Pediatricians who Prescribe Clotrimazole-Betamethasone Diproprionate (Lotrisone) often Utilize it in Inappropriate Settings Regardless of their Knowledge of the Drug's Potency
Divya Railan, Jill K. Wilson, Steven R. Feldman, and Alan B. Fleischer, Jr.
Dermatology Online Journal 8(2): 3

Department of Dermatology, Wake Forest University School of Medicinea

Abstract

Clotrimazole-betamethasone diproprionate (C-BMV) is a fluorinated, high potency topical steroid that has been formulated with clotrimazole in the brand-named product, Lotrisone. The product is frequently used inappropriately in intertriginous areas, particularly in children. The following evaluates the use of this combination based upon a survey of 106 US-based pediatricians with at least two years post-residency, who attended the 1999 American Academy of Pediatrics. Of pediatricians who prescribe C-BMV, 23% prescribe it for diaper dermatitis. 11% of C-BMV prescriptions exceed the recommended duration of therapy. Only 18% of prescribing pediatricians correctly identify "Lotrisone" as a high potency steroid. There is no significant association between knowledge of C-BMV potency and frequency of use (p>.1). These self-reported data confirm and complement the findings of previous studies that used representative national data to assess the use of C-BMV. Pediatricians continue to utilize C-BMV in inappropriate settings, such as diaper dermatitis, regardless of their knowledge of the agent's potency. Our advice is to refrain from using high-potency steroids, such as C-BMV, in pediatric cases as there are more appropriate, safer alternatives with many fewer side effects.



Introduction

Approximately 25% of patients seen by primary care physicians present with a primary or secondary skin complaint.[1] Fungal infections and atopic dermatitis, the two most common skin conditions seen by pediatricians, share many similarities, including scaly, erythematous patches, although each condition does have its unique features.[1] Perhaps because of the ambiguity inherent in diagnosing skin conditions, non-dermatologists are more likely than dermatologists to prescribe a combination agent to treat cutaneous fungal infections.[2] C-BMV cream (Lotrisone®) is a topical combination agent containing a fluorinated high-potency corticosteroid (betamethasone diproprionate) and an antifungal agent (clotrimazole). C-BMV lotion was recently approved by the FDA and is now being marketed. C-BMV, the most commonly prescribed dermatological agent and the 53rd most frequently utilized compound in the United States, is often prescribed by pediatricians to treat a variety of skin conditions[3,4] Current recommendations state that it not be applied for more than 4 weeks in nonoccluded areas, applied for more than 2 weeks in occluded areas, nor be utilized to treat diaper dermatitis. Pediatricians still commonly prescribe the product to children under the age of 5 and for diaper rash. Although pediatricians rarely prescribe single-agent, high-potency topical corticosteroids due to concerns over their associated side effect profiles, they frequently utilize clotrimazole-betamethasone diproprionate.[2,5] This seemingly incongruent use of corticosteroids may be the result of the pediatricians' unawareness of C-BMV's high potency. Pediatricians may also be unaware that single-agent therapy, in comparison to a combination of corticosteroid and antifungal agents, may be equally, if not more, effective and less expensive in treating cutaneous fungal infections.[6,7,8,9,10] Since topical corticosteroids are traditionally contraindicated in diaper dermatitis, acne, and skin infections, C-BMV should not be used by pediatricians to treat diaper rash or other skin conditions in children, especially in settings of occlusion, such as the diaper area.[14] The published product information for Lotrisone agrees with these recommendations and also states that the agent should not be used for children less than 12 years of age.[3] Betamethasone diproprionate, a high-potency agent with the potential to cause skin atrophy, striae, and tachyphylaxis, may cause suppression of the hypothalamus-pituitary-adrenal axis, Cushing's syndrome, intracranial hypertension, growth delay, and other systemic side effects in the pediatric patient due to their greater skin surface area to body weight ratio as compared to adults.[3,15] The use of topical corticosteroids for diaper dermatitis is especially risky as the percutaneous absorption increases significantly under such an occlusive dressing.

Despite these warnings, a representative survey of U.S. pediatricians revealed that C-BMV is frequently prescribed for diaper dermatitis and candidiasis.[6] Limitations of our previous work include difficulty in determining if the diagnoses and prescriptions were properly coded and the inability to obtain information regarding the decision to prescribe the drug and the recommended duration of therapy. The purpose of this study is to confirm that pediatricians utilize C-BMV in inappropriate settings and to determine if this use is due to their lack of awareness of the drug's potency.


