Rational Pharmacotherapy in Children: Challenges of Off-Label Use and Drug Safety

The field of pediatric clinical pharmacology faces persistent challenges in balancing therapeutic innovation with safety, particularly when treating conditions for which age-appropriate formulations or clinical data are limited. Off-label drug use in children remains both widespread and necessary, reflecting the historical underrepresentation of pediatric populations in clinical trials. Although such practices can be essential for providing timely treatment, they raise significant concerns regarding variations in dosing, drug formulation, efficacy extrapolation from adults, and long-term safety. Recent large-scale pharmacoepidemiologic analyses and multicentre studies have shown that off-label prescribing in pediatrics can reach rates of 30–70% depending on the drug class and setting, underlining the continued gap between regulatory approval and clinical necessity. These findings underscore the importance of developing a robust evidence base and improved governance frameworks to enhance rational pharmacotherapy in children.This Research Topic aims to close critical evidence gaps by bringing together multidisciplinary perspectives on pediatric off-label drug use and safety. It will examine the pharmacological, clinical, ethical, and regulatory dimensions that shape current prescribing patterns and safety outcomes. Contributors are encouraged to address key questions such as: What are the predictors and risk profiles of off-label medication use in children? How can pharmacovigilance systems and real-world data improve safety monitoring? What strategies can optimize benefit–risk assessment, evidence generation, and policy alignment across different healthcare systems? By aggregating research across clinical, regulatory, and methodological domains, this topic seeks to promote standardized and safer drug use practices tailored to pediatric physiology and population needs.This Research Topic will consider contributions spanning clinical evidence, policy analysis, and pharmacoepidemiologic evaluation. The scope is broad but focused on rational pharmacotherapy in children and adolescents, with a preference for work that bridges real-world evidence and clinical applicability. To gather further insights into the evolving landscape of pediatric drug use, we welcome submissions addressing, but not limited to, the following themes:o Epidemiology of pediatric off-label and unlicensed drug use in different healthcare settingso Advances in pediatric drug safety monitoring and pharmacovigilance approacheso Clinical pharmacokinetics and dose optimization in off-label contextso Risk–benefit evaluation and evidence translation for pediatric therapieso Global and national regulatory frameworks and policy harmonizationo Ethical considerations and informed consent practices in pediatric drug useo Digital health tools and real-world data applications for pediatric safety evaluationo Development, evaluation and management of pediatric-specific formulationso Implementation, interventions and optimization of pediatric medication guidelinesArticle types: Original Research, Systematic Reviews, Mini Reviews, Brief Research Reports, Case Reports, Case Series, and Perspective or Policy articles. Topic editors: Pavla Pokorna, Min Tian, Min Meng Source: https://www.frontiersin.org/research-topics/83965/rational-pharmacotherapy-in-children-challenges-of-off-label-use-and-drug-safety