Ciclopirox gel for seborrheic dermatitis of the scalp.
ABSTRACT Seborrheic dermatitis is a common inflammatory skin disorder that usually occurs in patients with pre-existing seborrhea. The etiology of seborrheic dermatitis is uncertain. Typically, sites dense with sebaceous glands support growth of the lipophilic yeast Malassezia furfur. Ciclopirox (Loprox) gel is a hydroxypyridone, broad-spectrum antifungal agent proven effective against the yeast M. furfur.
A multicenter, randomized, double-blind, vehicle controlled study of 178 subjects evaluated the efficacy of ciclopirox gel in treating seborrheic dermatitis of the scalp.
One hundred and seventy-eight subjects were randomized to apply either ciclopirox gel 0.77% twice daily, or vehicle twice daily for 28 days. Subjects' signs and symptoms of severity (erythema, scaling, pruritus and burning) were rated on a scale of 0-3 (none to severe); for inclusion, a minimum score of 4, for the sum of the individual ratings was required. Efficacy evaluations were performed at baseline, days 4, 8, 15, 22, 29, and at end-point (final visit, up to day 33). The primary efficacy variable was clinical response assessed by a global improvement, based on a scale of 0-5 (100% clearance to flare of treatment area). Changes in signs/symptoms severity scores within the target lesion were also evaluated.
Global evaluation scores demonstrated that significantly more ciclopirox-treated subjects achieved over 75% improvement compared with vehicle at days 22, 29, and endpoint (P < 0.01). Change-from-baseline mean score for total signs and symptoms was significantly greater in ciclopirox subjects compared with vehicle subjects at the same time points as above (P < 0.001), as well as day 15 (P < 0.01). Twenty-nine percent of subjects rated ciclopirox as having excellent cosmetic acceptability. There were only mild adverse events, with the most common being burning sensation in 13% of ciclopirox subjects and 9% of vehicle subjects.
Ciclopirox gel is effective and safe in the treatment of seborrheic dermatitis of the scalp.
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ABSTRACT: Ciclopirox is a topical antimycotic agent belonging to the chemical class of hydroxypyridones and not related to azoles or any other class of antifungal agents. Its antimicrobial profile includes nearly all of the clinically relevant dermatophytes, yeasts and moulds, and is therefore broader than that of most other antimycotics. It is also active against certain frequently azole-resistant Candida species and against some bacteria. The mechanism of action of ciclopirox is different from that of other topical antifungal drugs, which generally act through ergosterol inhibition. The high affinity of ciclopirox for trivalent metal cations, resulting in inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell, appears to be the major determinant of its antimicrobial activity. This unique and multilevel mechanism of action provides a very low potential for the development of resistance in pathogenic fungi, with cases of resistance rarely reported. Ciclopirox also displays mild anti-inflammatory effects in biochemical and pharmacological models; effects also shown in small clinical studies. Scavenging of reactive oxygen species released from inflammatory cells is a likely contributor to these anti-inflammatory effects. Ciclopirox, and its olamine salt, is available in multiple topical formulations, suitable for administration onto the skin and nails and into the vagina. The pharmaceutical forms most widely investigated are 1% ciclopirox olamine cream and 8% ciclopirox acid nail lacquer, but lotion, spray, shampoo, pessary, solution, gel and douche formulations have also been used. Ciclopirox penetrates into the deep layers of the skin, mucosal membranes and nail keratin, reaching concentrations exceeding the minimal fungicidal concentrations for most medically important fungi. A large number of clinical trials were and are still being performed with ciclopirox, starting in the early 1980s. Ciclopirox was first developed for fungal skin infections and vaginal candidiasis, and is currently well established in these indications. More recently, the drug has been clinically investigated in seborrhoeic dermatitis and onychomycosis, showing good efficacy and excellent tolerability. Emphasis in this review is given to a ciclopirox medicated nail lacquer, which is based on an original technology and has superior properties in terms of its affinity to keratin and nail permeation. It has been found to have superior efficacy and safety to another commercially available formulation in the treatment of onychomycosis. The safety features of ciclopirox are well known. The topical drug is devoid of systemic adverse reactions. Mild local reactions characterized by a burning sensation of the skin, irritation, redness, pain or pruritus, generally in less than 5% of treated patients, can be observed following skin and vaginal application. With nail application, the most common adverse event is the appearance of mild erythema in 5% of the treated population. As a general conclusion, although less effective than some oral antimycotic agents in various indications, ciclopirox compares very well in terms of the benefit/risk ratio due to its excellent tolerability and complete absence of serious adverse effects.Drugs 11/2010; 70(16):2133-52. · 4.63 Impact Factor
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ABSTRACT: Superficial fungal infections are among the most widespread diseases known to man. They target parts of the body as diverse in form and function as the skin, the nail, the buccal cavity, the eye and the vagina. Fungistatic azole drugs, that is, imidazole- and triazole-containing compounds (e.g. miconazole and itraconazole, respectively), have been the mainstay of antifungal therapy for many years. The polyene nystatin is effective in treating Candida infections but is inactive against cutaneous dermatophytes. The advent of the fungicidal allylamines (e.g. terbinafine) and their congeners (e.g. butenafine) has improved treatment options: the course of therapy is shorter and cure rates higher with fungicidal drugs. Other newer agents include the echinocandins (e.g. caspofungin) that are primarily intended for systemic administration but which may have a role in topical therapy. In order to elicit a pharmacologic response following topical administration, these agents must enter into and diffuse across the target biologic tissues, which have distinct architectures and compositions depending on their function. The rate and extent of transport will depend on the interplay between the drug's molecular properties and the characteristics of the biologic tissue. The drug may also interact with specific proteins or other membrane components. These interactions can prolong residence time and therapeutic effect; for example, azoles have an affinity for keratin (as do dermatophytes, their therapeutic target). Drug properties that increase permeability across a given membrane may render the molecule less effective at another biologic tissue; for example, the stratum corneum is a lipidic barrier, whereas the keratin-rich nail contains 10-fold less lipid and is perhaps best viewed as a hydrogel with very low lipid content. Consequently, both offer very different environments and drug delivery challenges compared with the oral and vaginal mucosae. In light of this, it is clear that formulation design and optimization are key steps in increasing the therapeutic efficacy of topical antifungal therapy. Furthermore, the formulation, which is the primary interface with the membrane, must not only be optimized with respect to the drug but also be compatible with the biologic tissue. Thus, developing effective formulations for topical therapy is a complex task. In this review, we provide a brief description of newer approaches in topical antifungal drug development and present a survey of recent work.American Journal of Drug Delivery 12/2005; 4(4):231-247.
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ABSTRACT: Seborrheic dermatitis is a chronic superficial fungal infection of the skin, particularly affecting sites rich in sebaceous glands. Although the precise etiology of seborrheic dermatitis is uncertain, yeasts of the genus Malassezia are known to play a causative role. Ciclopirox is a broad-spectrum, hydroxypyridone-derived, synthetic antifungal agent, which also has anti-inflammatory properties. Ciclopirox is effective both in vitro and in vivo against Malassezia yeasts, making it a valuable option for the treatment of seborrheic dermatitis. Varying frequencies and concentrations of ciclopirox shampoo have been shown to be effective and safe in the treatment of seborrheic dermatitis of the scalp.International Journal of Dermatology 02/2006; 45(1):66-9. · 1.34 Impact Factor