Post-Marketing Safety Concerns with Efgartigimod alfa: A Pharmacovigilance Analysis Based on the Food and Drug Administration Adverse Event Reporting System Database

Ticagrelor is a commonly used antiplatelet agent, but due to the stringent criteria for trial population inclusion and the limited sample size, its safety profile has not been fully elucidated. We utilized OpenVigil 2.1 to query the FDA Adverse Event Reporting System database and retrieved reports by the generic name "ticagrelor" published between 1 October 2010 and 31 March 2023. Adverse drug events (ADEs) were classified and described according to the preferred terms and system organ classes in the Medical Dictionary of Regulatory Activity. Proportional reporting ratio (PRR), reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were used to detect signals. The number of ADE reports with ticagrelor as the primary suspect drug was 12,909. The top three ADEs were dyspnea [1824 reports, ROR 7.34, PRR 6.45, information component (IC) 2.68], chest pain (458 reports, ROR 5.43, PRR 5.27, IC 2.39), and vascular stent thrombosis (406 reports, ROR 409.53, PRR 396.68, IC 8.02). The highest ROR, 630.24, was found for "vascular stent occlusion". Cardiac arrest (137 reports, ROR 3.41, PRR 3.39, IC 1.75), atrial fibrillation (99 reports, ROR 2.05, PRR 2.04, IC 1.03), asphyxia (101 reports, ROR 23.60, PRR 23.43, IC 4.51), and rhabdomyolysis (57 reports, ROR 2.75, PRR 2.75, IC 1.45) were suspected new adverse events of ticagrelor. The FAERS database produced potential signals associated with ticagrelor that have not been recorded in the package inserts, such as cardiac arrest, atrial fibrillation, asphyxia, and rhabdomyolysis. Further clinical surveillance is needed to quantify and validate potential hazards associated with ticagrelor-related adverse events.

ObjectiveTo investigate which fluoroquinolone is safer when combined with bedaquiline for tuberculosis treatment by using the FDA Adverse Event Reporting System (FAERS) database.MethodsWe selected data from the first quarter (Q1) of 2013 to the second quarter (Q4) of 2024 from the FDA FAERS database for disproportionality analysis. Signal detection was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM).ResultsThis study analyzed 12, 303, 879 reports from the FAERS database, including 722 reports related to the combination of bedaquiline and levofloxacin (with 2,723 adverse events) and 573 reports related to the combination of bedaquiline and moxifloxacin (with 2,233 adverse events). For the bedaquiline-levofloxacin regimen, these reports were categorized into 100 preferred terms (PTs) and 24 System Organ Classification (SOCs). The three most common SOCs were hepatobiliary disorders (n = 128, ROR 5.79, PRR 5.56, IC 2.48, EBGM 5.56), blood and lymphatic system disorders (n = 217, ROR 5.04, PRR 4.72, IC 2.24, EBGM 4.71), and metabolism and nutrition disorders (n = 185, ROR 3.44, PRR 3.27, IC 1.71, EBGM 3.27). In terms of PTs, the three strongest signals were portal fibrosis (ROR 330.64), hepatitis C RNA increased (ROR 301.24), and toxic optic neuropathy (ROR 238.11). Reports of prolonged QT interval on ECG (125 cases) and anemia (130 cases) were significantly more frequent than other PTs. For the bedaquiline-moxifloxacin regimen, these reports were categorized into 85 preferred terms (PTs) and 24 System Organ Classification (SOCs). The three most common SOCs were hepatobiliary disorders (n = 141, ROR 7.9, PRR 7.47, IC 2.9, EBGM 7.46), ear and labyrinth disorders (n = 40, ROR 4.03, PRR 3.97, IC 1.99, EBGM 3.97), and cardiac disorders (n = 141, ROR 3.08, PRR 2.95, IC 1.56, EBGM 2.95). The three strongest PT signals were chronic pyelonephritis (ROR 563.29), bronchopleural fistula (ROR 314.86), and toxic neuropathy (ROR 187.11). Prolonged QT interval on ECG (152 cases) remained the most frequently reported PT. In both treatment regimens, individuals under 45 years of age experienced a higher frequency and variety of AEs, indicating the need for enhanced monitoring. For those over 45, particular attention should be given to ECG changes, especially in men. Finally, some PTs with extremely high signal strength, such as chronic pyelonephritis (ROR 563.29), hepatitis C RNA increased (ROR 301.24), and bronchopleural fistula (ROR 301.24), may represent rare adverse events associated with the combination of bedaquiline-fluoroquinolone.ConclusionOur study suggests that the safety profile of bedaquiline combined with moxifloxacin does not appear superior to that of bedaquiline combined with levofloxacin in terms of cardiac, hepatic, and neurological effects. Therefore, in the BPaLM regimen, considering the substitution of moxifloxacin with levofloxacin may be worthwhile if their efficacy is proven to be similar. Increased monitoring may be required for individuals under 45 years of age and male MDR-TB patients.

