Lawrence F. Eichenfield, MD1; Elvira M. Gisoldi, MA2
AAD 2007 Poster 820
Comparative Absorption of 0.25% and 2% Miconazole Nitrate Preparations 1
Children’s Hospital and Health Center, San Diego, CA;
in Infants With Diaper Dermatitis 2
Barrier Therapeutics, Princeton, NJ
Introduction Methods Results
Evaluation of miconazole absorption • On Day 3, the rash scores were 1.89 ± 0.94 in the 0.25%
• Diaper dermatitis is the most common skin disorder among • This uncontrolled, open-label, noncrossover, clinical pharmacology • A total of 24 infants (12 male and 12 female) enrolled and • In the 19 infants treated for 7 days with multiple daily applications miconazole nitrate group and 2.60 ± 1.34 in the 2% miconazole
infants1,2 and is particularly common between 9 and12 months study evaluated male and female infants between the ages of 1 and completed the study. Nineteen infants received 0.25% miconazole of 0.25% miconazole nitrate ointment, blood concentrations of nitrate group
of age3 12 months who had been hospitalized for treatment of systemic nitrate ointment, and 5 infants received 2% miconazole nitrate miconazole absorbed were nondetectable (<1 ng/mL) in 83% • On Day 5, the rash scores were 0.84 ± 0.76 and 1.20 ± 0.84,
• The condition is usually caused by frictional irritation, particularly pathology, primarily gastroenteritis, and who had dermatologic cream. Blood samples were missing for 1 patient in the 0.25% (15 of 18 infants) and at or near the lower limit of detection respectively; and on Day 7 the scores were 0.32 ± 0.48 and
when the skin has been overhydrated by occlusive diapers after manifestations consistent with a diagnosis of moderate-to-severe miconazole nitrate group (3.0 to 3.8 ng/mL) in 17% (3 of 18 infants). Blood samples were 0.40 ± 0.55, respectively
urination or defecation diaper dermatitis. Moderate-to-severe diaper dermatitis was • At baseline, the severity of the diaper rash for half the subjects missing for 1 infant
• The moist environment under the diaper also makes the skin more defined as a rash evaluation score of 2 or higher (Table 1) was rated as moderate erythema with or without satellite • In the 5 infants treated with 2% miconazole nitrate cream,
susceptible to infection with microorganisms, which exacerbate the papules with maceration and chafing (rash score of 2). One fourth miconazole was nondetectable in 20% (1 infant) and concentrations
condition and may lead to potentially life-threatening systemic Table 1. Rash Evaluation Scale of the infants (n=6) had severe erythema with papulopustules and of 5.2 to 7.4 ng/mL were noted in 80% (4 infants) (Table 3).There
candidal infections4-6 maceration (rash score of 3) and one fourth of the infants (n=6) was no correlation between age, sex, weight, or diaper rash scores
• Clinical studies have identified Candida albicans as an important 0 = none had severe erythema with erosions or ulceration (rash score of 4) with blood concentration
factor in the evolution of diaper dermatitis2,7,8 (Figure 1) 1 = mild erythema with minimal maceration or chafing • At baseline, no significant differences were noted in the
• Typical medical treatments for 2 = moderate erythema with or without satellite papules demographics and patient characteristics between treatment
diaper dermatitis include application groups (Table 2)
Table 3. Distribution of Miconazole Blood
with maceration or chafing
of topical antifungal agents and Levels After 7 Days of Treatment
steroids2,9 3 = severe erythema with papulopustules and maceration Miconazole 0.25% Miconazole 2% Miconazole
• Topical corticosteroids are clinically
Table 2. Patient Demographics and
4 = severe erythema with erosions or ulceration concentration nitrate (n=19) nitrate (n=5)
effective for inflammation but are Baseline Conditions None detected 15 1
easily absorbed by the skin,10,11 0.25% 1-4 ng/mL 3 0
which is cause for concern when • Entry criteria included no known sensitivity to miconazole nitrate Miconazole 2% Miconazole 5-8 ng/mL 0 4
treating infants with dermatitis or zinc oxide, no active dermatological conditions other than Figure 2. Mean rash scores for all patients throughout the study.
Variable nitrate (n=19) nitrate (n=5) Overall
because the skin is more permeable diaper rash, and no known allergy or sensitivity to skin care Sex • All infants treated with multiple applications of miconazole nitrate
than adult skin10 toiletry products Male 9 3 12 had blood concentrations below 8 ng/mL. Of the 7 infants who had
• Infants may absorb proportionately • Participants were to remain hospitalized throughout the 7-day Female 10 2 12 detectable levels of miconazole nitrate, 3 in the 0.25% treatment
Figure 1. Presentation of
diaper dermatitis complicated
greater quantities of topical trial period Age (months) group had blood concentrations of 3.0, 3.5, and 3.8 ng/mL, and 4
medication than adults, and tests • Blood samples (0.5 mL of whole blood) for analysis of absorption in the 2% treatment group had blood concentrations of 5.2, 6.6, • Seven days of multiple daily applications resulted in blood
1-6 10 3 13
Photograph courtesy of Linda De Raeve, MD, VUB, have shown the potential for topical of miconazole nitrate were collected prior to treatment on Day 0 6.8, and 7.4 ng/mL (Table 4) concentrations of <8 ng/mL in all patients, and nondetectable
Brussels, Belgium, 2004.
