Risk of drug-induced angioedema: a pharmacovigilance study of FDA adverse event reporting system database.

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.

Comparative safety profiles of bispecific T-cell engagers and CAR-T therapies: Real-world insights from the FDA adverse event reporting system database

ABSTRACTBackgroundMelanosis is an acquired hyperpigmentation disorder that can be associated with the use of medications; timely identification and discontinuation of relevant medications is an important aspect of clinical management.ObjectiveThis study investigates the relationship between melanosis and drug exposure based on data from the FDA Adverse Event Reporting System (FAERS) database. We sought to determine the top drugs reported in association with melanosis in the FAERS.MethodsA retrospective analysis of FAERS data from January 2004 to June 2024 was conducted to identify reports related to melanosis, using the Comprehensive Medical Dictionary for Regulatory Activities (MedDRA) terminology. A total of 18 182 912 independent adverse event reports were processed, and signal mining analyses were performed to detect associations between drugs and melanosis. Disproportionality analyses were conducted using four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi‐item gamma Poisson shrinker (MGPS). The most frequently reported drugs and their associated adverse event reports were analyzed.ResultsHundred and one reports related to melanosis were screened, involving 73 drug names as primary suspect (PS). By combining and organizing the different names of drugs such as trade names and generic names, 66 drugs were obtained. The top five drugs associated with melanosis were talimogene laherparepvec (ROR: 1891.39), followed by ferrous sulfate (ROR: 997.14), minocycline (ROR: 176.05), vemurafenib (ROR: 97.64), and pembrolizumab (ROR: 19.73).ConclusionPatients who experience drug‐induced melanosis generally have bad outcomes, underscoring the imperative for heightened clinical surveillance regarding the risk of drug‐induced melanosis.

Central nervous system adverse events (AEs) occur when oxycodone is used in combination with benzodiazepines, antidepressants and anticonvulsants. There have been no reports of central nervous system AEs with oxycodone alone or in combination with oxycodone. Based on USA Food and Drug Administration Adverse Event Reporting System (FAERS) data, this study aims to explore the risk signals of central nervous system AEs with oxycodone alone or in combination with benzodiazepines, antidepressants and anticonvulsants, and to provide a reference for the safe and rational use of this drug. Extracted AEs data from the FAERS for oxycodone alone and in combination with benzodiazepines, antidepressants, and anticonvulsants from Q1 2004 to Q2 2021. The risk signal mining analysis of AEs was performed using the proportional imbalance method and Bayesian method. Number of reports ≥3 and lower 95% CI limit of reporting odds ratio (ROR)>1; number of reports ≥3, proportional reporting ratio (PRR)≥2 and χ2≥4; lower information components (IC) lower 95% CI limit (IC025)>0; empirical Bayes geometric mean (EBGM) lower 95% CI limit (EBGM05)>2, and N>0 were defined as positive signals. A total of 5 793 reports of central nervous system AEs with oxycodone alone were tapped, and 366, 622, and 740 reports of combined benzodiazepines, antidepressants, and anticonvulsants, respectively. Consumers and physicians were the main reporting population. The age distribution of oxycodone alone was mainly from 61 to 80 years old. The age distribution of oxycodone in combination with related drugs was mainly from 46 to 60 years old. The risk of AEs was greater in women than in men, and the United States was the predominant reporting country. Oxycodone alone was strongly associated with myoclonus [ROR=2.92, 95% CI 2.28 to 3.76); PRR=2.92, χ2(77.49); IC=1.52, IC025(0.65); EBGM=2.89, EBGM05(2.33)], delirium [ROR=4.69, 95% CI 4.24 to 5.21; PRR=4.66, χ2(1 052.64); IC=2.17, IC025(1.81); EBGM=4.50, EBGM05 (4.13)], mental disorder [ROR=2.95, 95% CI 2.53 to 3.44; PRR=2.94, χ2(206.93); IC=1.56, IC025(0.96); EBGM=2.95, EBGM05(2.58)], and acute central respiratory depression [ROR=2.87, 95% CI 2.68 to 3.08); PRR=2.82, χ2(971.62); IC=1.52, IC025(1.33), EBGM=2.87, EBGM05 (2.76)]. Combination of benzodiazepines was most strongly associated with mental disorder [ROR=10.08, 95% CI 9.38 to 10.78; PRR=9.90, χ2(64.06); IC=3.33, IC025 (1.65); EBGM=10.08, EBGM05(5.61)], and tremor [ROR=3.09, 95% CI 2.76 to 3.42); PRR=3.08, χ2(48.93); IC=1.63, IC025 (1.17); EBGM=3.09, EBGM05(2.34)]. Combination of antidepressants was most strongly associated with delirium [ROR=13.23, 95% CI 12.23 to 14.23; PRR=12.87, χ2(43.86); IC=3.69, IC025(1.36); EBGM=12.23, EBGM05 (5.32)] and somnolence [ROR=6.74, 95% CI 6.15 to 7.33); PRR=6.73, χ2(53.42); IC=2.75, IC025(1.52); EBGM=6.73, EBGM05(4.10)]. Combination of anticonvulsants was most strongly associated with myoclonus [ROR=17.89, 95% CI 17.46 to 18.32; PRR=17.72, χ2(971.39); IC=4.16, IC025(2.70); EBGM=17.89, EBGM05(12.46)] and delirium [ROR=4.86, 95% CI 4.45 to 5.27); PRR=4.82, χ2(69.49); IC=2.28, IC025 (1.51); EBGM=4.86, EBGM05(3.44)]. Based on pharmacovigilance studies of the FAERS database, clinical medication monitoring of oxycodone alone and in combination with benzodiazepines, antidepressants, and anticonvulsants should be strengthened to be alert to the occurrence of central nervous system-related AEs.

