US FDA Adverse Event Reporting Research Articles

Analysis of Inclisiran in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and Sex-specific Subgroups.

ABSTRACT Background our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety. Methods We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS). Results Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and Various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98). Conclusion Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Enhancing Transparency in Defining Studied Drugs: The Open-Source Living DiAna Dictionary for Standardizing Drug Names in the FAERS.

In refining drug safety signals, defining the object of study is crucial. While research has explored the effect of different event definitions, drug definition is often overlooked. The US FDA Adverse Event Reporting System (FAERS) records drug names as free text, necessitating mapping to active ingredients. Although pre-mapped databases exist, the subjectivity and lack of transparency of the mapping process lead to a loss of control over the object of study. We implemented the DiAna dictionary, systematically mapping individual free-text instances to their corresponding active ingredients and linking them to the World Health Organization Anatomical Therapeutic Chemical (WHO-ATC) classification. We retrieved all drug names reported to the FAERS (2004-December 2022). Using existing vocabularies and string editing, we automatically mapped free text to ingredients. We manually revised the mapping and linked it to the ATC classification. We retrieved 18,151,842 reports, with 74,143,411 drug entries. We manually checked the first 14,832 terms, up to terms occurring over 200 times (96.88% of total drug entries), to 6282 unique active ingredients. Automatic unchecked translations extend the standardization to 346,854 terms (98.94%). The DiAna dictionary showed a higher sensitivity compared with RxNorm alone, particularly for specific drugs (e.g., rimegepant, adapalene, drospirenone, umeclidinium). The most prominent drug classes in the FAERS were immunomodulating (37.40%) and neurologic drugs (29.19%). The DiAna dictionary, as a dynamic open-source tool, provides transparency and flexibility, enabling researchers to actively shape drug definitions during the mapping phase. This empowerment enhances accuracy, reproducibility, and interpretability of results.

Ocular toxicities in chimeric antigen receptor T-cell therapy: a real-world study leveraging FAERS database.

Aim: The purpose of this study was to comprehensively explore the ocular toxicity associated with chimeric antigen receptor (CAR) T-cell therapy. Materials & methods: Data were assembled from the US FDA's Adverse EventReporting System (FAERS) database from 2017 to 2023. Information componentand reporting odds ratiomethods were used for signal detection in total/categorized CAR T-cell therapy. Results: A total of17 positive signals (preferred term) were detected, yet noneof them weredocumented in the product information. Some adverse eventswere with death outcomes and overlapped a lot with cytokine-release syndrome. Conclusion: The ocular adverse eventsassociated with CAR-T cell therapy are noteworthy, and it is imperative to maintain increased alertness and institute early intervention strategies.

Strong opioids-induced cardiac, neurologic, and respiratory disorders: a real-world study from 2004 to 2023 based on FAERS.

Opioids are mainly used as adjuncts to the induction and maintenance of general anesthesia, postoperative analgesia, and treating moderate to severe cancer pain and chronic pain. However, the hazards of these drugs to various organ organs still need to be further explored. This study used the US FDA Adverse Event Reporting System (FAERS) database to determine whether commonly receiving opioids was higher than the baseline risk for all other medications. FAERS was asked about adverse events (AEs) for the opioids "morphine," "fentanyl," "oxycodone," "hydromorphone," "sufentanil," and "remifentanil" from the first quarter of 2004 (2004Q1) through the second quarter of 2023 (2023Q2). Disproportionality signaling analysis was performed by calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). AEs with system organ classes (SOCs) of "cardiac disease," "neurologic disease," and "respiratory, thoracic, and mediastinal disease" were then screened. The statistical analysis included 12,819,518 reports in the FAERS database from 2004Q1 to 2023Q2, of which 236,619 AEs were reported as "primary suspect" for the six drugs mentioned above, which were selected as "cardiac disorders," "nervous system disorders," and "respiratory, thoracic and mediastinal disorders." Some AEs identified in this study are consistent with the drug labeling, such as bradycardia, respiratory depression, and somnolence. In addition, some unexpected and significant acute adverse drug reactions (ADRs), such as toxic leukoencephalopathy and coma, may occur. This study identified potential new and unexpected ADRs for opioids, providing valuable evidence for safety studies of opioids.

