Reports Of Adverse Drug Reactions Research Articles

Descriptive analysis of adverse drug reaction reports for hypersensitivity reactions stratified in relation to different beta-lactam antibiotics.

β-lactam antibiotics (BLA) are commonly reported to induce hypersensitivity reactions. However, β-lactam antibiotic-stratified analyses are rare. In the presented study, β-lactam antibiotic associated hypersensitivity reactions were analyzed in the European adverse drug reaction (ADR) database. 923, 38, 222, and 99 hypersensitivity reports for penicillins and first-, second- and third-generation cephalosporins were reported. Differences with regard to demographical parameters, seriousness and types of hypersensitivity reactions, as well as in the number of hypersensitivity reports per outpatient prescriptions were observed between the different β-lactam antibiotics. The number of ADR reports classified as serious was higher for all generations of cephalosporins compared to penicillins. Additionally, anaphylactic reactions were more often reported for first- and second-generation cephalosporins compared to third-generation cephalosporins and penicillins, while bullous reactions were more often reported for first- and third-generation cephalosporins as opposed to second-generation cephalosporins and penicillins. The observed differences may be caused by differences between β-lactam antibiotics and their routes of administration (oral, intravenous), the patient populations, or the reporting of ADRs. Due to the methodological limitations of ADR database analysis, no conclusions can be drawn whether and to what extent the aforementioned factors influenced our results.

The Importance of Direct Patient Reporting of Adverse Drug Reactions in the Safety Monitoring Process.

All medicinal products authorized in the European Union are subjects of constant drug-safety monitoring processes. It is organized in a pharmacovigilance system that is designed to protect human health and life by the detection, analysis and prevention of adverse drug reactions (ADRs) and other drug-related problems. The main role of the aforementioned system is to collect and analyze adverse drug reaction reports. Legislation introduced several years ago allowed patients, their legal representatives and caregivers to report adverse drug reactions, which caused them to be an additional source of safety data. This paper presents the analysis of EudraVigilance data related to adverse drug reactions provided by patients, their representatives, as well as those obtained from healthcare professionals related to medicines which belong to M01A anti-inflammatory and antirheumatic products, a non-steroid group. The objective of the study was to identify the changes in the number and structure of adverse reaction reporting after the introduction of pharmacovigilance (PV) obligations in EU. A review of scientific literature was also conducted to assess the differences in adverse reactions reported by patients or their representatives and by healthcare professionals. We also identified other factors which, according to literature review, influenced the number of adverse reaction reports provided by patients. Analysis of data collected from the EudraVigilance showed that from 2011 to 2013 the number of reports made by patients and their caregivers increased by approx. 24 percentage points, and then, from 2014, it constituted around 30% of the total of reported reactions every year, so patient reporting is an important part of pharmacovigilance system and a source of drugs’ safety information throughout their use in healthcare practice. Additionally, there was no interrelationship between the seriousness of reported adverse reactions and the overall number of patient reports when compared to reports form healthcare professionals.

Comparative study of the adverse event profile of hydroxychloroquine before and during the Sars-CoV2 pandemic

AimsAt the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there were no clinically-tested medications for the effective treatment of coronavirus disease. In this context, on 5 March 2020, the French Public Health Council issued several recommendations for the therapeutic management of this new disease, including the use of hydroxychloroquine (HCQ). An unexpected cardiovascular safety signal was quickly identified as being more frequent than expected thanks to the reports of adverse drug reactions (ADRs) submitted to French regional pharmacovigilance centres (RPVC). The objective of this study was to compare all ADRs reported with HCQ used in its usual indication, collected before the pandemic period (1985 to 31 December, 2019) with those reported with the coronavirus disease 2019 (COVID-19) indication (1 January to 21 July, 2020).MethodsFor this purpose, reports were extracted from the French pharmacovigilance database and analysed for these two periods.ResultsOur study showed a different safety profile in COVID-19 patients with more cardiac disorders (57% of ADRs versus 5% before the pandemic period), especially QT interval prolongation, resulting from an interaction with azithromycin in more than 20% of cases. Hepatobiliary disorders were also significantly more frequent.ConclusionsThese observations could be associated with the effect of the virus itself on the various organs, the profile of the patients treated, and concomitant drug treatments.

