FDA calls for labeling changes, medication guides for two topical testosterone gels

The U.S. Food and Drug Administration today announced that it is requiring manufacturers of two prescription topical testosterone gel products, AndroGel 1% and Testim 1%, to include a boxed warning on the products’ labels. The agency is requiring this action after receiving reports of adverse effects in children who were inadvertently exposed to testosterone through contact with another person being treated with these products.

The gels are approved for use in men who either no longer produce testosterone or produce it in low amounts. Both products are applied once daily to the shoulders or upper arms. Only AndroGel 1% (Solvay Pharmaceuticals) is approved for application to the abdomen. Precautions in the current labels instruct users to wash their hands after using the product and to cover the treated skin with clothing.

“These drugs are approved for an important medical need, but can have serious, unintended side effects if not used properly,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research. “We must ensure that the adults using them are well informed about the precautions needed to protect children from secondary exposure.”

Reported side effects of secondary exposure

Despite the currently labeled precautions, as of Dec. 1, 2008, the FDA has received reports of eight cases of secondary exposure to testosterone in children ranging in age from 9 months to 5 years. The agency has received additional reports of secondary exposure since that time and is presently reviewing them.

Of the fully reviewed cases, adverse events included inappropriate enlargement of the genitalia, premature development of pubic hair, advanced bone age, increased libido and aggressive behavior.

In most cases, the signs and symptoms regressed when the child no longer was exposed to the product. However, in a few cases, enlarged genitalia did not fully return to age-appropriate size and bone age remained modestly greater than the child’s chronological age.

In some cases, children had to undergo invasive diagnostic procedures and, in at least one case, a child was hospitalized and underwent surgery due to a delay in recognizing the underlying cause of the signs and symptoms.

In most of the cases, users of these products failed to follow appropriate use instructions, resulting in direct contact between treated skin and the child.

Required label changes

The required label changes will provide additional information about the risk of secondary exposure and the steps that should be taken to reduce this risk. The FDA also is requiring that the manufacturers of these products develop a medication guide as part of a Risk Evaluation and Mitigation Strategy to ensure that the benefits of these products continue to outweigh their potential risks.

The FDA recommends the following precautions be taken to minimize the potential for secondary exposure:

Adults who use testosterone gels should wash their hands with soap and warm water after every application;
Adults should cover the application site with clothing once the gel has dried;
Adults should wash the application site thoroughly with soap and warm water prior to any situation where skin-to-skin contact with another person is anticipated;
Children and women should avoid contact with testosterone application sites on the skin of men who use these products; and
Adults should note that use of any similar, but unapproved, products from the marketplace — including the Internet — that can result in the same serious adverse effects should be avoided.

Health care professionals and consumers may report serious adverse events or product quality problems with the use of these gels to the FDA's MedWatch Adverse Event Reporting program.