ST LOUIS (MD Consult) - On May 7, 2009, the US Food and Drug Administration (FDA) announced that it is requiring manufacturers of 2 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 applying the product and to cover the treated skin with clothing. In most cases involving secondary exposure in children, patients who were prescribed the testosterone products failed to follow appropriate use instructions, resulting in direct contact between treated skin and a child.

As of Dec 1, 2008, the FDA has received reports of 8 cases of secondary exposure to testosterone in children aged 9 months to 5 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, premature development of pubic hair, advanced bone age, increased libido, and aggressive behavior. In most cases, the signs and symptoms regressed when the child was no longer 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 chronologic age.

In some cases of secondary exposure to testosterone, children had to undergo invasive diagnostic procedures. In at least 1 case, a child was hospitalized and underwent surgery as a consequence of a delay in recognizing the underlying cause of the signs and symptoms.

The label changes being required by the FDA will provide additional information about the risk of secondary exposure as well as 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 (REMS) to ensure that the benefits of these products continue to outweigh their potential risks.

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

• testosterone gels should be washed from hands with soap and warm water after every application;
• the application site should be covered with clothing after the gel has dried;
• before skin-to-skin contact occurs with another person, thorough washing of the application site with soap and warm water is necessary;
• children and women should avoid contact with testosterone application sites on the skin of men who use these products; and
• the use of any similar, but unapproved, products from the marketplace (including the Internet) 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 online, by telephone (1-800-FDA-1088), or by sending the postage-paid FDA form 3500 by mail to MedWatch, 5600 Fishers Lane, Rockville, Md 20852-9787, or by fax to 1-800-FDA-0178.
 

圣路易斯(MD Consult)——2009年5月7日，美国食品和药物管理局(FDA)宣布，将要求AndroGel 1%和Testim 1% 这2种处方类外用睾丸酮涂剂制造商在药品说明书中添加加框警告。FDA是在接到不良反应报告后采取这一行动的，报告指出儿童不慎接触睾丸酮涂剂使用者体表上的该药物(二次接触)后发生副作用。

 

该涂剂获批用于治疗不再产生睾酮或睾酮水平极低的男性患者。上述2款产品均为每天1次涂布于肩膀或上臂。只有AndroGel 1%获准用于腹部。目前的说明书指示使用者用后洗手，并穿衣遮蔽涂抹处以预防接触。涉及儿童睾酮二次接触的大多数案例，均是患者未严格遵循药物使用说明书，而造成涂抹处皮肤与小孩的直接接触。

 

截至2008年12月1日，美国FDA已收到8例年龄在9个月到5岁的儿童二次接触睾酮的报告。自12月份以来，接获的其他二次接触的报告目前正在审查之中。在已得到全面审查的报告中，罹患儿童发生的不良事件包括生殖器增大、耻毛滋长、骨龄超前、性欲提高和攻击性行为。不再接触该产品后，大多数儿童性早熟的症状和体征可以逆转。然而，在少数情况下，患儿增大的外生殖器不能没有完全恢复到与年龄相适的大小，且骨龄仍稍超前于实际年龄。

 

某些二次睾酮接触患儿不得不接受侵入性诊断措施。至少有1例患儿因未及时发现症状和体征发生的根本原因而住院，并进行了手术干预。

 

美国FDA要求修改目前的说明书，提供关于二次接触风险及减少此类风险措施的额外信息。FDA还要求制造商为这些产品提交一份用药指南，作为风险评估与降低计划(REMS)的一部分，以确保这些产品带来的好处仍远远超过了其潜在的风险。

 

FDA建议应采取以下预防措施，以尽量减少潜在睾丸酮涂剂的二次接触：

 

•每次使用睾丸酮涂剂后，应该用肥皂和温水洗手；

•涂抹部位应待涂剂干燥之后，穿衣遮蔽；

•在与他人发生皮肤间接触前，必须用肥皂和温水彻底清洗药物涂抹部位；

•儿童和妇女应避免接触睾酮涂剂使用男性的涂抹处皮肤；

•应避免使用任何市面上(包括互联网)未获批准的类似产品。

 

医学专业人士和消费者可向美国FDA MedWatch项目组在线举报在使用此类涂剂过程中出现的严重不良事件或产品质量问题，致电1-800-FDA-1088，传真1-800-FDA-0178或使用FDA提供的3500表格寄信至以下地址：5600 Fishers Lane, Rockville, MD 20852-9787。