Materials and Methods

One hundred and six pediatricians completed questionnaires at the 1999 American Academy of Pediatrics meeting. Pediatricians were considered eligible for completion of the questionnaire if they met the following criteria: U.S. based pediatrician in current clinical practice; at least two years in clinical practice past residency; and currently prescribing clotrimazole-betamethasone diproprionate. The final criterion was included because the primary purpose of the study was to assess awareness of the relative potency of the corticosteroid betamethasone diproprionate among physicians who do prescribe the drug. Our intent was not to assess the numbers of pediatricians that use the product, as this was already done in a representative sampling study of visits to the pediatrician in the United States.[5]

The questionnaire was also used to assess the appropriateness of C-BMV use, frequency and duration of use, and the skin conditions and patient populations targeted with treatment.

Participants were asked the following questions: 1) "What percentage of your patients are treated for the condition listed?" 2) "What percentage of these patients receive Lotrisone®?" 3) "What is the average age of these patients?" 4) "What is the average length of Lotrisone® therapy for these patients?"

To estimate the overall percentage of patients treated in a particular manner, we performed weighted averages of the pediatrician data then statistical analyses using the Statistical Analysis System-version 6.12 (SAS Institute, Cary, N.C.). Chi-square analysis and Fisher's Exact test assessed the statistical differences between means of groups.

We examined the clinical use of C-BMV in patients with the following conditions: tinea pedis, tinea cruris, tinea corporis, diaper dermatitis, cutaneous candidiasis, tinea versicolor, and atopic dermatitis. To test the hypothesis that inappropriate use of C-BMV is due to lack of knowledge of its potency, we examined the relationship between the physicians' knowledge of the relative potency of the corticosteroid agent and its clinical use by dichotomizing the data into pediatricians that prescribe/do not prescribe and pediatricians that know/do not know that it contains a high-potency corticosteroid.

The PDR recommends that C-BMV not be used for a duration greater than four weeks in nonoccluded areas or two weeks in the groin area or under occlusion.[3] We sought to determine if the duration of therapy often exceeds these recommendations by surveying pediatricians about length of clotrimazole-betamethasone therapy for the aforementioned conditions.


Results

C-BMV is most frequently prescribed for tinea pedis, tinea corporis, and tinea cruris (Figure 1). Of the patients diagnosed with these conditions, 44%, 39%, and 36% are treated with clotrimazole-betamethasone diproprionate, respectively. Other common uses include cutaneous candidiasis (36%), tinea versicolor (28%), atopic dermatitis (27%), and diaper dermatitis (23%, Figure 1). We also examined the proportion of physicians who do not prescribe C-BMV for any of their patients with certain skin conditions (Figure 2). For example, C-BMV is not prescribed for 41% of patients with diaper dermatitis.

The mean age of patients prescribed C-BMV for diaper dermatitis is 0.9 years, with an age range of 0.25 to 2 yrs. For all the conditions surveyed, the average age of patients treated with the combination agent ranges from 4 to 11 years. The age ranges of patients treated for each skin condition reveals the following: tinea pedis 1-21 yrs, tinea cruris 1-25 yrs, tinea corporis 1-25 years, tinea versicolor 1-16 yrs, cutaneous candidiasis 1-12 yrs, and atopic dermatitis 1-21 yrs.

To determine if C-BMV might be used for inappropriate lengths of time, the prescribed duration of therapy was assessed (Figure 4). The results revealed that 25% of cases of tinea cruris are treated for longer than the recommended duration, whereas only 3% of cases of cutaneous candidiasis are treated longer than recommended. To assess the pediatricians' knowledge of C-BMV's potency, participants were asked whether the agent contains a low, medium, or high potency topical corticosteroid. Only 18% of prescribing pediatricians correctly identified C-BMV as a high potency steroid (Figure 3). Of those that knew that it was a high potency topical corticosteroid, 33% correctly identified the topical corticosteroid as betamethasone diproprionate.

The degree of association between knowledge of C-BMV potency and use as a treatment for children with diaper dermatitis, candidiasis, dermatophyte infections, and atopic dermatitis was determined. The results revealed no significant association between the clinician's knowledge of the drug's potency and prescribing behavior (p's> .1).


Discussion

The findings of this study complement and confirm previous work published based on the NAMCS data.[6] Our survey reveals that pediatricians use C-BMV in inappropriate settings and further investigates their awareness of the agent's potency and recommended duration of use.

Pediatricians most frequently prescribe C-BMV for Food and Drug Administration (FDA)-approved indications including tinea pedis, tinea cruris, and tinea corporis. For each of these conditions, more effective, less costly single agent antifungal agents are available.[6,7,8,9,10] Studies have shown that there is no clinical advantage in treating patients with fungal infections with a combination agent as opposed to single-agent therapy.[6, 7, 8, 9, 10,13] C-BMV is also prescribed for a number of conditions, such as tinea versicolor, cutaneous candidiasis, and atopic dermatitis, for which it is neither the indicated nor optimal treatment modality. C-BMV is also utilized for diaper dermatitis, a condition for which it is specifically contraindicated. Our findings further support NAMCS data showing that C-BMV is used in inappropriate situations.