1783. Acute Kidney Injury Associations with Antibiotics: A Pharmacovigilance Study of the US FDA Adverse Event Reporting System

Abstract Background Antibiotic-associated acute kidney injury is found to be associated with many antibiotics like vancomycin, fluoroquinolones, penicillin combinations, and trimethoprim–sulfamethoxazole. Other antibiotics may also lead to acute kidney injury. Still, no study has systemically compared the cases of acute kidney injury reported to the US FDA Adverse Event Reporting System (FAERS) with the many available antibiotics. Therefore, the study aimed to evaluate the reporting associations between acute kidney injury and different classes of antibiotics through the analysis of the US FDA Adverse Event Reporting System (FAERS). Methods FAERS reports from 1 January 2015 to 31 December 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify AKI cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs) for the reporting associations between antibiotics and AKI were calculated. A reporting association was considered statistically significant when the lower limit of the 95% CI was > 1.0. Results A total of 2,042,801 reports (including 20,138 AKI reports) were considered. Colistin had the greatest proportion of acute kidney injury reports, representing 25% of all colistin reports. acute kidney injury RORs (95% CI) for antibiotics were, in descending order: colistin 33.10 (21.24–51.56), aminoglycosides 17.41 (14.49–20.90), vancomycin 15.28 (13.82–16.90), trimethoprim–sulfamethoxazole 13.72 (11.94–15.76), penicillin combinations 7.95 (7.09–8.91), clindamycin 6.46 (5.18–8.04), cephalosporins 6.07 (5.23–7.05), daptomycin 6.07 (4.61–7.99), macrolides 3.60 (3.04–4.26), linezolid 3.48 (2.54–4.77), carbapenems 3.31 (2.58–4.25), metronidazole 2.55 (1.94–3.36), tetracyclines 1.73 (1.26–2.36), and fluoroquinolones 1.71 (1.49–1.97). Conclusion This study found 14 classes of antibiotics having significant reporting associations with AKI. Among the antibiotics evaluated in this study, colistin had the highest acute kidney injury ROR and moxifloxacin had the lowest. Disclosures All Authors: No reported disclosures

A real-world analysis of tyrosine receptor kinase inhibitor-related toxicities in cancer treatment.

Background: This study analyzed real-world data from 2004 to 2023 to evaluate the toxicity profile of tyrosine receptor kinase (TRK) inhibitor therapy. Method: A retrospective analysis of USFDA Adverse Event Reporting System data was conducted to identify adverse events in patients receiving TRK inhibitor therapy. Result: Entrectinib demonstrated toxicities primarily in the cardiovascular and nervous systems, followed by the renal and urinary system. Common adverse effects included dizziness, renal impairment, constipation, heart failure and taste disorders. Larotrectinib induced adverse events mainly in the hepatobiliary and nervous systems, with peripheral neuropathy, myalgia, renal impairment and increased alanine aminotransferase commonly reported. Conclusion: Careful monitoring and supportive care strategies are essential for managing adverse events associated with TRK inhibitor therapy.

Rhabdomyolysis associated with newer-generation anti-seizure medications (ASMs): a real-world retrospective and pharmacovigilance study.