Evaluation of Awareness of Knowledge, Attitude and Practices of Nursing Students on Monitoring and Reporting of Adverse Drug Reactions in a Tertiary Care Hospital

Objectives: To assess the Knowledge, Attitude and Practices of nursing students on monitoring and reporting of adverse drug reactions in a tertiary care hospital. Methodology: This questionnaire based study was conducted in a tertiary care hospital on 85 Prefinal and final year nursing students. The study instrument was a pre designed questionnaire which included the Knowledge of the ADRs reporting, the attitudes towards the reporting, and the factors which could hinder the reporting. The students were given an educative and interactive session for clearance of their understanding about Pharmacovigilance. The post-session questionnaire was also completed to assess their understanding. Results: A total of 85 students participated. The median knowledge, attitude scores before the intervention were 42.5%, 46.6% respectively. After the intervention the scores increased significantly to 89.4%, 98.8% respectively. Keywords: Adverse Drug Reactions, Pharmacovigilance, Questionnaire, Knowledge Attitude and Practices, Nursing students

Pharmacovigilance Data as a Trigger to Identify Antimicrobial Resistance and Inappropriate Use of Antibiotics: A Study Using Reports from The Netherlands Pharmacovigilance Centre.

(1) Background: Antimicrobial resistance (AMR) requires urgent multidisciplinary solutions, and pharmacovigilance has the potential to strengthen current antimicrobial stewardship strategies. This study aimed to characterize AMR-relevant adverse drug reaction (ADR) reports submitted to The Netherlands Pharmacovigilance Centre; (2) Methods: We carried out a descriptive analysis of ADR reports submitted to Lareb, coded with AMR-relevant MedDRA Preferred Terms (PTs); (3) Results: Between 1998 and January 2019, 252 AMR-relevant ADR reports were submitted to Lareb. The most frequent antibiotics were tobramycin (n = 89; 35%), colistin (n = 30; 11.9%), cipro-floxacin (n = 16; 6.3%), doxycycline (n = 14; 5.5%), and aztreonam (n = 12; 4.8%). The PTs used included off label use (n = 91; 36.1%), drug ineffective (n = 71; 28.2%), product use in unapproved indication (n = 28; 11.1%), pathogen resistance (n = 14; 5.6%), and drug resistance (n = 13; 5.2%). 54% of the reports were on Watch antibiotics and 19% were involved in the Reserve group. In the Watch group, “off label use” and “product use in unapproved indication” were the most frequent PTs and the majority of reports on Reserve antibiotics were coded as “Off label”. A sharp increase in the number of reports was observed in the three consecutive years with 21 in 2013, 54 in 2014, and 83 in 2015; (4) Conclusions: In addition to existing AMR monitoring strategies, pharmacovigilance databases can serve as a source of data on suspected resistance and inappropriate use. Future research should explore how these AMR-relevant MedDRA Terms are used in resource-limited settings with less capacity to generate laboratory-confirmed resistance data.

Chinese-Named Entity Recognition From Adverse Drug Event Records: Radical Embedding-Combined Dynamic Embedding-Based BERT in a Bidirectional Long Short-term Conditional Random Field (Bi-LSTM-CRF) Model.

