Hepatitis-related adverse events associated with immune checkpoint inhibitors in cancer patients: an observational, retrospective, pharmacovigilance study using the FAERS database.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data. Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs. Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80-21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95-248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65-5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8-72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78-6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy. Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.

Comparative analysis of adverse events among intravesical drugs in bladder cancer: a real-world study on FAERS database.

BACKGROUND: Intravesical therapy is a commonly utilized treatment for non-muscle invasive bladder cancer (NMIBC). This study focuses on summarizing the signals of all intravesical drugs and aims to highlight the comprehensive differences in adverse events (AEs) between these drugs. RESEARCH DESIGN AND METHODS: We conducted pharmacovigilance data analysis based on the real-world big data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. RESULTS: We elucidated all signals compared with the overall FAERS database or other administration routes for Bacillus Calmette-Guerin (BCG), mitomycin, gemcitabine, valrubicin, and epirubicin. Notably, the distribution of reported AEs associated with intravesical therapy exhibited a noticeable inclination toward male patients. Furthermore, all five drugs demonstrated a disproportionate distribution in local AEs, particularly in renal and urinary disorders. Additionally, specific signals and findings were summarized for each individual drug. Finally, we highlighted the AEs that resulted in serious outcomes for each drug. CONCLUSION: We have compiled an overview of the AEs tied to intravesical drugs whilst considering their individual distinctions. These insightful findings serve to enrich our comprehension of the safety profiles and potential risks linked to intravesical therapy.

A pharmacovigilance study of chronic kidney disease in diabetes mellitus patients with statin treatment by using the US Food and Drug Administration adverse event reporting system.

Background: Statins were regarded as a main medication for managing hypercholesterolemia. Administration of statin therapy could reduce the incidence of cardiovascular disease in individuals diagnosed with type 2 diabetes mellitus (DM), which was recognized by multipal clinical guidelines. But previous studies had conflicting results on whether the long-term use of statins could benefit the renal function in diabetic patients. Aim: To evaluate the association between statin treatment and Chronic Kidney Disease in DM patients. Methods: This is a retrospective disproportionality analysis and cohort study based on real-world data. All DM cases reported in US Food and Drug Administration adverse event reporting system (FAERS) between the first quarter of 2004 and the fourth quarter of 2022 were included. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). We further compared the CKD odds ratio (OR) between the statins group and the other primary suspected drug group among the included diabetes mellitus cases. Results: We finally included 593647 DM cases from FAERS, 5113 (5.31%) CKD cases in the statins group and 8810 (1.77%) CKD cases in the control group. Data analysis showed that the statins group showed a significant CKD signal (ROR: 3.11, 95% CI: 3.00-3.22; IC: 1.18, 95% CI: 1.07-1.29). In case group with two or more statins treatment history, the CKD signal was even stronger (ROR: 19.56, 95% CI: 18.10-21.13; IC: 3.70, 95% CI:3.44-3.93) compared with cases with one statin treatment history. Conclusion: The impact of statin therapy on the progression of renal disease in individuals diagnosed with type 2 diabetes mellitus (DM) remains inconclusive. After data mining on the current FAERS dataset, we discovered significant signals between statin treatment and CKD in diabetic patients. Furthermore, the incidence rate of CKD was higher among DM patients who used statins compared to those who did not.

Adverse events associated with eteplirsen: A disproportionality analysis using the 2016-2023 FAERS data.

Background: Eteplirsen (Exondys 51) is an orphan drug approved for the treatment of Duchenne muscular dystrophy (DMD), having received accelerated approval from the U.S. Food and Drug Administration (FDA) in 2016. The primary aim of this study is to closely monitor adverse events (AEs) associated with eteplirsen and to identify emerging signals to better characterize their safety profile. Methods: AEs due to eteplirsen usage reported from the third quarter (Q3) of 2016 to the fourth quarter (Q4) of 2023 were collected from the FDA Adverse Event Reporting System (FAERS). The role_code of AEs mainly includes primary suspect (PS), secondary suspect (SS), concomitant (C), and interaction (I). This study targeted reports with a role_cod of 'PS.' According to the FDA deduplication rule, the latest FDA_DT is selected when the CASEID is the same, and the higher PRIMARYID is selected when the CASEID and FDA_DT are the same. Disproportionality analyses, encompassing four algorithms for reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian configuration promotion neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were utilized to quantify the signals of AEs associated with eteplirsen. Results: From the FAERS database, a total of 13,205,369 reports were amassed throughout the study duration. Following the eradication of duplicates, the number of reports with eteplirsen designated as the PS amounted to 1480 encompassed 25 organ systems. Among these, "general disorders and administration site conditions," "injury, poisoning, and procedural complications," "respiratory, thoracic, and mediastinal disorders," "infections and infestations," "vascular disorders," and "product issues" met at least one of the four computational criteria. Additionally, 55 Preferred Terms (PTs) aligned with the prescribed algorithms. The median time to AEs in these patients was 903 days with an interquartile range (IQR) of 269-1575 days. Moreover, 70.04 % of AEs manifested one year or more after the initiation of treatment. Conclusion: As an orphan drug granted accelerated approval, our study has confirmed well-known adverse drug reactions and identified potential safety issues associated with eteplirsen treatment. This has contributed to a deeper understanding of the complex interrelations between adverse reactions and the use of eteplirsen. The findings underscore the critical importance of ongoing monitoring and sustained observation to promptly detect and effectively manage AEs, thereby enhancing the overall safety and well-being of patients treated with eteplirsen for DMD.

