Adverse Drug Events Research Articles

Unveiling the association between fluoroquinolones and aortic diseases using real-world database analysis and pharmacological experiments

Fluoroquinolones, which are widely used antibiotics, have been linked to aortic disease, which prompted an FDA warning in 2018. Recent reports have challenged the perception that fluoroquinolones pose a significant risk for vascular diseases. This study aimed to investigate whether fluoroquinolones increase the risk of aortic diseases by focusing on the onset of aortic dissection. Levofloxacin (LVFX), a fluoroquinolone, was studied in vitro using cultured vascular cells and in vivo using a mouse model prone to aortic dissection. Risk of adverse drug events was analyzed using VigiBase, a global safety database, and a retrospective cohort analysis was conducted using the JMDC Claims database. LVFX resulted in endothelial cell injury and increased matrix metalloproteinases in vitro. However, in vivo studies showed no significant effect on elastin degradation or aortic dissection incidence. The effect of LVFX on endothelial injury was altered during the onset of dissection, exacerbating injury before onset but inhibiting it afterward. Safety database analysis showed no significant risk signals for aortic dissection associated with fluoroquinolones, which was supported by findings in the receipt database. Inconsistencies were observed in the in vitro and in vivo actions of fluoroquinolones and differences in their effects on aortic dissection and aneurysms. Despite cytotoxicity, the risk of aortic dissection was not significantly increased in clinical scenarios. Based on our findings, concerns regarding aortic diseases do not justify discontinuation of fluoroquinolone use. Further studies are needed to elucidate the conflicting actions of fluoroquinolones, taking into account background pathophysiology such as infection and inflammation.

Free Text Analysis: Identification of adverse drug events in clinical notes

ObjectiveTo explore the prevalence of adverse drug events (ADE) leading to drug changes using Artificial Intelligence (AI) based free text analysis of primary care encounter notes . ApproachWe used electronic medical record l encounter notes linked to population-based drug dispensation records. Dispensation records were used to identify drug switching to another agent in the same therapeutic class, which could suggest an undesirable side-effect requiring discontinuation of the drug. We annotated clinical notes by identifying ADEs after retrieving the last encounter note written for that patient on or before the identified date. We ran different AI models, including BERT and Large Language Models (LLMs), to identify ADEs. ResultsWe annotated 1085 notes with 362 ADEs. These were used to train BERT models (precision or PPV: 0.584 ) and prompt-based LLM (0.563) but with improved sensitivity (0.725) and specificity (0.739) . ConclusionsIdentifying ADEs requires deep medical knowledge and simple Natural Language Processing models trying to identify ADEs only on the basis of language of encounter notes was not successful based on the BERT model performance. Prompt based models have deep knowledge but were trained with the objective of producing grammatically correct, coherent sentences, not with the medical knowledge required. LLMs also require significant computational power. ImplicationsWhile AI does have significant potential to advance our capacity for complex analytic tasks the current LLMs are not yet able to adequately identify ADEs in a corpus of electronic clinical notes.

The High Prevalence and Complexity of Over-the-Counter Medication Misuse in Older Adults.

Older adults (≥65 years) are the largest consumers of over-the-counter (OTC) medications and exceptionally vulnerable to the risks of these medications, including adverse drug events (ADEs). However, little is known about how older adults select and use OTCs. This is the first multisite study designed to prospectively quantify the type and intended use of OTCs selected by older adults in community pharmacies where products are purchased. Older adults (n = 144) were recruited from 10 community pharmacies from a Midwestern health system. Participants were given hypothetical symptoms and asked to select one or more OTCs for self-treatment. They were asked to report how they would use the products at symptom onset and when symptoms persisted or worsened. They also reported their current medication list and health conditions. Participants' OTC selections were evaluated for 4 types of misuse: drug-age, drug-drug, drug-disease, and drug-label. Of the 144 participants, 114 (79%) demonstrated at least one type of misuse when describing how they would use their OTC selections at symptom onset. Drug-drug and drug-label misuse had the highest prevalence. Overall, 26 (18%) and 28 (19%) participants showed only drug-drug or drug-label misuse, respectively. Notably, 55 (38%) of participants demonstrated misuse in 2 or more misuse categories. Misuse potential was exacerbated when participants described treating persistent or worsening symptoms. The results highlight the high prevalence and complexity of OTC misuse in older adults and the need for additional work to improve OTC safety.

