Expert Opinion On Drug Safety[JOURNAL]
Sun
200 papers
COVID-19 vaccine safety studies- the need for a third group for extended monitoring.
Kaur U, Chakrabarti SS
Expert Opin Drug Saf · 2026 Jan · PMID 40737552 · Publisher ↗
INTRODUCTION: Studies assessing COVID-19 vaccine effectiveness have generally categorized individuals into 'vaccinated' and 'unvaccinated' groups. Long-term safety studies are sparse and have usually compared adverse eve...
INTRODUCTION: Studies assessing COVID-19 vaccine effectiveness have generally categorized individuals into 'vaccinated' and 'unvaccinated' groups. Long-term safety studies are sparse and have usually compared adverse events with background rates. Studies on timing of COVID-19 vaccination as a determinant of long COVID have provided variable results, while there is scarce data on timing of vaccination as a determinant of adverse events. AREAS COVERED: We discuss some of our observations as well as the global evidence on the timing of COVID-19 vaccination as a determinant of long-COVID and adverse events. This special report is hypothesis-generating and aims to propose a conceptual framework and not establish causality. EXPERT OPINION: We propose an alternative classification strategy for COVID-19 vaccinees, with special emphasis on individuals who received any dose of vaccination after recovering from natural COVID-19, i.e. the 'vaccine-after-COVID' (VAC) group. These individuals should be followed up for an extended period through multicentric and database studies. This may help in understanding the long-term safety of COVID-19 vaccines and the natural course of long COVID. Immunological characteristics of this group should also be scrutinized. The evidence gained might be useful in planning vaccination policies in the event of future pandemics.
Trends in the use of sodium-glucose cotransporter-2 inhibitors and characteristics of adverse event reporting in patients with heart failure in Japan: reports from the medical administration database and the adverse event reporting database.
Sato K, Kawada K, Ishida T … +8 more , Kubo T, Koji M, Aizawa F, Yagi K, Izawa-Ishizawa Y, Niimura T, Goda M, Ishizawa K
Expert Opin Drug Saf · 2025 Jul · PMID 40711847 · Publisher ↗
BACKGROUND: Heart failure (HF) is a global health issue with a high prevalence in aging populations. Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce HF-related hospitalizations and mortality; however, their adve...
BACKGROUND: Heart failure (HF) is a global health issue with a high prevalence in aging populations. Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce HF-related hospitalizations and mortality; however, their adverse drug events (ADEs) require further evaluation. RESEARCH DESIGN AND METHODS: Using the Japan Medical Data Center and Japanese Adverse Drug Event Report (JADER) databases, we analyzed prescribing trends and ADE risk factors. Multivariate logistic regression assessed associations between patient characteristics and ADEs, adjusting for age, sex, medication use, and comorbidities. Decision tree analyses stratified ADE risks. RESULTS: SGLT2 inhibitor prescriptions increased from 1.63% (2018) to 9.08% (2022), with a notable rise in 2021. JADER analysis showed an increasing number of ADE reports, primarily dehydration, urinary tract infections, and renal impairment. Decision tree analyses identified risk factors: dehydration (age ≥80 years, tolvaptan use), urinary tract infection (female sex, renal dysfunction), and renal impairment (angiotensin receptor-neprilysin inhibitor use, history of renal dysfunction). CONCLUSIONS: Personalized risk assessment and monitoring are crucial for optimizing SGLT2 inhibitor therapy, particularly in older patients with HF and renal impairment.
Suspected statin-related adverse drug reactions: analysis of spontaneous reports in Hubei Province, China (2014-2022).
Wang H, Bi H, Shangguan X … +4 more , Chen Z, Huang R, Chen X, Cai Y
Expert Opin Drug Saf · 2025 Jul · PMID 40668065 · Publisher ↗
INTRODUCTION: Statins, some of the most widely prescribed medications for the treatment of cardiovascular diseases, cause common and serious adverse drug reactions (ADRs). However, studies of statin-related ADRs in the C...
INTRODUCTION: Statins, some of the most widely prescribed medications for the treatment of cardiovascular diseases, cause common and serious adverse drug reactions (ADRs). However, studies of statin-related ADRs in the Chinese population are lacking. RESEARCH DESIGN AND METHODS: ADR reports of statins collected by the Hubei Adverse Drug Reaction Monitoring Center from 2014 to 2022 were analyzed. Statin safety was described using descriptive analysis and three signal mining methods: reporting odds ratio, proportional reporting ratio, and a combined standard method. RESULTS: ADRs were common in individuals aged 50-79 years. Most administration routes are oral. ADR reports of atorvastatin and rosuvastatin were numerous and serious. The reports mainly consisted of gastrointestinal disorders, hepatobiliary disorders. Three signal mining algorithms generated 91 identical drug - event combination signals, including 23 off-label ADRs. CONCLUSIONS: Atorvastatin was associated with a higher number of ADR reports and a higher proportion of serious ADRs than the other statins. Atorvastatin may cause off-label ADRs such as back pain, increased blood bilirubin, bone pain, hemorrhage, hepatic failure, and hepatocellular injury. Drug instructions should be enriched for better labeling of ADRs.
