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• This study analyzes Yasmin-related adverse events (AEs) using FAERS database data from 2004 to 2023. • Hepatobiliary, vascular, and psychiatric disorders were the top reported AEs for Yasmin users. • Novel adverse reactions like fear of disease and acute cor pulmonale identified with high signal strength. • Results emphasize the need for cautious prescribing and patient awareness of potential AEs with Yasmin. This study aimed to elucidate the scope and nature of adverse events (AEs) associated with Yasmin. Among the 17,035,572 AE reports collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 2004 and September 2023, 25,949 reports involved Yasmin. The demographic details, clinical outcomes, and sources of reports were extracted, and four algorithms were used to evaluate adverse drug reactions. The majority of the AE reports involved females aged 18–45 years. Hospitalization was the most frequently reported serious outcome (46.84 %), with death occurring in 292 patients (1.82 %). The highest number of reports originated from the United States. Adverse reactions spanned across 24 system organ categories (SOCs), and hepatobiliary, vascular, and psychiatric disorders were the most frequently reported AEs. A total of 229 Preferred Terms (PTs) were identified for adverse reactions, with high signal strength observed for conditions such as post-cholecystectomy syndrome. In addition, fear of disease, which has not been previously identified as an AE related to Yasmin, was also identified as a high signal strength side effect. The findings of the present study underscore the importance of monitoring and identifying potential AEs in patients receiving Yasmin, including those not currently listed in the medication instructions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential association between tumor lysis syndrome (TLS) and drugs for the treatment of malignant melanoma (MM). Methods: Reports of TLS recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004-2023q3) were identified. Demographic and clinical characteristics were described, and disproportionality signals were assessed through the Reporting Odds Ratio (ROR) and Information Component (IC). The latency of TLS with anticancer drugs was described based on parametric models. Subgroup analysis was conducted to explore the differences of TLS signals in different age and sex. Results: We found 5 (1.49%), 59 (17.61%), 79 (23.58%), 19 (5.67%), 13 (3.88%), 13 (3.88%), 33 (9.85%), 49 (14.63%), 16 (4.78%) TLS reports with pembrolizumab, nivolumab, ipilimumab, dabrafenib, vemurafenib, dacarbazine, "encorafenib and binimetinib", "nivolumab and ipilimumab", "dabrafenib and trametinib", respectively. The combination of encorafenib and binimetinib showed the strongest signal of TLS (IC025 = 3.98). The median days of latency of TLS with combination of encorafenib and binimetinib is 2 days, which was much shorter than nivolumab (22.0 days) and ipilimumab (21.5 days). TLS cases associated with drugs for MM were predominantly recorded in females and aged 25-65 years. After excluding confounding factors such as pre-existing diseases and co-treated drugs, the disproportionate signal of TLS with "encorafenib and binimetinib" remained strong. Conclusions: Stronger disproportionate signal of TLS was detected in MM patients using the combination of encorafenib and binimetinib than other drugs. Further research is needed to investigate the underlying mechanisms and identify patient-related predisposing factors to support safe prescribing of the combination of encorafenib and binimetinib. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: 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). Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Tralokinumab, a humanized monoclonal antibody targeting interleukin-13, has been primarily used for the treatment of moderate-tosevere atopic dermatitis. Given its extensive use in clinical practice, understanding its safety profile in the real-world setting is crucial. Methods: This study utilized disproportionality analysis to evaluate the safety of tralokinumab in clinical practice by analyzing all adverse event reports since 2021 in the FDA Adverse Event Reporting System database that identified tralokinumab as the primary suspected drug. Reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network were used for disproportionality analyses of adverse events related to tralokinumab. Additionally, the Weibull distribution was employed to model the risk of adverse events over time. Results: Adverse reactions documented on the drug label, such as injection site reactions, conjunctivitis, and upper respiratory infections, displayed positive signals. Additionally, potential adverse reactions not mentioned on the label were also identified, including dizziness, headache, nausea, vomiting, hair loss, and acne. The importance of adverse event monitoring, particularly in the first month after treatment initiation, was emphasized. Conclusion: This study has provided preliminary safety data on the real-world application of tralokinumab, confirming some known adverse reactions and revealing additional potential risks. The findings offer critical safety information for clinicians prescribing tralokinumab to treat atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Neuromuscular blocking agents (NMBAs) are primarily used during surgical procedures to facilitate endotracheal intubation and optimize surgical conditions. This study aimed to explore the adverse event signals of NMBAs, providing reference for clinical safety. Methods: This study collected reports of atracurium, cisatracurium, rocuronium, and vecuronium as primary suspect drugs in The US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2023. The adverse events (AEs) reported in the study were retrieved based on the Preferred Terms (PTs) of the Medical Dictionary for Regulatory Activities. In addition, we conducted disproportionality analysis on relevant reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A positive signal was generated when both algorithms show an association between the target drug and the AE. Results: A total of 11,518 NMBA-related AEs were reported in the FAERS database. The most AEs of rocuronium were collected. NMBA-related AEs involved 27 different system organs (SOCs), all of the four NMBAs had positive signals in “cardiac disorders,” “immune system disorders,” “respiratory, thoracic and mediastinal disorders” and “vascular disorders.” At the PTs level, a total of 523 effective AEs signals were obtained for the four NMBAs. AEs labled in the instructions such as anaphylaxis (include anaphylactic reaction and anaphylactic shock), bronchospasm, respiratory arrest and hypotension were detected positive signals among all NMBAs. In addition, we also found some new AEs, such as ventricular fibrillation for the four NMBAs, hyperglycaemia for atracurium, kounis syndrome and stress cardiomyopathy for rocuronium, hepatocellular injury for cisatracurium, hyperkalaemia for vecuronium. To further investigated the AEs associated with serious clinical outcomes, we found that cardiac arrest and anaphylaxis were the important risk factors for death due to NMBAs. Conclusion: NMBA-related AEs have a significant potential to cause clinically severe consequences. Our study provides valuable references for the safety profile of NMBAs, and considering the limitations of the FAERS database, further clinical data are needed to validate the findings of this study. [ABSTRACT FROM AUTHOR]

Abstract Congenital anomalies of the external ear can have a significant impact on a child’s development and quality of life. While genetic factors play a crucial role in the etiology of these anomalies, environmental factors such as drug exposure during pregnancy may also contribute to their occurrence. This study aims to investigate the association between drug exposure and congenital anomalies of the external ear using data from an adverse drug reaction report database. Using OpenVigil 2.1, we queried the FAERS database to retrieve adverse event reports from the first quarter of 2004 to the first quarter of 2024. To identify relevant cases, we used Medical Dictionary for Regulatory Activities terms focusing on congenital anomalies of the external ear. Drug generic names were sourced from the DrugBank database. To assess safety signals and rank drugs by their signal strength, we conducted a disproportionality analysis, generating reporting odds ratios (ROR) and proportional reporting ratios (PRR). A total of 20,754,281 AE reports were identified in the FAERS database from Q1 2004 to Q1 2024, of which 1763 were related to congenital anomalies of the external ear. Valproic acid (122 cases) was associated with the most cases, followed by mycophenolate mofetil (105 cases) and lamotrigine (65 cases). According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were primidone (ROR: 397.05, 95% CI 147.21, 1070.9; PRR: 388.71, 95% CI 145.89, 1035.7), valproic acid (ROR: 239.46, 95% CI 123.75, 463.37; PRR: 236.42, 95% CI 123.82, 451.43), tapazole (ROR: 198.35, 95% CI 63.49, 619.67; PRR: 196.25, 95% CI 62.97, 611.67), nevirapine (ROR: 138.24, 95% CI 82.9, 230.51; PRR: 137.23, 95% CI 82.44, 228.44), and sebivo (ROR: 117.1, 95% CI 48.51, 282.67; PRR: 116.37, 95% CI 48.17, 281.12). This study identified several drugs significantly associated with congenital anomalies of the external ear in the FAERS database using disproportionality analysis. The findings can help healthcare professionals better recognize and manage drug-induced congenital anomalies of the external ear, particularly when prescribing high-risk medications. Further research is needed to elucidate the mechanisms underlying these associations and develop strategies for preventing and mitigating drug-induced congenital anomalies of the external ear.

