Drug Reactions In Children Research Articles

Adverse Drug Reactions Causing Admission to a Paediatric Hospital

Objective(s)To obtain reliable information about the incidence of adverse drug reactions, and identify potential areas where intervention may reduce the burden of ill-health.DesignProspective observational study.SettingA large tertiary children’s hospital providing general and specialty care in the UK.ParticipantsAll acute paediatric admissions over a one year period.Main ExposureAny medication taken in the two weeks prior to admission.Outcome MeasuresOccurrence of adverse drug reaction.Results240/8345 admissions in 178/6821 patients admitted acutely to a paediatric hospital were thought to be related to an adverse drug reaction, giving an estimated incidence of 2.9% (95% CI 2.5, 3.3), with the reaction directly causing, or contributing to the cause, of admission in 97.1% of cases. No deaths were attributable to an adverse drug reaction. 22.1% (95% CI 17%, 28%) of the reactions were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44/249 (17.7%) of adverse drug reactions, the remainder originating from hospital. 120/249 (48.2%) reactions resulted from treatment for malignancies. The drugs most commonly implicated in causing admissions were cytotoxic agents, corticosteroids, non-steroidal anti-inflammatory drugs, vaccines and immunosuppressants. The most common reactions were neutropenia, immunosuppression and thrombocytopenia.ConclusionsAdverse drug reactions in children are an important public health problem. Most of those serious enough to require hospital admission are due to hospital-based prescribing, of which just over a fifth may be avoidable. Strategies to reduce the burden of ill-health from adverse drug reactions causing admission are needed.

Hepatotoxicidad por fármacos o productos naturales en niños

IntroductionThe incidence of adverse drug reactions in children has recently been established at 15.1 reactions per 1000 children. This represents 2% of admissions to a paediatric hospital, and is similar to adult patients. Only a small percentage (less than 8%) may have liver involvement, which can range from a slight increase in transaminases to fulminant hepatitis. The aim of this study was to determine the importance (frequency, types of presentation, severity and chronicity) of hepatotoxicity by drugs or natural remedies in the paediatric population. Patients and methodAll paediatric patients, neonates and children who had suspected hepatotoxic reactions notified by the eight participating Spanish hospitals. The Council for International Organizations of Medical Sciences (CIOMS) scale was used for the analysis of causality in each case. Results and conclusionsWe studied a total of 36 hepatotoxic reactions in 33 children. The drug classes most frequently involved were antimicrobials (71%). Amoxicillin-clavulanate was the individual drug responsible for the greatest number of cases (31.4%). We conclude that the registration of drugs associated with liver disease has proved a useful tool for creating an active network of motivated specialists in detecting and reporting incidents of toxic liver disease, ensuring increasing diagnostic accuracy.

Adverse Drug Reactions in Children – International Surveillance and Evaluation (ADVISE)

A previous meta-analysis reported that 9.5% of hospitalized children suffered from an adverse drug reaction (ADR); however, reported incidences among studies varied. To enhance the knowledge of ADRs in paediatric hospitalized patients at a global level we investigated the incidence and characteristics of ADRs in hospitalized children in European and non-European countries. A prospective observational cohort study was conducted in academic and non-academic hospitals in five countries: Australia, Germany, Hong Kong, Malaysia and the UK. Children aged 0-18 years admitted during a 3-month period (between 1 October 2008 and 31 December 2009) were recruited. The main outcome measures were incidence, causality and outcome of ADRs. A total of 1278 patients (1340 admissions) were included [Australia n = 146 (149 admissions), Germany n = 376 (407), Hong Kong n = 143 (149), Malaysia n = 300 (314) and the UK n = 313 (321)]. The median age was 2 years (interquartile range [IQR] 0-7). Patients received a total of 5367 drugs (median 3; IQR 2-5) and median length of hospital stay was 4 days (IQR 3-7). A total of 380 ADRs were identified in 211 patients. The resultant ADR incidence of 16.5% (95% CI 14.5, 18.7) varied significantly between countries (p < 0.001). The highest incidences were observed in Malaysia and the UK. 65.3% (n = 248) of ADRs were found to be probable, and 24% of the ADRs were serious, with one being fatal. By comparing data from five countries in Europe, Asia and Australia we have shown that the incidence of ADRs in hospitalized children is at least as high as incidences published in adults. However, the variation between countries was mainly due to different populations and treatment strategies. Particular attention should be given to opioid use in hospitalized children.

