Safety concerns prompt label changes and Medication Guide requirement for Testosterone Gel Products

The Food and Drug Administration is requiring manufacturers of two prescription topical testosterone gel products, AndroGel 1% and Testim 1%, to include a boxed warning on the products’ labels 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, and are often used by men living with HIV who have below normal testosterone levels.

Although the Precautions in the current labels instruct users to wash their hands after using the product and to cover the treated skin with clothing, FDA has received reports of cases of secondary exposure to testosterone in children ranging in age from nine months to five years. 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.

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, invasive diagnostic procedures were required.

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.

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:

• Online: www.fda.gov/MedWatch/report.htm
• Fax: (800) FDA-0178
• Phone: (800) FDA-1088
• Regular Mail: use postage-paid FDA form 3500 available at: www.fda.gov/MedWatch/getforms.htm and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787

AndroGel 1% is manufactured by Marietta, Ga.-based Solvay Pharmaceuticals. Testim 1% is made by Auxilium Pharmaceuticals, Malvern, Pa.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration