Absorption and efficacy of miconazole nitrate 0.25% ointment in infants with diaper dermatitis

Journal of Drugs in Dermatology, May, 2007 by Lawrence F. Eichenfield, Melissa L. Bogen

Abstract

Background: The potential for toxicity from systemic absorption of topical miconazole in infants is a concern.

Objective: To assess the relative safety of 0.25% miconazole based on the amount absorbed through the skin of infants with diaper dermatitis after multiple applications.

Methods: Of 24 infants with moderate to severe diaper dermatitis, 19 received 0.25% miconazole nitrate ointment and 5 received 2% miconazole nitrate cream for 7 days at each diaper change and after bathing. Blood samples were collected prior to treatment and after 7 days.

Results: In the 0.25% treatment group, blood concentrations of miconazole were nondetectable (<1 ng/mL) in 83% (15/18) and minimal (3.0 to 3.8 ng/mL) in 17% (3/18). Samples were missing for one patient. For the 5 infants in the 2% treatment group, miconazole concentration was nondetectable in 20% (1/5) and less than 7.4 ng/mL in 4 infants. No adverse events were noted.

Conclusions: Systemic absorption of 0.25% miconazole nitrate ointment was minimal, demonstrating its safety in the treatment of moderate to severe diaper dermatitis.

Introduction

Diaper dermatitis is the most common skin disorder among infants, (1,2) particularly between 9 and 12 months of age. (3) The moist environment under the diaper makes the skin more susceptible to infection with microorganisms, which exacerbate the condition and may lead to potentially life-threatening systemic candidal infections. (4-6) Clinical studies have identified Candida albicans (C. albicans) as an important factor in the evolution of diaper dermatitis. (2,7,8) In infants with diaper dermatitis, recovery of C. albicans on skin has ranged from 8% (9) to 77%. (10) In a series of studies, Dixon et al recovered C. albicans from the skin (41% of specimens) (11) and the feces (44% (11) and 39% (12) of specimens) of infants with diaper dermatitis.

Typical medical treatments for diaper dermatitis include application of topical antifungals, steroids, and combinations thereof. (2,13) Topical corticosteroids are clinically effective but easily absorbed by the skin, (14,15) which is cause for concern when treating infants with dermatitis because the skin of preterm infants is more permeable than adult skin. (14) Therefore, infants absorb proportionately greater quantities of topical medication than adults due to their relatively large surface areas, and tests have shown the potential for topical corticosteroids to cause suppression of the hypothalamic-pituitary axis with possible impairment of growth. (14,15) Moreover, many of these products are not approved by the US FDA for use on infants as young as 4 weeks. (2,16)

When C. albicans infections complicate diaper dermatitis, a topical antifungal is warranted. (13,17) Miconazole nitrate has been shown to be effective against C. albicans. (18,19) A 2% miconazole nitrate cream successfully treated Candida skin infections in the diaper area of premature and term infants and children. (20,21) Two trials compared 0.25% miconazole nitrate ointment with ointment base for the treatment of acute infant diaper dermatitis complicated by candidiasis. (13,22) The active treatment was well-tolerated and significantly more effective than the ointment base in treating diaper dermatitis. Miconazole nitrate 0.25% is the active ingredient in Vusion[TM] ointment, the first and only product indicated and specifically formulated for diaper dermatitis complicated by candidiasis (DDCC) in immunocompetent patients 4 weeks and older. (23)

Studies have shown that systemic absorption of miconazole after topical and vaginal application is minimal. (24,25) Prior to this study, absorption of miconazole nitrate through inflamed skin of infants with diaper dermatitis had not been evaluated. We conducted this study to determine the amount of miconazole nitrate ointment absorbed through the skin of infants with moderate to severe diaper dermatitis after multiple applications.

Materials and Methods

Study Design

This uncontrolled, open-label, noncrossover, clinical pharmacology study was conducted from July 1988 through June 1989 at the Hospital General Vasco de Quiroga in Morelia, Michoacan, Mexico. The study was accepted by the US FDA and approved by the institutional review board (IRB). Each participant's parent or legal guardian signed an informed consent form before the beginning of the study.

Patients

Male and female infants between the ages of 1 and 12 months who had been hospitalized for treatment of systemic pathology, primarily gastroenteritis, and who had dermatologic manifestations consistent with a diagnosis of moderate to severe diaper dermatitis were eligible for study inclusion. Moderate to severe diaper dermatitis was defined as a rash evaluation score of 2 or higher using the following scale: 0=none, 1=mild erythema with minimal maceration or chafing, 2=moderate erythema with or without satellite papules with maceration and chafing, 3=severe erythema with papulopustules and maceration, and 4=severe erythema with erosions or ulceration.