The Use of Off-label and Unlicensed Drugs for Neonates: A Report from a Teaching Hospital in Baghdad

Numan N. Hameed; Shealan Kh. Abbas

doi:10.32007/jfacmedbagdad.6512014

Authors

Numan N. Hameed Department of Pediatrics, College of Medicine, University of Baghdad, Baghdad, Iraq. https://orcid.org/0000-0001-5987-1693
Shealan Kh. Abbas Children Welfare Teaching Hospital, Medical City Complex, MOH, Baghdad, Iraq

DOI:

https://doi.org/10.32007/jfacmedbagdad.6512014

Keywords:

Drug Labeling, neonates, Neonatal Care Unit, Off-label drug, Unlicensed drugs

Abstract

Background: Neonates who are admitted to hospitals will need various drugs. The use of unlicensed or off-label drugs without scientific evidence makes this exposure unsafe.

Aim of study: We aimed to assess the use of drugs for neonates based on the British National Formulary for Children and IBM Micromedex Neofax.

Patients and methods: This is a descriptive study which reviewed the clinical files of enrolled neonates who have stayed in the hospital for more than 24 hours and received at least one drug. It was conducted in the neonatal care unit of the Children Welfare Teaching Hospital/ Medical City Complex in Baghdad during the period from 1st of January to 30th of June/2018. The data was entered on a predesigned format and analyzed by using the appropriate statistical methods.

Results: A total number of 1079 neonates were admitted to the NCU during the study period, of whom 967 were included in the current study with 597 (61.7%) males and 370 (38.3%) females. There were 424 (43.8%) preterm, 496 (51.3%) term and post term neonates, and 47 (4.9%) neonates with unknown gestational age. Different classes of drugs were used with a total of 56 drugs, of which 33.9% were unlicensed and 66.1% were off-label. Accordingly, 42.5% of the neonates received unlicensed drugs and almost all patients received at least one off-label drug. Major risk factors for such use include mechanical ventilation, male sex and prolonged hospitalization.

Conclusions: In hospitalized neonates, drugs were more frequently prescribed as an off-label rather than unlicensed. Almost all neonates were exposed to off-label formulations.

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References

Bhartiy SS, Shinde M, Nandeshwar S, Tiwari SC. Pattern of prescribing practices in the Madhya Pradesh, India. Kathmandu University (KUMJ). 2008;6(1):55-9. https://europepmc.org/article/med/18604116

American Academy of Pediatrics. Policy Statement: Off-label use of drugs in children. Pediatrics 2014; 133(3):563-7.

https://doi.org/10.1542/peds.2013-4060.

Giglio N. Pediatric pharmacology and use of unapproved drugs (off label). Archivos argentinos de pediatria. 2012;110(1):5.

Choonara I. Unlicensed and off-label drug use in children: implications for safety. Expert opinion on drug safety. 2004;3(2):81-3. https://doi.org/10.1517/eods.3.2.81.27342.

Bonati M. EARLY NEONATAL DRUG UTILIZATION IN PRETERM NEWBORNS IN NEONATAL INTENSIVE-CARE UNITS. Developmental Pharmacology and Therapeutics. 1988;11(1):1-7. https://doi.org/10.1159/000457657.

Giacoia GP, Taylor-Zapata P, Zajicek A. Drug studies in newborns: a therapeutic imperative. Clinics in perinatology. 2012;39(1):11-23. https://doi.org/10.1016/j.clp.2011.12.016.

Patel Brijal S, KubavatAmita R, Sondarva Divyesh B, Piparva Kiran G. Drug utilization study in neonatal intensive care unit at tertiary care hospital, Rajkot, Gujarat: a prospective study. World Journal of Pharmacy and Pharmaceutical Sciences. 2015;4(7):2034-42. https://doi.org/10.1590/1806-9282.20210831.

Hines RN, McCarver DG. The ontogeny of human drug-metabolizing enzymes: phase I oxidative enzymes. Journal of Pharmacology and Experimental Therapeutics. 2002;300(2):355-60. https://doi.org/10.1124/jpet.300.2.355

McCarver DG, Hines RN. The ontogeny of human drug-metabolizing enzymes: phase II conjugation enzymes and regulatory mechanisms. Journal of Pharmacology and Experimental Therapeutics. 2002;300(2):361-6.. https://doi.org/10.1124/jpet.300.2.361.

Dresser R, Frader J. Off-label prescribing: a call for heightened professional and government oversight. Journal of Law, Medicine & Ethics. 2009 Oct;37(3):476 86. https://doi.org/10.1111/j.1748-720X.2009.00408.x.

Dell’Aera M, Gasbarro AR, Padovano M, Laforgia N, Capodiferro D, Solarino B, Quaranta R, Dell’Erba AS. Unlicensed and off-label use of medicines at a neonatology clinic in Italy. Pharmacy world & science. 2007:361-7. https://doi.org/10.1007/s11096-006-9081-z.

Conroy S. Association between license status and medication errors. Archives of disease in childhood. 2011;96(3):305-6. https://doi.org/10.1136/adc.2010.191940.

