Naftifine

Abstract

Naftifine is an allylamine derivative for topical administration with a mechanism of action distinct from that of other classes of antifungal agents. It inhibits squalene epoxidase and may have certain anti- inflammatory properties, but its precise mechanism of action is as yet unclear. In vitro, naftifine has potent fungistatic and fungicidal activity against dermatophytes. This correlates well with its clinical and mycological activity in patients with dermatophytoses. There is improvement in clinical symptoms and overall therapeutic success after a 2- to 5-week course of therapy in a high percentage of patients (usually over 80%) with tinea cruris or corporis, and in a slightly smaller percentage of those with tinea pedis. Naftiflne is moderately active in vitro against moulds, but is generally less active against yeästs, including Candida albicans. However, it has proved reasonably effective in the treatment of patients with cutaneous candidiasis, although further studies are necessary to establish its place in therapy for this indication. In view of its good local tolerability, absence of systemic adverse effects, novel mechanism of action and effectiveness with once-daily application, naftiflne offers a useful addition to available pharmaceutical options in patients with dermatomycoses. Naftiflne, an allylamine derivative, is an antifungal agent with a complex and as yet incompletely understood mechanism of action, although inhibition of squalene epoxidase and, therefore, ergosterol biosynthesis would appear to play a central role. Unlike other antifungal agents, such as the azoles, naftiflne is selective to fungal sterol synthesis and is not likely to influence hepatic drug metabolism even if significant systemic concentrations are achieved (which with recommended topical application is apparently not the case). In vitro studies show naftifine to be à potent inhibitor of dermatophytes, with minimum inhibitory concentrations (MICs) against Trichophyton spp., Microsporum spp. and Epidermophyton floccosum of ⩽0.2 mg/L. It has moderate activity against Aspergillus spp. (MIC range 0.25 to 12.5 mg/L), Sporothrix schenckii (0.06 to 8 mg/L) and some strains of Candida parapsilosis, brumptii, scottii and ceylanoides (1 to 8 mg/L), but is generally poorly active in vitro against Candida spp. and other yeasts. Naftifine has both fungicidal and fungistatic activity, the former demonstrated in vitro against Trichophyton rubrum, Candida albicans, (MIC 50 mg/L) Blastomyces dermatitidis, Histoplasma capsulatum and S. schenckii at MICs. Indirect evidence of fungicidal activity also comes from in vivo studies showing naftifine to completely eradicate infections in guinea-pig hair follicles within 3 days; in comparison econazole had only 80% mycological efficacy after 7 days. There is some evidence to suggest that naftifine also has a more rapid effect than other antifungal agents in clinical practice, and this has been attributed to the fungicidal activity in addition to a proposed anti-inflammatory property which requires verification. In vitro and in vivo studies involving human skin indicate that naftifine penetrates the epidermis in concentrations sufficient to inhibit fungal growth. There are very few published data on the systemic absorption of naftifine, and systemic adverse effects have not been reported. About 2 to 6% of an applied dose of radiolabelled naftifine was absorbed cutaneously in healthy volunteers. Naftifine has undergone adequate investigation in controlled trials in patients with dermatophytoses to show that application of 1% cream once or twice daily for 3 to 4 weeks is very effective, both from a clinical and mycological viewpoint. Earlier studies employed a regimen involving twice-daily application, but the evidence suggests that once-daily application is equally effective. In comparisons of naftifine with vehicle only, the active treatment produced significantly better mycological and clinical cure rates. Mycological cure rates tended to be better in patients with tinea cruris or corporis (84 to 94% cure with naftifine vs 30 to 45% with vehicle only) than with tinea pedis (57 to 66% vs 19 to 38%, respectively). This difference was also apparent in other comparative studies. There were significant differences between naftifine and other antifungal agents in only a few controlled clinical trials, but both from a clinical and mycological perspective there were trends in favour of naftifine, and certainly evidence of a more rapid onset of action, in comparison with clotrimazole or econazole. Naftifine also proved equally as effective as fenticonazole and miconazole. Mycological cure rates with naftifine after at least 2 weeks’ treatment generally exceeded 80%. There was usually a rapid reduction in the severity of clinical symptoms, including erythema, pruritus, scaling, infiltration and exudation, and overall therapeutic success (combined mycological and clinical cure) in 70 to over 90% of patients. In a few studies naftifine alone was equally effective as an azole derivative in combination with a corticosteroid in patients with inflammatory or eczematous dermatomycoses. Results of an uncontrolled study suggest that naftifine 1% solution is effective in the treatment of pityriasis versicolor. Despite naftifine’s poor in vitro activity against Candida albicans, application of 1% cream twice daily for 3 to 4 weeks in patients with cutaneous candidiasis has proved effective in the small number of studies conducted, with mycological cure rates ranging from 83 to 93% and therapeutic success rates 2 weeks after the end of treatment in the range of 73 to 77%. Naftifine is well tolerated. Systemic adverse effects have not been reported in clinical trials, and although local irritation may occur in some patients it rarely requires treatment discontinuation. There have been a few reports of allergic contact dermatitis associated with naftifine application. Naftifine is available as a 1% cream or gel formulation and may be applied once or twice daily to infected sites, usually for a period of 3 to 4 weeks.