Topical treatment for fungal nail disease

Topical drugs in fungal nail disease

• antifungal drugs can be:
  • fungistatic
    • preventing further growth of fungal cells, or
  • fungicidal
    • killing fungal cells entirely

Recommendations when to use topical therapy as monotherapy (1):

• role of monotherapy with topical antifungals is limited to Superficial White Onychomycosis (SWO) (except in transverse or striate infections),
• early Distal and Lateral Subungal Onychomycosis (DLSO) (except in the presence of longitudinal streaks) when < 80% of the nail plate is affected with lack of involvement of the lunula,
• or when systemic antifungals are contraindicated

Topical drugs are usually applied daily for 12 months in order to allow the normal nail to grow and replace the regions damaged by infection:

• drugs formulated for topical application in onychomycosis include:
  • allylamine (e.g. butenafine, terbinafine),
  • azole (e.g. clotrimazole, efinaconazole, miconazole),
  • hydroxypyridone (e.g. ciclopirox),
  • morpholine-derivative (e.g. amorolfine, Kunzea oil) - 5% amorolfine nail lacquer used once or twice a week 6 months for fingernails and 12 months for toe nails is recommended by PHE (2)
  • benzoxaborole (e.g. tavaborole) classes
• azoles, allylamines, and morpholine-derivative drugs
  • inhibit ergosterol biosynthesis, an essential component of the cell wall
• hydroxypyridone-class drug ciclopirox
  • inhibits metalloproteases by binding metal ions (metalloproteases are enzymes that help with fungal cell survival)
• benzoxaborole-class drugs
  • inhibit protein translation by inhibiting the fungal leucine transfer ribonucleic acid (tRNA) synthetase
• application of topical treatments is usually daily for 12 months, with amorolfine applied once or twice weekly for 12 months
  
  
• topical treatments come in cream, lacquer, and solutions of varying concentrations (e.g. 5% to 10%) and are applied to the nail plate and skin surrounding the nail
  • in lacquers, alcohol solution is used to remove buildup of lacquer on the nails
  • topical treatments do not generally have drug interactions, which is useful where patients are already taking multiple oral medications
  • adverse events are usually related to skin reactions around the nail, such as rash, itching, or burning
  • a 40% urea ointment is available for the treatment of onychomycosis
    • urea ingredient provides non-surgical nail ablation of onychomycosis
      
      
• a systematic review concluded that (5):
  • there is
    • high-quality evidence that efinaconazole 10% solution is more effective in achieving complete cure
    • low-quality evidence that ciclopirox 8% lacquer may better lead to complete cure
    • moderate-quality evidence in support of tavaborole 5% solution and P-3051 (ciclopirox 8% hydrolacquer) probably being more likely to achieve complete cure
      • although for P-3051 the comparators are ciclopirox 8% lacquer or amorolfine 5%, rather than vehicle
    • not all patients can be expected to achieve complete cure, since reported cure rates in clinical studies, while better than vehicle, are still low

Reference:

• Ameen M et al. Guidelines for treatment of onychomycosis. British Journal of Dermatology 2014;171:937-958
• Public Health England 2017. Fungal skin and nail infections: Diagnosis and laboratory investigation - Quick reference guide for primary care.
• Gupta AK et al. Onychomycosis in the 21st Century: An Update on Diagnosis, Epidemiology, and Treatment.J Cutan Med Surg. Nov/Dec 2017;21(6):525-539
• Gupta AK et al. Update on current approaches to diagnosis and treatment of onychomycosis. Expert Rev Anti Infect Ther 2018 Dec;16(12):929-938.
• Foley K et al.Topical and device-based treatments for fungal infections of the toenails. Cochrane Systematic Review 16th January 2020.