Carvalho PR, Carvalho CG, Alievi PT, Martinbiancho J, Trotta EA. Prescription of drugs not appropriate for children in a Pediatric Intensive Care Unit. J Pediatr (Rio J). 2003;79(5):397-402. https://doi.org/10.2223/JPED.1069.

Kimland E, Bergman U, Lindemalm S, Böttiger Y. Drug related problems and off-label drug treatment in children as seen at a drug information centre. European journal of pediatrics. 2007; 166:527-32. https://doi.org/10.1007/s00431-006-0385-8.

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. European journal of clinical pharmacology. 2010;66:87-95. https://doi.org/10.1007/s00228-009-0722-8.

European Medicines Agency. Report on the Survey of all Pediatric Uses of Medicinal Products in Europe. 2013 EMA/794083/2009. https://www.ema.europa.eu/en/documents/report/report-survey-all-paediatric-uses-medicinal-products-europe_en.pdf.

Mazhar F, Akram S, Haider N, Hadi MA, Sultana J. Off-label and unlicensed drug use in hospitalized newborns in a Saudi tertiary care hospital: a cohort study. International Journal of Clinical Pharmacy. 2018; 700-3. https://doi.org/10.1007/s11096-018-0630-z.

Al-Alaiyan SAR, Al-Ghamdi N. Neonatal Dosage and Practical Guidelines Handbook. 2016. https://www.researchgate.net/publication/316235370_Neonatal_Dosage_and_Practical_Guidelines_Handbook

Abdul Rassoul AA, Wayyes ARM, Al-Ismaeli HK, Al-Rekabi MD. Alphabetical listing of Medicines. Iraqi Medicines Guide, 2016. https://www.researchgate.net/publication/321699546_Iraqi_Medicine_Guide.

British National formulary, BNFC for children September 2017-2018. https://vnras.com/wp-content/uploads/pdf/VNRAS-BNF-for-Children-BNFC-2016-2017-.pdf.

Young TE, Mangum BN, Neofax A. A Manual of Drugs used in neonatal care. Antimicrobials. Edition 23rd. Thomson Reuters, Montvale. 2010;7645:50-1.

Kumar P, Walker JK, Hurt KM, Bennett KM, Grosshans N, Fotis MA. Medication use in the neonatal intensive care unit: current patterns and off-label use of parenteral medications. The Journal of pediatrics. 2008;152(3):412-5. https://doi.org/10.1016/j.jpeds.2007.07.050.

Warrier I, Du W, Natarajan G, Salari V, Aranda J. (2006). Patterns of drug utilization in a neonatal intensive care unit. J Clin pharmacol; 46:449-455 https://doi.org/10.1177/0091270005285456.

Carvalho CG, Ribeiro MR, Bonilha MM, Fernandes Jr M, Procianoy RS, Silveira RC. Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores. Jornal de pediatria. 2012; 88:465-70. https://doi.org/10.2223/JPED.2231.

Lass J, Käär R, Jõgi K, Varendi H, Metsvaht T, Lutsar I. Drug utilisation pattern and off-label use of medicines in Estonian neonatal units. European journal of clinical pharmacology. 2011; 67:1263-71. https://doi.org/10.1007/s00228-011-1072-x.

Kieran EA, O'Callaghan N, O'Donnell CP. Unlicensed and off‐label drug use in an I rish neonatal intensive care unit: a prospective cohort study. Acta paediatrica. 2014;103(4):e139-42. https://doi.org/10.1111/apa.12541.

Chatterjee S, Mandal A, Lyle N, Mukherjee S, Singh AK. Drug utilization study in a neonatology unit of a tertiary care hospital in eastern India. Pharmacoepidemiology and drug safety. 2007;16(10):1141-5. https://doi.org/10.1002/pds.1469.

Liem TY, Krediet TG, Fleer A, Egberts TC, Rademaker CM. Variation in antibiotic use in neonatal intensive care units in the Netherlands. Journal of Antimicrobial Chemotherapy. 2010 Jun 1;65(6):1270-5. https://doi.org/10.1093/jac/dkq107.

Coelho HL, Rey LC, de Medeiros MS, Barbosa RA, Fonseca SG, Costa PQ. A critical comparison between the World Health Organization list of essential medicines for children and the Brazilian list of essential medicines (Rename). Jornal de pediatria. 2013; 89:171-8. https://doi.org/10.1016/j.jped.2013.03.004.

Zisovska E, Koshi B, Slaveska-Raichki R. A study of off-label and unlicensed medicines use in neonatal units. 2016: 65. https://doi.org/10.33320/maced.pharm.bull.2016.62.02.008.

Ballard CD, Peterson GM, Thompson AJ, Beggs SA. Off‐label use of medicines in paediatric inpatients at an A ustralian teaching hospital. Journal of paediatrics and child health. 2013;49(1):38-42. https://doi.org/10.1111/jpc.12065.

Cuzzolin L, Atzei A, Fanos V. Off-label and unlicensed prescribing for newborns and children in different settings: a review of the literature and a consideration about drug safety. Expert opinion on drug safety. 2006;5(5):703-18. https://doi.org/10.1517/14740338.5.5.703.

Cuzzolin L. Off-label drug in the newborn. Journal of Pediatric and Neonatal Individualized Medicine (JPNIM). 2014; 3(2):e030224-. https://doi.org/10.7363/030224