BackgroundWith the increasing variety of drugs, the incidence of adverse drug events (ADEs) is increasing year by year. Massive numbers of ADEs are recorded in electronic medical records and adverse drug reaction (ADR) reports, which are important sources of potential ADR information. Meanwhile, it is essential to make latent ADR information automatically available for better postmarketing drug safety reevaluation and pharmacovigilance.ObjectiveThis study describes how to identify ADR-related information from Chinese ADE reports.MethodsOur study established an efficient automated tool, named BBC-Radical. BBC-Radical is a model that consists of 3 components: Bidirectional Encoder Representations from Transformers (BERT), bidirectional long short-term memory (bi-LSTM), and conditional random field (CRF). The model identifies ADR-related information from Chinese ADR reports. Token features and radical features of Chinese characters were used to represent the common meaning of a group of words. BERT and Bi-LSTM-CRF were novel models that combined these features to conduct named entity recognition (NER) tasks in the free-text section of 24,890 ADR reports from the Jiangsu Province Adverse Drug Reaction Monitoring Center from 2010 to 2016. Moreover, the man-machine comparison experiment on the ADE records from Drum Tower Hospital was designed to compare the NER performance between the BBC-Radical model and a manual method.ResultsThe NER model achieved relatively high performance, with a precision of 96.4%, recall of 96.0%, and F1 score of 96.2%. This indicates that the performance of the BBC-Radical model (precision 87.2%, recall 85.7%, and F1 score 86.4%) is much better than that of the manual method (precision 86.1%, recall 73.8%, and F1 score 79.5%) in the recognition task of each kind of entity.ConclusionsThe proposed model was competitive in extracting ADR-related information from ADE reports, and the results suggest that the application of our method to extract ADR-related information is of great significance in improving the quality of ADR reports and postmarketing drug safety evaluation.

Spontaneous Reporting of Adverse Drug Reactions in a Pediatric Population in a Tertiary Hospital.

The pediatric population is a vulnerable group for adverse drug reactions (ADRs), and data on spontaneous reporting of ADRs in the hospital setting are scarce. We conducted a retrospective analysis of ADRs in pediatric patients spontaneously reported by health care professionals to a Pharmacovigilance Program in a tertiary hospital between 2010 and 2020, and we compared characteristics of ADRs between pediatric age subgroups. From 1787 spontaneously reported ADRs in an 11-year period, 103 (5.85%) were pediatric ADRs. The median age of patients with ADRs was 8.4 years (range 1 day–17 years) and 57.3% were male. The most frequent ADRs reported were nervous system disorders (13.6%) and the most frequently involved drugs were antineoplastics and immunodulators (32.4%). A 59.2% of the ADRs were serious and 55.3% were classified as being type B reactions. Medication errors were involved in 7.8% of the ADRs and 11.9% of the suspected drugs were used off-label. Spontaneous reports of ADRs in newborns, infants, and toddlers were more serious and less often described in the product data sheet than in children and adolescents (p < 0.001 and p = 0.004 respectively). Medication errors were more frequent in patients under two years of age. These results should be interpreted with caution due to under-reporting and biases in spontaneous reporting of ADRs.

Drug Induced Liver Injury: Perspective of the Adverse Drug Reaction Reports to the Portuguese Pharmacovigilance System from 2010 to 2019.

Background: Drug induced liver injury (DILI) is an adverse drug reaction that causes liver damage in a predictable (dose-dependent) or an unpredictable (idiosyncratic) fashion. We performed an assessment of DILI in Portugal, by analyzing the reports, sent to the Portuguese Pharmacovigilance System (PPS). Methods: A search was performed on the PPS database, in a 10-year time frame, from 1 January 2010 to 31 December 2019. Results: There was not a prevalence of either sex in any age group. Most reports (n = 1120, 55.0%) belonged to patients in the age group 19–64 years old. Hepatitis (n = 626, 26.7%) was the most common adverse drug reaction in our study. Hepatotoxicity (n = 362, 15.5%) and hepatitis (n = 333, 14.2%) were more frequent in age group 19–64 years old. Cholestasis was more prevalent in adults independently of age. Hepatic fibrosis and encephalopathy were more common in the elderly. Most patients consumed between one and four suspected drugs (n = 1867, 92%). Most patients in our study evolved to “cure” (n = 796; 39%). Hepatotoxicity (n = 23; 13.8%) and hepatitis (n = 610; 25.9%) had a female predominancy while choluria (n = 8; 4.8%) and splenomegaly (n = 8; 4.8%) were of male predominance. Conclusions: DILI is rare but can be fatal. As such, an active search of DILI is necessary.

Adverse drug reactions induced by cotrimoxazole: Still a lot of preventable harm.