Background: Tildrakizumab, the IL-23 inhibitor, is used to treat plaque psoriasis and psoriatic arthritis. Many studies have reported adverse drug reactions (ADRs) associated with Tildrakizumab. Objective: The aim of this study was to describe ADRs associated with Tildrakizumab monotherapy by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: The signals of Tildrakizumab-associated ADRs were quantified using disproportionality analyses such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms. Results: A total of 10,530,937 reports of ADRs were collected from the FAERS database, of which 1,177 reports were identified with tildrakizumab as the "primary suspect (PS)". Tildrakizumab-induced ADRs occurred against 27 system organ classes (SOCs). A total of 32 significant disproportionality Preferred Terms (PTs) conformed to the algorithms. Unexpected significant ADRs such as coronavirus infection, herpes simplex, diverticulitis, atrial fibrillation and aortic valve incompetence were also possible. The median time to onset of Tildrakizumabassociated ADRs was 194 days (interquartile range [IQR] 84-329 days), with the majority occurring, within the first 1 and 3 months after initiation of Tildrakizumab. Conclusion: This study identified a potential signal for new ADRs with Tildrakizumab, which might provide important support for clinical monitoring and risk prediction. [ABSTRACT FROM AUTHOR]

Objective: As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events. Research design and methods: We used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated. Results: In the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged <18 years, 18–64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure (n = 277) and embolic and thrombotic events, venous (n = 446) were the most frequently reported CVD-related AEs in ADCs. Conclusion: By mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality. [ABSTRACT FROM AUTHOR]

BackgroundFluoroquinolones are broad-spectrum antibiotics with significant antimicrobial activity. Despite their therapeutic benefits, they are associated with a range of adverse drug reactions (ADRs), particularly those affecting the central nervous system (CNS). This study aimed to analyze the psychiatric ADRs linked to fluoroquinolones using data from the FDA Adverse Event Reporting System (FAERS) database.MethodsA retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q4 2023. The data processing phase involved the FDA-recommended deduplication method, and ADRs were classified according to Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis was performed using the reporting odds ratio (ROR), and statistical significance was assessed using the Chi-square test or Fisher’s exact test.ResultsThe study identified 84,777 reports associated with fluoroquinolones, with 359,480 Preferred Terms-annotated entries, 27,816 of these reports were psychiatric ADRs. Mood disorders were the most frequently reported, including anxiety, depression, and delirium, with some reports escalating to suicidal ideation and behaviors. The Standardized MedDRA Query classification system was used to categorize these ADRs into Depression, Suicide/self-injury, Psychosis and psychotic disorders, and Non-infectious encephalopathy/delirium. Ciprofloxacin was most frequently linked to depression and suicidal ideation, while moxifloxacin showed a robust correlation with delirium. The risk of psychiatric ADRs varied by age group, with affective disorders more prevalent in adults under 65 and psychosis and delirium in those over 65.ConclusionFluoroquinolones are associated with a range of psychiatric ADRs, with notable differences between the drugs in the class. The study highlights the need for caution in prescribing fluoroquinolones, particularly for patients with pre-existing mental health conditions or those in higher risk age groups. The findings also underscore the importance of considering age-specific preventive strategies when administering these antibiotics.

Background: Drug-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. Methods: We 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. Results: A 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. Conclusion: Tiotropium 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.

Background: Fluoroquinolones, including ciprofloxacin, levofloxacin, and moxifloxacin, are extensively employed as broad-spectrum antibacterial agents. However, their use is discouraged during pregnancy due to potential adverse events (AEs). The aim of this study is to systematically investigate the association between fluoroquinolones (specifically ciprofloxacin, levofloxacin, and moxifloxacin) and AEs related to pregnancy, as well as their potential impact on congenital disorders. Methods: A disproportionality analysis was conducted utilizing FDA Adverse Event Reporting System (FAERS) data spanning from the first quarter of 2004 to September 2023. The objective was to identify potential AEs signatures associated with fluoroquinolones through conducting reporting odds ratios (RORs) and Bayesian confidence propagation neural networks (BCPNN). Assessing the potential risk of pregnancy-associated AEs involved comparing each fluoroquinolone with all other medications. Additionally, in-depth comparative analyses were carried out between various fluoroquinolones and a reference drug (azithromycin). Results: A total of 1159 cases were identified, involving AEs related to pregnancy and congenital disorders. Obvious disproportionate association of abortion spontaneous and other nine AEs was identified for fluoroquinolone during gestation. Upon comparison with all the other drugs, ciprofloxacin exhibited an elevated risk of spontaneous abortion, non-site specific bone disorders congenital and 10 other significant signals. Levofloxacin demonstrated an increased risk of congenital tongue disorders and three other significant signals. Moxifloxacin displayed a noteworthy signal indicating multiple congenital cardiac abnormalities. Conclusions: We present compelling evidence regarding pregnancy-related AEs and congenital disorders linked to fluoroquinolones. Considering perinatal and genotoxicity aspects, we explore whether levofloxacin or moxifloxacin might be preferable when fluoroquinolones are deemed necessary to balance the benefits of pregnant women and fetuses.

BackgroundLow molecular weight heparin (LMWH) is extensively utilized as an anticoagulant for the prevention and management of various thrombotic conditions. However, despite the widespread use of LMWH in clinical indications, its adverse events (AEs) have not received substantial attention, and there is a lack of systematic and comprehensive AE studies. This study aims to evaluate AE signals associated with LMWH in the overall population and in pregnancy women from the FDA Adverse Event Reporting System database.MethodsWe used the Standardized MedDRA Query to identify pregnancy-related AE reports. Disproportionality analyses were employed to identify LMWH-related AE by calculating the reporting odds ratios (ROR), proportional reporting ratios (PRR), bayesian confidence propagation neural network (BCPNN), and the empirical Bayesian geometric mean (EBGM).ResultsFor the overall population, the significantly reported adverse signals in SOCs were pregnancy, puerperium, and perinatal conditions, vascular disorders, blood and lymphatic system disorders, and product issues. The five strongest AEs signal of LMWH-related were anti factor X antibody positive (n = 6, ROR 506.70, PRR 506.65, IC 8.31, EBGM 317.03), heparin-induced thrombocytopenia test positive (n = 19, ROR 263.10, PRR 263.02, IC 7.65, EBGM 200.79), anti factor X activity increased (n = 10, ROR 255.93, PRR 255.89, IC 7.62, EBGM 196.61), heparin-induced thrombocytopenia test (n = 14, ROR 231.85, PRR 231.80, IC 7.51, EBGM 182.09), and spontaneous heparin-induced thrombocytopenia syndrome (n = 3, ROR 230.31, PRR 230.30, IC 7.50, EBGM 181.16). For pregnancy women, the five strongest AEs signals of LMWH-related included sternal fracture (n = 3, ROR 243.44, PRR 243.35, IC 6.61, EBGM 97.94), syringe issue (n = 12, ROR 97.49, PRR 97.34, IC 5.94, EBGM 61.21), bleeding time prolonged (n = 3, ROR 97.38, PRR 97.34, IC 5.94, EBGM 61.21), spinal compression fracture (n = 10, ROR 90.24, PRR 90.13, IC 5.87, EBGM 58.30), and injection site haematoma (n = 19, ROR 79.23, PRR 79.04, IC 5.74, EBGM 53.47). Additionally, unexpected AEs associated with LMWH in pregnancy women were observed, including premature baby death, placental necrosis, abortion, antiphospholipid syndrome, systolic dysfunction, compartment syndrome, body height decreased, rubella antibody positive, and ultrasound doppler abnormal.ConclusionThis study identified unexpected AE signals of LMWH-relate in pregnancy women. Our study could provide valuable evidence for the clinical practice of LMWH, especially for identifying AEs and ensuring safe usage in pregnancy women.

