Adverse drug reactions in newborns, infants and toddlers: Pediatric pharmacovigilance between present and future

Expert Opinion on Drug Safety

Volumn 11, Issue 1, 2012, Pages 95-105

  Fabiano, Valentina ^a   Mameli, Chiara ^a   Zuccotti, Gian Vincenzo ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Adverse drug reactions; Children; Newborns; Pharmacovigilance

Indexed keywords

ANTIBIOTIC AGENT; ANTICONVULSIVE AGENT; ANTIPYRETIC AGENT; ANTIVIRUS AGENT; CORTICOSTEROID; GENTAMICIN; IBUPROFEN; INDOMETACIN; NARCOTIC AGENT; NONSTEROID ANTIINFLAMMATORY AGENT; OCTREOTIDE; OXYMETAZOLINE; PALIVIZUMAB; PARACETAMOL; PHENOBARBITAL; PHENYLEPHRINE; PROPOFOL; SEDATIVE AGENT; VALPROIC ACID; XYLOMETAZOLINE;

APNEA; AUSTRALIA; BODY MASS; BODY SURFACE; BRAIN HEMORRHAGE; CANADA; CHILD; CHILD GROWTH; CHRONIC LUNG DISEASE; CHURG STRAUSS SYNDROME; COMA; CYTOMEGALOVIRUS INFECTION; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG METABOLISM; DRUG MONITORING; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG SENSITIVITY; DRUG SURVEILLANCE PROGRAM; DRUG USE; ELECTROLYTE DISTURBANCE; EUROPE; GASTROINTESTINAL DISEASE; HIGH RISK INFANT; HUMAN; INFANT; KERNICTERUS; KIDNEY FAILURE; NECROTIZING ENTEROCOLITIS; NEPHROTOXICITY; NEUTROPENIA; NEWBORN; NEWBORN INTENSIVE CARE; OFF LABEL DRUG USE; ORAL DRUG ADMINISTRATION; PEDIATRICIAN; PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA OF INFANCY; PHARMACODYNAMICS; PHARMACOGENOMICS; PHARMACOKINETICS; PULMONARY HYPERTENSION; RETINOPATHY; REVIEW; SEIZURE; STOMACH EMPTYING; TERATOGENESIS; TOTAL BODY WATER; UNSPECIFIED SIDE EFFECT; VIRUS INFECTION; WESTERN HEMISPHERE;

ADVERSE DRUG REACTION REPORTING SYSTEMS; AGE FACTORS; CHILD, PRESCHOOL; HUMANS; INCIDENCE; INFANT; INFANT, NEWBORN; OFF-LABEL USE; PHARMACEUTICAL PREPARATIONS; PHARMACOVIGILANCE;

EID: 84555191741     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2011.584531     Document Type: Review

References (125)

1. The importance of pharmacovigilance; safety monitoring of medicinal products. Geneva, World Health Organization, 2002
2. Napoleone E. Children and ADRs (Adverse Drug Reactions). Int J Ped 2010;11:4
3. Safety of Medicines. A guide to detecting and reporting adverse drug reactions. Why health professionals need to take action. Geneva, World Health Organization, 2002
4. World Health Organization. Lexicon of alcohol and drug terms published by the World Health Organization. Available from: www.who.int/substance-abuse/ terminology/who-lexicon/en. Accessed March 04, 2011
5. Nebeker JR, Barach P, Samore MH. Clarifying Adverse Drug Events: A Clinician's Guide to Terminology, Documentation, and Reporting. Ann Intern Med 2004;140:795-801 (Pubitemid 38623529)
6. World Health Organization. Promoting safety of medicines for children. 2007. Available from: www. who.int/medicines/publications/essentialmedicines/ Promotion-safe-med-children.pdf
7. Available online from: http://www.fda.gov/Drugs/ GuidanceComplianceRegulatory Information/Surveillance/AdverseDrugEffects/ default.htm. Last access on 24th April 2011
8. Available online from: http://eudravigilance.ema.europa.eu/highres. htm. Last access on 24th April 2011
9. European Medicine Agency-Committee for Medicinal Product for Human Use (CHMP). Guideline on conduct of pharmacovigilance for medicines used by the paediatric population. London, 2007
10. Available online from: http://www.ema.europa.eu. Last access on 24th April 2011
11. ICH E 11 Clinical investigation of medicinal products in the paediatric population. Published in the UK in: EU: Note for guidance on clinical investigation of medicinal products in the paediatric population (CPMP/ICH/2711/99). London, 2000; and in the US in: US: International Conference on Harmonisation. Guidance on E 11 clinical investigation of medicinal products in pediatric population; Notice. Fed Regist 2000;65:78493-4
