Ciclopirox olamine: head to foot

Journal of Drugs in Dermatology, Jan, 2003 by F. Emily Bell, C. Ralph Daniel, Daniel Melissa P.

Introduction

Ciclopirox is a hydroxylated pyridone, a unique substance in our topical treatment armamentarium. It first came to market in Europe and has been in use for a number of years (1). Worldwide it is or has been available as a spray, vaginal cream, powder, solution, cream, lotion, gel, and nail lacquer. The latter four are available in the United States at the time of this article. Ciclopirox gel differs from other formulations. It contains ciclopirox as a free acid, as opposed to an olamine salt. Superficial fungal infections and seborrheic dermatitis are two of the most common disorders seen in dermatology and indeed in medicine in general; ciclopirox is active against both, and literally may be used head to foot.

Mechanism

Ciclopirox differs structurally from other available anti-fungals and works differently. It has a unique and complex mode of action which mainly affects iron dependent enzyme systems (e.g. cytochromes, catalase, peroxidase) and cytoplasmic membranes (e.g. transport mechanisms) (2). It penetrates well into the stratum corneum (3). Ciclopirox may affect Malassezia furfur via damage to the cell membranes and disorganization of internal structures (2). Furthermore, with Candida albicans and Saccharomyces cerevisiae, ciclopirox may block the transmembrane transport of radiolabeled leucine (2). The other main classes of topical antifungals are the imidazoles, polyenes, allylamines, and benzylamines.

1) Imidazoles. Ciclopirox does not affect sterol biosynthesis, as do the azoles. The later are primarily fungistatic and work by inhibiting, ergosterol synthesis primarily affecting the cell wall.

2) Polyenes. These also work by binding to ergosterol, therefore disrupting the fungal cell membranes primarily in Candida.

3) Allylamines / benzylamines. These are closely related substances that suppress ergosterol at an earlier point than the azoles by inhibiting squalene epoxidase.

Spectrum of Activity

Antimicrobial Activity

Its uniformity of antimycotic activity distinguishes ciclopirox from most other topical antifungals (4). It has fungicidal and sporicidal activity in vitro (5). It can also be fungistatic at times (2). It is active against dermatophytes, yeasts and non-dermatophyte molds MIC range 0/9-3/9 g/ml (6,7). It has in vitro activity against many grain positive and gram negative bacteria including Proteus species, Psuedomonas species, Proprionibacteria aches, and Corynebacterium minutissimum (6).

Antiinflammatory Activity

Ciclopirox olamine may exhibit better antiinflammatory activity than 2.5% hydrocortisone (8). It may inhibit prostaglandin and leukotriene synthesis in human polymorphonuclear cells (2).

Clinical Uses

Seborrheic Dermatitis

About 3-4% of the population has or has had seborrheic dermatitis. Sebum-rich areas promote growth of lipophilic yeast like Pityrosporum ovale and Malassezia. It is effective against seborrheic dermatitis of the face and the scalp (9). It has been used in a shampoo form outside of the USA. Although there are no good studies to prove this, ciclopirox shampoo could be used empirically to decrease the chance of relapse and reinfection after tinea capitis is treated orally, as has been done empirically by clinicians with ketoconazole shampoo.

Tinea Versicolor

Clinical and mycologic cure rates have been recorded as high as 77% after two weeks of treatment (11).

Tinea Corporis/Cruris

At the end of 28 days with twice a day treatment, 2/3 of patients were clinically and mycologically cured (4).

Candidosis

Cutaneous candidosis was 83% clinically cured and 82% to 90% mycologically cured in one study (12). Vaginal candidosis was treated as an inserted cream, which cleared the condition 72% in one study (13) and as high as 91% in another (12).

Tinea Pedis

The drug is active against the common mycological causes of tinea pedis, Trichophyton rubrum and Trichophyton mentagrophytes. It also has antibacterial and anti-inflammatory properties that make it especially helpful in inflammatory conditions such as inflamed tinea pedis. One may experience mild transient burning after application. Ciclopirox powder may be used for drying as well as for its antimicrobial effect.

Onychomycosis

Lacquer is applied nightly to toenails. It has been shown to penetrate the nail plate. Cure is less than 10% (17). Other studies have been done with different formulations with varying results (15,16). Theoretically, especially in the lacquer form, it may be used to decrease relapse and reinfection of onychomycosis (18,19).

Safety

Ciclopirox olamine is pregnancy Category B (5). Safety and efficacy are unproven in lactating women (5). Ciclopirox olamine 1% cream is not associated with delayed hypersensitivity type contact sensitization, contact sensitizers, phototoxicity, or photo contact sensitization (2).

Discussion

The pedal complex (foot and nails) often acts as the reservoir for fungus to spread elsewhere. The author feels strongly that when seeing tinea on the body other than on the scalp, the pedal complex needs to be examined.