Objective: Rhabdomyolysis is a potentially fatal adverse reaction mostly triggered by certain medications. Few real-world studies have shown a clear association between newer-generation anti-seizure medications (ASMs) and rhabdomyolysis. We sought to quantify the risk and evaluate the clinical features and management of rhabdomyolysis associated with newer-generation ASMs. Methods: Data were retrieved from the US FDA Adverse Event Reporting System database (FAERS) from 2018 to 2022 on newer-generation ASMs to identify rhabdomyolysis events, and disproportionality analyses were conducted by estimating the reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs). Furthermore, case reports from 2012 to 31 December 2022 on newer-generation ASMs-induced rhabdomyolysis were retrieved for retrospective analysis. Results: A total of 1,130 rhabdomyolysis reports from the FAERS database were considered. Levetiracetam had the greatest proportion and the highest positive signal values of rhabdomyolysis. The RORs (95% CIs) for newer-generation ASMs were, in descending order, levetiracetam 8.01 (7.26-8.84), lamotrigine 3.78 (3.25-4.40), oxcarbazepine 3.47 (2.53-4.75), pregabalin 2.75 (2.43-3.12), lacosamide 1.85 (1.29-2.65), topiramate 1.64 (1.25-2.15), and gabapentin 1.32 (1.13-1.55). Twenty-six case reports showed evidence of rhabdomyolysis, and levetiracetam (65.4%) was the most frequently reported agent. The median age was 32years; typical initial symptoms included muscle weakness (34.8%), myalgia (34.8%), backache (17.4%), fatigue (13.0%) and leg pain (8.7%). The median time to onset of rhabdomyolysis was 2days. All cases had elevated creatine phosphokinase (CPK), and some cases were accompanied by elevated creatinine (57.1%) and myoglobinuria (53.8%). Cessation of ASMs could lead to complete clinical remission. The median time for creatine phosphokinase (CPK) normalization was 8days. Conclusion: This study identified 7 newer-generation ASMs with significant rhabdomyolysis reporting associations. Prescribers should be more aware of this risk and teach patients to recognize rhabdomyolysis signs/symptoms early.

Development and Application of a Data-Driven Signal Detection Method for Surveillance of Adverse Event Variability Across Manufacturing Lots of Biologics.

Postmarketing drug safety surveillance research has focused on the product-patient interaction as the primary source of variability in clinical outcomes. However, the inherent complexity of pharmaceutical manufacturing and distribution, especially of biologic drugs, also underscores the importance of risks related to variability in manufacturing and supply chain conditions that could potentially impact clinical outcomes. We propose a data-driven signal detection method called HMMScan to monitor for manufacturing lot-dependent changes in adverse event (AE) rates, and herein apply it to a biologic drug. The HMMScan method chooses the best-fitting candidate from a family of probabilistic Hidden Markov Models to detect temporal correlations in per lot AE rates that could signal clinically relevant variability in manufacturing and supply chain conditions. Additionally, HMMScan indicates the particular lots most likely to be related to risky states of the manufacturing or supply chain condition. The HMMScan method was validated on extensive simulated data and applied to three actual lot sequences of a major biologic drug by combining lot metadata from the manufacturer with AE reports from the US FDA Adverse Event Reporting System (FAERS). Extensive method validation on simulated data indicated that HMMScan is able to correctly detect the presence or absence of variable manufacturing and supply chain conditions for contiguous sequences of 100 lots or more when changes in these conditions have a meaningful impact on AE rates. Applying the HMMScan method to FAERS data, two of the three actual lot sequences examined exhibited evidence of potential manufacturing or supply chain-related variability. HMMScan could be utilized by both manufacturers and regulators to automate lot variability monitoring and inform targeted root-cause analysis. Broad application of HMMScan would rely on a well-developed data input pipeline. The proposed method is implemented in an open-source GitHub repository.

Analysis on the risk of myasthenia gravis related to immune checkpoint inhibitors based on the US FDA Adverse Event Reporting System.