12. Mulla H. Understanding developmental pharmacodynamics: importance for drug development and clinical practice. Pediatr Drugs 2010;12:223-33
13. Fillman SG, Duncan CE, Webster MJ, et al. Developmental co-regulation of the beta and gamma GABAA receptor subunits with distinct alpha subunits in the human dorsolateral prefrontal cortex. Int J Devl Neuroscience 2010;28:513-19
14. Ben-Ari Y. Seizures beget seizures: the quest for GABA as a key player. Crit Rev Neurobiol 2006;18:135-44 (Pubitemid 350194067)
15. Nandi R, Beachman D, Middleton J, et al. The functional expression of mu opioid receptors on sensory neurons is developmentally regulated; morphine analgesia is less selective in the neonate. Pain 2004;111:38-50 (Pubitemid 39141005)
16. Marshall JD, Kearns GL. Developmental pharmacodynamics of cyclosporine. Clinical Pharmacol Ther 1999;66:66-75 (Pubitemid 29350447)
17. Reinalter SC, Jeck N, Peters M, Seyberth HW. Pharmacotyping of hypokalaemic salt-losing tubular disorders. Acta Physiol Scand 2004;181:513-21 (Pubitemid 39078849)
18. Agunod M, Yamaguchi N, Lopez R, et al. Correlative study of hydrochloric acid, pepsin, and intrinsic factor secretion in newborns and infants. Am J Dig Dis 1969;14:400-14
19. Rennie JM, Roberton NRC. Textbook of neonatology. Edinburgh: Churchill Livingstone, 3rd edition 1999
20. Johnson PJ. Neonatal pharmacology-pharmacokinetics. Neonatal Netw 2011;30:54-61
21. Huang NN, High RH. Comparison of serum levels following the administration of oral and pa-enteral preparations of penicillin to infants and children of various age groups. J Pediatr 1953;6:57-68
22. Morselli PL. Antiepileptic drugs. In: Morselli PL, ed. Drug disposition during development. New York: Spectrum, 1977:311-60
23. Strolin-Benedetti M, Baltes EM. Drug metabolism and disposition in children. Fundam Clin Pharmacol 2003;17:281-99
24. Anderson BJ, van Lingen RA, Hansen TG, et al. Acetaminophen developmental pharmacokinetics in premature neonates and infants: a pooled population analysis. Anesthesiology 2002;96:1336-45 (Pubitemid 34587201)
25. Tetelbaum M, Finkelstein Y, Nava-Ocampo A, et al. Back to basics: Understanding drugs in children: Pharmacokinetic maturation. Pediatr Rev 2005;26:321-8
26. Routledge PA. Pharmacokinetics in children. J Antimicrob Chemother 1994;34:19-24 (Pubitemid 24311612)
27. Lugo R, Ward R. Basic pharmacokinetic principles. In: Polin R, Fox W, Abman S, editors, Fetal and neonatal physiology. 3rd edition. Harcourt Health Sciences, Philadelphia; 2004. p. 190-7
28. Touw DJ, Graafland O, Cranendonk A, et al. Clinical pharmacokinetics of phenobarbital in neonates. Eur J Pharm Sci 2000;12:111-16
29. Alfonso IALA, Gilman J, Gilman T, et al. Intravenous valproate dosing in neonates. J Child Neurol 2000;15:827-9 (Pubitemid 32151063)
30. Mazoit JX. Pharmacokinetic/pharmacodynamic modeling of anesthetics in children: therapeutic implications. Pediatr Drugs 2006;8:139-50
31. Ehrnebo M, Agurell S, Jalling B, Boreus LO. Age differences in drug binding by plasma proteins: studies on human foetuses, neonates and adults. J Eur Clin Pharmacol 1971;3:189-93
32. Windorfer A, Kuenzer W, Urbanek R. The influence of age on the activity of acetylsalicylic acid-esterase and protein-salicylate binding. Eur J Clin Pharmacol 1974;7:227-31
33. Kurz H, Michels H, Stickel HH. Differences in the binding of drugs to plasma proteins from newborn to adult man. Eur J Clin Pharmacol 1977;11:469-72 (Pubitemid 8143719)