To characterize the real-world safety profile of 23 monoclonal antibodies (mAbs) carrying US Food and Drug Administration (FDA) black box warnings (BBWs) by applying disproportionality analysis to safety reports in the FDA Adverse Event Reporting System (FAERS) from Q1 2021 to Q2 2025. Although mAbs have transformed the treatment of cancer, autoimmune, and rare diseases, several remain associated with serious or life-threatening adverse events (AEs) that warrant continuous postmarketing monitoring. FAERS reports involving the 23 mAbs were screened for BBW-related AEs using MedDRA Preferred Terms. Each drug-event pair was analyzed through 2×2 contingency tables. Disproportionality signals were identified using the proportional reporting ratio (PRR), reporting odds ratio (ROR), chi-square (χ²), and 95% confidence interval (CI) for ROR. Bayesian analysis was also performed using the Bayesian Confidence Propagation Neural Network (BCPNN) approach to calculate the Information Component (IC) and its lower bound (IC₀₂₅). A signal was considered present when the PRR was ≥2, χ² value was ≥4, and at least 3 individual case safety reports (ICSRs) were available for a given drug-event pair. ROR signals were considered statistically significant when the lower bound of the 95% CI exceeded 1. In addition, BCPNN analysis was performed, and signals were considered significant when the lower limit of the 95% CI of the IC 025 was greater than 0. Temporal patterns in adverse event reporting were examined by summarizing FAERS reports and corresponding disproportionality metrics for each drug-event pair on a quarterly basis from Q1 2021 to Q2 2025. Changes across quarters were evaluated by directly comparing the number of reported cases and calculated signal measures between time periods. The study looked at patterns over time using simple comparisons, without using formal statistical techniques such as time-series analysis or regression modeling to test significance or predict trends. Out of 13,462,218 total FAERS reports, 330,851 involved the 23 mAbs. The strongest signal was ipilimumab-immune-mediated dermatitis (PRR 232.12; ROR 250.41; IC₀₂₅ 4.21; χ² 4003.3). Panitumumab showed the highest Bayesian certainty for skin toxicity (IC₀₂₅ 4.61), and ipilimumab-immune-mediated enterocolitis had the highest χ² value (13,320.3). Reporting trends for most mAbs remained consistent over time, though immune checkpoint inhibitors demonstrated a gradual increase in signal intensity across quarters. BBW-related adverse events for mAbs remain prominent in postmarketing data. Immune-related toxicities, especially with checkpoint inhibitors, show rising trends. However, as disproportionality analyses are based from reporting patterns of adverse events within the FAERS database rather than true incidence rates, the identified signals should be considered exploratory and warrant confirmation through well-designed pharmacoepidemiological studies. These findings reinforce the need for continued pharmacovigilance to support risk-benefit evaluation and patient safety.

Real-world drug safety study of somatostatin analogs based on the food and drug administration adverse event reporting system database.

Background The comprehensive quantitative and comparative risk data of drug-induced erectile dysfunction (ED) are still lacking, and this study aims to supplement this information. Research design and methods We reviewed all the ED reports in the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023 and summarized a potential ED culprit-drug list and its corresponding reporting frequency. The reporting odds ratio (ROR) method was used to conduct disproportionality analysis. Results A total of 20,098 ED reports were retrieved from the FAERS database, which recorded 734 different ED culprit-drugs, involving 74 drug classes. Finasteride was the drug with the highest reporting frequency, and urologicals was the drug class with the highest reporting frequency. In disproportionality analysis, 209 drugs with positive signals showed a close relationship with ED occurrence, among which finasteride was the drug with the highest signal strength. Among 209 drugs with positive signals, 27 were compound preparations, and the risk level of compound preparations was usually higher than their single active ingredient. Conclusions Our study integrated quantitative and comparative ED risk data of 734 drugs by using the FAERS database, which can provide reference information for regulators, medical personnel, and others involved in drug management and use.

