efinaconazole and Tinea-Pedis

Approximately 20-25% of the population worldwide is affected by superficial cutaneous mycoses (SCM). SCM are cutaneous fungal infections with a wide array of systemic and topical treatment options. However, successful therapeutic outcomes are limited by patient non-adherence, medication side effects, potential drug interactions, antifungal resistance and disease recurrence. Advances in formulation technology have allowed for the development of more effective and safer therapies. In this article we will review several new and emerging pharmacotherapeutics for onychomycosis and tinea pedis.

Topics: Allylamine; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Education, Medical, Continuing; Humans; Imidazoles; Itraconazole; Onychomycosis; Tinea Pedis; Triazoles

We sought to evaluate the efficacy of efinaconazole topical solution, 10%, in patients with onychomycosis and coexisting tinea pedis.. We analyzed 1,655 patients, aged 18 to 70 years, randomized (3:1) to receive efinaconazole topical solution, 10%, or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point was complete cure rate (0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings) at week 52. Three groups were compared: patients with onychomycosis and coexisting interdigital tinea pedis on-study (treated or left untreated) and those with no coexisting tinea pedis.. Treatment with efinaconazole topical solution, 10%, was significantly more effective than vehicle use irrespective of the coexistence of tinea pedis or its treatment. Overall, 352 patients with onychomycosis (21.3%) had coexisting interdigital tinea pedis, with 215 of these patients (61.1%) receiving investigator-approved topical antifungal agents for their tinea pedis in addition to their randomized onychomycosis treatment. At week 52, efinaconazole complete cure rates of 29.4% were reported in patients with onychomycosis when coexisting tinea pedis was treated compared with 16.1% when coexisting tinea pedis was not treated. Both cure rates were significant compared with vehicle (P = .003 and .045, respectively), and in the latter subgroup, no patients treated with vehicle achieved a complete cure.. Treatment of coexisting tinea pedis in patients with onychomycosis enhances the efficacy of once-daily topical treatment with efinaconazole topical solution, 10%.

Topics: Administration, Topical; Adolescent; Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Onychomycosis; Tinea Pedis; Treatment Outcome; Triazoles; Young Adult

Recurrence (relapse or re-infection) in onychomycosis is common, occurring in 10% to 53% of patients. However, data on prevalence is limited as few clinical studies follow patients beyond 12 months. It has been suggested that recurrence after continuous terbinafine treatment may be less common than with intermittent or continuous itraconazole therapy, probably due to the fungicidal activity of terbinafine, although these differences tended not to be significant. Relapse rates also increase with time, peaking at month 36. Although a number of factors have been suggested to play a role in recurrence, only the co-existence of diabetes has been shown to have a significant impact. Data with topical therapy is sparse; a small study showed amorolfine prophylaxis may delay recurrence. High concentrations of efinaconazole have been reported in the nail two weeks' post-treatment suggesting twice monthly prophylaxis with topical treatments may be a realistic option, and may be an important consideration in diabetic patients with onychomycosis. Data suggest that prophylaxis may need to be continued for up to three years for optimal effect. Treating tinea pedis and any immediate family members is also critical. Other preventative strategies include avoiding communal areas where infection can spread (such as swimming pools), and decontaminating footwear.

Topics: Administration, Topical; Antifungal Agents; Comorbidity; Diabetes Mellitus; Drug Administration Schedule; Humans; Itraconazole; Morpholines; Naphthalenes; Onychomycosis; Prevalence; Recurrence; Terbinafine; Tinea Pedis; Triazoles

Onychomycosis and tinea pedis are common fungal infections affecting the nails and feet, respectively. Two newly approved topical agents for onychomycosis are efinaconazole and tavaborole, both of which have demonstrated respectable cure rates in clinical studies. For tinea pedis, naftifine 2% and luliconazole 1% are new agents, both administered for relatively short courses, that may foster greater adherence Semin Cutan Med Surg 35(supp6):S110-S113.

