title: Off-label use and harmful potential of drugs in a NICU in Brazil: A descriptive study.
abstract: BACKGROUND
  Neonates admitted to neonatal intensive care units (NICU) are exposed to a wide variety of drugs, most without any data on safety and efficacy.
  
  
  OBJECTIVE
  To describe the drugs prescribed to different groups of neonates hospitalized in a NICU, and to analyze off-label use and harmful potential of drugs, in terms of the potential risks.
  
  
  METHODS
  This was a six-month retrospective cohort study of drug use in a NICU, with neonates who were inpatients for a period of over 24 hours, and using prescription data from electronic medical records. Drug information found in the package leaflets, in the British National Formulary for Children 2012-2013, and in the Thomson Micromedex database were compared. Drugs and excipients considered potentially harmful were evaluated according to the literature.
  
  
  RESULTS
  One hundred ninety-two neonates were included in the study, with a mean gestational age (GA) of 33.3 weeks (SD ± 4.3), 75.0 % were preterm, with an average of 18.8 days of hospitalization (SD ± 18.1), and a total of 3617 neonates-day. 3290 prescriptions were registered, on average 17.1 prescriptions/neonate (SD ± 17.9) and 8.8 drugs/neonate (SD ± 5.9). The number of prescriptions and drugs was higher in neonates with GA <31 weeks (p <0.05). Anti-infectives for systemic use, blood, alimentary tract and metabolism drug groups were more frequent, varying according to the GA. Neonates (99.5 %) were exposed to unlicensed drugs (UL) and off label use (OL), more frequently in GA <28 weeks (p <0.05). Most OL drugs used were indicated for newborns. 15 potentially harmful drugs were used in more than 70 % of the neonates, and most were OL; exposure to harmful excipients occurred in 91.6 % of the neonates, a percentage even higher when considering immature neonates.
  
  
  CONCLUSIONS
  Immature neonates in a Brazilian NICU are exposed to a variety of OL, UL and potentially harmful drugs and excipients.
authors.affiliation: Pharmacy Department, Mother and Child Hospital of Brasilia, Brasília, Federal District, Brazil. alcidesiojr@gmail.com.|Doctoral Program in Development and Technological Innovation in Drugs, Federal University of Ceará, Fortaleza, Ceará, Brazil. alcidesiojr@gmail.com.|Mother and Child Hospital of Brasilia, SGAS, Av. L2 Sul, Quadra608, Módulo A, Asa Sul, Brasília, CEP 70203-900, DF, Brazil. alcidesiojr@gmail.com.
authors.forename: Alcidésio Sales
authors.initials: AS
authors.lastname: de Souza
authors.affiliation: Postgraduate Programme in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.|Federal University of Recôncavo da Bahia, Santo Antônio de Jesus, Bahia, Brazil.
authors.forename: Djanilson Barbosa
authors.initials: DB
authors.lastname: Dos Santos
authors.affiliation: Mother and Child Health Department, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Luís Carlos
authors.initials: LC
authors.lastname: Rey
authors.affiliation: Postgraduate Programme in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Marina Garruti
authors.initials: MG
authors.lastname: Medeiros
authors.affiliation: Neonatology Department, Mother and Child Hospital of Brasilia, Brasília, Federal District, Brazil.
authors.forename: Marta Gonçalves
authors.initials: MG
authors.lastname: Vieira
authors.affiliation: Doctoral Program in Development and Technological Innovation in Drugs, Federal University of Ceará, Fortaleza, Ceará, Brazil.|Postgraduate Programme in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Helena Lutéscia Luna
authors.initials: HLL
authors.lastname: Coelho
mesh_terms: D001938:Brazil; D004363:Drug Utilization / Q000706:statistics & numerical data*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D015931:Intensive Care, Neonatal / Q000379:methods* / Q000706:statistics & numerical data; D008297:Male; D056687:Off-Label Use / Q000706:statistics & numerical data*; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D018570:Risk Assessment