corticosteroids to cause and at the completion of treatment on Day 7, after the routine 7-12 9 2 11
levels in most of the 0.25% miconazole group
suppression of the hypothalamic-pituitary axis with possible blood testing for the underlying gastroenteritis Mean ± SD 7.16 ± 4.21 5.8 ± 4.08 6.87 ± 4.13
Table 4. Miconazole Blood Concentrations • The results of this study demonstrate the safety of 0.25%
impairment of growth.10,11 Moreover, many of these products are • 2% miconazole cream was tested in 5 of the 24 patients enrolled Range 1-12 1-10 1-12
miconazole nitrate ointment in the treatment of moderate-to-
not approved by the US Food and Drug Administration for use on • The test medications were applied sparingly at each diaper change Body weight (kg) in the 7 Infants With Detectable Levels severe diaper dermatitis
infants as young as 4 weeks2,12 and after bathing at least 5 times per day for 7 days to the clinically Mean ± SD 6.41 ± 2.76 4.96 ± 1.97 6.10 ± 2.64 Formulation Miconazole blood
• When C. albicans infection complicates diaper dermatitis, a topical affected area Range 2.8 - 10.5 2.8 - 7.1 2.8 - 10.5 concentration concentration (ng/mL)
antifungal is warranted9,13 • Treatment of the affected area was to continue, even if symptoms
• The antifungal agent, miconazole nitrate, has been shown to be of diaper dermatitis were no longer visible
0.25% 3.0 References
0.25% 3.5 1. Ward DB, Fleischer AB Jr, Feldman SR, Krowchuk DP. Arch Pediatr Adolesc Med. 2000;
effective against C. albicans14,15 • Use of other topical or systemic antifungal therapy or diaper rash* (n)
0.25% 3.8 154:943-946.
• A 2% miconazole nitrate cream successfully treated Candida skin corticosteroid treatment was not permitted. Only medications Score of 2 10 2 12 2. Shin HT. Dermatol Ther. 2005;18:124-135.
infections in the diaper area of premature and term infants as well already administered on admission to the study were permitted, 2% 5.2 3. Jordan WE, Lawson KD, Berg RW, Franxman JJ, Marrer AM. Pediatr Dermatol. 1986;3:198-207.
Score of 3 5 1 6
4. Randolph S. RN. 2002;65(3):41-44.
as children16,17 except those necessary for emergency reasons Score of 4 4 2 6 2% 6.6
5. Passeron T, Desruelles F, Gari-Toussaint M, Dageville C, Lacour JP. Pediatr Dermatol. 2004;
• Miconazole nitrate 0.25%/15% zinc oxide/81.35% white • Clinical evaluations of the diaper rash (if present) continued on 2% 6.8 21:260-261.
petrolatum ointment is the only product indicated and specifically treatment Days 1, 3, 5, and 7. On Day 7, another physical 0=No lesions 2% 7.4
6. Rowen JL,Tate JM, Nordoff N, Passarell L, McGinnis MR. J Clin Microbiol. 1999;37:3735-3737.
7. Rebora A, Leyden JJ. Br J Dermatol. 1981;105:551-555.
formulated for diaper dermatitis complicated by candidiasis in examination was conducted, and another blood sample was drawn 1=Light erythema with minimal maceration or desquamation
8. Weston WL, Lane AT,Weston JA. Pediatrics. 1980;66:532-536.
2=Moderate erythema with or without satellite papules with maceration and desquamation
immunocompetent patients 4 weeks and older18 for analysis 3=Severe erythema with papulopustules and maceration • No adverse events were reported for any infant in either 9. Spraker MK, Gisoldi EM, Siegfried EC, et al. Cutis. 2006;77:113-130.
• Prior to this study, absorption of miconazole nitrate through • The primary outcome measures were the evaluation of miconazole 4=Severe erythema with erosions or ulceration 10. West DP,Worobec S, Solomon LM. J Invest Dermatol. 1981;76:147-150.
treatment group 11. Munro DD. Dermatologica. 1976;152(suppl 1):173-180.
inflamed skin of infants with diaper dermatitis had not been absorption and the clinical evaluation 12. [No authors listed]. Nurse Pract. 2006;31:62.
evaluated • The patients' clinical response to therapy was indicated by the rash • Infants had initially been admitted to the hospital for treatment Clinical evaluation
13. Janniger CK,Thomas I. Cutis. 1993;52:153-155.
14. Drouhet E, Dupont B. Arzneimittelforschung. 1992;42:705-711.
evaluation score obtained on treatment Days 0, 1,3, 5, and 7 of gastrointestinal conditions and all had diaper dermatitis • Rash scores at baseline were 2.68 ± 0.82 in the 0.25% miconazole 15. Hawser S, Islam K. J Antimicrob Chemother. 1999;43:411-413.
• Any adverse events were assessed and recorded on Days 1, 3, 5, secondary to systemic pathology.The most common additional nitrate group and 3.00 ± 1.00 in the 2% miconazole nitrate group 16. Vanheule R, Adriaensen K, De Hauwere R,Van Cutsem J, De Crée J. Castellania. 1974;2:91-92.
Objective and 7. Participants were to be withdrawn from the study if adverse diagnoses on enrollment included diarrhea (n=9); intestinal (Figure 2)
17. MacKie RM, Scott E. Practitioner. 1979;222:124-126.
18. Vusion [package insert]. Princeton, NJ: Barrier Therapeutics; 2006.
reactions developed or the parent or legal guardian wished to symptoms, including amoebic dysentery and acute viral • At each evaluation, mean rash scores for all infants in the 0.25%
• To determine the absorption of 0.25% miconazole nitrate ointment withdraw the patient from the study. gastroenteritis (n=7); dehydration (n=7); or malnutrition (n=3).
through the skin of infants with moderate-to-severe diaper miconazole nitrate group were slightly lower than mean scores in
• Patients who were treated with miconazole nitrate for less than Some infants had multiple diagnoses the 2% miconazole nitrate group
dermatitis after multiple applications 7 days were considered not evaluable
This study was performed at the Hospital General Vasco de Quiroga in Morelia, Michoacan, Mexico.
This poster was sponsored by Barrier Therapeutics.