Search for drug‐induced acute kidney injury and ethical Kampo formulas utilizing the Japanese adverse drug event report database

Search for drug‐induced acute kidney injury and ethical Kampo formulas utilizing the Japanese adverse drug event report database

Efficiency of computerized clinical decision support systems involving anticoagulants: A flashmob study in Dutch hospital pharmacies.

Computerized decision support systems (CDSSs) aim to prevent adverse drug events. However, these systems generate an overload of alerts that are not always clinically relevant. Anticoagulants are frequently involved in these alerts. The aim of this study was to investigate the efficiency of CDSS alerts on anticoagulants in Dutch hospital pharmacies. A multicentre, single-day, cross-sectional study was conducted using a flashmob design in Dutch hospital pharmacies, which have CDSSs that operate on both a national medication surveillance database and on self-developed clinical rules. Hospital pharmacists and pharmacy technicians collected data on the number and type of alerts and time needed for assessing these alerts. The primary outcome was the CDSS efficiency on anticoagulants, defined as the percentage of alerts on anticoagulants that led to an intervention. Secondary outcomes where among other CDSSs efficiency related to any medications and the time expenditure. Descriptive data-analysis was used. Of the 69 hospital pharmacies invited, 42 (61%) participated. The efficiency of CDSS alerts on anticoagulants was 4.0% (interquartile range [IQR] 14.0%) for the national medication surveillance database alerts and 14.3% (IQR 40.0%) for alerts from clinical rules. For any medication, the efficiency was lower: 1.8% (IQR 7.5%) and 13.4% (IQR 21.5%) respectively. The median time for assessing the relevance of all alerts was 2 (IQR 1:21) h/day for pharmacists and 6 (IQR 5:01) h/day for pharmacy technicians. CDSS efficiency is generally low, both for anticoagulants and any medication, while the time investment is high. Optimization of CDSSs is needed.

Analysis of anticholinergic drugs associated with aspiration pneumonia using the Japanese adverse drug event report database: Supplementary insights from a scoping review

BackgroundJapan's super-aged society presents significant challenges, particularly with regard to managing aspiration pneumonia among older adults. We aimed to investigate the link between anticholinergic drug use and the incidence of aspiration pneumonia, primarily utilizing data from the Japanese Adverse Drug Event Report (JADER) database. MethodsThe primarily analysis included JADER data from the first quarter of 2004 through the third quarter of 2023, focusing on 2367 cases of aspiration pneumonia in individuals aged ≥60 years. The study examined the association of aspiration pneumonia with 49 drugs listed in the Anticholinergic Risk Scale, using the Reporting Odds Ratio for signal detection. A scoping review incorporating findings from MEDLINE and the Cochrane Library was conducted to validate these associations. ResultsThe primary analysis identified an increased risk of aspiration pneumonia associated with specific drugs, including clozapine, haloperidol, risperidone, quetiapine, and olanzapine. A total of 20 drugs were significantly associated with an increased risk of aspiration pneumonia. Our results emphasize the importance of considering the dopamine-blocking effects of these drugs, particularly in at-risk populations, such as older adults, and those with conditions, such as schizophrenia or Parkinson's disease. ConclusionsThe study highlights the importance of careful monitoring of anticholinergic drugs with potent dopamine-blocking effects, such as clozapine, haloperidol, risperidone, quetiapine, and olanzapine, to reduce the risk of aspiration pneumonia. Future research should include observational and interventional studies to further investigate these findings. Ethics and disseminationAs this study utilized pre-existing anonymized information, approval from an ethics committee was not required.

Overdose Detection Among High-Risk Opioid Users Via a Wearable Chest Sensor in a Supervised Injecting Facility: Protocol for an Observational Study.

