Gamma Poisson Shrinker Research Articles

Adverse events analysis of Relugolix (Orgovyx®) for prostate cancer based on the FDA Adverse Event Reporting System (FAERS).

Due to the limitations of clinical trials, some delayed and rare adverse events (AEs) may remain undetected, and safety information can be supplemented through post-market data analysis. This study aims to comprehensively analyze the AEs associated with Relugolix (Orgovyx®) using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Relugolix (Orgovyx®) therapy. Data of Relugolix (Orgovyx®) were collected from the FAERS database covering the period from the fourth quarter of 2020 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), Bayesian analysis confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) to detect positive signals. Totally, 5,382,189 reports were collected from the FAERS database, 4,397 reports of Relugolix (Orgovyx®) were identified as the 'primary suspected (PS)' AEs. Relugolix (Orgovyx®) induced AEs occurred in 26 organ systems. 58 significant disproportionality preferred terms (PTs) satisfying with the four algorithms were retained at the same time. Unexpected significant AEs such as Pollakiuria, and Prostatic specific antigen increased also occur. The median time of onset was 60 days. The majority of the AEs occurred within the first 30 days after Relugolix (Orgovyx®) initiation. Common AEs included Hot flush, Fatigue, Asthenia, Constipation, and Myalgia. These AEs should be focused on when using the drug to avoid serious consequences. In addition, the study results also suggested that the drug may exist Pollakiuria, Prostatic specific antigen increased and other AEs not mentioned in the manual, to supplement the AEs in the manual. This study is helpful for clinicians and pharmacists to improve their understanding of Relugolix (Orgovyx®) related AEs, and take timely prevention and treatment measures to ensure drug safety for patients.

Clinical adverse events to letairis: a real-world drug safety study based on FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background Letairis (ambrisentan), an endothelin receptor antagonist (ERA), is a critical medication for pulmonary arterial hypertension (PAH). Despite its efficacy, its safety profile is under scrutiny, warranting a detailed analysis. Research design and methods This study leveraged the FDA Adverse Event Reporting System (FAERS) from Q1 2007 to Q4 2023, focusing on Letairis as the primary suspect in adverse events. Employing advanced data mining techniques, such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), the study aimed to uncover safety signals. Results A total of 43,774 cases were identified, with Letairis implicated in 16,038,963 adverse event reports. There was a notable predominance of female patients (75.30%), with a median age around 64 years. Severe outcomes, including hospitalization (51.63%) and fatalities (20.44%), were prevalent. Signal strength analysis highlighted concerns in infections and infestations, as well as cardiac disorders. Conclusion The analysis underscores the need for vigilant pharmacovigilance and highlights Letairis’s potential to induce serious AEs, particularly in female and elderly populations. These findings are instrumental in guiding clinical practice and future drug safety assessments.

Disproportionality analysis of the safety profile of rufinamide in the real world: an evaluation of the FDA Adverse Event Reporting System database

ABSTRACT Background Rufinamide (RUF) is an antiepileptic drug recently introduced for managing seizures in Lennox-Gastaut syndrome (LGS), but its adverse reactions are not well understood. This study aims to evaluate RUF’s safety profile using data from the FDA Adverse Event Reporting System (FAERS). Methods Disproportionality analysis was conducted to assess RUF-associated adverse drug events (ADEs), using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-Poisson shrinker (MGPS). Results We collected 338 ADE reports related to RUF. Nervous system disorders were the most frequently reported signals, and several new ADEs were detected, including atonic seizures, sudden unexplained death in epilepsy, seizure clusters, multi-drug resistance, and Stevens-Johnson syndrome. Nearly half of the ADEs in pediatric patients were psychological or neurological. Disproportionality analysis within 4 weeks of treatment showed high RORs for QT shortening, sudden death, and atonic seizures. Conclusions Our study revealed prospective signals of new ADEs linked to RUF as well as revealed that both prescribers and patients were more conscious of the risks involved in its clinical use.

