What is the recommended treatment for a patient with fingernail onychomycosis?

Treatment of Fingernail Onychomycosis

Oral terbinafine 250 mg once daily for 6 weeks is the first-line treatment for fingernail onychomycosis caused by dermatophytes. 1, 2, 3

Diagnostic Confirmation Required Before Treatment

• Mycological confirmation is mandatory before initiating any antifungal therapy through KOH preparation, fungal culture, or nail biopsy to confirm dermatophyte infection 4, 3
• Treatment should never be started based on clinical appearance alone, as only about half of nail dystrophies are actually caused by fungus 5

First-Line Systemic Therapy: Terbinafine

Dosing and Duration

• Terbinafine 250 mg once daily for 6 weeks is the standard regimen for fingernail infections 1, 2
• Can be taken with or without food, as absorption is not affected by food intake 2
• The drug persists in nails for 6-6 months after treatment completion, allowing continued antifungal activity 2, 6

Why Terbinafine is Superior

• Terbinafine demonstrates fungicidal activity against dermatophytes with very low minimum inhibitory concentrations (approximately 0.004 μg/mL), making it significantly more effective than fungistatic azoles 1, 2
• Complete cure rates of 55% versus 26% for itraconazole at 72 weeks 1
• Long-term mycological cure without retreatment of 46% versus 13% for itraconazole at 5 years 1
• Minimal drug-drug interactions compared to azole antifungals, with only cytochrome P450 2D6 substrates (certain antidepressants, beta-blockers, antiarrhythmics) requiring caution 1, 2

Pre-Treatment Requirements

• Baseline liver function tests (ALT and AST) and complete blood count are required before initiating treatment 2, 6
• Particularly important in patients with history of hepatitis, heavy alcohol use, or hematological abnormalities 2

Absolute Contraindications

• Active or chronic liver disease 2
• Lupus erythematosus 2

Common Adverse Effects

• Gastrointestinal disturbances (nausea, diarrhea, abdominal pain) - most common at 49% of reported side effects 2
• Headache 4, 2
• Taste disturbance 4, 2
• Can aggravate psoriasis and cause subacute lupus-like syndrome 4, 2
• Serious adverse events occur in only 0.04% of patients 2

Second-Line Systemic Therapy: Itraconazole

If terbinafine is contraindicated or not tolerated, itraconazole is the second-line alternative. 4, 1

Dosing Options

• Pulse therapy: 400 mg daily (200 mg twice daily) for 1 week per month for 2 pulses (2 months total) 4, 6
• Continuous therapy: 200 mg daily for 12 weeks 4, 1
• Pulse therapy is more economical and convenient while maintaining equivalent efficacy to continuous dosing 5, 7

Administration Requirements

• Must be taken with food and acidic beverages for optimal absorption 4, 6
• Baseline liver function tests required 6
• Monitor hepatic function tests in patients with pre-existing deranged results, those receiving continuous therapy for more than one month, and with concomitant hepatotoxic drug use 4, 6

Contraindications

• Heart failure (due to negative inotropic effects) 6
• Active liver disease or hepatotoxicity 6

Drug Interaction Cautions

• Significant interactions with statins - concurrent use may increase statin levels, requiring careful monitoring or temporary dose adjustment 6
• More extensive drug interactions than terbinafine due to effects on multiple cytochrome P450 enzymes 1

Third-Line Systemic Therapy: Fluconazole

Fluconazole 150-450 mg once weekly for 3 months can be used when both terbinafine and itraconazole cannot be tolerated. 4, 1

• Lower efficacy than terbinafine and itraconazole but offers convenient once-weekly dosing 1
• Requires dose adjustment in renal impairment 4, 1
• Baseline liver function tests and complete blood count required 4
• Monitor liver function tests during high-dose or prolonged therapy 4, 6

