Skip to main content Back to Top


Pediatric Labeling Improves After Federal Prompting

Kate Traynor

A federal effort to improve the pediatric information in drug labeling led to research that revealed important details about the pharmacokinetics, dosage, and safety of certain medications when given to young patients, according to a recent report in the Journal of the American Medical Association (JAMA).

The report, which was written by three physicians and a pharmacist from the Food and Drug Administration (FDA), examined products whose new pediatric labeling was approved under the "pediatric exclusivity" program of the Food and Drug Administration Modernization Act of 1997 (FDAMA). According to the report, 33 of 53 drug products that received marketing exclusivity under FDAMA after the manufacturer performed pediatric clinical studies underwent subsequent labeling revisions to reflect the products' use in children.

Of the 33 products with revised pediatric labeling, 12 had labeling changes that the report described as "[s]ignificant new dosing and/or safety information."

A change in the labeling for the sedative propofol, for example, was prompted by research that found the drug increased the risk of death among children treated in an intensive care unit. According to the JAMA report, pediatric research also found that the coadministration of propofol and fentanyl could cause a dangerous slowing of the heart rate in children.

FDAMA-inspired pediatric research earned etodolac a new indication for the treatment of juvenile rheumatoid arthritis in children age 6–16 years. Pediatric research likewise identified specific dosage requirements for the product in young people.

According to the report, the labeling for buspirone hydrochloride, an antianxiety drug that is effective when taken by adults, was revised after pediatric studies were unable to demonstrate efficacy or safety for the product in children.

The JAMA report stated that the clinical studies leading to labeling revisions were undertaken by product manufacturers in response to written requests from FDA. Three of the products—gabapentin, fluoxetine hydrochloride, and midazolam hydrochloride—were among 17 drugs identified by the American Academy of Pediatrics in 1996 as medications widely used in children without the help of specific information in the products' labeling.

The report described as "trial and error" the pediatric administration of medications that have not been labeled for use in children. According to the authors, two thirds of the drugs used to treat children lack labeling that addresses the products' safety and efficacy in young patients.

Drug products included in the study were identified from among 242 medications for which FDA had requested pediatric studies between July 1998 and April 1, 2002. The report's authors noted that, between the end of the study and January 2003, pediatric labeling revisions were made for an additional 16 drugs, bringing to 49 the total number of drugs with pediatric labeling revisions.

A federal court ruling last October prohibits FDA from requiring manufacturers of new drug products to conduct safety and efficacy testing in pediatric patients. The judicial decision rendered invalid the so-called "Pediatric Rule" of 1998, through which FDA had required pediatric studies for drug products likely to be beneficial for children.