The hidden risk in children’s medicines: excipients

Excipients are everything in a medicine other than the active ingredient: the solvents that keep it dissolved, the preservatives that stop it spoiling, the sweeteners and flavours that make it palatable. In adults they are usually inert in practice. In neonates and young infants, that assumption does not always hold.

A lesson from the 1980s

The clearest warning came from neonatal intensive care units in the early 1980s, when deaths among premature babies were linked to benzyl alcohol, a preservative in flush solutions and some injectable medicines. Affected infants developed a pattern of metabolic acidosis and breathing problems that became known as gasping syndrome. Newborns could not metabolise benzyl alcohol fast enough, and it accumulated.

The excipients under scrutiny

Several common excipients now carry specific warnings or thresholds for young children:

• Ethanol, used as a solvent, can affect the developing nervous system.
• Propylene glycol can accumulate in newborns, whose ability to clear it is limited.
• Benzyl alcohol and some other preservatives remain a concern in neonates.
• Certain sugars and sweeteners need care in children with metabolic conditions.

The EMA maintains guidance on excipients that must be declared on the label, with thresholds that in several cases are lower for children.

Better data for formulators

A long-standing problem has been the lack of accessible safety data for excipients in children. The Safety and Toxicity of Excipients for Paediatrics database, known as STEP, was built by European and US paediatric formulation initiatives to collect that evidence in one place.

Designing it out

The best practice now is to avoid problematic excipients from the start rather than justifying them later. That pushes formulators towards solid dosage forms, which need fewer solvents and preservatives, and towards single-dose presentations that do not need preserving at all.