Opioid overdose is a global health crisis, affecting over 27 million individuals worldwide, with more than 100,000 drug overdose deaths in the United States in 2022-2023. This protocol outlines the development of the PneumoWave chest biosensor, a wearable device being designed to detect respiratory depression in real time through chest motion measurement, intending to enhance early intervention and thereby reduce fatalities. The study aims to (1) differentiate opioid-induced respiratory depression (OIRD) from nonfatal opioid use patterns to develop and refine an overdose detection algorithm and (2) examine participants' acceptability of the chest biosensor. The study adopts an observational design over a 6-month period. The biosensor, a small device, will be worn by consenting participants during injecting events to capture chest motion data. Safe injecting facilities (SIF) in Melbourne, Victoria (site 1), and Sydney, New South Wales (site 2), which are legally sanctioned spaces where individuals can use preobtained illicit drugs under medical supervision. Each site is anticipated to recruit up to 100 participants who inject opioids and attend the SIF. Participants will wear the biosensor during supervised injecting events at both sites. The biosensor will attempt to capture data on an anticipated 40 adverse drug events. The biosensor's ability to detect OIRD will be compared to the staff-identified events that use standard protocols for managing overdoses. Measurements will include (1) chest wall movement measured by the biosensor, securely streamed to a cloud, and analyzed to refine an overdose detection algorithm and (2) acute events or potential overdose identified by site staff. Acceptability will be measured by a feedback questionnaire as many times as the participant is willing to throughout the study. As of April 2024, a total of 47 participants have been enrolled and data from 1145 injecting events have already been collected, including 10 overdose events. This consists of 17 females and 30 males with an average age of 45 years. Data analysis is ongoing. This protocol establishes a foundation for advancing wearable technology in opioid overdose prevention within SIFs. The study will provide chest wall movement data and associated overdose data that will be used to train an algorithm that allows the biosensor to detect an overdose. The study will contribute crucial insights into OIRD, emphasizing the biosensor's potential step forward in real-time intervention strategies. DERR1-10.2196/57367.

Rapid de-escalation of anti-MRSA therapy guided by S. aureus nares screening for patients with pneumonia: protocol of a randomized controlled trial (SNAP study).

The current Infectious Disease Society of America and American Thoracic Society (IDSA/ATS) guidelines recommend linezolid or vancomycin as an empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospitalized patients with specific risk factors,. A nasal PCR-assay for MRSA, with its high negative predictive value, can guide a rapid antibiotic de-escalation avoiding unnecessary anti-MRSA treatment. The indiscriminate use of these drugs has contributed to the emergence of resistant S. aureus strains leading to adverse effects without any survival benefit, increasing hospital stays and associated costs. Aim of the study is the use of this diagnostic tool to reduce empirical anti-MRSA treatment duration in pneumonia, shortening antimicrobial therapy days while measuring in-hospital mortality, length of stay and adverse drug event incidence. It is a prospective, randomized single-center controlled trial planned to be conducted in the Azienda Consorziale Policlinico di Bari. The research project will have a duration of 12 months following the approval of the Ethical Committee of the University of Bari. The minimum sample size is 38 patients per group, for a total of 76 subjects, calculated assuming a standard deviation of 10, a power of 90%, a type I error of 5% and a 10% drop-out rate. We will enroll eligible patients ensuring their evidence-based management according to guidelines, we will perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative. For both arms, follow-up visits will be on day 2, 5, 7, 14, and 28 relatives to the enrollment visit (day 0). Data will be collected on the clinical course of pneumonia and laboratory tests. Our study will provide evidence on the duration (in days) of the antibiotic intake as a primary outcome of the study. Secondary outcome measures include in-hospital mortality, the length of stay and days of mechanical ventilation (in VAP), and the incidence of adverse events related to the administration of the therapy. https://classic.clinicaltrials.gov/ct2/show/NCT06238297, identifier NCT06238297.

Effectiveness of a Mobile App (Meds@HOME) to Improve Medication Safety for Children With Medical Complexity: Protocol for a Randomized Controlled Trial.

