Optimising Formulations for Paediatric Patients with Inherited Metabolic Disorders: The Case Study of Levocarnitine

Inherited metabolic disorders (IMDs) are rare genetic conditions that disrupt normal biochemical pathways, leading to potentially life-threatening metabolic imbalances. Early diagnosis, often through newborn screening, and treatment can significantly improve outcomes, but pharmacological management presents unique challenges that are amplified by developmental immaturity, altered pharmacokinetics, and heightened sensitivity to drug excipients. The selection of excipients becomes especially important in IMDs such as primary carnitine deficiency (PCD), where lifelong supplementation is required. Substances such as parabens, benzoates, saccharin sodium, propylene glycol, and ethanol are generally safe in adults, but may potentially contribute to metabolic crises or cumulative toxicity in neonates due to immature organ systems and altered metabolism. Current regulatory frameworks are addressing these concerns through guidelines, labelling revisions, and tools such as the STEP and SEEN databases, which compile paediatric safety data for excipients. Despite regulatory progress, significant gaps in excipient transparency, standardisation, and labelling persist, complicating clinical decision making. Healthcare providers often lack access to precise excipient concentrations and may unintentionally exceed safe thresholds in polypharmacy scenarios. This opinion paper underscores the critical need for age-appropriate, excipient-conscious drug formulations for children with IMDs. It advocates for improved regulatory oversight, increased formulation transparency, and interdisciplinary collaboration to minimise risk and enhance the safety of paediatric treatments, particularly for neonates requiring chronic therapy.