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Optimizing Topical Therapy for Onychomycosis: The Importance of Patient Education

Onychomycosis is a fungal infection of the nail unit due to dermatophytes, yeasts, and nondermatophyte molds (NDMs). It accounts for approximately 50% of all nail disorders seen in clinical practice and is estimated to affect 10% to 12% of the US population.1,2 Oral medications approved by the US Food and Drug Administration (FDA) include terbinafine and itraconazole, which have demonstrated good efficacy in treating onychomycosis but are associated with potential drug-drug interactions and systemic side effects.3,4 Although liver failure associated with these drugs is rare,5 many patients are anxious about systemic adverse events and therefore prefer to use topical therapies for onychomycosis.

Many patients desire topical therapy but not every patient is an appropriate candidate. Patients who will likely respond well to topical therapy include those with superficial onychomycosis, distal lateral subungual onychomycosis that involves less than 50% of the nail plate surface area (without matrix involvement and a nail plate thickness less than 2 mm), and only up to 3 or 4 nails affected.6 In patients who have contraindications to oral therapy, topical therapy may be the only treatment option. To maximize efficacy of FDA-approved topical agents for onychomycosis therapy, patient education is of utmost importance. Failure to properly counsel the patient on proper medication application may result in decreased antifungal efficacy; poor patient compliance due to lack of improvement; and progression of disease, leading to increased onychodystrophy and pain.

Before initiating therapy, patients should be counseled that treatment with topical drugs is long, requiring daily application of the medication for 6 months for fingernails and 12 months for toenails, based on average nail growth rates (2–3 mm per month for fingernails; 1 mm per month for toenails).7 Patients also are advised to avoid nail polish application during the course of therapy, as clinical trials were performed without nail polish and the true efficacy with nail polish is unknown.8-10 Because patients who have had onychomycosis for shorter durations generally have better cure rates than those who have disease for longer durations, it is prudent to initiate topical therapy as early as possible.11,12 Treating the feet with an antifungal while treating the nails for onychomycosis further enhances efficacy.13,14 There are 3 FDA-approved topical therapies for onychomycosis: ciclopirox nail lacquer 8%, efinaconazole solution 10%, and tavaborole solution 5%.15-17

Ciclopirox is a hydroxypyridone with broad-spectrum antimicrobial activity against dermatophytes, NDMs, yeasts, and bacteria. Its mechanism of action is to chelate polyvalent cations, such as Fe3+, and inhibit fungal metal-dependent enzymes responsible for the degradation of toxic metabolites.15 Ciclopirox nail lacquer 8% was FDA approved for the treatment of onychomycosis in 1999, making it the first topical approved for this purpose. Its indication is for immunocompetent patients with mild to moderate onychomycosis (Trichophyton rubrum) without lunula involvement, with mycologic cure rates of 29% to 36% and complete cure rates of 5.5% to 8.5% (toenails).15 It is the only FDA-approved topical treatment for both fingernails and toenails. Using a brush applicator, it is applied daily to the nail plate and its undersurface, hyponychium, and 5 mm of the surrounding skin. It is important to counsel the patient to remove the lacquer from the nail plate weekly because failure to do so will result in accumulation of numerous layers of medication, such that the active drug cannot reach the site of infection (Figures 1 and 2). The nail plate also should be trimmed and filed weekly by the patient, with monthly clipping/debridement by a physician recommended.6,15

Figure 1. Appearance of the great toenail after application of ciclopirox nail lacquer 8% daily for 6 months without weekly removal of the lacquer. The great toenail shows accumulation of multiple layers of medication, preventing penetration of the active drug to the site of infection. Prior to presenting to our office, the patient was not counselled on proper application.

Figure 2. After vigorous rubbing of the great toenail with alcohol and clipping the lacquer accumulation, the numerous layers of medication were removed from the nail plate. The patient was then counseled on proper medication application.