This study aimed to characterize the safety profiles of rivaroxaban-associated suspected adverse events by mining the Food and Drug Administration Adverse Event Reporting System (FAERS). A disproportionality analysis of spontaneously reported suspected adverse drug reactions (ADRs) was conducted. The reports in FAERS from 2014 to 2024 were compiled. Frequentist and Bayesian statistics were both applied to calculate drug-AE combinations in system organ classes and preferred-term levels. Reporting odds ratio (ROR), proportional reporting ratio (PRR), the Medicines and Healthcare products Regulatory Agency (MHRA), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods were analyzed and used to compare the suspected AEs. Of 77,384 ADR reports, 66,705 (86.20%) were serious rivaroxaban AE reports. The most common age group was above 65years. The suspected adverse effects of rivaroxaban emerging for system organ classes (SOCs) primarily included "Gastrointestinal disorders"; "Injury, poisoning, and procedural complications", "Nervous system disorders" and "Vascular disorders". Ranked by EBGM, the top signal strength of suspected AE signals of rivaroxaban under ROR algorithm at the preferred-term (PT) level were "Haemorrhagic arteriovenous malformation" (N = 571, ROR = 756.520, PRR = 754.029, Information Component (IC) = 7.197, Empirical Bayesian Geometric Mean (EBGM) = 146.725), "Gastrointestinal vascular malformation haemorrhagic" (N = 197, ROR = 211.138, PRR = 210.950, IC = 6.614, EBGM = 97.923), and "Diverticulum intestinal haemorrhagic" (N = 722, ROR = 169.898, PRR = 169.210, IC = 6.458, EBGM = 97.920). Moreover, uncommon but significantly suspected AE signals, such as "Coagulation factor X level increased", "Basal ganglia haematoma", and "Proctitis haemorrhagic" were observed. Notably, "Gastrointestinal haemorrhage" (N = 13,436, ROR = 80.477, PRR = 74.460, IC = 5.729, EBGM = 53.042), "Upper gastrointestinal haemorrhage"(N = 2,872, ROR = 73.978, PRR = 72.797, IC = 5.706, EBGM = 52.198) and "Internal haemorrhage" (N = 2,368, ROR = 91.979, PRR = 80.899, IC = 5.813, EBGM = 56.212) exhibited relatively high occurrence rates and signal strengths. From 2014 to 2024, the IC values of rivaroxaban-associated suspected AEs for "Surgical and medical procedures" and "Cardiac disorders" showed an annual increasing trend in the time-span analysis. Based on the various visulization plots, a key discovery is that "Gastrointestinal hemorrhage" emerged as the most significant suspected AE across five algorithms. The exciting finding was that the MGPS algorithm revealed a higher risk of suspected AEs under the "Investigations" category. However, the results of the analyses of the other algorithms at the SOC level were not akin to this. Moreover, the results of signal mining for the three main types of indication populations with adverse drug reactions (ADRs), including Atrial fibrillation, Cerebrovascular accident prophylaxis, and Deep vein thrombosis were shown that "Gastrointestinal haemorrhage", "Epistaxis", "Haematuria", "Rectal haemorrhage", and "Upper gastrointestinal haemorrhage" were detected as the most common and significant signals of suspected adverse events. Rivaroxaban has risks of various suspected adverse reactions while providing therapeutic effects and being used widely. Our pharmacovigilance study may provide valuable hints that practitioners should closely monitor occurrences of "Gastrointestinal disorders", "Injury, poisoning, and procedural complications" and "Nervous system disorders", and other events in clinical applications. Consequently, it remains to persist in monitoring rivaroxaban, assessing the associated risks in the future.

