A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS)
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ABSTRACT:
SUBMITTER: Zou S
PROVIDER: S-EPMC10642055 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundLoop diuretics, including furosemide, torsemide, and bumetanide, are widely utilized in the management of volume overload-related conditions. Although previous studies have extensively documented risks such as electrolyte imbalances, ototoxicity, and nephrotoxicity, real-world evidence regarding novel or underrecognized adverse event (AE) signals remains limited and underexplored.MethodsUsing data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2024, we conducted a disproportionality analysis integrating Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), combined with multivariate logistic regression. It is considered a significant signal when one of the four indicators meets the criteria. The temporal characteristics were elucidated via time-to-onset (TTO) analysis.ResultsA total of 24,875 AE reports were analyzed, with furosemide accounting for 89.18%, torsemide for 8.33%, and bumetanide for 2.47%. Commonly reported risks included electrolyte imbalances, fluid balance disorders, and nephrotoxicity. Several novel safety signals were identified: furosemide was significantly associated with vitamin B1 deficiency (TTO = 71 days), Wernicke's encephalopathy (TTO = 2167 days), and gastrointestinal mucosal pigmentation (TTO = 549.1 days). Torsemide was associated with palisaded neutrophilic granulomatous dermatitis (TTO = 62.8 days), systemic infection (TTO = 548.3 days), pemphigoid (TTO = 470.6 days), bleeding events (involving the respiratory, gastrointestinal, and urinary tracts), and prolonged prothrombin time (TTO = 159.4 days). Bumetanide was linked to blood ketone body increased (TTO = 9.0 days), metabolic encephalopathy (TTO = 1786.0 days), and immune hypersensitivity reactions (Stevens-Johnson syndrome, pemphigoid, and lip swelling).ConclusionThis study identified both common and drug-specific AEs associated with loop diuretics, particularly focusing on the metabolic and immune risks of long-term use. To enhance patient safety, clinicians are advised to develop personalized monitoring strategies based on individual patient characteristics. For furosemide, monitoring and supplementation of vitamin B1 and magnesium are recommended. For torsemide, attention should be given to coagulation function and delayed hypersensitivity reactions. For bumetanide, close monitoring of metabolic disorders and immune-related skin lesions is essential. These findings support individualized therapy and precise pharmacovigilance, ensuring safer and more effective use of loop diuretics.
| S-EPMC11912766 | biostudies-literature
Project description:Avatrombopag is a next-generation thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in patients with chronic liver disease scheduled to undergo surgery and thrombocytopenia in patients with chronic immune thrombocytopenia. However, realistic data on its post-marketing long-term safety and tolerability in large sample populations are incomplete. The adverse event (AE) reports of avatrombopag were analyzed based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker to calculate and evaluate the ratio and association between avatrombopag and specific AEs. In the FAERS database, data from the second quarter of 2018 to the fourth quarter of 2023 were extracted for this study, a total of 1217 avatrombopag-related AEs reports were included for analysis. Based on four calculation methods, this study identified and 32 preferred terms associated with avatrombopag. Common AEs in the product label such as thrombosis, headache, contusion, petechiae, and gingival bleeding were detected. AEs not mentioned in the product label, such as photopsia and ear discomfort were also detected. The first 30 days after initiation of medication were the most common period for both serious and non-serious AEs. This study demonstrates the common AEs and the potential AEs associated with avatrombopag in real-world practice, which could provide valuable cautionary evidence for clinicians and pharmacists to manage safety issues with avatrombopag.
| S-EPMC11574250 | biostudies-literature
Project description:In this study, we delved into the safety profile of alpelisib, an FDA-approved treatment for hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer, and PIK3CA-Related Overgrowth Spectrum (PROS). Despite its approval, real-world, long-term safety data is lacking. Our research scrutinizes the FDA database to assess alpelisib 's safety. We retrospectively analyzed data from April 2019 to June 2023 using four algorithms. Among 7,609,450 reports, 6692 implicated alpelisib as the primary suspected drug, uncovering adverse events (AEs) across 26 organ systems. Notably, we identified 21 previously unlisted AEs. Furthermore, differences in AEs emerged between patients with PIK3CA-mutated breast cancer and those with PROS. This study provides vital insights for healthcare professionals to navigate AEs in clinical practice and informs future research for enhancing alpelisib 's safety profile.
| S-EPMC10944239 | biostudies-literature
Project description:ObjectiveThis study aimed to analyze the FAERS database to identify adverse event associated with sunitinib to offer valuable insights for the judicious utilization of medication in clinical settings.MethodsVarious disproportionality analysis techniques, such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPN), and multi-gamma Poisson shrinkage (MGPS), were employed to analyze adverse drug reaction (ADR) reports pertaining to sunitinib in the FAERS database from its market introduction up to the first quarter of 2023. Subsequently, a secondary screening process was conducted to identify reliable positive signals.ResultsThe analysis of sunitinib adverse event signals at the system-organ classification level encompassed 27 organ systems, with gastrointestinal and endocrine disorders emerging as the predominant SOCs. A total of 237 significant adverse events meeting all four algorithms were detected. Notably, this study revealed previously unreported adverse events, including pleural effusion and ascites, while potential adrenal toxicity-related adverse events, highlighted in the drug's specification, were not identified in this analysis. The study examined the relationship between the duration of sunitinib dosing and the onset of adverse events, revealing a median onset of 48 days (IQR, 15-160 days). The findings indicated that a majority of adverse events manifested early in the dosing period, with tumor progression, disease progression, and mortality becoming more prevalent after one year of treatment.ConclusionIn the clinical utilization of sunitinib, vigilant monitoring of potential adverse reactions is imperative during the initial phase of drug administration. In addition to the documented adverse reactions outlined in the drug specification, healthcare providers should remain attentive to potential adverse reactions such as pleural effusion, ascites, and tumor development.
