Adverse Drug Reactions In Children Research Articles

Genomic variations associated with risk and protection against vincristine-induced peripheral neuropathy in pediatric cancer patients

Vincristine-induced peripheral neuropathy is a common and highly debilitating toxicity from vincristine treatment that affects quality of life and often requires dose reduction, potentially affecting survival. Although previous studies demonstrated genetic factors are associated with vincristine neuropathy risk, the clinical relevance of most identified variants is limited by small sample sizes and unclear clinical phenotypes. A genome-wide association study was conducted in 1100 cases and controls matched by vincristine dose and genetic ancestry, uncovering a statistically significant (p < 5.0 × 10−8) variant in MCM3AP gene that substantially increases the risk of neuropathy and 12 variants protective against neuropathy within/near SPDYA, METTL8, PDE4D, FBN2, ZFAND3, NFIB, PAPPA, LRRTM3, NRG3, VTI1A, ARHGAP5, and ACTN1. A follow-up pathway analysis reveals the involvement of four key pathways, including nerve structure and development, myelination, neuronal transmission, and cytoskeleton/microfibril function pathways. These findings present potential actionable genomic markers of vincristine neuropathy and offer opportunities for tailored interventions to improve vincristine safety in children with cancer. This study is registered with ClinicalTrials.gov under the title National Active Surveillance Network and Pharmacogenomics of Adverse Drug Reactions in Children (ID NCT00414115, registered on December 21, 2006).

Adverse Drug Reactions in Children with Congenital Heart Disease: A Scoping Review.

Congenital heart disease (CHD) is one of the leading causes of death. Safe and timely medical interventions, especially in children, can prolong their survival. The drugs prescribed for children with CHD are mainly based on the outcomes of drug therapy in adults with cardiovascular diseases, and their adverse drug reactions (ADRs) might be different. Therefore, the aim of this study was to investigate ADRs in children with CHD. This was a scoping review conducted in 2023. PubMed, Web of Science, Scopus, the Cochrane Library, Ovid, ProQuest, and Google Scholar databases were searched. All studies that reported ADRs for children with CHD and were published in English by 1 November 2023 were included in this study. Finally, the results were reported using a content analysis method. A total of 87 articles were included in the study. The results showed that symptoms/signs/clinical findings, and cardiovascular disorders were the most common ADRs reported in children with CHD. The results also showed that most of the ADRs were reported for prostaglandin E1, amiodarone, prostaglandin E2, dexmedetomidine, and captopril, respectively. The review underscores the wide array of ADRs in children with CHD, particularly in antiarrhythmics, diuretics, beta-blockers, anticoagulants, and vasodilators, which affected cardiovascular, respiratory, endocrine, metabolic, genitourinary, gastrointestinal, and musculoskeletal systems. Tailored treatment is imperative, considering individual patient characteristics, especially in the vulnerable groups. Further research is essential for optimizing dosing, pharmacogenetics, and alternative therapies to enhance patient outcomes in CHD management.

Analysis of spontaneous reports of adverse drug reactions in children of different ages

Analysis of spontaneous reports of adverse drug reactions in children of different ages

Cutaneous adverse drug reactions in children with a focus on hypersensitivity to systemic drugs: A narrative review

Drug hypersensitivity in children is rare compared to adults. Children more frequently develop an infection-associated exanthema. Nevertheless, about 95% of children with drug hypersensitivity present with mucocutaneous involvement. Early recognition of typical clinical symptoms is important to reduce morbidity and mortality. We review relevant type I and type IV disorders of drug hypersensitivity in children and discuss their differential diagnoses and treatment.

Anticancer therapy-induced adverse drug reactions in children and preventive and control measures.