34. Vieira I, Sonnier M, Cresteil T. Developmental expression of CYP2E1 in the human liver: hypermethylation control of gene expression during the neonatal period. Eur J Biochem 1996;238:476-83
35. Treluyer J-M, Jacqz-Aigrain E, Alvarez F, Cresteil T. Expression of CYP2D6 in developing human liver. Eur J Biochem 1991;202:583-88
36. Sonnier M, Cresteil T. Delayed ontogenesis of CYP1A2 in the human liver. Eur J Biochem 1998;251:893-98 (Pubitemid 28108986)
37. Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology-drug disposition, action, and therapy in infants and children. N Engl J Med 2003;349:1157-67 (Pubitemid 37122329)
38. Wildt SN, Kearns GL, Leeder JS, et al. Cytochrome P450 3A: ontogeny and drug disposition. Clin Pharmacokinet 1999;37:485-505 (Pubitemid 30032252)
39. Wildt SN, Kearns GL, Leeder JS, et al. Glucuronidation in humans: pharmacogenetic and developmental aspects. Clin Pharmacokinet 1999;36:439-43
40. Murry DJ, Crom WR, Reddick WE, et al. Liver volume as a determinant of drug clearance in children and adolescents. Drug Metab Dispos 1995;23:1110-16
41. Kanamori M, Takahaski H, Echizen H, et al. Developmental changes in the liver weight-and body-weight normalized clearance of theophylline, phenytoine and cyclosporine in children. Int J Clin Pharmacol Ther 2002;40:485-92 (Pubitemid 35331932)
42. Robillard JE, Guillery EN, Petershack JA. Renal function during fetal life. In: Barratt TM, Avner ED, Harmon WE, eds. Pediatric nephrology. 4th edition. Baltimore: Lippincott Williams & Wilkins 1999:21-37
43. Routledge PA. Pharmacokinetics in children. J. Antimicrob Chemother 1994;34:19-24 (Pubitemid 24311612)
44. Bird NJ, Henderson BL, Lui D, et al. Indexing glomerular filtration rate to suit children. J Nucl Med 2003;44:1037-44
45. Hayton WL. Maturation and growth of renal function: dosing renally cleared drugs in children. AAPS Pharm Sci 2002;2:e3
46. Neville KA, Becker ML, Glodman JL, et al. Developmental pharmacogenomics. Pedatr Anesth 2011;21:255-65
47. Hines RN. The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacol Ther 2008;118:250-67
48. Hines RN, Koukouritaki SB, Poch MT, et al. Regulatory polymorphism and their contribution to interindividual differences in the expression of enzymes influencing drug and toxicant disposition. Drug Metab Rev 2008;40:263-301 (Pubitemid 352000944)
49. Trevino LR, Sjimasaki N, Yang W, et al. Germline genetic variation in an organic anion transporter polypeptyde associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol 2009;27:5972-78
50. Gilman JT. Therapeutic drug monitoring in the neonate and paediatric age group-problems and clinical pharmacokinetic implications. Clin pharmacokin 1990;19:1-10 (Pubitemid 20204821)
51. Burns JP. Research in children. Crit Care Med 2003;31(Suppl 3):S131-6 (Pubitemid 36379557)
52. Conroy S, McIntyre J, Choonara I, et al. Drug trials in children: problems and the way forward. Br J Clin Pharmacol 2000;49:93-97 (Pubitemid 30068285)
53. Conroy S, Choonara I, Impicciatore I, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children. Br Med J 2000;320:79-82 (Pubitemid 30173044)
54. Schirm E, Tobi H, Jong-Van D, den Berg LTW. Unlicensed and off label drug use by children in the community: cross sectional study. BMJ 2002;324:1312-13 (Pubitemid 34606774)
55. Pandolfini C, Campi R, Clavenna A, et al. Italian paediatricians and off-label prescriptions: loyal to regulatory or guideline standards? Acta Paediatr 2005;94:753-57 (Pubitemid 40839806)
56. Conroy S, Carroll WD. Prescribing in pediatrics. Arch Dis Child Educ Pract 2009;94:55-9
57. Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr 2005;164:552-58 (Pubitemid 41225059)
