Suspected Adverse Drug Reactions Research Articles

Long-term hepatobiliary disorder associated with trastuzumab emtansine pharmacovigilance study using the FDA Adverse Event Reporting System database

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11–6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18–2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92–3.68; IC = 1.53, 95%CrI = 1.35–1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.

Associations between Suspected Adverse Drug Reactions of HMG-CoA Reductase Inhibitors and Polypharmacology Using a National Registry Approach

Aims: The aim of this study was to explore the suspected adverse drug reaction (ADR) data of five licensed statins in the UK: atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin. A secondary aim was to determine if there are any associations between the polypharmacological properties of the statins and their associated muscle-related side effects. Methods: The chemical database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL), was used to obtain data on the pharmacological interactions of statins with human proteins. The Medicines and Healthcare Products Regulatory Agency’s (MHRA) Yellow Card scheme was used to obtain reports of suspected ADRs from 2018 to 2022. The OpenPrescribing database was used to obtain the prescribing rates for statistical interpretation. Results: The study found no significant difference between the statins association with suspected ADRs across all organ classes (X2, p > 0.05). Fluvastatin was found to have a higher incidence of ADRs/100,000 Rx across multiple system organ classes. Conclusions: No significant difference was found between the suspected ADR incidence of the statins across all system organ classes.

Recording of suspected adverse drug reaction reporting in veterinary free-text clinical narratives.

To use text mining approaches to identify instances of suspected adverse drug reactions recorded in first opinion veterinary free-text clinical narratives, and to evaluate whether these were also reported to either the Veterinary Medicines Directorate or the relevant Marketing Authorisation holder in order to derive an estimate of the suspected adverse drug reaction (sADR) minimum under-reporting rate. To characterise sADR reports and explore whether particular features are associated with report submission. Two regular expressions were developed to identify mentions of "adverse drug reactions" and "side effects" in the free-text clinical narratives of electronic health records contained within the Small Animal Veterinary Surveillance Network database. Consultations containing a match for the developed regular expressions were manually reviewed for inclusion and further classified to determine the suspected product, seriousness and expectedness of the event, and an indication of whether the event had been reported. The associations between event characteristics and reporting were explored using Fisher's exact tests. A total of 10,565 records were manually reviewed from which 827 sADRs were identified. Approximately 90% of these sADRs were not recorded as reported. Suspected adverse drug reactions that were not considered "expected" were recorded as reported more frequently than "expected" sADRs. However, clinical severity did not appear to impact on whether there was a record of reporting. This is the first estimate of under reporting sADRs based on real world evidence from veterinary clinical records. The under-reporting rate implied by this study highlights that further interventions are required to improve reporting rate within the veterinary profession in order to support pharmacovigilance activities and improve drug safety.

Suspected adverse drug reactions of rivaroxaban reported in the United States food and drug administration adverse event reporting system database: a pharmacovigilance study.

