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
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
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;
should wash the application site thoroughly with soap and warm water
prior to any situation where skin-to-skin contact with another person
- Children and women should avoid contact with testosterone application sites on the skin of men who use these products; and
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.