Neurological and Psychiatric Adverse Events Associated with Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer Patients: Insights from a Pharmacovigilance Study via the FDA Adverse Event Reporting System.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have revolutionised cancer therapy, particularly breast cancer therapy. However, concerns about their potential to cause neurological and psychiatric adverse events (AEs) have emerged, and these concerns remain underexplored. This study aimed to investigate the signals related to neurological and psychiatric AEs associated with CDK4/6 inhibitor use. A retrospective study was performed to analyse reports of AEs associated with the use of CDK4/6 inhibitors (abemaciclib, ribociclib and palbociclib) from the first quarter of 2015 to the fourth quarter of 2023 on the basis of the FDA Adverse Event Reporting System (FAERS). Both the reporting odds ratio (ROR) and the multi-item gamma Poisson shrinker (MGPS) were used for signal detection. The timing of events was assessed with the Weibull shape parameter (WSP). The management, analysis and presentation of the data were performed via Python (version 3.8) and R software (version 4.3.2). A total of 19,001 AE reports in which CDK4/6 inhibitors were identified as the 'primary suspect drug' were included in this study. These events were predominantly observed in patients aged 65 to 85 years. Through an ROR analysis, 85 positive signals for neurological and psychiatric AEs associated with CDK4/6 inhibitors were identified. The MGPS method revealed 61 positive AE signals for neurological and psychiatric AEs associated with CDK4/6 inhibitors. A total of 34 positive AE signals were identified by both the ROR and MGPS analyses. The WSP indicated that the onset times for AEs associated with all three CDK4/6 inhibitors tended to be early in drug therapy, suggesting a propensity for early failuretype. The present study revealed neurological and psychiatric AEs associated with CDK4/6 inhibitors that often occur early in treatment. Significant signals include spinal cord herniation and cerebral microangiopathy. Close monitoring of these AEs is crucial. Further studies are necessary to verify the connection between CDK4/6 inhibitors and neurological and psychiatric AEs.

Exploring SGLT-2 inhibitors and sarcopenia in FAERS: a post-marketing surveillance study

ABSTRACT Background The sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) is associated with body weight loss but the composition of the losing weight remains unclear. Research design and methods Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi- item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of SGLT-2i-associated musculoskeletal and connective tissue disorders AEs. Results The search retrieved a total of 3,206 cases of musculoskeletal and connective tissue disorder-related AEs during the reporting period. This included 1,061 cases for Canagliflozin, 1,052 cases for Dapagliflozin, 1,074 cases for Empagliflozin, and 19 cases for Ertugliflozin. Fifteen preferred terms (PTs) with significant disproportionality were retained. No musculoskeletal and connective tissue system-related AE signals were reported for Ertugliflozin. We identified a risk of muscle necrosis with Canagliflozin use, a risk of sarcopenia with Dapagliflozin use, and a chance of muscle atrophy with Dapagliflozin and Empagliflozin prescriptions. Most cases occurred within the first month after SGLT-2i initiation, and AEs can persist beyond 360 days of use. Conclusions Our study identified potential new musculoskeletal and connective tissue disorder-related AE signals associated with SGLT-2 inhibitors.

Signal detection of immune thrombocytopenia associated with immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have become an important treatment modality for various malignancies. Due to excessive inflammatory and immune responses, immune-related adverse events (irAEs), such as rash, pruritis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism and fatigue, can occur. Acquired immune thrombocytopenia is a rare irAE that can lead to severe low platelet counts and hemorrhage. A retrospective observational analysis was conducted on data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We searched for all reports recorded in the FAERS covering the period from 2011 Q1 to 2023 Q4 for target agents. Signal analysis was performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithm. Nonparametric tests were used to compare the time to onset of thrombocytopenia-associated fractures between different regimens. There were 404 reports of immune thrombocytopenia in the FAERS database. Immune thrombocytopenia was associated with all ICIs except tremelimumab, and signals were detected by all 4 methods. The median time to the onset of immune thrombocytopenia caused by PD-1, PD-L1 and CTLA-4 inhibitors was 47 days (range: 21-139.2), 21 days (range: 13–131) and 9 days (range: 7–27), respectively. The Weibull shape parameter test revealed that pembrolizumab-, durvalumab-, and ipilimumab-induced thrombocytopenia had a random failure-type profile, and nivolumab- and atezolizumab-induced thrombocytopenia were characterized by an early failure-type profile. There was a significant reporting signal of ICI-induced thrombocytopenia associated with most ICIs. Immune thrombocytopenia has a greater incidence in males, elderly individuals and Asian populations, and PD-1 inhibitors were the most common cause. Clinicians should be aware of the signs of potential serious adverse events.

