What are the systemic treatment options for onychomycosis (fungal infection of the toenails)?

From the Guidelines

Systemic treatment for toenail fungus typically involves oral antifungal medications, with terbinafine (Lamisil) 250mg daily for 12 weeks being the most effective first-line option. Alternatives include itraconazole (Sporanox) 200mg twice daily for one week per month, repeated for 3-4 months, or fluconazole (Diflucan) 150-300mg once weekly for 6-12 months 1.

Key Considerations

• Before starting treatment, confirm the diagnosis with a fungal culture or KOH preparation, and consider baseline liver function tests since these medications can cause hepatotoxicity 1.
• Monitor for side effects including headache, gastrointestinal upset, rash, and taste disturbances 1.
• Treatment success requires patience as visible improvement may take months, with complete nail regrowth taking 9-12 months 1.
• These oral medications work by inhibiting ergosterol synthesis, disrupting fungal cell membranes, and are necessary for toenail infections because topical treatments rarely penetrate the nail bed sufficiently 1.
• Patients should continue treatment for the full prescribed duration even if visual improvement occurs earlier to prevent recurrence, and should keep feet clean and dry to support treatment efficacy 1.

Specific Treatment Options

• Terbinafine is superior to itraconazole both in vitro and in vivo for dermatophyte onychomycosis and should be considered the first-line treatment, with itraconazole as the next best alternative 1.
• Itraconazole has broader antimicrobial coverage for Candida and nondermatophyte moulds, and is often used to treat these types of infections 1.
• Fluconazole may be a useful alternative in patients unable to tolerate terbinafine or itraconazole, but has lower efficacy rates compared to these medications 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

Terbinafine tablets, USP are indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (tinea unguium).

The systemic treatment option for onychomycosis (fungal infection of the toenails) is terbinafine (PO), an allylamine antifungal.

• The dosage is one 250 mg tablet once daily for 12 weeks for treatment of toenail onychomycosis 2.
• Efficacy has been demonstrated in clinical trials, with mycological cure rates of 70% and effective treatment rates of 59% in patients with toenail onychomycosis 2.
• Clinical cure (mycological cure plus 0% nail involvement) was achieved in 38% of patients with toenail onychomycosis 2.

From the Research

Systemic Treatment Options for Onychomycosis

The following are systemic treatment options for onychomycosis:

• Itraconazole: effective against dermatophytes, Candida species, and nondermatophyte moulds, with a preferred regimen of pulse therapy 3, 4
• Terbinafine: effective against dermatophytes, with a higher cure ratio than other drugs for dermatophyte onychomycosis, and a preferred regimen of continuous once daily therapy 3, 4, 5, 6
• Fluconazole: effective against onychomycosis, but with a lower cure rate compared to itraconazole and terbinafine, and a preferred regimen of once weekly treatment 3, 4, 7
• Griseofulvin: not effective against Candida species or nondermatophyte moulds, and rarely used for treatment of onychomycosis due to low cure rates and high relapse rates 3, 5
• Ketoconazole: may be used to treat tinea versicolor, but not commonly used for onychomycosis due to potential liver toxicity 3, 5

Treatment Regimens

The following are treatment regimens for the systemic treatment options:

• Itraconazole: 200mg twice daily for 1 week per month for 3 pulses 3
• Terbinafine: 250 mg/day for 12 weeks 3, 6
• Fluconazole: 150 mg/week until the abnormal-appearing nail plate has grown out, typically over a period of 9 to 18 months 3, or 150 mg once weekly for 3 months 7

Efficacy and Safety

The efficacy and safety of the systemic treatment options are as follows:

• Terbinafine: high cure rates against dermatophytes, with a clinical cure rate of 81.3% and a mycological cure rate of 75% 7, and a safe and effective therapy for the treatment of onychomycosis 6
• Itraconazole: effective against dermatophytes, Candida species, and nondermatophyte moulds, with a clinical cure rate of 77.8% and a mycological cure rate of 61.1% 7
• Fluconazole: lower cure rate compared to itraconazole and terbinafine, with a clinical cure rate of 37.5% and a mycological cure rate of 31.2% 7