Abstract Recent studies focused on exploring phosphodiesterase type 5 inhibitors (PDE5Is)-related hearing impairment. This study aimed to comprehensively explore real-world hearing impairment associated with PDE5Is based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). The characteristics and correlation of PDE5Is-related hearing impairment reported in the FAERS database from the fourth quarter of 2003 to the second quarter of 2023 were analyzed using disproportionality analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) were used to analyze the adverse events (AEs) of hearing impairment. A total of 1,438 reported cases of hearing impairment were associated with four PDE5Is, revealing statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) with the SMQ. The average age of all patients was more than 55 years, over 70% of AEs were reported in men. Most of the reported cases were from the United States. Reports for all the drugs indicated an increase since 2008, except for avanafil. This study showed that the disability rates of PDE5Is were 8.14–40%, the rates of initial or prolonged hospitalization were 6.21–10.24%, and the rates of required intervention were 3.31–9.45%. The pharmacovigilance study identified a potential risk of hearing impairment associated with PDE5Is, indicating the need for continuous monitoring and appropriate management.

Recent studies focused on exploring phosphodiesterase type 5 inhibitors (PDE5Is)-related hearing impairment. This study aimed to comprehensively explore real-world hearing impairment associated with PDE5Is based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). The characteristics and correlation of PDE5Is-related hearing impairment reported in the FAERS database from the fourth quarter of 2003 to the second quarter of 2023 were analyzed using disproportionality analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) were used to analyze the adverse events (AEs) of hearing impairment. A total of 1,438 reported cases of hearing impairment were associated with four PDE5Is, revealing statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) with the SMQ. The average age of all patients was more than 55 years, over 70% of AEs were reported in men. Most of the reported cases were from the United States. Reports for all the drugs indicated an increase since 2008, except for avanafil. This study showed that the disability rates of PDE5Is were 8.14–40%, the rates of initial or prolonged hospitalization were 6.21–10.24%, and the rates of required intervention were 3.31–9.45%. The pharmacovigilance study identified a potential risk of hearing impairment associated with PDE5Is, indicating the need for continuous monitoring and appropriate management. [ABSTRACT FROM AUTHOR]

• Real-world safety of Levetiracetam based on FAERS and disproportionality analysis. • Levetiracetam carries a potential risk of causing rhabdomyolysis, SJS, TEN, DRESS. • Be mindful of spontaneous abortion and stillbirth in pregnant women. • Suspicious signals such as drug interaction warrant heightened attention. Levetiracetam is a relatively new and widely utilized anti-seizure medication; however, limited information is available regarding its adverse effects. This study aims to thoroughly investigate, evaluate, and present evidence on the safety profile of Levetiracetam, relying on data from the FDA Adverse Event Reporting System (FAERS) database to facilitate informed clinical decision-making. We employed various statistical measures, including Reporting Odds Ratio (ROR), Proportionate Reporting Ratio (PRR), and analysis by the Medicines and Healthcare Products Regulatory Agency (MHRA), to identify signals of adverse reactions associated with Levetiracetam. Positive signals consistent with Designated Medical Event (DME) were singled out for focused comparison and discussion. The analysis of 26,182 adverse events linked to Levetiracetam as the primary suspected drug revealed 692 positive signals spanning 22 System Organ Classes (SOCs). Nervous system disorders were the most frequently reported, followed by psychiatric disorders, and general disorders and administration site conditions. 11 positive signals consistent with Preferred Terms (PTs) in DME were identified, predominantly concentrated in 6 SOCs. Among these, rhabdomyolysis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) exhibited relatively large values of A, ROR, and Chi-squared. Additionally, PTs related to spontaneous abortion, drug interaction, urethral atresia, ventricular septal defect, and atrial septal defect showed significant strength. The study indicates that Levetiracetam carries a potential risk of causing rhabdomyolysis, SJS, TEN, DRESS as well as spontaneous abortion. Signals related to drug interaction, urethral atresia, ventricular septal defect, and atrial septal defect warrant heightened attention in clinical use. [ABSTRACT FROM AUTHOR]

Introduction: Linezolid is an oxazolidinone antibiotic that is active against drugresistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups. Results: A total of 11,176 reports of linezolid as the “primary suspected” drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia (n = 1,139, ROR 21.98), anaemia (n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis (n = 90, ROR 4.33), and electrocardiogram QT prolonged (n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs (n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment (n = 46). Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings. [ABSTRACT FROM AUTHOR]

Background: With the increased use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in cancer patients, adverse events (AEs) have garnered considerable interest. We conducted this pharmacovigilance study to evaluate the AEs of BCR-ABL1 TKIs in cancer patients using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: To query AE reports from the FAERS database, we used OpenVigil 2.1. Descriptive analysis was then employed to describe the characteristics of TKIs-associated AE reports. We also utilized the disproportionality analysis to detect safety signals by calculating the proportional reporting ratio (PRR) and reporting odds ratios (ROR). Results: From the FAERS database, a total of 85,989 AE reports were retrieved, with 3,080 significant AE signals identified. Specifically, imatinib, nilotinib, dasatinib, bosutinib, and ponatinib had significant AE signals of 1,058, 813, 232, 186, and 791, respectively. These significant signals were further categorized into 26 system organ classes (SOCs). The AE signals of imatinib and ponatinib were primarily associated with general disorders and administration site conditions. On the other hand, nilotinib, dasatinib, and bosutinib were mainly linked to investigations, respiratory, thoracic and mediastinal disorders, and gastrointestinal disorders, respectively. Notably, new signals of 245, 278, 47, 55, and 253 were observed in imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, respectively. Conclusions: The results of this study demonstrated that AE signals differ among the five BCR-ABL1 TKIs. Furthermore, each BCR-ABL1 TKI displayed several new signals. These findings provide valuable information for clinicians aiming to reduce the risk of AEs during BCR-ABL1 TKI treatment. [ABSTRACT FROM AUTHOR]

Introduction: Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL- 4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab. Methods: Spontaneous reports were used from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities® (MedDRA®). Safety signal strength was assessed by the Reporting Odds Ratio (ROR). Results: 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24-63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4--29.3). Conclusion: Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation. [ABSTRACT FROM AUTHOR]