Owing to a broad spectrum and low cost antimicrobial, cotrimoxazole is largely prescribed. However, its use is associated with various adverse drug reactions (ADRs) that warrant to ensure rational prescribing. This study aimed to describe spontaneous reports of cotrimoxazole ADRs and to evaluate the quality of prescription in patients who had ADRs. Suspected cotrimoxazole-induced ADRs cases reported to the Bordeaux regional pharmacovigilance center (France) during a 5-year period were described. Seriousness was assessed according to international criteria. Quality of prescription was assessed by compliance with the Summary of Product Characteristics (SPC) and relevance of cotrimoxazole indication. Then, an ADR was considered as preventable if the cotrimoxazole indication was not relevant, or potentially preventable if indication was relevant but the prescription was not compliant with the SPC. A total of 96 cases were analyzed: median age was 60.5years (range: 4-94); 59.4% of patients were male. ADRs were mostly cutaneous disorders (n = 46) and hematological disorders (n = 25). A total of 60 serious ADRs occurred in 55 patients. Prescribers complied with all SPC recommendations in 21.9% of cases. Indication of cotrimoxazole was relevant or highly relevant in 41 cases. In 58% of cases, the occurrence of a cotrimoxazole-induced ADR would have been preventable or potentially preventable. In a context of increasing interest for this antibiotic to treat infections due to resistant bacteria, physicians should be more aware of the potential consequences of inappropriate prescribing cotrimoxazole and reserve its use when there is no alternative and under suitable monitoring.

Pragmatic pharmacoeconomic analyses by using post-market adverse drug reaction reports: an illustration using infliximab, adalimumab, and the Canada vigilance adverse reaction database

BackgroundThe prediction of the real-world cost of adverse drug reactions (ADRs) has historically relied on the data from randomized controlled trials (RCT). However, trial conditions do not always reflect the real-world applications of pharmaceutical products; hence, they may not accurately portray the actual risks of ADRs associated with them. The objective of this study is two-fold: (a) demonstrate whether and how post-market and RCT ADR data could lead to different conclusions for a set of drugs of interest, and (b) evaluate the potential economic impact of the post-market ADRs associated with those drugs.MethodsWe selected two TNF-α inhibitor biologics, infliximab and adalimumab, and used the Canada Vigilance Adverse Reaction (CVAR) online database as a source of post-market ADR data. Adverse reaction data from RCTs were obtained from ClinicalTrials.gov. Direct healthcare costs associated with adverse reactions were obtained from Canadian Institute for Health Information (CIHI) or Interactive Health Data Application, Alberta. We calculated post-market ADR rates and compared them with those found in the randomized controlled trials of these two drugs. Using the post-market data, we estimated the costs associated with serious ADRs from three perspectives: patient, health system, and societal.ResultsFor both drugs, the post-market and RCT data exhibited significantly different adverse reaction rates for several different clinical outcomes. As a general trend, more serious adverse reactions, such as death, appeared to have a higher rate in post-market applications compared to the clinical trials. The estimated average annual economic burden of the severe adverse reaction outcomes ranged from $10 million to $20 million for infliximab and $6 million to $19 million for adalimumab.ConclusionsThe frequency and severity of post-market adverse reactions associated with pharmaceutical products may significantly differ from those detected in the clinical trials. Despite possible methodological differences, this is due to the fact that post-market data reflect the externalities of the real-world that are absent in RCTs. The economic burden of adverse reactions can be substantial, and the cost calculated using post-market data is better reflective of the cost of ADRs in the real-world.

Evaluation of Adverse Drug Reactions in Paediatric Patients: A Retrospective Study in Turkish Hospital.