In recent years, considerable achievements have been made in pediatric oncology with the innovation and development of antitumor drugs. However, compared to adults, children as a special group have not yet matured fully in terms of liver and kidney function. Moreover, pediatric patients are prone to more adverse drug reactions (ADRs) from the accumulation of antineoplastic drugs due to their smaller body size and larger body surface area. Chemotherapy-related ADRs have become a non-negligible factor that affects cancer remission. To date, studies on ADRs in pediatric cancer patients have emerged internationally, but few systematic summaries are available. Here, we reviewed the various systemic ADRs associated with antitumor drugs in children and adolescent patients, as well as the advances in strategies to cope with ADRs, which consisted of neurotoxicity, hematological toxicity, cardiotoxicity, ADRs of the respiratory system and gastrointestinal system and urinary system, ADRs of the skin and its adnexa, allergic reactions, and other ADRs. For clinicians and researchers, understanding the causes, symptoms, and coping strategies for ADRs caused by anticancer treatments will undoubtedly benefit more children.

Meta-analysis of the efficacy and adverse drug reactions of adrenergic alpha-antagonists in treating children with ureteral calculi.

This meta-analysis investigated the efficacy and adverse drug reactions (ADRs) of three different adrenergic alpha-antagonists during the treatment of pediatric ureteral stones. Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry until January 2022. We identified 7 articles, including six RCTs and one cohort study. 610 children received either adrenergic alpha-antagonists or placebo. The results confirmed that the three different adrenergic alpha-antagonists could significantly increase the ureteral calculi expulsive rate and shorten the ureteral calculi expulsive time, regardless of the size of the stone "<5 mm" or "5-10 mm". Subgroup analysis suggested that all three adrenergic alpha-antagonists increased the ureteral calculi expulsive rate. Tamsulosin and silodosin also have the effect of shortening ureteral calculi expulsive time, while doxazosin has an insignificant effect on ureteral calculi expulsive time. Besides, tamsulosin and silodosin obviously reduced the number of pain episodes caused by ureteral calculi in children. We analyzed the treatment-emergent adverse events (TEAEs) caused by the treatment of three different adrenergic alpha-antagonists to explore their ADRs. The probability of ADRs was increased after treatment with adrenergic alpha-antagonists. Further subgroup analysis revealed the application of tamsulosin was positively correlated with ADRs in children with ureteral calculi, while the application of doxazosin and silodosin had no statistically significant effect on the probability of TEAEs. In a conclusion, this article systematically analyzed the efficacy and ADRs of three different adrenergic alpha-antagonists, and provided reference and guidance for the application of adrenergic alpha-antagonists to treat children ureteral calculi.

Médicaments responsables de toxidermie chez des enfants de phototype foncé à Dakar

IntroductionToxidermia in the paediatric population accounts for 35 to 36% of adverse drug reactions in children [1]. In 2% of cases, they can affect the vital and/or functional prognosis [2]. The aim of this work was to determine the drugs responsible of toxidermia in pediatric population in a hospital environment in Dakar. MethodologyThis was a cross-sectional, observational, descriptive study, over a period of 10 years, of children seen in the 3 dermatological university hospitals of reference in Dakar. ResultsWe collected 116 cases, representing a hospital incidence of 0.08%. The sex ratio was 1.23. The mean age of the patients was 7 years. The types of toxidermia were Stevens Johnson/Lyell syndrome in 42.2%, EPF in 11.2%, EMP in 10.3%, urticaria in 8.6%. Mucosal involvement was found in 50.9%. Complications were hydro-electrolytic disorders in 22.4%, infection in 7.7% and hypothermia in 1.7%. The incriminated drug classes were antibiotics in 41.4%, antiepileptics in 17.2%, non steroidal anti-inflammatory drugs in 15.5%, analgesics in 15.5% and antimalarials in 8.6%. Traditional plants were incriminated in 7.7% of cases. ConclusionAntibiotics and antiepileptics are the most common drugs involved in children toxidermia in Dakar. Stevens Johnson/Lyell syndrome is the most frequent clinical form.

