Off-label medicine use in children and adolescents: results of a population-based study in Germany

BMC Public Health

Antje Neubert²  Wolfgang Rascher²  Wanli Zhuang¹  Giselle Sarganas³  Ingrid-Katharina Wolf¹  Hildtraud Knopf¹ 

[1] Department of Epidemiology and Health Monitoring, Robert Koch Institute, General-Pape-Str. 62-66, 12101, Berlin, Germany;Department of Paediatrics and Adolescent Medicine, Paediatric Clinical Study Center, University Hospital Erlangen, Loschgestr. 15, 91054, Erlangen, Germany;Institute of Clinical Pharmacology and Toxicology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

关键词: Under-dosing;    KiGGS study;    Paediatric;    Children;    Off-label;   

Others  :  1162051
DOI  :  10.1186/1471-2458-13-631

 received in 2013-02-21, accepted in 2013-06-26,  发布年份 2013

【 摘 要 】

Background

Population-based self-reported data on off-label medicine use independent from health care provisions are lacking. The purpose of this study is to investigate off-label medicine use in children and adolescents in Germany in a non-clinical setting and to identify prevalence, determinants and spectrum of off-label medicine use.

Methods

Data were obtained from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) conducted by the Robert Koch Institute (2003–2006). 17,450 randomly selected children aged 0–17 years took part in the drug interviews. Of those, 8,899 took at least one medicine during the 7 days preceding the interview. Off-label medicine use was defined as the discrepancy between actual use and the intended use described in the summary of product characteristics. Off-label medicine use was stratified into off-label indication, off-label age, off-label over-dosing, and off-label under-dosing.

Results

The prevalence rate of off-label medicine use among those who used medicines amount of is 40.2%. The prevalence rate is significantly higher in boys (41.4%), in children aged 3 to 6 years (48.7%), without migration background (40.9%), with high social status (42.5%), living in small (42.0%) and medium sized cities (41.6%), and with a poor parents rated health status (41.7%). 12,667 preparations (attributable in respect to off-label use) were taken by 8,899 children. 30% of the medicines have been used off-label. Off-label medicine use was highest in preparations of the ATC-class “C00 Cardiovascular System”. In all origins of medicine, all age groups and all ATC-classes under-dosing was the most frequent reason for off-label medicine use.

Conclusions

There is a considerable level of self-reported off-label medicines use in the general paediatric population. Further investigations are needed to examine in how far off-label medicine use is based on lack of knowledge or on empiricism in paediatric pharmacotherapy. Attention also needs to be paid to under-dosing which potentially exposes drug users to risks of side effects without the benefit of a therapeutic effect. Clinical trials for licensing of paediatric medicines, education of health care professionals, but also of parents and carers are needed to ensure the rational use of medicines.