Purpose: To detect the possible safety signal of purine antimetabolites associated with Pneumocystis jirovecii pneumonia through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database. Methods: A case/non‐case retrospective disproportionality analysis was performed in the publicly available FAERS database using AERSmine (2004Q1–2021Q3). Four models were developed to explore the signal strength of PAs among different populations with possible confounding factors. Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) was used as the data mining algorithm for the analysis. A value of ROR‐1.96SE > 1 and PRR ≥ 2 with an associated X2 value of 4 or more was considered the threshold for a signal. Results: A total of 7073 reports associated with Pneumocystis jirovecii pneumonia were present in the database, of which 899 reports were associated with purine antimetabolites. A crude signal strength of ROR 15.76(14.70–16.91) was obtained for purine antimetabolites associated PJP, with the highest signal strength reported with fludarabine and thioguanine [ROR 19.63(17.42–22.13); 19.45(13.21–28.63)]. Stratifying the cases based on autoimmune disorders and the cancer population revealed an ROR of 3.33(2.46–4.50) and 2.93(2.26–3.79) respectively. The highest risk of PJP with use of PAs was observed amongst children with a higher risk of nearly 2 times than the adult population [ROR 11.57(9.16–14.62)]. Conclusions: Our study provided evidence on the occurrence of PJP with the use of purine antimetabolites among the autoimmune and cancer population. We identified signals for PJP with azathioprine, mercaptopurine, thioguanine, cladribine, fludarabine, and clofarabine. More research with a superior epidemiological study design of a defined population is required to validate these findings. [ABSTRACT FROM AUTHOR]

Background and purpose: The development and approval of inhibitors of cyclin-dependent kinase 4/6 (CDK4/6) is an essential milestone in treating hormone receptor-positive metastatic breast cancer. The efficacy of these drugs is similar, but the adverse events (AE) are different, directly affecting the physician's choice of drug. There is no systematic study on the safety of CDK4/6 inhibitors in the real world. In this study, we compared the differences in AE of CDK4/6 inhibitors through signal mining in the FDA Adverse Event Reporting System (FAERS) and identified unknown AE signals to provide a reference for the clinical choice of treatment and monitoring AE. Methods: All data in the FAERS database were extracted from the first quarter of 2004 to the first quarter of 2023. After removing duplicates, data were analyzed by the disproportionality method for reports ranking palbociclib, abemaciclib, or ribociclib as the primary suspect. Signals were identified using the reporting odds ratio (ROR) and MHRA methods. Positive signals were required to meet the following criteria: the number of reports ≥3, the lower limit of the 95% confidence interval of the ROR >1, proportional reporting ratios (PRR) >2, and the χ2 >4. Results: A total of 85 562 reports of AE associated with CDK4/6 inhibitors were identified. The highest signal intensity of palbociclib was observed in hematologic and lymphatic AE (leukopenia ROR = 20.01). Palbociclib had lower AE signals in the gastrointestinal, hepatic, and renal systems than the other drugs (diarrhea ROR = 1.95, gamma-glutamyltransferase increased ROR = 0.36, blood creatinine increased ROR = 1.01). Abemaciclib had the strongest signal in the gastrointestinal system (diarrhea ROR = 13.54); it also showed a strong AE signal in the hepatic and renal systems (gamma-glutamyltransferase increased ROR = 2.58, blood creatinine increased ROR = 7.74) and a lower AE signal than the other drugs in the blood and lymphatic systems (leukopenia ROR = 5.34). Ribociclib had a lower AE signal intensity in the blood and lymphatic system than palbociclib (leukopenia ROR = 7.55); however, among hepatic AE, ribociclib had the highest signal intensity of increased gamma-glutamyltransferase (ROR = 4.05). In rare severe hepatic systemic AE, abemaciclib had the strongest signal in hepatic failure (ROR = 3.50) and drug-induced liver injury (ROR = 4.68). Erythema multiforme was a newly identified signal in the abemaciclib reports (ROR = 3.06). Conclusion: The safety profile of CDK4/6 inhibitors varies. Analysis of the FAERS database revealed hematologic and lymphatic system toxicities for palbociclib and ribociclib and gastrointestinal and hepatorenal toxicities for abemaciclib. Erythema multiforme was found as a novel severe AE for abemaciclib. Individualized drug selection and monitoring of AE based on the patient’s physiological status and AE are needed during treatment.

Abstract Background Rucaparib 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. Methods Disproportionality 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. Results A 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. Conclusion Our study demonstrated potential new AEs of rucaparib, and further studies were expected to confirm the results.

Introduction: Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL-4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab.Methods: Spontaneous reports were used from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities® (MedDRA®). Safety signal strength was assessed by the Reporting Odds Ratio (ROR).Results: 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24–63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4–29.3).Conclusion: Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation.

Background and purpose: The development and approval of inhibitors of cyclin-dependent kinase 4/6 (CDK4/6) is an essential milestone in treating hormone receptor-positive metastatic breast cancer. The efficacy of these drugs is similar, but the adverse events (AE) are different, directly affecting the physician's choice of drug. There is no systematic study on the safety of CDK4/6 inhibitors in the real world. In this study, we compared the differences in AE of CDK4/6 inhibitors through signal mining in the FDA Adverse Event Reporting System (FAERS) and identified unknown AE signals to provide a reference for the clinical choice of treatment and monitoring AE. Methods: All data in the FAERS database were extracted from the first quarter of 2004 to the first quarter of 2023. After removing duplicates, data were analyzed by the disproportionality method for reports ranking palbociclib, abemaciclib, or ribociclib as the primary suspect. Signals were identified using the reporting odds ratio (ROR) and MHRA methods. Positive signals were required to meet the following criteria: the number of reports ≥3, the lower limit of the 95% confidence interval of the ROR ＞1, proportional reporting ratios (PRR) ＞2, and the χ2 ＞4. Results: A total of 85 562 reports of AE associated with CDK4/6 inhibitors were identified. The highest signal intensity of palbociclib was observed in hematologic and lymphatic AE (leukopenia ROR=20.01). Palbociclib had lower AE signals in the gastrointestinal, hepatic, and renal systems than the other drugs (diarrhea ROR=1.95, gamma-glutamyltransferase increased ROR=0.36, blood creatinine increased ROR=1.01). Abemaciclib had the strongest signal in the gastrointestinal system (diarrhea ROR=13.54); it also showed a strong AE signal in the hepatic and renal systems (gamma-glutamyltransferase increased ROR=2.58, blood creatinine increased ROR=7.74) and a lower AE signal than the other drugs in the blood and lymphatic systems (leukopenia ROR=5.34). Ribociclib had a lower AE signal intensity in the blood and lymphatic system than palbociclib (leukopenia ROR=7.55); however, among hepatic AE, ribociclib had the highest signal intensity of increased gamma-glutamyltransferase (ROR=4.05). In rare severe hepatic systemic AE, abemaciclib had the strongest signal in hepatic failure (ROR=3.50) and drug-induced liver injury (ROR=  4.68). Erythema multiforme was a newly identified signal in the abemaciclib reports (ROR= 3.06). Conclusion: The safety profile of CDK4/6 inhibitors varies. Analysis of the FAERS database revealed hematologic and lymphatic system toxicities for palbociclib and ribociclib and gastrointestinal and hepatorenal toxicities for abemaciclib. Erythema multiforme was found as a novel severe AE for abemaciclib. Individualized drug selection and monitoring of AE based on the patient’s physiological status and AE are needed during treatment. [ABSTRACT FROM AUTHOR]

Objective: Quetiapine, an atypical second‐generation antipsychotic drug, is approved for treatment of schizophrenia, bipolar disorder, and depression. Due to the limitations of clinical trials, the association between quetiapine and rare cardiac adverse events (AEs) is still unclear. This study is to evaluate quetiapine‐associated cardiac AEs through data mining of FDA Adverse Event Reporting System (FAERS). Methods: Reporting odds ratio (ROR) was used to quantify the signals of quetiapine‐related cardiac AEs from the first quarter (Q1) of 2018–2022 Q1. Serious and nonserious cases were compared, and signals were prioritized using a rating scale. Results: A total of 1004 cases of quetiapine‐associated cardiac AEs were identified, with 31 signals being detected, among which 13 AEs were identified as new and unexpected signals. Besides, nine and 22 cardiac AEs were identified as moderate and weak clinical priority. The median TTO for moderate and weak clinical priority signals were 0 and 4 days, respectively. All of the cardiac AEs had early failure type characteristics, suggesting that most of the patients developed cardiac AEs in a few days after quetiapine treatment, and that the risk of cardiac AEs occurrence would be gradually decreased over time. Conclusion: Our study provided valuable evidence for health‐care professionals to mitigate the risk of quetiapine‐associated cardiac AEs based on an extensive analysis of a real‐world, large‐sample FAERS database, and prioritize cardiac AE signals. [ABSTRACT FROM AUTHOR]

