Ciclopirox Olamine 1% Cream A Preliminary Review of its Antimicrobial Activity and Therapeutic Use

Abstract

Synopsis: Ciclopirox olamine¹ is a substituted pyridone antimycotic, unrelated to the imidazole derivatives, with activity against a broad spectrum of dermatophytes, yeasts, actinomycetes, molds, other fungi, and a variety of Gram-positive and Gram-negative bacteria. The efficacy of ciclopirox olamine cream has been demonstrated in open and placebo-controlled studies in patients with superficial dermatophyte or yeast infections, and in double-blind comparative trials in patients with dermatomycoses, topical ciclopirox olamine was comparable to or better than clotrimazole in efficacy and caused a similar number of side effects. Ciclopirox olamine penetrates through fingernails and in preliminary studies has been successfully used in onychomycoses. However, further studies are needed to establish the role of ciclopirox in the treatment of onychomycoses and dermatomycoses relative to that of the more recently introduced antifungal agents. Antimicrobial Studies: The antimicrobial profile of ciclopirox is broader than that of some antimycotics in that it includes dermatophytes, Candida, and important Gram-positive and Gram-negative bacteria. Against common fungal pathogens, in vitro ciclopirox olamine produces complete inhibition at low concentrations of 1 to 4 mg/L when certain antagonising test substrates are avoided. The activity of ciclopirox, unlike that of clotrimazole and miconazole, is only moderately diminished in the presence of albumin added to the incubation medium. The primary site of action at concentrations below 20 mg/L appears to be the cell membrane, where transmembrane transport at least of amino acids into the fungal cell is blocked. At higher concentrations, ciclopirox alters fungal cell membrane integrity allowing leakage of intracellular material. The latter phenomenon has also been reported with nystatin, clotrimazole and miconazole. Pharmacokinetic Studies: Following topical application of ciclopirox olamine (36 to 37mg) as 1% cream to human skin about 1.3% of the dose is absorbed systemically. Peak serum concentrations reach 0.01 mg/L 6 hours after application. In cadaverous skin, concentrations inhibitory for tested fungi are present within 1 to 2 hours after application and are maintained in the epidermis during the application period. Following application of radiolabelled ciclopirox olamine to human skin, most radioactivity is found on the skin surface, in the hair follicles, and uppermost skin layers. Ciclopirox olamine penetrates through the fingernail. Ciclopirox is excreted in urine with approximately 80% of an oral dose excreted as the glucuronide metabolite. Therapeutic Trials: Open and a few controlled trials in patients with dermatomycoses have revealed that ciclopirox olamine is more effective than placebo and at least as effective as clotrimazole. Controlled trials have yet to be conducted to compare ciclopirox with tolnaftate, miconazole, or other antifungal agents. The overall profile and incidence of side effects for ciclopirox olamine is similar to clotrimazole. Preliminary studies in onychomycoses have indicated potential usefulness of ciclopirox in this difficult-to-treat infection and of the vaginal cream in the therapy of vaginal and vulvovaginal candidal infection. Side Effects: In clinical trials, side effects occurred in 1 to 4% of patients and were limited to irritation, redness, pain, burning or itching. In very few patients, treatment was discontinued because of irritation of unknown origin. Dosage and Administration: In dermatological infections, ciclopirox olamine 1% cream is applied twice daily and gently rubbed into the affected and surrounding skin area. Clinical improvement can occur within the first week of treatment, but if no clinical improvement has occurred after 4 weeks of treatment (2 weeks for tinea versicolor), the diagnosis should be re-examined.