Drug Utilisation and Off-Label Use on a German Neonatal Intensive Care Unit: A Retrospective Cohort Study and 10-Year Comparison

Abstract

Pharmacotherapy of neonates is complex and marked to a large extent of off-label use. The implementation of the Paediatric Regulation (2007) gave hope for a change in the safety and efficacy for drugs used in neonatal intensive care units (NICU). This study investigates drug utilisation patterns and off-label use in a German neonatal intensive care unit (NICU) in 2014. A 12-months retrospective, observational cohort study was performed at the NICU of the University Children’s Hospital Erlangen, Germany. Licensing status was determined using the Summary of Product Characteristics (SmPC). Results are compared with a similar study conducted 10 years earlier. The study included 204 patients (57.8% male) (2004: 183) and 2274 drug prescriptions were recorded (2004: 1978). The drugs that were mostly prescribed were drugs for the nervous system (2004: 22.6%; 2014: 26.9%) and anti-infectives for systemic use (2004: 26.0%; 2014: 24.9%);34.3% (2004) and 39.2% (2014) of all prescriptions were off-label;62.7% of all patients received at least one off-label or unlicensed drug (2004: 70%). For 13 drugs, the licensing status changed either from off-label to label (n = 9) or vice versa (n = 4). Overall, there was no significant change neither in terms of the drugs used nor regarding their licensing status. Further studies are needed to validate these findings in a European context.

Drug utilisation in neonatal units in England and Wales: a national cohort study

“…Extremely preterm infants receive, on average, 17 different drugs and spend 94% of their time on medications despite the exclusion of routine prescriptions such as multivitamins. A study from Germany reported 11 drugs per infant in two cohorts (2004 and 2014) [ 9 ]. Other studies have also reported a high burden of drug use in preterm infants.…”

c4c: Paediatric pharmacovigilance: Methodological considerations in research and development of medicines for children – A c4c expert group white paper

“…Polypharmacy is common in neonates and children admitted to intensive care, and off‐label or unlicensed use is particularly common in these patients. 129 , 130 , 131 , 132 This is associated with the need to manipulate the formulation, for example by crushing tablets or dilution. 129 Medication errors due to drug manipulation and drug administration errors are common in children and can have serious consequences.…”

“…Therefore, it needs to be possible to administer the formulation, for example, to a premature neonate weighing just 500 g and an adolescent weighing 70 kg. Polypharmacy is common in neonates and children admitted to intensive care, and off‐label or unlicensed use is particularly common in these patients 129–132 . This is associated with the need to manipulate the formulation, for example by crushing tablets or dilution 129 .…”

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

“…Pharmaceutical treatment in the neonatal department is challenging and off-label medicine use, i.e., use of a medicine outside its regulatory approved marketing authorization, is high. [1][2][3][4][5] It is well known that infants in the neonatal intensive care unit (NICU) are exposed to a large number of medicines. This was once again demonstrated in a recent international review of studies of drug utilization in the NICUs showing a high mean number of medicines per infant, with several studies reporting >30 medicines per infant.…”