Off-label use and pharmacovigilance among infants: analysis of the Thai Health Product Vigilance National Database

Background: A lack of drug safety and efficacy studies in pediatric patients is a major problem contributing to inappropriate drug use among this population. The prevalence of ‘off-label’ drug use is high in pediatric patients, leading to an increased risk of adverse events (AEs). A pharmacovigilance database is useful for healthcare providers in monitoring AEs associated with off-label drug use. Objectives: The aim of this study was to explore the characteristics of AEs reported among pediatric patients aged 1\ua0month to 2\ua0years who received off-label drugs, using information derived from the Thai pharmacovigilance database. Methods: Spontaneous reports of AEs in pediatric patients aged 1\ua0month to 2\ua0years were derived from the Thai Health Product Vigilance Center (HPVC) database for the period of January 1984 to November 2013. Off-label drug use was defined as drug use outside the age range indicated by US FDA and European Medicines Agency (EMA) drug labeling. Descriptive statistics were used to describe demographics and Anatomical Therapeutic Chemical (ATC) drug classes. Reporting odds ratios were used to evaluate associations between off-label drug use and AE seriousness and the occurrence of critical AEs. Results: A total of 22,294 AE reports were collected, with 21,390 AE reports meeting the inclusion criteria. These reports were further classified as those involving off-age drug use (5.2\ua0%), age-label drug use (65.2\ua0%), and unclear/unfound age labeling (29.6\ua0%). Of those containing off-age drug use, most were in the ATC anatomical main group of nervous system agents (24.1\ua0%), followed by systemic anti-infective agents (20.5\ua0%). There was a significant association between off-label drug use and the occurrence of critical AEs. Conclusions: Off-label drug use is associated with unwanted AEs. Therefore, assessing the risk versus benefit of each drug should be taken into consideration before prescribing off-label drugs for pediatric patients