Introduction: Regulatory agencies are responsible for order the use of off-label (OL) and unlicensed drugs (UL) prescriptions in neonatal intensive care (NICU). However, these criteria may differ between agencies in different countries. The aim of this study were defining the incidence of off-label (OL) and unlicensed drugs (UL) prescriptions in a sample of NICU patients according to American Food and Drug Administration (FDA) and Brazilian National Health Surveillance Agency (Anvisa) and analyzing the divergences between the results. Methods: Prospective cohort study developed between August 2017 and July 2018 with neonates admitted for more than 24 hours in a teaching maternity hospital. The drugs were investigated for prescription OL and UL through DrugDexMicromedex® and the official Brazilian drug information. The kappa correlation coefficient was used to assess the agreement between the FDA and Anvisa criteria. Kappa values <0.200 were considered non-concordant. Results: During the study period, 220 neonates and 17421 prescribed items were evaluated. The proportion of neonates with at least one medication prescribed as OL does not differ between the agencies FDA and Anvisa (96.4% vs 98.6%). The FDA and Anvisa differ as to the OL classification in the ages approved for use and indications, mainly in antimicrobials for systemic use and cardiovascular drugs. When comparing drug information between the FDA and Anvisa, we highlight that the Brazilian agency is less accurate. Conclusion: The use of OL and UL drugs in neonatal intensive care is high when assessed by both regulatory agencies; however, the FDA is more accurate in describing the ages and indications approved for use.Introduction: Regulatory agencies are responsible for order the use of off-label (OL) and unlicensed drugs (UL) prescriptions in neonatal intensive care (NICU). However, these criteria may differ between agencies in different countries. The aim of this study were defining the incidence of off-label (OL) and unlicensed drugs (UL) prescriptions in a sample of NICU patients according to American Food and Drug Administration (FDA) and Brazilian National Health Surveillance Agency (Anvisa) and analyzing the divergences between the results. Methods: Prospective cohort study developed between August 2017 and July 2018 with neonates admitted for more than 24 hours in a teaching maternity hospital. The drugs were investigated for prescription OL and UL through DrugDexMicromedex® and the official Brazilian drug information. The kappa correlation coefficient was used to assess the agreement between the FDA and Anvisa criteria. Kappa values <0.200 were considered non-concordant. Results: During the study period, 220 neonates and 17421 prescribed items were evaluated. The proportion of neonates with at least one medication prescribed as OL does not differ between the agencies FDA and Anvisa (96.4% vs 98.6%). The FDA and Anvisa differ as to the OL classification in the ages approved for use and indications, mainly in antimicrobials for systemic use and cardiovascular drugs. When comparing drug information between the FDA and Anvisa, we highlight that the Brazilian agency is less accurate. Conclusion: The use of OL and UL drugs in neonatal intensive care is high when assessed by both regulatory agencies; however, the FDA is more accurate in describing the ages and indications approved for use.2023-07-08