What is the recommended treatment for onychomycosis in an adult patient with no severe liver disease, no drug interactions, and who is not pregnant or breastfeeding?

Treatment for Nail Fungal Infection

Terbinafine is the first-line systemic treatment for dermatophyte onychomycosis, with superior efficacy compared to itraconazole and cure rates of 70-80% for toenails and 80-90% for fingernails. 1

Confirm Diagnosis Before Treatment

• Always obtain mycological confirmation (microscopy and culture) before starting treatment to avoid treating non-fungal nail dystrophy, as only about half of nail dystrophies are actually caused by fungus 1, 2, 3
• Dermatophytes cause the vast majority of cases, with Trichophyton rubrum being most common 1, 4
• Yeasts and non-dermatophyte molds should be interpreted carefully—they are often secondary infections or saprophytes in previously damaged nails 1

First-Line Systemic Treatment: Terbinafine

For dermatophyte onychomycosis (the most common type), terbinafine is superior to all other agents both in vitro and in vivo 1

Dosing

• 250 mg daily for 6 weeks for fingernails 1
• 250 mg daily for 12 weeks for toenails 1
• Terbinafine persists in nails for 6 months after treatment completion due to its long half-life 5

Monitoring

• Baseline liver function tests and complete blood count are recommended 1
• Monitor for hepatotoxicity, though idiosyncratic liver reactions are rare 1
• Reversible taste disturbance occurs in approximately 1 in 400 patients 1

Drug Interactions

• Plasma concentrations reduced by rifampicin, increased by cimetidine 1
• Monitor patients taking tricyclic antidepressants, SSRIs, atypical antipsychotics, beta blockers, or tamoxifen for drug-drug interactions 3

Contraindications

• Hepatic impairment 1
• Not recommended during pregnancy or breastfeeding 6
• Use not adequately studied in renal impairment (creatinine clearance ≤50 mL/min) 6

Second-Line Systemic Treatment: Itraconazole

Use itraconazole when terbinafine is contraindicated or not tolerated, or when treating Candida onychomycosis 1, 5

Pulse Dosing Regimen (Preferred)

• 400 mg daily (200 mg twice daily) for 1 week per month 5
• 2 pulses (2 months total) for fingernails 5
• 3 pulses (3 months total) for toenails 5
• Must be taken with food and acidic beverages for optimal absorption 5

Monitoring

• Baseline liver function tests required 5
• Monitor hepatic function tests when receiving continuous therapy for more than one month 5
• Monitor with concomitant use of hepatotoxic drugs including statins 5

Drug Interactions (Critical)

• Contraindicated with terfenadine, astemizole, sertindole, midazolam, cisapride due to enhanced toxicity 1
• Increases levels of warfarin, digoxin, ciclosporin, and simvastatin (increased risk of myopathy) 1, 5
• Caution with statins—may require temporary dose adjustment 5

Contraindications

• Heart failure (negative inotropic effects) 5
• Hepatotoxicity or active liver disease 5
• Pregnancy 1

Third-Line Option: Fluconazole

Consider fluconazole when both terbinafine and itraconazole are contraindicated or not tolerated 1, 5

Dosing

• 150-450 mg once weekly for at least 6 months for toenail infections 5
• 12-16 weeks for fingernails, 18-26 weeks for toenails 1
• Fewer drug interactions with statins compared to itraconazole 5

Monitoring

• Baseline liver function tests and complete blood count 1, 5
• Monitor liver function tests during high-dose or prolonged therapy 1, 5

Topical Therapy

Topical therapy alone is appropriate only for mild-to-moderate onychomycosis with limited nail involvement (<50-65% of nail plate) and no matrix involvement 7

When to Use Topical Therapy

• Patients who cannot tolerate oral therapy due to drug interactions, hepatic impairment, or other contraindications 7
• Very distal infection or superficial white onychomycosis 1
• As adjunct to systemic therapy to enhance cure rates 5

Topical Options

• Efinaconazole 10% solution: Applied daily for 48 weeks, with mycological cure rates approaching 50% and complete cure in 15% 5, 8
• Amorolfine 5% lacquer: Applied once or twice weekly for 6-12 months, with approximately 50% cure rate for distal infections 1, 5
• Ciclopirox 8% lacquer: Applied daily for up to 48 weeks, with 34% mycological cure vs 10% placebo (but only 8% clinical cure) 5

Combination Therapy

Combining systemic and topical antifungals provides antimicrobial synergy, wider antifungal spectrum, increased cure rates, and suppression of resistant mutants 5

• Add topical amorolfine or ciclopirox to systemic therapy for enhanced efficacy 5
• Particularly useful in severe cases or treatment failures 5

Special Considerations for Candida Onychomycosis

Itraconazole is the first-line treatment for Candida onychomycosis, with superior cure rates (92%) compared to terbinafine (40%) 1, 5

• Use pulse regimen: 400 mg daily for 1 week per month 1, 5
• Minimum 2 pulses for fingernails, 3-4 pulses for toenails 1, 5
• Most yeast infections associated with paronychia can be treated topically with imidazole lotion alternating with antibacterial lotion 1

Adjunctive Measures

Nail Debridement

• Nail trimming and debridement used concurrently with pharmacologic therapy improve treatment response 3
• Thick nails may respond poorly to treatment and require mechanical debridement 5
• Subungual dermatophytoma may require mechanical removal before antifungal therapy 5

Footwear Decontamination (Critical for Prevention)

• Discard old contaminated footwear if possible 5
• Decontaminate shoes with naphthalene mothballs sealed in plastic bags for minimum 3 days to kill fungal arthroconidia 5, 7
• Apply antifungal powders inside shoes regularly 5, 7
• Consider periodic spraying of terbinafine solution into shoes 5
• Recurrence rates are 40-70% without preventive measures 7

Other Preventive Measures

• Wear protective footwear in gyms, hotel rooms, and communal bathing facilities 7
• Wear cotton, absorbent socks 7
• Keep nails as short as possible 7
• Avoid sharing nail clippers 5

Monitoring and Follow-Up

• Monitor for at least 48 weeks (preferably 72 weeks) from start of treatment to identify potential relapse 1, 5
• Reevaluate 3-6 months after initiating treatment to assess response 7
• Full nail regrowth takes up to 18 months for toenails—do not discontinue treatment prematurely 7
• Consider culture at end of treatment to confirm mycological clearance, especially in high-risk groups 1
• Mycological cure rates are typically about 30% better than clinical cure rates—successful eradication doesn't always render nails completely normal if they were dystrophic prior to infection 1, 8

Common Pitfalls and Treatment Failure

A consistent failure rate of 20-30% occurs even with optimal terbinafine therapy 1

Causes of Treatment Failure

• Poor compliance 1
• Poor absorption 1
• Immunosuppression 1
• Subungual dermatophytoma preventing drug penetration 1
• Incorrect diagnosis made on clinical grounds alone 8
• Premature discontinuation before full nail regrowth 7

Management of Treatment Failure

• Carefully consider reasons for failure 1
• Consider alternative drug or nail removal combined with further course of therapy to cover period of regrowth 1
• Partial nail avulsion may be indicated for subungual dermatophytoma 1
• Complete nail avulsion prior to treatment can achieve cure rates close to 100%, though this is neither feasible nor necessary in most cases 1

Agents NOT Recommended

Griseofulvin is not recommended as first-line treatment due to lower efficacy (30-40% mycological cure), lengthy treatment duration (12-18 months for toenails), and higher relapse rates 1, 5, 4