58. Conroy S, McIntre J, Choonora I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed 1999;80:F142-4
59. Dall'Aera M, Gasbarro AR, Padovano M, et al. Unlicensed and off-label use of medicines at a neonatology clinic in Italy. Pharm World Sci 2007;29:361-7 (Pubitemid 47196657)
60. Avenel S, Bomkratz A, Dassieu G, et al. The incidence of prescriptions without marketing product license in a neonatal intensive care unit. Arch Pediatr 2000;7:143-7 (Pubitemid 30091004)
61. O'Donnell CP, Stone RS, Morley CJ. Unlicensed and off-label drug use in an Australian neonatal intensive care unit. Pediatrics 2002;110(5):e52
62. 't Jong GW, Vulto AG, de Hoog M, et al. A survey of the use of off-label and unlicensed drugs in a Dutch children's hospital. Pediatrics 2001;108:1089-93 (Pubitemid 33021180)
63. Dess̀i A, Salemi C, Fanos V, Cuzzolin L. Drug treatments in a neonatal setting: focus on the off-label use in the first month of life. Pharm World Sci 2010;32:120-4
64. Neubert A, Lukas K, Leis T, et al. Drug utilization on a preterm and neonatal intensive care unit in Germany: a prospective, cohort-based analysis. Eur J Clin Pharmacol 2010;66:87-95
65. Porta A, Esposito S, Menson E, et al. Off-label antibiotic use in children in three European countries. Eur J Clin Pharmacol 2010;66:919-27
66. Choonara I, Conroy S. Unlicensed and off-label drug use in children. Implications for safety. Drug safety 2002;25:1-5 (Pubitemid 34208327)
67. Gill AM, Leach HJ, Hughes J, et al. Adverse drug reactions in a paediatric intensive care unit. Acta Paediatr 1995;84:438-41
68. Turner S, Nunn AJ, Fielding K, et al. Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: a prospective study. Acta Paediatr 1999;88:965-8 (Pubitemid 29448261)
69. Clarkson A, Ingleby E, Choonara I, et al. A novel scheme for the reporting of adverse drug reactions. Arch Dis Child 2001;84:337-9 (Pubitemid 32328630)
70. 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 Opin Drug Saf 2006;5:703-18 (Pubitemid 44322888)
71. Impicciatore P, Choonara I, Clarkson A, et al. 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 (Pubitemid 32862772)
72. Clavenna A, Bonati M. Adverse drug reactions in childhood: a review of prospective studies and safety alerts. Arch Dis Child 2009;94:724-8
73. Moore TJ, Weiss RS, Kaplan S, Blaisdell CJ. Reported adverse drug events in infants and children under 2 years of age. Pediatrics 2002;110:e53
74. Kimland E, Rane A, Ufer M, Panagiotidis G. Paediatric adverse drug reactions reported in Sweden from 1987 to 2001. Pharmacoepidemiol Drug Saf 2005;14:493-9 (Pubitemid 40990744)
75. Le J, Nguyen T, Law AV, Hodding J. Adverse drug reactions among children over a 10-year period. Pediatrics 2006;118:555-62 (Pubitemid 46085410)
76. Carleton BC, Smith MA, Gelin MN, Heathcote SC. Paediatric adverse drug reaction reporting: understanding and future directions. Can J Clin Pharmacol 2007;14:e45-57
77. Aagaard L, Weber CB, Hansen EH. Adverse drug reactions in the paediatric population in Denmark. A retrospective analysis of reports to the Danish Medicine Agency from 1998 to 2007. Drug Saf 2010;33:327-39
78. AIFA-Ministero della Salute. Bollettino d'Informazione sui Farmaci (BIF) XIII 2006:5;210-14
79. Moore TJ, Weiss SR, Blaisdell CR. Reported fatal and serious adverse reactions associated with palivizumab abstract. Pediatr Acad Soc 2002. Available from: http://www.pas-meeting.org/2002baltimore/latebreaker-files/lbabstracts. htm#7062. Accessed March 20, 2011
80. Bourgeois FT, Mandl KD, Valim C, Shannon MW. Pediatric adverse drug events in the outpatient setting: an 11-year national analysis. Pediatrics 2009;124:e744-50