This study aimed to characterize the safety profiles of rivaroxaban-associated suspected adverse events by mining the Food and Drug Administration Adverse Event Reporting System (FAERS). A disproportionality analysis of spontaneously reported suspected adverse drug reactions (ADRs) was conducted. The reports in FAERS from 2014 to 2024 were compiled. Frequentist and Bayesian statistics were both applied to calculate drug-AE combinations in system organ classes and preferred-term levels. Reporting odds ratio (ROR), proportional reporting ratio (PRR), the Medicines and Healthcare products Regulatory Agency (MHRA), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods were analyzed and used to compare the suspected AEs. Of 77,384 ADR reports, 66,705 (86.20%) were serious rivaroxaban AE reports. The most common age group was above 65years. The suspected adverse effects of rivaroxaban emerging for system organ classes (SOCs) primarily included "Gastrointestinal disorders"; "Injury, poisoning, and procedural complications", "Nervous system disorders" and "Vascular disorders". Ranked by EBGM, the top signal strength of suspected AE signals of rivaroxaban under ROR algorithm at the preferred-term (PT) level were "Haemorrhagic arteriovenous malformation" (N = 571, ROR = 756.520, PRR = 754.029, Information Component (IC) = 7.197, Empirical Bayesian Geometric Mean (EBGM) = 146.725), "Gastrointestinal vascular malformation haemorrhagic" (N = 197, ROR = 211.138, PRR = 210.950, IC = 6.614, EBGM = 97.923), and "Diverticulum intestinal haemorrhagic" (N = 722, ROR = 169.898, PRR = 169.210, IC = 6.458, EBGM = 97.920). Moreover, uncommon but significantly suspected AE signals, such as "Coagulation factor X level increased", "Basal ganglia haematoma", and "Proctitis haemorrhagic" were observed. Notably, "Gastrointestinal haemorrhage" (N = 13,436, ROR = 80.477, PRR = 74.460, IC = 5.729, EBGM = 53.042), "Upper gastrointestinal haemorrhage"(N = 2,872, ROR = 73.978, PRR = 72.797, IC = 5.706, EBGM = 52.198) and "Internal haemorrhage" (N = 2,368, ROR = 91.979, PRR = 80.899, IC = 5.813, EBGM = 56.212) exhibited relatively high occurrence rates and signal strengths. From 2014 to 2024, the IC values of rivaroxaban-associated suspected AEs for "Surgical and medical procedures" and "Cardiac disorders" showed an annual increasing trend in the time-span analysis. Based on the various visulization plots, a key discovery is that "Gastrointestinal hemorrhage" emerged as the most significant suspected AE across five algorithms. The exciting finding was that the MGPS algorithm revealed a higher risk of suspected AEs under the "Investigations" category. However, the results of the analyses of the other algorithms at the SOC level were not akin to this. Moreover, the results of signal mining for the three main types of indication populations with adverse drug reactions (ADRs), including Atrial fibrillation, Cerebrovascular accident prophylaxis, and Deep vein thrombosis were shown that "Gastrointestinal haemorrhage", "Epistaxis", "Haematuria", "Rectal haemorrhage", and "Upper gastrointestinal haemorrhage" were detected as the most common and significant signals of suspected adverse events. Rivaroxaban has risks of various suspected adverse reactions while providing therapeutic effects and being used widely. Our pharmacovigilance study may provide valuable hints that practitioners should closely monitor occurrences of "Gastrointestinal disorders", "Injury, poisoning, and procedural complications" and "Nervous system disorders", and other events in clinical applications. Consequently, it remains to persist in monitoring rivaroxaban, assessing the associated risks in the future.

Antimicrobial Use and Adverse Drug Reaction in Newborns with Neonatal Sepsis: A Prospective Observational Study from a Tertiary Care Teaching Hospital

Introduction: Neonatal Sepsis (NS) is a major cause of morbidity and mortality worldwide, especially in developing countries like India. The role of antimicrobials is life-saving in NS. To achieve a good prognosis, early diagnosis and appropriate treatment are required. Data related to the irrational use of antimicrobials in neonates are limited. Aim: To evaluate the drug usage pattern and Adverse Drug Reactions (ADRs) of antimicrobials in NS. Materials and Methods: A prospective observational study was conducted among 350 neonates who were admitted and diagnosed with NS from January to December 2021 in the Neonatal Intensive Care Unit (NICU) of PDU Medical College and Civil Hospital, Rajkot, Gujarat, India. Demographic data such as age, sex, birth weight, and clinical data such as type of delivery, type of sepsis, culture-sensitivity status, and antimicrobials used were recorded. Suspected ADRs were reported in the pharmacovigilance database. Categorical data were analysed in percentage, whereas some clinical data were analysed with mean and median using Microsoft Office Excel-2019. Results: In the present study, 172 (49.15%) male and 178 (50.85%) female neonates were almost equally affected. The mean gestational age and birth weight were 35 ± 3.6 weeks and 2 ± 0.7 kg, respectively. Early-Onset Neonatal Sepsis (EONS) cases were more at 273 (78%) compared to Late-Onset Neonatal Sepsis (LONS). Seventeen different antimicrobials were used. The average number of antimicrobials used per case was 2.9. The Piperacillin Tazobactam was the most commonly used antimicrobial in 173 cases (49.43%) in early-onset sepsis, while Meropenem was used in 40 cases (11.43%) in late-onset sepsis. Coagulase-negative Staphylococcus was the most commonly isolated organism in 15 cases (4.2%), followed by Klebsiella Pneumoniae in 13 cases (3.7%). Twelve out of 17 antimicrobials (70.59%) were not included in the first list of essential medicines for children of India in 2011. Six ADRs were reported in the present study. Conclusion: In all admitted cases of sepsis, empirical therapy was given, but variations from standard recommendations were observed in dose and frequency. A periodic survey of antimicrobial use patterns in NS will be useful in the rational selection of empirical therapy.