Adverse drug reactions in children and adolescents on daily antitubercular regimen: An observational longitudinal study

ObjectivesSubsequent to introduction of daily fixed dose combination (FDC) regimen with increased dosages and inclusion of ethambutol in continuation phase of antitubercular therapy (ATT) in India, this study was done to evaluate adverse drug reactions (ADRs) in children and adolescents. MethodsLongitudinal observational study conducted in tertiary teaching hospital. Children (1 month–18 year), with newly diagnosed drug sensitive tuberculosis, started on daily FDC regimen of ATT, were included. Participants were followed up at 2 weeks, 8 weeks and 6 months. Division of AIDS (DAIDS) severity grading and World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment was done. ResultsIn 99 participants, 29 experienced ADRs. Most commonly ADRs involved hepatobiliary (11.1%) and gastrointestinal (8.1%) systems. Grade 3 severity noted in 35.5% ADRs. Certain causality classified in 19.3%. Presence of ADRs was significantly higher in participants with vs without malnutrition [40.5% vs 21.1% (p = 0.036)]. Tendency for more severe ADRs noted in participants with vs without malnutrition [Grade 3 ADRs out of all ADRs: 64.7% vs 0% (p < 0.001)]. ConclusionIncidence and severity of ADRs has increased after introduction of daily FDC of ATT. Most common ADR observed were hepatobiliary. Malnutrition and less weight for age were risk factors for occurrence and severity of ADRs.

Adverse Drug Reactions in Children: Comparison of Reports Collected in a Pharmacovigilance Project Versus Spontaneously Collected ADR Reports.

Adverse drug reactions (ADRs) and medication errors in children may result from a lack of appropriate drugs, dosages, and pharmaceutical forms. In addition, children may respond differently to drugs than adults. Reporting of ADRs in the pediatric population is therefore of importance in order to increase the amount of safety data. However, different methodological approaches are used to collect ADRs. The aim of the present study was to analyze whether there were differences in the ADRs collected in the KiDSafe project (845 ADR reports) compared with the spontaneous ADR reports sent to EudraVigilance (697 reports) in the same time period. The strengths and limitations of these two different approaches should be discussed. The same inclusion criteria were applied for the systematically collected ADRs in the KiDSafe project and the spontaneous reports from EudraVigilance, and only reportsof ADRs coded with hospitalization were considered. In both datasets, the number of reports (related to number of hospitals), their documentation quality (VigiGrade), causal relationship (World Health Organization-Uppsala Monitoring Centre [WHO-UMC] criteria), most frequently reported drugs and ADRs, demographical parameters of the patients, reported medical histories, and the seriousness of ADR reports were analyzed descriptively. The results of the two analyses were compared. There was considerable underreporting of ADRs via the spontaneous reports (0.4 reports per hospital; 697/1902) compared with 70.4 reports per hospital (845/12) in the systematically collected KiDSafe reports. Documentation quality assessment yielded similar results in both datasets. Among the 10 most frequently reported drugs, anticonvulsants such as levetiracetam (6.6%), valproic acid (5.6%), oxcarbazepine (3.6%), and lamotrigine (3.4%) were mainly reported in the KiDSafe reports, while in the EudraVigilance reports, mite allergen extract (4.4%) and allergens (3.6%) were preferentially reported. Seizures were the most frequently reported clinically specific ADRs in the KiDSafe reports, whereas anaphylactic reactions and urticaria were prominent in the spontaneous reports from EudraVigilance. Notably, the proportion of reports referring to medication errors and other medication safety related issues were more prominent in KiDSafe than in the spontaneous reports (27.8% vs. 12.6% and 46.0% vs. 29.0%, respectively). In general, reports from both data sources contributed to the identification of ADRs and dedicated issues related to drug therapy. However, these differed by nature and strength of the signal, likely due to the characteristics of the individual method. A combined approach could likely compensate for limitations inherent to the single approaches, but will most likely only be applied to dedicated pharmacovigilance topics or research objectives.