Peripheral neuropathies induced by BRAF+MEK inhibitor combinations: a real-world study based on FAERS database 2011-2022.
Wang Y, Zheng J, Zhang Z … +2 more , Mai H, Su L
Expert Opin Drug Saf · 2025 Jul · PMID 40611526 · Publisher ↗
BACKGROUND: BRAF/MEK inhibitors (BRAFi+MEKi) like may cause peripheral neuropathies (PN). This study analyzes FAERS data to assess PN signals across BRAFi+MEKi combinations. RESEARCH DESIGN AND METHODS: Disproportionalit...
BACKGROUND: BRAF/MEK inhibitors (BRAFi+MEKi) like may cause peripheral neuropathies (PN). This study analyzes FAERS data to assess PN signals across BRAFi+MEKi combinations. RESEARCH DESIGN AND METHODS: Disproportionality analysis was conducted to quantify the signals of BRAFi+MEKi-associated PN on FAERS database from January 2011 to December 2022. Additionally, we examined the onset times and prognosis of BRAFi+MEKi-associated PN. RESULTS: A total of 268 reports of BRAFi+MEKi-associated PN were identified in the study, with a median age range of 60.00 to 69.00 years. All three combination therapies exhibited positive signals for PN, and notably, Encorafenib and Binimetinib (E+B) displayed the strongest association with PN (ROR 3.05[2.47,3.76], IC1.57[1.26]). The associations between PN and different BRAFi+MEKi combinations remained persisted in the gender and age stratification analysis, with all three combination therapies showing an elevated number of disproportionality signals in males compared to females. CONCLUSION: According to our findings, BRAFi+MEKi-associated PN tends to occur several months after initiation and may lead to serious outcomes. Male sex is more likely to be a risk factor associated with PN. Prompt identification and intervention for BRAFi+MEKi-associated PN are crucial, and additional fundamental research is required to validate the underlying mechanism as observed in our study.
Exploring tumor lysis syndrome linked to immune checkpoint inhibitors: insights from the FAERS pharmacovigilance database.
Yuan Y, He W, Tong L … +4 more , Liu M, Tang W, Yang W, Pan X
Expert Opin Drug Saf · 2025 Jul · PMID 40605365 · Publisher ↗
BACKGROUND: The increasing use of immune checkpoint inhibitors (ICIs) has raised concerns about immune-related adverse events (irAEs), including tumor lysis syndrome(TLS), traditionally linked to cytotoxic chemotherapy....
BACKGROUND: The increasing use of immune checkpoint inhibitors (ICIs) has raised concerns about immune-related adverse events (irAEs), including tumor lysis syndrome(TLS), traditionally linked to cytotoxic chemotherapy. This study investigates the association between ICIs and TLS, analyzing clinical characteristics, treatment regimens, and outcomes. RESEARCH DESIGN AND METHODS: ICIs-associated TLS cases reported in the FDA Adverse Event Reporting System (FAERS) from Q1 2011 to Q1 2024 were analyzed. Disproportionality analysis and Weibull shape parameter (WSP) modeling were used to assess reporting trends and onset patterns. RESULTS: Among 364 TLS cases, anti-PD-1 were most frequently implicated ( = 210), followed by anti-PD-L1 ( = 109) and anti-CTLA-4 ( = 45). Combination therapies accounted for 61.0% of cases, with distinct disease distributions: dual ICIs in melanoma (36.36%), ICIs plus chemotherapy in lung cancer (47.37%), and ICIs plus antiangiogenic therapy in hepatocellular carcinoma (59.14%). The median onset time was 9 days (IQR: 3-23.75), with WSP analysis indicating an early failure pattern (β = 0.75, 95% CI: 0.66-0.85). CONCLUSIONS: ICIs are significantly associated with TLS, particularly in combination regimens, necessitating early risk identification and close monitoring. Given the rising use of ICIs, proactive management and ongoing pharmacovigilance are essential to mitigate severe outcomes.
Evaluating safety risks of ischaemic colitis with taxanes: a disproportionality analysis based on FDA adverse event Reporting system.