Adverse drug reactions in children--a systematic review.

BackgroundAdverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided.Methods and FindingsWe searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable.ConclusionsThere is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further work is needed to address how such ADRs may be prevented.

Analysis Of Adverse Drug Reactions In Children

S U N D A Y 374 Analysis Of Adverse Drug Reactions In Children G. M. Park, J. H. Seo, H. Y. Kim, Y. W. Hwang, Y. S. Na, Y. C. Song, J. H. Yu, S. J. Hong; Childhood Asthma Atopy Center, Department of Pediatrics, Department of Pharmacy, Asan Medical Center, University of Ulsan College of Medicine, seoul, REPUBLIC OF KOREA, Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Diseases, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, seoul, REPUBLIC OF KOREA, Department of Pharmacy, Asan Medical Center, University of Ulsan College of Medicine, seoul, REPUBLIC OF KOREA, Childhood Asthma Atopy Center, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, seoul, REPUBLIC OF KOREA. RATIONALE: The incidence of adverse drug reactions(ADRs) is increasing. However, the studies about the prevalence of ADRs in children are rare compared to reports in adult. In order to investigate the causative drugs and clinical features of ADRs in children, we performed a study in a tertiary university hospital of Korea. METHOD: We prospectively collected ADR data by a computerized spontaneous reporting system at our university hospital. ADR data of children under the age 18 collected from January 2005 to May 2011 were analyzed. RESULTS: 1924 ADR cases were reported in 1086 male(56%) and 838 female(44%), and mean age was 9.365.9 years(0-18 years). Antibiotics(n5769, 45%) were the most common causative drugs, followed by analgesics(n5144, 9%) such as tramadol and opiate, non-steroidal antiinflammatory agents(NSAIDs) and acetylsalicylic acid(n5124, 7%), radiocontrast media(n577, 5%) and sedatives(n570, 4%). The most common clinical features were skin manifestations(n5961, 52%) such as urticaria, pruritus, skin rash and angioedema.Gastrointestinal symptoms(n5402, 22%) were the second clinical features, followed by respiratory symptoms(n5157, 9%) including mainly dyspnea. Among antibiotics, penicillin/s-lactamase inhibitors(n580, 16%), third-generation cephalosporins(n578, 15%) and glycopeptides(n566, 13%) were the most frequently reported causative drugs. CONCLUSION: Antibiotics were reported most common causative drug of ADRs in children and the clinical features were mainly skin reactions. Close monitoring system may be useful to detect ADRs early in children.

Active surveillance of adverse drug reactions in children in five Italian paediatric wards

Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing authorization, due to the limited number of trials performed in the paediatric population. Few studies monitored the incidence of ADRs in Italian hospitalized children, that cannot be compared for methodological reasons. A 6-month prospective observational study was, therefore, conducted on the paediatric wards of five hospitals in the Campania Region, Italy. Data were collected on all patients admitted to the wards during the study period through a structured questionnaire administered to the mothers and through a hospital chart review. Of the 752 patients enrolled, 86.2% were exposed to one or more drugs during hospitalization. The therapeutic class most prescribed was systemic antibacterial agents (47%). Six ADRs occurred during hospitalization (incidence 0.9%; 95% CI 0.2% - 1.7%). In addition, one child was admitted to a hospital for an ADR. Five out of seven ADRs occurred in girls. The skin was the most affected organ. The medications implicated were amoxicillin, acyclovir, ibuprofen, ceftriaxone, paracetamol, and ranitidine. According to the Naranjo probability criteria, six ADRs were probably, and one possibly, related to the suspected drug. In conclusion, this study reveals that ADRs may be under-reported in children hospitalized in the Campania Region. Consequently, healthcare personnel should be alert to the possibility of ADRs. More accurate reporting of ADRs in children would result in safer use of drugs in such patients.