Efinaconazole is a triazole with antifungal activity against dermatophytes, NDMs, and Candida species. Its mechanism of action is inhibition of lanosterol 14α-demethylase, an enzyme involved in the biosynthesis of ergosterol, which is a component of the fungal cell membrane. Efinaconazole solution 10% was FDA approved in June 2014 for the treatment of toenail onychomycosis due to T rubrum and Trichophyton mentagrophytes, with package insert mycologic cure rates of 53.4% to 55.2% and complete cure rates of 15.2% to 17.8%.9,16 It is applied with a brush applicator to the nail plate, as well as its undersurface, nail folds, and hyponychium. Two drops are recommended for the great toenail and one drop for all other toenails, and no removal of the solution or debridement is required.6,16

Tavaborole is a benzoxaborole with antifungal activity against dermatophytes, NDMs, and yeasts. Its mechanism of action is inhibition of fungal aminoacyl transfer RNA synthetase, thus impeding protein synthesis.18 Tavaborole solution 5% was FDA approved in July 2014 for the treatment of toenail onychomycosis due to T rubrum and T mentagrophytes, with mycologic cure rates of 31.1% and 35.9% and complete cure rates of 6.5% and 9.1%, respectively.11,17 It is applied with a glass pointed-tip dropper to the nail plate, such that the entire nail is covered as well as under the nail tip. No removal of the solution or debridement is required.17

Topical therapies for onychomycosis require long treatment durations, thus excellent compliance and adherence to the treatment protocol are vital to maximize efficacy. Dermatologists who prescribe ciclopirox nail lacquer 8% should counsel patients to remove the lacquer with alcohol weekly, such that the antifungal penetrates the nail plate to reach the site of infection. Monthly debridement also must be clarified before initiating therapy. With all topical therapy for onychomycosis, it is important to treat early, treat concurrently for tinea pedis, and avoid use of nail polish so that patients have the best possible cure rates.

References
  1. Lipner SR, Scher RK. Onychomycosis: diagnosis and therapy. In: Razzaghi-Abyaneh M, Shams-Ghahfarokhi M, Rai M, eds. Medical Mycology: Current Trends and Future Prospects. Boca Raton, FL: CRC Press; 2015:28.
  2. Scher RK, Rich P, Pariser D, et al. The epidemiology, etiology, and pathophysiology of onychomycosis. Semin Cutan Med Surg. 2013;32(2 suppl 1):S2-S4.
  3. Lamisil [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 1997.
  4. Sporanox [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2001.
  5. National Institutes of Health. Terbinafine. LiverTox website. https://livertox.nlm.nih.gov/Terbinafine.htm. Accessed November 7, 2018.
  6. Lipner SR, Scher RK. Onychomycosis: topical therapy and devices. In: Rubin AI, Jellinek NJ, Daniel CR III, et al, eds. Scher and Daniel’s Nails: Diagnosis, Surgery, Therapy. 4th ed. Cham, Switzerland: Springer International Publishing; 2018:173-184.
  7. Lipner SR, Scher RK. Nail growth evaluation and factors affecting nail growth. In: Humbert P, Fanian F, Maibach HI, et al, eds. Agache’s Measuring the Skin. 2nd ed. Berlin, Germany: Springer; 2017:867-881.
  8. Gupta AK, Elewski BE, Sugarman JL, et al. The efficacy and safety of efinaconazole 10% solution for treatment of mild to moderate onychomycosis: a pooled analysis of two phase 3 randomized trials. J Drugs Dermatol. 2014;13:815-820.
  9. Elewski BE, Rich P, Pollak R, et al. Efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase III multicenter, randomized, double-blind studies. J Am Acad Dermatol. 2013;68:600-608.
  10. Elewski BE, Aly R, Baldwin SL, et al. Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase-III studies. J Am Acad Dermatol. 2015;73:62-69.
  11. Rich P. Efinaconazole topical solution, 10%: the benefits of treating onychomycosis early. J Drugs Dermatol. 2015;14:58-62.
  12. Lipner SR, Scher RK. Efinaconazole 10% topical solution for the topical treatment of onychomycosis of the toenail. Expert Rev Clin Pharmacol. 2015;8:719-731.
  13. Del Rosso JQ. Onychomycosis of toenails and post-hoc analyses with efinaconazole 10% solution once-daily treatment: impact of disease severity and other concomitant associated factors on selection of therapy and therapeutic outcomes. J Clin Aesthet Dermatol. 2016;9:42.
  14. Lipner SR, Scher RK. Management of onychomycosis and co-existing tinea pedis. J Drugs Dermatol. 2015;14:492-494.
  15. Penlac [package insert]. Berwyn, PA: Dermik Laboratories; 2004.
  16. Jublia [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals, LLC; 2014.
  17. Kerydin [package insert]. Palo Alto, CA: Anacor Pharmaceuticals, Inc; 2014.
  18. Rock FL, Mao W, Yaremchuk A, et al. An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science. 2007;316:1759-1761.
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Author and Disclosure Information

