Pediatric drug labeling: improving the safety and efficacy of pediatric therapies.

Context: Approximately 50% to 75% of drugs used in pediatric medicine have not been studied adequately to provide appropriate labeling information. In 1997, Congress passed the Food and Drug Administration Modernization Act (FDAMA), which encouraged pediatric drug development by providing an incentive in the form of additional marketing exclusivity.

Objective: To identify new drug labeling information from pediatric studies submitted to the FDA in response to written requests.

Design And Setting: Between July 1998 and April 1, 2002, the FDA requested studies on 242 drugs, and 53 drugs were granted exclusivity. As of January 2003, 49 drugs have new labels. Data from the studies of the first 33 drugs with new pediatric information on the label as of April 2002 are included. Significant labeling information was analyzed along with baseline data and types of studies requested.

Main Outcome Measures: Safety data and pediatric information for labeled drugs.

Results: There were 53 studies for 33 drug products, 12 (23%) were evaluated for safety only; 23 (43%), safety and efficacy; and 18 (34%), pharmacokinetics and/or pharmacodynamics. Significant new dosing and/or safety information was identified for 12 (36%) drugs. New dosing information was determined for 7 of these drugs. Safety information was defined for gabapentin, propofol, sevoflurane, the combination of ribavirin and interferon alfa-2b, and various betamethasone-containing dermatologic preparations. There was a higher percentage of deaths reported with patients who received propofol compared with controls in the pediatric intensive care unit. Seizures were seen in patients administered sevoflurane. Patients receiving a combination of ribavirin and interferon alfa-2b experienced an increased incidence of suicidal ideation when compared with adults. An unexpectedly high percentage of those receiving betamethasone-containing dermatologic preparations had documented hypopituitary-adrenal axis suppression.

Conclusion: The FDAMA has stimulated pediatric clinical studies resulting in improved understanding of the pharmacokinetics of drugs prescribed in pediatric medicine, important dose changes, and improved safety for children taking certain drugs.