How should I treat onychomycosis in an adult with oral terbinafine, including dose, duration, monitoring, contraindications, and alternatives?

Treatment of Onychomycosis with Oral Terbinafine

Terbinafine 250 mg once daily for 12 weeks is the first-line treatment for dermatophyte toenail onychomycosis in adults, achieving mycological cure rates of 70-80% and demonstrating superior efficacy compared to all other oral antifungal agents. 1

Dosing Regimen

Standard Adult Dosing

• Toenail infections: 250 mg once daily for 12 weeks 1
• Fingernail infections: 250 mg once daily for 6 weeks 1
• Severe infections with extensive nail involvement: Consider extending treatment to 16 weeks 1

Continuous vs. Pulse Therapy

• Continuous daily dosing is superior to intermittent pulse regimens and should be used preferentially 1
• While pulse therapy (500 mg daily for 1 week per month) has been studied, continuous therapy yields better outcomes 2

Pre-Treatment Requirements

Mycological Confirmation

• Always obtain microscopy and culture before initiating systemic therapy, as only approximately 50% of nail dystrophies are fungal in origin 1
• Dermatophytes (particularly Trichophyton rubrum) cause the vast majority of onychomycosis cases 1

Baseline Laboratory Monitoring

• Obtain baseline liver function tests (ALT, AST) and complete blood count before starting therapy 1
• Baseline monitoring is particularly important in patients with: 1
  • History of heavy alcohol consumption
  • Prior hepatitis or known liver disease
  • Pre-existing abnormal liver enzymes
  • Concurrent hepatotoxic medications

Ongoing Monitoring

Routine Monitoring Strategy

• For low-risk patients with normal baseline tests, routine periodic liver function monitoring is NOT required during the standard 12-week treatment course unless clinical symptoms develop 3
• Monitor hepatic function tests if treatment extends beyond one month or in high-risk patients 3
• Discontinue terbinafine immediately if biochemical evidence of liver injury or clinical symptoms of hepatotoxicity develop 3

High-Risk Patient Monitoring

• Patients with pre-existing liver disease, heavy alcohol use, or concurrent hepatotoxic medications require closer monitoring throughout therapy 3

Contraindications and Special Populations

Absolute Contraindications

• Significant hepatic impairment 1
• Renal impairment with creatinine clearance ≤50 mL/min (terbinafine is primarily cleared by the kidneys) 3

Patients with Chronic Kidney Disease

• Terbinafine is contraindicated when CrCl ≤50 mL/min 3
• Alternative approach: Use topical therapy (amorolfine 5% lacquer once or twice weekly for 6-12 months, or ciclopirox 8% lacquer once daily for up to 48 weeks) 3
• If systemic therapy is absolutely necessary and hepatic function is normal, consider itraconazole with appropriate dose adjustment 3

Patients with Controlled Hepatitis B

• Terbinafine remains first-line in patients with virologically suppressed hepatitis B and normal transaminases, provided baseline liver function tests are normal and patients are counseled about heightened hepatotoxicity risk 3

Safety Profile and Adverse Effects

Common Adverse Effects

• Gastrointestinal disturbances (nausea, diarrhea) occur in approximately 49% of reported side effects 3
• Dermatological events (rash, pruritus, urticaria) occur in 23% of cases 3
• Reversible taste disturbance occurs in approximately 1 in 400 patients 1
• Headache 1

Rare but Serious Adverse Effects

• Idiosyncratic hepatotoxicity (rare but potentially severe) 1
• Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare) 3
• Subacute lupus-like syndrome 1
• Aggravation of psoriasis 1
• Very rare permanent taste disturbance 3

Drug Interactions

Clinically Significant Interactions

• Rifampicin reduces terbinafine plasma levels 1
• Cimetidine increases terbinafine levels 1
• Potential interactions with drugs metabolized by CYP2D6 (certain antidepressants, β-blockers, antiarrhythmics) 1
• Terbinafine has relatively few drug interactions compared to azole antifungals, making it preferable in patients on multiple medications 4