81. Shinomiya K, Kajima M, Tajika H, et al. Renal failure caused by eyedrops containing phenylephrine in a case of retinopathy of prematurity. J Med Invest 2003;50:203-06 (Pubitemid 38019770)
82. Alpay A, Ermis B, Ugurbas SC, et al. The local vasoconstriction of infant's skin following instillation of mydriatic eye drops. Eur J Clin Pharmacol 2010;66:1161-4
83. Meyburg J, Kolker S, Hoffmann GF, Zilow E. Coma in neonates following nasal decongestant drops? Deutsches Arzteblatt 2006;103A:3411-13
84. Knight DB. The treatment of patent ductus arteriosus in preterm infants. A review and overview of randomized trials. Semin Neonatol 2001;6:63-73 (Pubitemid 32127004)
85. Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2005;19:CD003481
86. Ahlfors CE, Wennberg RP. Bilirubin-albumin binding and neonatal jaundice. Semin Perinatol 2004;28:334-9
87. Marshall BC, Koch WC. Antivirals for cytomegalovirus infection in neonates and infants: focus on pharmacokinetics, formulations, dosing, and adverse events. Pediatr Drugs 2009;11:309-21
88. Laje P, Halaby L, Adzick NS, Stanley CA. Necrotizing enterocolitis in neonates receiving octreotide for the management of congenital hyperinsulinism. Pediatr Diabetes 2010;11:142-7
89. Holmes LB. Human teratogens: Update 2010. Birth Defects Res 2011;91:1-7
90. Costei AM, Kozer E, Ho T, et al. Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med 2002;156:1129-32 (Pubitemid 36343460)
91. Jaiswal S, Coombs RC, Isbister GK. Paroxetine withdrawal in a neonate with historical and laboratory confirmation. Eur J Pediatr 2003;162:723-4 (Pubitemid 37255509)
92. Sanz EJ, De-las-Cuevas C, Kiuru A, et al. Selective serotonine reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 2005;365:482-7 (Pubitemid 40215730)
93. Ahmed M, Parameshwaran A, Swamy P. Neonatal convulsions secondary to paroxetine withdrawal. J Pak Med Assoc 2007;57:162 (Pubitemid 351235518)
94. Murray KL, Miller KM, Pearson DL. Neonatal withdrawal syndrome following in utero exposure to paroxetine, clonazepam and olanzapine. J Perinatol 2007;27:517-18 (Pubitemid 47180413)
95. Pogliani L, Schneider L, Dilillo D, et al. Paroxetine and neonatal withdrawal syndrome. BMJ Case Reports 2010; doi:10.1136/bcr.12.2009.2528
96. Saulnier PJ, Piguel X, Perault-Pochat MC, et al. Hypoglycaemic seizure and neonatal acute adrenal insufficiency after maternal exposure to prednisone during pregnancy: a case report. Eur J Pediatr 2010;169:763-65
97. Shirkey HC. Therapeutic orphans-everybody's business. Ann Pharmacother 2006;40:1174
98. Kalikstad B, Skjerdal A, Hansen TWR. Compatibility of drug infusions in the NICU. Arch Dis Child 2010;95:745-8
99. Bradley JS, Wassel RT, Lee L, et al. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics 2009;123:e609-13
100. Kearns GL. Impact of developmental pharmacology on pediatric study design: overcoming the challenges. J Allergy Clin Immunol 2000;106(Suppl):S128- 38 (Pubitemid 32015205)
101. MacLeod S. Therapeutic Drug Monitoring in Pediatrics: How Do Children Differ? Ther Drug Monit 2010;32:253-6
102. Wong IC, Galeb MA, Franklin BD, et al. Incidence and nature of dosing errors in paediatric medications-a systematic review. Drug Safety 2004;27:661-70 (Pubitemid 38980451)
103. Ross LM, Wallace J, Paton JY. Medication errors in a paediatric teaching hospital in the UK: five years operational experience. Arch Dis Child 2000;83(6):492-7
104. Raju TN, Kecskes S, Thornton JP, et al. Medication errors in neonatal and paediatric intensive-care units. Lancet 1989;2:374-6 (Pubitemid 19189076)