Liao Y, Zeng Y, Su X … +6 more , Lin W, Lin X, Weng L, Yang J, Zhuang W, Wu J
Expert Opin Drug Saf · 2025 Jul · PMID 40600776 · Publisher ↗
BACKGROUND: Ischaemic colitis (IC) is a rare yet serious gastrointestinal condition, increasingly reported in patients receiving taxanes-based chemotherapy. So far, the correlation between the two remains unclear. The ai...
BACKGROUND: Ischaemic colitis (IC) is a rare yet serious gastrointestinal condition, increasingly reported in patients receiving taxanes-based chemotherapy. So far, the correlation between the two remains unclear. The aim of this study is to assess the safety concerns associated with taxanes use in relation to IC. RESEARCH DESIGN AND METHODS: Disproportionality analyses (Reporting Odds Ratio [ROR], Proportional Reporting Ratio [PRR], Bayesian Confidence Propagation Neural Network [BCPNN], Multi-item gamma Poisson Shrinker [MGPS]) were conducted using the FDA Adverse Event Reporting System (FAERS, 2005 Q1-2023 Q2). RESULTS: Significant IC signals were detected across taxanes: paclitaxel (ROR 4.07, PRR 4.07, BCPNN 2.02, MGPS 4.05), nab-paclitaxel (ROR 2.99, PRR 2.99, BCPNN 1.58, MGPS 2.98,), and docetaxel (ROR 3.63, PRR 3.63, BCPNN 1.85, MGPS 3.59). Reports were predominantly from Japan and the U.S.A. with IC developing within 16 days in half of the patients. CONCLUSION: Taxanes may substantially increase IC risk, necessitating vigilant gastrointestinal monitoring and characterization of high-risk populations. Further clinical validation is required to confirm these findings.
Safety profile of letrozole in the real world: a disproportionality analysis of FAERS database and systematic review of case reports.
Liang C, Zhang Y, An P … +2 more , Zuo W, Zhang B
Expert Opin Drug Saf · 2025 Jul · PMID 40590361 · Publisher ↗
BACKGROUND: Letrozole is an aromatase inhibitor for breast cancer. Most of the safety data of letrozole came from clinical trials, while real-world information is insufficient. RESEARCH DESIGN AND METHODS: FAERS data wer...
BACKGROUND: Letrozole is an aromatase inhibitor for breast cancer. Most of the safety data of letrozole came from clinical trials, while real-world information is insufficient. RESEARCH DESIGN AND METHODS: FAERS data were analyzed using OpenVigil 2 for disproportionality signals. A systematic review of PubMed, Embase, and CINAHL identified letrozole-related ADR case reports, evaluated by Naranjo Scale. RESULTS: The analysis of FAERS (2004 Q1-2023 Q4) identified 1,165 ADR signals from 29,631 cases, with general disorders, gastrointestinal, and musculoskeletal connective tissue disorders being the most frequent system organ classes (SOCs). Fatigue (3,431 cases), nausea (2,421), diarrhea (1,943), arthralgia (1,756), and alopecia (1,640) were the top reported signals. Novel signals included nitrituria and retinal phototoxicity, with 14 SOCs identified in the top 20 high-PRR signals. The systematic review included 45 cases from 40 publications, with skin/subcutaneous (13 cases) and musculoskeletal disorders (9 cases) most common. Notably, 26.67% of ADRs (12/45) were unreported in labeling, including rhabdomyolysis, systemic sclerosis, and acute kidney injury. CONCLUSIONS: Clinicians need to pay attention to rhabdomyolysis when letrozole combined with catecholaminergic agents. Patient education on urine output monitoring is essential due to potential kidney injury. Bone marrow suppression and reproductive toxicity risks require clinical attention.
Efficacy and safety of omitting 5-fluorouracil bolus in combination chemotherapy regimens for gastrointestinal cancers: a systematic review and meta-analysis.
Ilhan Y, Balcık OY, Sahın E … +8 more , Merc Cetınkaya A, Almuradova E, Bardakcı M, Dınckal C, Karateke M, Bır Yucel K, Onder AH, Ergun Y
Expert Opin Drug Saf · 2026 Jun · PMID 40590359 · Publisher ↗
INTRODUCTION: This meta-analysis aimed to evaluate the impact of omitting the 5-FU bolus in chemotherapy regimens for gastrointestinal cancers on treatment efficacy and toxicity. METHODS: We searched major databases and...