| S-EPMC11409130 | biostudies-literature
Project description:BackgroundAn increasing number of clinical studies have highlighted the use of atezolizumab in tumor immunotherapy. However, There is still a lack of comprehensive research on its associated adverse events (AEs). To improve our understanding of its toxicological profile and to provide valuable clinical insights regarding into the effectiveness of immunotherapy, this study utilized data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to conduct a retrospective analysis of AEs linked to atezolizumab.MethodsWe extracted the reports of AEs related to atezolizumab from the FAERS database from the first quarter of 2004 to the first quarter of 2024. We quantified them using the reporting odds ratio (ROR) and proportional reporting ratio (PRR), along with chi-square value (χ²), and conducted systematic classification of the AE signal mining results through SAS 9.4 software.ResultsA total of 19,563 valid reports were incorporated, involving 20 distinct system organ class categories. The AEs related to atezolizumab, reported at the preferred term level, mainly encompassed anemia [ROR 2.33, 95% confidence interval (CI) lower limit 2.09, PRR 2.31, χ² 255.977], febrile neutropenia (ROR 2.81, 95% CI lower limit 2.50, PRR 2.79, χ² 333.586), neutrophil count decreased (ROR 2.14, 95% CI lower limit 1.89, PRR 2.13, χ² 150.688), white blood cell count decreased (ROR 2.35, 95% CI lower limit 2.03, PRR 2.34, χ² 136.673), sepsis (ROR 2.21, 95% CI lower limit 1.91, PRR 2.20, χ² 117.741), alanine aminotransferase increased (ALT) (ROR 2.86, 95% CI lower limit 2.44, PRR 2.85, χ² 180.031), and aspartate aminotransferase increased (AST) (ROR 2.79, 95% CI lower limit 2.38, PRR 2.78, χ² 170.955).ConclusionsApart from various degrees of hepatotoxicity, such as increased ALT and AST, the immune-related hematological toxicity of atezolizumab should also be noted. In clinical practice, healthcare providers should always be vigilant for the occurrence of such medication-related AEs and take measures to enhance the safety of clinical medication use.
| S-EPMC11881481 | biostudies-literature
Project description:ObjectiveQuetiapine, 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).MethodsReporting 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.ResultsA 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.ConclusionOur 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.
| S-EPMC10401141 | biostudies-literature
Project description:BackgroundSome studies suggest that potential safety issues about PCSK9 inhibitors have not been sufficiently explored in clinical trials, including musculoskeletal adverse events (MAEs).ObjectiveTo examine the association between use of PCSK9 inhibitors with and without concurrent statins and risk of MAEs. Patients and Methods. FDA Adverse Event Reporting System (FAERS) dataset of PCSK9 inhibitors and statins from October 2015 to June 2021 was queried. The reporting odds ratio (ROR) with relevant 95% confidence interval (95% CI) was calculated as the index of disproportionality. Outcome of MAEs of different PCSK9 inhibitors regimens was also investigated.Results3,185 cases of PCSK9 inhibitor-associated MAEs were recorded. PCSK9 inhibitor class alone demonstrated a strong link to MAEs (ROR 5.92; 95% CI 5.70-6.15), and evolocumab was associated with more reports of MAEs than alirocumab. Concomitant use with statins leaded to an increased occurrence of MAEs (ROR 32.15 (25.55-40.46)), and the risk differed among different statins. The PCSK9 inhibitors were safer than statins in terms of hospitalization rate and death rate (15.64% vs. 36.83%; 0.72% vs. 3.53%).ConclusionsThis pharmacovigilance investigation suggests that PCSK9 inhibitors are associated with MAEs. The risk significantly increases when combined with statins. Increased laboratory and clinical monitoring are required to timely diagnose and manage MAEs.
| S-EPMC8808238 | biostudies-literature
Project description:Misoprostol was originally used to treat gastric ulcers, and has been widely used in abortion, cervical maturation, induced labour and postpartum hemorrhage. But there are still many undetected adverse events (AEs). The purpose of this study was to provide a comprehensive overview of the safety of misoprostol. Adverse events related to misoprostol were collected from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2024. This study used proportional disequilibrium methods such as reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) to detect AEs. After analyzing 17,427,762 adverse event reports, a total of 2032 adverse events reports related to misoprostol were identified, involving 23 system organ classes and 30 preferred terms. The most common AEs were foetal exposure during delivery(n = 201), uterine tachysystole(n = 95), uterine rupture (n = 95), and heart rate decreased (n = 93). Although most AEs complied with the drug instruction, new AEs signals such as congenital aqueductal stenosis and congenital brain damage were also identified. Clinicians should make appropriate evaluation when using misoprostol, closely monitor the indicators of patients, and have appropriate countermeasures for possible adverse events.
| S-EPMC11743753 | biostudies-literature
Project description:BackgroundTeriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use.ObjectiveTo investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference.MethodsFAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals.ResultsOut of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%).ConclusionOur findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide's clinical use.
| S-EPMC11335658 | biostudies-literature
Project description:Antistaphylococcal penicillins such as nafcillin and oxacillin are among the first choices of treatment for severe invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections, although there has been limited safety evaluations between individual agents. Using the FDA Adverse Event Reports System (FAERS), oxacillin was observed to have a lower proportion of reports of acute renal failure (reporting odds ratio [ROR], 5.3 [95% confidence interval {CI}, 3.1 to 9.3] versus 21.3 [95% CI, 15.8 to 28.6], respectively) and hypokalemia (ROR, 0.7 [95% CI, 0.1 to 4.8] versus 11.4 [95% CI, 7.1 to 18.3], respectively) than nafcillin.
| S-EPMC7038239 | biostudies-literature