Background: Rucaparib 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. Methods: Disproportionality 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. Results: A 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. Conclusion: Our study demonstrated potential new AEs of rucaparib, and further studies were expected to confirm the results. [ABSTRACT FROM AUTHOR]

• Our study using the FDA Adverse Event Reporting System (FAERS) identified 232 valuable positive signals related to adverse reactions to Lacosamide. • The most frequently reported system organ classifications (SOCs) were nervous system disorders, psychiatric disorders, and injury, poisoning, and procedural complications. • Two signals of stevens-johnson syndrome and ventricular fibrillation were consistent with PT signals on the designated medical event (DME) list, and the inclusion of rhabdomyolysis as a rare ADR is also noteworthy. • The research highlights the potential risks of cardiac arrest, ventricular fibrillation, stevens-johnson syndrome, and rhabdomyolysis associated with the clinical use of Lacosamide. • Understanding these adverse reactions is crucial for the safe and appropriate use of Lacosamide in the treatment of focal seizures. Lacosamide is licensed for the treatment of focal seizures in both adults and children, however there is little information available on its adverse reactions. Using the FDA Adverse Event Reporting System (FAERS), we seek to assess adverse occurrences that may be related to Lacosamide. On the basis of the FAERS database from the fourth quarter of 2008 to the second quarter of 2022, disproportionality analysis was carried out using the reporting odds ratio (ROR) method, the United Kingdom Medicines and Healthcare Products Regulatory Agency omnbius standard (MHRA) method, and the bayesian confidence propagation neural network (BCPNN) method. We extracted valuable positive signals for designated medical event (DME) screening, focused on the evaluation and comparison of safety signals appearing in DME with system organ classification (SOC) analysis. A total of 10,226 adverse reaction reports with Lacosamide as the primary suspect drug were obtained, with 30,960 reported cases, detecting 232 valuable positive signals, involving a total of 20 SOCs, of which the most frequently reported SOCs were nervous system disorders (6537 cases, 55.21%), psychiatric disorders (1530 cases, 12.92%), injury poisoning and procedural complications (1059 cases, 8.94%). According to 232 valuable positive signals with DME screening results, two signals of stevens-johnson syndrome and ventricular fibrillation were consistent with PT signals on the DME list, with the two SOCs focusing on skin and subcutaneous tissue disorders and cardiac disorders, respectively. Our research demonstrates that the clinical use of Lacosamide should be noticed and avoided in relation to ADRs since it raises the risk of cardiac arrest, ventricular fibrillation, stevens-johnson syndrome, and rhabdomyolysis. [ABSTRACT FROM AUTHOR]

Aims: Secukinumab, the first interleukin 17A inhibitor, is widely used to treat immune diseases, including plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Recently, many studies have reported adverse events associated with secukinumab, including gastrointestinal disorders, infections and infestations, and hypersensitive and nervous system disorders. Objective: Here, we aimed to explore the clinical characteristics, outcomes and time to onset of the four main toxicities of secukinumab using post‐marketing data. Methods: Our study utilized data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2015 to 2021, using disproportionality analysis. Toxicities were defined based on the standardized Medical Dictionary for Regulatory Activities queries. Two disproportionality methods were used to detect potential signals: information component (IC) and reporting odds ratio (ROR). The signals were defined as ROR025 > 1 and IC025 > 0. Results: A total of 73 945 398 records were included in this study, of which 300 665 records were related to secukinumab. Diarrhoea (N = 3538), nasopharyngitis (N = 3458), pruritus (N = 4277) and rash (N = 3270) were the most common adverse events. Inflammatory bowel disease (IC025/ROR025 = 3.25/9.69), genital candidiasis (IC025/ROR025 = 3.46/11.54), dermatitis psoriasiform (IC025/ROR025 = 1.94/4.04) and anosmia (IC025/ROR025 = 1.62/3.17) had the highest IC025 values of all toxicities. The time to onset of the four toxicities was mainly concentrated in the first month. Some patients simultaneously presented with two or more toxicities. Conclusion: This pharmacovigilance study systematically explored the four main toxicities of secukinumab and provided new safety signals based on past safety information. Some high‐risk signals need to be given attention. [ABSTRACT FROM AUTHOR]

Aims: To identify and characterize ocular adverse events (oAEs) that are significantly associated with proprotein convertase subtilisin‐like/kexin type 9 (PCSK9) inhibitors using the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We conducted a disproportionality analysis of PCSK9 inhibitors in the FAERS (01/2004–12/2021). The association between PCSK9 inhibitors and oAEs was evaluated using the information component (IC) and the reporting odds ratio (ROR), and the difference in oAEs between evolocumab and alirocumab was compared using the ROR. Different sensitivity analyses were conducted to evaluate the robustness of results. Results: A total of 103 531 reports involving at least 1 PCSK9 inhibitor were found in the FAERS. PCSK9 inhibitors were associated with higher reporting of increased lacrimation (IC 0.27 [95% confidence interval {CI} 0.02–0.45]; ROR 1.21 [95% CI 1.04–1.40]), seasonal allergy (IC 0.39 [95% CI 0.04–0.64]; ROR 1.32 [95% CI 1.07–1.62]) and eye operation (IC 0.66 [95% CI 0.04–1.10]; ROR 1.60 [95% CI 1.11–2.30]) compared with the full database, and there was no difference between evolocumab and alirocumab. Sensitivity analyses showed that the disproportionate signals of increased lacrimation disappeared after excluding cases with other lipid‐lowering agents in the combined drugs. Except for eye operations, most of these adverse events occurred within 30 days of the first dose, and all 3 oAEs were mostly reported in women and individuals >65 years. Conclusion: This pharmacovigilance study identified a possible signal of ocular disorders associated with PCSK9 inhibitors and encourages paying attention to at‐risk populations in PCSK9 inhibitors medication. [ABSTRACT FROM AUTHOR]

