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.
Similar content being viewed by others
References
Turkish Population and Health Survey Reports 1998 and 2008. Turkish Statistical Institute (TURKSTAT). www.turkstat.gov.tr.
van den Anker JN. Managing drugs safely. Semin Fetal Neonatal Med. 2005;10(1):73–81.
Rx MediaPharma 2010. Levent Üstünbaş, editor. İnteraktif ilaç bilgi kaynağı. www.eczanet.com.
Taketemo CK, Hodding JH, Kraus DM. Pediatric dosage handbook. 11th ed. Ohio: Lexi-Comp’s; 2004. ISBN1-59195-093-7.
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.
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.
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.
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.
Shah SS, Hall M, Goodman DM, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007;161(3):282–90.
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.
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.
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.
Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr. 2005;164:552–8.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Brion F, Nunn AJ, Rieutord A. Extemporaneous (magistral) preparation of oral medicines for children in European hospitals. Acta Paediatr. 2003;92:486–90.
Rakhmanina NY, van den Anker JN. Pharmacological research in pediatrics: from neonates to adolescents. Adv Drug Deliv Rev. 2006;58(1):4–14.
Beggs SA, Cranswick NE, Reed MD. Improving drug use for children in the developing world. Arch Dis Child. 2005;90:1091–3.
Hill P. Off license and off label prescribing in children: litigation fears for physicians. Arch Dis Child. 2005;90(Suppl I):i17–8.
Pharmaceutical and Medical Preparations Law. Law No: 1262 Acceptance Date: 14th, 1928.
Turkish Medical Deontology Regulation. Law No: 4/12578, Acceptance Date: 13th Jan, 1960.
Off-Labeled use of Drug Regulation. Circular numbered 115-2006.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Oguz, S.S., Kanmaz, H.G. & Dilmen, U. Off-label and unlicensed drug use in neonatal intensive care units in Turkey: the old-inn study. Int J Clin Pharm 34, 136–141 (2012). https://doi.org/10.1007/s11096-011-9604-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11096-011-9604-0