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http://dx.doi.org/10.5765/JKACAP.2011.22.2.067

Off-label or Unlicensed Drug Prescriptions in Child and Adolescent Psychiatry  

Lee, So-Young Irene (Department of Psychiatry, College of Medicine, Soonchunhyang Bucheon Hospital, Soonchunhyang University)
Publication Information
Journal of the Korean Academy of Child and Adolescent Psychiatry / v.22, no.2, 2011 , pp. 67-73 More about this Journal
Abstract
The purpose of licensing system is to ensure that the medicines are examined for safety, efficacy and quality. Nevertheless, off-label or unlicensed drug usages in pediatric practice is widespread in Korea and worldwide. Psychotropics are one of the most commonly used off-label or unlicensed drugs. The most valid approach to face this dilemma will be to have more evidences from pediatric pharmacological studies. Clinicians, in addition, need to monitor closely their off-label or unlicensed drug prescriptions to minimize the trial and error in practice. Researchers should publish their experiences and provide guidelines. Pharmaceutical companies, regulatory authorities, and consumer organizations should endeavor altogether for the children's right to get safe and efficacious drugs as adults do. Here, the definition as well as the current status of off-label and unlicensed drug prescriptions will be introduced. Critical issues regarding the off label drugs are discussed. In addition, I will describe the present condition as to the off-label and unlicensed drugs in child and adolescent psychiatry and the authorization process of off-label drug prescription in Korea. Lastly, direction we should like to take in this field will be mentioned.
Keywords
Pediatrics; Psychotropic Drugs; Drug labeling; Off-label Use; Unlicensed;
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1 Glauser TA. Behavioral and psychiatric adverse events associated with antiepileptic drugs commonly used in pediatric patients. J Child Neurol 2004;19:25-38.   DOI
2 Mirakhur RK. Induction characteristics of propofol in children: Comparison with thiopentone. Anaesthesia 1988;43:593-598.   DOI   ScienceOn
3 Henney J. Withdrawal of troglitazone and cisapride. JAMA. 2000; 283:2228.   DOI   ScienceOn
4 Safer DJ, Zito JM, Gardner JE. Pemoline hepatotoxicity and postmarketing surveillance. J Am Acad Child Adolesc Psychiatry 2001; 40:622-629.   DOI   ScienceOn
5 US Food and Drug Administration. Center for Drug Evaluation and Research;2008.
6 National Assembly of the Republic of Korea. The system of law knowledge. [accessed on 1 Feb 2011]. Available from URL: http://likms.assembly.go.kr/law/jsp/main.jsp.
7 Korean Food and Drug Administration. Announcement for medications that cannot be used together and medications that are prohibited in children and adolescents. [accessed on 1 Feb 2011]. Avai-lable from http://www.kfda.go.kr/index.kfda?mid=56&seq=12394
8 Boos J. Off-label use-label off use? Ann Onco 2003;14:1-5.   DOI   ScienceOn
9 Kimland E, Bergman U, Lindemalm S, Bottiger Y. Drug related problems and off-label drug treatment in children as seen at a drug information centre. Eur J Pediatr 2007;166:527-532.   DOI
10 Schirm E, Tobi H, de Jong-van den Berg LT. Risk factors for unlicensed and off-label drug use in children outside the hospital. Pediatrics 2003;111:291-295.   DOI   ScienceOn
11 Korean Academy of Child and Adolescent Psychiatry. Clinical Prac-tice Committee report: the off-label medications used by in the me-mbers in the Korean Academy of Child and Adolescent Psychiatry. [accessed on 8 Jul 2010]. Available from http://www.kacap.or.kr.
12 US Food and Drug Administration. Cumulative list of all products that have received orphan designation: total active designations: 2002. [accessed on 8 Jul 2010]. Available from http://www.fda.gov/ downloads/ForIndustry/DevelopingProductsforRareDiseasesConditions/ HowtoapplyforOrphanProductDesignation/ UCM162066.xls.
13 Yaffe SJ, Aranda JV. Neonatal and pediatric pharmacology: therapeutic principles in practice, 3rd ed. Philadelphia: WB Saunders; 2005.
14 Carrey N. Developmental neurobiology: Implications for pediatric psychopharmacology. Can J Psychiatry 2001;46:810-818.   DOI
15 Horen B, Montastruc JL, Lapeyre-Mestre M. Adverse drug reactions and off-label drug use in paediatric outpatients. Br J Clin Ph-armacol 2002;54:665-670.   DOI   ScienceOn
16 Turner S, Nunn AJ, Fielding K, Choonara I. Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: A prospective study. Acta Paediat 1999;88:965-968.   DOI
17 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. Dtsch Arztebl Int 2009;106:25-31.
18 US Food and Drug Administration. Pediatric exclusivity labeling changes. [accessed on 20 Sep 2007]. Available from http://www.fda. gov/cder/pediatric/ labelchange.htm.
19 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;60:349-353.
