Drug Profile

The FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee met on June 29, 2000, to discuss, among other issues, the safety labeling for Lotrisone, which contains the potent steroid betamethasone and clotrimazole, an antifungal agent. The committee recommended that a prominent warning should be added to the tube and box of the product to inform parents that Lotrisone should not be used in children under 12 or for the treatment of diaper rash.

This combination drug is approved by the FDA for the topical treatment of athlete’s foot, ringworm of the scalp and body, and jock itch due to several different types of fungi. Its approved use is for periods of two to four weeks, depending on the type of infection. We list this drug as Do Not Use because it is an irrational combination due to the addition of the powerful steroid betamethasone to the antifungal drug clotrimazole. Even Lotrisone's professional labeling is forced to state: “Effective treatment without the risks associated with topical corticosteroid [betamethasone] use may be obtained using a topical antifungal agent [such as clotrimazole] that does not contain a corticosteroid, especially for noninflammatory tinea infections.”[1]

The drug was first cleared for sale in July 1984 and in 2000 5.4 million prescriptions were dispensed for Lotrisone, ranking it as the 76th most frequently prescribed drug in the United States. The advent of the new warning recommended by the advisory committee has caused the drug to dip to 140th place with 2.8 million prescriptions in 2001. Lotrisone has since fallen off the list of the most frequently prescribed drugs in the United States.

The basis for the advisory committee’s recommendation was that the safety and efficacy of Lotrisone had not been proven for children under 12 or for diaper rash. Several of the advisory committee members noted that many doctors are not aware that betamethasone is a potent steroid that can cause serious and permanent adverse effects in children because it is readily absorbed through the skin.

In preparation for the June 2000 meeting, the FDA’s Office of Postmarketing Drug Risk Assessment was asked to provide an analysis of all adverse drug reactions reported to the agency since the drug was first marketed. The agency had received 344 reports of adverse events due to Lotrisone by the time of the committee meeting, many of which reported more than one event, leading to a total of 761 reactions. It must always be kept in mind that the FDA believes that only about 1 in 10 adverse reactions is reported. The three most common adverse reactions reported were that Lotrisone was not effective (19%), skin reactions (10%), and aggravation of the original condition for which the drug was prescribed (8.5%).[2]

The original professional product labeling or package insert for Lotrisone stated that the drug had not been shown to be safe and effective in children less than 12 years old.[3] The drug was relabeled in 1991 to say: “The use of LOTRISONE Cream in diaper dermatitis [diaper rash] is not recommended.”[4] Despite these facts, using data from a market research firm, the FDA estimated that between 1992 and 1997 approximately 20% of all Lotrisone prescriptions were for children under 12 years of age and 7.2% of these were for children 1 year old or younger. When a drug is prescribed for a use that is not approved, or in an age group in which the drug has not been tested, this is termed an “off-label” use. This type of use can present significant safety problems, since there is, by definition, a lack of evidence that the benefits outweigh the risks.

In children one year old or younger, Lotrisone was most commonly prescribed for the treatment of a yeastlike fungus (candidiasis) of the skin and nails that accounted for 37.7% of its use. Diaper rash accounted for 29.3% of its use, and fungal infections of the body, head, or groin, 8.6% of prescriptions in this age group. All of these uses are off-label.

A serious adverse reaction, growth retardation, was seen in a 1-year-old child treated for diaper rash for 27 weeks. There were 12 adverse reaction reports in children 2 to 6 years old and 19 in the 7 to 12 age group.