Nifedipine, a dihydropyridine calcium channel blocker, is widely used in the management of hypertension and as a tocolytic agent to delay preterm labor, including in pregnant women. However, its safety profile, particularly in pregnant populations, remains insufficiently characterized. This study aimed to evaluate adverse event (AE) signals associated with nifedipine use, with a specific focus on pregnancy-related outcomes. Nifedipine-related AEs reported in U.S. Food and Drug Administration Adverse Event Reporting System database (Q1 2004–Q4 2024) were analyzed. Disproportionality analysis was conducted using 4 established signal detection methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker. Pregnancy-related reports were identified using Standardized MedDRA Queries, and subgroup analyses were conducted for pregnant women. In the overall population, significant signals at the System Organ Class level were observed for pregnancy-related conditions, vascular disorders, and cardiac disorders. The strongest prominent preferred term signal was gingival hypertrophy (n = 52; ROR = 100.55, PRR = 100.23, information component [IC] = 6.61, empirical Bayesian geometric mean [EBGM] = 97.42). Among pregnant women, prominent signals at the System Organ Class level included vascular disorders, respiratory disorders, and cardiac disorders. The strongest preferred term signal was acute pulmonary edema (n = 27; ROR = 67.23, PRR = 66.70, IC = 5.87, EBGM = 58.29), followed by cardiogenic shock (n = 11; ROR = 41.80, PRR = 41.67, IC = 5.26, EBGM = 38.25), pulmonary edema (n = 51; ROR = 38.57, PRR = 38.00, IC = 5.14, EBGM = 35.15), and hypoxia (n = 28; ROR = 20.62, PRR = 20.46, IC = 4.29, EBGM = 19.62). Several unexpected pregnancy-related AEs were also detected, including eclampsia, fetal distress, placental disorders, and intrauterine growth restriction. This study identified unexpected AE signals associated with nifedipine use during pregnancy. The findings offer valuable insights to guide clinical decision-making and promote safer use of nifedipine in pregnant populations.

Low 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. We 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). For 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. This 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.