INTRODUCTION: This meta-analysis aimed to evaluate the impact of omitting the 5-FU bolus in chemotherapy regimens for gastrointestinal cancers on treatment efficacy and toxicity. METHODS: We searched major databases and congress proceedings until 25 October 2024 to identify studies comparing 5-FU bolus and non-5-FU bolus regimens in patients with gastrointestinal cancers. The studies included those reporting on progression-free survival (PFS), overall survival (OS), and adverse events in metastatic gastrointestinal cancer patients. RESULTS: The analysis included 7 studies with 12,698 patients. No significant differences in PFS (HR: 0.94, 95% CI: 0.83-1.07) or OS (HR: 0.96, 95% CI: 0.89-1.03) were found between the 5-FU bolus and non-bolus groups. However, significantly higher rates of grade 3-4 neutropenia (OR: 0.46, 95% CI: 0.37-0.57) and any grade thrombocytopenia (OR: 0.53, 95% CI: 0.35-0.80) were observed in the 5-FU bolus group. No significant differences were found for other toxicities like febrile neutropenia, diarrhea, or nausea. CONCLUSIONS: This meta-analysis demonstrates that the omission of 5-FU bolus from the commonly used 5-FU-based chemotherapy regimens in gastrointestinal cancers, with the use of only 5-FU infusion, may reduce the risk of hematologic toxicities such as neutropenia and thrombocytopenia without affecting survival outcomes in metastatic gastrointestinal cancers. PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42024602968.
Safety issues of tofacitinib in rheumatoid arthritis patients: real-world pharmacovigilance.
Zeng Y, Jiang J, Luo D … +6 more , Zheng B, Liu M, Huang S, Wu J, Dou X, Zhou S
Expert Opin Drug Saf · 2025 Jul · PMID 40583856 · Publisher ↗
BACKGROUND: Tofacitinib is the first oral tsDMARD approved for the treatment of rheumatoid arthritis, often used as monotherapy or in combination with conventional synthetic DMARDs. However, its safety profile has yet to...
BACKGROUND: Tofacitinib is the first oral tsDMARD approved for the treatment of rheumatoid arthritis, often used as monotherapy or in combination with conventional synthetic DMARDs. However, its safety profile has yet to be systematically evaluated. Our study is the largest pharmacovigilance analysis of real-world data on the safety of tofacitinib. METHODS: Using the FAERS database (from Q1 2012 to Q1 2024), we extracted reports where tofacitinib was the primary suspect, conducting subgroup analyses stratified by gender and age. Positive signals were assessed through disproportionality analysis (criteria: ROR, PRR, BCPNN, and EBGM), identifying common ADRs across five subgroups. Further, we extracted reports with complete information on confounding factors (age, gender, weight, report time) for multivariate logistic regression to evaluate the independent effects of the intersecting ADRs. RESULTS: Our study reveals that, beyond known adverse reactions (such as upper respiratory tract infections and nasopharyngitis), tofacitinib is associated with numerous unreported adverse reactions, including systemic infections, tumor progression, and thrombotic risks. Many of these adverse reactions exhibit significant variability across different AD populations. CONCLUSIONS: Enhanced monitoring is recommended for RA patients, especially those with comorbid malignancies, cardiovascular events, or infection risks, during tofacitinib therapy.
Use of medroxyprogesterone acetate and risk of meningiomas: a comparative safety study.
Frey C, Sodhi M, Fatehi M … +2 more , Kezouh A, Etminan M
Expert Opin Drug Saf · 2025 Jul · PMID 40583195 · Publisher ↗
BACKGROUND: Medroxyprogesteroneacetate (MPA), a widely used hormonal contraceptive, has been associated with increased risk of meningiomas. However, the risk of meningiomas associated with MPA compared to oral contracept...
BACKGROUND: Medroxyprogesteroneacetate (MPA), a widely used hormonal contraceptive, has been associated with increased risk of meningiomas. However, the risk of meningiomas associated with MPA compared to oral contraceptives containing ethinylestradiol-levonorgestrel (EE-LNG) remains unclear. This study aimed to evaluate the relative risk of meningiomas in women using MPA versus EE-LNG. RESEARCH DESIGN AND METHODS: A nested case-control study was conducted using the PharMetrics Plus database (2006-2020). The cohort included new users of MPA and EE-LNG. Incident meningioma cases were matched to controls based on age and calendar time. Conditional logistic regression was used to account for confounders, including prior radiotherapy, hormonal contraceptive use, and obesity. MAIN OUTCOME MEASURES: The primary outcome was the incidence rate ratio (IRR) of meningiomas in MPA users compared to EE-LNG users. RESULTS: Among women using MPA for more than one year, the adjusted IRR for meningiomas was 3.55 (95% CI: 1.85-6.85), indicating a significantly higher risk compared to EE-LNG users. CONCLUSIONS: MPAuse is linked to a substantially increased risk of meningiomas, underscoring the importance of assessing its long-term use. Further research is warranted to confirm these findings and guide clinical practice.
Adverse event profiles of four monomethyl auristatin E-conjugated antibody drug conjugates: a disproportionality analysis based on the US FDA adverse event reporting system (FAERS) database.