Drug safety in paediatric patients is a serious public health concern around the world. The paediatric patients are more prone to adverse drug reactions (ADRs) than adults. Moreover, there is a scarcity of information about ADRs in paediatric patients. This study was conducted to determine the frequency, causality, severity, preventability of paediatric patients’ ADRs reported in a tertiary care hospital in Adana, Turkey. A retrospective study was conducted on all spontaneously reported ADRs between January 01, 2020, to July 30, 2021, in paediatric patients. The ADRs reports were evaluated in terms of gender, age, ADR characteristics, suspected drugs and reporting source. All included ADRs reports were characterized according to the Naranjo Algorithm/World Health Organization (WHO) causality scales, Hartwig/Siegel and Common Terminology Criteria for Adverse Events (CTCAE) severity scales, the modified Schoumock and Thornton preventability scale and hospital pharmacovigilance center criteria for seriousness. Therapeutic groups were also coded using the WHO-Anatomical Therapeutic and Chemical (ATC) classification. During the study period, 8,912 paediatric patients who were admitted had 16 ADRs with 1.7 ADRs/1,000 admissions. The majority of ADRs were found in infants (31.2%) and children (56.2%) as compared to adolescents (12.5%). ADRs were observed more in females (81.2%) than males. Skin (62.5%) was the most affected organ due to the ADRs, and maculopapular rash and erythema multiforme were the most commonly reported symptoms. Most ADRs were probable/likely (93.7%), severe (50%), preventable or probably preventable (43.7%) and serious (37.5%). Antibiotics (93.7%) were found to be the most common cause of ADRs in paediatric patients. The majority of ADRs were associated with vancomycin (68.7%). Most of the ADRs were reported by a medical doctor in this study. This small sample size study highlights significant problems of ADRs in paediatric patients, mainly caused by antibiotics and with a majority of ADRs manifest as skin reactions. Furthermore, a high proportion of the identified ADRs were found to be preventable. More focused efforts are needed at the national level to avoid preventable ADRs in hospitals. Monitoring and management of ADRs and future studies would be beneficial for better patient care and safety.

Current Status of Adverse Drug Reaction Reporting by the Physicians in A Medical College Hospital

Background: In order to improve the spontaneous Adverse Drug Reaction (ADR) reporting practice by the physicians, there is an obligatory need to investigate the current situation of ADR reporting by them. The study was conducted to observe the ADR reporting pattern among physicians in a tertiary medical college hospital.&#x0D; Materials and methods: This was a descriptive cross sectional study carried out in a tertiary medical college hospital during the study period of March 2020 to October 2020. Data were collected from 100 physicians working on different departments using self designed pretested questionnaire by convenient sampling technique.&#x0D; Results: Among the 100 respondents 70 provided response to questionnaire giving a response rate 70%. Most of the respondents (61.43%) had adequate knowledge on ADR reporting. A good number of respondents showed positive attitude but there is no practice of ADR reporting though most of the respondents (84.3%) had experienced it in last 1 year. Most of the respondents experienced ADR with antibiotic (81.35%), NSAIDs (33.89%) &amp; anticonvulsants (15.25%) and maximum (44.06%) experienced ADR was with skin, 30.50% with GIT and 23.03% with respiratory system involvement. The cause of under reporting was mainly due to inaccessible ADR form, busy schedule, unaware of how and whom to report and lack of motivation to report. The respondents would be encouraged to report ADR if they were provided with simple &amp; available reporting form, regular guideline &amp; bulletin.&#x0D; Conclusion: There is an urgent need for educational training &amp; seminar regarding our national online reporting system to emphasizing ADR reporting.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.20 (2); July 2021; Page 8-13

A system for reporting and evaluating adverse drug reactions of herbal medicine in Taiwan from 1998 to 2016

The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan’s herbal medicines adverse reaction database and facilitate epidemiological analysis.

Accuracy of Antibiotic Allergy Documentation and the Validity of Physicians' Decision in a Pediatric Tertiary Care Setting.

