Product Substitution as a Way Forward in Avoiding Potentially Harmful Excipients in Neonates.
OBJECTIVE
Our objectives were to explore the possibility of avoiding neonatal exposure to potentially harmful excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol and ethanol-through product substitution in Europe.


METHODS
We performed a 3-day service evaluation survey and a 1-day point prevalence study in 20 and 21 European countries, respectively. Analysis included active pharmaceutical ingredients (APIs) used in ≥10 % of units. We calculated the potential reduction in number of products with EOI through substitution in three stages: (1) similar API and route of administration, (2) plus similar dosage form and (3) plus similar strength. The reduction of individual exposure was analysed according to the second-stage criteria.


RESULTS
We identified 137 products for 25 APIs that contained EOI. Substitution with EOI-free product(s) was available for 88 % (n = 120), 66 % (n = 91) and 31 % (n = 42) of products according to the first-, second- and third-stage criteria, respectively. Overall, 456 (63 % of 726) neonates received products containing EOI. Substitution of the products that had alternatives with similar API and dosage form would reduce the number of exposed neonates from 456 to 257 (44 % reduction).


CONCLUSIONS
EOI-free formulations are available for a substantial number of products currently used in European neonates. Replacement of only the most frequently used products may spare almost half of neonates from unnecessary exposure to EOI.
Institute of Microbiology, University of Tartu, Tartu, Estonia. georgi.nellis@kliinikum.ee.|Neonatal Unit, Children's Clinic, Tartu University Hospital, N. Lunini 6, Tartu, 51014, Estonia. georgi.nellis@kliinikum.ee.
Georgi
G
Nellis
Institute of Microbiology, University of Tartu, Tartu, Estonia.|Clinic of Anaesthesiology and Intensive Care, Paediatric Intensive Care Unit, Tartu University Hospital, Tartu, Estonia.
Tuuli
T
Metsvaht
Neonatal Unit, Children's Clinic, Tartu University Hospital, N. Lunini 6, Tartu, 51014, Estonia.
Heili
H
Varendi
Pharmacy Department, Tartu University Hospital, Tartu, Estonia.
Jana
J
Lass
Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
Jennifer
J
Duncan
Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
Anthony J
AJ
Nunn
Neonatal Unit, Liverpool Women's Hospital, Liverpool, UK.|Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Mark A
MA
Turner
Institute of Microbiology, University of Tartu, Tartu, Estonia.
Irja
I
Lutsar
D002626:Chemistry, Pharmaceutical; D005060:Europe; D005079:Excipients / Q000009:adverse effects / Q000737:chemistry*; D006801:Humans; D007231:Infant, Newborn
D005079:Excipients