Product Substitution as a Way Forward in Avoiding Potentially Harmful Excipients in Neonates

Paediatr Drugs. 2016 Jun;18(3):221-30. doi: 10.1007/s40272-016-0173-5.


Objectives: 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.

MeSH terms

  • Chemistry, Pharmaceutical*
  • Europe
  • Excipients / adverse effects
  • Excipients / chemistry*
  • Humans
  • Infant, Newborn


  • Excipients