Increase of cannabis and cocaine use by pregnant women in France from 2005 to 2018: Insights of the annual cross sectional OPPIDUM survey

Substance use disorders during pregnancy are associated with antenatal, neonatal and long-term adverse drug reactions in children. The aim of this study was to describe, using data from OPPIDUM survey, the evolution of illicit substance use or diverted prescription drug use among pregnant women visiting French addiction care centres from 2005 to 2018. The current study focused on women of childbearing age (15-44years old) identified as pregnant, and included in the OPPIDUM survey from 2005 to 2018. OPPIDUM is a French nationwide survey repeated each year since 1995, which anonymously collects information on drug abuse and dependence observed in patients recruited in addiction care centres. Patterns of illicit substance use, psychoactive medications, and opioid maintenance treatment (OMT) were described over time (by period of 2 years) and changes between 2005-2006 and 2017-2018 were investigated. From 2005 to 2018, 784 pregnant women were included in the OPPIDUM survey (median age 28, interquartile range (IQR): 25-33). The proportion of women using exclusively cannabis (1.2% vs. 17.1%, P=0.0004) and cocaine (including crack) use (4.7% vs. 14.3%, P=0.0384) significantly increased over the period. Considering the first substance reported as leading to dependence, heroin significantly decreased (78.8% vs. 50.0%, P=0.0002) whereas cannabis significantly increased (5.9% vs. 25.7%, P=0.0005). This study highlighted an important change of patterns of drug use by French pregnant women over a 14-year-period. Health professionals must be aware of these changes to adapt prevention and care among women of childbearing age and pregnant women.

Fatal adverse drug reactions in children: A descriptive study in the World Health Organization pharmacovigilance database, 2010-2019.

Adverse drug reactions (ADRs) represent a significant public health burden. There are few data on fatal ADRs in children. This population is particularly at risk due to metabolic and physiological immaturity, frequent off-label drug use and limited paediatric clinical pharmacology studies. The study investigated the main characteristics of drug-related deaths registered in World Health Organization pharmacovigilance database, during the past decade. Fatal outcomes registered between 2010 and 2019 in children (<18 y) and reported by physicians were investigated. Age, sex and suspected drugs were described and disproportionality analyses investigated differences according to sex, age and continents with calculation of reporting odds ratio and its 95% confidence interval. Among the 1 198 560 reports registered in children, 1585 (0.13%) were fatal. They occurred mainly in boys, aged 28 days-23 months. Reports mostly came from the Americas and Europe and involved, besides anti-infectious drugs (mainly vaccines), central nervous system (vigabatrin, paracetamol, methylphenidate…) and antineoplastic/immunomodulating (mainly thalidomide) and cardiovascular (mainly bosentan) drugs without major differences between boys and girls. Large differences were found according to continents and age. The risk of reporting was higher in boys, in children aged <23 months, in the Americas and Africa. Fatal ADRs represented a small part (around 1/1000) of total registered ADRs, occurred more frequently in boys and during the first 2 years of life. Beside anti-infectious drugs (vaccines), neuropsychiatric drugs were the most frequently involved, with large differences according to continents and classes of age.

Adverse effects of Anticancer Chemotherapy in Childhood Cancer: A Prospective Study in a Moroccan hospital

Objective: To determine the incidence and frequency of adverse drug reactions (ADRs) induced by cancer chemotherapy in pediatric inpatients. Patients and methods: This was a six-month prospective observational study in the pediatric hematology-oncology department of the children's hospital of Rabat. This study took into account ADRs manifested by in inpatient children and undergoing cancer chemotherapy. A modified version of the Moroccan Poison Control and Pharmacovigilance Centre's notification form was used to collect demographic, clinical, cancer treatment and ADR-related data. The causality, severity and preventability were assessed for each adverse event. Results: 106 patients out of 118 followed have developed a total of 266 ADRs. The most frequent ADRs were anemia (14.3%), infections (9.4%), leukopenia (8.6%) and fever (8.3%). Vincristine (16.3%), etoposide (14%) and cytarabine (13%) were the most frequently administered products. Cytarabine followed by etoposide were the drugs most involved in ADRs. The majority of ADRs (55.6%) were probable according to the WHO method of causality assessment. Conclusion: Cancer chemotherapy is associated with a high risk of developing ADRs, particularly hematological ADRs in children. Pediatric patients receiving cytarabine and daunorubicin combinations and regimens including anthracyclines should receive more attention. Risk management plans need to be implemented by health care teams in this area.