In an attempt to explain the frequent use of C-BMV by pediatricians in inappropriate settings, some researchers hypothesized that the use may be the result of a general unawareness of the agent's high-potency.[2] Our results revealed that the majority of surveyed pediatricians underestimate the relative potency of the corticosteroid contained in clotrimazole-betamethasone diproprionate. Though most pediatricians are unaware of the potency of clotrimazole-betamethasone diproprionate, they still prescribe it. Even those pediatricians aware that C-BMV contains a high potency agent continue to prescribe it in inappropriate settings.

Two other explanations may account for our findings. First, pediatricians may experience difficulty in distinguishing common fungal from inflammatory skin disorders. Although improving pediatricians' ability to differentiate fungal from inflammatory disorders may be one approach to decreasing the use of C-BMV in inappropriate settings, there is no tested method for accomplishing this goal, though one would expect increased education to be of help.[11,12] On the other hand, pediatricians may rightly believe that some common skin disorders, such as diaper rash, consist of both fungal and inflammatory components that require combination treatment. From a pragmatic perspective, there may be a need for a combination anti-inflammatory/antifungal agent without the side effect potential associated with a high potency, fluorinated corticosteroid agent.

Use of C-BMV is least appropriate in the youngest patients due to their increased susceptibility to side effects. Children possess a greater skin surface area to body weight ratio that places them at higher risk for hypothalamic-pituitary-adrenal axis suppression, growth delay, and other systemic side effects.[3,15] The results of our previous study, which suggested that pediatricians even prescribe C-BMV in patients less than or equal to 4 years of age, are confirmed by this current study (Table 1).[5] These findings are consistent with NAMCS data suggesting that 56% of pediatricians' use of C-BMV is for children between the ages of 0-4 years.[5]

Table 1. Synopsis of Questionnaire Results (expressed as mean, and the lower and upper limits of 95% confidence interval)
Condition percentage of patients treated for this condition percentage of these who receive clotrimazole-betamethasone diproprionate average age of these patients (years) length of therapy (weeks)
Tinea Pedis 9 (-2, 20) 30 (12, 48) 11 (9, 13) 3 (1, 4)
Tinea Cruris 6 (-5, 17) 25 (7, 42) 11(8, 14) 2
Tinea Corporis 14 (3, 25) 31 (16, 47) 7 (5, 10) 2 (1, 4)
Tinea Versicolor 8 (-3, 19) 15 (-2, 31) 9 (7, 11) 3 (1, 4)
Diaper Dermatitis 20 (10, 30) 14 (0, 28) .9(.5, 1.3) .2 (0, .2)
Cutaneous Candidiasis 7 (-5, 19) 20 (3, 37) 6 (3, 9) 2 (1, 3)
Atopic Dermatitis 18 (7, 28) 13 (-2, 38) 4 (1, 7) 3 (0, 6)

This study does possess some important limitations. Though the survey provides a summary of pediatrician practices, it is based on pediatricians' self-appraisal, rather than an actual assessment of prescription practices. This limits our confidence in the absolute frequency of use of the drug, though we expect that the results are qualitatively accurate. Moreover, because the survey was completed only by pediatricians who prescribe clotrimazole-betamethasone diproprionate, the results may not generalize to pediatricians who do not prescribe the drug, as these two groups of physicians may be qualitatively different. Further study of these pediatricians is indicated to determine the reasons they do not prescribe the drug, particularly if they do not prescribe because they are aware of its high potency and contraindications.

In order to encourage physicians to provide honest answers, we attempted to assure anonymity by not collecting any information on the prescribing physician other than their use of betamethasone dipropionate/clotrimazole. This also had the advantage of minimizing the length of the survey to encourage participation. A limitation of this approach is that we cannont assess differences in prescribing patterns by physician demographics, nor do we have any information on how representative our sample is of U.S. pediatricians. Our findings do provide unique information on self-reported use of the combination steroid/antifungal product by a sample of U.S. pediatricians, but a weakness of the study is clearly the limited information of the generalizability of the information.