Suspected cutaneous adverse drug reactions reported with traditional medicines: analysis of data for United Nations Asia region from WHO VigiBase.

Background: Data on traditional medicine-induced cutaneous adverse drug reactions (ADRs) is very scarce. The current secondary analysis based on the WHO database (VigiBase) of individual case safety reports (ICSRs) focuses on the suspected cutaneous ADRs linked to traditional medicines (TMs). Methods: All the ICSRs reported between 1st January 2016 and 30th June 2021 from the UN Asia region in VigiBase where at least one TM was suspected to cause cutaneous ADRs were included in the study. Data regarding demographic details, suspected drug, adverse reaction as per MedDRA term, the seriousness of the reaction, de-challenge, re-challenge, and clinical outcome for suspected cutaneous ADRs associated with TM were obtained from VigiBase and analyzed for frequency of reported events and suspected medicines. Findings: Total 3,523 ICSRs with 5,761 ADRs related to "skin and subcutaneous tissue disorders" were included in the analysis. Amongst these, 6.8% of ICSRs were reported as serious. Pruritus (29.6%), rash (20.3%), urticaria (18.9%), and hyperhidrosis (3.3%) were commonly reported ADRs. Artemisia argyi H.Lév. and Vaniot. (14.9%), Ginkgo biloba L. (5.1%), Vitis vinifera L. (4%), Vitex agnus-castus L. (3.8%), Silybum marianum (L.), Gaertn (3.5%), and Viscus album L. (2.7%) were some commonly suspected TMs for cutaneous ADRs. There were 46 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported with TMs during the study period. Death was reported in 5 ICSRs. Interpretation: TMs are linked with various cutaneous ADRS ranging from pruritus to toxic epidermal necrolysis which may have serious consequences. TMs listed as suspected offending agents in this analysis, should be kept in mind while dealing with suspected cutaneous ADRs. Clinicians should be more vigilant in detecting and reporting events associated with TMs.

Adverse Drug Reactions of Antiepileptic Drugs in Neurology Department of M.Y.H Indore, India: An Observational, Prospective Study

Background: Epilepsy is the second most common neurological disorder that affects 1 percent of global population. Since antiepileptics have narrow therapeutic index having multiple adverse drug reactions (ADRs) thus have significant safety concerns. The aim of this study was to observe adverse drug reactions due to antiepileptics in neurology department M.Y.H. Indore, India.
 Methods: An observational prospective study was done from November 2021 to January 2022. Patients having history of seizures attending neurology outpatient department at MYH Hospital, who were on antiepileptic drugs were recruited. Suspected adverse drug reaction forms were recorded and their causality assessment was done by Naranjo’s scale.
 Results: Data of total 70 patients were recorded. Males reporting ADRs due to antiepileptics were 67.1% and females 32.8%. Using Naranjo’s scale, we noted 93.3% ADRs as “probable” and 6.7% as “possible”. Common causes of prescribing antiepileptic drugs were known case of epilepsy (78.5%),old case of neurocysticercosis (11.4%),post traumatic(4.3%),gliosis (2.8%) and tuberculoma (2.8%) .Most ADRs were dermatological 76% (rashes),central nervous system (16%) (nocturnal enuresis, poor school performance, dizziness, headache, sleep disturbances, personality changes) ,Gastrointestinal (8%) (gastric irritation, nausea, vomiting and hepatotoxicity) .Most common drug for causing ADRs were sodium valproate(58.5%),carbamazepine(17.14%),phenytoin(14.2%),leviteracetam(7.1%),and lamotrigine(2.8%).
 Conclusion: Our study aimed us to know the incidence and patterns of adverse drug reactions due to antiepileptics in a tertiary care institute of central India. Despite of recent advances and novel therapies used for the treatment of epilepsy, conventional drugs like sodium valproate, phenytoin and carbamazepine still are the first choice for the management and treatment of seizures and their ADRs are very common.