Irinotecan is a widely used chemotherapeutic agent for treating colorectal, pancreatic, and ovarian cancers. Despite its therapeutic efficacy, the safety profile of irinotecan necessitates continuous pharmacovigilance due to its association with severe adverse drug events (ADEs). Given its global use, cross-national signal detection may reveal region-specific risks or unrecognized adverse effects. We conducted a retrospective pharmacovigilance analysis of irinotecan-associated ADEs using two large spontaneous reporting systems: the U.S. FDA Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Report (JADER) database. ADE reports between 2004 and 2024 were extracted. Disproportionality analyses were performed using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and Multi-item gamma Poisson shrinker (MGPS). A total of 11,344 ADE reports from FAERS and 7,822 from JADER were identified. These reports involved 27 system organ classes (SOCs). In FAERS, the most frequently affected SOC was gastrointestinal disorders (n = 6,888), while in JADER it was blood and lymphatic system disorders (n = 3,389). Disproportionality analysis revealed 388 and 67 preferred terms (PTs) significantly associated with irinotecan in FAERS and JADER, respectively, with 38 overlapping signals. These included both expected ADEs (e.g., neutropenia, diarrhea, thrombocytopenia, stomatitis) and unexpected signals such as second primary malignancies, hyperammonaemia, and hiccups. Notable FAERS-specific signals included skin toxicity (n=100, ROR 33.89 (27.79-41.34), PRR 33.80, EBGM05 28.03, IC025 4.76), aphasia [n=65, ROR 3.57 (2.8-4.55), PRR 3.56, EBGM05 2.90, IC025 1.47], and hepatic failure [n=56, ROR 3.09 (2.38-4.02), PRR 3.09, EBGM05 2.48, IC025 1.24], while JADER-specific signals included fatigue [n=73, ROR 4.69 (3.71-5.93), PRR 4.67, EBGM05 3.57, IC025 0.51], hyperammonaemia [n=67, ROR 7.24 (5.56-9.27), PRR 7.21, EBGM05 5.32, IC025 1.10], and cholinergic syndrome [n=27, ROR 5.54 (3.76-8.16), PRR 5.53, EBGM05 3.61, IC025 0.74]. Over half of all reported ADEs occurred within one month of irinotecan administration (53.1% in FAERS, 61.7% in JADER). The median time to onset was 28 days [IQR 9-76] in FAERS and 17 days [IQR 9-57] in JADER. This comparative analysis revealed multiple consistent and unexpected signals related to irinotecan use. The findings emphasize the importance of region-specific pharmacovigilance and the need for heightened awareness of both labeled and unlabeled toxicities. Our results support continued monitoring and further investigation into temporal patterns and regional differences in irinotecan-related adverse events to enhance clinical safety.

Background: Valproate(VPA) is widely used for treating epilepsy, bipolar disorder, and migraines. However, its use during pregnancy raises concerns due to potential adverse events (AEs) on fetal development. Previous studies have linked VPA to neural tube defects, cardiac malformations, and cognitive impairments in offspring. Despite these risks, some pregnant women continue VPA therapy due to medical necessity, highlighting the need for a comprehensive evaluation of its AEs. This study aims to systematically assess AEs with VPA use during pregnancy from the FDA Adverse Event Reporting System (FAERS) database. Methods: We utilized the Standardized MedDRA Query to detect AEs associated with pregnancy. Disproportionality analyses were conducted to pinpoint AEs related to VPA, employing metrics including the Reporting Odds Ratios (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and the Empirical Bayesian Geometric Mean (EBGM) to ascertain the associations. Results: The significantly reported adverse signals in SOCs were Social circumstances, Ear and labyrinth disorders, Congenital, familial and genetic disorders, Psychiatric disorders, Nervous system disorders, and Eye disorders. The five strongest signals for VPA-related included Physical disability(n=345, ROR 387.63,PRR 380.87,IC025 5.15,EBGM 46.55), Foetal anticonvulsant syndrome (n=387, ROR 217.87,PRR 213.62,IC025 5.06,EBGM 42.55),Tension(n=216, ROR453.25,PRR 448.30,IC025 5.01,EBGM 47.40),Social problem(n=212, ROR370.64,PRR 366.67,IC025 4.98,EBGM 46.33), and Deformit(n=340, ROR157.44,PRR 154.75,IC025 4.94,EBGM 39.61). An in-depth analysis of AEs in fetus found that the five strongest signals for VPA-related to the fetus included Foetal anticonvulsant syndrome (n=387, ROR 217.87,PRR 213.62,IC025 5.06,EBGM 42.55), Neural tube defect (n=218, ROR 42.679,PRR 42.21,IC025 4.19,EBGM 23.72), Spina bifida (n=347, ROR 22.12,PRR 21.74,IC025 3.73,EBGM 15.62), Dysmorphism (n=270, ROR 20.69,PRR 20.42,IC025 3.63,EBGM 14.94), Congenital cardiovascular anomaly (n=141, ROR 19.59,PRR 19.46,IC0253.44,EBGM14.42). Additionally, Autism spectrum disorder, Congenital nose malformation, Foot deformity, Neurodevelopmental disorder are high intensity signal. Conclusion: VPA use in pregnancy demonstrates robust pharmacovigilance signals for teratogenic outcomes. These findings corroborate clinical warnings, urging strict avoidance of VPA in pregnancy when possible. Risk-benefit assessments and alternative therapies are critical for necessitated cases, alongside vigilant prenatal monitoring. Further research is needed to confirm causality and explore underlying mechanisms.

