Update on Immunomodulating Topical Agents and NSAIDS

Topical Immunomodulating Agents

In March 2005, the Food and Drug Administration (FDA) issued a public health advisory to inform health care professionals and patients about a potential cancer risk from use of the new immunomodulating topical agents, tacrolimus (Protopic) and pimecrolimus (Elidel). These drugs are widely used in dermatology for the short-term and intermittent longterm treatment of atopic dermatitis in patients older than 2 years of age.

Protopic and Elidel are calcineurin inhibitors and immunosuppressants. Although their exact mechanism of action is not known, they exert direct immunosuppressive effects by inhibiting T- cell activation and the subsequent release of cytokines. The value of this new class of agents stems from the fact that they work as well as steroids, but without the associated side effects of skin atrophy and rosacea-like dermatitis.

Increased safety concerns are based on preliminary analysis of data from animal studies, case reports in a small number of patients, and knowledge of how drugs in this class work. In animals, the carcinogenicity signal is strong and dose-dependent. The potential exists for increased systemic absorption of these topical agents through abraded skin. In addition, children have a greater body surface area to mass ratio than adults, potentially increasing risk in the pediatric population.

It may take human studies of 10 years or longer to determine if use of these immunomodulating topical agents is linked to cancer. In the meantime, this risk is uncertain, and the FDA advises clinicians to “use Elidel and Protopic only as second-line agents for short- term and intermittent treatment of atopic dermatitis (eczema) in patients unresponsive to or intolerant of other treatments.”

Nonsteroidal Anti-Inflammatory Drugs (NSAIDS)

In April of this year, the FDA announced several important changes related to use of nonsteroidal anti-inflammatory drugs (NSAIDs). Rofecoxib (Vioxx) was withdrawn from the market in 2004 because of concerns about adverse cardiovascular events. More recently one of the COX-2 inhibitors, valdecoxib (Bextra), was withdrawn from the market based on concerns about cardiovascular events and serious skin reactions, including deaths.

Celecoxib (Celebrex) is the only COX-2 inhibitor still on the market. The FDA decided that the benefits of Celebrex outweigh the risks. However, a boxed warning has been added to the label to emphasize cardiovascular and gastrointestinal risks associated with this drug. In addition, patients will receive a Medication Guide on safety risks each time a prescription is dispensed. This guide will stress the importance of using the lowest effective dose of Celebrex for the shortest time possible.

Similar labeling changes will also apply to nonselective NSAIDs, such as ibuprofen and naproxen.

References

Food and Drug Administration (FDA). (2005). FDA issues public health advisory informing health care providers of safety concerns associated with the use of two eczema drugs, Elidel and Protopic. Rockville, MD: National Press Office.

Food and Drug Administration (FDA). (2005). 2005 safety alerts for drugs, biologies, medical devices, and dietary supplements. Retrieved June 6, 2005, from http://www.fda.gov/medwatch/ SAFETY/ 2005/safety05.htm#Bextra

Janice Zeigler Cuzzell, MA, RN, is Dermatology Regional Clinical Coordinator, Genentech, Inc., Savannah, GA, and is a Dermatology Nursing Editorial Board Member.

Copyright Anthony J. Jannetti, Inc. Aug 2005