Dr. Lipner is from Weill Cornell Medicine, New York, New York. Mr. Ko is from Duke University School of Medicine, Durham, North Carolina.

The authors report no conflict of interest.

Correspondence: Shari R. Lipner, MD, PhD, 1305 York Ave, New York, NY 10021 ([email protected]).

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Dr. Lipner is from Weill Cornell Medicine, New York, New York. Mr. Ko is from Duke University School of Medicine, Durham, North Carolina.

The authors report no conflict of interest.

Correspondence: Shari R. Lipner, MD, PhD, 1305 York Ave, New York, NY 10021 ([email protected]).

Author and Disclosure Information

Dr. Lipner is from Weill Cornell Medicine, New York, New York. Mr. Ko is from Duke University School of Medicine, Durham, North Carolina.

The authors report no conflict of interest.

Correspondence: Shari R. Lipner, MD, PhD, 1305 York Ave, New York, NY 10021 ([email protected]).

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Onychomycosis is a fungal infection of the nail unit due to dermatophytes, yeasts, and nondermatophyte molds (NDMs). It accounts for approximately 50% of all nail disorders seen in clinical practice and is estimated to affect 10% to 12% of the US population.1,2 Oral medications approved by the US Food and Drug Administration (FDA) include terbinafine and itraconazole, which have demonstrated good efficacy in treating onychomycosis but are associated with potential drug-drug interactions and systemic side effects.3,4 Although liver failure associated with these drugs is rare,5 many patients are anxious about systemic adverse events and therefore prefer to use topical therapies for onychomycosis.

Many patients desire topical therapy but not every patient is an appropriate candidate. Patients who will likely respond well to topical therapy include those with superficial onychomycosis, distal lateral subungual onychomycosis that involves less than 50% of the nail plate surface area (without matrix involvement and a nail plate thickness less than 2 mm), and only up to 3 or 4 nails affected.6 In patients who have contraindications to oral therapy, topical therapy may be the only treatment option. To maximize efficacy of FDA-approved topical agents for onychomycosis therapy, patient education is of utmost importance. Failure to properly counsel the patient on proper medication application may result in decreased antifungal efficacy; poor patient compliance due to lack of improvement; and progression of disease, leading to increased onychodystrophy and pain.

Before initiating therapy, patients should be counseled that treatment with topical drugs is long, requiring daily application of the medication for 6 months for fingernails and 12 months for toenails, based on average nail growth rates (2–3 mm per month for fingernails; 1 mm per month for toenails).7 Patients also are advised to avoid nail polish application during the course of therapy, as clinical trials were performed without nail polish and the true efficacy with nail polish is unknown.8-10 Because patients who have had onychomycosis for shorter durations generally have better cure rates than those who have disease for longer durations, it is prudent to initiate topical therapy as early as possible.11,12 Treating the feet with an antifungal while treating the nails for onychomycosis further enhances efficacy.13,14 There are 3 FDA-approved topical therapies for onychomycosis: ciclopirox nail lacquer 8%, efinaconazole solution 10%, and tavaborole solution 5%.15-17

