Safety concerns over testosterone gel prompt FDA to require label changes

May 7 2009

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 (secondary exposure).

The gels are approved for use in men who either no longer produce testosterone or produce it in very low amounts. Both products are applied once daily, to the shoulders or upper arms. Only AndroGel 1% 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, M.D., 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."

In 2007, 1.4 million prescriptions for AndroGel-the most commonly dispensed gel form of testosterone-were dispensed by U.S. retail pharmacies. Approximately 25,000 of those were dispensed for off-label use in women. During the same period, some 370,000 prescriptions were dispensed for Testim, according to data from SDI: Vector One National. 

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 nine months to five years. Since that time, additional reports of secondary exposure have been received by the agency and are presently under review.

Of the fully reviewed cases, adverse events reported in these children included inappropriate enlargement of the genitalia (penis or clitoris), 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.

Signs of inappropriate virilization (development of male secondary sexual characteristics) in children and the possibility of secondary testosterone exposure should be brought to a health care provider's attention.

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.

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 (side effects) or product quality problems with the use of these gels to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.