A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System(FAERS) Event for Belatacept.

The objective of the study is to systematically identify and evaluate the adverse drug reactions (ADRs) associated with the combination therapy of systematically and bevacizumab in patients with unresectable hepatocellular carcinoma (HCC). Data were extracted from the Food and Drug Administration (FDA) Adverse Event Reporting System FDA Adverse Event Reporting System database. Disproportionality analysis was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR) and Bayesian confidence propagation neural network (BCPNN) of information components (IC). Time-to-onset (TTO) profiles were analyzed using the Weibull shape parameter (WSP) test, while cumulative incidences were assessed using the Kaplan‒Meier method. Valuable preferred term (PT) signals were identified for designated medical event (DME) screening, comparing these signals with system organ class (SOC) analysis. A total of 2,831 adverse events (AEs) reports were identified in the FAERS database, of which 124 positive AEs were detected across multiple SOCs. The median TTO of AEs was 43 days, with the highest proportion occurring within 0-30 days of TTO (n = 450, 41.17%). The WSP test indicated that patients with abnormal hepatic function and hepatic failure exhibited early failure-type profiles. Ten PT signals consistent with those on the DME list were identified, involving six SOCs. Our study provides valuable pharmacological insights for early clinical intervention in managing ADRs and offers significant clinical benefits for HCC patients undergoing combination therapy with atezolizumab and bevacizumab.

IntroductionPexidartinib, an oral selective colony-stimulating factor 1 receptor (CSF1R) inhibitor, is the only systemic therapy approved by the U.S. Food and Drug Administration (FDA) for tenosynovial giant cell tumor (TGCT). While clinical trials have defined its initial safety profile, their limited sample sizes and short follow-up restrict the detection of rare or delayed adverse events (AEs), underscoring the need for real-world pharmacovigilance.MethodsUsing the FDA Adverse Event Reporting System (FAERS) database, we conducted a disproportionality analysis to characterize the post-approval safety profile of pexidartinib and identify unlabeled AEs, applying reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods.ResultsAmong 7,168,342 FAERS reports, 668 implicated pexidartinib as the primary suspect, with AEs reported across 26 organ systems. Sixty-seven preferred terms met the criteria of all four signal detection methods, including 16 not listed in the FDA-approved label.DiscussionThe overall safety profile was largely consistent with clinical trial findings, while newly detected AEs suggest possible rare or delayed toxicities in broader patient populations. These results highlight the importance of continuous post-marketing surveillance and support the need for prospective studies to clarify causal relationships.

