Clotrimazole/betamethasone diproprionate: a review of costs and complications in the treatment of common cutaneous fungal infections.

The use of antifungal/corticosteroid combinations as topical therapy for dermatophytoses has been criticized as being less effective, more expensive, and the cause of more adverse cutaneous reactions than antifungal monotherapy. The combination of clotrimazole and betamethasone diproprionate (Lotrisone) is a mix of an azole antifungal and a high-potency corticosteroid, and is one of the most widely prescribed of these combinations. Our objective was to describe the beneficial and deleterious effects of Lotrisone in the treatment of common cutaneous fungal infections and its relative cost-effectiveness. We did a literature review documenting clinical trial data and adverse reactions to Lotrisone and collected a cost analysis of topical antifungal prescribing data over a 2-month period from a large midwestern staff-model health maintenance organization (HMO). Lotrisone is approved by the U.S. Food and Drug Administration (FDA) for the treatment of tinea pedis, tinea cruris, and tinea corporis in adults and children more than 12 years of age. Treatment is limited to 2 weeks in the groin area and 4 weeks on the feet. The most concerning adverse effects of Lotrisone were reported in children and included treatment failure, striae distensae, hirsuitism, and growth retardation. This combination was also reported to have decreased efficacy in clearing candidal and Trichophyton infections as compared to single-agent antifungals. Lotrisone was considerably more expensive than clotrimazole alone and was found to account for more than 50% of topical antifungal expenditures as prescribed by primary care physicians, but only 7% of topical antifungals prescribed by dermatologists. We found that Lotrisone was shown to have the potential to induce many steroid-related side effects and to be less cost effective than antifungal monotherapy. This combination should be used judiciously in the treatment of cutaneous fungal infections and may not be appropriate for use in children.

A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapy.

BACKGROUND: Mucositis occurs in almost all radiotherapy-treated head and neck cancer patients, in approximately 75% of patients receiving hematopoietic marrow transplantation, and in approximately 40% of all patients who receive chemotherapy. Mucositis is painful, may affect all oral functions, and is a dose- and rate-limiting toxicity of therapy for cancer. Radiation-associated mucositis (onset, intensity, and duration) has been shown in recent clinical trials to be modified by the use of antibacterial/antifungal lozenges. PURPOSE: The aim of this collaborative two-center phase II study was to assess the toxicity and microbiologic efficacy of an economically viable antimicrobial lozenge in the management of patients receiving radiation therapy for head and neck cancer. MATERIALS AND METHODS: Seventeen patients scheduled to receive radical or postoperative radiotherapy were provided with bacitracin, clotrimazole, and gentamicin (BCoG) lozenges (one lozenge dissolved in the mouth qid from day 1 of radiotherapy until completion). Ease of use and palatability of the lozenges, patients' symptoms (swallowing and pain), and quantitative and qualitative microbiologic evaluation of an oral rinse collection was conducted at least once weekly during radiation therapy. RESULTS: No significant side effects were reported from the use of the lozenges. The lozenges were well tolerated at the beginning of treatment by all patients, with some minor difficulty associated with oral discomfort toward the end of the treatment. Microbiologic evaluation showed consistent elimination of yeast organisms in all patients. In four patients there was no growth of gram-negative bacilli on culture, whereas in two patients, fluctuating counts were seen, and one patient had increased counts. The remaining patients had significant reduction in the gram-negative bacilli counts. CONCLUSIONS: This study demonstrated that the BCoG lozenge is tolerable and microbiologically efficacious, achieving elimination of Candida in all patients and reduction in gram-negative flora in most patients. A phase III study is underway to evaluate the clinical efficacy of this lozenge.

Use of clotrimazole/betamethasone diproprionate by family physicians.

BACKGROUND AND OBJECTIVES: Clotrimazole/betamethasone diproprionate contains a fluorinated, high-potency topical corticosteroid and is the most frequently prescribed topical agent in the United States. Family physicians are more likely than pediatricians and dermatologists to use this product when faced with a common fungal infection. To better understand the settings in which US family physicians recommend the use of clotrimazole/betamethasone diproprionate, we determined the diagnoses and characteristics of patients for whom family physicians prescribe this drug. METHODS: Data from the National Ambulatory Medical Care Survey were used to determine the demographic characteristics of patients who were given a prescription for clotrimazole/betamethasone diproprionate, the diagnoses of patients treated with the drug, and the potency of other topical corticosteroids by family physicians. Wholesale costs of drugs were used to estimate potential drug cost savings obtainable by switching to specific monotherapy agents. RESULTS: Clotrimazole/betamethasone diproprionate was prescribed at 3.1% of visits to family physicians but at only .6% of visits to dermatologists for either inflammatory or fungal/candidal conditions. Family physicians frequently prescribed clotrimazole/betamethasone diproprionate to children under age 5 and for use on genital skin disorders. Dermatologists rarely used clotrimazole/betamethasone diproprionate in these settings. CONCLUSIONS: The frequent use by family physicians of clotrimazole/betamethasone diproprionate in high-risk settings is of concern. Use of alternative agents with anti-inflammatory and antifungal properties without the risks associated with the use of high-potency topical corticosteroids may be the most practical approach to replacing use of clotrimazole/betamethasone diproprionate.

Adherence to cotrimoxazole treatment for acute lower respiratory tract infections in rural Bangladeshi children.

