How should I diagnose and treat onychomycosis in a healthy adult, including first‑line oral therapy, dosing, duration, monitoring, and alternatives?

Diagnosis and Treatment of Onychomycosis in Healthy Adults

Diagnostic Confirmation Before Treatment

Always obtain mycological confirmation before initiating systemic antifungal therapy—only about 50% of nail dystrophies are actually fungal infections. 1

• Perform potassium hydroxide (KOH) preparation, fungal culture, or nail biopsy to confirm the diagnosis before prescribing oral antifungals 2, 1
• Culture is essential to identify the specific pathogen (dermatophyte vs. yeast vs. non-dermatophyte mold) because treatment selection depends on the organism 1, 3
• Dermatophytes (especially Trichophyton rubrum) cause the vast majority of onychomycosis cases 4, 5

First-Line Oral Therapy: Terbinafine

Oral terbinafine 250 mg once daily is the first-line systemic treatment for dermatophyte onychomycosis, demonstrating superior efficacy compared to all other agents with cure rates of 70–80% for toenails and 80–90% for fingernails. 1, 6

Dosing and Duration

• Fingernail onychomycosis: 250 mg once daily for 6 weeks 2, 6
• Toenail onychomycosis: 250 mg once daily for 12 weeks (may extend to 16 weeks in severe cases with extensive nail involvement) 2, 4
• The tablet may be taken with or without food 6
• Optimal clinical effect appears months after treatment completion due to the time required for healthy nail outgrowth 2

Pre-Treatment Assessment and Monitoring

• Obtain baseline liver function tests (ALT, AST) and complete blood count before starting therapy 2, 1, 6
• Ongoing hepatic monitoring is required only if pre-existing liver dysfunction exists, if the patient has heavy alcohol use, takes concurrent hepatotoxic medications, or develops symptoms suggesting hepatotoxicity 4, 2
• In patients with known or suspected immunodeficiency, consider monitoring complete blood counts if treatment exceeds 6 weeks 2
• Clinical reassessment should occur 3–6 months after therapy initiation 6
• Follow patients for at least 48 weeks from treatment start to detect relapses 1, 4

Contraindications

• Active or chronic liver disease 2, 6
• Systemic lupus erythematosus 6
• History of allergic reaction to oral terbinafine (risk of anaphylaxis) 2

Common Adverse Effects

• Gastrointestinal symptoms (nausea, diarrhea, abdominal pain) occur in approximately 49% of patients 6
• Headache is frequent 6
• Taste disturbance occurs in approximately 1 in 400 patients and can be permanent; if taste alteration develops, discontinue terbinafine immediately 2, 1
• Smell disturbance, including loss of smell, may be prolonged or permanent; discontinue if this occurs 2

Rare but Serious Adverse Events

• Hepatotoxicity leading to liver failure, transplant, or death has been reported 2
• Stevens-Johnson syndrome and toxic epidermal necrolysis 6
• Subacute lupus-like syndrome and exacerbation of psoriasis 1, 6
• Severe neutropenia (reversible upon discontinuation) 2
• Depressive symptoms 2

Instruct patients to report immediately any persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools—these require immediate discontinuation and hepatic evaluation. 2

Drug Interactions

• Rifampicin decreases terbinafine plasma levels 4
• Cimetidine increases terbinafine levels 4
• Potential interactions with drugs metabolized by CYP2D6 (certain antidepressants, β-blockers, antiarrhythmics) 4

Second-Line Oral Therapy: Itraconazole

Itraconazole is indicated when terbinafine is contraindicated, not tolerated, or when treating Candida onychomycosis (where it achieves 92% cure rates vs. 40% with terbinafine). 1, 4

Dosing Regimens

• Pulse therapy (preferred): 400 mg daily (200 mg twice daily) for 1 week per month 1, 4
  • Fingernails: 2 pulses (2 months total) 1, 4
  • Toenails: 3 pulses (3 months total) 1, 4
• Continuous therapy: 200 mg daily for 12 weeks 4
• Must be taken with food and acidic beverages for optimal absorption 4, 1