Background and objective: Sacituzumab govitecan (SG), the first antibody-drug conjugate targeting human trophoblast cell-surface antigen 2 (Trop-2), has been approved by the Food and Drug Administration (FDA) for the treatment of advanced or metastatic breast cancer and urothelial cancer. However, there is currently a dearth of information regarding the safety profiles of SG in a large sample cohort. The objective of the present study is to investigate SG-related adverse events (AEs) in real-world settings leveraging the FDA Adverse Event Reporting System (FAERS) database to guide the safety management of clinical medication.Methods: The FAERS database was retrospectively queried to extract reports associated with SG from April 2020 to March 2023. To identify and evaluate potential AEs in patients receiving SG, various disproportionality analyses such as 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: Overall, 2069 reports of SG as the “primary suspect” were identified. Noteworthy, SG was significantly associated with an increased risk of blood lymphatic system disorders (ROR, 7.18; 95% CI, 6.58–7.84) and hepatobiliary disorders (ROR, 2.68; 95% CI, 2.17–3.30) at the System Organ Class (SOC) level. Meanwhile, 61 significant disproportionality preferred terms (PTs) simultaneously complied with all four algorithms were adopted. Therein, anemia, thrombocytopenia, neutropenia, leukopenia, diarrhea, asthenia, alopecia, and electrolyte imbalance were consistent with the common AEs described in the clinical trials and specification of SG. Furthermore, unexpected significant AEs include colitis (ROR, 12.09; 95% CI, 9.1–16.08), heart rate increased (ROR, 5.11; 95% CI, 3.84–6.79), sepsis (ROR, 4.77; 95% CI, 3.59–6.34), cholestasis (ROR, 6.28; 95% CI, 3.48–11.36), blood bilirubin increased (ROR, 4.65; 95% CI, 2.42–8.94) and meningitis (ROR, 7.23; 95% CI, 2.71–19.29) were also be detected. The median time to onset of SG-related AEs was 14 [interquartile range (IQR), 7–52] days, with the majority occurring within the initial month of SG treatment.Conclusion: Our study validates the commonly known AEs and also found some potentially emerging safety issues related to SG in real-world clinical practice, which could provide valuable vigilance evidence for clinicians and pharmacists to manage the safety issues of SG.

BackgroundDeutetrabenazine is a widely used drug for the treatment of tardive dyskinesia (TD), and post-marketing testing is important. There is a lack of real-world, large-sample safety studies of deutetrabenazine. In this study, a pharmacovigilance analysis of deutetrabenazine was performed based on the FDA Adverse Event Reporting System (FAERS) database to evaluate its relevant safety signals for clinical reference.MethodsAdverse events (AEs) of FAERS with deutetrabenazine as the primary suspect drug were collected from the first quarter (Q1) of 2017 to Q1 of 2024. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were used to mine AEs risk signals of deutetrabenazine. AEs were standardized and classified using the System Organ Class (SOC) and Preferred Terms (PTs) from Medical Dictionary for Regulatory Activities (MedDRA) version 23.0.ResultsA total of 3,583 AEs with deutetrabenazine as the primary suspect drug were collected in this study. We found that these AEs involved 23 SOCs, and the positive signals were mainly concentrated in systemic disease and various reactions at the site of administration (n = 1816, ROR = 1.23, PRR = 1.18, IC = 0.24, EBGM = 1.18), neurological disorders (n = 1736, ROR = 3.02, PRR = 2.60, IC = 1.38, EBGM = 2.60) and psychiatric disorders (n = 1,659, ROR = 4.15, PRR = 3.52, IC = 1.82, EBGM = 3.52). We eventually identified 100 valid PTs that met the criteria of the four algorithms. Drug ineffective, dyskinesia, depression, somnolence, suicidal ideation were considered to be the common PTs of deutetrabenazine. Tongue thrust (n = 4, ROR 253.47, PRR 253.35, IC 7.88, EBGM 235.95), grunting (n = 5, ROR 78.49, PRR 78.45, IC 6.26, EBGM 76.71) and drooling (n = 17, ROR 13.21, PRR 13.19, IC 3.72, EBGM 13.14) were not mentioned in the specification, but the high signal intensity suggested that they may be the potential adverse reactions.ConclusionThe efficacy of deutetrabenazine may be accompanied by some potential adverse effects in several systems. Adverse events in psychiatric, neurologic, gastrointestinal and respiratory need to be monitored in clinical practice.