Topics: Administration, Cutaneous; Antifungal Agents; Humans; Imidazoles; Onychomycosis; Recurrence; Tinea; Tinea Pedis; Triazoles

Onychomycosis is a common nail infection that often co-exists with tinea pedis. Surveys have suggested the diseases co-exist in at least one third of patients, although actual numbers may be a lot higher due to significant under-reporting. The importance of evaluating and treating both diseases is being increasingly recognized, however, data on improved outcomes, and the potential to minimize re-infection are limited. We review a recent post hoc analysis of two large studies treating mild to moderate onychomycosis with efinaconazole topical solution, 10%, demonstrating that complete cure rates of onychomycosis are significantly improved when any co-existing tinea pedis is also treated.

Topics: Administration, Topical; Antifungal Agents; Clinical Trials as Topic; Humans; Onychomycosis; Severity of Illness Index; Tinea Pedis; Triazoles

The therapeutic efficacy of KP-103, a triazole derivative, for 10 guinea pigs with interdigital tinea pedis or tinea corporis was investigated. Topical KP-103 solution (0.25 to 1%) was dose-dependently effective in treating both dermatophytoses. A 1% KP-103-treatment rendered all infected skins culture-negative on day-2 posttreatment. A high negative-culture rate was obtained with 1% solutions of butenafine and lanoconazole but not with 1% neticonazole solution. The follow up study performed on day-30 and day-9 posttreatment demonstrated that the relapse rates for 1% KP-103-treated animals with tinea pedis and for those with tinea corporis were 20 and 30%, respectively, and that these values were the same as those for 1% butenafine-treated animals, but lower than those for 1% lanoconazole-treated animals (55 and 80%, respectively). When a single dose of 1% KP-103 was applied to the back skin 48 hr before fungal inoculation, 9 of the 10 animals were protected from the dermatophytosis, suggesting that active KP-103 is retained in skin tissue for at least 48 hr after dosing. Moreover, it was suggested that KP-103 retains a high activity in the horny layer because of its lower keratin-affinity. The effectiveness of KP-103 against dermatophytoses may be due to the favorable pharmacokinetic properties in the skin tissues, together with its potent antifungal activity.

Topics: Animals; Antibiotic Prophylaxis; Antifungal Agents; Aspergillus flavus; Disease Models, Animal; Drug Evaluation, Preclinical; Guinea Pigs; Keratins; Male; Microbial Sensitivity Tests; Secondary Prevention; Tinea; Tinea Pedis; Toes; Treatment Outcome; Triazoles; Trichophyton

We developed a new technique for culture study that successfully recovers fungi from drug-treated skin tissues, in which tissue specimens were homogenized, dialyzed against water, digested with trypsin, and then washed with PBS, to eliminate the drug that remaining in the skin tissue specimens. With this modified culture method, we reevaluated the efficacy of KP-103, neticonazole, and lanoconazole in a guinea pig interdigital tinea pedis model. Guinea pigs with tinea pedis were topically treated with a 1% solution of KP-103 or a reference drug once a day for 10 consecutive days. Five days after the last treatment, left and right feet were subjected to culture study by the conventional and modified recovery culture methods, respectively. One hundred percent (20/20) of lanoconazole-treated feet were judged as culture-negative by the conventional culture method, but 85% (17/20) of the feet were shown to be culture-positive when the modified recovery culture method was used. On the other hand, KP-103 achieved high rates of culture-negative rates, 95% (19/20) and 85% (17/20), in both conventional and modified culture methods, respectively. Furthermore, on day-30 posttreatment, KP-103 sterilized 14 of the 20 infected feet, whereas neticonazole and lanoconazole were not effective even in reducing fungal burden. KP-103 proved to be highly effective in achieving mycological cure and preventing relapse against tinea pedis presumably because of its good bioavailability in the skin based on its low keratin-affinity, along with its potent antifungal activity.

