Safety gaps in pediatric liquid antihypertensive compounding: a scoping review and regulatory-based safety assessment

Background Extemporaneous liquid antihypertensive formulations are widely used in pediatrics but frequently lack detailed reporting of excipient safety data, particularly regarding age-specific physiological vulnerability and cumulative exposure. Methods A scoping review was conducted in accordance with PRISMA-ScR guidelines to map excipients used in pediatric extemporaneous antihypertensive liquid formulations. A regulatory-oriented assessment was applied, emphasizing age-appropriate safety considerations and exposure-based risk principles, including theoretical daily intake expressed as mg/kg/day. Results Forty-two studies were included. Reporting of excipient concentrations, age targets, and safety justifications was heterogeneous and often incomplete. Vehicles, co-solvents, preservatives, buffers, antioxidants, surfactants, and flavoring agents were identified, with selection typically driven by a focus on physicochemical stability rather than patient-centered criteria, such as age-appropriate excipient safety, dose flexibility, and acceptable volumes. Exposure-based considerations were addressed by a limited number of studies (n = 5). Exposure calculations based on typical pediatric dosing showed that concentrations considered acceptable in adult formulations may translate into clinically relevant toxicity risks in neonates and infants. Based on observed patterns, a conceptual risk stratification framework was developed to categorize excipients according to age-dependent toxicity, cumulative dose burden, and functional tolerability. Conclusions The available literature on compounding antihypertensive formulations mainly emphasizes physicochemical performance, with less attention given to exposure-related safety parameters in pediatric patients. Integrating total daily excipient exposure metrics and structured justification for excipient selection may improve alignment with regulatory expectations and support safer, patient-centered compounding practices in pediatric clinical care.