105. Vincer MJ, Murray JM, Yuill A, et al. Drug errors and incidents in a neonatal intensive care unit. A quality assurance activity. Am J Dis Child 1989;143:737-40 (Pubitemid 19145413)
106. Chedoe I, Molendijk HA, Dittrich ST, et al. Incidence and nature of medication errors in neonatal intensive care with strategies to improve safety: a review of the current literature. Drug Saf 2007;30:503-13 (Pubitemid 46873075)
107. AIFA-Ministero della Salute. Bollettino d'Informazione sui Farmaci (BIF) XVI 2009:1;24-8
108. Fabiano V, Mameli C, Zuccotti GV. Paediatric pharmacology: Remember the excipients. Pharmacol Res 2011; doi:10.1016/j.phrs.2011.01.006
109. Zuccotti GV, Fabiano V. Safety issues with ethanol as an excipient in drugs intended for pediatric use. Exp Opin Drug Saf 2011; doi:10.1517/14740338. 2011.565328
110. Vallano A, Cereza G, Pedros C, et al. Obstacles and solutions for spontaneous reporting of adverse drug reactions in the hospital. Br J Clin Pharmacol 2005;60:653-8 (Pubitemid 41705386)
111. Eland IA, Belton KJ, van Grootheest AC, et al. Attitudinal survey of voluntary reporting of adverse drug reactions. Br J Clin Pharmacol 1999;48:623-7 (Pubitemid 29454245)
112. Ball D, Tisocki T. Adverse drug reaction reporting by general medical practitioners and retail pharmacists in Harare-a pilot study. Cent Afr J Med 1998;44:190-5 (Pubitemid 128516867)
113. Nebeker JR, Barach P, Samore MH. Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting. Ann Intern Med 2004;140:795-801 (Pubitemid 38623529)
114. Kaletra (lopinavir/ritonavir): Label Change-Serious Health Problems in Premature Babies. Available online from: http://www.fda.gov/Safety/MedWatch/ SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm246167.htm (Accessed on 2011 March, 21)
115. Clarkson A, Conroy S, Burroughs K, Choonara I. Surveillance for adverse drug reactions in children: a paediatric regional monitoring centre. Paediatr Perinat Drug Ther 2004;6:20-3 (Pubitemid 39107205)
116. Dormann H, Muth-Selbach U, Krebs S, et al. Incidence and costs of adverse drug reactions during hospitalization: computerized monitoring versus stimulated spontaneous reporting. Drug Saf 2000;22:161-8 (Pubitemid 30072060)
117. Honigman B, Light P, Pulling RM, Bates DW. A computerized method for identifying incidents associated with adverse drug events in outpatients. Int J Med Inf 2001;61:21-32 (Pubitemid 32194423)
118. Weiss J, Krebs S, Hoffmann C, et al. Survey of adverse drug reactions on a pediatric ward: a strategy for early and detailed detection. Pediatrics 2002;110:254-7 (Pubitemid 34833007)
119. Neubert A, Dormann H, Weiss J, et al. Are computerized monitoring systems of value to improve pharmacovigilance in paediatric patients? Eur J Clin Pharmacol 2006;62:959-65 (Pubitemid 44657631)
120. van Puijenbroek E, Conemans J, van Grootheest K. Spontaneous ADR Reports as a Trigger for Pharmacogenetic Research. A prospective observational study in the Netherlands. Drug Safety 2009;32:255-64
121. Howland RH. Pharmacogenetics and Pharmacovigilance. Drug Safety 2009;32:265-70
122. Loo TT, Ross CJD, Sistonen J, et al. Pharmacogenomics and active surveillance for serious adverse drug reactions in children. Pharmacogenomics 2010;11:1269-85
123. Brewer T, Colditz GA. Postmarketing surveillance and adverse drug reactions: current perspectives and future needs. JAMA 1999;281:824-9 (Pubitemid 29113743)
124. de Vries WT, van Roon EN. Low quality of reporting adverse drug reactions in paediatric randomized controlled trials. Arch Dis Child 2010;95:1023-6
125. Castro-Pastrana LI, Carleton BC. Improving pediatric drug safety: need for more efficient clinical translation of pharmacovigilance knowledge. J Popul Ther Clin Pharmacol 2011;18:e76-88