Ciclopirox is a hydroxypyridone with broad-spectrum antimicrobial activity against dermatophytes, NDMs, yeasts, and bacteria. Its mechanism of action is to chelate polyvalent cations, such as Fe3+, and inhibit fungal metal-dependent enzymes responsible for the degradation of toxic metabolites.15 Ciclopirox nail lacquer 8% was FDA approved for the treatment of onychomycosis in 1999, making it the first topical approved for this purpose. Its indication is for immunocompetent patients with mild to moderate onychomycosis (Trichophyton rubrum) without lunula involvement, with mycologic cure rates of 29% to 36% and complete cure rates of 5.5% to 8.5% (toenails).15 It is the only FDA-approved topical treatment for both fingernails and toenails. Using a brush applicator, it is applied daily to the nail plate and its undersurface, hyponychium, and 5 mm of the surrounding skin. It is important to counsel the patient to remove the lacquer from the nail plate weekly because failure to do so will result in accumulation of numerous layers of medication, such that the active drug cannot reach the site of infection (Figures 1 and 2). The nail plate also should be trimmed and filed weekly by the patient, with monthly clipping/debridement by a physician recommended.6,15

Figure 1. Appearance of the great toenail after application of ciclopirox nail lacquer 8% daily for 6 months without weekly removal of the lacquer. The great toenail shows accumulation of multiple layers of medication, preventing penetration of the active drug to the site of infection. Prior to presenting to our office, the patient was not counselled on proper application.

Figure 2. After vigorous rubbing of the great toenail with alcohol and clipping the lacquer accumulation, the numerous layers of medication were removed from the nail plate. The patient was then counseled on proper medication application.

Efinaconazole is a triazole with antifungal activity against dermatophytes, NDMs, and Candida species. Its mechanism of action is inhibition of lanosterol 14α-demethylase, an enzyme involved in the biosynthesis of ergosterol, which is a component of the fungal cell membrane. Efinaconazole solution 10% was FDA approved in June 2014 for the treatment of toenail onychomycosis due to T rubrum and Trichophyton mentagrophytes, with package insert mycologic cure rates of 53.4% to 55.2% and complete cure rates of 15.2% to 17.8%.9,16 It is applied with a brush applicator to the nail plate, as well as its undersurface, nail folds, and hyponychium. Two drops are recommended for the great toenail and one drop for all other toenails, and no removal of the solution or debridement is required.6,16

Tavaborole is a benzoxaborole with antifungal activity against dermatophytes, NDMs, and yeasts. Its mechanism of action is inhibition of fungal aminoacyl transfer RNA synthetase, thus impeding protein synthesis.18 Tavaborole solution 5% was FDA approved in July 2014 for the treatment of toenail onychomycosis due to T rubrum and T mentagrophytes, with mycologic cure rates of 31.1% and 35.9% and complete cure rates of 6.5% and 9.1%, respectively.11,17 It is applied with a glass pointed-tip dropper to the nail plate, such that the entire nail is covered as well as under the nail tip. No removal of the solution or debridement is required.17

Topical therapies for onychomycosis require long treatment durations, thus excellent compliance and adherence to the treatment protocol are vital to maximize efficacy. Dermatologists who prescribe ciclopirox nail lacquer 8% should counsel patients to remove the lacquer with alcohol weekly, such that the antifungal penetrates the nail plate to reach the site of infection. Monthly debridement also must be clarified before initiating therapy. With all topical therapy for onychomycosis, it is important to treat early, treat concurrently for tinea pedis, and avoid use of nail polish so that patients have the best possible cure rates.

