Efficacy of topical clotrimazole vs. topical tolnaftate in the treatment of otomycosis. A randomized controlled clinical trial / Eficácia do clotrimazol tópico versus tolnaftato tópico no tratamento da otomicose: um ensaio clínico controlado randomizado

Abstract Introduction: Otomycosis, an infection of the ear canal by fungi, is prevalent in hot and humid weather. Nevertheless, there is not sufficient evidence for the effectiveness of different topical antifungal treatments. Tolnaftate, is a topical antifungal agent described to be effective in the treatment of otomycosis. Currently there are not sufficient studies that prove its efficacy. Objectives: To compare the efficacy of clotrimazole and tolnaftate administration in the treatment of otomycosis. Material and methods: A controlled, randomized and open clinical trial included patients diagnosed with fungal external otitis who were treated with topical antifungals, randomized into two treatment groups: (1) clotrimazole cream; (2) tolnaftate solution. They were microscopically evaluated at one and two weeks of treatment to determine resolution of disease. Recurrence and complications were recorded. Demographic and clinical variables were collected and analyzed. Follow-up and final outcomes (absence of infection) were compared between groups. Results: Forty eight patients were included, 28 in the clotrimazole group and 20 in the tolnaftate group. Spring was the weather most commonly associated with otomycosis, while otic manipulation was the risk factor more common in both groups. Predominant symptoms were itching and otic fullness. Aspergillus niger organism was isolated most frequently. Treatment with clotrimazole resulted in 75% resolution vs 45% resolution with treatment with tolnaftate at one week of treatment (p = 0.007). The Tolnaftate treatment group demonstrated higher recurrence rates and treatment failures, 20% and 15% respectively. Conclusions: Clotrimazole cream treatment is more effective than tolnaftate for uncomplicated otomycosis. More studies are needed to corroborate our results.

Resumo Introdução: Otomicose, uma infecção fúngica do canal auditivo externo, é prevalente em climas quentes e úmidos. No entanto, a literatura não apresenta evidências suficientes sobre os diferentes tratamentos antifúngicos tópicos. O tolnaftato é um antifúngico tópico descrito como eficaz no tratamento da otomicose; entretanto, sua eficácia não está suficientemente comprovada. Objetivo: Comparar a eficácia do uso de clotrimazol e tolnaftato no tratamento da otomicose. Material e método: Ensaio clínico controlado e randomizado; incluiu pacientes diagnosticados com otite externa fúngica tratados com antifúngicos tópicos, randomizados em dois grupos de tratamento: 1) clotrimazole (creme); 2) solução de tolnaftato. Eles foram avaliados microscopicamente uma e duas semanas após o início do tratamento para avaliar a resolução da doença. Recorrência e intercorrências foram registradas; além disso, as variáveis demográficas e clínicas foram coletadas e analisadas. Os dados do acompanhamento e desfechos finais (ausência de infecção) foram comparados entre os grupos. Resultados: O estudo incluiu 48 pacientes, 28 dos quais foram alocados ao grupo clotrimazole e 20 ao grupo tolnaftato. A primavera foi a estação mais comum; a manipulação foi o fator de risco mais comum em ambos os grupos. Os sintomas mais comuns foram coceira e plenitude auricular. Aspergillus niger foi o micro-organismo mais comumente isolado. Após uma semana, o tratamento com clotrimazol apresentou uma taxa de resolução de 75% vs. 45% com o tratamento com tolnaftato (p = 0,007). O tratamento com tolnaftato apresentou maiores taxas de recidiva e falhas: 20% e 15%, respectivamente. Conclusões: Em casos de otomicose não complicada, o uso de clotrimazol (creme) é mais eficaz do que o de tolnaftato. Mais estudos são necessários para corroborar os presentes resultados.

Efficacy of topical clotrimazole vs. topical tolnaftate in the treatment of otomycosis. A randomized controlled clinical trial.

INTRODUCTION: Otomycosis, an infection of the ear canal by fungi, is prevalent in hot and humid weather. Nevertheless, there is not sufficient evidence for the effectiveness of different topical antifungal treatments. Tolnaftate, is a topical antifungal agent described to be effective in the treatment of otomycosis. Currently there are not sufficient studies that prove its efficacy. OBJECTIVES: To compare the efficacy of clotrimazole and tolnaftate administration in the treatment of otomycosis. MATERIAL AND METHODS: A controlled, randomized and open clinical trial included patients diagnosed with fungal external otitis who were treated with topical antifungals, randomized into two treatment groups: (1) clotrimazole cream; (2) tolnaftate solution. They were microscopically evaluated at one and two weeks of treatment to determine resolution of disease. Recurrence and complications were recorded. Demographic and clinical variables were collected and analyzed. Follow-up and final outcomes (absence of infection) were compared between groups. RESULTS: Forty eight patients were included, 28 in the clotrimazole group and 20 in the tolnaftate group. Spring was the weather most commonly associated with otomycosis, while otic manipulation was the risk factor more common in both groups. Predominant symptoms were itching and otic fullness. Aspergillus niger organism was isolated most frequently. Treatment with clotrimazole resulted in 75% resolution vs 45% resolution with treatment with tolnaftate at one week of treatment (p=0.007). The Tolnaftate treatment group demonstrated higher recurrence rates and treatment failures, 20% and 15% respectively. CONCLUSIONS: Clotrimazole cream treatment is more effective than tolnaftate for uncomplicated otomycosis. More studies are needed to corroborate our results.

Qualitative and quantitative analysis of related substances in clotrimazole cream / 药学学报

For qualitative and quantitative analysis of related substances in clotrimazole cream, HPLC-Q-TOF spectrometer was used to analyze the fragmentation pathways and identify structures of the related substances. Five related substances named by BP (2018) were identified as impurity A ((2-chlorophenyl)-diphenylmethanol), impurity B (para-clotrimazole isomer), impurity E (2-chlorobenzophenone), impurity F (1-tritylimidazole) and impurity 4 (9-(2-chlorophenyl)-fluorene), respectively, by using impurity references matching and comparison with the literature data. Four related substances were detected in clotrimazole cream except impurity E, and 9-(2-chlorophenyl)-fluorene is the first identified impurity in this preparation. To establish an HPLC method for determination of the related substances in Clotrimazole Cream, the Agilent Poroshell Bonuns RP column was used (100 mm×4.6 mm, 2.7 μm) with UV detection at 215 nm. The mobile phase was acetonitrile-10 mmol·L-1 dipotassium phosphate buffer (adjusted with phosphoric acid to pH of 5.80) with a flow rate of 1.0 mL·min-1. Gradient elution was used. The column temperature was maintained at 40℃. A good linear behavior was achieved between component's concentrations and peak area for impurity A, B, E, F within the range of 0.20-10.02 μg·mL-1, 0.20-10.00 μg·mL-1, 0.20-10.10 μg·mL-1, 0.10-5.01 μg·mL-1 with the correlation coefficients were 0.999 7, 1.000 0, 1.000 0, 0.999 9, respectively. The average recoveries were 94.3%, 95.0%, 100.0%, 99.6% with RSDs were 2.8%, 2.2%, 1.1%, 2.7%, respectively (n=9). LOQ were 200.4, 200.0, 202.0, 100.2 ng·mL-1, respectively. LOD were 57.25, 57.14, 57.71, 28.63 ng·mL-1, respectively. The developed method was simple, rapid, accurate and effective for testing related substances in clotrimazole cream to control its quality, ensuring the safety of clinical medication.