To evaluate the risk of myasthenia gravis (MG) associated with immune checkpoint inhibitors (ICI). Adverse event (AE) reports related to MG, myasthenic syndrome, and MG crisis for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab in the US FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q3 2022 were collected. The proportional reporting odds ratio (PRR) method was used to evaluate the correlation between the six drugs and the three AEs. Statistical significance was defined as having reports ≥3, PRR ≥ 2, and chi-square (χ2 ) ≥ 4. A total of 36, 78, 276, 380, 5, and 53 AE reports were collected for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For myasthenic syndrome, the PRR values reflecting the correlation with the drugs were 27.83 (χ2 = 102.66), 26.20 (χ2 = 235.67), 44.17 (χ2 = 1313.98), 32.09 (χ2 = 1229.54), 21.31 (χ2 = 151.15), and 0 for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG, the PRR values reflecting the correlation with the drugs were 24.21 (χ2 = 682.04), 18.34 (χ2 = 900.27), 39.32 (χ2 = 7945.15), 26.93 (χ2 = 6636.45), 14.73 (χ2 = 566.47), and 15.69 (χ2 = 54.77) for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG crisis, there were no data for durvalumab, atezolizumab, avelumab, and ipilimumab; the PRR values reflecting the correlation with the drugs were 16.54 (χ2 = 225.23) and 9.20 (χ2 = 119.14) for pembrolizumab and nivolumab, respectively. All six drugs were statistically correlated with their corresponding AEs. ICI may lead to ICIs-associated MG during therapy. Analysis of FAERS data identified signals for AEs of MG with ICI regimens. Practitioners should consider the factors that may increase the likelihood of MG. The findings support a continued surveillance and risk factor identification.

A real-world disproportionality analysis of Rucaparib: Post-marketing Pharmacovigilance Data

BackgroundRucaparib has been approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. However, the long-term safety of rucaparib in large sample population was unknown. The presented study aimed to evaluate rucaparib-associated adverse events (AEs) according to the real-world pharmacovigilance database.MethodsDisproportionality analysis was conducted to assess the association between rucaparib and its AEs. Data were collected from the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS) between January 2017 and June 2022. The characteristics of rucaparib-related AEs, and the onset time were further analyzed.ResultsA total of 9,296,694 AE reports were recorded in the FAERS during the study period, among which 7,087 reports were associated with rucaparib. About 135 rucaparib-related AE signals in 15 system organ class (SOCs) were identified. The most common AEs included anaemia, thrombocytopenia, nausea, vomiting, fatigue, blood creatinine increase, alanine aminotransferase increase, and aspartate aminotransferase increase, which were listed in the label for rucaparib. Of note, 21 new and unexpected significant AEs that off-label were also found in our study, such as preferred term (PTs) of intestinal obstruction, gastrooesophageal reflux disease, blood iron decreased, dehydration, and hypersomnia. The median onset time of rucaparib-related AEs was 12 days (interquartile range [IQR] 1–62 days), and had early failure types.ConclusionOur study demonstrated potential new AEs of rucaparib, and further studies were expected to confirm the results.

EPH41 Association of Ustekinumab with Carpal Tunnel Syndrome, Cutaneous Lupus Erythematosus, Basedow's Disease and Melanocytic Naevus: A Disproportionality Analysis in Usfda Adverse Event Reporting System Database

Ustekinumab is a human immunoglobulin G1 kappa monoclonal antibody acting as an antagonist of the p40 subunit of interleukin-12 and interleukin-23, that is approved by USFDA for use in Plaque Psoriasis in 2009 and for Crohn disease in 2016. This study aimed at detecting side effects in early stages that are associated with Ustekinumab by conducting disproportionality analysis of the FDA Adverse Event Reporting System (FAERS).

Identifying Safety Subgroups at Risk: Assessing the Agreement Between Statistical Alerting and Patient Subgroup Risk.