BackgroundPatients allergic to antibiotics are at higher risk of receiving treatment with a broader spectrum, more harmful, and expensive agents. The aims of this study were (1) to assess the quality of documentation of antibiotics allergies in the electronic medical records (EMR) in a Pediatric tertiary care setting, and (2) to determine the validity of physicians’ decision to hold antibiotics prescriptions.MethodsThis is a retrospective cohort study at King Abdullah Specialized Children Hospital, Riyadh, Saudi Arabia. A review of the EMR and all Adverse Drug Reaction (ADR) reports of pediatric patients 1–14 years old, with a documented allergy to antibiotics from June 2016 until June 2019. The quality of documentation of antibiotics allergy was assessed based on the presence of four parameters: 1) allergy alert notification, 2) allergy severity classification, 3) setting notes, and 4) symptoms’ description. In addition, all physicians’ reports of allergy to antibiotics were cross-classified according to their corresponding ADR reports, and the validity of physicians’ documentation of allergy was assessed.ResultsOf a total of 105 Pediatric patients’ EMR, documentation of antibiotics allergy was available in 98 (93.3%), with the presence of symptoms description (83%), allergy notes (87%), severity (67%), and signs of alert (50.8%). Overall documentation quality was good for only 23.5% of patients, while it was poor for 35.7%. Physicians’ documentation of antibiotics allergy was 0.82 sensitive [with 0.18 risk of allergy] and 0.60 specific [with 0.40 unnecessary restrictions of prescriptions]. Of all children with possible/actual allergies, only 38.9% were referred to the immunology clinic.ConclusionThe quality of documentation of antibiotic allergy in children and the validity of physicians’ decisions are less than satisfactory. Therefore, improving communications between all healthcare providers regarding patients’ allergy status and follow-up for further assessment of the reaction is recommended to improve patient care.

Improving the data quality of spontaneous ADR reports: a practical example from Malta

ABSTRACT Background Adverse drug reaction (ADR) reporting rates and high-quality data within case summary reports are crucial to detect emerging safety concerns and implement regulatory action. In this study we aimed to improve the data quality and reporting rates of ADR reports in Malta through a series of national activities. Research design and methods Between April 2018 and July 2019, we carried out the following activities: i) a review of wholesale dealers ADR reporting forms; ii) a series of educational workshops targeting physicians and pharmacists; iii) a quality system audit of the Authority’s ADR management process. Results Twelve wholesaler dealer forms were reviewed, and 155 improvements were identified. Incident reporting forms modified to capture ADRs had the most opportunities for improvement. Five workshops were organized and in total 62 physicians and 22 pharmacists attended. Although feedback from participants was positive, in our case, an increase in reporting was not observed following the workshops. The quality system audit resulted in the introduction of the ‘four-eye principle’ to the Authority’s ADR management process. Conclusions The implementation of such activities is expected to contribute to the overall pharmacovigilance systems in Malta and our experience could benefit other entities involved in spontaneous ADR reporting.

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.

Situation analysis of the pharmacovigilance system in Nepal using the indicator-based pharmacovigilance assessment tool (IPAT)

Abstract Objectives The aim of this study was to assess the national and regional pharmacovigilance centres in Nepal in terms of their policy frameworks, structure and functioning. Methods A descriptive cross-sectional study was conducted during January 2021 among regional pharmacovigilance centres, and the national pharmacovigilance centre and the Ministry of Health and Population. The indicator-based pharmacovigilance assessment tool (IPAT) consisting of 43 indicators (26 core and 17 supplementary) assessing different aspects of pharmacovigilance was used. Key findings Of a total of 14 candidates representing regional pharmacovigilance centres, 12 agreed to participate. The national pharmacovigilance centre located at the Department of Drug Administration had an acceptable level of infrastructure and manpower but poor functioning and weak collaboration with regional centres. There are no policies and procedures specifically related to pharmacovigilance and no requirement for pharmaceutical companies to report adverse drug reactions (ADRs). The national centre received only 42 ADR reports during the evaluation period. The regional centres are mostly located (10 out of 14) in the Kathmandu Valley and had qualified manpower and basic resources. There were poor process indicators suggesting problems with functioning in terms of ADR reporting, signal generation and drug safety communication. Conclusions Underreporting of ADRs, weak processes and poor coordination among centres limit functioning of the system. Creating more awareness, involving consumers and pharmaceutical companies in the reporting process, and conducting more training programmes are needed for the proper functioning of pharmacovigilance services in Nepal.

