Treatment for Onychomycosis
First-Line Systemic Treatment
Oral terbinafine 250 mg daily is the definitive first-line treatment for onychomycosis caused by dermatophytes, given for 6 weeks for fingernails or 12 weeks for toenails, based on superior efficacy, fungicidal properties, and cost-effectiveness compared to all alternatives. 1, 2, 3
Why Terbinafine is Superior
- Terbinafine inhibits squalene epoxidase, depleting ergosterol and accumulating squalene, which directly kills dermatophytes rather than just inhibiting their growth—this fungicidal mechanism translates to higher cure rates and lower relapse rates. 1, 2
- The American Academy of Dermatology endorses terbinafine as first-line therapy based on the highest quality evidence (Grade A-I). 4, 1
- FDA-approved indication confirms terbinafine tablets are indicated for onychomycosis of toenails or fingernails due to dermatophytes. 5
Dosing and Duration
- Standard dosing: 250 mg orally once daily for 6 weeks (fingernails) or 12 weeks (toenails). 1, 2
- Confirm diagnosis with KOH preparation, fungal culture, or nail biopsy before initiating treatment. 5
Side Effects and Contraindications
- Common side effects include headache, taste disturbance (1:400 patients), and gastrointestinal upset. 4, 1
- Can aggravate psoriasis and cause lupus-like syndrome. 1, 2
- Contraindicated in hepatic impairment. 1
- Drug interactions: plasma concentrations reduced by rifampicin, increased by cimetidine. 4
Alternative First-Line: Itraconazole Pulse Therapy
Itraconazole 200 mg twice daily for 1 week per month is the preferred alternative when terbinafine is contraindicated or for specific organisms (Candida, nondermatophyte molds). 1, 2
Dosing Regimen
- Pulse therapy: 200 mg twice daily for 1 week per month—2 pulses for fingernails, 3 pulses for toenails. 1, 2
- Take with food and acidic pH for better absorption. 1, 2
When to Choose Itraconazole Over Terbinafine
- For Candida species: Itraconazole achieves 92% cure rate versus only 40% with pulse terbinafine. 1, 2
- For nondermatophyte molds (Scopulariopsis, Aspergillus, Fusarium, Acremonium): Itraconazole is the treatment of choice with 88% cure rates for Scopulariopsis due to broader antimicrobial coverage. 1, 2
- For dermatophytes: Terbinafine remains superior with better cure rates and lower relapse rates (Grade A-I evidence). 4, 1
Contraindications and Monitoring
- Contraindicated in heart failure due to negative inotropic effect. 1, 2
- Requires liver function monitoring for treatment durations longer than 1 month. 4, 2
- Significant drug interactions: enhanced toxicity with warfarin, antihistamines (terfenadine, astemizole), antipsychotics (sertindole), midazolam, digoxin, cisapride, ciclosporin, and simvastatin. 4
Topical Treatments: Limited Role
Topical therapy should only be used for superficial white onychomycosis, very early distal lateral subungual onychomycosis, or when systemic therapy is contraindicated. 1, 2, 3
Amorolfine 5% Nail Lacquer
- Effective in approximately 50% of cases when infection is limited to the distal portion of the nail. 4, 2, 3
- Rare side effects include local burning, pruritus, and erythema. 2
Ciclopirox 8% Nail Lacquer
- FDA-approved as a component of comprehensive management including monthly removal of unattached, infected nails by a healthcare professional. 6
- Mycological cure rate of 34% compared to 10% with placebo. 2
- Common side effects include periungual and nail fold erythema. 2
- Not recommended for concomitant use with systemic antifungals. 6
Efinaconazole and Tavaborole
Special Population Considerations
Diabetic Patients
Terbinafine is the preferred agent for diabetic patients due to lower risk of drug interactions and hypoglycemia. 1, 2, 3
- Onychomycosis is a significant predictor for foot ulcers in diabetics, making treatment particularly important in this population. 1, 2, 3
Immunosuppressed Patients (HIV, Transplant Recipients)
Terbinafine and fluconazole are preferred due to lower risk of interactions with antiretrovirals. 1, 2, 3
- Most cases are due to T. rubrum. 1
- Avoid itraconazole and ketoconazole due to significant drug interactions with antiretrovirals. 1
Pediatric Patients
Pulse itraconazole therapy is the recommended first-line treatment: 5 mg/kg/day for 1 week every month for 2 months (fingernails) or 3 months (toenails). 1, 2, 3
- Terbinafine alternative dosing (weight-based): <20 kg: 62.5 mg/day; 20-40 kg: 125 mg/day; >40 kg: 250 mg/day. 1, 2
- Duration for terbinafine: 6 weeks for fingernails, 12 weeks for toenails. 1
- Pediatric cure rates are higher (88-100%) than adults with faster response to treatment. 1, 2
Second-Line Treatment: Griseofulvin
Griseofulvin is relegated to third-line status with only 30-40% mycological cure rates and high relapse rates, indicated only when other agents are unavailable or contraindicated. 1, 2, 3
- Duration: 6-9 months for fingernails, 12-18 months for toenails. 1, 2
- Weakly fungistatic, acts by inhibiting nucleic acid synthesis. 4
- Side effects include nausea and rashes in 8-15% of patients. 4
- Contraindicated in pregnancy, lupus erythematosus, porphyria, and severe liver disease. 4
- Drug interactions: warfarin, ciclosporin, oral contraceptive pill. 4
- Despite low cost, poor cure rates necessitate further treatment, making cost-effectiveness ratio relatively high. 4
Emerging Therapies: Insufficient Evidence for Routine Use
- Photodynamic therapy: 44.3% cure rate at 12 months, but evidence remains limited. 1, 2, 3
- Laser therapy (1064nm Nd:YAG, near infrared diode 870/930nm): Promising results but insufficient evidence for strong recommendations. 1, 7, 9
- FDA-approved lasers only for temporary increases in clear nail, with suboptimal clinical results. 9
Prevention of Recurrence
Onychomycosis has 40-70% recurrence rates, necessitating aggressive preventive strategies. 1, 2, 3
- Wear protective footwear in public facilities. 1, 2, 3
- Use absorbent and antifungal powders in shoes. 1, 2, 3
- Keep nails short. 1, 2, 3
- Avoid sharing nail clippers. 1, 2, 3
- Promptly treat tinea pedis infections to reduce recurrence risk. 8
- Amorolfine may be effective as prophylactic treatment. 2
Baseline Monitoring and Safety
- Obtain baseline liver function tests and complete blood count before treatment. 2
- Ongoing monitoring required for prolonged or high-dose therapy, or in patients at risk due to concomitant hepatotoxic medications. 2
- Surveillance of liver function recommended for patients with pre-existing abnormal results or receiving continuous therapy for more than 1 month. 2