Off-Label Medication Use in a Serbian Neonatal Intensive Care Unit: A Single-Center Retrospective Cohort Study

Background/Objectives: The main objective of this study was to describe the prevalence and prescribing patterns of off-label and unlicensed medication use in a tertiary neonatal intensive care unit in Serbia and to evaluate differences according to gestational age. Methods: This retrospective single-center cohort study included 257 neonates hospitalized in a tertiary neonatal intensive care unit between January and December 2023. Medication prescriptions were classified as off-label or unlicensed according to the approved Summary of Product Characteristics in Serbia. Clinical and prescribing data were analyzed descriptively, with predefined patient-level outcomes compared across gestational-age groups using non-parametric analyses. Results: A total of 1919 distinct medication prescription records were identified, of which 1642/1919 (85.6%) were classified as off-label and 27/1919 (1.4%) as unlicensed. At the patient level, 252/257 neonates (98.1%) were exposed to at least one off-label medication, whereas 26/257 (10.1%) were exposed to at least one unlicensed medication. Anti-infectives for systemic use accounted for the largest therapeutic-class prescription count. Off-label prescribing was primarily related to age and dosing recommendations. Medication utilization varied across gestational age groups; however, extremely preterm neonates also had substantially longer hospitalizations, and the observed differences should therefore be interpreted as unadjusted prescribing patterns rather than an independent effect of gestational age. Conclusions: Off-label prescribing was highly prevalent in this Serbian tertiary neonatal intensive care unit, whereas patient exposure to unlicensed medications was relatively uncommon. The observed differences across gestational age groups should be interpreted in the context of differences in hospitalization duration and clinical complexity. These findings characterize prescribing patterns and regulatory gaps in neonatal pharmacotherapy and identify areas requiring further neonatal-specific clinical research.