Characteristics of adverse reactions among antipsychotic drugs using the Korean Adverse Event Reporting System database from 2010 to 2019.

Retrospective studies using spontaneous reporting system databases have provided a great understanding of adverse drug reactions (ADRs) in the real world, complementing the data obtained from randomized controlled trials. However, there have been few reports on large-scale epidemiological studies on the adverse effects of antipsychotics in Asia. This study aimed to investigate the characteristics of antipsychotic ADRs using a nationwide pharmacovigilance database. Data were collected from the Korea Adverse Event Reporting System database between 2010 and 2019. The study subjects were selected using the International Classification of Disease codes for diseases related to psychosis and Electronic Data Interchange codes for amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. The causality assessment of "possible," "probable," or "certain" by the World Health Organization-Uppsala Monitoring Center System causality category was selected. All data were descriptively analyzed. In total, 5067 adverse events associated with antipsychotic drugs were reported. The antipsychotics that commonly resulted in ADRs were quetiapine (47.7%), olanzapine (11.3%), and clozapine (10.7%). Serious ADRs were most commonly observed with clozapine. Gastrointestinal and central nervous system problems occurred within a month when ADRs were classified according to the time of onset. In contrast, metabolic and bone marrow-related symptoms occurred after long-term use. Sedation and nausea were the most common ADRs in children and adolescents, whereas constipation and dizziness were common in adults and the elderly. This study extends our knowledge of antipsychotic ADRs in the Asian population.

Simplifying the drug provocation test in non-immediate hypersensitivity reactions to amoxicillin in children: The experience of a tertiary care allergy unit.

BackgroundMild non‐immediate reactions (NIR) to beta‐lactams (βLs) are the most common manifestation of adverse drug reactions in children, and the drug provocation test (DPT) remains the gold standard for diagnosis. However, there are still controversies about the protocol that should be used, especially regarding the administration of doses and the DPT length.ObjectiveThis study aimed to evaluate a pediatric population with a history of mild NIR to amoxicillin (AMX) or to amoxicillin‐clavulanic acid (AMX/CL) who underwent a diagnostic workup including a DPT with the culprit drug, to understand if a graded DPT or, instead, a single full dose could be the most appropriate way of administration in clinical practice.MethodsThe data of children were retrospectively analyzed for a 5‐year period, with demographic and clinical characteristics collected. We reported the allergy workup and the results of the DPT performed with the administration of incremental doses and a prolonged DPT at home for a total of 5 days.ResultsThree hundred fifty‐four patients were included. Overall, 23/354 (6.5%) DPTs were positive: 11/23 patients showed a reaction after 2–8 h after the last dose on the 1st or 2nd day (1 reacted 30 min after the last dose), 1/23 reacted with urticaria 30 min after the first dose, 11/23 reacted at home on the 5th day of the DPT.ConclusionThis paper indirectly suggests that a single therapeutic dose administered on the 1st day of a DPT could be safe in the diagnostic workup of mild NIR to AMX/CL. Moreover, this could be less time‐consuming as patients would spend less time in the hospital, also considering the public health restrictions imposed during the COVID‐19 pandemic.

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice.

Introduction Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The ‘Therapeutic Drug Monitoring (TDM)-VIGIL’ study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved (‘on-label’), and off-label use in clinical practice. Methods Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. Results 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4–10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). Conclusion Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings.

Adverse Drug Reactions in the Pediatric Population: Findings From the Adverse Drug Reaction Monitoring Center of a Teaching Hospital in Odisha (2015-2020).

