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Safety of Medication in Paediatrics
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Vårdvetenskap)
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: In paediatrics, the limited documentation to guide medication, the lack of suitable dosage forms, and the continuous development in childhood present a scenario where safety of medication is a particular challenge.

Aim: To explore reported adverse drug reactions (ADRs) and the challenges in prescribing and administering medicines in paediatrics, in order to identify and suggest areas needing international surveillance within medication safety and improvement in the clinical setting.

Methods: Four exploratory studies were conducted. Worldwide reporting of suspected ADRs (individual case safety reports, ICSR) with ages 0-17 years were examined overall. Twenty published case reports and ICSRs for adolescents, who developed a rare and incompletely documented ADR (rhabdomyolysis) during antipsychotic medicine use, were analysed in-depth. Prescribed doses of anti-inflammatory medicines were studied in a UK electronic health record database. Transcribed focus group interviews with 20 registered nurses from four paediatric wards in Sweden were analysed for factors that may promote or hinder safe medication practices. Descriptive statistics, multiple regression, and content analyses were used.

Results: Although, skin reactions and anti-infective medicines were most frequently reported, and more reported in paediatric patients than in adults, medication errors and adverse reactions related to psychostimulant medicines were reported with increased frequency during 2005 to February 2010. The in-depth case analysis emphasised the need for increased vigilance following changes in patients’ medicine regimens, and indicated that ICSRs could contribute with clinically valuable information. Prescribed dose variations were associated with type of dosage form. Tablets and capsules were prescribed with a higher dose than liquid dosage forms. Six themes emerged from the interviews: preparation and administration was complex; medication errors caused considerable psychological burden; support from nurse colleagues was highly valued; unfamiliar medication was challenging; clear dose instructions were important; nurses handling medications needed to be accorded higher priority.

Conclusions: Age-specific screening of ICSRs and the use of ICSRs to enhance knowledge of ADRs and medication errors need to be developed. Access to age-appropriate dosage forms is important when prescribing medicines to children. To improve medication safety practices in paediatric care, interdisciplinary collaborations across hospitals on national or even global levels are needed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 81 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 883
Keyword [en]
paediatrics, adverse drug reaction, drug-related problem, medication error, patient safety, individual case safety reports, pharmacovigilance, medication, nurses, health care personnel, dosage form, NSAID, dosing, prescription, antipsychotic medicines, postmarketing surveillance
National Category
Medical and Health Sciences
Research subject
Medical Science
URN: urn:nbn:se:uu:diva-197323ISBN: 978-91-554-8632-7OAI: oai:DiVA.org:uu-197323DiVA: diva2:613743
Public defence
2013-05-16, Gustavianum Auditorium Minus, Akademigatan 3, Uppsala, 09:15 (English)
Available from: 2013-04-24 Created: 2013-03-22 Last updated: 2013-08-30Bibliographically approved
List of papers
1. Suspected Adverse Drug Reactions Reported For Children Worldwide: An Exploratory Study Using VigiBase
Open this publication in new window or tab >>Suspected Adverse Drug Reactions Reported For Children Worldwide: An Exploratory Study Using VigiBase
2011 (English)In: Drug Safety, ISSN 0114-5916, Vol. 34, no 5, 415-428 p.Article in journal (Refereed) Published
Abstract [en]


As a first step towards implementing routine screening of safety issues specifically related to children at the Uppsala Monitoring Centre, this study was performed to explore reporting patterns of adverse reactions in children.



The first aim of this study was to characterize and contrast child reports against adult reports in an overall drug and adverse reaction review. The second aim was to highlight increases in reporting of specific adverse reactions during recent years subdivided by age group.


Study Design

This was an exploratory study of internationally compiled individual case safety reports (ICSRs).



Reports were extracted from the WHO global ICSR database, VigiBase, up until 5 February 2010. The reports in VigiBase originate from 97 countries and the likelihood that a medicine caused the adverse effect may vary from case to case. Suspected duplicate and vaccine reports were excluded from the analysis, as were reports with age not specified. The Medical Dictionary for Regulatory Activities (MedDRA (R)) and the WHO Anatomical Therapeutic Chemical (ATC) classification were used to group adverse reactions and drugs.



In the general review, reports from 1968 to 5 February 2010 were divided into child (aged 0-17 years) and adult (>= 18 years) age groups. To highlight increases in reporting rates of specific adverse reactions during recent years, reports from 2005 to February 2010 were compared with reports from 1995 to 1999. The ten adverse reactions with the greatest difference in the proportion of reports between the two time periods were reviewed. In the latter analysis, the reports were subdivided into age groups: neonates 27 days; infants 28 days-23 months; children 2-11 years; and adolescents 12-17 years.



