Pediatric Drug Safety

by Food and Drug Administration (FDA)

Despite seven days, "about 26 hours a day," spent preparing to testify about the labeling of drugs for children's use, Wendy Goldberg told Food and Drug Administration experts at a 1997 hearing, "I have become neither a scientist nor a doctor. Not even close." But, she said, "I do know one thing — I use a lot of medicines on Abby that are not approved by the FDA for use on children her age."

Of the nine-item laundry list of medicines Goldberg's 6-year-old daughter Abby was taking for her severe asthma, not a single one was tested or approved in the United States for children under 12. "I feel as though I am testing drugs on my own child, every day, and it isn't helping anyone," Goldberg said.

While some drugs do come with pediatric use information (notably, vaccines and antibiotics), asthma medications by no means stand alone in their lack of labeling for kids' treatment. Other types of drugs that often lack pediatric labeling include those for depression, epilepsy, severe pain, gastrointestinal problems, allergic reactions, and high blood pressure.

Overall, more than half of the drugs approved every year that are likely to be used in children are not adequately tested or labeled for treating youngsters, according to FDA estimates. Safety and effectiveness information is especially sparse for the over 7 million children under age 2.

A recent survey by the agency identified the 10 drugs that were prescribed most often to children in 1994 that lacked pediatric labeling. Together, they were prescribed for kids more than 5 million times.

"At times, children have been harmed and maybe even killed because of a lack of knowledge of how drugs would affect them," says Robert M. Ward, M.D., chair of the American Academy of Pediatrics' Committee on Drugs. Among Ward's historical examples: the deaths of a number of newborn babies in the 1960s when their immature livers were unable to break down the antibiotic chloramphenicol. "Those types of therapeutic misadventures are certainly part of pediatric medicine, and we'd rather they didn't repeat," he says.

To help prevent future chloramphenicol-type disasters, FDA finalized a rule last December requiring manufacturers of many drugs to provide information about how their drugs can safely and effectively be used in children (from newborns to adolescents), including information on the proper doses for kids.

A Healthy Dose of Regulation

The pediatric studies rule, published in the Dec. 2, 1998, Federal Register, requires that new drugs (generally prescription drugs, including biologics, or drugs derived from living organisms) that are important in the medical treatment of children or will be commonly used in children include labeling information on safe pediatric use.

The information would usually be required when a drug is approved. For drugs already on the market, FDA can require children's studies in certain compelling circumstances — when pediatric labeling could avoid significant risks to kids, for example.

The rule expands on a 1994 regulation that simplified the information needed for a manufacturer to label its drugs for children's use. That rule required drug makers to look at existing data and determine if they could support safe and effective use in children.

"That was the voluntary effort, and we weren't making much headway," says Rosemary Roberts, M.D., chair of the pediatric subcommittee in FDA's Center for Drug Evaluation and Research. "Most manufacturers just went back to saying that safety and effectiveness had not been established for children."

Without pediatric data about a drug, Roberts says, doctors are sometimes reluctant to treat a child with it. "Some physicians won't even try a drug in a child if they don't have enough information," she says. It is legal, however, to prescribe a drug for use in children despite its approval only for adults (termed "off-label" use).

If doctors decide against using adult drugs in their young patients because the appropriate dose is unknown, children may be deprived of useful treatments, especially some AIDS drugs and other breakthrough therapies that carry considerable risks.

Doctors can be faced with quite a dilemma, says Timothy Westmoreland of the Elizabeth Glaser Pediatric AIDS Foundation. "Do you choose to withhold a potentially effective drug that is useful in adults or expose a child to a drug you don't know is safe?"

Because of their immature organs and different metabolic and immune systems, children react unlike adults to many drugs. Treating children with adult drugs, then, can carry the risk of unforeseen adverse reactions.

Besides the chloramphenicol tragedy, other serious adverse reactions in children have included:

• jaundice in newborns from sulfa drugs
• seizures and cardiac arrest from the local anesthetic bupivacaine
• withdrawal symptoms from prolonged use of the painkiller fentanyl.
• staining of teeth from the antibiotic tetracycline

"It can be a real guessing game as to whether we're treating a child effectively," Roberts says. "Sometimes a child's body will handle the drug very much like an adult's, she explains, "while other times a child's body will react quite differently. There may be no way of knowing in advance."

While dosing information sometimes becomes available to physicians through references such as journal articles and pediatric handbooks, it may take years for this information to appear. Even then, the information may not be based on adequate testing and may contain gaps, about its use in certain age groups, for example.

Even if the correct dose is known, the medicine will do no good, of course, if a child can't ingest it. So the 1998 rule in some cases requires manufacturers to make a special formulation of a drug product — liquid or chewable tablet instead of a tablet that must be swallowed whole, for example — to enable kids to take the drug.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.