Evaluation of drugs and risk factors requiring therapeutic drug monitoring in the Neonatal Intensive Care Unit: a retrospective study

BACKGROUND: Neonates in the Neonatal Intensive Care Units (NICU) often receive medications requiring therapeutic drug monitoring (TDM) due to their immature organ function and the narrow therapeutic windows of these drugs. Despite its critical role in optimizing dosing and minimizing toxicity, data on the prevalence and risk factors associated with TDM-requiring drugs in neonates is limited. This study aims to estimate the potential burden of TDM-requiring drug use in a NICU where routine TDM is not implemented and to identify key clinical and demographic factors associated with their use. METHODS: A retrospective, descriptive study was conducted on neonates admitted to a NICU between January 1, 2019, and July 1, 2024. Patients who received at least one TDM-requiring drug were included. The drugs included in the patients' treatments that required TDM were accepted as antibiotics (vancomycin, gentamicin, amikacin), antiepileptics (phenytoin, phenobarbital, carbamazepine, valproic acid, levetiracetam) and digoxin. Data were analyzed using chi-square, Mann-Whitney U, Kruskal-Wallis, and binary logistic regression tests. RESULTS: Among 3754 neonates, 1404 (37.4%) received TDM-requiring drugs, with 1375 meeting inclusion criteria. The most commonly TDM-requiring drugs were gentamicin (62.5%), vancomycin (13.6%), and amikacin (11.5%). Risk factors significantly associated with TDM included mechanical ventilation (OR = 4.3, 95% CI: 3.2-5.5), total parenteral nutrition (OR = 4.0, 95% CI: 3.1-5.2), and NICU hospitalization ≥ 10 days (OR = 7.3, 95% CI: 5.4-9.9). CONCLUSION: A substantial proportion of neonates in the NICU are exposed to medications requiring TDM. In a setting where routine TDM is not implemented, this finding highlights a potential unmet need for monitoring. Mechanical ventilation, prolonged NICU hospitalization, and total parenteral nutrition were identified as key risk factors. Identifying these high-risk groups may support targeted monitoring strategies and optimize resource allocation in NICUs where TDM is not routinely available. TRIAL REGISTRATION: Not applicable.