Safety and Efficacy of Off-label and Unlicensed Medicines in Children

Background: The aim of this study was to explore the use of off-label/unlicensed drugs to confirm the safety and efficacy of their prescription in children in Korea. Methods: In this retrospective study, we analyzed data of patients who received any of the 32 drugs between January-December 2014 in tertiary hospitals in Korea, including demographics, diagnoses, reasons for the medication, administration route, and details of adverse drug reactions. Additionally, the mortality in the cohort was assessed. The primary outcomes were efficacy and safety, including mortality, of these drugs in pediatric patients. The secondary outcomes were the current statuses of the use of off-label/unlicensed drugs in two centers. Results: Totally, 5,130 prescriptions were found in 2,779 patients. Age (73.5%) and indication (11.7%) were the most frequent reasons for prescriptions being off-labeled/unlicensed. Approximately 88% of the prescriptions were effective, and 19% of the patients developed adverse drug reactions. The number of prescriptions was significantly higher in children with adverse drug reactions than it was in those without (2.8 vs. 1.5; P < 0.001). The number of prescribed off-label/unlicensed medicines and age at prescription were independently associated with adverse drug events (odds ratio, 1.55 and 1.1; P < 0.001 and 0.034, respectively). Conclusion: Children are still prescribed medicines that are not authorized in terms of age, weight, indications, or routes of administration. Therefore, many old products require re-assessment of authorization. More prospective clinical studies should be performed to confirm the efficacy and safety of drugs in the pediatric population.