The atypical antipsychotics and sexual dysfunction: a pharmacovigilance-pharmacodynamic study.

Background: Atypical antipsychotics (AAPs)-induced sexual dysfunction (SD) is a frequent issue in clinical practice, often underestimated by clinicians and not extensively researched. The current study aimed to quantify the strength of association between the use of different AAPs and SD using real-world data from the FDA Adverse Event Reporting System (FAERS), as well as investigate the receptor mechanisms that are involved. Methods: Data from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were queried through OpenVigil 2.1. Disproportionality analysis was estimated using the reporting odds ratio (ROR) and information component (IC) methods, and linear regression was used to investigate the relationship between ROR and receptor occupancy which was estimated using in vitro receptor binding profiles. Results: Our analysis yielded 4839 reports that co-mentioned AAP and SD events, and the findings revealed statistical associations between 12 AAPs and SD. The highest signal value was identified for iloperidone reporting retrograde ejaculation with iloperidone (ROR = 832.09, ROR025 = 552.77; IC = 9.58, IC025 = 6.36), followed by compulsive sexual behavior with aripiprazole (ROR = 533.02, ROR025 = 435.90; IC = 7.30, IC025 = 5.97), and psychosexual disorder for aripiprazole (ROR = 145.80, ROR025 = 109.57; IC025 = 6.47, IC025 = 4.86). Different characteristics of the SD side effects in each AAPs were discovered after further data mining. Regression analysis revealed potential effects for receptor occupancy of D2, D3, and 5-HT1A receptors on ROR. However, no significant correlation persisted following sensitivity analyses. Conclusion: This is the first study to investigate the AAP-SD associations by using FAERS. In this study, we report for the first time a significant association between aripiprazole and SD based on real-world data. The study suggests that different AAPs have varying levels of association with SD, and the D2, D3, and 5-HT1A receptor occupancy may contribute to potential mechanisms. The findings of this study warrant further validation of more studies and clinical causality assessment.

Adverse drug events associated with fluorouracil use in patients with metastatic colorectal cancer: a real-world pharmacovigilance study based on the FDA adverse event reporting system.

BACKGROUND: Fluorouracil (5-FU) is widely used to treat metastatic colorectal cancer (mCRC), but real-world safety data is limited. Our study aimed to evaluate 5-FU's safety profile in a large mCRC population using the FAERS database. RESEARCH DESIGN AND METHODS: We conducted disproportionality analyses to identify adverse drug events associated with 5-FU use in mCRC patients from 2004 to 2023. Subgroup analyses, gender difference analyses, and logistic regression were also performed. RESULTS: We identified 1,458 reports with 5-FU as the primary suspected drug, with males accounting for 48.8% of reports. Gastrointestinal disorders were the most common adverse event (864 cases), while pregnancy-related conditions showed the strongest signal intensity (ROR = 2.97). We found 19 preferred terms with positive signals, including ischemic hepatitis (ROR = 59.32), blood iron increased (ROR = 59.32), and stress cardiomyopathy (ROR = 51.94). Males were more susceptible to weight loss and skin toxicity. Most adverse events occurred within the first month of 5-FU administration. CONCLUSION: Our study provides a comprehensive analysis of 5-FU's safety profile in mCRC patients, helping healthcare professionals mitigate risks in clinical practice.

Safety assessment of Yasmin: Real-world adverse event analysis using the FAERS database.