This study will pilot-test the mobile app, Medication Safety @HOME-Meds@HOME intervention to improve medication administration accuracy, reduce preventable adverse drug events, and ultimately improve chronic care management for children with medical complexity (CMC). The Meds@HOME app was co-designed with CMC families, secondary caregivers (SCGs), and health professionals to support medication management for primary caregivers (PCGs) and SCGs of CMC. We hypothesize that Meds@HOME will improve caregivers' medication administration accuracy, reduce preventable adverse drug events, and ultimately improve chronic care management. This study aims to evaluate the effectiveness of Meds@HOME on medication administration accuracy for PCGs and SCGs. This study will recruit up to 152 PCGs and 304 SCGs of CMC who are prescribed at least 1 scheduled high-risk medication and receive care at the University of Wisconsin American Family Children's Hospital. PCGs will be randomly assigned, for the 6-month trial, to either the control group (not trialing Meds@HOME) or the intervention group (trialing Meds@HOME) using 1:1 ratio. The Meds@HOME app allows caregivers to create a child profile, store medication and care instructions, and receive reminders for upcoming and overdue care routines and medication refills. Surveys completed both at the start and end of the trial measure demographics, medication delivery knowledge, confidence in the CMC's caregiving network, and comfort with medical information. Univariate and multivariate generalized estimation equations will be used for primary statistical analysis. The primary outcome is the PCG's rate of medication administration accuracy measured as correct identification of each of the following for a randomly selected high-risk medication: indication, formulation, dose, frequency, and route at baseline and after 6 months. Secondary outcomes include SCG medication administration accuracy (indication, formulation, dose, frequency, and route), count of University of Wisconsin hospital and emergency department encounters, PCG-reported medication adherence, count of deaths, and PCG medication confidence and understanding. Recruitment for this study began on November 29, 2023. As of May 15, 2024, we have enrolled 94/152 (62%) PCGs. We expect recruitment to end by August 1, 2024, and the final participant will complete the study by January 28, 2025, at which point we will start analyzing the complete responses. We expect publication of results at the end of 2025. The Meds@HOME mobile app provides a promising strategy for improving PCG medication safety for CMC who take high-risk medications. In addition, this protocol highlights novel procedures for recruiting SCGs of CMC. In the future, this app could be used more broadly across diverse caregiving networks to navigate complex medication routines and promote medication safety. ClinicalTrials.gov NCT05816590; https://clinicaltrials.gov/study/NCT05816590. DERR1-10.2196/60621.

A real-world pharmacovigilance study of esketamine nasal spray.

Mining and updating the post-marketing safety signals of esketamine nasal spray for better identification of adverse drug event (ADE) signals and medication monitoring during clinical use to ensure patient medication safety. Downloading data from the US Food and Drug Administration Adverse Event Reporting System from Q1 2019 to Q2 2023, the reporting odds ratio, proportional reporting ratio, Multi-item Gamma Poisson Shrinker, and Bayesian Confidence Propagation Neural Network methods of the disproportionality method were used to mine and analyze ADEs, and finally to screen for signals of ADEs with esketamine nasal spray as the primary suspected drug. The Preferred Terminology of the Medical Dictionary of Regulatory Activities (version 26.0) was used to standardize the description of ADEs and to attribute ADEs to the System Organ Classification. A total of 5132 ADEs reports of esketamine nasal spray as the primary suspected drug were obtained from the Food and Drug Administration Adverse Event Reporting System. The most frequently observed ADEs are dissociation, sedation, and hypertension, while some new rare signals have been detected, such as interstitial cystitis, substance abuse, and drug diversion. The present study identified significant new ADEs signals for esketamine nasal spray, which may provide a source for healthcare professionals to assess patients' symptoms and risk identification.

Safety assessment of basiliximab using real-world adverse event data from the FDA Adverse Event Reporting System Database: A retrospective observational study.

This study analyzed adverse drug events (ADEs) associated with basiliximab, sourced from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, spanning the first quarter of 2004 to the fourth quarter of 2023. We collected ADE data for basiliximab from 2004 Q1 to 2023 Q4. After standardization, we employed several signal quantification methods for analysis, such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propensity for Neural Networks (BCPNN), and empirical bayes geometric mean (EBGM). In this analysis of 1520 ADEs reports citing basiliximab as the primary suspect, we identified 295 preferred terms across 24 system organ classifications (SOCs). The 3 most prevalent SOCs were investigated (n = 1403, ROR 2.84, PRR 2.54, IC 1.34, EBGM 2.54), infections and infestations (n = 1198, ROR 2.85, PRR 2.59, IC 1.37, EBGM 2.59), and renal and urinary disorders (n = 903, ROR 6.01, PRR 5.48, IC 2.45, EBGM 5.47). Increased blood creatinine and pyrexia were the most frequently reported adverse events (AEs) associated with basiliximab, and cytomegalovirus infection also demonstrated significant signal intensity. Notably, this study revealed some adverse reactions beyond basiliximab drug instructions, such as mitral valve calcification, diastolic dysfunction, pelvic fluid collection, testicular swelling, soft tissue necrosis, and muscle necrosis. Although basiliximab offers therapeutic benefits, it carries the risk of several adverse reactions. Clinicians should monitor patients for signs of increased serum creatinine level, fever, cytomegalovirus infection, anaphylactic shock, mitral valve calcification, diastolic dysfunction, pelvic fluid collection, testicular swelling, soft tissue necrosis, muscle necrosis, and other events during clinical use.