A real-world pharmacovigilance study using disproportionality analysis of United States Food and Drug Administration Adverse Event Reporting System events for vinca alkaloids: comparing vinorelbine and Vincristine

ABSTRACT Background Vinca alkaloids are widely used in cancer treatment for their ability to target microtubule dynamics. While their efficacy in treating certain cancers is well-established, the full spectrum of their adverse event profiles remains an area of ongoing research. Methods We analyzed AEs related to vinorelbine and vincristine using a retrospective case/non-case approach with data from the FDA Adverse Event Reporting System (FAERS). We applied various algorithms to detect AE signals: the reporting odds ratio (ROR) and proportional reporting ratio (PRR) measured disproportionality and association strength; the Bayesian confidence propagation neural network (BCPNN) calculated the Information Component (IC) for associations against background rates; and the multi-item gamma Poisson shrinker (MGPS) yielded empirical Bayes geometric mean (EBGM) values, accounting for reporting variability. Results Both medications significantly involve the blood and lymphatic systems, with vinorelbine reporting 401 cases in this System Organ Class (SOC), exhibiting a ROR of 17.4, PRR of 12.4, IC of 3.63, and EBGM of 12.38. An intersection analysis of Preferred Terms (PTs) has uncovered previously unreported AEs shared by both drugs, including posterior reversible encephalopathy syndrome and inappropriate antidiuretic hormone secretion. Conclusions This analysis highlights the need for ongoing research of the risks associated with vinorelbine and vincristine.

A Real-World Study on Adverse Reactions of Belimumab Based on the FDA Adverse Event Reporting System Database.

This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy. Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease. Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

Safety assessment of Tafamidis: a real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events

ObjectiveTafamidis-associated adverse events (AEs) were investigated retrospectively by data mining the US Food and Drug Administration Adverse Event Reporting System (FAERS) to inform clinical safety.MethodsData were gathered from the FAERS database, which spans the second quarter of 2019 to the fourth quarter of 2023. A total number of 8532 reports of Tafamidis-related adverse events were detected after evaluating 8,432,351 data. Disproportionality analyses were used to quantify the signal and assess the significance of Tafamidis-associated AEs using four algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the multi-item gamma Poisson shrinker (MGPS) and the Bayesian confidence propagation neural network (BCPNN).ResultsAmong the 8532 reports of AEs with Tafamidis as the primary suspected drug, Tafamidis-induced AEs were identified as occurring in 27 system organ classes (SOC). A total of 207 Tafamidis-induced AEs were detected which simultaneously complied with the four algorithms. Our analysis also identified new adverse reactions including Hypoacusis, Deafness, and Essential hypertension. The median onset of adverse reactions associated with Tafamidis was 180 days (interquartile range [IQR] 51–419 days).ConclusionTafamidis is a drug that has shown favorable safety and tolerability results in clinical trials. However, a number of adverse reactions associated with Tafamidis have been identified through analysis of the FAERS database. In clinical applications, it is recommended to closely monitor patients’ hearing while using Tafamidis. In addition, it is hoped that further experimental and clinical studies will be conducted in the future to understand the mechanism of occurrence between Tafamidis and adverse reactions such as primary hypertension, hyperlipidemia, and height reduction.