Background: Although ibrutinib has been widely used to treat haematological malignancies, many studies have reported associated cardiovascular events. These studies were primarily animal experiments and clinical trials. For more rational clinical drug use, a study based on post-marketing data is necessary. Aim: Based on post-marketing data, we investigated the clinical features, time to onset, and outcomes of potential cardiovascular toxicities of ibrutinib. Methods: This disproportionality study utilised data from the 2014–2021 United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used two disproportionality methods information component (IC) and reporting odds ratio (ROR)) to detect the potential cardiovascular toxicities of ibrutinib. Positive signals were defined as IC025 > 0 and ROR025 > 1. Results: A total of 10 cardiovascular events showed positive signals: supraventricular tachyarrhythmias, haemorrhagic central nervous system vascular conditions, ventricular tachyarrhythmias, cardiac failure, ischaemic central nervous system vascular conditions, cardiomyopathy, conduction defects, myocardial infarction, myocardial infarction disorders of sinus node function, and torsade de pointes/QT prolongation. Cardiomyopathy and supraventricular tachyarrhythmias were the two most common signals. Disorders of sinus node function were observed for the first time, which may be a new adverse effect of ibrutinib. Conclusions: This pharmacovigilance study systematically explored the adverse cardiovascular events of ibrutinib and provided new safety signals based on past safety information. Attention should be paid to some high-risk signals. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the association of pulmonary sepsis with immune checkpoint inhibitors by conducting an analysis using data from the Food and Drug Administration pharmacovigilance database. Compared to chemotherapy or targeted therapy, a robust signal emerged for nivolumab and atezolizumab. Co-administration of immune checkpoint inhibitors and glucocorticoids or proton pump inhibitors synergistically increased the risk of pulmonary sepsis. These signals should promote both prospective research and multidisciplinary proactive monitoring by healthcare professionals. Background: Although some sepsis cases were reported with immune checkpoint inhibitors (ICIs) in clinical trials, the link between pulmonary sepsis and ICIs remains mostly unknown. We aim to investigate the association between pulmonary sepsis and ICIs, and to describe the clinical features. Methods: A disproportionality analysis was performed using FAERS data and compared rates of pulmonary sepsis in cancer patients receiving ICIs vs. other drug regimens (such as chemotherapy and targeted therapy). Associations between ICIs and sepsis were assessed using reporting odds ratios (ROR) and information component (IC). We also detected drug interaction signals based on the Ω shrinkage measure. Age and gender distribution were compared between pulmonary sepsis and all adverse events associated with ICIs. Results: We identified 120 reports of pulmonary sepsis associated with ICIs between Q1, 2011 to Q3, 2021. A total of 82 of 120 (68.3%) patients on ICIs suffered from pulmonary sepsis and progressed to death. In addition, there is no significant difference in age and gender in the occurrence of pulmonary sepsis in cancer patients on ICIs. Overall ICIs, nivolumab, and atezolizumab still have a significant signal of pulmonary sepsis (ROR025 > 1, IC025 > 0, p < 0.001) compared with targeted therapy (such as tyrosine kinase inhibitors) or chemotherapy. Co-administration of ICIs and glucocorticoids or proton pump inhibitors synergistically increased the risk of pulmonary sepsis (Ω025 > 0). Conclusions: Our study suggested ICIs, especially nivolumab and atezolizumab, tended to increase the risk of pulmonary sepsis more than other anticancer regimens. Clinicians should be vigilant in the prevention and management of pulmonary sepsis during ICIs therapy. [ABSTRACT FROM AUTHOR]

Sugammadex, a selective steroidal neuromuscular blocking agent reversal agent, is increasingly employed for the rapid restoration of neuromuscular function. This study aimed to conduct a comprehensive evaluation of sugammadex's safety profile. Adverse events (AEs) related to sugammadex reported in the FDA Adverse Event Reporting System (FAERS) database from January 2009 to September 2023 were extracted. Disproportionality analysis with four measures: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) were employed to detect significant AEs. We also inspected for unexpected AEs absent from the sugammadex FDA approval documentation and categorized AEs based on the latest version (26.1) of 'Important Medical Event Terms List (IME list)' developed by the EudraVigilance Expert Working Group. A total of 1452 reports were linked to sugammadex. At the preferred terms (PTs) levels, 98 sugammadex-related AEs were identified, including "anaphylactic reaction", "bradycardia", "bronchospasm" and "cardiac arrest". Among them, 37 representing unexpected events were absent from official FDA labeling, and 50 AEs were recognized as IME warranting observation. Notably, 19 PTs denoted serious AEs were absent from labeling yet needing IME surveillance, including: "Kounis syndrome", "angioedema", "pulseless electrical activity" and "laryngeal edema". The study identified unexpected and potentially life-threatening AEs associated with sugammadex, a valuable agent for rapidly reversing neuromuscular blockade. Clinicians are advised to be mindful of these potential risks, particularly in patients with allergies or existing cardiovascular or respiratory conditions. • Comprehensive evaluation of sugammadex's safety profile conducted. • Emphasis on sugammadex's unexpected, potentially fatal side effects. • Unlisted in label, 19 serious adverse events require 'Important Medical Event Terms List' surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: This real-world post-marketing research described clinical features of adrenal insufficiency with anticancer drugs targeting vascular endothelial growth factor receptor reported to the Food and Drug Administration pharmacovigilance database. A robust signal emerged for multi-targeted tyrosine kinase inhibitors, especially in combination with immunotherapy, namely checkpoint inhibitors in renal cancer. These signals should promote both prospective research and a multidisciplinary proactive monitoring by healthcare professionals. These findings strengthen the role of timely pharmacovigilance to detect and characterize post-marketing adverse events of special interest, thus supporting patient care. Background: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports of AI recorded in FAERS (January 2004–March 2022) were identified through the high-level term "adrenal cortical hypofunctions". Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs). Results: Out of 147,153 reports with VEGFR-TKIs, 314 cases of AI were retained, mostly of which were serious (97.1%; hospitalization recorded in 44.9%). In a combination regimen with ICIs (43% of cases), VEGFR-TKIs were discontinued in 52.2% of the cases (26% as monotherapy). The median time to onset was 72 days (IQR = 14–201; calculated for 189 cases). A robust disproportionality signal emerged, also in comparison with other anticancer drugs (ROR = 2.71, 95%CI = 2.42–3.04; IC = 0.25, 95%CI = 0.07–0.39). Cabozantinib, sunitinib and axitinib generated robust disproportionality even after ROR adjustment. Conclusions: We call pharmacologists, internists, oncologists and endocrinologists to raise awareness of serious AI with VEGFR-TKIs, and to develop dedicated guidelines, especially for combination regimens with immunotherapy. [ABSTRACT FROM AUTHOR]

Aims: As a new type of drug developed rapidly in recent years, Janus kinase inhibitors (JAKinibs) have caused controversy due to possible adverse reactions of thromboembolism. The aim of this study was to analyse and evaluate the association between thromboembolic events and the use of JAKinibs, on the base of the latest data in the Food and Drug Administration's Adverse Event Reporting System. Methods: A disproportionality analysis was conducted, utilizing data from 1 January 2012 to 30 September 2021 in the FAERS. For each drug‐adverse event pair, reporting odds ratio (ROR) and information components (IC) were calculated. Results: A total of 15 positive safety signals were detected within the FAERS: ruxolitinib was significantly associated with portal vein thrombosis (ROR025 = 3.49, IC025 = 1.50); tofacitinib immediate release with pulmonary embolism (ROR025 = 2.09, IC025 = 1.02) and thrombosis (ROR025 = 1.15, IC025 = 0.18); tofacitinib extended release with pulmonary embolism (ROR025 = 1.27, IC025 = 0.26) and thrombosis (ROR025 = 1.29, IC025 = 0.33); baricitinib with deep vein thrombosis (ROR025 = 8.27, IC025 = 3.00), portal vein thrombosis (ROR025 = 1.97, IC025 = 0.63), pulmonary embolism (ROR025 = 7.90, IC025 = 2.94), thrombosis (ROR025 = 2.04, IC025 = 0.93) and venous thrombosis (ROR025 = 2.15, IC025 = 0.81); upadacitinib with pulmonary embolism (ROR025 = 1.25, IC025 = 0.25), pulmonary thrombosis (ROR025 = 5.32, IC025 = 2.33) and thrombosis (ROR025 = 2.72, IC025 = 1.39); and filgotinib with pulmonary embolism (ROR025 = 4.83, IC025 = 2.10). In the analysis of the time to onset of thromboembolic events, no obviously recognizable pattern was found. Several safety signals with embolic and thrombotic events (Standardised MedDRA Query) were found in the study. Conclusion: This pharmacovigilance study covered 8 types of JAKinib that are already on the market, and provided new safety signals based on past safety information. Some of these signals still need more medical evidence. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to identify the most common and top drugs associated with the risk of torsades de pointes (TdP) based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.Materials and methodsWe used OpenVigil 2.1 to query FAERS database and data from the first quarter of 2004 to the third quarter of 2021 were retrieved. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP cases. We listed the most common drugs associated with the reported TdP cases. Then, the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for the reporting association between different drugs and TdP risk were calculated. Meanwhile, comparisons were conducted with the QT drug lists of CredibleMeds® in an attempt to identify drugs with a potential risk of TdP that were not on the list.ResultsA total of 9,217,181 adverse event reports were identified, of which 3,807 (0.04%) were related to TdP. TdP was more likely to occur in the elderly and females. Amiodarone (464 cases) was associated with most cases of TdP. According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were tolazoline (ROR 1615.11, 95% confidence interval [CI] 455.59–5725.75, PRR 969.46, χ2 2960.10), levomethadyl (ROR 1211.01, 95% CI 302.75–4844.04, PRR 807.67, χ2 1677.03), ibutilide (ROR 1118.74, 95% CI 425.00–2944.91, PRR 765.77, χ2 3845.27), halofantrine (ROR 660.55, 95% CI 184.21–2368.69, PRR 519.22, χ2 1076.31), and isoproterenol (ROR 352.20, 95% CI 227.19–546.00, PRR 307.82, χ2 6692.53). Approximately half of the top 50 drugs (22 for ROR, 30 for PRR) were not outlined on the QT drug lists of CredibleMeds®.ConclusionApproximately half of the top risk drugs (22 for ROR, 30 for PRR) were not outlined in the QT drug lists of CredibleMeds®. Notably, potential risks are of great importance and should be closely monitored in clinical practice. Also, further research is needed to investigate the association between these drugs and TdP.

