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International Journal of Clinical Pharmacy

, Volume 34, Issue 1, pp 136–141 | Cite as

Off-label and unlicensed drug use in neonatal intensive care units in Turkey: the old-inn study

  • S. Suna Oguz
  • H. Gozde Kanmaz
  • Ugur Dilmen
Research Article

Abstract

Background Recently several developed countries have improved the safety and efficacy of drugs used in infants and pediatric patients. Most drugs administered to adults have licensed approvals outlining indications, doses, and the recommended route of administration. However, many drugs that are given to children are unlicensed or used off-label. Objectives To assess the extent and nature of unregistered and off-label drug use in neonatal intensive care units (NICUs) in Turkey, and to explore awareness and views of the general public on the unlicensed use of medicine in preterm and term infants in developing countries. Study Design A prospective observational study of a dynamic cohort of 464 neonates from 17 NICUs in Turkey. All medications administered to neonates who were hospitalized and admitted to the NICU over a 24-h period were recorded. The prescriptions were analyzed to determine whether the medicines were used in a licensed or unlicensed manner. Results In total, 1,315 prescriptions comprising 93 different medicines were written. We found that 62.3% of the drugs prescribed to the neonates over the 24-h period were unlicensed or off-labeled. Conclusions The present study indicates that unlicensed and off-label medicines are frequently used in preterm and term infants in Turkish NICUs. This finding is consistent and reported in other countries. We believe that the needs of the neonatal population must be a priority and access to safe and appropriate medicines requires urgent attention.

Keywords

Neonates Off-label drug Turkey Unlicensed drug 

Notes

Acknowledgments

Special thanks to Esra Arun Ozer from Tepecik Training and Research Hospital, Güner Karatekin from Zeynep Kamil Maternity and Children’s Education and Training Hospital, Nurullah Okumus from Dr. Sami Ulus Maternity and Children’s Hospital, Nihal Demirel from Etlik Zubeyde Hanım Maternity and Children’s Education and Training Hospital, Seyhan Erişir Oygucu from Diyarbakır Children’s Hospital, Gokhan Buyukkale from Sanlıurfa Children’s Hospital, Murat Saygili from Urfa Maternity Hospital, Sevim Ünal from Ankara Children’s Hematology and Oncology Research Hospital,Neonatology Department, Erdal Peker from Yuzuncu Yil University School of Medicine, Department of Pediatrics, Division of Neonatology, Bilge Tanyeri from Gaziantep Children’s Hospital, Sinan Uslu from Sisli Etfal Children’s Hospital, Ahmet Karadag from İnonu University, School of Medicine Turgut Ozal Medical Center, Department of Pediatrics, Division of Neonatology, Rahmi Örs from Selcuk University, School of Medicine Meram Medical Center, Department of Pediatrics, Division of Neonatology, Esat Köklü from Trabzon Maternal and Child Health State Hospital, Hasan Kahveci from Nenehatun Maternity State Hospital, Yaşar Bildirici from Eskişehir Maternal Child Health State Hospital for their collaboration to the study, sharing information and kind support.

Funding

None.

Conflicts of interest

All authors declare that they have no conflict of interest.