We currently recommend that C-BMV cream not be utilized by pediatricians in the treatment of any childhood skin condition as there are many other more effective and less toxic treatment options for the common fungal and inflammatory skin diseases. Lotrisone lotion was recently approved by the FDA and the current marketing efforts may expand or reduce C-BMV's use depending on whether or not pediatricians become more aware of its potential dangers. If the patient appears to have a fungal infection by both clinical skin exam and on KOH scrapings, then a topical antifungal should be prescribed.[5] When patients present with inflammatory skin conditions, such as atopic dermatitis, low- to mid-potency topical steroids may be combined with moisturizers, oral antibiotic therapy, and antihistamines to control the itching and reduce inflammation and eradicate concomitant infection.[16] Topical tacrolimus ointment (Protopic) may be prescribed to treat dermatitis without concern for skin atrophy, even when used in diaper area.[17,18,19] Diaper dermatitis, a type of irritant dermatitis, may respond to a barrier cream, and a low-potency topical corticosteroid.[5] When secondary infection with yeast occurs, as is common, or the diagnosis is uncertain, an antifungal agent may be used in combination with a topical antiinflammatory of the appropriate potency, with its associated contraindications and treatment recommendations clearly considered. In conclusion, C-BMV should not be used for the treatment of childhood skin disorders as it may cause atrophy and suppression of the hypothalamus-pituitary-adrenal axis, especially when applied to the diaper area under occlusion, and is not the most effective nor the most cost-effective treatment option.

References

1. Krowchuk DP, Bradman DD, and Fleischer AB. Dermatologic services provided to children and adolescents by primary care and other physicians in the United States. Pediatric Dermatology 1994;11:199-203.

2. Smith EB, Fleischer AB, Feldman SR. Nondermatologists are more likely than dermatologists to prescribe antifungal/corticosteroid products: an analysis of office visits for cutaneous fungal infections, 1990-1994. J Am Acad Dermatol 1998;39:43-47.

3. Lotrisone® product information. In Physician's Desk Reference®, 53rd ed. Montvale, New Jersey: Medical Economics Co., Inc.; 1999:2859-2861.

4. Anonymous. American Druggist: February, 1999:42-43.

5. Fleischer AB and Feldman SR. Prescription of high-potency corticosteroid agents and clotrimazole betamethasone diproprionate by pediatricians. Clin Therapeutics 1999;21:1-7.

6. Smith EB, Breneman DL, Griffith RF, Hebert AA, Hickman JG, Maloney MJ, et al. Double-blind comparison of naftifine cream and clotrimazole/betamethasone diproprionate cream in the treatment of tinea pedis. J Am Acad Dermatol 1992;26:125-126.

7. Rosen T, Elewski BE. Failure of clotrimazole betamethasone diproprionate cream in the treatment of Microsporum canis infections. J Am Acad Dermatol 1995; 32:1050-1.

8. Reynolds RD, Boiko S, Lucky AW. Exacerbation of tinea corporis during treatment with 1% clotrimazole/betamethasone diproprionate 1% cream (Lotrisone cream): a letter. Am J Dis Child 1991; 145:1224-5.

9. Barkey WF. Striae and persistent tinea corporis related to prolonged use of betamethasone diproprionate 0.05% cream/clotrimazole 1% cream (Lotrisone cream): a letter. J Am Acad Dermatol 1987; 17:518-519.

10. Martin MV. Nystatin-resistance of Candida albicans isolates from two cases of oral candidiasis. Br J Oral Surg 1982; 20:294-8.

11. Graduate Medical Education Directory, 1999-2000:223-232.

12. Prose NS. Dermatology training during the pediatric residency. Clin Pediatrics 1988; 27:100-103.

13. Evans EG, James IG, Seaman RA, Richardson MD. Does naftifine have anti-inflammatory properties? A double-blind comparative study with 1% clotrimazole/1% hydrocortisone in clinically diagnosed fungal infection of the skin. Br J Dermatol, 1993 Oct; 129(4):437-42.

14. Chosidow O, Lebrun-Vignes B, Bourgault-Villada I. Local corticosteroid therapy in dermatology. Presse Med 1999; 28(37):2050-6.

15. Howard R, Tsuchiya A. Adult Skin Disease in the Pediatric Patient. Dermatol Clin 1998 Jul; 16(3):593-598.

16. Habif T. Clinical Dermatology, third edition. Chapt 5, pp117-121.

17. Hiroi J. Pharmacological profile and clinical effect of tacrolimus ointment (Protopic ointment) for atopic dermatitis. Nippon Yakurigaku Zasshi 2001 May; 117(5):351-7.

18. Frankel SJ, Kerdel FA. Topical Tacrolimus. Skin Therapy: a letter. 2001 6(4):1-2,5.

19. Berkersky I, Fitzsimmons W, Tanase A, Maher RM, Hodorh E, Lawrence I. Nonclinical and early clinical development of Tacrolimus ointment for treatment of atopic dermatitis. J Am Acad Derm 2001 Jan; 44(1 Suppl):s17-27.

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Title:

Pediatricians who Prescribe Clotrimazole-Betamethasone Diproprionate (Lotrisone) often Utilize it in Inappropriate Settings Regardless of their Knowledge of the Drug's Potency

Journal Issue:

Dermatology Online Journal, 8(2)

Author:

Railan, Divya;
Feldman, Jill K. WilsonSteven R.;
Jr, Alan B. Fleischer

Publication Date:

2002

Publication Info:

Dermatology Online Journal, UC Davis

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