Causative drugs and clinical outcome in Stevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and SJS-TEN overlap in children

Background:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe adverse drug reactions in children.Objectives:The objective was to study the causative drugs and outcome in children with SJS, SJS-TEN overlap, and TEN.Materials and Methods:Retrospective analysis of all the in-patient records of children below 18 years of age with the diagnosis of SJS, SJS-TEN overlap, and TEN was carried out.Results and Conclusions:Twenty children were identified, eight patients each were diagnosed as SJS and TEN and four as SJS-TEN overlap. Multiple drugs were implicated in 15 cases while single drug was responsible in 5 cases. Antibiotics (40.7%) were implicated as the commonest cause followed by NSAIDS (25.9%) and anticonvulsants (7.4%). Seventeen patients recovered completely and three patients died.

Using pharmacogenetics to understand adverse drug reactions in children.

Two patients undergo chemotherapy for osteosarcoma of the right proximal tibia. The patients are the same age, were diagnosed within two years of one another, and received identical chemotherapy regimens consisting of cisplatin, doxorubicin and methotrexate. Treatment was successful – both patients are alive and well. However, after only two cycles of chemotherapy, one patient developed bilateral hearing loss with a progressive decline in audiological function, while the other patient’s hearing remained unimpaired. Ototoxicity is a well-characterized adverse drug reaction (ADR) to cisplatin, but why two patients who are so alike can experience profoundly different outcomes is perplexing. Heterogeneity of drug response is a common issue encountered in clinical practice.

Adverse drug reactions in children requiring hospital admission.

To study the incidence of adverse drugs reactions (ADRs) in children admitted to Lady Ridgeway Hospital (LRH), Colombo. A prospective hospital based descriptive study. Medical units of LRH, Colombo. Information was collected by a hospital based investigator who visited the medical units at LRH from February to December 2002. The Naranjo algorithm was used to classify the information. During the 11 month study period, 63 admissions were due to ADRs, the commonest being secondary to administration of antibiotics. ADRs accounted for only 0.16% of admissions as compared to about 2% in North America. The commonest ADRs were due to antibiotics.

Off-label and unlicensed medicine use and adverse drug reactions in children: a narrative review of the literature

The use of unlicensed and off-label medicines in children is common because trials in children have not usually been performed during the drug development process. Consequently, the information available to paediatricians may not always be as detailed or as robust as that available when prescribing a medicine that is licensed for an approved indication. This has led to concerns that children may be receiving drugs at dosages that either lack efficacy or present safety problems. The latter in particular has received a great deal of attention. In this narrative review, we have evaluated the use of off-label and unlicensed medicines in children and whether and how frequently this predisposes to adverse drug reactions.

Adverse drug reactions: causes, types, pathways and mechanisms

An adverse drug reaction is defined as an appreciably harmful or unpleasant reaction resulting from an intervention related to having received medication. This article describes adverse drug reactions in children and young people, their causes, types, pathways and mechanisms. Part two, to be published in June, will address the rights of those who are offered and receive prescribed drugs.