Onychomycosis is a fungal infection of the nail unit due to dermatophytes, yeasts, and nondermatophyte molds (NDMs). It accounts for approximately 50% of all nail disorders seen in clinical practice and is estimated to affect 10% to 12% of the US population.1,2 Oral medications approved by the US Food and Drug Administration (FDA) include terbinafine and itraconazole, which have demonstrated good efficacy in treating onychomycosis but are associated with potential drug-drug interactions and systemic side effects.3,4 Although liver failure associated with these drugs is rare,5 many patients are anxious about systemic adverse events and therefore prefer to use topical therapies for onychomycosis.

Many patients desire topical therapy but not every patient is an appropriate candidate. Patients who will likely respond well to topical therapy include those with superficial onychomycosis, distal lateral subungual onychomycosis that involves less than 50% of the nail plate surface area (without matrix involvement and a nail plate thickness less than 2 mm), and only up to 3 or 4 nails affected.6 In patients who have contraindications to oral therapy, topical therapy may be the only treatment option. To maximize efficacy of FDA-approved topical agents for onychomycosis therapy, patient education is of utmost importance. Failure to properly counsel the patient on proper medication application may result in decreased antifungal efficacy; poor patient compliance due to lack of improvement; and progression of disease, leading to increased onychodystrophy and pain.

Before initiating therapy, patients should be counseled that treatment with topical drugs is long, requiring daily application of the medication for 6 months for fingernails and 12 months for toenails, based on average nail growth rates (2–3 mm per month for fingernails; 1 mm per month for toenails).7 Patients also are advised to avoid nail polish application during the course of therapy, as clinical trials were performed without nail polish and the true efficacy with nail polish is unknown.8-10 Because patients who have had onychomycosis for shorter durations generally have better cure rates than those who have disease for longer durations, it is prudent to initiate topical therapy as early as possible.11,12 Treating the feet with an antifungal while treating the nails for onychomycosis further enhances efficacy.13,14 There are 3 FDA-approved topical therapies for onychomycosis: ciclopirox nail lacquer 8%, efinaconazole solution 10%, and tavaborole solution 5%.15-17

Ciclopirox is a hydroxypyridone with broad-spectrum antimicrobial activity against dermatophytes, NDMs, yeasts, and bacteria. Its mechanism of action is to chelate polyvalent cations, such as Fe3+, and inhibit fungal metal-dependent enzymes responsible for the degradation of toxic metabolites.15 Ciclopirox nail lacquer 8% was FDA approved for the treatment of onychomycosis in 1999, making it the first topical approved for this purpose. Its indication is for immunocompetent patients with mild to moderate onychomycosis (Trichophyton rubrum) without lunula involvement, with mycologic cure rates of 29% to 36% and complete cure rates of 5.5% to 8.5% (toenails).15 It is the only FDA-approved topical treatment for both fingernails and toenails. Using a brush applicator, it is applied daily to the nail plate and its undersurface, hyponychium, and 5 mm of the surrounding skin. It is important to counsel the patient to remove the lacquer from the nail plate weekly because failure to do so will result in accumulation of numerous layers of medication, such that the active drug cannot reach the site of infection (Figures 1 and 2). The nail plate also should be trimmed and filed weekly by the patient, with monthly clipping/debridement by a physician recommended.6,15

Figure 1. Appearance of the great toenail after application of ciclopirox nail lacquer 8% daily for 6 months without weekly removal of the lacquer. The great toenail shows accumulation of multiple layers of medication, preventing penetration of the active drug to the site of infection. Prior to presenting to our office, the patient was not counselled on proper application.

Figure 2. After vigorous rubbing of the great toenail with alcohol and clipping the lacquer accumulation, the numerous layers of medication were removed from the nail plate. The patient was then counseled on proper medication application.

