Massive presence of off-label medicines in Danish neonatal departments. A nationwide survey using national hospital purchase data

Abstract

Background and Purpose Pharmaceutical treatment in the neonatal intensive care unit (NICU) is challenging, and newborns are often exposed to numerous different medicines during their hospitalization There is currently insufficient knowledge of gestational age dependent medicine disposition, and accordingly the use of off-label medication, i.e., use of medicines outside its approved marketing authorization, is high. This study aims to estimate the off-label medication use in Danish neonatal departments. Experimental Approach By using data from the Danish National Pharmaceutical Hospital Purchase Database, we identified the most commonly occurring medicines and estimated the on/off-label ratios for premature and term neonates. Data was extracted on ATC level 5 and based on defined daily doses as per WHO. Key Results Data included was covering the 4 high-level NICUs and 10 of 13 of the intermediate/standard level neonatal departments in Denmark. Of the identified medication, 87% and 70% did not have approved marketing authorization for use in premature and full-term neonates, respectively. Furthermore one-fifth of the top 100 medicines did not have a (Danish) marketing license. Overall, off-label medication was widespread covering virtually all ATC groups and no ATC group had an off-label level lower than 50%. Finally, in 21% of medications, additives from 8 different chemical groups with potential deleterious effects for neonates were identified. Conclusion Off-label medication in the Danish neonatal departments is widespread, and the current state of neonatal official regulatory drug approval leaves both patients and neonatologists in a limbo between legal pharmaco-regulation and clinical need for pharmacotherapy in neonatology.

Adverse drug reactions in neonates: a brief analysis of the FDA adverse event reporting system

“…Drug trials in neonates are scarce; as a consequence, up to 90% of the treatments in neonates are off-label, raising concerns about the risks of adverse drug reactions (ADRs) (Stark et al, 2021;Gade et al, 2023). Given the limited clinical testing in such instances, spontaneous ADR reporting is an important tool for expanding knowledge on and OPEN ACCESS increasing drug safety in neonates; however, it is well known that the applicability of the currently available data is undermined by underreporting (Khalili et al, 2020).…”