This study evaluates compliance with taking oral cotrimoxazole in an ALRI control programme in rural Bangladesh. Health workers administered the first dose to children with moderate disease and entrusted relatives to give the remaining doses. A team of medical assistants visited the families of cases 3 to 5 days after initiating treatment and counted the remaining tablets. Medical assistants undertook 367 visits to families of children under treatment at a mean (SD) of 4.4 (0.99) days after treatment began. All children appeared to have been given the antibiotic, but one-quarter were being under-dosed on the day of the visit. Under-dosing did not correlate with any of the socio-demographic variables studied, and seemed to be homogeneously distributed in the community. Under-dosed children did not seem to have a higher risk of subsequent ALRI episodes during the study period. There was no indication of progression to severe disease or death in home-managed cases of moderate pneumonia in this study. These findings raise a question about the need for 5 days of oral antibiotic in the management of moderate pneumonia. Careful studies of the effect on subsequent morbidity, mortality and antibiotic resistance of providing briefer treatment for moderate episodes of ALRI are required. If a briefer course proves effective, this would have important implications for funding programmes of control of ALRI in the community.

Nondermatologists are more likely than dermatologists to prescribe antifungal/corticosteroid products: an analysis of office visits for cutaneous fungal infections, 1990-1994.

BACKGROUND: Dermatologists have greater accuracy than nondermatologists for diagnosis of skin disease. However, it is not clear whether this affects medical outcome. OBJECTIVE: We tested the hypothesis that nondermatologists would be more likely than dermatologists to prescribe combination products for the treatment of common fungal skin infections. METHODS: We analyzed office-based physician visits for fungal skin infections recorded in the 1990-1994 National Ambulatory Medical Care Survey. RESULTS: There were 4.1 million visits for cutaneous fungal disease of which 82% were to nondermatologists. Nondermatologists were more likely to prescribe combination agents (34.1%) than dermatologists (4.8%, p=0.001). If the percentage of combination agents used by nondermatologists was reduced to that of dermatologists, an estimated $24.9 million or $10.3 million would be saved if clotrimazole or ketoconazole, respectively, were the substituted drug for the combination agent clotrimazole/betamethasone dipropionate. CONCLUSION: Nondermatologists are more likely to use a more expensive, less effective regimen than are dermatologists, suggesting that dermatologists are more cost-effective than nondermatologists in the treatment of common fungal skin disorders.

A cost analysis of topical drug regimens for dermatophyte infections.

OBJECTIVE: To examine the extra cost of using higher-priced drugs as initial therapy for dermatophyte infections, because the many available effective drugs vary considerably in cost. DESIGN: Cost analysis from the purchaser's perspective, comparing two prototypical regimens to treat tinea pedis: one in which all patients initially receive a lower-priced drug and those with unresponsive infections receive a higher-priced drug at a follow-up office visit, and one in which all patients receive the higher-priced drug from the outset. The reference drug was miconazole, an imidazole available without a prescription, for which reported overall efficacy rates are 70% to 100%. MAIN OUTCOME MEASURES: The threshold efficacy rate (the efficacy rate of miconazole below which it is always less expensive to use a specific higher-priced drug first) and the extra cost (of beginning therapy with a higher-priced drug). RESULTS: Assuming the Medicare-approved charge for a follow-up visit ($21.98), it is less expensive to begin therapy with a prescription drug only if the efficacy rate of miconazole is less than 55%; this threshold efficacy rate varied from 26% (for a $0 total cost of the follow-up visit) to 79% (for an $89 total cost of the follow-up visit). If the efficacy rate of miconazole is 70%, the extra cost per patient for all patients to receive the least expensive prescription antifungal drug instead of miconazole first was $15.23 and $8.64 if total visit costs were $0 and $21.98; miconazole remained the less expensive alternative as long as the total cost of the follow-up visit was less than $50.76. CONCLUSION: For reported efficacy rates and standard costs of a follow-up office visit, using miconazole first and then treating only those patients with unresponsive infections with a higher-priced prescription drug is less expensive than treating all patients with the higher-priced drug.

The value of prophylactic (monthly) clotrimazole versus empiric self-treatment in recurrent vaginal candidiasis.

OBJECTIVE: To determine the comparative efficacy and cost benefit of prophylactic monthly (perimenstrual) clotrimazole, versus empiric self-treatment with the same agent at the onset of symptoms in recurrent vulvovaginal candidiasis. DESIGN: Prospective, randomised, open cross-over study of women with proven recurrent vulvovaginal candidiasis. Clinical and microbiological assessments were done every two months for 12 months. SETTING: Women's Clinic of a University Teaching Hospital. SUBJECTS: Twenty-three otherwise healthy, non-pregnant women with greater than four proven episodes of candida vaginitis in the last year were enrolled into the study. INTERVENTION: Patients were randomised to receive: (1) a single dose of prophylactic clotrimazole 500 mg ovule just before or on the last day of the menses each month for 6 months; (2) or a single dose of clotrimazole 500 mg ovule empirically at the onset of symptoms for 6 months. After the first 6 months patients were crossed-over to the opposite regimen. MAIN OUTCOME MEASURES: Symptoms of recurrent vulvovaginitis during each period, and number of clotrimazole ovules used for each 6 month period. The personal preference of the patients for the two different regimens were assessed at the end of study. RESULTS: During the prophylactic 6 months period of the study, 23 patients had 50 episodes of symptomatic vaginitis (mean 2.2 episodes per patient), versus 86 episodes (mean 3.7 episodes/patient) during the empiric self-treatment 6 months period (P = 0.05). However, during the prophylactic period a total of 168 clotrimazole ovules were used (mean 7.3 per patient), versus 84 ovules (mean 3.6 per patient) during the empiric self-treatment period, p < 0.001. The personal preference of the patients for the type of regimen employed were 17 (73.9%) in favour of the empirical treatment, versus 4 (17.4%) in favour of the prophylactic treatment and 2 (8.7%) no personal preference, p < 0.01. CONCLUSION: Empiric self-treatment is more cost-effective and preferable to patients than cyclical monthly prophylactic use of 500 mg clotrimazole vaginal ovules.