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Comparing Oral Meds for Toenail Fungal Infection

JAMA; 2018 Jan 23/30; Kreijkamp-Kaspers, et al

Both terbinafine (Lamisil) and azole-based medications (ketoconazole, fluconazole and itraconazole) were associated with higher clinical and mycological cure rates compared with placebo in treating toenail fungal infection, according to a recent clinical evidence synopsis. The synopsis was based on 48 randomized controlled trails from 1984-2014 and included 10,200 patients (mean age 36-68 years) from 21 countries. Comparisons included terbinafine vs placebo, azoles vs placebo, terbinafine vs azoles, azoles vs griseofulvin, terbinafine vs griseofulvin, and terbinafine plus azole vs terbinafine in monotherapy. Among the findings:

  • Terbinafine was associated with higher clinical cure rates vs placebo (370 vs 62 per 1,000 patients, respectively) and mycological cure rates (755 vs 167).
  • Treatment with azoles was associated with higher clinical cure rates vs placebo (309 vs 14 per 1,000 patients, respectively) and mycological cure rates (431 vs 74).
  • Azoles were associated with lower clinical cure rates vs terbinafine (471 vs 575 per 1,000 patients; P = .006) and mycological cure rates (525 vs 682; P < .001).
  • Griseofulvin (a nonazole antifungal) was associated with clinical and mycological cure rates that were similar to azoles.
  • Terbinafine was associated with a lower recurrence rate vs placebo, as were azoles.
  • Recurrence rates were not different for azoles vs terbinafine.
  • Adverse events were not different between the active and placebo groups and terbinafine vs azoles.
  • Patients treated with griseofulvin had more adverse events vs azoles.


Kreijkamp-Kaspers S, Hawke KL, van Driel ML. Oral medications to treat toenail fungal infection. JAMA.2018;319(4):397–398. doi:10.1001/jama.2017.20160.


Fungal infection of the nail, also known as onychomycosis and tinea unguium, are common and have a prevalence of 2-14%. Up to a third of patients with diabetes can have onychomycosis. It is most commonly caused by dermatophytes, but yeasts and non-dermatophyte molds can also cause the infection. The diagnosis is made clinically and confirmed by culture or visualizing hyphae under microscopy. Neither test is perfect, with microscopy approximately 80% sensitive and culture with a sensitivity of only 60%. The only topical medication, ciclopirox, does not work very well with a mycotic cure rate of 29% to 36%, and a clinical cure rate of 6% to 9%.1 The above evidence-based review supports the recommendations that terbinafine and itraconazole are first-line treatments with terbinafine the preferred medication.2— Neil Skolnik, MD

  1. Westerberg DP, Voyack MJ. Onychomycosis. Am Fam Physician. 2013;88(11):762-770.
  2. Ameen M, Lear JT, Madan V, et al. British Association of Dermatologists’ guidelines for the management of onychomycosis 2014. Br J Dermatol. 2014;171(5):937-958.