The following HTML text is provided to enhance online
readability. Many aspects of typography translate only awkwardly to HTML.
Please use the page image
as the authoritative form to ensure accuracy.
Addressing the Barriers to Pediatric Drug Development: Workshop Summary
tion also exists among children of different ages in their ability to metabolize, absorb, excrete, and transform medications (ICH, 2000; Roberts et al., 2003). As noted above, however, minimal information is available on the safety and efficacy of drugs in pediatric patients, and the younger the age group, the more likely this is to be the case (Roberts et al., 2003).
Recent studies of medications for pediatric patients have revealed several unsuspected differences in efficacy by age group. For example, a study by the Pediatric AIDS Clinical Trials Group compared combinations of drugs for treating children with HIV. Results indicated that a regimen of two daily doses of nelfinavir (Viracept) was pharmacokinetically superior to three daily doses, particularly in smaller, younger children. These were unexpected and positive findings for clinicians attempting to increase medication adherence and reduce the development of drug resistance (Floren et al., 2003; McKinney, 2003).
Because most drugs prescribed for children have not been tested in pediatric populations, important information on their risks and appropriate use for these patients is not available on the product labels. These labels provide health care professionals with details on the use of the drugs, including information from carefully controlled clinical studies. Poor labeling is often an indicator of inadequate study. Off-label use occurs when drugs are prescribed for purposes other than those included under the terms of the FDA product approval (Roberts et al., 2003). Off-label use of drugs is common in adults but far more prevalent in children. While such use can be beneficial to the patient, it can also result in adverse reactions due to a lack of understanding of the drug’s pharmacokinetics in this population.
Current laws employ both incentives and mandates to encourage drug makers to test their products in pediatric populations and to enhance the pediatric information provided on drug labels. The result has been a substantial increase in pediatric drug trials, with corresponding information being added to the labels for 115 drugs. Examples of drugs for which labeling changes have affected dosing and risk include loratadine (Claritin) and fluvoxamine maleate (Luvox). In a single-dose pharmacokinetic study of pediatric subjects (age 2 to 5 years) it was found that children receiving a 5-mL dose of CLARITIN Syrup containing 5 mg of loratadine had comparable range of pharmacokinetic parameters (AUC and Cmax) to adults and older children who had received a tablet or syrup containing 10 mg of loratadine. Likewise, fluvoxamine maleate, used to treat obsessive-compulsive disorder, was found to be most effective in adolescents at the recommended adult dose, but girls aged 8 to 11