Health Letter, July 2013
In February 2013, the Food and Drug Administration (FDA) issued a statement that parents and caregivers of small children play a critical role in helping to identify dangerous side effects from drugs or medical devices. The agency is encouraging consumers to report kids’ problems with medical products to catch these problems earlier and better protect children.
Indeed, consumer reports made a difference in 2009, when the FDA added a new black-box warning to products containing testosterone gel to prevent children from being exposed to side effects from the hormones. The new warnings were added following eight reports of infants, toddlers and young children developing disturbing symptoms of abnormal growth and extremely early puberty after coming into contact with an adult who used the product.
Only a small proportion of adverse events in children are ever reported, but the FDA relies heavily on such information to identify problems affecting this vulnerable population. Learn how you can help identify problems more quickly by staying vigilant for drug side effects in children and working with your child’s pediatrician to report these issues to the FDA when they occur.
Overdiagnosis Of ‘Low T’
Testosterone products (such as Androgel and Testim) are FDA-approved to raise testosterone levels in adult men who have been diagnosed with a condition known as hypogonadism, which results in low testosterone levels, sometimes called “low T.” Unfortunately, it is easy for doctors to mistakenly diagnose hypogonadism in patients who do not really have the condition, due to its commonly experienced symptoms, such as fatigue, loss of energy and decreased sexual desire. These symptoms, especially decreased sexual desire, can have a psychological cause for which treatment with testosterone is not appropriate. Older men are especially vulnerable to overdiagnosis because testosterone levels decrease naturally with age. Overdiagnosis and overprescribing of testosterone raise serious health concerns as the hormone may be associated with increased risk of prostate cancer, infertility and certain cardiovascular risks.
Reporting works: Case study
Jacob* was 6 months old when his mother noticed that he had started growing hair in his pubic area. The hair started out so light that it was barely noticeable, but by the time Jacob was 16 months old it had thickened and grown dark enough that his mother became nervous and pointed the issue out to his pediatrician. She also told the doctor she was concerned that his genitalia seemed larger than normal.
The pediatrician administered an X-ray and physical exam. Jacob’s medical team told his parents that the infant’s bones had developed beyond the appropriate stage for a boy of his age and that he was growing more quickly than normal. After ruling out central precocious puberty, a condition usually caused by problems with the central nervous system, the doctor took blood tests that revealed a potential clue to Jacob’s condition: the boy’s testosterone levels were six times higher than the normal range for an infant.
Jacob’s father, Adam, immediately thought about his own medication. Adam had been using a testosterone cream twice a day, hoping to increase his sex drive, which was diminished as a result of his depression. Jacob had been sleeping in the same bed as his parents, and Adam would hug Jacob and hold the child on his bare chest for skin-to-skin contact.
Adam read the package insert for the testosterone gel and learned that testosterone can be transmitted to other people by touching the skin where the gel has been applied. He thought he may have exposed Jacob by accident, but he was too embarrassed to tell Jacob’s pediatrician about his concerns. Instead, he stopped sleeping in the same bed with Jacob and made sure not to hug or hold his son without a shirt on. At Jacob’s next doctor’s visit, his condition had improved but was not fully resolved.
Luckily, Adam was eventually able to admit to his son’s pediatrician that he had been using testosterone gel and had taken steps to protect Jacob. The doctor shared this information with the medical community by writing up Jacob’s story in a “case report” that was published in a pediatric medical journal.
Jacob’s case report became one of eight cases prompting the FDA to investigate testosterone gel to see if it was causing problems in children. All eight of these cases involved boys or girls younger than 6, with strikingly similar symptoms, who were exposed to testosterone through skin contact with their fathers. When the fathers eliminated exposure to the gel, for example by protecting their children with clothing to avoid skin contact, some (but not all) of these signs and symptoms improved.
Testosterone is not approved for use in children, and its safety and efficacy have not been established in this age group. During clinical trials of testosterone for adults, researchers noticed elevated testosterone levels in women who had experienced skin-to-skin contact with a male partner for as little as 15 minutes a day. This transfer of testosterone could be prevented by wearing clothing to cover the area on which the cream had been applied (usually the arms and shoulders). The risk of transfer through skin contact was described in the professional labeling for testosterone products, which also warned patients to wash their hands after applying the cream and avoid contact with pregnant women. However, at the time, these warnings were not prominent on the label.
At the FDA’s request, the manufacturer of one testosterone product, Androgel, reported 17 additional cases of adverse events in children and more than 100 cases of adult exposure. It is not clear why the manufacturer did not report the additional cases until the FDA’s request.
Thanks to the case reports, the FDA announced in May 2009 that it would require testosterone products to carry a boxed warning to help prevent accidental exposure in children. The products also now include a medication guide that more clearly outlines the risks to children and instructs men on how to avoid these risks by washing hands and wearing protective clothing.
“Those reports from consumers made a difference,” said Jo Wyeth, a safety evaluator at the FDA, in a recent FDA statement to consumers. Wyeth worked with the families and doctors who had reached out to the FDA to raise concerns about the testosterone products. “We want to prevent these harmful situations from happening to others,” said Wyeth.
Low reporting rates
In 2012, the FDA received nearly 900,000 adverse event and medication error reports (reports of injuries or negative effects seen in patients taking a drug), but only 5 percent were associated with children younger than age 18. The reporting probably represents only a small fraction of the true number of adverse events occurring in children. To boost these numbers, the FDA is encouraging more consumers to report adverse events directly to the agency.
The FDA relies heavily on post-market adverse event reports to learn critical information about drug side effects in children. This is because it is relatively rare for drug manufacturers to conduct pre-market clinical trials in the more vulnerable pediatric population. Even when a manufacturer does conduct a pediatric trial, the test group tends to be smaller than in trials enrolling adults and may cover a limited age range.
Adverse event reports are thus especially helpful for detecting risks in children. Consumers and pediatricians can help the FDA identify problems and warn other families more quickly by staying vigilant and reporting negative events when they occur.
Adverse events can be reported to the FDA using the agency’s MedWatch reporting program (see text box below).
How to Report an Adverse Event
You can submit a report to the FDA using the MedWatch reporting system by calling 1-800-FDA-1088 or by visiting www.fda.gov and typing in MedWatch in the search box. You also can submit a report by contacting the drug’s manufacturer, which is required by law to pass the report along to the FDA.
Remember: If you do report an adverse event in more than one place, include the same detailed information in each report so the FDA can identify duplicates.
The FDA requires high-quality reports to identify issues with drugs. Reports that lack essential information, such as the patient’s age or length of exposure to the medical product, may not be helpful to the FDA.
“What I have found to be most helpful in reports from consumers is a clear statement about the event, followed by a more detailed description of what happened,” Wyeth told consumers in the FDA’s recent announcement. The FDA also recommends including information regarding:
- Product name, type, dose and how it was administered;
- How long the product was used;
- Age of the child;
- Other medications or medical conditions present at the time of the event;
- Outcome (such as what happened to the child if the medical product was stopped); and
- Contact information for the person submitting the report and for the child’s health care professional.
You can ask your pediatrician for help filling out an adverse event reporting form. Your child’s doctor will be best able to recognize the type of information the FDA will need, including technical information such as results from blood tests or X-ray results.
If FDA safety evaluators find something significant in your report, they may contact you or your child’s doctor with follow-up questions. Do not get discouraged if you do not hear back from the FDA after submitting your report; it usually takes multiple reports of similar incidents before the FDA will investigate a problem. When you take the time to report, you are taking an important step toward ensuring that children across the country stay protected from serious risks.
* Names added to a case that was reported anonymously to preserve patient privacy.