A total of 3 472 183 reports were included in the study, of which 7.7% (268 145) were reports for children (0-17 years). Fifty-three percent of the child reports were for males, whilst 39% of reports in the adult group were for males. The proportion of reports involving children among Asian reports was 14% and was 15% among reports from Africa and Latin America, including the Caribbean. Among reports from North America, Oceania and Europe, 7% of the reports involved children. For the ATC drug classification groups, the largest difference in percentage units between the child and adult groups was seen for the anti-infective (33 vs 15%), respiratory (11 vs 5%) and dermatological (12 vs 7%) drug groups. Skin reactions were most commonly reported for the children; these were recorded in 35% of all reports for children and 23% of all reports for adults. Medication error-related terms in the younger age groups were reported with an increased frequency during recent years. This was particularly noticeable for the infants aged 28 days-23 months, recorded with accidental overdose and drug toxicity. Reactions reported in suspected connection to medicines used for attention-deficit hyperactivity disorders (ADHD) completely dominated the 2- to 11-year age group and were also common for the adolescents. This study presents variations in the reporting pattern in different age groups in VigiBase which, in some cases, could be due to susceptibilities to specific drug-related problems in certain age groups. Other likely explanations might be common drug usage and childhood diseases in these age groups.



Reports in VigiBase received internationally for more than 40 years reflect real concerns for children taking medicines. The study highlights adverse reactions with an increased reporting during recent years, particularly those connected to the introduction of ADHD medicines in the child population. To enhance patient safety, medication errors indicating administration and dosing difficulties of drugs, especially in the younger age groups, require further attention.

National Category
Pharmaceutical Sciences
urn:nbn:se:uu:diva-155257 (URN)10.2165/11587540-000000000-00000 (DOI)000291238200005 ()
Available from: 2011-06-20 Created: 2011-06-20 Last updated: 2013-12-09Bibliographically approved
2. Rhabdomyolysis Reported for Children and Adolescents Treated with Antipsychotic Medicines: A Case Series Analysis
Open this publication in new window or tab >>Rhabdomyolysis Reported for Children and Adolescents Treated with Antipsychotic Medicines: A Case Series Analysis
Show others...
2012 (English)In: Journal of child and adolescent psychopharmacology, ISSN 1044-5463, E-ISSN 1557-8992, Vol. 22, no 6, 440-451 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Rhabdomyolysis is a rare and potentially serious adverse drug reaction (ADR) to antipsychotic medicines. The aim of this study was to investigate the clinical circumstances surrounding the diagnosis of rhabdomyolysis in children and adolescents treated with antipsychotic medicines. We also critically reviewed individual case safety reports (ICSRs) of suspected ADRs to evaluate how clinically useful they can be in a case series analysis. Methods: This was a descriptive and an exploratory study. Published case reports and ICSRs from the World Health Organization (WHO) Global ICSR database, VigiBase, reported with rhabdomyolysis and antipsychotic medicines for patients <= 17 years years of age were described. Reporting patterns of ICSRs with rhabdomyolysis and antipsychotic medicines were explored in VigiBase for children and adolescents and for adults. The VigiBase ICSRs were also systematically evaluated regarding the report content. Results: Of the 26 evaluated reports, 6 co-reported neuroleptic malignant syndrome (NMS) and 20 reports concerned rhabdomyolysis in the absence of NMS. The reported suspected antipsychotic medicines for these 20 reports were olanzapine, risperidone, haloperidol, paliperidone, quetiapine, clozapine, cyamemazine, and aripiprazole. In VigiBase, rhabdomyolysis (in the absence of NMS) was reported more frequently with olanzapine relative to all reports for children and adolescents with antipsychotic medicines. In the range of events that preceded rhabdomyolysis, muscle pains and abdominal pain were commonly recorded to have started during the week prior to the diagnosis. Other preceding symptoms were general weakness and dark urine. Onset of rhabdomyolysis for most patients occurred at any time within 2 months of starting antipsychotic treatment, in several cases triggered by changes to the patient's drug therapy or known risk factors of rhabdomyolysis. It was found that ICSRs can contribute with additional information, but that access to free text and narratives were crucial in order to capture clinically useful features of rhabdomyolysis. Conclusion: Monitoring of children and adolescents needs to be intensified during dose increases, or when a new, added, or switched antipsychotic medicine is introduced to their drug regimen, and during exposure to known risk factors for rhabdomyolysis. The development of seemingly nonserious events, such as abdominal pain, muscle pain, weakness, and dark urine, should be followed up during antipsychotic use, as they might be precursory events to rhabdomyolysis that eventually could develop into acute renal failure.