Mortality Rates and Causes of Death in Children with Epilepsy Prescribed Antiepileptic Drugs

Patients with epilepsy, including children, have an increased risk of mortality compared with the general population. Antiepileptic drugs (AEDs) were the most frequent class of drugs reported in a study looking at fatal suspected adverse drug reactions in children in the UK. The objective of the study was to identify cases and causes of death in a paediatric patient cohort prescribed AEDs with an associated epilepsy diagnosis. This was a retrospective cohort study supplemented with general practitioner-completed questionnaires, post-mortem reports and death certificates. The setting was UK primary care practices contributing to the General Practice Research Database. Participants were children and adolescents aged 0-18 years prescribed AEDs between 1993 and 2005. Causality assessment was undertaken by a consensus panel comprising paediatric specialists in neuropathology, neurology, neuropsychiatry, paediatric epilepsy, pharmacoepidemiology and pharmacy to determine crude mortality rate (CMR) and standardized mortality ratios (SMRs), and the likelihood of an association between AED(s) and the event of death. There were 6190 subjects in the cohort (contributing 26,890 person-years of data), of whom 151 died. Median age at death was 8.0 years. CMR was 56.2 per 10,000 person-years and the SMR was 22.4 (95% CI 18.9, 26.2). The majority of deceased subjects had severe underlying disorders. Death was attributable to epilepsy in 18 subjects; in 9 the cause of death was sudden unexpected death in epilepsy (SUDEP) [3.3 per 10 000 person-years (95% CI 1.5, 6.4)]. AEDs were probably (n = 2) or possibly (n = 3) associated causally with death in five subjects. Two status epilepticus deaths were associated causally with AED withdrawal. Children prescribed AEDs have an increased risk of mortality relative to the general population. Most of the deaths were in children with serious underlying disorders. A small number of SUDEP cases were identified. AEDs are not a major cause of death but in a small proportion of cases, a causal relationship between death and AEDs could not be excluded.

Questionnaire for parents about understanding adverse drug reactions in children and attitude to receive propaganda and education

Objective:To investigate the situation of parents in understanding adverse drug reactions(ADRs) and attitude to receive propaganda and education in pediatrics,and analyse the influential factors for reporting ADRs by parents,so as to find the way to improve rate of reporting ADRs.Methods:The questionnaires were distributed to parents in four hospitals where pediatric patients were treated in Shanghai.Results: Totally 600 questionnaires were sent out,and 552 questionnaires responded(the rate of recovery was 92%).It was found that 52% parents could not correctly understand ADRs.It was the main reason why they did not report ADRs.87.8% of them were eager to learn knowledges about children's ADRs.They paid high attention to ADRs occurring in nervous and dermatological systems of children.Conclusion:It is obvious that the parents lack knowledge and understanding of children' ADRs,but their attitude to receive education is active.The training should be strengthened in the future.

Adverse drug reactions in children: reports to the UK yellow card scheme 2000–2009

AimsRational use of medicines in children requires knowledge of both the efficacy and adverse drug reaction (ADR) profile of individual drugs. The Medicines and Healthcare Regulatory Authority (MHRA) in the...

Detecting Unexpected Adverse Drug Reactions in Children

Detecting Unexpected Adverse Drug Reactions in Children

Adverse Drug Reactions In Children; Clinical And Laboratory Characteristics

RATIONALE: Adverse drug reactions (ADR) are more common in adults compared to the pediatric population. ADR may occur with different mechanisms and represent in wide clinical spectrum. In this report we evaluated clinical and laboratory characteristics of children with ADR.

Comparison of clinicoepidemiologic features of cutaneous adverse drug reactions in children and adults

Comparison of clinicoepidemiologic features of cutaneous adverse drug reactions in children and adults

Toward the integration of personalized and systems medicine: challenges, opportunities and approaches.

