Adverse Effects of Lotrisone Cream Used in Infants

Abstract

To the Editor. In keeping with the Food and Drug Administration's (FDA's) mission to promote and protect public health by assuring the safety and effectiveness of drugs, we write to advise pediatricians and other health practitioners of important adverse events associated with the use of Lotrisone cream in children. Lotrisone cream was approved by the FDA for use in the United States in July 1984. It is marketed by Schering and is a combination of clotrimazole, USP, a synthetic antifungal agent, and betamethasone dipropionate, USP, a synthetic corticosteroid, for dermatologic use. It is labeled for twice-daily use for 2 weeks in tinea cruris and tinea corporis and 4 weeks in tinea pedis, dermatophyte infections resulting from Trichophyton rubrum, Trichophyton mentagrophytes,Epidermophyton floccosum, and Microsporum canis.1A recent review of adverse events to Lotrisone cream reported to the FDA's MedWatch reporting program indicated that of the 153 cases for whom complete data were available, 41 (27%) were <12 years old. Thirteen of these were between the ages of 5 months and 2.5 years, and in 10 of them the stated indication for use was diaper dermatitis. In 64% of these infants the duration of therapy exceeded 2 weeks (range: 4–80 weeks). Adverse events reported in this age group included hirsutism, benign intracranial hypertension, skin atrophy, growth retardation, application site reaction, aggravation of the condition, and ineffectiveness of the cream. We must point out that underreporting is a well-recognized feature of spontaneous reporting systems such as this, so the numbers of adverse events may in fact be higher than reported.2Although there are no efficacy data for children, usage data suggest that Lotrisone cream is widely used in children under 12. IMS Health's National Prescription Audit Plus (NPA Plus), a survey of pharmacies for prescriptions dispensed in the continental United States, showed that total Lotrisone prescriptions ranged from 4.4 million in 1993 to 5 million in 1998. IMS Health's National Disease and Therapeutic Index (NDTI), which surveys treatment patterns and diseases at patient visits to office-based medical practices in the continental United States, indicated that 20% of the Lotrisone prescriptions were for children aged 12 and under, 14% were for children aged 6 and under, and 7% were for infants <1 year old. NDTI data further showed that diaper dermatitis was the most frequently mentioned indication for Lotrisone cream prescriptions among children 0 to 2 years old. In addition 2 recent articles based on analysis of National Center for Health Statistics survey data3,4 confirm the widespread prescribing of clotrimazole-betamethasone diproprionate in young children, particularly by pediatricians and nondermatologists.The Precautions section of the package insert includes a statement that “safety and efficacy have not been established in children under 12 years old” and specifically that “the use of Lotrisone in diaper dermatitis is not recommended.” The Dosage and Administration section of the label also states that “Lotrisone cream should not be used with occlusive dressings,” an effect simulated by diapers in infants.This review thus suggests that Lotrisone is widely used in children <12 years old, including for diaper dermatitis in infants, an indication and age group not recommended by the product labeling. Off-label use of drugs may often be appropriate and is not generally subject to FDA regulation. However, as stated in product labeling, the use of Lotrisone in diaper dermatitis is not recommended.