What is the most effective antifungal topical treatment for onychomycosis (fungal infection of the nails)?

From the Guidelines

The most effective topical antifungal for nail infections (onychomycosis) is amorolfine 5% nail lacquer, which should be applied once or twice weekly for 6-12 months, as it has been shown to be effective in around 50% of cases of distal fingernail and toenail onychomycosis 1.

Key Considerations

• Amorolfine 5% nail lacquer is a broad-spectrum antifungal that inhibits the delta 14 reductase and delta 8 and delta 7 isomerase enzymes in the ergosterol biosynthetic pathway, making it fungicidal against C. albicans and T. mentagrophytes 1.
• The treatment should be applied after removal of as much of the diseased areas of the nail as possible by gentle filing, and it persists in the nail for 14 days after treatment is completed 1.
• While ciclopirox 8% nail lacquer is also an effective option, with a mycological cure rate of 34% compared to 10% with placebo, amorolfine 5% nail lacquer has been shown to be more effective in some studies 1.

Important Notes

• Topical treatments generally work best for mild to moderate infections limited to a few nails, and complete clearing typically takes many months 1.
• For severe infections or those involving multiple nails, oral antifungals like terbinafine may be more effective but require prescription and monitoring for side effects 1.
• Patients should be aware that the clinical improvement obtained with amorolfine and other topical antifungals may not be synonymous with mycological cure, which has invariably lower rates, often by 30% 1.

From the FDA Drug Label

INDICATIONS AND USAGE ... Ciclopirox Topical Solution, 8%, (Nail Lacquer), as a component of a comprehensive management program, is indicated as topical treatment in immunocompetent patients with mild to moderate onychomycosis of fingernails and toenails without lunula involvement, due to Trichophyton rubrum The results of use of Ciclopirox Topical Solution, 8%, (Nail Lacquer), in treatment of onychomycosis of the toenail without lunula involvement were obtained from two double-blind, placebo-controlled studies conducted in the US At Week 48 (plus Last Observation Carried Forward) for the Intent-to-Treat (ITT) Population Study 312Study 313 ActiveVehicleActiveVehicle

• Clear nail and negative mycology † ≤ 10% nail involvement and negative mycology ‡ Negative KOH and negative culture Complete Cure*6/110 (5.5%)1/109 (0.9%)10/118 (8.5%)0/117 (0%) Almost Clear†7/107 (6.5%)1/108 (0.9%)14/116 (12%)1/115 (0. 9%) Negative Mycology Alone‡30/105 (29%)12/106 (11%)41/115 (36%)10/114 (9%)

Based on the provided information from the drug label of ciclopirox (TOP) 2, the most effective antifungal topical for nails is ciclopirox topical solution, 8% (nail lacquer).

• Complete cure rates were 5.5% and 8.5% in the two studies, respectively.
• Almost clear rates were 6.5% and 12% in the two studies, respectively. It is essential to note that ciclopirox topical solution, 8%, (nail lacquer) should be used as part of a comprehensive management program, including removal of the unattached, infected nails as frequently as monthly, by a health care professional.

From the Research

Effective Antifungal Topical for Nails

• The most effective antifungal topical for nails can be determined by examining the mycologic cure rates of various treatments, with higher rates indicating greater effectiveness.
• Ciclopirox 8% nail lacquer has been shown to have a mycologic cure rate of 34% in US studies 3 and 52.6% in worldwide studies 3.
• However, more recent studies have introduced newer agents such as efinaconazole 10% solution and tavaborole 5% solution, which have demonstrated superior mycologic cure rates compared to ciclopirox 8% nail lacquer 4.
• Efinaconazole 10% solution has been shown to have mycologic cure rates comparable to those achieved with oral itraconazole 4.
• Tavaborole 5% solution has also reported treatment success rates superior to ciclopirox 8% nail lacquer, although it is in an earlier phase of development for onychomycosis 4.
• Combination therapy with oral and topical antifungals, such as terbinafine and amorolfine, has also been shown to be effective in treating onychomycosis, with additive or synergistic effects observed in vitro 5.

Comparison of Antifungal Topicals

• Ciclopirox 8% nail lacquer has been the only available topical antifungal agent for many years, but its efficacy has been disappointing, with poor therapeutic outcomes and unimpressive cure rates 4.
• Newer agents such as efinaconazole 10% solution and tavaborole 5% solution have been developed to address the limitations of ciclopirox 8% nail lacquer, and have demonstrated superior efficacy in clinical trials 4.
• The choice of antifungal topical for nails may depend on various factors, including the severity of the infection, the presence of underlying conditions, and the patient's preferences and lifestyle.
• Further studies are needed to determine the optimal treatment approach for onychomycosis, including the use of combination therapy and the role of newer topical antifungals 6, 4.