Topics: Animals; Antifungal Agents; Colony Count, Microbial; Culture Media; Drug Evaluation, Preclinical; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Male; Microbial Sensitivity Tests; Models, Animal; Time Factors; Tinea Pedis; Treatment Outcome; Triazoles; Trichophyton

The therapeutic efficacy of KP-103, a novel topical triazole, in a guinea pig tinea unguium model was investigated. Experimental tinea unguium and tinea pedis were produced by inoculation of Trichophyton mentagrophytes SM-110 between the toes of the hind paw of guinea pigs. One percent solution (0.1 ml) of KP-103, amorolfine, or terbinafine was topically applied to the nails and whole sole of an infected foot once daily for 30 consecutive days, and terbinafine was also orally administered at a daily dose of 40 mg/kg of body weight for 30 consecutive days, starting on day 60 postinfection. The fungal burdens of nails and plantar skin were assessed using a new method, which makes it possible to recover infecting fungi by removing a carryover of the drug remaining in the treated tissues into the culture medium. Topically applied KP-103 inhibited the development of nail collapse, significantly reduced the fungal burden of the nails, and sterilized the infected plantar skin. On the other hand, topical amorolfine and topical or oral terbinafine were ineffective for tinea unguium, although these drugs eradicated or reduced the fungal burden of plantar skin. The in vitro activities of amorolfine and terbinafine against T. mentagrophytes SM-110 were 8- and 32-fold, respectively, decreased by the addition of 5% keratin to Sabouraud dextrose broth medium. In contrast, the activity of KP-103 was not affected by keratin because its keratin affinity is lower than those of the reference drugs, suggesting that KP-103 largely exists in the nails as an active form that was not bound to keratin and diffuses in the nail without being trapped by keratin. The effectiveness of KP-103 against tinea unguium is probably due to its favorable pharmacokinetic properties in the nails together with its potent antifungal activity.

Topics: Administration, Oral; Administration, Topical; Animals; Antifungal Agents; Guinea Pigs; Male; Microbial Sensitivity Tests; Morpholines; Naphthalenes; Onychomycosis; Terbinafine; Tinea Pedis; Triazoles; Trichophyton

The in vitro activity of KP-103, a novel triazole derivative, against pathogenic fungi that cause dermatomycoses and its therapeutic efficacy against plantar tinea pedis and cutaneous candidiasis in guinea pigs were investigated. MICs were determined by a broth microdilution method with morpholinepropanesulfonic acid-buffered RPMI 1640 medium for Candida species and with Sabouraud dextrose broth for dermatophytes and by an agar dilution method with medium C for Malassezia furfur. KP-103 was the most active of all the drugs tested against Candida albicans (geometric mean [GM] MIC, 0.002 microg/ml), other Candida species including Candida parapsilosis and Candida glabrata (GM MICs, 0.0039 to 0.0442 microg/ml), and M. furfur (GM MIC, 0.025 microg/ml). KP-103 (1% solution) was highly effective as a treatment for guinea pigs with cutaneous candidiasis and achieved mycological eradication in 8 of the 10 infected animals, whereas none of the imidazoles tested (1% solutions) was effective in even reducing the levels of the infecting fungi. KP-103 was as active as clotrimazole and neticonazole but was less active than lanoconazole and butenafine against Trichophyton rubrum (MIC at which 80% of isolates are inhibited [MIC(80)], 0.125 microg/ml) and Trichophyton mentagrophytes (MIC(80), 0.25 microg/ml). However, KP-103 (1% solution) exerted therapeutic efficacy superior to that of neticonazole and comparable to those of lanoconazole and butenafine, yielding negative cultures for all samples from guinea pigs with plantar tinea pedis tested. This suggests that KP-103 has better pharmacokinetic properties in skin tissue than the reference drugs. Because the in vitro activity of KP-103, unlike those of the reference drugs, against T. mentagrophytes was not affected by hair as a keratinic substance, its excellent therapeutic efficacy seems to be attributable to good retention of its antifungal activity in skin tissue, in addition to its potency.

Topics: Animals; Antifungal Agents; Blood Proteins; Candida; Candidiasis, Cutaneous; Culture Media; Disease Models, Animal; Guinea Pigs; Hair; Microbial Sensitivity Tests; Tinea Pedis; Treatment Outcome; Triazoles; Trichophyton