References

  1. 1.
    Turkish Population and Health Survey Reports 1998 and 2008. Turkish Statistical Institute (TURKSTAT). www.turkstat.gov.tr.
  2. 2.
    van den Anker JN. Managing drugs safely. Semin Fetal Neonatal Med. 2005;10(1):73–81.PubMedCrossRefGoogle Scholar
  3. 3.
    Rx MediaPharma 2010. Levent Üstünbaş, editor. İnteraktif ilaç bilgi kaynağı. www.eczanet.com.
  4. 4.
    Taketemo CK, Hodding JH, Kraus DM. Pediatric dosage handbook. 11th ed. Ohio: Lexi-Comp’s; 2004. ISBN1-59195-093-7.Google Scholar
  5. 5.
    Gasbarro AR, Padovano M, Laforgia N, Capodiferro D, Solarino B, et al. Unlicensed and off-label use of medicines at a neonatology clinic in Italy. Pharm World Sci. 2007;29(4):361–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Dick A, Keady S, Mohamed F, Brayley S, Thomson M, Lloyd BW, Heuschkel R, Afzal NA. Use of unlicensed and off-label medications in pediatric gastroenterology with a review of the commonly used formularies in the UK. Aliment Pharmacol Ther. 2003;17:571–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Conroy S, Choonara I, Impicciatore P, et al. Survey of unlicensed and off label drug use in pediatric wards in European countries. European network for drug investigation in children. Br Med J. 2000;320(7227):79–82.CrossRefGoogle Scholar
  8. 8.
    Craig JS, Henderson CR, Magee FA. The extent of unlicensed and off-label drug use in the pediatric ward of a district general hospital in Northern Ireland. Ir Med J. 2001;94(8):237–40.PubMedGoogle Scholar
  9. 9.
    Shah SS, Hall M, Goodman DM, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007;161(3):282–90.PubMedCrossRefGoogle Scholar
  10. 10.
    Hsien L, Breddemann A, Frobel AK, Heusch A, Schmidt KG, Läer S. Off-label drug use among hospitalized children: identifying areas with the highest need for research. Pharm World Sci. 2008;30(5):497–502.PubMedCrossRefGoogle Scholar
  11. 11.
    Morales-Carpi C, Estañ L, Rubio E, Lurbe E, Morales-Olivas FJ. Drug utilization and off-label drug use among Spanish emergency room pediatric patients. Eur J Clin Pharmacol. 2010;66(3):315–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Chalumeau M, Tréluyer JM, Salanave B, Assathiany R, Chéron G, Crocheton N, Rougeron C, Mares M, Bréart G, Pons G. Off label and unlicensed drug use among French office based pediatricians. Arch Dis Child. 2000;83(6):502–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr. 2005;164:552–8.PubMedCrossRefGoogle Scholar
  14. 14.
    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. Pharm World Sci. 2007;29(4):361–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Avenel S, Bomkratz A, Dassieu G, Janaud JC, Danan C. The incidence of prescriptions without marketing product license in a neonatal intensive care unit. Arch Pediatr. 2000;7(2):143–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Barr J, Brenner-Zada G, Heiman E, Pareth G, Bulkowstein M, Greenberg R, Berkovitch M. Unlicensed and off-label medication use in a neonatal intensive care unit: a prospective study. Am J Perinatol. 2002;19(2):67–72.PubMedCrossRefGoogle Scholar
  17. 17.
    Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed. 1999;80(2):F142–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Arda B, Kavas V, Demirkazık A, Akbulut H. What can we say about off-label drug use in oncology in the light of ethics? TK Tıp Etiği Hukuku Tarihi Dergisi. 2003;11(4):249–52.Google Scholar
  19. 19.
    Cakmak HB, Demir M, Buken NO. Ethical evaluation of off-label use in Turkey: Bevacizumab as an example. J Retina-Vitreous. 2008;16(4):311–5.Google Scholar
  20. 20.
    Kockaya G, Polat M, Vural IM, et al. Off-label and unlicensed oncology medicine use in Turkey: a retrospective analysis of computer records of the Turkish Ministry of Health. J Pharm Health Serv Res. 2011;2(1):53–7.CrossRefGoogle Scholar
  21. 21.
    Stewart D, Rouf A, Snaith A, et al. Attitudes and experiences of community pharmacists towards pediatric off-label prescribing: a prospective survey. Br J Clin Pharmacol. 2007;64(1):90–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Neubert A, Wong IC, Bonifazi A, et al. Defining off-label and unlicensed use of medicines for children: results of a Delphi survey. Pharmacol Res. 2008;58(5–6):316–22.PubMedCrossRefGoogle Scholar
  23. 23.
    Sherwin CM, Svahn S, Van der Linden A, et al. Individualized dosing of amikacin in neonates: a pharmacokinetic/pharmacodynamic analysis. Eur J Clin Pharmacol. 2009;65(7):705–13.PubMedCrossRefGoogle Scholar
  24. 24.
    Gokmen T, Erdeve O, Altug N, Oguz SS, Uras N, Dilmen U. Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight preterm infants with patent ductus arteriosus. J Pediatr. 2011;158(4):549–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Brion F, Nunn AJ, Rieutord A. Extemporaneous (magistral) preparation of oral medicines for children in European hospitals. Acta Paediatr. 2003;92:486–90.PubMedCrossRefGoogle Scholar
  26. 26.
    Rakhmanina NY, van den Anker JN. Pharmacological research in pediatrics: from neonates to adolescents. Adv Drug Deliv Rev. 2006;58(1):4–14.PubMedCrossRefGoogle Scholar
  27. 27.
    Beggs SA, Cranswick NE, Reed MD. Improving drug use for children in the developing world. Arch Dis Child. 2005;90:1091–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Hill P. Off license and off label prescribing in children: litigation fears for physicians. Arch Dis Child. 2005;90(Suppl I):i17–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Pharmaceutical and Medical Preparations Law. Law No: 1262 Acceptance Date: 14th, 1928.Google Scholar
  30. 30.
    Turkish Medical Deontology Regulation. Law No: 4/12578, Acceptance Date: 13th Jan, 1960.Google Scholar
  31. 31.
    Off-Labeled use of Drug Regulation. Circular numbered 115-2006.Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Neonatal Intensive Care UnitZekai Tahir Burak Maternity Teaching HospitalCebeci, AnkaraTurkey

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