Disproportionality analysis of drug-induced dry mouth using data from the United States food and drug administration adverse event reporting system database

BackgroundDrug-induced dry mouth is an adverse reaction that can significantly affect the quality of life and mental state of patients. In this study, we aimed to identify the most common drugs associated with dry mouth using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. MethodsWe accessed data from the FAERS database between the first quarter of 2004 and the first quarter of 2024. The Medical Dictionary for Regulatory Activities was used to identify reports of dry mouth, and disproportionality analyses (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker) were performed to examine the risk signals for dry mouth and its causative drugs. ResultsA total of 75,899 adverse event reports were related to dry mouth. Tiotropium bromide monohydrate (2080 cases) was associated with the majority of dry mouth cases. Disproportionality analysis revealed that the top five drugs with the highest reporting odds ratio (ROR) were darifenacin, solifenacin succinate, fesoterodine fumarate, tolterodine tartrate, and niraparib. Moreover, eight of the top 19 drugs that caused dry mouth were not identified as having major side effects in the package inserts. ConclusionTiotropium bromide monohydrate was the most frequently reported drug for dry mouth, whereas darifenacin had the highest ROR. Collectively, our findings emphasize the necessity for improved recognition and management of drug-induced dry mouth, particularly for medications not adequately flagged for this side effect in their labels.

Post-marketing safety profile of solriamfetol: A real-world disproportionality analysis using FDA adverse event reporting system (FAERS) database

Solriamfetol is a selective dopamine and noradrenalin reuptake inhibitor applied in adult patients with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA). However, the post-marketing safety profile of solriamfetol in large number of people was unrevealed. The purpose of our study is to unravel solriamfetol's adverse events (AEs) in real-world to refine medication safety using Food and Drug Administration Adverse Event Reporting System (FAERS) database. We derived the data associated with solriamfetol from FAERS between 2019 and 2023, and removed the duplicated entries. We evaluated the disproportionality of solriamfetol's AEs by reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS). Among 8,846,085 AE reports, 1659 recorded solriamfetol as the ‘primary suspected (PS)’. 74 significant disproportionality preferred terms (PTs) were retained across 27 organ systems. Moreover, 16 unexpected AEs not mentioned in the FDA label of solriamfetol were identified. Our findings provided the post-marketing safety profile of solriamfetol, highlighting potential solriamfetol's AEs. Further researches are significant to define the causality between solriamfetol and newly identified AEs.

Mining and evaluation of adverse event signals for capmatinib based on the FAERS database.

To conduct a comprehensive data analysis based on the FDA's Adverse Event Reporting System (FAERS) to mine possible adverse event (AE) signals of Capmatinib, providing valuable references for its clinical application. Capmatinib was the primary suspected drug in the search of FAERS database from the second quarter of 2020 to the fourth quarter of 2023. Data processing, screening, and classification were performed using methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). A total of 1,991 AE reports directly related to Capmatinib were screened, identifying 269 Preferred Terms (PTs) involving 26 System Organ Classes (SOCs). Besides the AEs recorded in the drug label (such as edema, nausea, fatigue, and dyspnea), the study unearthed other high-risk AEs not listed in the label, including Renal and urinary disorders, Vocal cord paralysis, and Ear and labyrinth disorders. Among these, renal and urinary disorders, and ear and labyrinth disorders had a higher frequency and intensity of signals, suggesting that their mechanisms of occurrence could be a future research direction. This study uncovered new potential AEs of Capmatinib based on the FAERS database, providing reference for its safe clinical use. Special attention should be given to the occurrence of ear and labyrinth disorders and renal and urinary disorders, primarily presenting as pseudo-acute kidney injury, during treatment.

Adverse event signal mining and severe adverse event influencing factor analysis of Lumateperone based on FAERS database.