Doi Y, Ieiri I, Uchida M … +1 more , Hirota T
Expert Opin Drug Saf · 2025 Jun · PMID 40576197 · Publisher ↗
BACKGROUND: Antibody-drug conjugates (ADCs) with monomethyl auristatin E (MMAE) have recently become prevalent in cancer treatment. This study aimed to comprehensively examine the adverse events (AEs) associated with reg...
BACKGROUND: Antibody-drug conjugates (ADCs) with monomethyl auristatin E (MMAE) have recently become prevalent in cancer treatment. This study aimed to comprehensively examine the adverse events (AEs) associated with regulatory-approved MMAE-conjugated ADCs using the FDA Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: A disproportionality analysis of reports from July 2011 to September 2024 was conducted to detect AE signals in adult patients with cancer receiving any of the four MMAE-conjugated ADCs (brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and tisotumab vedotin) using reporting odds ratio and information component. RESULTS: FAERS yielded 12,655 reported cases with 4,958 drug-AE pairs. Positive signals observed across the four MMAE-ADCs included 'blood and lymphatic system disorders' and 'metabolism and nutrition disorders' at the system organ class, and anemia, febrile neutropenia, hypokalemia, peripheral neuropathy, and pneumonitis for individual AEs, with 54 other overlapping AEs shared by at least three of the ADCs. CONCLUSIONS: FAERS analysis revealed overlapping safety signals in MMAE-conjugated ADCs. Although further research is necessary to clarify the causal relationships, our findings provide a basis for understanding the characteristics of possible AEs in MMAE-ADCs, aiding clinical decision-making for patient safety management.
Enhancing therapeutic strategies and drug development for patients with kidney disease.
Tsang YP, Aryeh KS, Wang K … +3 more , Himmelfarb J, Yeung CK, Kelly EJ
Expert Opin Drug Saf · 2026 Jan · PMID 40568828 · Full text
INTRODUCTION: Kidney diseases, including chronic kidney disease and acute kidney injury, pose major global health challenges due to their high prevalence and impact on morbidity and mortality. Despite medical advances, t...
INTRODUCTION: Kidney diseases, including chronic kidney disease and acute kidney injury, pose major global health challenges due to their high prevalence and impact on morbidity and mortality. Despite medical advances, there remains an urgent need for improved drug development and therapeutic strategies to treat these conditions. AREAS COVERED: This review examines how renal transporters influence drug handling, highlighting the impact of altered transporter function on toxin accumulation, organ injury, and systemic toxicity. We also address pharmacokinetic and pharmacodynamic changes in kidney diseases, recent advances in preclinical models like microphysiological systems, emerging therapies, and biomarkers for early detection and monitoring. EXPERT OPINION: A robust understanding of transporter function and disease-specific pharmacokinetic shifts is crucial for optimizing drug development. While MPS show promise in predicting drug responses and nephrotoxicity by more accurately simulating human kidney physiology, current hurdles include complexity, cost, and scalability. Emerging biomarkers require stringent validation to ensure specificity and reliability in kidney disease. Targeting transporters offers novel therapeutic and drug repurposing opportunities. Moving forward, refining and validating these models and biomarkers, alongside patient-tailored therapies, will improve personalized medicine and management. Attentive integration of these innovations could significantly reduce morbidity and improve outcomes worldwide for patients with kidney disease.
Neural dysfunction, inflammatory disorder, and metabolic interference feature in amantadine-related adverse drug events: a perspective from FAERS and network toxicology.
Yang J, Tian Y, Luo Y … +10 more , Luo HW, Wang YL, Chen B, Jiang X, Liu GY, Wu YQ, Liu Z, Ye RL, Wang C, Guan XL
Expert Opin Drug Saf · 2025 Jun · PMID 40546104 · Publisher ↗
BACKGROUND: Adverse drug events (ADEs) related to amantadine gradually increase as the drug is broadly acknowledged for remission of Parkinson's disease or Parkinsonism. The ADEs vary according to the affected organs and...
BACKGROUND: Adverse drug events (ADEs) related to amantadine gradually increase as the drug is broadly acknowledged for remission of Parkinson's disease or Parkinsonism. The ADEs vary according to the affected organs and the potential mechanisms remain elusive. METHODS: We mined data from the FAERS Database and employed network toxicology to appraise amantadine-related ADEs and dissect the toxicological mechanisms. RESULTS: We found 1,917 ADE reports relevant to amantadine that embodied 1,871 intense-signal ADEs (implicating 134 preferred terms (PTs)). Of those PTs, 69 were undeclared in current amantadine insert. System organ class (SOC) term-based analysis showed that PDGFRB, STAT3, and PRKCD, as well as the enriched pathways such as Neuroactive ligand - receptor interaction and Toll-like receptor signaling pathway were instrumental in amantadine-related Death outcome. Toxicological analysis for the representative undeclared ADEs showed that the toxic targets like STAT3, MAPK1, and CYP3A4 played central roles in amantadine toxicity and adverse events. Molecular docking revealed high-affinity binding of amantadine to MAPK1, MAPK3, HSP90AA1, CYP3A4, and CYP2C19 which were involved in neural function, inflammation, and metabolism. CONCLUSION: The mechanisms underlying amantadine-related ADEs allow new insights into pharmacovigilance for amantadine use.