Esketamine was approved for the treatment of treatment-resistant depression in 2019. After the approval of esketamine, numerous concerns have been raised regarding its long-term safety and tolerability. A previous systematic pharmacovigilance study on esketamine-related adverse events (AEs) was published in 2020; however, it has not been updated 2 years later. The primary aim of this study was to detect and characterize neurological safety signals of esketamine to partially update the knowledge in this field using the FDA pharmacovigilance database. Reporting odds ratio (ROR) was calculated for esketamine-related neurological AEs from 2019 to 2021 with a signal considered when the lower limit of the 95% confidence interval (CI) of ROR (ROR025) exceeded one. Severe and non-severe cases were compared using an independent samples t -test or chi-squared (χ2) test, and a rating scale was used to prioritize the signals. The database contained 720 cases of esketamine-associated neurological AEs, with 21 signals detected, ranging from a ROR025 of 1.05 (disturbance in attention) to 204.00 (sedation). 16 latest neurological AEs emerged in the second year of marketing approval of esketamine, with eight signals detected. The associations between esketamine and nervous system disorders persisted when stratifying by sex, age, and reporter type, whereas the spectrum of neurological AEs differed in stratification regimens. Esketamine dosage, antidepressant polypharmacy, or co-prescription with benzodiazepines affected AEs severity (t = 2.41, p = 0.017; χ2 = 6.75, p = 0.009; and χ2 = 4.10, p = 0.043; respectively), while age and sex did not (p = 0.053 and p = 0.397, respectively). Three signals were categorized as moderate clinical priority [i.e., sedation, dizziness, and dysgeusia (priority points 7, 5, and 5, respectively)], showing the same early failure type profiles. Notably, seven detected disproportionality signals were not previously detected in clinical trials. Although the majority of results were in line with those obtained in the previous study, there were discrepancies in the spectrum of neurological AEs and the effects of several risk factors on AEs severity among the two studies that should be recognized and managed early in clinical treatments. [ABSTRACT FROM AUTHOR]

Background: Clinical trials frequently reported anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) associated with cardiac adverse drug events (AEs) but minimal postmarketing data. We aimed to research real-world cardiac disorders associated with ALK-TKIs based on the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Extract reports from the FAERS from the first quarter of 2016 to the second quarter of 2021 were obtained. Data mining of cardiac disorders associated with ALK-TKIs was carried out using disproportionality analysis to determine the clinical characteristics of AEs. Results: In total, 605 cases were screened out. These events were found to be more prevalent in patients ≥45 years (50.74%) and women (50.74%). The onset time of cardiac disorders was variable and concentrated within 2 months, with a median time of 33 days. The outcomes tended to be poor, with 20.93% fatality proportion. Cardiac arrhythmia was a common adverse event of ALK-TKIs, especially bradycardia. Crizotinib and lorlatinib showed positive signals in cardiac disorders, especially in heart failure, and brigatinib presented no signals. The study also found that myocarditis caused by ceritinib and cardiomyopathy caused by lorlatinib may be potential new adverse drug reactions. Conclusion: ALK-TKIs were reported more frequently in cardiotoxicity than other drugs and could often manifest earlier. We also found potential new AE signals in specific drugs and need more clinical studies to confirm. Our study helps fill the safety information of ALK-TKIs in the heart and provides directions for further research. [ABSTRACT FROM AUTHOR]

Esketamine was approved for the treatment of treatment-resistant depression in 2019. After the approval of esketamine, numerous concerns have been raised regarding its long-term safety and tolerability. A previous systematic pharmacovigilance study on esketamine-related adverse events (AEs) was published in 2020; however, it has not been updated 2 years later. The primary aim of this study was to detect and characterize neurological safety signals of esketamine to partially update the knowledge in this field using the FDA pharmacovigilance database. Reporting odds ratio (ROR) was calculated for esketamine-related neurological AEs from 2019 to 2021 with a signal considered when the lower limit of the 95% confidence interval (CI) of ROR (ROR025) exceeded one. Severe and non-severe cases were compared using an independent samples t-test or chi-squared (χ2) test, and a rating scale was used to prioritize the signals. The database contained 720 cases of esketamine-associated neurological AEs, with 21 signals detected, ranging from a ROR025 of 1.05 (disturbance in attention) to 204.00 (sedation). 16 latest neurological AEs emerged in the second year of marketing approval of esketamine, with eight signals detected. The associations between esketamine and nervous system disorders persisted when stratifying by sex, age, and reporter type, whereas the spectrum of neurological AEs differed in stratification regimens. Esketamine dosage, antidepressant polypharmacy, or co-prescription with benzodiazepines affected AEs severity (t = 2.41, p = 0.017; χ2 = 6.75, p = 0.009; and χ2 = 4.10, p = 0.043; respectively), while age and sex did not (p = 0.053 and p = 0.397, respectively). Three signals were categorized as moderate clinical priority [i.e., sedation, dizziness, and dysgeusia (priority points 7, 5, and 5, respectively)], showing the same early failure type profiles. Notably, seven detected disproportionality signals were not previously detected in clinical trials. Although the majority of results were in line with those obtained in the previous study, there were discrepancies in the spectrum of neurological AEs and the effects of several risk factors on AEs severity among the two studies that should be recognized and managed early in clinical treatments.