Identifying individual characteristics or underlying conditions linked to adverse drug reactions (ADRs) can help optimise the benefit-risk ratio for individuals. A systematic evaluation of statistical methods to identify subgroups potentially at risk using spontaneous ADR report datasets is lacking. In this study, we aimed to assess concordance between subgroup disproportionality scores and European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC) discussions of potential subgroup risk. The subgroup disproportionality method described by Sandberg et al., and variants, were applied to statistically screen for subgroups at potential increased risk of ADRs, using data from the US FDA Adverse Event Reporting System (FAERS) cumulative from 2004 to quarter 2 2021. The reference set used to assess concordance was manually extracted from PRAC minutes from 2015 to 2019. Mentions of subgroups presenting potential differentiated risk and overlapping with the Sandberg method were included. Twenty-seven PRAC subgroup examples representing 1719 subgroup drug-event combinations (DECs) in FAERS were included. Using the Sandberg methodology, 2 of the 27 could be detected (one for age and one for sex). No subgroup examples for pregnancy and underlying condition were detected. With a methodological variant, 14 of 27 examples could be detected. We observed low concordance between subgroup disproportionality scores and PRAC discussions of potential subgroup risk. Subgroup analyses performed better for age and sex, while for covariates not well-captured in FAERS, such as underlying condition and pregnancy, additional data sources should be considered.

Risk factors of immune checkpoint inhibitor-associated acute kidney injury: evidence from clinical studies and FDA pharmacovigilance database

BackgroundSeveral risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study.MethodsWe search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR).ResultsA total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78–2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24–1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01–1.65), diuretics (OR = 2.00, 95%CI 1.38–2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04–1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15–1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25–2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96–3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91–2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95–3.57), NSAIDs (ROR = 3.06, 95%CI 2.81–3.32) or diuretics (ROR = 2.82, 95%CI 2.50–3.19) were observed significant signals associated with AKI in ICIs-treated patients.ConclusionsConcurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

Propofol-associated serious adverse events: an analysis of the FAERS database

ABSTRACT Propofol is an ultra-fast-acting intravenous anesthetic, which is rapidly metabolized primarily into inactive compounds in the live and then excreted in the urine. The purpose of this study is to explore the risk signals of propofol based on the US FDA Adverse Event Reporting System database. The risk signals of propofol-related adverse reactions in adverse event (AE) reports from 2004 to 2021 in the US FAERS were mined using ratio-report method (ROR) and the ratio-report ratio method (PRR) methods. We screened out 1651 pairs AE reports using propofol as primary suspect (PS) drugs. ROR, PRR, BCPNN and MGPS methods were used to calculate respectively, there are 363 positive preferred terms (PT) signals with 9549 cases. Among them, the top 3 adverse reactions associated with using propofol from the FAERS database were anaphylactic shock, hypotension and propofol infusion syndrome. The top 3 systems of the body associated with adverse reaction of propofol from the FAERS database were General disorders, Cardiac disorders and administration site conditions and Respiratory, thoracic and mediastinal disorders. The top 4 indication of using propofol from the FAERS database, including anaesthesia, induction of anaesthesia, sedation, general anaesthesia. There are many adverse reactions that are not included in the drug insert of propofol and involve a wide range of organs and/or systems. Caution should be exercised in the clinical use of propofol.

IL-17 inhibitor-associated inflammatory bowel disease: A study based on literature and database analysis.