Efinaconazole is a triazole with antifungal activity against dermatophytes, NDMs, and Candida species. Its mechanism of action is inhibition of lanosterol 14α-demethylase, an enzyme involved in the biosynthesis of ergosterol, which is a component of the fungal cell membrane. Efinaconazole solution 10% was FDA approved in June 2014 for the treatment of toenail onychomycosis due to T rubrum and Trichophyton mentagrophytes, with package insert mycologic cure rates of 53.4% to 55.2% and complete cure rates of 15.2% to 17.8%.9,16 It is applied with a brush applicator to the nail plate, as well as its undersurface, nail folds, and hyponychium. Two drops are recommended for the great toenail and one drop for all other toenails, and no removal of the solution or debridement is required.6,16

Tavaborole is a benzoxaborole with antifungal activity against dermatophytes, NDMs, and yeasts. Its mechanism of action is inhibition of fungal aminoacyl transfer RNA synthetase, thus impeding protein synthesis.18 Tavaborole solution 5% was FDA approved in July 2014 for the treatment of toenail onychomycosis due to T rubrum and T mentagrophytes, with mycologic cure rates of 31.1% and 35.9% and complete cure rates of 6.5% and 9.1%, respectively.11,17 It is applied with a glass pointed-tip dropper to the nail plate, such that the entire nail is covered as well as under the nail tip. No removal of the solution or debridement is required.17

Topical therapies for onychomycosis require long treatment durations, thus excellent compliance and adherence to the treatment protocol are vital to maximize efficacy. Dermatologists who prescribe ciclopirox nail lacquer 8% should counsel patients to remove the lacquer with alcohol weekly, such that the antifungal penetrates the nail plate to reach the site of infection. Monthly debridement also must be clarified before initiating therapy. With all topical therapy for onychomycosis, it is important to treat early, treat concurrently for tinea pedis, and avoid use of nail polish so that patients have the best possible cure rates.

