Off-label Use and Harmful Potential of Drugs in a NICU in Brazil: A Descriptive Study

Overview

Journal BMC Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2016 Jan 23

PMID 26795213

Citations 29

Authors

Alcidesio Sales de Souza Jr

Djanilson Barbosa Dos Santos

Luis Carlos Rey

Marina Garruti Medeiros

Marta Goncalves Vieira

Helena Lutescia Luna Coelho

Affiliations

Soon will be listed here.

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.

Citing Articles

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de Barros Fernandes T, Ramos S, Leitzke L, Junior R, de Araujo J, de Souza Junior A BMC Pediatr. 2024; 24(1):177.

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Santos L, Santos J, Moehlecke Iser B, Kock K, Bo K Rev Paul Pediatr. 2023; 42:e2023023.

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Compounded medications for cardiovascular use in neonatology: an integrative review.

Greenhalgh L, Passos M, Agrizzi A, Monteiro M Rev Paul Pediatr. 2022; 41:e2021167.

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References

Fjalstad J, Laukli E, van den Anker J, Klingenberg C . High-dose gentamicin in newborn infants: is it safe?. Eur J Pediatr. 2013; . DOI: 10.1007/s00431-013-2194-1. View

Moore D, MacDonald N . Preventing ophthalmia neonatorum. Paediatr Child Health. 2015; 20(2):93-6. PMC: 4373584. View

Souza Jr A, Santos D, Fonseca S, Medeiros M, Batista L, Turner M . Toxic excipients in medications for neonates in Brazil. Eur J Pediatr. 2014; 173(7):935-45. DOI: 10.1007/s00431-014-2272-z. View

Kieran E, OCallaghan N, ODonnell C . Unlicensed and off-label drug use in an Irish neonatal intensive care unit: a prospective cohort study. Acta Paediatr. 2014; 103(4):e139-42. DOI: 10.1111/apa.12541. View

Giacoia G, Taylor-Zapata P, Zajicek A . Drug studies in newborns: a therapeutic imperative. Clin Perinatol. 2012; 39(1):11-23. DOI: 10.1016/j.clp.2011.12.016. View

Neubert A, Wong I, Bonifazi A, Catapano M, Felisi M, Baiardi P . Defining off-label and unlicensed use of medicines for children: results of a Delphi survey. Pharmacol Res. 2008; 58(5-6):316-22. DOI: 10.1016/j.phrs.2008.09.007. View

Choonara I . Unlicensed and off-label drug use in children: implications for safety. Expert Opin Drug Saf. 2004; 3(2):81-3. DOI: 10.1517/eods.3.2.81.27342. View

Henderson-Smart D, Steer P . Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev. 2010; (1):CD000273. PMC: 11380529. DOI: 10.1002/14651858.CD000273.pub2. View

Lass J, Kaar R, Jogi K, Varendi H, Metsvaht T, Lutsar I . Drug utilisation pattern and off-label use of medicines in Estonian neonatal units. Eur J Clin Pharmacol. 2011; 67(12):1263-71. DOI: 10.1007/s00228-011-1072-x. View

10.

Malcolm W, Cotten C . Metoclopramide, H2 blockers, and proton pump inhibitors: pharmacotherapy for gastroesophageal reflux in neonates. Clin Perinatol. 2012; 39(1):99-109. DOI: 10.1016/j.clp.2011.12.015. View

11.

Coelho H, Rey L, Medeiros M, Barbosa R, Cruz Fonseca S, Costa P . A critical comparison between the World Health Organization list of essential medicines for children and the Brazilian list of essential medicines (Rename). J Pediatr (Rio J). 2013; 89(2):171-8. DOI: 10.1016/j.jped.2013.03.004. View

12.

Cotten C, McDonald S, Stoll B, Goldberg R, Poole K, Benjamin Jr D . The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants. Pediatrics. 2006; 118(2):717-22. DOI: 10.1542/peds.2005-2677. View

13.

Pritchard D, Baber N, Stephenson T . Should domperidone be used for the treatment of gastro-oesophageal reflux in children? Systematic review of randomized controlled trials in children aged 1 month to 11 years old. Br J Clin Pharmacol. 2005; 59(6):725-9. PMC: 1884866. DOI: 10.1111/j.1365-2125.2005.02422.x. View

14.

Jain L . The conundrum of off-label and unlicensed drug usage in neonatology. J Pediatr (Rio J). 2012; 88(6):449-51. DOI: 10.2223/JPED.2243. View

15.

Neubert A, Lukas K, Leis T, Dormann H, Brune K, Rascher W . Drug utilisation on a preterm and neonatal intensive care unit in Germany: a prospective, cohort-based analysis. Eur J Clin Pharmacol. 2009; 66(1):87-95. DOI: 10.1007/s00228-009-0722-8. View

16.

Terrin G, Passariello A, De Curtis M, Manguso F, Salvia G, Lega L . Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics. 2011; 129(1):e40-5. DOI: 10.1542/peds.2011-0796. View

17.

Borges A, Campos M, Pereira L . Evaluation of unlicensed and off-label antiepileptic drugs prescribed to children: Brazilian Regulatory Agency versus FDA. Int J Clin Pharm. 2013; 35(3):425-31. DOI: 10.1007/s11096-013-9755-2. View

18.

DellAera M, Gasbarro A, Padovano M, Laforgia N, Capodiferro D, Solarino B . Unlicensed and off-label use of medicines at a neonatology clinic in Italy. Pharm World Sci. 2007; 29(4):361-7. DOI: 10.1007/s11096-006-9081-z. View

19.

de Cock R, Knibbe C, Kulo A, de Hoon J, Verbesselt R, Danhof M . Developmental pharmacokinetics of propylene glycol in preterm and term neonates. Br J Clin Pharmacol. 2012; 75(1):162-71. PMC: 3555055. DOI: 10.1111/j.1365-2125.2012.04312.x. View

20.

Carvalho C, Ribeiro M, Bonilha M, Fernandes Jr M, Procianoy R, Silveira R . Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores. J Pediatr (Rio J). 2012; 88(6):465-70. DOI: 10.2223/JPED.2231. View