Lumateperone has been approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in adults since 2019, however, there is still a lack of data report on adverse reactions in real-world settings. Conducting data mining on adverse events (AEs) associated with Lumateperone and investigating the risk factors for serious AEs can provide valuable insights for its clinical practice. AE reports in the FDA Adverse Event Reporting System (FAERS) from 2019 Q4 (FDA approval of Lumateperone) to 2024 Q1 were collected and analyzed. Disproportionality in Lumateperone-associated AEs was evaluated using the following parameters: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for Lumateperone-induced severe AEs. A total of 2,644 reports defined Lumateperone as the primary suspected drug was collected, including 739 reports classified as severe AEs and 1905 reports as non-severe AEs. The analysis revealed that 130 preferred terms (PTs) with significant disproportionality were based on the four algorithms, 67 (51.53%) of which were not included in the product labeling, affecting 6 systems and organs. In addition, dizziness (81 cases) was the most reported Lumateperone-associated severe AEs, and tardive dyskinesia showed the strongest signal (ROR = 186.24). Logistic regression analysis indicated that gender, bipolar II disorder, and concomitant drug use are independent risk factors for Lumateperone-associated severe AEs. Specifically, female patients had a 1.811-fold increased risk compared with male patients (OR = 1.811 [1.302, 2.519], p = 0.000), while patients with bipolar II disorder had a 1.695-fold increased risk compared with patients diagnosed with bipolar disorder (OR = 1.695 [1.320, 2.178], p = 0.000). Conversely, concomitant use of CYP3A4 inhibitors or drugs metabolized by CYP3A4 was associated with a decreased risk of severe AEs (OR = 0.524 [0.434, 0.633], P = 0.000). Collectively, this study provides critical insights into the safety profile of Lumateperone. It highlights the need for cautious use in high-risk populations, such as females and individuals with bipolar II disorder, and emphasizes the importance of monitoring for AEs, including dizziness and tardive dyskinesia. Healthcare also should remain alert to potential AEs not listed in the prescribing information to ensure medical safety.

Antibody-drug conjugates-related interstitial lung diseases: data mining of the FAERS database

ABSTRACT Background Interstitial lung diseases (ILD) is a serious adverse event (AE) associated with antibody-drug conjugates (ADCs). This study aims to delve deeply into the signals of AE associated with ILD linked to ADCs. Research design and methods The AE reports were extracted from the first quarter of 2004 to the fourth quarter of 2023 based on the FDA Adverse Event Reporting System (FAERS) database. Signal mining was performed using the reporting odds ratio (ROR) method and the multi‐item gamma Poisson shrinker (MGPS) method. Data management, analysis, and visualization were carried out using Python, R software, and MySQL. Results A total of 1389 AE reports related to ILD with 11 types of ADCs as the primary suspected drugs were obtained. The age groups most represented were 61–80 age group. ILD-related AE signals were detected for 11 ADCs in the study. Trastuzumab deruxtecan showed the strongest signals in both for ROR and MGPS methods. The median onset time vary from 8 days to 207 days. Conclusions The signals of ILD AE associated with ADCs are notably strong. ILD should be closely monitored and assessed in the clinical use of ADCs taking full account of the efficacy and risks of these drugs.

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.

A discovery and verification approach to pharmacovigilance using electronic healthcare data.

Pharmacovigilance is vital for drug safety. The process typically involves two key steps: initial signal generation from spontaneous reporting systems (SRSs) and subsequent expert review to assess the signals' (potential) causality and decide on the appropriate action. We propose a novel discovery and verification approach to pharmacovigilance based on electronic healthcare data. We enhance the signal detection phase by introducing an ensemble of methods which generated signals are combined using Borda count ranking; a method designed to emphasize consensus. Ensemble methods tend to perform better when data is noisy and leverage the strengths of individual classifiers, while trying to mitigate some of their limitations. Additionally, we offer the committee of medical experts with the option to perform an in-depth investigation of selected signals through tailored pharmacoepidemiological studies to evaluate their plausibility or spuriousness. To illustrate our approach, we utilize data from the German Pharmacoepidemiological Research Database, focusing on drug reactions to the direct oral anticoagulant rivaroxaban. In this example, the ensemble method is built upon the Bayesian confidence propagation neural network, longitudinal Gamma Poisson shrinker, penalized regression and random forests. We also conduct a pharmacoepidemiological verification study in the form of a nested active comparator case-control study, involving patients diagnosed with atrial fibrillation who initiated anticoagulant treatment between 2011 and 2017. The case study reveals our ability to detect known adverse drug reactions and discover new signals. Importantly, the ensemble method is computationally efficient. Hasty false conclusions can be avoided by a verification study, which is, however, time-consuming to carry out. We provide an online tool for easy application: https://borda.bips.eu.

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.