Insights from pharmacovigilance and pharmacodynamics on cardiovascular safety signals of NSAIDs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat fever, pain, and inflammation. Concerns regarding their cardiovascular safety have been raised. However, the underlying mechanism behind these events remains unknown. We aim to investigate the cardiovascular safety signals and receptor mechanisms of NSAIDs, employing a comprehensive approach that integrates pharmacovigilance and pharmacodynamics. This study utilized a pharmacovigilance-pharmacodynamic approach to evaluate the cardiovascular safety of NSAIDs and explore potential receptor mechanisms involved. Data were analyzed using the OpenVigil 2.1 web application, which grants access to the FDA Adverse Event Reporting System (FAERS) database, in conjunction with the BindingDB database, which provides target information on the pharmacodynamic properties of NSAIDs. Disproportionality analysis employing the Empirical Bayes Geometric Mean (EBGM) and Reporting Odds Ratio (ROR) methods was conducted to identify signals for reporting cardiovascular-related adverse drug events (ADEs) associated with 13 NSAIDs. This analysis encompassed three System Organ Classes (SOCs) associated with the cardiovascular system: blood and lymphatic system disorders, cardiac disorders, and vascular disorders. The primary targets were identified through the receptor-NSAID interaction network. Ordinary least squares (OLS) regression models explored the relationship between pharmacovigilance signals and receptor occupancy rate. A total of 201,231 reports of cardiovascular-related ADEs were identified among the 13 NSAIDs. Dizziness, anemia, and hypertension were the most frequently reported Preferred Terms (PTs). Overall, nimesulide and parecoxib exhibited the strongest signal strengths of ADEs at SOC levels related to the cardiovascular system. On the other hand, our data presented naproxen and diclofenac as drugs of comparatively low signal strength. Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were identified as central targets. OLS regression analysis revealed that the normalized occupancy rate for either COX-1 or COX-2 was significantly inversely correlated with the log-transformed signal measures for blood and lymphatic system disorders and vascular disorders, and positively correlated with cardiac disorders and vascular disorders, respectively. This suggests that higher COX-2 receptor occupancy is associated with an increased cardiovascular risk from NSAIDs. Cardiovascular safety of NSAIDs may depend on pharmacodynamic properties, specifically, the percentage of the occupied cyclooxygenase isoenzymes. More studies are needed to explore these relations and improve the prescription process.

Assessing Response Rates and Sleep Disorder Prevalence: Insights from a Propranolol Treatment Study for Infantile Haemangiomas.

Infantile haemangiomas (IHs) sometimes require treatment with propranolol. Sleep disturbances are the most frequently reported side effects. Monitoring adverse drug events necessitates repeated hospital visits, which can be challenging during a pandemic. To explore the effectiveness of a new electronic questionnaire in identifying sleep disturbances related to treatment with propranolol and potential confounding factors. To evaluate the response rate to the questionnaire. To report the proportion of patients on propranolol with sleep disturbances. In an observational, prospective cohort study, caregivers provided clinical information during ambulatory visits and via an electronic questionnaire after an 8-week treatment course with propranolol and at the time of treatment interruption. Adverse drug reaction reporting forms were assessed for causality. The questionnaire response rate was 91%, and the completion rate was 100%. A total of 59% of patients experienced sleep disturbances during propranolol treatment, which were considered adverse reactions. Sleep disorders were frequent during sleep regression phases and in subjects who fell asleep during physical contact with caregivers or bed-sharing with parents. The application of this questionnaire allows for identifying adverse sleep events associated with propranolol in IHs and potential confounders. Counselling on sleep hygiene is recommended before treatment onset.