National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-191787 (URN)10.1089/cap.2011.0134 (DOI)000312440000007 ()
Available from: 2013-01-14 Created: 2013-01-14 Last updated: 2013-08-30Bibliographically approved
3. Dose Variations Associated with Formulations of NSAID Prescriptions for Children A Descriptive Analysis of Electronic Health Records in the UK
Open this publication in new window or tab >>Dose Variations Associated with Formulations of NSAID Prescriptions for Children A Descriptive Analysis of Electronic Health Records in the UK
2011 (English)In: Drug Safety, ISSN 0114-5916, Vol. 34, no 4, 307-317 p.Article in journal (Refereed) Published
Abstract [en]

Background: NSAIDs, particularly ibuprofen, are commonly prescribed for children but there is limited published research on real-life prescribed doses for this class of drugs. Objective: The aim of the study was to investigate if variations in NSAID doses prescribed to children can be explained by patient age, indication, dosage form, type of NSAID or year of prescription. Study Design: Recorded daily doses for drugs within the 'Anti-rheumatics, non-steroidal plain' anatomical classification were studied. First prescriptions of a distinct NSAID substance within 13-month time periods in a patient's history were included. To enable grouping and comparison of NSAIDs, doses were analysed as prescribed daily doses (PDDs) relative to the adult defined daily dose, stated as the relative PDD (rPDD) in this study. Multiple regression analysis was performed with the rPDD as the response variable, and age, indication, dosage form, NSAID substance and year of prescription as the explanatory variables. Setting: Prescriptions from the Intercontinental Medical Statistics (IMS) Health Disease Analyzer database containing electronic health records of general practitioners in the UK issued from 1988 to December 2005. Patients: Data for children aged 2-11 years with NSAID prescriptions including daily dose information. Results: A total of 21 473 first prescriptions for 19 695 patients were studied. The vast majority of prescriptions were for ibuprofen (n = 20855), which were therefore analysed separately. The other NSAID prescriptions were grouped (n = 618), containing diclofenac, indometacin, mefenamic acid, naproxen and piroxicam ('NSAID group'). The rPDD varied considerably with dosage form in both the ibuprofen and NSAID groups. In particular, tablets/capsules were prescribed at higher doses than liquid dosage forms. In the NSAID group, naproxen was prescribed at noticeably higher doses. The rPDD varied only slightly with age in both groups. Prescriptions indicated for rheumatic disease were associated with lower doses than other indications in the NSAID group. The rPDD was not influenced by year of prescription. Conclusions: This study shows a correlation between higher prescribed NSAID doses and tablet/capsule formulation, and highlights the need for careful choice of dose formulation when prescribing medicines for children.

National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-152910 (URN)000289539700005 ()21417503 (PubMedID)
Available from: 2011-05-03 Created: 2011-05-03 Last updated: 2013-08-30Bibliographically approved
4. Challenges of safe medication practice in paediatric care: A nursing perspective
Open this publication in new window or tab >>Challenges of safe medication practice in paediatric care: A nursing perspective
2013 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 5, 532-538 p.Article in journal (Refereed) Published
Abstract [en]


To explore nurses' experiences of handling medications in paediatric clinical practice, with a focus on factors that hinder and facilitate safe medication practices.


Twenty nurses (registered nurses) from four paediatric wards at two hospitals in Sweden were interviewed in focus groups. The interviews were analysed using content analysis.


Six themes emerged from the analysed interviews: the complexity specific for nurses working on paediatric wards are hindrances to safe medication practices; nurses concerns about medication errors causes a considerable psychological burden; the individual nurse works hard for safe medication practices and values support from other nurse colleagues; circumstances out of the ordinary are perceived as critical challenges for maintaining patient safety; nurses value clear instructions, guidelines and routines but these are often missing, variable or changeable; management, other medical professionals, the pharmacy, the pharmaceutical industry and informatics support need to respond to the requirements of the nurses working situations to improve safe medication practices.


Weaknesses were apparent in the long chain of the medication delivery process. A joint effort by different professions involved in that delivery process, and a nationwide collaboration between hospitals is recommended to increase safe medication practices in paediatric care.

medication errors, paediatric nurses, safe medication practice
National Category
Medical and Health Sciences
Research subject
Caring Sciences
urn:nbn:se:uu:diva-197329 (URN)10.1111/apa.12212 (DOI)000317361400030 ()23432129 (PubMedID)
Available from: 2013-03-22 Created: 2013-03-22 Last updated: 2013-08-30Bibliographically approved

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