Personalized medicine: from disease-centered to human-centered medicine Personalized medicine deals with individual diversities and the complexity of the human body. Current healthcare models are diseaseoriented and focus on pathogens and environmental or external factors [4]. Personalized medicine would enable the change from such disease-centered medicine to human-centered medicine. Pharmacogenomics arose in response to such recognition. Pharmacogenomics studies genetic variations among individuals to predict disease susceptibility and responses to therapeutic agents [5,6]. The investigation of genetic diversity may enable the identification of optimal drug targets for certain patient populations, and empower physicians to make the right decisions. By focusing on patients’ genetic or biomarker profiles, pharmacogenomics represents the evolution from treating the disease itself to treating the malfunction of an individual person, the ‘root’ of the disease [7]. With such practices, patients can be regrouped and drugs can be recategorized. For instance, similar diseases may require different treatments, while different diseases may be treated with the same or similar approaches. Because of the diversity of patients’ biological backgrounds, the same disease may be caused by genetic variation in different people, who will respond differently to the same drug. For example, polymorphisms in the ABCB1 gene contribute to cancer risk and different therapeutic responses [8]. Patients with certain genotypes, such as 1236C/C, showed poorer survival than patients with other genotypes. Such situations require individualized treatments for the same disease (cancer) to ensure the best possible results. On the other hand, Challenges & new concepts in biomedicine In this era of change, biomedicine is heading toward a revolutionary new path. This path is a transformation from reductionism toward a holistic paradigm, from ‘one-size-fits-all’ therapeutics towards personalized medicine. Such changes are necessary to meet the challenges in healthcare and the pharmaceutical industry, for example, the high costs in healthcare, low efficacy of drugs and increased incidents of adverse drug reactions (ADRs). ADRs are one of the leading causes of death and illness in the USA [1]. Although the research and development costs in the pharmaceutical industry are soaring, high-profile drug withdrawals are elevating, while the US FDA’s approval for new drugs is decreasing [2]. At the same time, the gap between biomedical science and clinical practice has made it hard to translate scientific advancements into improved healthcare. These challenges and difficulties are calling for the development of new strategies, new concepts, or even a new kind of medicine to meet these goals:

Identifying genomic and developmental causes of adverse drug reactions in children.

Adverse drug reactions are a concern for all clinicians who utilize medications to treat adults and children; however, the frequency of adult and pediatric adverse drug reactions is likely to be under-reported. In this age of genomics and personalized medicine, identifying genetic variation that results in differences in drug biotransformation and response has contributed to significant advances in the utilization of several commonly used medications in adults. In order to better understand the variability of drug response in children however, we must not only consider differences in genotype, but also variation in gene expression during growth and development, namely ontogeny. In this article, recommendations for systematically approaching pharmacogenomic studies in children are discussed, and several examples of studies that investigate the genomic and developmental contribution to adverse drug reactions in children are reviewed.

1253 Adverse Drug Reactions in Children Admitted to a Tertiary Care Center

Background and aims: Knowledge of adverse drug reactions (ADR) is scant in the pediatric population compared to adults. Our goul was to determine the incidence of ADR in hospitalized patients, identify the drugs involved, the most frequent clinical manifestations and their follow-up. Methods: Retrospective study of clinical records of patients hospitalized in a tertiary care hospital, in which an ADR was reported, over a 16 years period. Results: We identified 188 ADR, 0.46% of total admissions. The ADR was the reason for admission in 20,2%. The most common diagnoses were infectious diseases. Children had a mean age of 4.0±3.8 years, 57,4% were male and a past history of allergy or immunodeficiency was reported in 26.7%. The most frequent clinical manifestations were mucocutaneous (51.6%), followed by cardiovascular (14.4%) and gastrointestinal (12.2%). The drugs most often implicated were antibiotics (40.3%), especially vancomycin (19.7%) and amoxicillin-clavulanate (18.4%), followed by chemotherapeutic agents (8.0%), vaccines (6.9%) and steroids (5.9%). Intravenous administration was associated with 54,3% of ADR and the time from first drug administration to ADR was > 48 hours in 51.6%. The reactions were mild in 83.5%, but 3 cases required admission to ICU, with one fatality. Only 14 children (7.4%) were referred to a consultation for follow-up. Conclusions: Our data showed a low incidence of ADR compared to recent prospective studies, but the type of reactions and drugs involved were similar. It is necessary to alert health professionals to occurrence of ADR in order to implement their coding and reporting to the authorities.