【 授权许可】

   
2013 Knopf et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Dost FH: The blood levels. Kinetics of the concentration processes in the circulating liquid. Georg Thieme, Leipzig 1953. DNB 450 986 519. 362 pages 96 figures
• [2]Ceci A, Felisi M, Baiardi P, Bonifazi F, Catapano M, Giaquinto C, Nicolosi A, Sturkenboom M, Neubert A, Wong I: Medicines for children licensed by the European medicines agency (EMEA): the balance after 10 years. Eur J Clin Pharmacol 2006, 62(11):947-952.
• [3]EMEA: The paediatric regulation. Paediatric team. Scientific advice, paediatrics & orphan drugs sektor. 2007. http://wwwemaeuropaeu/docs/en_GB/document_library/Presentation/2009/10/WC500004243pdf webcite
• [4]Bucheler R, Schwab M, Morike K, Kalchthaler B, Mohr H, Schroder H, Schwoerer P, Gleiter CH: Off label prescribing to children in primary care in Germany: retrospective cohort study. BMJ 2002, 324(7349):1311-1312.
• [5]Muhlbauer B, Janhsen K, Pichler J, Schoettler P: Off-label use of prescription drugs in childhood and adolescence: an analysis of prescription patterns in Germany. Deutsches Arzteblatt int 2009, 106(3):25-31.
• [6]Neubert A, Dormann H, Weiss J, Egger T, Criegee-Rieck M, Rascher W, Brune K, Hinz B: The impact of unlicensed and off-label drug use on adverse drug reactions in paediatric patients. Drug Saf 2004, 27(13):1059-1067.
• [7]Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, Knoeppel C, Seyberth H, Pandolfini C, Raffaelli MP, et al.: Survey of unlicensed and off label drug use in paediatric wards in european countries. European network for drug investigation in children. BMJ 2000, 320(7227):79-82.
• [8]Chalumeau M, Treluyer JM, Salanave B, Assathiany R, Cheron G, Crocheton N, Rougeron C, Mares M, Breart G, Pons G: Off label and unlicensed drug use among French office based paediatricians. Arch Dis Child 2000, 83(6):502-505.
• [9]Craig JS, Henderson CR, Magee FA: The extent of unlicensed and off-label drug use in the paediatric ward of a district general hospital in Northern Ireland. Ir Med J 2001, 94(8):237-40.
• [10]Jong GW T, Eland IA, Sturkenboom MC, van den Anker JN, Stricker BH: Unlicensed and off label prescription of drugs to children: population based cohort study. BMJ 2002, 324(7349):1313-1314.
• [11]Ekins-Daukes S, Helms PJ, Simpson CR, Taylor MW, McLay JS: Off-label prescribing to children in primary care: retrospective observational study. Eur J Clin Pharmacol 2004, 60(5):349-353.
• [12]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):703-718.
• [13]Pandolfini C, Bonati M: A literature review on off-label drug use in children. Eur J Pediatr 2005, 164(9):552-558.
• [14]Pandolfini C, Campi R, Clavenna A, Cazzato T, Bonati M: Italian paediatricians and off-label prescriptions: loyal to regulatory or guideline standards? Acta paediatrica 2005, 94(6):753-757.
• [15]Bazzano ATM-SR, Schonlau M, Suttorp MJ, Brook RH: Off-label prescribing to children in the United States outpatient setting. Academic pediatrics 2009, 9(2):81-88.
• [16]Lass JIA, Pisarev H, Leinemann T, Lutsar I: Off label use of prescription medicines in children in outpatient setting in Estonia is common. Pharmacoepidemiol Drug Saf 2011, 20(5):474-481.
• [17]Olsson JKE, Pettersson S, Odlind V: Paediatric drug use with focus on off-label prescriptions in Swedish outpatient care–a nationwide study. Acta Paediatr 2011, 100(9):1272-1275.
• [18]Lindell-Osuagwu L, Korhonen MJ, Saano S, Helin-Tanninen M, Naaranlahti T, Kokki H: Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature. J Clin Pharm Ther 2009, 34(3):277-287.
• [19]Kurth BM, Kamtsiuris P, Holling H, Schlaud M, Dolle R, Ellert U, Kahl H, Knopf H, Lange M, Mensink GB, et al.: The challenge of comprehensively mapping children’s health in a nation-wide health survey: design of the German KiGGS-Study. BMC Publ Health 2008, 8:196. BioMed Central Full Text
• [20]Lange M, Kamtsiuris P, Lange C, Schaffrath Rosario A, Stolzenberg H, Lampert T: Sociodemographic characteristics in the German health interview and examination survey for children and adolescents (KiGGS) - operationalisation and public health significance, taking as an example the assessment of general state of health. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 2007, 50(5–6):578-589.
