Contraindicated drug-drug interactions and associated adverse drug reactions in an observational cohort study of 4543 paediatric hospitalized patients.

BACKGROUND AND PURPOSE: Drug-drug interactions (DDIs) are associated with an increased risk of adverse drug reactions (ADRs). Hospitalized children are particularly vulnerable to DDIs and ADRs due to polypharmacy, frequent use of unlicensed or off-label medications, and dosing regimens often extrapolated from adult data. The aims of this study were to characterize contraindicated DDIs detected in paediatric hospital wards and to assess whether these interactions were associated with ADRs. EXPERIMENTAL APPROACH: Medication and ADR data were prospectively collected over a 2-year observational period in hospitalized children. Patients aged ≤15 years, hospitalized for >3 days and receiving at least two medication during their stay were eligible. Potential contraindicated DDIs were identified using the algorithm implemented in the Thériaque database, based on the official DDI Thesaurus issued by the French National Agency for the Safety of Medicines and Health Products (ANSM). KEY RESULTS: A total of 4543 hospitalized children were included; 12.5% experienced at least one DDI, and 4.3% had at least one contraindicated DDI. Overall, 4225 DDIs were identified, including 709 classified as contraindicated. Thus 72% of the contraindicated DDIs occurred in three departments: paediatric cardiology, developmental psychopathology ward and pulmonology/allergology/cystic fibrosis. Most contraindicated DDIs (80%) were observed in children aged 2-11 years and 12-15 years. CONCLUSION AND IMPLICATIONS: Although a large number of DDIs were detected in hospitalized paediatric patients, contraindicated DDIs were rarely associated with clinically relevant ADRs. These findings highlight the need to improve the specificity and clinical relevance of DDI alert systems in paediatric inpatient settings.