JAMA: The Journal of the American Medical Association

The authors investigated different oral antifungal medications used to treat toenail fungal infections.

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Compared with placebo, high-quality evidence supports better clinical (ie, normal appearance of the toenail) and mycological (negative culture, microscopy, or both) results with both terbinafine and azole-based treatments.

However, on direct comparison, azoles did not perform as well as terbinafine for positive cure rates. Terbinafine 250 mg orally once daily for 3 to 4 months is preferred over the azoles.

Terbinafine works up to 70% of the time in selected patients who still have growing nails and mild to moderate involvement. There are also fewer concerns for drug interactions and hepatotoxicity with terbinafine.

Itraconazole or fluconazole including pulse therapy regimens are preferred when a yeast or mold is identified as the cause of the onychomycosis, but the treatment failure rate (24%–69%) makes this a second-line drug.

Ketoconazole should be avoided in view of cases of fatal hepatotoxicity since safer alternatives are available. 

Griseofulvin is simply not as effective and would need to be used for a prolonged time until the nail completely grows out.