Descriptive analysis of adverse drug reaction reports in children and adolescents from Germany: frequently reported reactions and suspected drugs

BackgroundAdverse drug reactions (ADRs) in the pediatric population may differ in types and frequencies compared to other populations. Respective studies analyzing ADR reports referring to children have already been performed for certain countries. However, differences in drug prescriptions, among others, complicate the transferability of the results from other countries to Germany or were rarely considered. Hence, the first aim of our study was to analyze the drugs and ADRs reported most frequently in ADR reports from Germany referring to children contained in the European ADR database (EudraVigilance). The second aim was to set the number of ADR reports in relation to the number of drug prescriptions. These were provided by the Research Institute for Ambulatory Health Care in Germany.MethodsFor patients aged 0–17 years 20,854 spontaneous ADR reports were received between 01/01/2000–28/2/2019. The drugs and ADRs reported most frequently were identified. Stratified analyses with regard to age, sex and drugs used “off-label” were performed. Reporting rates (number of ADR reports/number of drug prescriptions) were calculated.ResultsMethylphenidate (5.5%), ibuprofen (2.3%), and palivizumab (2.0%) were most frequently reported as suspected. If related to the number of drug prescriptions, the ranking changed (palivizumab, methylphenidate, ibuprofen). Irrespective of the applied drugs, vomiting (5.4%), urticaria (4.6%) and dyspnea (4.2%) were the ADRs reported most frequently. For children aged 0–1 year, drugs for the treatment of nervous system disorders and foetal exposure during pregnancy were most commonly reported. In contrast, methylphenidate ranked first in children older than 6 years and referred 3.5 times more often to males compared to females. If age- and sex-specific exposure was considered, more ADR reports for methylphenidate referred to children 4–6 years and females 13–17 years. Drugs for the treatment of nervous system disorders ranked first among “off-label” ADR reports.ConclusionsOur analysis underlines the importance of putting the number of ADR reports of a drug in context with its prescriptions. Additionally, differences in age- and sex-stratified analysis were observed which may be associated with age- and sex-specific diseases and, thus, drug exposure. The drugs most frequently included in “off-label” ADR reports differed from those most often used according to literature.

Surveillance of adverse drug reactions at an adverse drug reaction monitoring centre in Central India: a 7-year surveillance study

ObjectivesTo analyse and present the occurrence and severity of spontaneous adverse drug reaction (ADR) reports prospectively registered at an ADR monitoring centre (AMC) in Central India.Setting and dataThe survey was...

Adverse Drug Reactions to First-line Anti-tubercular Drugs Based on Individual Case Safety Report in a Single Tertiary Hospital

Background/Aims: Tuberculosis has incidence and mortality rates that are among the highest for all communicable diseases. Adverse drug reactions (ADRs) to anti-tubercular drugs are common, and have a major impact on treatment maintenance and prognosis. It is important to understand the characteristics of ADRs and establish a suitable management plan. Methods: We retrospectively reviewed patients with ADRs during treatment with first-line antitubercular drugs such as isoniazid, rifampicin, ethambutol, and pyrazinamide from 2009 to 2018. Age, sex, and total treatment period, and the onset, severity, seriousness, and system organ class of ADRs, were analyzed to understand the characteristics of first-line anti-tubercular drug-related ADRs. Results: A total of 1,606 of 5,482 patients (29.3%) experienced ADRs after administration of first-line anti-tubercular drugs. The incidence of ADRs related to isoniazid, rifampicin, ethambutol, and pyrazinamide was 22.2%, 21.3%, 24.5%, and 29.6%, respectively. A total of 2,098 ADR reports were made (mean of 1.3 ± 0.6 per patient). The rates of mild, moderate, and severe ADRs were 32.4%, 61.1%, and 6.5%, respectively. There were 127 reports (6.1%) of serious ADRs. Skin and appendage disorders were most frequently reported (27.5%), followed by gastrointestinal disorders (17.5%), and liver and biliary system disorders (13.1%). The total treatment period was longer in patients who experienced ADRs (224.0 ± 3.1 days vs. 247.0 ± 4.7 days, &lt;i&gt;p&lt;/i&gt; = 0.009). Conclusions: The incidence of ADRs to first-line anti-tuberculosis drugs was 29.3%, and 6.5% were severe ADRS. ADRs prolonged the overall treatment duration, indicating the importance of their detection and management.