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Bruce C Carleton
M Anne Smith
Michaela N Gelin
Susan C Heathcote


Adverse drug reactions, adverse drug reaction voluntary reporting, paediatrics



Severe adverse drug reactions (ADRs) are an important cause of childhood morbidity and mortality. 95% of ADRs are likely not reported, less than 25% of marketed drugs can be advertised as safe and effective in children; yet over 50% of Canadian children receive prescription drugs annually.


To increase understanding of reported ADRs in Canadian children.


A retrospective analysis of 1193 suspected ADRs reported to Health Canada (January 1998 - May 2002). These  data  were  a  paediatric  subset  of  the  Canadian  Adverse  Drug  Reaction  Information  System database.


58.6% of ADRs were for children over 13 years.   61% of reports were defined by Health Canada as serious. Case outcomes include: death (n=41) and recovered with sequelae (n=14). 4 reports of interacting drugs had fatal outcomes. Drugs most frequently cited include: isotretinoin (n=56), paroxetine (n=42), methylphenidate (n=41), amoxicillin (n=40), and valproic acid (n=32). Most frequent reaction descriptors include: psychiatric disorders (isotretinoin and paroxetine) and nervous system disorders (valproic acid, bupropion and carbamazepine). Causal links between suspected ADRs and clinical outcomes have not been established.


Current ADR reporting is insufficient to improve patient safety. More detailed reporting, including case outcomes, is needed. Mandatory ADR reporting is unlikely to improve underreporting. Trained surveillance personnel located in major health centres and solely dedicated to ADR reporting may provide a more accurate determination of ADRs in Canadian children

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1. Whyte J, Greenan E. Drug usage and adverse reactions in hospitalized patients. Acta Paediatr- Scand. 1977;66:767-775.
2. Mitchell AA, Goldman P, Shapiro S, Slone D. Drug utilization and reported adverse reaction in hospitalized children. Am J Epidemiol. 1979;110(2):196 -204.
3. Menniti-Ippolito F, Raschetti R, De Cas R, Giaquinto C, Cantarutti L. Active monitoring of adverse drug reactions in children. Lancet. 2000;355:1613-1614.
4. Impicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C. Incidence of adverse drug reactions in paediatric in/out patients: a systematic review and meta- analysis of prospective studies. Br J Clin Pharmacol. 2001;52:77-83.
5. Jonville-Bera A, Giraudeau B, Blanc P, Beau- Salinas F, Autret-Leca E. Frequency of adverse drug reactions in children: A prospective study. Br J Clin Pharmacol. 2002;53:207- 210.
6. Temple M, Robinson R, Miller J, Hayes J, Nahata M. Frequency and preventability of adverse drug reactions in paediatric patients. Drug Safety. 004;27(11):819-829.
7. Drug and Health Products Branch, Health Canada. Report of suspected adverse reaction due to health products marketed in Canada [form]. http://www.hc dpt/adverse_e.html (accessed 30 June 2005).
8. Fletcher A. Spontaneous adverse drug reporting versus event monitoring: A comparison. J R Soc Med. 1991;84:341- 344.
9. Mittman N, Knowles S, Gomez M, et al. Evaluation of the extent of under- reporting of serious adverse drug reactions. Drug Saf. 2004;27:477-487.
10. Health Canada. Therapeutic Products Directorate. Canadian Adverse Drug Reaction Newsletter. July 2001;11(3). Available at:
11. Statistics Canada. Table 051-0001. Available at:
12. Lane RM. SSRI-induced extrapyramidal side effects and akathisia: Implications for treatment. J Psychopharmacology. 1998;12:192 -214.
13. Hoehn-Saric R, Lipsey JR, McLeod DR. Apathy and indifference in patients on fluvoxamine and fluoxetine. J Clin Psychopharmacol. 1990;10:343-345.
14. Garland EJ, Baerg EA. A motivational syndrome associated with selective serotonin reuptake inhibitors in children and adolescents. J Child & Adolescent Psychopharmacology. 2001;11:181-186.
15. Preda A, MacLean RW, Mazure CM, Bowers MB. Antidepressant associated mania and psychosis resulting in psychiatric admission. J Clinical Psychiatry. 2001;62:30- 33.16. WHO-ART:http://www.who - .
17. MeDRA:
18. Khaled LA, Ahmad F, Brogan T, et al. Prescription medicine use by one million Canadian children. Paediatrics and Child Health.2003;8(Suppl A):6A-54A.
19. Yaffe SJ, Aranda JV. Therapeutic principles and practice. Philadelphia: WB Saunders Co, 1991.
20. Brewer T, Colditz GA. Postmarketing surveillance and adverse drug reactions: Current perspectives and future needs. JAMA.1999;281:824-828.
21. Kaushal R, Bates DW, Landrigan C, et al. Medication errors and adverse drug events in paediatric inpatients. JAMA. 2001;285:2114-2120.
22. Carleton BC, Poole RL, Milton J, Travis J, Grinder D. The pediatric adverse drug reaction reporting system. J Ped Phar Prac. 1999;4:284-307.
23. Conroy S, Choonara I, Impicciatore M, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. BMJ. 2000;320:79-82.
24. Centre for Drug Evaluation and Research. Preventable Adverse Drug Reactions: A focus on Drug Interactions. Food and Drug Administration. (August 5, 2005)
25. Hasford J, Goettler M, Munter K-H, Muller- Oerlinghausen B. Physicians’ knowledge and attitudes regarding the spontaneous reporting system for adverse drug reactions. Journal of Clinical Epidemiology. 2002;55:945-950.
26. Cosentino C, Leoni O, Banfi F, Lecchini S, Frigo G. Attitudes to adverse drug reaction reporting by medical practitioners in a northern Italian district. Pharmacological Research. 1997; 35;85- 88.
27. Health Canada. Therapeutic Products Directorate. Canadian Adverse Drug Reaction Newsletter. July 2005;15(3). Available at - mps/medeff/bulletin/carn-bcei_v15n3_e.html