Metabolic adverse drug reactions in geriatric patients in Odisha

Background: Geriatric patients are at a greater risk of developing adverse drug reaction (ADR) because of changed metabolic activity and renal status associated with aging. As most of the elderly patients suffer from multiple chronic diseases (Diabetes, Hypertension, Arthritis, constipation, peptic ulcer disease, etc.), they are under polypharmacy and the risk of ADRs is exacerbated by multiple medications. Metabolic ADRs include weight gain, hypoglycemia, hyponatremia, hypokalemia, and the endocrinal abnormality are the frequent cause of hospital admission in geriatric patients. Most metabolic ADRs due to drugs are treatable. There are few such studies conducted in India regarding metabolic ADR in geriatric patients. Hence, this study aims to evaluate the metabolic ADRs encountered in geriatric patients with the following objectives in Odisha. Aim and Objectives: The prevalence and spectrum of metabolic ADRs in geriatric population were studied. The causality assessment, severity assessment, and preventability were done using standard scales. Materials and Method: This was a prospective and observational study conducted from September 2016 to September 2018 in Department of Pharmacology in collaboration with Department of Geriatric Medicine and Department of Medicine of SCB Medical College and Hospital. All geriatric patients (≥60 years) with ADR, reporting to the above departments, were included in the study. The detailed information of type of ADRs and its characteristics was filled up in Suspected ADR Reporting Form designed by Indian pharmacopeia commission version 1.3. The incidence and spectrum of metabolic ADRs were observed. Their causality, severity, and preventability were evaluated by the WHO-UMC System, Hartwig’s Severity Scale, and Schumock Thornton Preventability Scale, respectively. Result: A total of 236 ADRs were reported in 2 years, out of which 28.8% were metabolic ADRs. Metabolic ADRs were more reported in young old patients and often encountered ADR was hypoglycemia 73.5% due to use of oral anti diabetics. About 29% of the metabolic ADRs had a causal relation of probable association. About 94.2% were moderate in severity and 89.7% metabolic ADRs could be probably preventable. Conclusion: There was a probable causal association of metabolic ADR with the drug used and they were moderate verity. The metabolic ADRs found in our study can be preventable with appropriate means.

Impact of the Role of the Clinical Pharmacist on the Underreporting of Adverse Drug Reactions at a Peruvian hospital.

Background: The clinical pharmacists play a key role in the Pharmacovigilance System. They are integrated to the health team performing pharmacotherapeutic follow-up (PF), drug information, at third level care hospital. The objective of this study was to assess the impact of the clinical pharmacists' role in increasing the reporting of suspected adverse drug reactions (SADRs) after including in-service training (IST) in their role, as well as to characterize the reported ADRs. Methods: A longitudinal study was performed, reports of SADRs received through medical interconsultations were evaluated, before and after applying IST, in 2 periods: January 2017 to June 2018 and July 2018 to December 2019. Results: Interconsultations after IST were increased by 168,4%; of these, 75 were ADRs reported to the Dirección General de Medicamentos, Insumos y Drogas (DIGEMID). Internal Medicine and Pneumology services reported more SADR in both periods. There was significant statistical difference in ADRs' causality (P = .001) and type (P = .009). Severe ADRs highlighted after IST (4 vs 12). The most affected organ and system in both periods was skin and appendages. Conclusion: The reporting of SADRs augmented, reflected in an increase in medical interconsultations as a modality of SADR notification, after including IST to the role of the clinical pharmacist, allowing the development of convenient FP, which led to the evaluation of SARs. A higher number of serious ADRs were reported.

Vaccine Vigilance System: Considerations on the Effectiveness of Vigilance Data Use in COVID-19 Vaccination.