Background and objectiveThe incidence of adverse drug reactions (ADRs) in hospitalized children varies from 0.6-16.8%. There is a lack of uniformity and an absence of quality reporting with respect to the collection of data on ADRs worldwide, resulting in a scarcity of data regarding ADRs in children. In light of this, we aimed to analyze various factors related to ADRs in the pediatric population in the ADR Monitoring Center (AMC) of a teaching hospital in Odisha, India.MethodsThis was a record-based study conducted by the department of pharmacology in collaboration with the department of pediatrics. Detailed information regarding all ADR cases in children (<14 years of age) was collected in a format designed by the Indian Pharmacopoeia Commission (IPC). A total of 105 ADRs reported during a five-year period (2015-20) were subjected to analysis.ResultsThe largest number of ADRs were reported in the age group zero to five years (41%). Males were affected more compared to females (1.7:1). Cutaneous ADRs were the most common type (86.5%) followed by the involvement of the gastrointestinal system (10%); 21% of cases were serious in nature, i.e., they required either hospitalization or led to a prolonged hospital stay. Antibiotics were the major drug category involved in causing drug reactions (66%) and among them, ceftriaxone (24.6%) was the most common causative agent.ConclusionsOne-fifth of the pediatric cases of ADRs were serious in nature. The most common causative agent was antibiotics, especially beta-lactams. There is an urgent need to raise awareness among healthcare professionals by conducting training programs to encourage the spontaneous reporting of ADRs, which will help to ensure drug safety in the pediatric population.

Status and Safety Signals of Cephalosporins in Children: A Spontaneous Reporting Database Study.

Introduction: Cephalosporins are widely used in clinical treatment of children, but it is difficult to carry out clinical trials and there is no strong evidence of their safety. Therefore, adverse drug reactions (ADR) of cephalosporins can be a public health problem that deserves attention. Methods: ADR reports collected by the Hubei Adverse Drug Reaction Monitoring Center from 2014 to 2019 were analysed. The safety of Cephalosporins was described by descriptive analysis and three signal mining methods, including the reporting odd ratio (ROR), proportional reporting ratio (PRR), and comprehensive standard method (MHRA). Results: The findings indicated that the age groups of 0–1 and 2–3 years had the highest rates of reporting ADRs. Children aged 0–4 years reported more ADRs, while the proportion of severe ADRs was lower than the average (6.63%). Among the 37 cephalosporins, the severe ADRs of ceftezole, ceftazidime, cefoperazone/sulbactam, cefotaxime, ceftriaxone were reported more and the proportion of severe ADRs was higher. The proportion of severe ADRs of most cephalosporin compound preparations was higher than that of corresponding single components. A total of 99.18% of the cases improved after treatment. There were four deaths whose ADRs were mainly anaphylactic shock, dyspnoea, and anaphylactoid reaction. In signal mining, the three methods produced 206 signals that were the same, and 73 of them were off-label ADRs. Conclusion: ADRs were common but not serious in children aged 0–4 years. And the reported rate of serious ADRs in children aged over 4 years increased with age. ADR reports of ceftezole, ceftazidime, cefoperazone/sulbactam, cefotaxime, ceftriaxone were numerous and serious, and the safety of cephalosporin compound preparations in children was doubtful. Ceftezole may cause off-label ADRs including tremor, face oedema, cyanosis, pallor, rigors, and palpitation. The labeling of ADRs in children in cephalosporin instructions and the record of allergic history need to be improved.

Global Perspective of Paediatric Pharmacovigilance and its Importance: Where Have We Reached?

Pharmacovigilance is a tool proposed during the post-marketing process of the pharmaceutical product lifecycle to monitor drug safety in everyday life and to identify adverse drug reactions. The identification of adverse reactions, however, is a significant cause of concern and a challenge to pharmacovigilance structures. Regulators use three basic principles in determining the risk-benefit balance to decide whether to approve a drug or a biological product and to maintain it on the market: safety, quality and effectiveness. In particular, paediatric patients, especially new-borns and infants, are at risk of drug-related adverse reactions. Drugs are also prescribed in an unlicensed and/or off-label manner to new-borns, infants and teenagers, leading paediatric patients to a higher risk of experiencing adverse drug reactions (ADRs). ADRs in children &lt; 2 years of age are often reported and can often be alarming. The practise of paediatric pharmacovigilance needs to be strengthened by stimulating spontaneous paediatric reporting and successful post-marketing surveillance. The current study highlights the importance of paediatric pharmacovigilance and the role of different stakeholders like healthcare providers, regulators, and consumers in increasing the ADR reporting rate. Also, it discusses the pharmacovigilance tools and various initiatives that are taken by various regulatory authorities like the United States, the United Kingdom, Japan, and India.