Pharmacovigilance insights into antibody-drug conjugates: a multi-database analysis of adverse events in leukemia treatment.
Wu H, Fan X, Wu S … +3 more , Sun Y, Yu M, Liu Z
Expert Opin Drug Saf · 2025 Jun · PMID 40522479 · Publisher ↗
BACKGROUND: Gemtuzumab ozogamicin and inotuzumab ozogamicin play a crucial role in leukemia treatment. This study aims to explore multiple databases to identify adverse event (AE) signals that could enhance the safe use...
BACKGROUND: Gemtuzumab ozogamicin and inotuzumab ozogamicin play a crucial role in leukemia treatment. This study aims to explore multiple databases to identify adverse event (AE) signals that could enhance the safe use of these drugs. METHODS DESIGN AND METHODS: The FDA Adverse Event Reporting System (FAERS) database ASCII packages, covering 83 quarters from Q1 2004 to Q3 2024, were imported into SAS software (version 9.4) for data cleaning and analysis. Signal detection methods included the ROR, PRR, BCPNN and MGPS. The Japanese Adverse Drug Event Report database (JADER) and WHO Adverse Drug Event Report database (VigiAccess) were used to validate the results. RESULTS: In FAERS and VigiAccess, the most frequent positive PT signal for gemtuzumab ozogamicin was 'febrile neutropenia.' In FAERS, the most frequent positive PT signal for inotuzumab ozogamicin was 'death.' The top five PTs with the highest signal intensity for both drugs across the three databases consistently included 'fibrin degradation products increased' and 'veno-occlusive liver disease.' CONCLUSION: Mining multiple databases enabled the identification of SOCs and AEs strongly associated with frequent adverse reactions to gemtuzumab ozogamicin and inotuzumab ozogamicin, offering valuable insights for clinical dosing guidance.
Risk of musculoskeletal disorders associated with Bruton's tyrosine kinase inhibitors: a disproportionality analysis of FAERS database and meta-analysis.
Zuber M, Thomas C, Taj S … +5 more , Rashid M, Undela K, Ramanarayanan J, Hernandez-Ilizaliturri FJ, Villa Zapata L
Expert Opin Drug Saf · 2025 Jun · PMID 40518694 · Publisher ↗
BACKGROUND: Randomized controlled trials (RCTs) have reported an increased risk of musculoskeletal disorders with BTK inhibitors (BTKis). We conducted a disproportionality analysis using the FDA Adverse Event Reporting S...
BACKGROUND: Randomized controlled trials (RCTs) have reported an increased risk of musculoskeletal disorders with BTK inhibitors (BTKis). We conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) and a meta-analysis of RCTs to further investigate. RESEARCH DESIGN AND METHODS: A retrospective case/non-case study was performed using FAERS reports through Q2 2024. Disproportionality analysis calculated Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC) to identify signals (PRR ≥2, lower bound ROR > 1, IC > 0). A meta-analysis calculated risk ratios (RR) for musculoskeletal outcomes. RESULTS: In FAERS, ibrutinib was associated with increased reports of muscle spasms [PRR: 2.2 (χ : 521.9), LB ROR: 2.1, IC = 1.0]. Acalabrutinib showed higher risks for myalgia [PRR: 2.4, LB ROR: 2.0, IC = 0.9] and bone pain [PRR: 2.2, LB ROR: 1.6, IC = 0.6]. In the meta-analysis, ibrutinib was associated with higher risks of arthralgia (RR: 1.46, 95% CI 1.21-1.76), muscle spasm (RR: 2.32, 95% CI 1.72-3.12), and back pain (RR: 1.22, 95% CI 0.75-1.96). CONCLUSIONS: Findings from FAERS and meta-analysis suggest a stronger association between BTKis, particularly ibrutinib, and musculoskeletal adverse events.
Safety and effectiveness of empagliflozin in Japanese patients with heart failure: a 1-year post-marketing surveillance study stratified by age.
Yamamoto K, Naito Y, Watanabe S
Expert Opin Drug Saf · 2025 Jun · PMID 40512403 · Publisher ↗
BACKGROUND: The sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin is approved in Japan for the treatment of heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and HF with preserved le...
