Abstract
The persistent lack of information on the paediatric use of most medicinal products is a major hindrance towards an optimal treatment of paediatric patients. Several studies have documented the high prevalence of off-label use in paediatric population. No comprehensive studies, however, exist that analyse in full all prescriptions for all dispensed drugs, especially in view of the recent intervention by the European Medicine Agency to tackle this issue. We have assessed the drug prescription pattern in the paediatric outpatient population of Lombardy, which has a reliable record of such prescriptions focusing on off-label drug use. We analysed all dispensed outpatient prescriptions to children aged 0–18 years and the proportion of off-label drug use in 2011, using data from the regional administrative prescriptions database. A total of 4,027,119 prescriptions were dispensed, of which 133,619 (3.3 %) were off-label. The anatomical therapeutic chemical classes most involved in off-label prescriptions were antibiotics for systemic use (33,629), alimentary tract and metabolism (31,739) and respiratory tract (31,458). The highest rate (8 %) of off-label drug prescriptions was observed in the age range 0–1. The study revealed also an inappropriate prescription pattern for fluoroquinolones and drugs targeting the cardiovascular and musculoskeletal systems. We identified inappropriate prescriptions for specific drug classes, highlighting the need of increasing pharmacological studies in the paediatric patients and specific critical drugs/drug classes in which such studies are particularly urgent. Depending on the region, inappropriate paediatric drug prescriptions may affect different drug classes, indicating the need of tailoring specific programmes of information.
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References
Art. 3 D. Lgs. 17 febbraio 1998, n.23, convertito, con modificazioni nella Legge 8 aprile 1998, n.94.1
Bradley JS, Jackson MA (2011) The use of systemic and topical fluoroquinolones. Pediatrics 128(4):1034–1045
Bücheler R, Schwab M, Mörike K, Kalchthaler B, Mohr H, Schröder H, Schwoerer P, Gleiter CH (2002) Off-label prescribing to children in primary care in Germany: retrospective cohort study. BMJ 324:1311–1312
Choonara I (2007) Regulation of drugs for children in Europe. BMJ 335:1221–1222
Choonara I (2013) Educational paper: aspects of clinical pharmacology in children—pharmacovigilance and safety. Eur J Pediatr 172:577–580
Cizman M (2003) The use and resistance to antibiotics in the community. Int J Antimicrob Agents 21(4):297–307
Clavenna A, Bonati M (2009) Drug prescriptions to outpatient children: a review of the literature. Eur J Clin Pharmacol 65(8):749–755
Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, Knoeppel C, Seyberth H, Pandolfini C, Raffaelli MP, Rocchi F, Bonati M, Jong G, de Hoog M, van den Anker J (2000) Survey of unlicensed and off-label drug use in paediatric wards in European countries. European network for drug investigation in children. BMJ 320:79–82
Etminan M, Forooghian F, Brophy JM, Bird ST, Maberley D (2012) Oral fluoroquinolones and the risk of retinal detachment. JAMA 307(13):1414–1419
European commission. European commission, Regulation (EC) no 1901⁄2006 of the European Parlament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768 ⁄ 92, Directive 2001 ⁄ 20 ⁄ EC, Directive 2001⁄83⁄EC and Regulation (EC) No 726⁄2004. Official J 2006; L378:1–19. http://ec.europa.eu/health/files/eudralex/vol-1/reg_2006_1901/reg_2006_1901_en.pdf. Accessed 16 Jan 2008
European Medicines Agency (London 2006) Assessment of the paediatric needs cardiovascular products. Doc. Ref.: EMEA/439649/2006. http://www.emea.europa.eu/pdfs/human/peg/43964906en.pdf. 2 Nov 2007
European Medicines Agency. Priority list of off-patent medicinal products for pediatric studies London: EMEA, 2012 (EMEA/98717/2012)
Guidelines for ATC Classification and DDD Assignment 2011. Oslo, Norway, WHO Collaborating Centre for Drug Statistics Methodology, 2010
Harrison JN, Cluxton-Keller F, Gross D (2012) Antipsychotic medication prescribing trends in children and adolescents. J Pediatr Health Care 26(2):139–145
Hoppu K (2007) Paediatric clinical pharmacology: at the beginning of a new era. Eur J Clin Pharmacol 64(2):201–205
Kimland E, Odlind V (2012) Off-label drug use in pediatric patients. Clin Pharmacol Ther 91(5):796–801
Morales-Carpi C, Estañ L, Rubio E, Lurbe E, Morales-Olivas FJ (2010) Drug utilization and off-label drug use among Spanish emergency room paediatric patients. Eur J Clin Pharmacol 66:315–320
Neubert A, Dormann H, Weiss J, Egger T, Criegee-Rieck M, Rascher W, Brune K, Hinz B (2004) The impact of unlicensed and off-label drug use on adverse drug reactions in paediatric patients. Drug Saf 27:1059–1067
Pandolfini C, Bonati M (2004) A literature review on off-label drug use in children. Eur J Pediatr 164:552–558
Polachek H, Leibovitz E, Dagan R (2011) Joint cartilage lesions caused by quinolones in young animals—can we generalize to children? Harefuah 150(9):721–724
Rossignoli A, Clavenna A, Bonati M (2007) Antibiotic prescription and prevalence rate in the outpatient paediatric population: analysis of surveys published during 2000–2005. Eur J Clin Pharmacol 63:1099–1106
Schirm E, Tobi H, Jong-van D, den Berg LT (2003) Risk factors for unlicensed and off-label drug use in children outside the hospital. Pediatrics 111:291–295
Stahlmann R, Lode HM (2013) Risks associated with the therapeutic use of fluoroquinolones. Expert Opin Drug Saf 12:497–505
Stam J, van Stuijvenberg M, Grüber C, Mosca F, Arslanoglu S, Chirico G, Braegger CP, Riedler J, Boehm G, Sauer PJ (2012) Antibiotic use in infants in the first year of life in five European countries. Acta Pædiatrica 101(9):929–934
Sturkenboom MC, Felisi M, Manfredi C, Neubert A, Cantarutti L, Padula R, Sen F, Verhamme K (2009) Paediatric status and off-label use of drugs in children in Italy, United Kingdom and the Netherlands. Pharmaceuticals Policy Law 11(1):51–59
Sturkenboom MC, Verhamme KM, Nicolosi A, Murray ML, Neubert A, Caudri D, Picelli G, Sen EF, Giaquinto C, Cantarutti L, Baiardi P, Felisi MG, Ceci A, Wong IC (2008) Drug use in children: cohort study in three European countries. BMJ 337:a2245
Sukkar E (2012) European researchers are urged to do more trials in children, conference hears. BMJ 344:2350
Tuleu C, Breitkreutz J (2013) Educational paper: formulation-related issues in pediatric clinical pharmacology. Eur J Pediatr 172:717–720
Working Group Pediatrico dell’AIFA. La prima lista dei farmaci cardiovascolari autorizzati per un uso pediatrico
Acknowledgments
This study has been supported by grants from Agenzia Italiana del Farmaco (AIFA) and the Regional Centre of Pharmacovigilance of Regione Lombardia.
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The authors declare that they have no conflict of interest
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Carla Carnovale and Valentino Conti contributed equally to the work
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Carnovale, C., Conti, V., Perrone, V. et al. Paediatric drug use with focus on off-label prescriptions in Lombardy and implications for therapeutic approaches. Eur J Pediatr 172, 1679–1685 (2013). https://doi.org/10.1007/s00431-013-2111-7
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DOI: https://doi.org/10.1007/s00431-013-2111-7