Clinical Characteristics and Outcome Predictors in Drug-Resistant Tuberculosis: A Comprehensive Analysis

Background: Drug-resistant tuberculosis (DR-TB) poses significant challenges to public health, with poor outcomes frequently observed in affected patients. This study aims to evaluate the characteristics and factors associated with poor outcomes in patients with drug-resistant pulmonary tuberculosis at Liwa Hospital from January 2018 to May 2023. Methods: A retrospective, cross-sectional single-center analysis was conducted on 408 patients admitted to Liwa Hospital. Among these, 28 patients diagnosed with drug-resistant tuberculosis (DR-TB) were selected for detailed analysis based on their treatment outcomes and clinical data. Inclusion criteria encompassed patients aged 18 years or older with confirmed drug-resistant TB, while patients younger than 18, those with latent tuberculosis, and those with extra-pulmonary tuberculosis were excluded. Results: The majority of patients were between 18-40 years old (60.7%), predominantly male (85.7%), and Asian (96.4%). Comorbidities included diabetes (46.4%) and hypertension (21.4%). Clinical characteristics revealed cough (28.6%) and fever with cough (7.1%) as common symptoms. Primary resistance was observed in 92.9% of cases, with 96.4% being newly diagnosed TB cases. Adverse drug events were minimal, with 7.1% experiencing nausea and vomiting. Radiological findings showed unilateral TB in 53.6% and cavitary TB in 57.1% of cases. Laboratory analysis indicated elevated HbA1c (9.83 ± 3.25), CRP (25.94 ± 5.16 mg/L), and white blood cell count (9.94 ± 4.59 x 10^9 cells/L). Rifampicin resistance was the most prevalent (42.9%), followed by isoniazid resistance (25.0%). Regarding treatment outcomes, age, hypertension, and diabetes mellitus were found to be significantly associated with poor outcomes in patients (p=0.05). Conclusion: The study identified significant associations between treatment outcomes and age, hypertension, and diabetes status, with higher proportions of poor outcomes observed in patients. Comprehensive management strategies targeting these factors are essential to improve outcomes in patients with drug-resistant TB. Further research is warranted to develop tailored interventions for this population.

The Ability and Tasks of Pharmacovigilance and Adverse Drug Events in India a Global Scenario

Clinical trials are the first stage of pharmacovigilance, which continues until the medication is put on the market. Social media's introduction provides access to healthcare data that hasn't been vetted by conventional techniques of data collection. Enhancing clinical and scientific understanding of pharmacovigilance could be greatly aided by using natural language processing tools to retrieve patient reports of adverse medication occurrences from social media. Signal detection encompasses all side effects connected to a medication. The primary goal of the study is to extract information from the FAERS data, which includes both organized and unstructured patient information on prior adverse drug reactions. The study examines how the side effects of acetaminophen and ibuprofen are extracted and managed using the proper techniques.

Exploring the top 30 drugs associated with drug-induced constipation based on the FDA adverse event reporting system.

This project aims to identify the top 30 drugs most commonly associated with constipation and their signal values within the FDA Adverse Event Reporting System database. We extracted adverse drug events (ADEs) related to constipation from the FAERS database spanning from January 1, 2004, to September 30, 2023. We compiled the 30 most frequently reported drugs based on the frequency of constipation events. We employed signal detection methodologies to ascertain whether these drugs elicited significant signals, including reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and information component given by the Bayesian confidence propagation neural network. Furthermore, we conducted a time-to-onset (TTO) analysis for drugs generating significant signals using the medians, quartiles, and the Weibull shape parameter test. We extracted a total of 50, 659, 288 ADEs, among which 169,897 (0.34%) were related to constipation. We selected and ranked the top 30 drugs. The drug with the highest ranking was lenalidomide (7,730 cases, 4.55%), with the most prevalent drug class being antineoplastic and immunomodulating agents. Signal detection was performed for the 30 drugs, with constipation risk signals identified for 26 of them. Among the 26 drugs, 22 exhibited constipation signals consistent with those listed on the FDA-approved drug labels. However, four drugs (orlistat, nintedanib, palbociclib, and dimethyl fumarate) presented an unexpected risk of constipation. Ranked by signal values, sevelamer carbonate emerged as the drug with the strongest risk signal [reporting odds ratio (95% CI): 115.51 (110.14, 121.15); PRR (χ2): 83.78 (191,709.73); EBGM (EB05): 82.63 (79.4); IC (IC025): 6.37 (4.70)]. A TTO analysis was conducted for the 26 drugs that generated risk signals, revealing that all drugs exhibited an early failure type. The median TTO for orlistat was 3days, the shortest of all the drugs, while the median TTO for clozapine was 1,065days, the longest of all the drugs. Our study provides a list of drugs potentially associated with drug-induced constipation (DIC). This could potentially inform clinicians about some alternative medications to consider when managing secondary causes of constipation or caring for patients prone to DIC, thereby reducing the incidence and mortality associated with DIC.

