18–26 weeks (toenails) or 12–16 weeks (fingernails) is reserved for cases where both first-line agents are unsuitable. 5, 2

• Requires baseline liver function tests and complete blood count. 5

• Less effective than first-line agents. 2

Griseofulvin should not be used as first-line therapy due to low efficacy (30–40% cure rate), prolonged treatment requirements, and high relapse rates. 5

Management of Treatment Failure

If treatment fails at 3–6 months, identify the cause before retreating: 2

• Poor compliance or absorption
• Immunosuppression
• Subungual dermatophytoma (fungal ball requiring debridement)
• Zero nail growth

Retreatment options include repeating the terbinafine course immediately (no waiting period required) or switching to itraconazole. 1, 2

Adjunctive Measures to Prevent Reinfection

• Footwear decontamination is essential: apply antifungal powders inside shoes regularly, use naphthalene mothballs, or discard old contaminated footwear. 5, 2

• Wear protective footwear (sandals, water shoes) in public pools and locker rooms. 5

• Keep nails short and clean. 5

• Avoid sharing nail clippers with infected family members. 5

• Screen and treat all household members for onychomycosis and tinea pedis simultaneously to reduce recurrence risk. 5

Key Clinical Pitfalls

• Do not treat without mycological confirmation, as non-fungal nail dystrophies will not respond and expose patients to unnecessary drug risks. 5

• Do not use terbinafine for Candida onychomycosis—itraconazole is preferred due to broader antimicrobial coverage. 1

• Do not assume treatment failure at 12 weeks—terbinafine continues to work for months after completion due to prolonged nail concentrations. 1

• Do not overlook renal impairment—terbinafine clearance decreases with severe kidney disease and may require dose adjustment. 2