(1) Background: The safety of medicines has been receiving increased attention to ensure that the risks of taking medicines do not outweigh the benefits. This is the reason why, over several decades, the pharmacovigilance system has been developed. The post-authorization pharmacovigilance system is based on reports from healthcare professionals and patients on observed adverse reactions. The reports are collected in databases and progressively evaluated. However, there are emerging concerns about the effectiveness of the established passive pharmacovigilance system in accelerating circumstances, such as the COVID-19 pandemic, when billions of doses of new vaccines were administered without a long history of use. Currently, health professionals receive fragmented new information on the safety of medicines from competent authorities after a lengthy evaluation process. Simultaneously, in the context of accelerated mass vaccination, health professionals need to have access to operational information-at least on organ systems at higher risk. Therefore, the aim of this study was to perform a primary data analysis of publicly available data on suspected COVID-19 vaccine-related adverse reactions in Europe, in order to identify the predominant groups of reported medical conditions after vaccination and their association with vaccine groups, as well as to evaluate the data accessibility on specific syndromes. (2) Methods: To achieve the objectives, the data publicly available in the EudraVigilance European Database for Suspected Adverse Drug Reaction Reports were analyzed. The following tasks were defined to: (1) Identify the predominant groups of medical conditions mentioned in adverse reaction reports; (2) determine the relative frequency of reports within vaccine groups; (3) assess the feasibility of obtaining information on a possibly associated syndrome-myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). (3) Results: The data obtained demonstrate that the predominant medical conditions induced after vaccination are relevant to the following categories: (1) "General disorders and administration site conditions", (2) "nervous system disorders", and (3) "musculoskeletal and connective tissue disorders". There are more reports for mRNA vaccines, but the relative frequency of reports per dose administered, is lower for this group of vaccines. Information on ME/CFS was not available, but reports of "chronic fatigue syndrome" are included in the database and accessible for primary analysis. (4) Conclusions: The information obtained on the predominantly reported medical conditions and the relevant vaccine groups may be useful for health professionals, patients, researchers, and medicine manufacturers. Policymakers could benefit from reflecting on the design of an active pharmacovigilance model, making full use of modern information technologies, including big data analysis of social media and networks for the detection of primary signals and building an early warning system.

Suspected adverse drug reactions of the type 2 antidiabetic drug class dipeptidyl-peptidase IV inhibitors (DPP4i): Can polypharmacology help explain?

To interpret the relationship between the polypharmacology of dipeptidyl-peptidase IV inhibitors (DPP4i) and their suspected adverse drug reaction (ADR) profiles using a national registry. A retrospective investigation into the suspected ADR profile of four licensed DPP4i in the United Kingdom using the National MHRA Yellow Card Scheme and OpenPrescribing databases. Experimental data from the ChEMBL database alongside physiochemical (PC) and pharmacokinetic (PK) profiles were extracted and interpreted. DPP4i show limited polypharmacology alongside low suspected ADR rates. We found a minimal statistical difference between the unique ADR profiles ascribed to the DPP4i except for total ADRs (χ2 ; p< .05). Alogliptin consistently showed the highest suspected ADR rate per 1 000 000 items prescribed. Saxagliptin showed the lowest suspected ADR rate across all organ classes but did not reach statistical difference (χ2 ; p> .05). We confirmed the Phase III clinical trial data that showed gastrointestinal and skin reactions are the most reported ADRs across the DPP4i class and postulated underlying mechanisms for this based on possible drug interactions. The main pharmacological mechanism behind the ADRs is attributed to interactions with DPP4 activity and/or structure homolog (DASH) proteins which augment the immune-inflammatory modulation of DPP4.

Impact of suspected adverse drug reactions on mortality and length of hospital stay in the hospitalised patients: a meta-analysis.

To estimate the risk of mortality and length of stay in hospitalised patients who have experienced suspected adverse drug reactions (ADRs) as compared to patients who did not experience suspected ADRs. A systematic literature search was conducted on databases for observational and randomised controlled studies conducted in any inpatient setting that reported deaths and/or length of hospital stay in patients who had suspected ADRs and did not have suspected ADRs during hospitalisation. PRISMA guidelines were strictly followed during the review. The methodological quality of included studies was assessed using a tool designed by Smyth et al. for the studies of adverse drug reactions. The meta-analytic summary of all-cause mortality was estimated using odds ratio-OR (95% CI) and length of stay using mean difference-MD (95% CI). Both outcomes were pooled using a random effect model (DerSimonian and Laird method). Subgroup and meta-regression were performed based on study variables: study design, age group, study ward, study region, types of suspected ADRs (ADRAd-suspected ADRs that lead to hospitalisation and ADRIn-suspected ADRs that occur following hospitalisation), study duration, sample size and study period. The statistical analysis was conducted through the 'Review manager software version 5.4.1 and JASP (Version 0.14.1)'. After screening 475 relevant articles, 55 studies were included in this meta-analysis. Patients having suspected ADRs had reported significantly higher odds of all-cause mortality [OR: 1.50 (95% CI: 1.21-1.86; I2 = 100%) than those patients who did not have suspected ADRs during hospitalisation. Study wards, types of suspected ADRs and sample size were observed as significant predictors of all-cause mortality (p < 0.05). Patients having suspected ADRs had reported significantly higher mean difference in hospital stay [MD: 3.98 (95% CI: 2.91, 5.05; I2 = 99%) than those patients who did not have suspected ADRs during hospitalisation. Types of suspected ADRs and study periods were observed as significant predictors of length of stay (p < 0.05). Suspected ADRs significantly increase the risk of mortality and length of stay in hospitalised patients. CRD42020176320.