Second-Line Systemic Alternatives

Itraconazole

• Indicated when terbinafine is contraindicated, not tolerated, or for Candida onychomycosis 1
• Continuous dosing: 200 mg daily for 12 weeks 1
• Pulse dosing: 400 mg daily for 1 week per month for 3 cycles (toenails) or 2 cycles (fingernails) 1
• Must be taken with food and acidic beverages for optimal absorption 1
• Contraindicated in heart failure due to negative inotropic effects 1
• Critical drug interactions: Contraindicated with terfenadine, astemizole, cisapride, midazolam; increases levels of warfarin, digoxin, ciclosporin, and simvastatin (increasing myopathy risk) 1
• Baseline and periodic hepatic function monitoring required 1

Fluconazole

• Third-line option when both terbinafine and itraconazole are unsuitable 1
• Dosing: 150-450 mg once weekly for minimum 6 months (toenails) or 12-16 weeks (fingernails) 1
• Requires 50% dose reduction when GFR <45 mL/min 3
• Baseline liver function tests and complete blood count required, with repeat testing during high-dose or prolonged therapy 1

Griseofulvin

• NOT recommended as first-line due to low mycological cure rates (30-40%), prolonged treatment duration (12-18 months for toenails), and higher relapse rates 1

Adjunctive Topical Therapy

Combination Approach

• Adding topical antifungals to systemic therapy enhances cure rates through antimicrobial synergy and broader antifungal spectrum 1
• 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

Special Consideration: Candida Onychomycosis

Treatment Selection Based on Organism

• Terbinafine is markedly less effective against Candida (approximately 40% cure rate) compared to dermatophytes 1
• Itraconazole is preferred for Candida nail infections, achieving 92% cure rates versus 40% with terbinafine 1
• Differentiate Candida paronychia (nail fold infection) from true Candida onychomycosis (nail plate invasion), as treatment approaches differ 1

Treatment Failure and Management

Expected Failure Rates

• Even with optimal terbinafine therapy, a consistent failure rate of 20-30% occurs in all studies 5, 1

Common Causes of Treatment Failure

• Poor patient compliance 1
• Inadequate drug absorption 1
• Immunosuppression 1
• Subungual dermatophytoma (tightly packed fungal mass preventing drug penetration) 5
• Zero nail growth 5

Management of Treatment Failure

• Reassess adherence and confirm diagnosis with repeat mycological testing 1
• Consider partial nail avulsion for subungual dermatophytoma before retreatment 5, 1
• Switch to alternative systemic agent (itraconazole or fluconazole) 1
• Complete nail avulsion can achieve near-100% cure rates in selected refractory cases 1

Follow-Up and Outcome Assessment

Monitoring Timeline

• Follow patients for at least 48 weeks (preferably 72 weeks) from treatment initiation to detect relapse 1
• End-of-therapy culture is recommended, especially in high-risk groups, to confirm mycological clearance 1

Expected Outcomes

• Mycological cure rates are typically ~30% higher than clinical cure rates, as complete nail normalization may lag behind fungal eradication 1
• Terbinafine persists in nails for up to 30 weeks after treatment completion due to its long half-life 1

Preventive Measures to Reduce Recurrence

Footwear Decontamination

• Decontaminate or replace contaminated footwear to eliminate fungal reservoirs 1
• Place naphthalene mothballs in shoes and seal in plastic bags for minimum 3 days 1
• Apply antifungal powders inside shoes regularly 1
• Consider periodic spraying of terbinafine solution into shoes 1

General Hygiene Measures

• Keep nails short and clean 1
• Wear cotton absorbent socks 1
• Use antifungal powders on feet 1
• Avoid sharing nail clippers 1

Comparative Efficacy Data

Terbinafine vs. Itraconazole

• At 72 weeks follow-up, terbinafine demonstrates approximately twice the mycological cure rate (76% vs 38% after 12 weeks; 81% vs 49% after 16 weeks) compared to itraconazole pulse therapy 4
• At 5-year follow-up, terbinafine maintains superior outcomes: complete cure 35% vs 14%, mycological cure 46% vs 13%, clinical cure 42% vs 18% 4
• Relapse rates are lower with terbinafine: mycological relapse 23% vs 53%, clinical relapse 21% vs 48% 4

Cost-Effectiveness

• Terbinafine's greater clinical effectiveness translates into superior cost-effectiveness compared to itraconazole, fluconazole, and griseofulvin 4, 6