• [21]Schenk L, Ellert U, Neuhauser H: Children and adolescents in Germany with a migration background. Methodical aspects in the german health interview and examination survey for children and adolescents (KiGGS). Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 2007, 50(5–6):590-599.
• [22]Knopf H: Medicine use in children and adolescents. Data collection and first results of the German health interview and examination survey for children and adolescents (KiGGS). Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 2007, 50(5–6):863-870.
• [23]Gelbe liste. 2005. http://www.gelbe-liste.de webcite
• [24]Rote liste. 2005. http://www.rote-liste.de webcite
• [25]Muhlbauer B: Off-label Use of prescription drugs in childhood and adolescence-an analysis of prescription patterns in Germany reply. Deutsches Arzteblatt Int 2009, 106(12):210-210.
• [26]Choonara I: Unlicensed and off-label drug use in children: implications for safety. Expert Opin Drug Saf 2004, 3(2):81-83.
• [27]Bajcetic M, Jelisavcic M, Mitrovic J, Divac N, Simeunovic S, Samardzic R, Gorodischer R: Off label and unlicensed drugs use in paediatric cardiology. Eur J Clin Pharmacol 2005, 61(10):775-779.
• [28]Jong GW T, van der Linden PD, Bakker EM, van der Lely N, Eland IA, Stricker BH, van den Anker JN: Unlicensed and off-label drug use in a paediatric ward of a general hospital in the Netherlands. Eur J Clin Pharmacol 2002, 58(4):293-297.
• [29]Schirm E, Tobi H, de Jong-van den Berg LTW: Unlicensed and off label drug use by children in the community: cross sectional study. Brit Med J 2002, 324(7349):1312-1313.
• [30]Porta A, Esposito S, Menson E, Spyridis N, Tsolia M, Sharland M, Principi N: Off-label antibiotic use in children in three European countries. Eur J Clin Pharmacol 2010, 66(9):919-927.
• [31]Dryden M, Johnson AP, Ashiru-Oredope D, Sharland M: Using antibiotics responsibly: right drug, right time, right dose, right duration. J Antimicrob Chemother 2011, 66(11):2441-2443.
• [32]McDonnell Norms G: Antibiotic overuse: the influence of social norms. J Am Coll Surg 2008, 207(2):265-275.
• [33]Faden D, Faden HS: The high rate of adverse drug events in children receiving prolonged outpatient parenteral antibiotic therapy for osteomyelitis. Pediatr Infect Dis J 2009, 28(6):539-541.
• [34]Granowitz EV, Brown RB: Antibiotic adverse reactions and drug interactions. Critical care clinics 2008, 24(2):421-442. xi
• [35]Novotny J, Novotny M: Adverse drug reactions to antibiotics and major antibiotic drug interactions. Gen Physiol Biophys 1999, 18 Spec No:126-139.
• [36]Ekins-Daukes S, McLay JS, Taylor MW, Simpson CR, Helms PJ: Antibiotic prescribing for children. Too much and too little? Retrospective observational study in primary care. Br J Clin Pharmacol 2003, 56(1):92-95.
• [37]Ahmed U, Spyridis N, Wong IC, Sharland M, Long PF: Dosing of oral penicillins in children: is big child = half an adult, small child = half a big child, baby = half a small child still the best we can do? BMJ 2011, 343:d7803.
• [38]Menson EN, Walker AS, Sharland M, Wells C, Tudor-Williams G, Riordan FAI, Lyall EGH, Gibb DM, St CHPS: Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997–2005: cohort study. Brit Med J 2006, 332(7551):1183-1186.
• [39]Kazouini A, Mohammed BS, Simpson CR, Helms PJ, McLay JS: Paracetamol prescribing in primary care: too little and too much? Br J Clin Pharmacol 2011, 72(3):500-504.
• [40]Du Y, Knopf H: Self-medication among children and adolescents in Germany: results of the national health survey for children and adolescents (KiGGS). Br J Clin Pharmacol 2009, 68(4):599-608.
• [41]Bi P, Tong S, Parton KA: Family self-medication and antibiotics abuse for children and juveniles in a Chinese city. Social Sci Med 2000, 50(10):1445-1450.
• [42]Kogan MD, Pappas G, Yu SM, Kotelchuck M: Over-the-counter medication use among US preschool-age children. Jama-J Am Med Assoc 1994, 272(13):1025-1030.
• [43]Tobi H, Meijer WM, Tuinstra J, den de Jong-van BLTW: Socio-economic differences in prescription and OTC drug use in Dutch adolescents. Pharm World Sci 2003, 25(5):203-206.