Adverse Drug Reactions in Breastfed Infants: A Cross-Sectional Study of Lactating Mothers.

Background: Breastfeeding-related adverse drug reactions (ADRs) are thought to be uncommon as reported cases are globally low. The nonspecific nature of these reactions and a lack of awareness and difficulty in identification of ADRs by mothers and clinicians may result in these ADRs being underreported. Aims: This study hypothesized that breastfeeding-related infant ADRs are more frequent than reported. As a first-hand account of breastfeeding mothers, this study aimed to evaluate the impact of the perceived ADRs on the continuation of breastfeeding and maternal treatment. Methods: Women currently breastfeeding or having breastfed in the last 12 months were invited to complete an online survey. The survey comprised 42 questions in 5 sections to obtain data from breastfeeding mothers, including their use of medicines during lactation, perceptions of infant adverse reactions attributable to maternal medication use and its potential impact on breastfeeding. Results: This online survey was completed by 339 women, 42% of whom reported taking at least one medication during breastfeeding. ADRs were reported in 23 infants where a possible or probable causal relationship indicated by a Naranjo score of 1-8 was established in 16 (11.3%). Antibiotics (n = 12) and opioids (n = 2), including tramadol and oxycodone were identified as the most common adverse reaction-causing drugs. The average age of infants at the time of the perceived ADR was 25.6 days (95% confidence interval; 4-85 days; median age 17.5 days). Conclusion: Suspected ADR reporting in this study was significantly greater than those reported to the regulatory body, the Australian Therapeutics Goods Administration, which shows that common breastfeeding-related infant ADRs are underreported.

Pharmacovigilance reporting during seasonal malaria chemoprevention campaign: Findings from northern Nigeria

BackgroundSeasonal malaria chemoprevention (SMC) campaign is known to reduce malaria-related morbidity and mortality among children aged 3 -59 months in the Sahel regions of Africa. However, the success of the intervention may be adversely affected by the absence of a robust pharmacovigilance system to monitor safety. This paper aims to describe our pharmacovigilance reporting experience during the campaigns conducted across seven states in Nigeria in 2020. MethodsThe SMC campaigns were held over four cycles from July to November 2020, with nearly 12 million eligible children reached by trained community drug distributors. Suspected adverse drug reactions were reported routinely through the national pharmacovigilance (PV) system. Completed PV forms submitted to the National Agency for Food, Drugs Administration and Control were retrieved and analyzed. ResultsThe adverse drug reaction (ADR) reporting across the seven states was low, with no ADR reports from five states. The ADRs reported included abdominal pain, weakness, diarrhea, fever, rash, and vomiting. Vomiting was the most reported ADR, accounting for almost half (28/57) of all reported cases. Children aged 12–59 months accounted for most (∼86%, 49/57) of the ADR reports, with over 70% (40/57) of these reports completed by community health extension workers. The system organ classification of ADRs showed that the gastrointestinal system was mainly affected (65%, 37/57). ConclusionOur experience suggests gaps with the pharmacovigilance surveillance system, highlighting the need to consider an active surveillance system, address behavioural factors, and explore the use of a digital reporting system.

Angiotensin II receptor blockers (ARBs) and manufacturing contamination: A retrospective National Register Study into suspected associated adverse drug reactions.