BACKGROUND: This study aimed to elucidate the scope and nature of adverse events (AEs) associated with Yasmin. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Compartment syndrome associations with drugs: a pharmacovigilance study of the FDA adverse event reporting system (FAERS).

BACKGROUND: Compartment syndrome is an uncommon but life-threatening condition. No study has comprehensively compared compartment syndrome (CS) association with available drugs. The objective of this study was to estimate the association between CS and drugs using the FDA Adverse Event Report System (FAERS). RESEARCH DESIGN AND METHODS: FAERS reports from the first quarter of 2004 to the third quarter of 2023 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CS cases. Reporting odds ratio (ROR), corresponding to 95% confidence intervals (95% CI) were calculated to detect a positive signal. RESULTS: A total of 2197 reports were considered in the study after the inclusion criteria were applied. Totally 100 drugs were found to be associated with CS. The median time for drug-associated CS was 45 days. CONCLUSIONS: By analyzing the FAERS database, the study revealed that certain drugs are significantly associated with compartment syndrome. Further studies are needed to verify whether these drugs are associated with such a risk.

Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: a disproportionality analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS. AIM: This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHOD: A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3. RESULTS: There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57). CONCLUSION: This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA adverse event reporting system.

BACKGROUND: ThePhosphoinositide 3-kinases (PI3Ks) family plays a crucial role intumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibitingPI3Kδ) were developed to target the PI3K pathway. However, the toxicity limitstheir application to some extent. It's necessary to investigate the adverseeffects (AEs) of these inhibitors. RESEARCH DESIGNAND METHODS: We conducted acomparative analysis of the safety signals of AEs in PI3K inhibitors usingdisproportionality analysis in the FDA Adverse Event Reporting System database(FAERS). RESULTS: Our studyidentified significant safety signals for metabolic disorders with all PI3Kinhibitors. Notable safety signals for gastrointestinal disorders were observedwith most PI3K inhibitors, with the exception of copanlisib. Common AEs shared amongall PI3K inhibitors included colitis and dehydration. Alpelisib displayedunique AEs associated with metabolic disorders, whereas copanlisib exhibitedidiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnsonsyndrome emerged as a common severe adverse event (SAE) among alpelisib,copanlisib, and idelalisib, while febrile neutropenia was prevalent amongcopanlisib, duvelisib, and idelalisib. Intestinal perforation was solelyassociated with alpelisib. CONCLUSIONS: The safety profiles of the five PI3K inhibitorsvary concerning adverse events. These findings could guide drug selection andinform future prospective research.

Safety of tildrakizumab: a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database from 2018-2023.

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 Tildrakizumab-associated 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.

Hypersensitivity Reactions Induced by Iodinated Contrast Media in Radiological Diagnosis: A Disproportionality Analysis Based on the FAERS Database.

PURPOSE: This study aimed to evaluate the Pharmacovigilance (PV) and severity of hypersensitivity reactions induced by non-ionic Iodinated Contrast Media (ICM) in the radiology diagnosis reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We retrospectively reviewed the reports of ICM-induced hypersensitivity reactions submitted to the FAERS database between January 2015 and January 2023 and conducted a disproportionality analysis. The seven most common non-ionic ICM, including iohexol, iopamidol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, were chiefly analyzed. Our primary endpoint was the PV of non-ionic ICM-induced total hypersensitivity events. STATA 17.0 MP was used for statistical analysis. RESULTS: In total, 35357 reports of adverse reaction events in radiology diagnosis were retrieved from the FAERS database. Among them, 6181 reports were on hypersensitivity reaction events (mean age: 57.1 ± 17.8 years). The hypersensitivity reaction-related PV signal was detected for iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, but not for iopamidol. The proportion of iomeprol-induced hypersensitivity reactions and the probability of ioversol-induced severe hypersensitivity reactions have been found to be significantly increased. CONCLUSION: The probability and severity of hypersensitivity reaction events in non-ionic ICM are different. Iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol have higher risks compared to iopamidol. In addition, the constituent ratio of hypersensitivity reactions induced by iomeprol is significantly increased, and the associated probability induced by ioversol is significantly increased.

Neuronal toxicity of monoclonal antibodies (mAbs): an analysis of post-marketing reports from FDA Adverse Event Reporting System (FAERS) safety database.