Objective: Few real-world studies have shown clear association between interleukin (IL)-17 inhibitors and inflammatory bowel disease (IBD) onset. This study investigated the reporting prevalence and evaluated the clinical features and management of IL-17 inhibitor-related IBD events. Methods: We used the US FDA Adverse Event Reporting System database and retrieved data, from 2015 to 2022, on IL-17 inhibitors to identify gastrointestinal inflammatory events and conduct disproportionality analyses by estimating the reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs). Furthermore, case reports and case series, from 2015 to 30 November 2022, on IBD induced by IL-17 inhibitors were collected for retrospective analysis. Results: A total of 388 cases of primary suspected IL-17 inhibitor-associated gastrointestinal events were reported (268 IBD and 120 colitis), including 348 cases involving secukinumab (SEC), 36 cases involving ixekizumab (IXE), and 4 cases involving brodalumab (BRO). Statistically significant reporting rates of total IBD events were observed for SEC and IXE (ROR = 2.13, 95% CI [1.96-2.30] and ROR = 2.79, 95% CI [2.39-3.27], respectively), whereas BRO did not trigger a safety signal. Twenty-nine studies, which included 34 cases, showed evidence of IBD, following SEC (79.4%) and IXE (20.6%) treatment. The median age was 42years; typical initial symptoms included diarrhea (90.9%), abdominal pain (57.6%), bloody diarrhea (51.5%), and fever (36.4%). The median time to onset of IBD symptoms was 2.9months. Some cases were accompanied by elevated white blood cell (WBC) count (87.5%), erythrocyte sedimentation rate (ESR; 85.7%), C-reactive protein (CRP; 100%), and fecal calprotectin (FC; 100%). Cessation of IL-17 inhibitors plus treatment with corticosteroids and TNF antagonists, as either monotherapy or in combination, could lead to complete clinical remission. The median time to remission after IL-17 inhibitor discontinuation was 4weeks. Conclusion: IL-17 inhibitor treatment is associated with exacerbation and new onset of IBD and colitis. Obtaining a detailed patient history before initiation of treatment and monitoring gastrointestinal symptoms and intestinal inflammatory biomarkers during IL-17 inhibitor treatment is important for safe use of these drugs.

Updated insights on cardiac risks of CD19-directed chimeric antigen receptor T-cell therapy: a pharmacovigilance study.

Aim: Comprehensively characterize the cardiotoxicity of CD19-directed chimeric antigen receptor T-cell (CAR-T) products. Materials & methods: Data between 2017 and2021 in the USFDA's Adverse Event Reporting System database were utilized. Disproportionality was measured using reporting odds ratio and information component. Hierarchical clustering analysis was performed to explore the relationships among cardiac events. Results: Tisagenlecleucel exhibited the highest percentage of death (53.24%) and life-threatening (13.39%) outcomes. Axicabtagene ciloleucel and tisagenlecleucel were equal in the number of positive signals (n=15), while the former had excessive reporting of several cardiac events versus the latter, such as atrial fibrillation, cardiomyopathy, cardiorenal syndromeand sinus bradycardia. Conclusion: Several cardiac risks should be considered for CAR-T treatment and these events might varyin frequency and severity following different CAR-T agents.

Deliberate Self-Poisoning: Real-Time Characterization of Suicidal Habits and Toxidromes in the Food and Drug Administration Adverse Event Reporting System.

Deliberate self-poisoning (DSP) using drugs is the preferred method of suicide at a global level. Its investigation is hampered by limited sample sizes and data reliability. We investigate the role of the US FDA Adverse Event Reporting System (FAERS), a consolidated pharmacovigilance database, in outlining DSP habits and toxidromes. We retrieved cases of 'intentional overdose' and 'poisoning deliberate' from the FAERS (January 2004-December 2021). Using descriptive and disproportionality analyses, we estimated temporal trends, potential risk factors, toxidromes, case-fatality rates and lethal doses (LDs) for the most frequently reported drugs. We retrieved 42,103 DSP cases (17% fatal). Most cases were submitted in winter. Reports of DSP involved younger people, psychiatric conditions, and alcohol use, compared with non-DSP, and fatality was higher in men and older patients. Suspected drugs were mainly antidepressants, analgesics, and antipsychotics. Multiple drug intake was recorded in more than 50% of the reports, especially analgesics, psychotropics, and cardiovascular agents. The most frequently reported drugs were paracetamol, promethazine, amlodipine, quetiapine, and metformin. We estimated LD25 for paracetamol (150g). Worldwide coverage of the FAERS complements existing knowledge about DSP and may drive tailored prevention measures to timely address the DSP phenomenon and prevent intentional suicides.

Allograft rejection following immune checkpoint inhibitors in solid organ transplant recipients: A safety analysis from a literature review and a pharmacovigilance system.