BACKGROUND: The sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin is approved in Japan for the treatment of heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and HF with preserved left ventricular ejection fraction (HFpEF). We conducted a post-marketing surveillance study of empagliflozin for HF in Japan. RESEARCH DESIGN & METHODS: This was a 1-year prospective, multicenter, observational study of patients with chronic HF who had not previously received empagliflozin. The primary endpoint was incidence of adverse drug reactions (ADRs). Prespecified effectiveness endpoints were all-cause death, cardiovascular (CV) death, and hospitalization for HF (HHF). RESULTS: 1,166 patients were included (61.0% male, mean age 74.9 years). At baseline, mean left ventricular ejection fraction was 49.0%, mean body mass index was 24.2 ± 4.6 kg/m, and 34.2% had type 2 diabetes. ADRs occurred in 61 (5.2%) patients overall, 5.8% of those aged ≥ 75 years, 6.2% of those aged 65 to < 75 years, and 2.2% of those aged < 65 years. Incidences of all-cause death, CV death, and HHF were 3.0, 0.9, and 2.5 per 100 PY, respectively. CONCLUSIONS: In this 1-year post-marketing surveillance study, empagliflozin was generally well-tolerated in patients with HF in Japan. TRIAL REGISTRATION: ClinicalTrials.gov identifier is NCT05262764.
Comprehensive post-marketing safety analysis of tildrakizumab: insights from the FDA adverse event reporting system.
Zhao K, Xiao S, Zhao Y … +1 more , Tu C
Expert Opin Drug Saf · 2025 Jun · PMID 40512376 · Publisher ↗
BACKGROUND: Tildrakizumab is a biologic agent approved for the treatment of moderate to severe psoriasis. Although its safety has been established in clinical trials, its real-world safety profile remains to be further i...
BACKGROUND: Tildrakizumab is a biologic agent approved for the treatment of moderate to severe psoriasis. Although its safety has been established in clinical trials, its real-world safety profile remains to be further investigated. RESEARCH DESIGN AND METHODS: This study analyzed adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) database between the first quarter of 2018 and the first quarter of 2024. Four disproportionality analysis methods were applied: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Subgroup analyses, sensitivity analyses, and Weibull distribution modeling were conducted. RESULTS: A total of 1,263 reports involving 2,344 AEs were included. Several known AEs were confirmed, and unexpected AEs such as urinary tract infections, herpes zoster, atrial fibrillation, and basal cell carcinoma were identified. Sensitivity analysis further confirmed the reliability of the overall findings. CONCLUSIONS: This study confirmed some known AEs and identified several unexpected AEs, highlighting the importance of early-stage monitoring. These findings may provide preliminary insights into the safe use of tildrakizumab. However, the FAERS database has limitations, including reporting bias, incomplete clinical information, and the inability to establish causality. These findings warrant further validation through prospective studies.
Constipation-predominant irritable bowel syndrome treatment options Linaclotide, Lubiprostone, Plecanatide, and Tenapanor: analysis of the FDA Adverse Event Reporting System (FAERS) database.
Andrews MB, Adler DG
Expert Opin Drug Saf · 2025 Jun · PMID 40503810 · Publisher ↗
BACKGROUND: FDA approved treatments for constipation-predominant irritable bowel syndrome (IBS-C) include secretagogues (Linaclotide, Lubiprostone, and Plecanatide) and a retainagogue (Tenapanor). The FDA Adverse Event R...
BACKGROUND: FDA approved treatments for constipation-predominant irritable bowel syndrome (IBS-C) include secretagogues (Linaclotide, Lubiprostone, and Plecanatide) and a retainagogue (Tenapanor). The FDA Adverse Event Reporting System (FAERS) database collects suspected medication-related adverse events (AEs). RESEARCH DESIGN AND METHODS: Reports in FAERS from the date of each medication's FDA approval until 30 June 2024 were analyzed. Reports containing other suspected medications or a reason for use outside of IBS and/or constipation were excluded. RESULTS: Linaclotide was most associated with diarrhea ( = 2,082, 24.1%), abdominal pain ( = 815, 9.4%), abdominal bloating ( = 795, 9.2%), and nausea/vomiting ( = 266, 3.1%). Plecanatide was most associated with diarrhea ( = 137, 20.4%), abdominal pain ( = 76, 11.3%), abdominal bloating ( = 62, 9.2%), and nausea/vomiting ( = 34, 5.1%). Tenapanor was most associated with diarrhea ( = 51, 32.9%), abdominal pain ( = 13, 8.4%), and abdominal bloating and nausea/vomiting ( = 11 each, 7.1%). Lubiprostone was most associated with dyspnea ( = 221, 13.0%), nausea/vomiting ( = 161, 9.5%), chest pain ( = 157, 9.3%), abdominal pain ( = 85, 5.0%), and diarrhea ( = 79, 4.7%). CONCLUSIONS: This post-marketing analysis of the FAERS database revealed diarrhea, abdominal pain, bloating, and nausea/vomiting were the most frequently reported AEs across all medications. Novel findings include the potential for clinically significant dehydration from Linaclotide-induced diarrhea and Lubiprostone-associated dyspnea and chest pain.