References
  1. Lipner SR, Scher RK. Onychomycosis: diagnosis and therapy. In: Razzaghi-Abyaneh M, Shams-Ghahfarokhi M, Rai M, eds. Medical Mycology: Current Trends and Future Prospects. Boca Raton, FL: CRC Press; 2015:28.
  2. Scher RK, Rich P, Pariser D, et al. The epidemiology, etiology, and pathophysiology of onychomycosis. Semin Cutan Med Surg. 2013;32(2 suppl 1):S2-S4.
  3. Lamisil [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 1997.
  4. Sporanox [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2001.
  5. National Institutes of Health. Terbinafine. LiverTox website. https://livertox.nlm.nih.gov/Terbinafine.htm. Accessed November 7, 2018.
  6. Lipner SR, Scher RK. Onychomycosis: topical therapy and devices. In: Rubin AI, Jellinek NJ, Daniel CR III, et al, eds. Scher and Daniel’s Nails: Diagnosis, Surgery, Therapy. 4th ed. Cham, Switzerland: Springer International Publishing; 2018:173-184.
  7. Lipner SR, Scher RK. Nail growth evaluation and factors affecting nail growth. In: Humbert P, Fanian F, Maibach HI, et al, eds. Agache’s Measuring the Skin. 2nd ed. Berlin, Germany: Springer; 2017:867-881.
  8. Gupta AK, Elewski BE, Sugarman JL, et al. The efficacy and safety of efinaconazole 10% solution for treatment of mild to moderate onychomycosis: a pooled analysis of two phase 3 randomized trials. J Drugs Dermatol. 2014;13:815-820.
  9. Elewski BE, Rich P, Pollak R, et al. Efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase III multicenter, randomized, double-blind studies. J Am Acad Dermatol. 2013;68:600-608.
  10. Elewski BE, Aly R, Baldwin SL, et al. Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase-III studies. J Am Acad Dermatol. 2015;73:62-69.
  11. Rich P. Efinaconazole topical solution, 10%: the benefits of treating onychomycosis early. J Drugs Dermatol. 2015;14:58-62.
  12. Lipner SR, Scher RK. Efinaconazole 10% topical solution for the topical treatment of onychomycosis of the toenail. Expert Rev Clin Pharmacol. 2015;8:719-731.
  13. Del Rosso JQ. Onychomycosis of toenails and post-hoc analyses with efinaconazole 10% solution once-daily treatment: impact of disease severity and other concomitant associated factors on selection of therapy and therapeutic outcomes. J Clin Aesthet Dermatol. 2016;9:42.
  14. Lipner SR, Scher RK. Management of onychomycosis and co-existing tinea pedis. J Drugs Dermatol. 2015;14:492-494.
  15. Penlac [package insert]. Berwyn, PA: Dermik Laboratories; 2004.
  16. Jublia [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals, LLC; 2014.
  17. Kerydin [package insert]. Palo Alto, CA: Anacor Pharmaceuticals, Inc; 2014.
  18. Rock FL, Mao W, Yaremchuk A, et al. An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science. 2007;316:1759-1761.
References
  1. Lipner SR, Scher RK. Onychomycosis: diagnosis and therapy. In: Razzaghi-Abyaneh M, Shams-Ghahfarokhi M, Rai M, eds. Medical Mycology: Current Trends and Future Prospects. Boca Raton, FL: CRC Press; 2015:28.
  2. Scher RK, Rich P, Pariser D, et al. The epidemiology, etiology, and pathophysiology of onychomycosis. Semin Cutan Med Surg. 2013;32(2 suppl 1):S2-S4.
  3. Lamisil [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 1997.
  4. Sporanox [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2001.
  5. National Institutes of Health. Terbinafine. LiverTox website. https://livertox.nlm.nih.gov/Terbinafine.htm. Accessed November 7, 2018.
  6. Lipner SR, Scher RK. Onychomycosis: topical therapy and devices. In: Rubin AI, Jellinek NJ, Daniel CR III, et al, eds. Scher and Daniel’s Nails: Diagnosis, Surgery, Therapy. 4th ed. Cham, Switzerland: Springer International Publishing; 2018:173-184.
  7. Lipner SR, Scher RK. Nail growth evaluation and factors affecting nail growth. In: Humbert P, Fanian F, Maibach HI, et al, eds. Agache’s Measuring the Skin. 2nd ed. Berlin, Germany: Springer; 2017:867-881.
  8. Gupta AK, Elewski BE, Sugarman JL, et al. The efficacy and safety of efinaconazole 10% solution for treatment of mild to moderate onychomycosis: a pooled analysis of two phase 3 randomized trials. J Drugs Dermatol. 2014;13:815-820.
  9. Elewski BE, Rich P, Pollak R, et al. Efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase III multicenter, randomized, double-blind studies. J Am Acad Dermatol. 2013;68:600-608.
  10. Elewski BE, Aly R, Baldwin SL, et al. Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase-III studies. J Am Acad Dermatol. 2015;73:62-69.
  11. Rich P. Efinaconazole topical solution, 10%: the benefits of treating onychomycosis early. J Drugs Dermatol. 2015;14:58-62.
  12. Lipner SR, Scher RK. Efinaconazole 10% topical solution for the topical treatment of onychomycosis of the toenail. Expert Rev Clin Pharmacol. 2015;8:719-731.
  13. Del Rosso JQ. Onychomycosis of toenails and post-hoc analyses with efinaconazole 10% solution once-daily treatment: impact of disease severity and other concomitant associated factors on selection of therapy and therapeutic outcomes. J Clin Aesthet Dermatol. 2016;9:42.
  14. Lipner SR, Scher RK. Management of onychomycosis and co-existing tinea pedis. J Drugs Dermatol. 2015;14:492-494.
  15. Penlac [package insert]. Berwyn, PA: Dermik Laboratories; 2004.
  16. Jublia [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals, LLC; 2014.
  17. Kerydin [package insert]. Palo Alto, CA: Anacor Pharmaceuticals, Inc; 2014.
  18. Rock FL, Mao W, Yaremchuk A, et al. An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science. 2007;316:1759-1761.
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