Monitoring Requirements

• Baseline liver function tests before initiation 4
• Monitor hepatic function in patients with pre-existing liver abnormalities or when continuous therapy exceeds one month 1, 4
• Monitor hepatic function with concomitant use of hepatotoxic drugs including statins 4

Contraindications and Critical Drug Interactions

• Contraindicated in heart failure due to negative inotropic effects 4
• Contraindicated in pregnancy 4
• Contraindicated with: terfenadine, astemizole, sertindole, midazolam, cisapride (enhanced toxicity) 4
• Markedly increases levels of: warfarin, digoxin, ciclosporin, simvastatin (increasing myopathy risk) 4
• Exercise caution with statins; temporary dose adjustment may be necessary 4

Third-Line Oral Therapy: Fluconazole

Fluconazole is reserved for cases where both terbinafine and itraconazole are unsuitable; it is less effective than first-line agents. 6, 1

Dosing and Duration

• 150–450 mg once weekly for a minimum of 6 months 4, 6
• Fingernails: 12–16 weeks 1, 4
• Toenails: 18–26 weeks 1, 4

Monitoring

• Baseline liver function tests and complete blood count 4
• Continued hepatic monitoring during high-dose or prolonged therapy 4

Adjunctive Topical Therapy

Combining systemic therapy with topical antifungal lacquers enhances cure rates through antimicrobial synergy and broader antifungal spectrum. 4

• Amorolfine 5% lacquer: Apply once or twice weekly for 6–12 months 4, 1
• Ciclopirox 8% lacquer: Apply once daily for up to 48 weeks 4, 1
• Topical agents alone are generally insufficient for nail plate infections and should not be used as monotherapy except in very distal or superficial white onychomycosis 1, 7

Special Considerations for Candida Onychomycosis

Itraconazole is the first-line agent for Candida nail infections, not terbinafine. 4, 6

• For Candida paronychia (nail fold infection without plate invasion): topical imidazole (clotrimazole or miconazole) applied until cuticle integrity is restored 1, 4
• For Candida onychomycosis (nail plate invasion): itraconazole pulse therapy 400 mg daily for 1 week per month for 2 months (fingernails) or 3–4 months (toenails) 1, 4

Treatment Failure Management

Even with optimal terbinafine therapy, a consistent failure rate of 20–30% occurs. 1

Common Causes of Failure

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

Management Strategies

• Reassess adherence and confirm diagnosis 4
• Consider partial nail avulsion for subungual dermatophytoma before retreatment 1
• Switch to an alternative systemic agent 1
• Complete nail avulsion can achieve near-100% cure rates in selected refractory cases 1

Prevention and Recurrence Reduction

• Decontaminate footwear by placing naphthalene mothballs in shoes and sealing in plastic bags for minimum 3 days 4
• Apply antifungal powders inside shoes regularly 4
• Consider periodic spraying of terbinafine solution into shoes 4
• Treat all infected family members simultaneously, as household transmission is common 7, 4
• Wear protective footwear in public pools and locker rooms 7
• Keep nails short and clean 4

Agents NOT Recommended as First-Line

Griseofulvin is no longer recommended as first-line therapy due to low mycological cure rates (30–40%), prolonged treatment duration (12–18 months for toenails), and higher relapse rates. 1, 4, 6

Critical Clinical Pitfalls

• Never initiate systemic antifungal therapy without mycological confirmation—this prevents unnecessary treatment of psoriasis, lichen planus, and other non-fungal nail dystrophies 1, 4
• Do not use terbinafine for Candida infections—it has only 40% efficacy vs. 92% with itraconazole 4
• Premature discontinuation leads to treatment failure—complete the full prescribed course even if nails appear improved 4
• Mycological cure rates are typically 30% higher than clinical cure rates—complete nail normalization lags behind fungal eradication 4
• Yeasts and non-dermatophyte molds are often secondary colonizers in previously damaged nails rather than primary pathogens 1, 4