What is the recommended terbinafine dosing, monitoring, and alternative therapy for an adult with confirmed toenail onychomycosis, including pediatric weight‑based dosing and contraindications?

Terbinafine Dosing for Toenail Onychomycosis

For confirmed toenail onychomycosis in adults, prescribe terbinafine 250 mg once daily for 12 weeks, with baseline liver function tests and complete blood count required before initiating therapy. 1

Standard Adult Dosing

• Terbinafine 250 mg once daily for 12 weeks is the first-line treatment for dermatophyte toenail onychomycosis, achieving mycologic cure rates of 70-80% 1, 2
• Treatment duration may be extended to 16 weeks for severe infections with extensive nail involvement 1
• The drug persists in nails for 6 months after treatment completion due to its lipophilic properties and long half-life, allowing continued fungicidal activity 2, 3
• Terbinafine demonstrates superior efficacy compared to itraconazole, fluconazole, and griseofulvin, with approximately twice the mycologic cure rates of itraconazole (76% vs 38% at 72 weeks) 4

Pediatric Weight-Based Dosing

For children aged 1-12 years with toenail onychomycosis 1:

• <20 kg body weight: 62.5 mg daily for 12 weeks
• 20-40 kg body weight: 125 mg daily for 12 weeks
• >40 kg body weight: 250 mg daily for 12 weeks (adult dose)

Note that terbinafine is not FDA-approved for pediatric onychomycosis, though it is licensed for use in children in some jurisdictions 3

Mandatory Pre-Treatment Monitoring

Before initiating terbinafine, obtain: 1, 2

• Liver function tests (ALT and AST)
• Complete blood count

Ongoing monitoring is required if: 1, 3

• History of hepatitis or liver disease
• Heavy alcohol use
• Concomitant hepatotoxic medications
• Pre-existing deranged liver function tests

Absolute Contraindications

Terbinafine is contraindicated in: 2, 3

• Active or chronic liver disease
• Lupus erythematosus
• Significant hepatic impairment

Alternative Systemic Therapies

Second-Line: Itraconazole

Use when terbinafine is contraindicated or not tolerated 1, 2:

• Continuous dosing: 200 mg daily for 12 weeks
• Pulse therapy: 400 mg daily for 1 week per month for 3 cycles (total 3 months)
• Must be taken with food and acidic beverages for optimal absorption 1
• Contraindicated in heart failure due to negative inotropic effects 1
• Significant drug interactions with statins, warfarin, digoxin, ciclosporin, and simvastatin 2
• Baseline and ongoing hepatic function monitoring required 1

Third-Line: Fluconazole

Reserved for patients intolerant to both terbinafine and itraconazole 1, 2:

• Dosing: 150-450 mg once weekly for at least 6 months
• Baseline liver function tests and complete blood count required 1
• Monitor liver function during high-dose or prolonged therapy 1
• Fewer drug interactions with statins compared to itraconazole 2

Common Adverse Effects of Terbinafine

1, 3, 4:

• Gastrointestinal complaints (most common): nausea, diarrhea, abdominal pain
• Headache
• Taste disturbance (reversible, occurs in ~1 in 400 patients)
• Can aggravate psoriasis
• Subacute lupus-like syndrome
• Rare but serious: Stevens-Johnson syndrome and toxic epidermal necrolysis

Drug Interactions

Terbinafine has minimal drug-drug interactions compared to azole antifungals, making it safer for patients on multiple medications 2, 3:

• Rifampicin reduces terbinafine plasma levels 2
• Cimetidine increases terbinafine plasma levels 2
• Potential interaction with drugs metabolized by cytochrome P450 2D6 (certain antidepressants, beta-blockers, antiarrhythmics) 3

Treatment Monitoring and Follow-Up

• Re-evaluate at 3-6 months after treatment initiation to assess response 2, 5
• Monitor for at least 48 weeks (preferably 72 weeks) from treatment start to detect relapse 2
• End-of-therapy culture is recommended to confirm mycological clearance 2
• Mycologic cure rates are typically ~30% higher than clinical cure rates; complete nail normalization may lag behind fungal eradication 2

Management of Treatment Failure

Even with optimal terbinafine therapy, a consistent failure rate of 20-30% occurs 2:

• Reassess adherence and confirm diagnosis with repeat mycology 2
• Consider alternative systemic agents (itraconazole or fluconazole) 2
• Evaluate for subungual dermatophytoma, which may require mechanical removal before retreatment 2
• If therapeutic failure is confirmed at 3-6 months, immediately resume treatment without additional waiting period 3

Adjunctive Topical Therapy

Combination of systemic and topical therapy enhances cure rates through antimicrobial synergy 2, 5:

• Amorolfine 5% lacquer: Apply once or twice weekly for 6-12 months 1
• Ciclopirox 8% lacquer: Apply once daily for up to 48 weeks 1
• Topical therapy provides wider antifungal spectrum and suppresses resistant mutants 2

Critical Clinical Caveats

• Confirm diagnosis with mycology (microscopy and culture) before initiating therapy, as only ~50% of nail dystrophies are fungal 2
• Terbinafine is superior for dermatophyte infections but significantly less effective against Candida (40% cure rate vs 92% with itraconazole) 2
• For Candida onychomycosis, itraconazole is the preferred agent 1, 2
• Continuous daily dosing is superior to intermittent/pulse dosing with terbinafine 6
• Decontaminate or replace footwear to prevent reinfection using naphthalene mothballs sealed in plastic bags for minimum 3 days 2