Disproportionality analysis of cardiac adverse events associated with lenvatinib using the Japanese Adverse Drug Event Report database.

This study was conducted to examine disproportionality, times to onset, incidence rates and outcomes of lenvatinib-associated cardiac adverse events (AEs) using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and May 2023. Data on cardiac AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Furthermore, Weibull distribution parameters were calculated. Of the 2 230 863 reports analysed, we identified 7684 reports of AEs associated with lenvatinib, including 317 cardiac AEs. Signals were detected for eight cardiac AEs: hypertension, cardiac failure, myocarditis, myocardial infarction, immune-mediated myocarditis, cardiomyopathy, angina unstable and cardiotoxicity. Among these, fatal outcomes were observed for cardiac failure, myocarditis and myocardial infarction. Histograms of median times to onset for the eight detected cardiac AE signals showed that AEs occurred at a median of 3.5-134.5days after lenvatinib administration. The Weibull distributions showed that cardiac failure occurred early after administration (early failure type), myocarditis occurred in a dose-dependent manner (wearout failure type), and myocardial infarction occurred constantly throughout the exposure period (random failure type). We focused on cardiac AEs associated with lenvatinib as post-marketing AEs. Serious outcomes can arise after lenvatinib administration. Patients should be monitored for signs of onset of these AEs not only at the start of administration, but also over an extended period.

Re-Exposure to Culprit Medication Following Adverse Drug Event Diagnosis in Canadian Emergency Department Patients: A Cohort Study.

The magnitude of repeat exposures to culprit medications after hospital discharge is not well studied. We combined prospective cohort data with administrative health data to understand the frequency of repeat exposures to culprit medications after discharge and the risk factors for their occurrence. This was a retrospective analysis of three prospective cohorts of patients who presented to the hospital with an adverse drug event in British Columbia, from 2008 to 2015 (n = 849). We linked prospectively identified adverse drug events to administrative data to examine patterns of redispensing of culprit medications. We used Cox regression to assess risk factors for re-exposure, and conducted subgroup analyses for essential vs. nonessential medications. Among 849 diagnosed adverse drug events, 45.2% had subsequent culprit medication redispensing within a year of hospital discharge. The factors associated with re-exposures included atrial fibrillation, adverse drug event type (e.g. adverse reaction), culprit medication type, and longer historical duration of medication use. Re-exposures to culprit medications occurred in almost half of the adverse drug events diagnosed in emergency departments. Many of these were appropriate re-exposures to essential medications for indications in which the risk of uncontrolled disease likely outweighed the risk of a repeat adverse event. More research is needed to understand re-exposures to nonessential medications or medications with safer alternatives.

High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database.

Cetirizine and Loratadine are the two best-selling second-generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions. ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs. A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle-aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n=326, ROR 6.75), sneezing (n=251, ROR 15.24), and nasal congestion (n=185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n=2556, ROR 10.52 vs. Loratadine, n=1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n=233, ROR 3.3), while Loratadine was associated with nervousness (n=145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n=138, ROR 8.13), potentially leading to serious adverse consequences. Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

Risk analysis of enfortumab vedotin: A real-world approach based on the FAERS database

PurposeTo analyze the risk of enfortumab vedotin (EV), a targeted therapy for advanced bladder cancer, using real-world data from the U.S. Food and Drug Administration's Federal Adverse Event Reporting System (FAERS). MethodsA retrospective pharmacovigilance analysis was conducted using FAERS data from Q1 2020 to Q1 2024. Adverse drug events (ADEs) related to EV were identified and categorized according to the System Organ Classes (SOCs) and specific events. Statistical methods, such as the proportional reporting ratio, reporting odds ratio (ROR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean were used to detect safety signals. ResultsOf the 7,449,181 FAERS case reports, 1,617 EV-related ADEs were identified, including 101 preferred terms and 22 SOCs. The key SOCs included skin and subcutaneous tissue, metabolic, and nutritional disorders. Rare ADEs, such as lichenoid keratosis (n = 4; ROR 26.89), small intestinal perforation (n = 3; ROR 24.51), pigmentation disorder (n = 9; ROR 18.16), and cholangitis (n = 8; ROR 17.48), showed significant disproportionality. ConclusionWhile most findings aligned with the existing data, new signs such as lichenoid keratosis and small intestinal perforation were identified. Further studies are necessary to validate these findings and emphasize the need for the clinical monitoring of EV-related ADEs.