The study aimed to conduct a multidimensional evaluation of potential adverse events (AEs) of escitalopram oxalate based on the FDA adverse event reporting system (FAERS) database. This study utilized the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-poisson shrinker (MGPS) to mine and analyze data from the FAERS database from the first quarter of 2004 to the second quarter of 2023. There was a total of 19,854 AE reports related to escitalopram oxalate, extracting 625 preferred terms (PTs), and covering 27 system organ classes (SOCs). The results showed that the number of reports by females was significantly higher than males, accounting for 57.68%. The reporting number was higher in 2018 and 2019, accounting for 9.50% and 10.18% of the total reports, respectively. The main reporters were consumers and other health professionals, accounting for 26.99% and 26.75% respectively. The majority of the reports were primarily from the United States. Newly emerging AE signals such as intentional overdose (n = 691, ROR 8.51, PRR 8.45, IC 3.05, Empirical Bayesian Geometric Mean (EBGM) 8.35), suicide attempt (n = 665, ROR 8.58, PRR 8.52, IC 3.06, EBGM 8.42), serum serotonin (n = 5, ROR 1044.78, PRR 1044.71, IC 2.56, EBGM 392.39), anti-actin antibody positive (n = 5, ROR 626.87, PRR 626.83, IC 2.56, EBGM 313.91), among others, were not mentioned in the drug's label. While escitalopram oxalate has clear benefits in the treatment of depression and other mental health disorders, the presence of AEs also suggests risks associated with its use. Particularly concerning are risks of suicide and changes in serum serotonin levels.

Ribociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of advanced hormone receptor-positive (HR+) breast cancer. The presented study aimed to evaluate the ribociclib-associated adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Data were collected from the FAERS database covering the period from the first quarter of 2017 to the first quarter of 2023. Disproportionality analyses were employed to quantify the associated AE signals of ribociclib and detect the risk signals using reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the empirical Bayes geometric mean (EBGM), and MedDRA was used to systematically classify the results. A total of 9533 AE reports of ribociclib were obtained using data from the FAERS database, and ribociclib-associated AEs targeted 23 system organ classes (SOCs) after conforming to the four algorithms simultaneously. The common significant SOCs were identified, including benign, malignant and unspecified neoplasms, immune system disorders, etc. The significant AE signals were then mapped to preferred terms (PTs), associated with tumorigenesis and haematologic toxicity, which have emerged in the study, usually reported in patients with ribociclib. Of note, unexpected significant AEs, including "left atrial enlargement", "erysipelas", "polyneuropathy", "glomerular filtration rate decreased", "ageusia", and so on, were uncovered in the label. Our study provides real-world safety data on post-marketing surveillance and highlights potential new and unexpected AE signals during ribociclib treatment.

To explore adverse event (AE) signals of Ceftazidime/avibactam (CZA) based on the FDA Adverse Event Reporting System (FAERS) database. AE reports primarily associated with CZA were retrieved from the FAERS database from the second quarter of 2015 to the second quarter of 2023. Signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods. A total of 750 AEs reports with CZA as the preferred suspected drug were obtained, identifying 66 preferred terms (PTs) involving 24 system organ classes (SOCs). Besides, the AEs already mentioned in the drug label, this study also revealed some new, clinically valuable potential AEsignals, such as Cholestasis (n = 14, ROR 29.39, PRR 29.15, IC 3.34, EBGM 29.11), Drug-induced liver injury (n = 8, ROR 9.05, PRR 9.01, IC 2.25, EBGM 9.01), Hepatocellular injury (n = 7, ROR 13.90, PRR 13.84, IC 2.41, EBGM 13.63), Haemolytic anaemia (n = 5, ROR 24.29, PRR 24.22, IC 2.42, EBGM 40.53), etc. Additionally, AE signals with higher intensity were identified, such as Hypernatraemia (n = 5, ROR 40.73, PRR 40.61, IC 2.31, EBGM 24.19), Toxic epidermal necrolysis (n = 4, ROR 11.58, PRR 11.55, IC 1.89, EBGM 11.54). Therefore, special vigilance for these potential AEs is warranted when using CZA clinically. This study highlights the potential AEs and risks associated with the clinical use of CZA, particularly the risks related to Cholestasis, Drug-induced liver injury, Haemolytic anaemia, Hypernatraemia, and Toxic epidermal necrolysis.