Analysis of the relationship between histamine H1 receptor antagonists and broad dementia events using the FAERS, JADER, and CVAR databases.
Kan J, Chen Y, Gu Q … +5 more , Hu N, Qiao Y, Chen Y, Chen D, Zhang H
Expert Opin Drug Saf · 2025 Jun · PMID 40501012 · Publisher ↗
BACKGROUND: Recent studies suggest histamine H1 receptor antagonists (H1RAs) may elevate broad dementia events risk, though real-world data remain scarce. METHODS: This pharmacovigilance study analyzed FDA Adverse Event...
BACKGROUND: Recent studies suggest histamine H1 receptor antagonists (H1RAs) may elevate broad dementia events risk, though real-world data remain scarce. METHODS: This pharmacovigilance study analyzed FDA Adverse Event Reporting System (FAERS), Japanese Adverse Drug Event Report (JADER), and Canada Vigilance Adverse Reaction (CVAR) databases from January 2004 to June 2024. Using disproportionality analyses such as the reporting odds ratio (ROR) and proportion reporting ratio (PRR), time-to-onset analysis, propensity score matching, and multivariate regression, we compared broad dementia event signals among first-generation H1RAs (FG-H1RAs), second-generation H1RAs (SG-H1RAs), and benzodiazepines (BDs). RESULTS: According to the FAERS database, FG-H1RAs (ROR = 3.33, 95%CI 3.22-3.44; PRR = 3.11, χ2 = 5426.01), SG-H1RAs (ROR = 2.03, 95%CI 1.98-2.07; PRR = 1.97, χ2 = 3706.58), and BDs (ROR = 2.74, 95%CI 2.68-2.80; PRR = 2.6, χ2 = 8338.34) were significantly associated with broad dementia events, with FG-H1RAs having a stronger association with broad dementia events compared to SG-H1RAs (aROR = 0.60, 95%CI 0.54-0.67, < 0.001). Analysis of the JADER and CVAR databases yielded similar results. FG-H1RAs exhibited immediate broad dementia events reporting (median = 0 days), while SG-H1RAs showed delayed onset (median = 1 day), both with early risk decay. CONCLUSION: This study provides evidence for the association between H1RAs treatment and broad dementia events, highlighting signaling differences among H1RAs. However, large-scale, high-quality epidemiological studies are still needed for validation.
Clozapine-treated patients and myocardial infarction in adults: a pharmacovigilance study in VigiBase interpreted in the context of the literature.
De Las Cuevas C, Sanz EJ, de Leon J
Expert Opin Drug Saf · 2025 Jun · PMID 40481717 · Publisher ↗
BACKGROUND: Clozapine is the best treatment for treatment-resistant schizophrenia (TRS) but is associated with metabolic adverse drug reactions (ADRs). RESEARCH DOSING/METHODS: The international pharmacovigilance databas...
BACKGROUND: Clozapine is the best treatment for treatment-resistant schizophrenia (TRS) but is associated with metabolic adverse drug reactions (ADRs). RESEARCH DOSING/METHODS: The international pharmacovigilance database (VigiBase) uses the information component (IC) as a disproportionality analysis. On 1 July 2024, we studied in VigiBase: 1) the myocardial infarction (MI) ICs for antipsychotics and 2) clozapine reports for MI since clozapine's introduction. After excluding 298 patients with incomplete data, 1490 adults were studied for fatal outcomes using logistic regression with adjusted odds ratios (aOR) and survival analysis. RESULTS: Clozapine was associated with the highest IC (IC = 0.903; IC = 0.835). Olanzapine (IC = 0.524; IC = 0.398) showed a lower but significant association. The ICs for quetiapine, risperidone and haloperidol were non-significant or negative. Mortality in 1490 adult clozapine-treated patients with MI was 68%. Using a baseline age 18-44 years, age 45-64 years had a significant ( < 0.001) aOR = 1.87 with CI 1.43-2.44, while age ≥65 years had a significant ( < 0.001) aOR = 4.07 with CI 2.77-5.97. High clozapine doses (>600 mg/day) displayed an aOR = 2.18 for fatal outcomes. CONCLUSION: A MI IC around 0.9 is higher than that of other antipsychotics, but we cannot rule out that it is explained by TRS present in clozapine-treated patients.
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