BACKGROUND: Monoclonal antibodies (mAbs) are pivotal in treating various diseases, including cancers and autoimmune disorders. Despite their therapeutic benefits, mAb therapy has been associated with neurological toxicity. OBJECTIVES: This study aimed to assess the occurrence of neuronal toxicity associated with mAbs, utilizing data from the FDA Adverse Event Reporting System (FAERS) safety database. The study also sought to delineate the medical characteristics of the reported cases. METHODS: A comprehensive analysis of neurological adverse events reported in the FAERS database was conducted, employing computational methodologies such as proportional relative risk (PRR), information component (IC025), and chi-square (χ2). Individual case safety reports (ICSRs) pertaining to neurological disorders linked to mAbs from the date of first global marketing authorization until June 30, 2023, were meticulously examined. RESULTS: The FAERS safety database contains 79,022 ICSRs linking mAbs to nervous system disorders. Rituximab, bevacizumab, denosumab, nivolumab, and trastuzumab were frequently cited. Reported adverse events include headache, peripheral neuropathy, dizziness, and cerebrovascular accident. Most ICSRs (85.81%) were serious, mainly affecting females (57.04%) with a 14.09% fatality rate. Panitumumab, atezolizumab, bevacizumab, and trastuzumab showed strong drug-event associations. Signal disproportionate reporting (SDR) analysis flagged myasthenia gravis, peripheral neuropathy, and neurotoxicity across multiple mAbs, suggesting potential signals. CONCLUSIONS: Interdisciplinary collaboration between oncologists and neurologists is crucial for safe mAb use. Our study enhances understanding of mAb neurological safety. Disproportionality signal analysis provides valuable evidence for risk mitigation.

Sexual Dysfunction Induced by Antidepressants-A Pharmacovigilance Study Using Data from VigiBaseTM.

Sexual dysfunction is a common side effect of antidepressants, significantly impacting patients' quality of life and treatment adherence. This study investigates the relationship between sexual dysfunction and antidepressants by analyzing data from VigiBase™, the World Health Organization's global database of individual case safety reports. In this study, we examined, for the first time, reports related to sexual response-desire, arousal, and orgasm-by grouping appropriate side effect terms and calculated the reporting odds ratios (RORs) for various antidepressants. The findings of this study highlight a high disproportional reporting of sexual dysfunction, particularly with selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. In contrast, agents such as agomelatine, bupropion, and mirtazapine showed a lower association. Furthermore, we investigated the correlation between reporting odds ratios and the binding affinities of antidepressants to specific neurotransmitter receptors and transporters, unveiling significant relationships that provide insights into the pharmacodynamic pathways underlying these adverse effects. For instance, a positive correlation was observed between the serotonin transporter and side effects in the category desire: r (19) = 0.67, p = 0.001 These insights underscore the necessity for clinicians to consider sexual side effects when prescribing antidepressants and to monitor and address these issues to improve patient outcomes.

Safety assessment of sildenafil use in neonates: a real-world data analysis based on the FDA adverse event reporting system (FAERS).

BACKGROUND: The safety of neonatal sildenafil use remains uncertain. This study aimed to investigate adverse events (AEs) associated with sildenafil use in neonates. RESEARCH DESIGN AND METHODS: We collected data on AEs associated with sildenafil use in neonates from the US Food and Drug Administration Adverse Event Reporting System database, spanning from its inception of the database in 2004 to 2023. Disproportionality measures were employed to analyze the correlation between AEs and sildenafil. RESULTS: Sildenafil was identified as the primary suspect drug in 75 AE reports, involving 214 AEs. Three system organ classes, namely, eye disorders, hepatobiliary disorders, and vascular disorders were associated with sildenafil use. Six preferred terms, namely, flushing, retinopathy of prematurity, hyperbilirubinemia, pulmonary hemorrhage, hypotension, and diarrhea were associated with sildenafil use. Notably, hyperbilirubinemia and pulmonary hemorrhage were previously unreported AEs associated with sildenafil use. CONCLUSION: The results highlight the ongoing uncertainty surrounding the safety of neonatal sildenafil use and provide vital support for risk monitoring and identification in neonates receiving sildenafil. Additionally, the study underscores the need for continuous safety surveillance in neonates treated with sildenafil and suggests further exploration of the precise causal relationships between AEs and sildenafil.

Post-marketing safety surveillance of fostamatinib: an observational, pharmacovigilance study leveraging FAERS database.

