Background Appropriate drug formulations are essential for efficacy and safety of medicine.

Purpose Our aim was to assess the extent of use of extemporaneously prepared/modified products and to assess the age-appropriateness of licensed formulations in European neonatal units in cardiovascular medicines group.

Materials and Methods The study is based on ESNEE (European Study of Neonatal Excipient Exposure) database, containing information on 21 European countries neonatal units drug use. The suitability of formulations was assessed among industrial preparations, based on: inclusion of certain ‘risk’ excipients (EOI) – parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride, immeasurable dose, manipulations before administration to neonates. Sources: British National formulary for Children (2012), Summaries of Product Characteristics and Patient Information Leaflets.

Results Out of 130 cardiovascular medicines prescribed (n = 59 enteral, n = 66 parenteral, n = 5 topical), 20% (n = 26) were prepared by local pharmacies and 15% (n = 19) were commercial solid oral formulations, that needed extemporaneous modification. Immeasurable volume was found in 18% (n = 19) of industrial formulations (tablets n = 18, capsules n = 1). EOI were found in 22% (n = 23) of drugs. The extent was highest in oral liquid formulations (76%, n = 13/17), containing commonly parabens (n = 8), propylene glycol (n = 7), ethanol (n = 6). Of parenteral formulations 11% (n = 7) contained EOI, frequently ethanol (n = 5) that was found in alprostadil, digoxin and dopamine solutions. Solid oral commercial formulations (n = 19) were free of EOI. When dosing and excipients were both considered, most industrial parenteral medicines (86%, n = 55/64) and only 6% (n = 2) of enteral medicines were age-appropriate for neonates. Altogether 45% (n = 58/130) of drugs were produced industrially, EOI free and suitable for dosing. Most of these (n = 55) were for parenteral use. Medications, that were frequently used in departments (furosemide, dopamine, epinephrine), were all parenteral and all of them, except one dopamine preparation, were EOI free.

Conclusions Although the use of enteral route of administration is common in European neonatal units, majority of oral formulations are unappropriate for neonates. Further research in dosage forms suitability and substitution possibilities between European countries is required.