This study aimed to systematically characterize transplant rejection after immune checkpoint inhibitors (ICIs) initiation in solid organ transplant recipients (SOTRs). Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database and case reports in the literature. Disproportionality analysis including information component and reported odds ratio (ROR) was performed to access potential risk signals. A total of 168 patients with transplant rejection after ICIs usage were identified in the FAERS database, and 89 cases were identified in the literature review. ICIs were significantly associated with transplant rejection (ROR025 : 2.2). A strong risk signal was found for combination therapy with pembrolizumab and ipilimumab compared to monotherapy. Immune checkpoint inhibitors were significantly associated with transplant rejection in SOTRs.

Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have significantly improved clinical effects on glycemic control. However, real-world data concerning the difference in gastrointestinal adverse events (AEs) among different GLP-1 RAs are still lacking. Our study aimed to characterize and compare gastrointestinal AEs among different marketed GLP-1 RAs (exenatide, liraglutide, dulaglutide, lixisenatide, and semaglutide) based on real-world data. Disproportionality analysis was used to evaluate the association between GLP-1 RAs and gastrointestinal adverse events. Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database between January 2018 and September 2022. Clinical characteristics, the time-to-onset, and the severe proportion of GLP-1 RAs-associated gastrointestinal AEs were further analyzed. A total of 21,281 reports of gastrointestinal toxicity were analyzed out of 81,752 adverse event reports, and the median age of the included patients was 62 (interquartile range [IQR] 54-70) years old. Overall GLP-1 RAs were associated with increased risk of gastrointestinal system disorders (ROR, 1.46; 95% CI, 1.44-1.49), which were further attributed to liraglutide (ROR, 2.39; 95% CI, 2.28-2.51), dulaglutide (ROR, 1.39; 95% CI, 1.36-1.42), and semaglutide (ROR, 3.00; 95% CI, 2.89-3.11). Adverse events uncovered in the labels included gastroesophageal reflux disease, gastritis, bezoar, breath odor, intra-abdominal hematoma, etc. Furthermore, it was observed that semaglutide had the greatest risk of nausea (ROR, 7.41; 95% CI, 7.10-7.74), diarrhea (ROR, 3.55; 95% CI, 3.35-3.77), vomiting (ROR, 6.67; 95% CI, 6.32-7.05), and constipation (ROR, 6.17; 95% CI, 5.72-6.66); liraglutide had the greatest risk of abdominal pain upper (ROR, 4.63; 95% CI, 4.12-5.21) and pancreatitis (ROR, 32.67; 95% CI, 29.44-36.25). Most gastrointestinal AEs tended to occur within one month. Liraglutide had the highest severe rate of gastrointestinal AEs (23.31%), while dulaglutide had the lowest, with a severe rate of 12.29%. GLP-1 RA were significantly associated with gastrointestinal AEs, and the association was further attributed to liraglutide, dulaglutide, and semaglutide. In addition, semaglutide had the greatest risk of nausea, diarrhea, vomiting, constipation, and pancreatitis, while liraglutide had the greatest risk of upper abdominal pain. Our study provided valuable evidence for selecting appropriate GLP-1 RAs to avoid the occurrence of GLP-1 RA-induced gastrointestinal AEs.

Serious Cardiovascular Adverse Event Associated with Hydroxychloroquine with Azithromycin in Patient with COVID-19 : A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS)

The use of Hydroxychloroquine combine with Azythromycin for the treatment of coronavirus disease (COVID-19) it may increases the risk of serious cardiovascular advere events. WHO not recommended for the use of HCQ to treat the COVID-19 because it has serious side effect on heart like Arrhythmia ,cardiac toxicity. In the following describe the risk of serious cardiovascular adverse event using HCQ is combined with Azythromycin it compared with that therapeutic alternatives. Some clinical trial that reporting the combine of HCQ with AZ demonstrated better efficacy than signal drug combination of HCQ and AZ has synergestic effect against viral infectious. The FAERS that evaluate adverse effect reports ,medication error reports and product quality complaint resulting in adverse effect that were submitted to FDA. The performing the test to analysis to case series using the US FDA Adverse Event Reporting System(FAERS).