20 Pandolfini C, Impicciatore P, Provasi D, Rocchi F, Campi R, Bonati M; Italian Paediatric Off-label Collaborative Group. Off-label use of drugs in Italy: A prospective, observational and multicentre study. Acta Paediatr 2002;91:339-347.   DOI
21 Hsien L, Breddemann A, Frobel AK, Heusch A, Schmidt KG, Laer S. Off-label drug use among hospitalized children: Identifying areas with the highest need for research. Pharm World Sci 2008;30: 497-502.   DOI
22 Winterfeld U, Le Heuzey MF, Acquaviva E, Mouren MC, Brion F, Bourdon O. Psychotropic medication use in the child and adolescent psychiatry wards of a French hospital. Pharm World Sci 2008; 30:600-604.   DOI
23 Hugtenburg JG, Heerdink ER, Tso YH. Psychoactive drug prescribing by Dutch child and adolescent psychiatrists. Acta Paediatr 2005; 94:1484-1487.   DOI   ScienceOn
24 Zito JM, Derivan AT, Kratochvil CJ, Safer DJ, Fegert JM, Greenhill LL. Off-label psychopharmacologic prescribing for children: History supports close clinical monitoring. Child Adolesc Psychiatry Ment Health 2008;2:24.   DOI   ScienceOn
25 Efron D, Hiscock H, Sewell JR, Cranswick NE, Vance AL, Tyl Y, Luk ES. Prescribing of psychotropic medications for children by Australian pediatricians and child psychiatrists. Pediatrics 2003;111: 372-375.   DOI   ScienceOn
26 American Academy of Pediatrics. Committee on Drugs. Unapproved used of approved drugs: The Physician, the Package insert, and the Food and Drug Administration. Subject Review. Pediatrics 1996;98:143-145.
27 Mehler-Wex C, KÖlch M, Kirchheiner J, Antony G, Fegert JM, Gerlach M. Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy. Child Adolesc Psychiatry Ment Health 2009;3:14.   DOI   ScienceOn
28 Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, 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;320:79-82.   DOI   ScienceOn
29 Blumer JL, Off-label uses of drugs in children. Pediatrics 1999;104: 598-602.
30 DeVeaugh-Geiss J, March J, Shapiro M, Andreason PJ, Emslie G, Ford LM, et al. Child and adolescent psychopharmacology in the new millennium: a workshop for academia, industry, and government. J Am Acad Child Adolesc Psychiatry 2006;45:261-270.   DOI   ScienceOn
31 Hill P. Off licence and off label prescribing in children: litigation fears for physicians. Arch Dis Child 2005;90:17-18.   DOI   ScienceOn
32 Banner W. Off label prescribing in children. BMJ 2002;324:1290-1291.   DOI
33 McIntyre J, Conroy S, Avery A, Corns H, Choonara I. Unlicensed and off label prescribing of drugs in general practice. Arch Dis Child 2000;83:498-501.   DOI
34 Bazzano AT, Mangione-Smith R, Schonlau M, Suttorp MJ, Brook RH. Off-label prescribing to children in the United States outpatient setting. Acad Pediatr 2009;9:81-88.   DOI   ScienceOn
35 Department of Health and Human Services. 45 CFR Part 46, Subpart D: protections for children involved as subjects in research. Rockville: Food and Drug Administration;1983. p.9814-9820.
36 Shah SS, Hall M, Goodman DM, Feuer P, Sharma V, Fargason C Jr, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med 2007;161:282-290.   DOI   ScienceOn
37 Chalumeau M, Tréluyer JM, Salanave B, Assathiany R, Cheron G, Crocheton N, et al. Off label and unlicensed drug use among French office based paediatricians. Arch Dis Child 2000;83:502-505.   DOI
38 National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Report and Recommendations. Appendix: Belmont Report: ethical principles and guidelines for the protection of human subjects of research. Washington DC: US Government Printing Office;1979. p.23192-23197.
39 Department of Health and Human Services. 21 CFR Part 201, and 601: regulations requiring ma-nufacturers to assess the safety and effectiveness of new drugs and biological products in pediatric patients. Rockville: Food and Drug Administration;1998. p.66632-66672.
40 US Congress. Food and Drug Administration Modernization Act of 1997 (FDAMA). 1997. Public Law 105-115.
41 US Congress. Best Pharmaceuticals for Children Act (BPCA). 2002. Public Law 107-109.
42 US Congress. Pediatric Research Equity Act. 2003. Public Law 108-155.
43 Committee for Proprietary Medicines (CPMP). Clinical investigation of medicinal products in children. 17-03-1997. Report CP-MP/EWP/462/95. Canary Wharf, London: The European Agency for the Evaluation of Medicinal Products. Human Medicines Evaluation Unit;1997.
44 Sutherland JM. Fatal cardiovascular collapse of infants receiving large amounts of chloramphenicol. AMA J Dis Child 1959;97:761-767.
45 European Commission. Better medicines for children. Brussels: DG Enterprise. Unit F2-Paediatric Initiative;2002.
46 Neubert A, Wong ICK, Bonifazi A, Catapano M, Felisi M, Baiardi P, et al. Defining off-label and unlicensed use of medicines for children: Results of a Delphi Survey. Pharm Res 2008;58:316-322.   DOI   ScienceOn
47 Turner S, Nunn AJ, Choonara I. Unlicensed drug use in children in the UK. Paed Perinatal Drug Ther 1997;1:52-55.
48 Lenz W. Epidemiology of congenital malformations. Ann N Y Acad Sci 1965;123:228-236.   DOI
49 Beecher HK. Ethics and clinical research. N Engl J Med 1966;274: 1354-1360.   DOI   ScienceOn
50 Grodin MA, Glantz LH, editors. Children as Research Subjects: Science, Ethics & Law. New York: Oxford University Press; 2004.
51 Rothman DJ. Were Tuskegee and Willowbrook "studies in nature"? Hastings Center Report;1982. p.5-7.
52 World Medical Association. Declaration of Helsinki. [cited on 8 Jul 2010]. Available from: http://www.wma.net/en/30publications/10po-licies/b3/index.html.