OBJECTIVE: Fostamatinib, an FDA-approved oral small-molecule spleen tyrosine kinase (SYK) inhibitor, is used to treat thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have not responded to previous treatments. However, comprehensive safety data is lacking. This study uses the FDA Adverse Event Reporting System (FAERS) database to explore real-world adverse events (AEs) related to fostamatinib, aiming to inform its clinical use. METHODS: The FAERS database was retrospectively queried to extract reports associated with fostamatinib from 2019 to 2023. To identify and evaluate potential AEs in patients receiving fostamatinib, various disproportionality analyses such as 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) were employed. RESULTS: A total of 23 AE signals were included in our analysis. Among them, hypertension, blood pressure increase, blood pressure abnormality, hepatic enzyme increase, and diarrhea were consistent with the common AEs described for fostamatinib in clinical trials. In addition, unexpected serious AEs were detected including cerebral thrombosis and necrotizing soft tissue infection. The median time to onset of fostamatinib-related AEs was 86 days. CONCLUSION: Our investigation revealed several possibly emergent safety concerns associated with fostamatinib in real-world clinical practice, which might provide essential vigilance evidence for clinicians and pharmacists to manage the safety issues of fostamatinib.

Cardiac adverse events associated with lacosamide: a disproportionality analysis of the FAERS database.

Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide.

Disproportionality analysis of data from VigiBase and other global product safety databases on toxicity of iron chelating agents.

BACKGROUND: Iron chelators; deferasirox, deferiprone and deferoxamine, used to treat iron toxicities due to excessive ingestions or blood transfusions, may cause serious adverse reactions. RESEARCH DESIGN AND METHODS: This study investigates pharmacovigilance data to uncover unknown safety information. Disproportionality analysis was conducted using VigiBase, the WHO global database of individual case safety reports, to known safety profile of products and FDA Adverse Event Reporting System, reviewing over 117.000 iron chelator cases between 2010 and 2020. RESULTS: Commonly reported adverse events for iron chelators are general disorders and administration site conditions and GI related disorders. Reporting Odds Ratio was calculated for iron chelator associations to headache (common), blurred vision (rare) and sepsis (serious). Strong association between deferoxamine and blurred vision (ROR: 2.47 in VigiBase and 3.04 in FAERS), deferiprone and sepsis (ROR; 5.95 in VigiBase and 1.24 in FAERS) were identified. However, results showed some inconsistent associations, such as headache and deferiprone, blurred vision and deferasirox association as per FAERS data; sepsis and deferasirox and deferoxamine association as per VigiBase data. 45 new potential signals with different associative values were suggested. CONCLUSION: The study identified strong associations between specific iron chelators and adverse events, though some inconsistencies were observed in the data. These findings, including the 45 new potential signals, suggest areas for further review and validation with additional data.

A pharmacovigilance study of FDA adverse events for sugammadex.

BACKGROUND: 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. METHODS: 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. RESULTS: 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". CONCLUSION: 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.

Immune-related adverse events of immune checkpoint inhibitors combined with angiogenesis inhibitors: A real-world pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database (2014-2022).

INTRODUCTION: Although immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) has become increasingly used for cancers, the impact of combination therapy on immune-related adverse events (irAEs) in real-world settings has not been well elucidated to date. METHODS: The FDA Adverse Event Reporting System (FAERS) database from 2014 to 2022 was retrospectively queried to extract reports of irAEs referred as standardized MedDRA queries (SMQs), preferred terms (PTs) and system organ classes (SOCs). To perform disproportionality analysis, information component (IC) and reporting odds ratio (ROR) were calculated and lower limit of 95 % confidence interval (CI) for IC (IC025) > 0 or ROR (ROR025) > 1 with at least 3 reports was considered statistically significant. RESULTS: Compared to ICIs alone, ICIs + AGIs demonstrated a lower IC025/ROR025 for irAEs-SMQ (2.343/5.082 vs. 1.826/3.563). Regarding irAEs-PTs, there were fewer irAEs-PTs of significant value in ICIs + AGIs than ICIs alone (57 vs. 150 PTs) and lower signal value for most PTs (88 %) in ICIs + AGIs. Moreover, lower IC025 for most of irAEs-SOCs in ICIs + AGIs (11/13) compared with ICIs alone was observed. As for outcomes of irAEs, ICIs + AGIs showed a lower frequency of "fatal" for irAEs-SMQ than ICIs alone (4.88 % vs. 7.83 %), so as in cardiac disorder (SOC) (15.45 % vs. 26.37 %), and respiratory, thoracic and mediastinal disorders (SOC) (13.74 % vs. 20.06 %). Similarly, there were lower occurrence and fewer fatality of irAEs in ICIs + AGIs + chemotherapy (CT) than ICIs + CT. CONCLUSION: ICIs combined with AGIs may reduce incidence and mortality for most of irAEs compared to ICIs alone whether or not with CT.