Onychomycosis Treatment
First-Line Treatment Recommendation
Oral terbinafine 250 mg once daily is the first-line treatment for dermatophyte onychomycosis: 6 weeks for fingernails and 12 weeks for toenails, achieving mycological cure rates of 76-81% and complete cure rates of 55-80%. 1, 2, 3
Treatment Algorithm by Disease Severity and Patient Factors
Mild to Moderate Disease (≤50% nail involvement, no matrix involvement)
Topical therapy is appropriate for limited disease:
- Efinaconazole 10% solution applied daily is the preferred topical agent, with superior nail penetration and efficacy compared to other topicals 1, 4, 5
- Tavaborole 5% solution is particularly useful in patients with renal or hepatic impairment due to minimal systemic absorption 1
- Ciclopirox 8% lacquer applied daily for up to 48 weeks is an alternative, though it requires monthly professional nail debridement and is indicated only when systemic therapy is contraindicated 6, 1, 7
- Amorolfine 5% lacquer applied once or twice weekly for 6-12 months is another option for superficial and distal disease 6, 2
Severe or Extensive Disease (>50% involvement or matrix involvement)
Systemic therapy is mandatory:
- Terbinafine 250 mg daily remains superior to all alternatives, with 70-90% cure rates depending on nail location 1, 2
- Terbinafine demonstrates fungicidal activity against dermatophytes and minimal drug-drug interactions compared to azoles 1
- Baseline liver function tests (ALT, AST) and complete blood count are required before initiating terbinafine, especially in patients with history of heavy alcohol consumption, hepatitis, or hematological abnormalities 6, 2
Treatment by Causative Organism
Dermatophyte Onychomycosis (Most Common)
- Terbinafine 250 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) is first-line 1, 2, 3
- Itraconazole is second-line: either pulse therapy (400 mg daily for 1 week per month for 2-3 pulses) or continuous therapy (200 mg daily for 12 weeks) 1, 2
Candida Onychomycosis
- Itraconazole is the most effective agent when Candida invades the nail plate, using 400 mg daily for 1 week per month: 2 pulses for fingernails, 3-4 pulses for toenails 2
- Terbinafine may require higher doses or longer duration for Candida species, particularly C. albicans 8
Non-Dermatophyte Molds
- Limited data exists, but azoles (itraconazole) have broader spectrum coverage 8
- Voriconazole has shown efficacy in resistant cases, though not FDA-approved for onychomycosis 9
Special Population Considerations
Patients with Liver Disease
Topical therapy is the safest option to completely avoid hepatotoxicity risk:
- Efinaconazole 10% solution or tavaborole 5% solution are preferred topical agents 1, 4
- If systemic therapy is absolutely necessary, baseline and periodic liver function monitoring is mandatory 6, 2
- All oral antifungals carry hepatotoxicity risk; itraconazole requires monitoring especially with concomitant hepatotoxic drugs 6
Diabetic Patients
- Terbinafine is the agent of choice due to low risk of drug interactions and no hypoglycemia risk 1, 2
- Itraconazole should be avoided due to contraindication in heart failure (common in diabetics) and negative inotropic effects 1
- Treatment is particularly important as onychomycosis significantly predicts foot ulcers and cellulitis in diabetics 2
Immunocompromised Patients (HIV, Transplant Recipients)
- Terbinafine or fluconazole are preferred due to lower risk of drug interactions with antiretrovirals and immunosuppressive medications 1, 2
- Itraconazole has significant interactions with antiretrovirals and should be avoided 2
- Griseofulvin is the least effective in HIV-positive patients 2
Pediatric Patients (Age 1-12 Years)
- Terbinafine daily dosing by weight: 62.5 mg/day for <20 kg, 125 mg/day for 20-40 kg, 250 mg/day for >40 kg, for 6 weeks (fingernails) or 12 weeks (toenails) 2
- Cure rates are higher in pediatric populations than adults 2
- Efinaconazole 10% solution is FDA-approved for patients aged 6 years and above 5
Patients on Statins
- Fluconazole 150-450 mg once weekly for at least 6 months has fewer drug interactions with statins compared to itraconazole 1
- Itraconazole has significant interactions with statins and should be avoided or used with extreme caution 1
Critical Pre-Treatment Requirements
Mycological confirmation is mandatory before initiating any antifungal therapy:
- Obtain nail specimens for KOH preparation, fungal culture, or nail biopsy to confirm diagnosis 1, 2, 3
- The most common cause of treatment failure is incorrect diagnosis made on clinical grounds alone 2
- Treatment should never commence without laboratory confirmation 6, 2
Essential Adjunctive Measures
Monthly professional nail debridement and patient self-care are critical for success:
- Monthly removal of unattached, infected nail by a healthcare professional with competence in nail procedures 1, 7
- Weekly trimming and filing away loose nail material by the patient 1
- Decontamination or replacement of contaminated footwear to eliminate fungal reservoirs 1
- Application of antifungal powders and periodic spraying of terbinafine solution into shoes 1
- Always wear protective footwear in communal bathing facilities, gyms, and hotel rooms 2
Follow-Up and Monitoring
Re-evaluate patients 3-6 months after treatment initiation:
- Assessment should include both clinical improvement and mycological cure (negative microscopy and culture) 1, 2
- A follow-up period of at least 48 weeks from treatment start is ideal to identify potential relapse 1
- Up to 18 months may be required for complete toenail plate regrowth 1
Management of Treatment Failure (20-30% of Cases)
Common causes include poor adherence, poor drug absorption, immunosuppression, dermatophyte resistance, and dermatophytoma (compact fungal mass preventing drug penetration): 2
After First Treatment Failure:
- Resume terbinafine 250 mg daily for another 6 weeks (fingernails) or 12 weeks (toenails) after confirming dermatophyte infection and repeating pre-treatment checks 1
After Second Treatment Failure:
- Switch to itraconazole 200 mg daily for 12 weeks or 400 mg daily for 1 week per month for 2-3 pulses 1
- Consider partial nail removal if dermatophytoma subungual is present 2
Important Caveats and Pitfalls
All oral antifungals cause gastrointestinal side effects in approximately 49% of patients:
- Common adverse effects include nausea, diarrhea, taste disturbance, headache, and gastrointestinal upset across all agents 6, 8
- No oral antifungal is truly "benign" to the stomach; topical therapies are the only gastric-benign option 6
Do not expect complete clinical normalization even with mycological cure:
- Nails may have pre-existing dystrophy from trauma or non-fungal disease that will not resolve 2
Griseofulvin is no longer the treatment of choice: