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Drug utilisation pattern and off-label use of medicines in Estonian neonatal units

  • Pharmacoepidemiology and Prescription
  • Published:
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Abstract

Objectives

To characterise neonatal hospital drug use and to compare the availability of drug information between Estonian Summaries of Product Characteristics (SPCs) and other sources.

Study design

This was a prospective cohort study in which pharmacotherapy information on neonates admitted to Tartu University Clinics between 1 February and 1 August 2008 and to Tallinn Children’s Hospital between 1 February and 1 August 2009 was collected. Drug labelling status was determined according to Estonian SPCs, and neonatal information was compared with the British National Formulary for Children (BNFC) and the Thomson Micromedex database.

Results

Of 490 hospitalised neonates, 71% received pharmacotherapy. Within the entire study period, there were 1981 prescriptions for 115 products, with a median of four (interquartile range 2–7) products per child. Antibacterial, cardiovascular and central nervous system drugs were the most commonly prescribed. All treated preterm neonates received at least one unlicensed or age-related off-label prescription. All prescriptions for alimentary, genitourinary, musculoskeletal and sensory system drugs were off-label. There were large differences in the neonatal information provided by the different sources, with the largest differences found for term neonates, for whom the information was available for 67, 38 and 24% of prescriptions according to the BNFC, Micromedex and Estonian SPC, respectively.

Conclusions

The high rate of age-related off-label prescribing for neonates calls for urgent action from medical professionals and others to reinforce effective and safe pharmacotherapy for this age group. The existing SPCs should be regularly updated and more closely harmonised to each other.

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References

  1. Neubert A, Lukas K, Leis T, Dormann H, Brune K, Rasher W (2010) Drug utilization on a preterm and neonatal intensive care unit in Germany: a prospective, cohort–based analysis. Eur J Clin Pharmacol 66:87–95

    Article  PubMed  Google Scholar 

  2. Kumar P, Walker JK, Hurt KM, Bennett KM, Grosshans N, Fotis MA (2008) Medication use in the neonatal intensive care unit: current patterns and off-label use of parenteral medications. J Pediatr 152:412–415

    Article  PubMed  Google Scholar 

  3. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR (2006) Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics 117:1979–1987

    Article  PubMed  Google Scholar 

  4. Tobin JR (2010) Use of pharmaceuticals “Off-Label” in the neonate. Best Pract Res Clin Anaesthesiol 24:451–460

    Article  PubMed  Google Scholar 

  5. Dessi A, Salemi C, Fanos V, Cuzzolin L (2010) Drug treatments in a neonatal setting: focus on the off-label use in the first month of life. Pharm World Sci 32:120–124

    Article  PubMed  Google Scholar 

  6. Lindell-Osuagwu L, Korhonen MJ, Saano S, Helin-Tanninen M, Naaranlahti T, Kokki H (2009) Off–label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature. J Clin Pharm Ther 34:277–287

    Article  PubMed  CAS  Google Scholar 

  7. Dell'Aera M, Gasbarro AR, Padovano M, Laforgia N, Capodiferro D, Solarino B et al (2007) Unlicensed and off–label use of medicines at a neonatology clinic in Italy. Pharm World Sci 29:361–367

    Article  PubMed  Google Scholar 

  8. ’t Jong GW, van der Linden PD, Bakker EM, van der Lely N, Eland IA, Stricker BHC, van den Anker JN (2002) Unlicensed and off–label drug use in a paediatric ward of a general hospital in the Netherland. Eur J Clin Pharmacol 58:293–297

    Article  PubMed  Google Scholar 

  9. O'Donnell CPF, Stone RJ, Morley CJ (2002) Unlicensed and off–label drug use in Australian neonatal intensive care unit. Pediatrics 110:1–4

    Article  Google Scholar 

  10. Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A et al (2000) Survey of unlicensed and off–label drug use in paediatric wards in European countries. Br Med J 320:79–82

    Article  CAS  Google Scholar 

  11. U.S. Food and Drug Administration (2003) Pediatric Research Equity Act. Pub Law 650:108–155

    Google Scholar 

  12. European Union (2006) Regulation (EC) No 1901/2006 as amended Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004. Official Journal of the European Union, Brussels

  13. Ceci A, Felisi M, Baiardi P, Bonifazi F, Catapano M, Giaquinto C et al (2006) Medicines for children licensed by the European Medicines Agency (EMEA): the balance after 10 years. Eur J Clin Pharmacol 62:947–652

    Article  PubMed  CAS  Google Scholar 

  14. Benjamin DK, Smith PB, Murphy MD, Roberts R, Mathis L, Avant D et al (2006) Peer–reviewed publication of clinical trials completed for pediatric exclusivity. JAMA 296:1266–1273

    Article  PubMed  CAS  Google Scholar 

  15. Ward RM, Kern SE (2009) Clinical trials in neonates: a therapeutic imperative. Clin Pharm Ther 86:585–587

    Article  CAS  Google Scholar 

  16. Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE (2003) Developmental pharmacology – drug disposition, action, and therapy in infants and children. N Engl J Med 349:1157–1167

