Safety Concerns Lead to Label Changes For Topical Testosterone

In May 2009, the Food and Drug Administration (FDA) announced that labels of two topical testosterone gel products, ANDROGEL 1% and TESTIM 1%, must include a black box warning on the products’ labels.

The FDA’s decision to require stronger labeling is the result of multiple reports that the agency received of side effects in children who were inadvertently exposed to testosterone through contact with another person being treated with these products.

These two gels are approved by the FDA 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 on the current professional product labels (package inserts) instruct users to wash their hands after using the drug and to cover the treated skin with clothing.

As of Dec. 1, 2008, the FDA had received reports of eight cases of secondary exposure to testosterone in children ranging in age from 9 months to 5 years. Since that time, additional reports of secondary exposure have been received by the agency and are presently under review. The reports are likely much lower than the actual number of exposure to topical testosterone — only a small fraction of serious adverse drug reactions are ever reported to the FDA.

In the cases that were fully reviewed by the FDA, the adverse events reported in 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 subsided when the children no longer were exposed to the testosterone gel. However, in some cases, enlarged genitalia did not fully return to age-appropriate size, and bone age remained modestly greater than the children’s actual age.

In some cases, children had to undergo invasive diagnostic procedures to find the cause, 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.

FDA recommendations

The FDA recommends the following steps be taken to minimize the potential for secondary testosterone 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.

What You Can Do

Patients using testosterone gel should read the FDA-required Medication Guide before use. The Medication Guides for testosterone gel and other drugs can be obtained from the FDA’s Web site at http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm or by asking a pharmacist.

Patients should follow the directions carefully for the proper use of these products to avoid secondary testosterone exposure in children.

Contact a health care provider if the signs of inappropriate virilization (development of male secondary sexual characteristics) in children appear.

Consumers may report serious 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.

Call MedWatch at (800) FDA-1088 to request a form via mail, or fill out the form online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm.

To return the completed form via regular mail, use postage-paid FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787. FDA also accepts completed forms via fax at (800) FDA-0178.