Exposure to potentially harmful excipients in neonates admitted to intensive care units using compounded medicines

Compounding allows the use of medicines in paediatric patients that are not always available in appropriate dosages. Some of the commonly used excipients have been associated with toxicity events in neonates.

To evaluate the exposure to potentially harmful excipients (PHEs) in neonates using compounded medicines and admitted to the neonatal intensive care unit (NICU) of a university hospital in Portugal.

Observational study with neonates using the 10 most prescribed compounded liquid oral medicines with a PHE in a hospital NICU. The daily intake of excipients listed in the European Study of Neonatal Exposure to Excipients (ESNEE) was calculated in NICU newborns (September 2019 to August 2020) by summing the daily dose of excipients in the compounded and all commercial medicines prescribed (Ethics CHUSJ CE-OP84-2021).

65 neonates used the 10 most prescribed compounded medicines containing a PHE. These neonates had 629 prescriptions, with 139 containing at least 1 PHE (31 different compounded or commercial medicines), resulting in 241 exposures to an ESNEE PHE: 125 propylparaben (89.9% of the prescriptions), 98 propylene glycol (70.5%), 6 benzyl alcohol (4.3%), 5 ethanol (3.6%), 4 sodium benzoate (2.9%), 2 sorbitol (1.4%) and 1 polysorbate 80 (0.7%). Excessive daily intakes of propylene glycol were found in 49 newborns (75.4%), followed by benzyl alcohol in 5 newborns (7.7%). One neonate was exposed to an excessive amount of 5 ESNEE PHEs and 2 other neonates to 3 ESNEE PHEs.

The frequent use of PHEs in compounded medicines for neonates was identified, and neonates were exposed to PHEs exceeding the maximum recommended daily intake. Propylene glycol was the excipient most associated with these events.