    Article  PubMed  CAS  Google Scholar 

  17. De Wildt SN, Knibbe CAJ (2009) Knowledge of developmental pharmacology and modeling approaches should be used to avoid useless trials in children. Eur J Clin Pharmacol 65:849–850

    Article  PubMed  Google Scholar 

  18. BMJ Group. British National Formulary for Children 2009. RPS Publishing, London

  19. Thomson Reuters. Thomson Micromedex database. Available at: http://www.thomsonhc.com/hcs/libraria. Thomson Reuters, New York. Accessed February 2009

  20. Young TE, Magnum B (2009). Neofax 2009, 22nd edn. Thomson Reuters, New Yor

  21. Statistics Estonia. Available at:http://pub.stat.ee/px/web.2001/Database/Rahvastik. Accessed May 2009

  22. National Institute for Health Development. Available at: http://www.tai.ee/?id=3796. Accessed May 2009

  23. Varendi H, Toome L, Andersson P, Ilmoja M, Kallas E, Maipuu L, Saik P, Ringmets I, Ormisson A (2010) Vastsündinute haigestumus ja suremus Eestis 2007–2008. Eesti Arst 89:790–799

    Google Scholar 

  24. Neubert A, Wong ICK, Bonifazi A, Catapano M, Felisi M, Baiardi P, Giaquinto C, Knibbe CAJ, Sturkenboom MCJM, Ghaleb MA, Ceci A (2008) Defining off-label and unlicensed use of medicines for children: Results of a Delphi survey. Pharmacol Research 58:316–322

    Article  Google Scholar 

  25. WHO Collaborating Centre for Drug Statistics Methodology. Available at:http://www.who.no/atcddd. Accessed February 2009

  26. StatsDirect (2008) StatsDirect statistical software. Available at: http://www.Statsdirect.com StatsDirect, Sale, Cheshire

  27. Warrier I, Du W, Natarajan G, Sal V (2006) Patterns of Drug Utilization in a Neonatal Intensive Care Unit. J Clin Pharmacol 46:449–455

    Article  PubMed  Google Scholar 

  28. Porta A, Esposito S, Menson E, Spyridis N, Tsolia M, Sharland M, Principi N (2010) Off-label antibiotic use in children in three European countries. Eur J Clin Pharmacol 66:919–129

    Article  PubMed  Google Scholar 

  29. Tafuri G, Trotta F, Leufkens HG (2009) Off–label use of medicines in children: can available evidence avoid useless paediatric trials? Eur J Clin Pharmacol 65:209–216

    Article  PubMed  Google Scholar 

  30. Conroy S (2011) Association between license status and medication errors. Arch Dis Child 96:305–30-6

    Google Scholar 

  31. Metsvaht T, Ilmoja ML, Parm Ü, Maipuu L, Lutsar I (2010) Comparison of ampicillin plus gentamicin vs. penicillin plus gentamicin in empiric treatment of neonates at risk of early onset sepsis. Acta Paediatr 99:665–672

    PubMed  CAS  Google Scholar 

  32. Evaluation of antibiotics (ciprofloxacin and fluconazole) for the treatment of infections in preterm and term neonates (TINN). Available at: http://cordis.europa.eu/fetch?CALLER=FP7_PROJ_EN&ACTION=D&DOC=1&CAT=PROJ&QUERY=01283eff1c1c:c701:31dd2bcc&RCN=89361. Accessed January 2011

  33. European multicenter network to evaluate pharmacokinetics, safety and efficacy of Meropenem in neonatal sepsis and meningitis (NEOMERO). Available at: http://cordis.europa.eu/fetch?CALLER=FP7_PROJ_EN&ACTION=D&DOC=5&CAT=PROJ&QUERY=012b93d407b8:2418:4339fd03&RCN=93635. Accessed January 2011

  34. European Medicines Agency (2010) Revised priority list for studies into off-patent paediatric medicinal products. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000092.jsp&murl=menus/regulations/regulations.jsp&mid=WC0b01ac05800260a4&jsenabled=true. Accessed January 2011

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Conflict of interest statement

Any of the authors declare no competing interest.

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Authors and Affiliations

  1. Institute of Microbiology, Tartu University, Tartu, Estonia

    Jana Lass & Irja Lutsar

  2. Pharmacy Department, Tartu University Clinics, L. Puusepa 8, 50406, Tartu, Estonia

    Jana Lass

  3. Tallinn Children’s Hospital, Tallinn, Estonia

    Ruth Käär

  4. Department of Pharmacy, Tartu University, Tartu, Estonia

    Kaarin Jõgi

  5. Tartu University Clinics Children’s Hospital, Tartu, Estonia

    Heili Varendi & Tuuli Metsvaht

Authors
  1. Jana Lass
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  2. Ruth Käär
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  3. Kaarin Jõgi
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  4. Heili Varendi
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  5. Tuuli Metsvaht
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  6. Irja Lutsar
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Correspondence to Jana Lass.

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Lass, J., Käär, R., Jõgi, K. et al. Drug utilisation pattern and off-label use of medicines in Estonian neonatal units. Eur J Clin Pharmacol 67, 1263–1271 (2011). https://doi.org/10.1007/s00228-011-1072-x

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  • DOI: https://doi.org/10.1007/s00228-011-1072-x

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