The aim of this study was to determine if any suspected adverse drug reactions (ADRs) observed with the use of angiotensin II receptor blockers (ARBs) could be linked to either (a) their unique respective physicochemical and pharmacological profiles and (b) the recently disclosed suspected carcinogenic manufacturing contaminants found in certain sartan drug class batches. The pharmacology profiles of ARBs were data-mined from the Chemical Database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL). Suspected ADR data (from 01/2016-10/2022, inclusive) and prescribing rates of ARBs over a 5-year prescribing window (from 09/2016 to 08/2021, inclusive) were obtained via analysis of the United Kingdom Medicines and Healthcare products Regulatory Authority (MHRA) Yellow Card drug analysis profile and Open prescribing databases, respectively. The overall suspected ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied were found to be different between the sartan drug class members (chi-squared test, P < .05). There is a greater relative rate of reports for valsartan across all investigated organ classes of ADRs, than other ARBs, despite valsartan's more limited pharmacological profile and similar physicochemical properties to other sartans. The disparity in ADR reporting rates with valsartan vs other ARBs could be due to the dissimilarity in formulation excipients, patient factors and publicity surrounding batch contaminations, amongst others. Cancer-related ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied are not statistically significant (chi-squared test, P > .05) based on the datasets used over the 5-year period. No connection between ARB pharmacology and their suspected ADRs could be found. No conclusion between sartan batch contaminations and increased suspected cancer-related ADRs was found.

Evaluation of potential drug-drug interactions and adverse drug reactions among chronic kidney disease patients: An experience from United Arab Emirates

Purpose: To determine the prevalence and assessing nature of potential drug-drug interactions (pDDIs) and adverse drug reactions (ADRs) among chronic kidney disease (CKD) patients.Methods: This was a prospective observational study involving adult CKD patients. Occurrence of pDDIs was evaluated using Micromedex database 2.0. Suspected ADRs during the study period were documented and assessed.Results: Overall prevalence of pDDIs was found to be 85.3 %. A total of 811 pDDIs with 225 different pairs of interacting drugs were identified. Majority of the patients had ≥ 3 pDDIs regardless of type of severity. Thirty-five ADRs were identified in 25 CKD patients. Hyperkalemia was the most-commonly suspected ADR. Logistic regression analysis revealed that age (OR: 1.04, 95 % CI: 1.01 - 107), length of hospital stay (OR: 1.15, 95 % CI: 1.0 - 1.32), presence of comorbidity like diabetes (OR: 9.1, 95 % CI: 3.2 - 25.3) and number of drugs prescribed (OR: 6.88, 95 % CI: 1.5 - 30.0) were positively correlated with occurrence of pDDIs. Length of hospital stay (OR: 1.05, 95 % CI: 0.99 - 1.06) and number of drugs (OR: 0.16, 95 % CI 0.03 - 0.84) were identified as independent predictors of occurrence of ADRs.Conclusion: Prevalence of pDDIs was high in the study population. A majority of the pDDIs were of major severity type, fair documentation grade, and of unspecified onset. A majority of suspected ADRs were probably of moderate in severity and not preventable type.

Corrigendum: Suspected Adverse Drug Reactions in Pediatric Cancer Patients in China: An Analysis of Henan Province Spontaneous Reporting System Database

[This corrects the article DOI: 10.3389/fonc.2021.807171.].

Estimation of the Under-Reporting of Suspected Serious Adverse Drug Reactions in Japan Using An Interrupted Time Series Analysis.

Spontaneous reports of adverse drug reactions (ADRs) are an essential data source for pharmacovigilance activities. However, spontaneous reporting is affected by under-reporting, which can lead to bias in statistical signal detection and failure to identify potential drug-associated risks. This study aimed to estimate the degree of under-reporting of suspected serious ADRs (sADRs) in spontaneous reports in Japan. The new active ingredients approved in Japan between 2010 and 2016 for which all-case surveillance was conducted were selected for this study. Data of sADR reports were extracted from the Japanese Adverse Drug Event Report database (JADER). An interrupted time series (ITS) analysis was conducted to compare the number of sADR reports (sADR cases) obtained in the all-case surveillance period with that obtained in the spontaneous report period (after all-case surveillance had been completed). The ITS analysis of all sADR cases revealed that 24 (68.6%) of the 35 investigated drugs showed a statistically significant decrease in the intercept (level) in the spontaneous reporting period compared with that in the all-case surveillance period. The median of the reduction rate of the level was 60.1%. The number of drugs with a statistically significant decrease in the level of cases with sADRs in the Important Medical Event list and in that leading to death was 19/35(54.3%) and 6/35 (17.1%), respectively. This study demonstrated the existence of sADR under-reporting in spontaneous reports in Japan quantitatively. Meanwhile, it was suggested that information on sADRs was reported appropriately according to their level of severity.