Topical Therapy Options

When to Consider Topical Therapy

• Topical therapy alone is appropriate for mild, superficial, or distal onychomycosis involving less than 50% of the nail plate without matrix involvement 4, 8
• Can be used as adjunct to systemic therapy for enhanced cure rates 6

FDA-Approved Topical Agents

• Efinaconazole 10% solution: Applied daily for 48 weeks, with mycological cure rates approaching 50% and complete cure in 15% 6, 9
• Tavaborole 5% solution: Applied daily 9
• Ciclopirox 8% lacquer: Applied once daily for up to 48 weeks, showing 34% mycological cure versus 10% with placebo, but clinical cure only 8% versus 1% 6, 8
• Amorolfine 5% lacquer (approved in Europe): Applied once or twice weekly for 6-12 months 4, 6

Important Limitation

• Topical agents should not be used concomitantly with systemic antifungals, as no studies have determined whether topical therapy might reduce the effectiveness of systemic agents 8

Combination Therapy Strategy

Combining systemic and topical antifungals provides superior outcomes through antimicrobial synergy, wider antifungal spectrum, improved fungicidal activity, increased cure rates, and suppression of resistant mutants. 6

• Particularly beneficial when response to monotherapy is likely to be poor 4
• Consider adding amorolfine 5% lacquer (once or twice weekly) or ciclopirox 8% lacquer (once daily) to systemic terbinafine 6

Follow-Up and Monitoring

• Re-evaluate patients 3-6 months after treatment initiation 1, 2
• If disease persists at 3-6 months, additional treatment can be started immediately without waiting period 2, 6
• Assessment should include both clinical improvement and mycological cure (negative microscopy and culture) 4, 6
• Follow-up period of at least 48 weeks from start of treatment is ideal to identify potential relapse 4, 6

Treatment Failure Management

If First Course of Terbinafine Fails

• Confirm the infection is due to dermatophytes (terbinafine is less effective against Candida) 6
• Repeat pre-treatment checks (liver function tests and complete blood count) 6
• Can immediately resume terbinafine 250 mg daily for another 6 weeks without additional waiting period 6

If Second Course Fails

• Switch to itraconazole as second-line alternative: 200 mg daily for 12 weeks or 400 mg daily for 1 week per month for 2 pulses 6
• Consider fluconazole 450 mg weekly for at least 6 months if intolerance to both terbinafine and itraconazole 6

Special Considerations for Candida Onychomycosis

If mycological testing confirms Candida species (rather than dermatophytes), itraconazole becomes the first-line treatment. 4, 6

• Itraconazole 400 mg daily for 1 week per month for 2 months (2 pulses) for fingernail Candida infection 4, 6
• Itraconazole has superior cure rate of 92% versus 40% for terbinafine in Candida infections 6
• Most yeast infections with paronychia can be treated topically with imidazole lotion alternating with antibacterial lotion 4

Prevention of Recurrence

Onychomycosis has high reinfection and recurrence rates, requiring preventive measures. 10, 9

• Decontaminate or replace contaminated footwear - place naphthalene mothballs in shoes and seal in plastic bags for minimum 3 days 6
• Apply antifungal powders inside shoes regularly 6
• Consider periodic spraying of terbinafine solution into shoes 6
• Keep nails short and clean 6
• Avoid sharing nail clippers 6

Common Pitfalls to Avoid

• Never start treatment without mycological confirmation - this leads to unnecessary treatment of non-fungal nail dystrophies 4, 5
• Do not use griseofulvin as first-line therapy - it has lower efficacy (30-40% mycological cure), requires 12-18 months of treatment, and has higher relapse rates 6
• Avoid combining topical and systemic therapy without evidence of benefit - the FDA label for ciclopirox specifically states concomitant use with systemic antifungals is not recommended 8
• Do not prescribe itraconazole to patients with heart failure - it has negative inotropic effects 6
• Monitor for drug interactions with itraconazole and statins - concurrent use significantly increases statin levels 6