Background: Clinical trials frequently reported anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) associated with cardiac adverse drug events (AEs) but minimal postmarketing data. We aimed to research real-world cardiac disorders associated with ALK-TKIs based on the Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: Extract reports from the FAERS from the first quarter of 2016 to the second quarter of 2021 were obtained. Data mining of cardiac disorders associated with ALK-TKIs was carried out using disproportionality analysis to determine the clinical characteristics of AEs.Results: In total, 605 cases were screened out. These events were found to be more prevalent in patients ≥45 years (50.74%) and women (50.74%). The onset time of cardiac disorders was variable and concentrated within 2 months, with a median time of 33 days. The outcomes tended to be poor, with 20.93% fatality proportion. Cardiac arrhythmia was a common adverse event of ALK-TKIs, especially bradycardia. Crizotinib and lorlatinib showed positive signals in cardiac disorders, especially in heart failure, and brigatinib presented no signals. The study also found that myocarditis caused by ceritinib and cardiomyopathy caused by lorlatinib may be potential new adverse drug reactions.Conclusion: ALK-TKIs were reported more frequently in cardiotoxicity than other drugs and could often manifest earlier. We also found potential new AE signals in specific drugs and need more clinical studies to confirm. Our study helps fill the safety information of ALK-TKIs in the heart and provides directions for further research.

Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring. Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP). Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value >2, and lower limit of 95% confidence interval (CI)> 1. Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09–2.30) and 2.13 (95% CI, 1.04–4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54–8.18) and 2.85 (95% CI, 1.15–7.08), respectively. Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring.Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP).Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value >2, and lower limit of 95% confidence interval (CI)> 1.Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09–2.30) and 2.13 (95% CI, 1.04–4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54–8.18) and 2.85 (95% CI, 1.15–7.08), respectively.Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice.

Background: Although ibrutinib has been widely used to treat haematological malignancies, many studies have reported associated cardiovascular events. These studies were primarily animal experiments and clinical trials. For more rational clinical drug use, a study based on post-marketing data is necessary. Aim: Based on post-marketing data, we investigated the clinical features, time to onset, and outcomes of potential cardiovascular toxicities of ibrutinib. Methods: This disproportionality study utilised data from the 2014–2021 United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used two disproportionality methods information component (IC) and reporting odds ratio (ROR)) to detect the potential cardiovascular toxicities of ibrutinib. Positive signals were defined as IC025 > 0 and ROR025 > 1. Results: A total of 10 cardiovascular events showed positive signals: supraventricular tachyarrhythmias, haemorrhagic central nervous system vascular conditions, ventricular tachyarrhythmias, cardiac failure, ischaemic central nervous system vascular conditions, cardiomyopathy, conduction defects, myocardial infarction, myocardial infarction disorders of sinus node function, and torsade de pointes/QT prolongation. Cardiomyopathy and supraventricular tachyarrhythmias were the two most common signals. Disorders of sinus node function were observed for the first time, which may be a new adverse effect of ibrutinib. Conclusions: This pharmacovigilance study systematically explored the adverse cardiovascular events of ibrutinib and provided new safety signals based on past safety information. Attention should be paid to some high-risk signals.

OBJECTIVE: The present study aims to identify potential safety signals of chloroquine (CQ) and hydroxychloroquine (HCQ), over the period preceding their repurpose as COVID-19 treatment options, through the analysis of safety data retrieved from the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database. MATERIALS AND METHODS: We performed a disproportionality analysis of FAERS data between the first quarter of 2004 and December 2019 using the OpenVigil2.1-MedDRA software. Disproportionality was quantified using the reporting odds ratio (ROR) and its 95% confidence interval (CIs). The reported mortality of CQ and HCQ was also investigated. RESULTS: The dataset contained 6,635,356 reports. Comparison of the RORs revealed significant differences between CQ and HCQ for the following adverse events: cardiomyopathy, cardiac arrhythmias, retinal disorders, corneal disorders, hearing disorders, headache, hepatic disorders, severe cutaneous reactions, musculoskeletal disorders, and cytopenia. Only CQ was associated with psychotic disorders, suicide, self-injury, convulsions, peripheral neuropathy, and decreased appetite. In multivariable logistic regression, death was more frequently associated with CQ use, advanced age, male sex, co-reported suicide and self-injury, cardiomyopathy, cardiac arrhythmias, and decreased appetite. CONCLUSIONS: O ur r esults c onfirm p reviously published evidence and suggest that HCQ has a safer clinical profile compared to CQ, and thus could serve as the drug of choice for future therapeutic purposes. [ABSTRACT FROM AUTHOR]

Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings.Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities.Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals.Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1–Q3: 4–85 days) for ischemic heart disease, with the longest time being 68 days (Q1–Q3: 21–139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%).Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.

This study was to scientifically and systematically explore the association between cardiotoxicity and immune checkpoint inhibitors (ICIs) and also to characterize the spectrum of ICI-related cardiac complications. From the first quarter of 2014 to the fourth quarter of 2019, data from the FDA Adverse Event Reporting System database were selected to conduct the disproportionality analysis. Reporting odds ratios and information components were used to evaluate the signal after statistical shrinkage transformation. In total, 7,443,137 cases and 36,326,611 drug-adverse event pairs were collected, among which 9,271 cases were identified to be related to ICI-induced cardiotoxicities. The number of male patients was much higher than that of females (5,579 vs. 3,031) and males presented a slightly higher reporting frequency than females in general, which was statistically significant (ROR = 1.04, 95%CI: 0.99–1.09, p < 0.001). Simultaneously, the proportion of serious or life-threatening outcomes in males was significantly higher than in females (ROR = 1.05, 95%CI: 0.96–1.15, p < 0.001). Importantly, ICIs were associated with over-reporting frequencies of cardiotoxicities in general (ROR025 = 1.06, IC025 = 0.08). PD-1 and PD-L1 were found to be related to cardiac adverse events, corresponding to ROR025 = 1.06, IC025 = 0.08, and ROR025 = 1.06, IC025 = 0.08, respectively, while anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) was significantly associated with some specific adverse events rather than common adverse events. The spectrum of cardiotoxicities induced by ICIs mostly differed among individual agents, but also demonstrated some common features. Dyspnea (N = 2,527, 21.25%), myocarditis (N = 614, 5.16%), atrial fibrillation (N = 576, 4.84%), cardiac failure (N = 476, 4.00%), and pericardial effusion (N = 423, 3.56%) were the top five cardiac adverse events reported in the database. Among them, myocarditis was the only one caused by all ICIs with strong signal value and high risk, warranting further attention. Overall, this investigation mainly showed the profile of cardiotoxicities caused by ICIs, which varied between different ICI therapies, but also shared some similarities in specific symptoms such as myocarditis. Therefore, it is vital and urgent to recognize and manage ICI-related cardiotoxicities, known to frequently occur in clinical practice, at the earliest point.

Background: Osteoporosis, which is a major public health concern, has been known to reduce health-related quality of life. Some studies have suggested that antipsychotics could perhaps cause osteoporosis by increasing serum prolactin levels. However, the association between antipsychotics and the risk for developing osteoporosis has been controversial.Objective: The present study aimed to assess the association between antipsychotic use and onset of osteoporosis in real-world settings.Methods: A multimethod data-mining approach using different algorithms and databases was used. First, disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2017) with reporting odds ratio (ROR) and information component (IC) being used to indicate a signal. Furthermore, a sequence symmetry analysis using data from a large Japanese administrative claims database (2005-2017; JMDC Inc, Japan) was conducted. Short-term intervals (ie, 12, 24, and 36 months) were set to investigate the association between antipsychotic use and onset of osteoporosis using the adjusted sequence ratio (SR) to indicate a signal.Results: No potential association between osteoporosis and all antipsychotics was observed in the FAERS database, except for perphenazine, which exhibited significant signals using both ROR and IC. Moreover, no potential association between osteoporosis and antipsychotics was observed in the JMDC claims database, except for sulpiride and aripiprazole. None of the antipsychotics indicated significant signals using all analyzed items (ROR, IC, and adjusted SR).Conclusion and Relevance: Real-world data show no association between antipsychotic use and the onset of osteoporosis. Further pharmacoepidemiological studies are needed for causality assessment. [ABSTRACT FROM AUTHOR]