A real-world pharmacovigilance study of cardiac adverse events induced by sugammadex in the FDA adverse event reporting system

ABSTRACT Background Sugammadex is a novel agent that reverses neuromuscular blockade during general anesthesia. Recent case reports have raised concerns regarding potential cardiac adverse events (CAEs). However, no large-scale real-world studies have yet evaluated the potential link between sugammadex and CAEs. Research design and methods Data from the FDA Adverse Event Reporting System were obtained. The association between sugammadex and CAE was evaluated using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. Serious outcomes resulting from sugammadex-related CAEs were assessed, and complications associated with CAEs were evaluated. Results Nineteen CAEs were identified and classified into two categories: cardiac arrhythmias and coronary artery disorders. The most frequent CAEs were bradycardia (n = 202), cardiac arrest (n = 119), tachycardia (n = 30), and Kounis syndrome (n = 22). Subgroup analysis based on age, sex, and weight revealed parallel findings. The CAEs most likely to result in serious consequences were pulseless electrical activity and cardiac arrest. The most common concurrent adverse effects with CAEs were hypotension (n = 51), anaphylactic reactions (n = 46), and anaphylactic shock (n = 23). Conclusion This study suggests a potential link between sugammadex and CAEs, highlighting the need for careful monitoring and personalized risk assessment, especially in patients with cardiovascular risk factors.

Analysis of lumateperone data for patients with schizophrenia using related adverse events from the FDA adverse reporting system

ABSTRACT Background Our study utilized the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) to analyze and study the adverse event (AEs) signals of second-generation antipsychotic drug lumateperone, providing a reference for clinical safety monitoring in the treatment of schizophrenia. Methods The International Dictionary of Medical Terminology (version 26.0) was used to standardize the preferred system organ category (SOC) and preferred terminology (PT) for adverse drug events (ADE) data related to lumateperone. ADE signals were classified and described using four algorithms: reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian confidence-propagation neural network (BCPNN) and Multinomial gamma-poisson shrinkage (MGPS). Result Among the 2542 case reports collected from the FAERS database, 1762 reports with lumateperone as a ‘principal suspect(PS)’ AEs were identified. Lumateperone-induced AEs occurred in 26 system organ categories (SOC). A total of 118 significant disproportionate preferred terms (PTs) meeting the requirements of 4 algorithms were retained, and unexpected major events, such as burning sensation, tremor, migraine etc. may also occur. The median time to onset of lumateperone-related adverse events was 9 days (interquartile range [IQR] 2–31.25 days), and most AEs occurred within the first 10 days and 1 month after initiation of lumateperone therapy. Conclusion Our research may provide a better understanding of the potential adverse events that may be caused by lumateperone and those not recorded in the drug instructions, providing valuable signals for clinical use.

A real-world pharmacovigilance study of KRAS G12C mutation inhibitors based on the food and drug administration adverse event reporting system.

Sotorasib and adagrasib have been widely used for the non-small cell lung cancer (NSCLC) patients harboring Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation. It's necessary to assess their safety profiles in the real-world population. A retrospective pharmacovigilance was conducted to examine adverse events (AEs) associated with sotorasib and adagrasib therapies using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Disproportionality analysis was performed employing Venn analysis and four data-mining algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS). The most commonly reported system organ classes (SOCs) for both adagrasib and sororasib were general, gastrointestinal, and investigations disorders. Notably, sotorasib exhibited significant signals for neoplasms and hepatobiliary disorders in four algorithms. Specifically, AEs related to neoplasms were predominantly associated with lung malignancies, all of which were consistent with the therapeutic indications of KRAS G12C mutation inhibitor. A total of 19 common AEs were identified in sotorasib and adagrasib, spanning gastrointestinal, general, hepatobiliary, investigations, metabolism, musculoskeletal, neoplasms, and respiratory disorders. 4 severe AEs (SAEs) were identified in sotorasib, with 3 SAEs displaying significant signals in four algorithms, including drug-induced liver injury, pancreatitis, and hepatic failure. In adagrasib, only 2 SAEs were detected, with renal failure showing significant signals in four algorithms. This study offers a comprehensive evaluation of the major safety signals associated with sotorasib and adagrasib, providing valuable information for clinicians regarding drug selection and safety considerations, thereby facilitating the design of future prospective safety studies.