Adverse drug reaction monitoring through active surveillance in the inpatients of general medicine ward of a tertiary care hospital

Objective: To monitor and analyze the adverse drug reactions (ADRs) by active surveillance in the inpatients of the department of general medicine of a tertiary care hospital. Materials and Methods: This was a cross-sectional study on the patients aged 18–70 years conducted for a period of 6 months. Patients' medical history, any new symptoms after commencing treatment, and their details were obtained after direct interviews. The case report forms were also reviewed. Suspected ADRs were documented in consultation with the attending physicians. Descriptive statistics was used to analyze the data for the occurrence, relatedness to the drug, seriousness, preventability, severity, intensity, and predictability of ADRs. Results: Fifty-three women and 47 men consented to participate, the majority of whom were between the ages of 20 and 30 years. Thirty suspected ADRs were detected in 24 out of 100 patients. The most common indications for which the drugs were prescribed were depression, psychosis, bipolar disorder, atopic dermatitis, and cervical spondylitis. Of the 30 ADRs, 28 were probably related, and 2 were possibly due to the prescribed drugs. Seven ADRs were serious in nature. Four ADRs were definitely preventable, seven were probably preventable, and nineteen were not preventable. Maximum ADRs were caused by immunosuppressants including steroids. Dermatological reactions were the most common manifestations of ADRs followed by that of central nervous system. There were four rare ADRs, namely, escitalopram-induced duodenitis, phenobarbitone-induced pancytopenia, quetiapine-induced thrombocytopenia, and aripiprazole-induced ocular gyrus syndrome. ADRs were mostly mild to moderate in intensity. Conclusion: Monitoring the ADRs through active surveillance is helpful to get a detailed information and to detect rare ADRs.

Pharmacovigilance in Geriatric Patient- A Prospective Observational Study Done in a Tertiary Care Hospital of Odisha, India

Introduction: Geriatrics is a speciality that focuses on healthcare of elderly people. Geriatric population is defined as people above 60 years of age. Geriatric population constitute 8.14% of total population in India. They have diverse physiological and pathological profiles which have an impact on the pharmacokinetic and pharmacodynamic properties of the administered drug. Very often they are under polypharmacy due to multisystem involvement and thereby subjected to numerous drug interactions and Adverse Drug Reactions (ADRs). There are few studies conducted in India regarding ADRs in Geriatric Patients and none in Odisha, India. Aim: Pharmacovigilance study in Geriatric patients was taken up in a tertiary care hospital to assess the spectrum, cause, severity and preventability of ADRs. Materials and Methods: This prospective, observational study was conducted in Department of Pharmacology in collaboration with Departments of Geriatric Medicine, Medicine and Skin and Venereal Disease (VD) of SCB Medical College and Hospital, Cuttack, Odisha, India. All geriatric patients (aged ≥60 years) diagnosed with ADR, from September 2016 to September 2018, were included. The detailed information of type of ADR and its characteristics were filled up in Suspected ADR Reporting Form. The prevalence and profile of ADRs in geriatric patients were studied. Their causality, severity and preventability were assessed by World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) System, Modified Hartwig’s Severity Scale and Schumock and Thornton Preventability Scale, respectively. Results: A total of 236 geriatric ADRs were reported in two years, out of which, the most common ADRs were cutaneous 100 (42.4%), followed by metabolic 68 (28.8%) and Gastrointestional (GI) involvement 26 (11%). Out of the geriatric ADRs, 128 (54.2%) ADRs were possible, 65% were moderate in intensity and 70.3% ADRs were probably preventable. Conclusion: Cutaneous and metabolic ADRs were most common in geriatric patients in present study. Majority of ADRs were possibly caused due to the drug used, were of moderate intensity and probably preventable.