Adverse reactions related to proton pump inhibitors in pediatric population: an analysis of spontaneous reporting data

ABSTRACT Background The use of proton pump inhibitors (PPIs) has increased in the last 10 years in children. Data regarding their safety profile are limited. The aim of this study was to analyze data from the Italian spontaneous reporting system (SRS) database to evaluate the incidence and characteristics of PPI-related adverse drug reactions (ADRs) in children. Research design and methods This was an observational, retrospective study analyzing PPI-related ADR reports in children in the Italian SRS database between January 1st, 2001, and December 31st, 2020. ADRs were coded according to the system organ class term level. Factors associated with ADR seriousness were investigated. Results Seventy spontaneous reports of ADRs related to PPIs were analyzed. Esomeprazole and lansoprazole caused the highest number of ADRs equally (27% respectively), and the most frequently reported ADRs presented with gastrointestinal (24%) and/or skin manifestations (21.3%). More than a half of PPI prescriptions were off label for pediatric population. Serious ADRs were 19 (27.1%). Serious ADRs were more frequent in reports presenting PPIs combined with other drugs in comparison to reports with PPI single therapies (p = 0.03). Conclusions PPI-related ADRs in children are mostly not serious, and combination therapy seems to be associated with ADR seriousness.

Translation, transcultural adaptation and validation to Brazilian Portuguese of tools for adverse drug reaction assessment in children

BackgroundChildren are more vulnerable to adverse drug reactions (ADRs) due to complex changes in the body during the growth process and lack specific pharmacoepidemiologic studies. Causality and Avoidability assessment of ADRs are relevant to clinical guidelines development and pharmacovigilance. This study aimed to translate and transcultural adapt two new tools—Liverpool Causality Assessment Tool (LCAT) and the Liverpool Avoidability Assessment Tool (LAAT)—to Brazilian-Portuguese and evaluate the psychometric properties of these tools to analyse ADRs in Brazilian children.MethodsThe validation of the cross-cultural adaptation of tools was obtained by the functional (conceptual, semantic, operational, and measurement) equivalence between the original and translated versions of each instrument. The translated version of LCAT and LAAT was applied to assessing the twenty-six case reports of suspected adverse drug reactions in a Brazilian teaching paediatric hospital. The inter-rater reliability (a pharmacist and a physician) was evaluated using Cronbach’s alpha. The exact agreement percentages (%EA) and extreme disagreement (%ED) were computed. Overall Kappa index was calculated with a 95% confidence interval.ResultsThere was a need to modify some terms translated into Portuguese for semantic and conceptual equivalence. The Cronbach’s alpha coefficient values obtained were 0.95 and 0.85, and the weighted Kappa (95% confidence interval) were 0.82 (0.67–0.97) and 0.68 (0.45–0.91) for LCAT and LAAT, respectively. The Brazilian-Portuguese versions of the LCAT and LAAT showed reliable and valid tools for the diagnosis and follow-up of ADRs in children.ConclusionThe methodological approach allowed the translation, transcultural adaptation, and validation to Brazilian-Portuguese of two easy and quick to perform tools for causality and avoidability of ADRs in children by a multidisciplinary expert specialist committee, including the authors of original tools. We believe these versions may be applied by professionals (patient safety teams) and researchers in Brazil in groups or by a single reviewer.Trial registrationThis study was evaluated and approved by the Research Ethics Committee (Instituto de Pediatria e Puericultura Martagão Gesteira – Federal University of Rio de Janeiro – Number: 3.264.238.