BackgroundThe profiles of cardiovascular toxicity associated with angiogenesis inhibitors, including intravenous monoclonal antibodies (mAbs) and oral tyrosine kinase inhibitors (TKIs), targeting vascular endothelial growth factor (VEGF) remain poorly elucidated in real-world settings. This pharmacovigilance analysis aimed to comprehensively investigate the frequency, spectrum, timing, and outcomes of cardiovascular toxicities associated with angiogenesis inhibitors and to explore the differences in such patterns between mAbs and TKIs.MethodsDisproportionality analysis was performed by leveraging reports from the FDA Adverse Event Reporting System (FAERS) database from 2014 to 2021. Cardiovascular adverse events (AEs) were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs). Reporting odds ratio (ROR) and information components (ICs) were calculated with statistical shrinkage transformation formulas and a lower limit of 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0, with at least three reports being considered statistically significant.ResultsA total of 757,577 reports of angiogenesis inhibitors and 70,668 (9.3%) reports of cardiovascular AEs were extracted. Significant disproportionality was detected in angiogenesis inhibitors for cardiovascular AEs (IC025/ROR025 = 0.35/1.27). Bevacizumab (31.8%), a mAb, presented the largest number of reports, followed by sunitinib (12.4%), a TKI. Hypertension (SMQ) was detected with the strongest signal value (IC025/ROR025 = 1.73/3.33), followed by embolic and thrombotic events (SMQ) (IC025/ROR025 = 0.32/1.26). Hypertension showed the shortest time to onset with a median (interquartile range) value of 23 (8, 69) days, while embolic and thrombotic events had the longest value of 51 (16, 153) days. Notably, hypertension presented the lowest proportions of death and life-threatening events (10.9%), whereas embolic and thrombotic events posed the highest (29.3%). Furthermore, both mAbs (IC025/ROR025 = 0.47/1.39) and TKIs (IC025/ROR025 = 0.30/1.23) showed increased cardiovascular AEs. Hypertension was detected in both agents (IC025/ROR025 = 1.53/2.90 for mAbs and IC025/ROR025 = 1.83/3.56 for TKIs) with a shorter time to onset of 17 (6, 48) days for TKIs than mAbs of 42 (14, 131) days. By contrast, embolic and thrombotic events were detected for mAbs (IC025/ROR025 = 0.90/1.87) without TKI (IC025/ROR025 = −0.08/0.95).ConclusionAngiogenesis inhibitors were associated with increased cardiovascular toxicity with a discrepancy between intravenous mAbs and oral TKIs, deserving distinct monitoring and appropriate management.

Drug-induced liver injury associated with antiseizure medications from the FDA Adverse Event Reporting System (FAERS)

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11–6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18–2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92–3.68; IC = 1.53, 95%CrI = 1.35–1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.

Background This study aims to systematically evaluate adverse events (AEs) associated with hydrocortisone through the FDA Adverse Event Reporting System (FAERS) database. Research designs AE reports associated with hydrocortisone from Q1 2014 to Q4 2023 were extracted from the FAERS database. Multiple disproportionality analysis techniques, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM), were employed for signal detection. In addition, we also analyzed the time to onset of AEs. Results Analysis of 7,532 hydrocortisone-associated AEs from the FAERS database revealed significant signals across multiple system organ claasses. The strongest associations were found in endocrine disorders (ROR: 13.39), ear and labyrinth disorders (ROR: 3.05), and immune system disorders (ROR: 2.17). Additionally, the study uncovered unexpected AEs such as splenic peliosis and lymphoid tissue hypoplasia. 63.9% of the AEs occurred within 7 days of treatment. Conclusions Based on disproportionality analysis of FAERS data, this study provides new insights into the safety of hydrocortisone in the real-world setting. Future prospective studies should be conducted to validate the findings of this investigation.

Introduction: Drug-induced intestinal necrosis is a severe and potentially life-threatening condition characterized by the death of the intestinal tissue. Typical symptoms include abdominal pain, vomiting, diarrhea, and fever. This can rapidly progress to severe complications such as septic shock and peritonitis. Early recognition and prompt discontinuation of the offending drug are crucial to mitigate the risk of severe complications and improve patient outcomes. This is a real-world pharmacovigilance study evaluating the association between various drugs and intestinal necrosis. Methods: The Food and Drug Administration (FDA) maintains the Adverse Event Reporting System (FAERS) database. As of December 31, 2024, the database contained 30,179,725 reported events. This database was queried to identify all reported cases of ‘Gastrointestinal necrosis’, ‘Gastrointestinal mucosal necrosis’, ‘intestinal gangrene’, and ‘gastrointestinal gangrene’. All medications implicated were identified by their generic names. The database does not report how the diagnosis of necrosis was confirmed, nor whether other causes were ruled out. A disproportionality analysis was conducted, wherein Reporting Odds Ratios (ROR) were calculated. An ROR >1 is considered a significant signal. Results: A total of 3752 cases were reported to the FAERS from 1970-2024. 3701 were characterized as severe, including 1589 deaths (42.35%). The most common reported drugs were – Docetaxel (3.86%; ROR: 13.9 [11.77, 16.41]; P < 0.05), Adalimumab (3.46%; ROR: 1.45 [1.22, 1.73]; P < 0.05), Fluorouracil (3.38%; ROR: 13.89 [11.64, 16.58]; P < 0.05), Clozapine (3.22%; ROR: 6.99 [5.83, 8.38]; P < 0.05), Cyclophosphamide (3.14%; ROR: 6.94 [5.83, 8.26]; P < 0.05), Methotrexate (3.11%; ROR: 5.00 [4.16, 6.01]; P < 0.05), Paclitaxel (3.04%; ROR: 9.09 [7.54, 10.95]; P < 0.05), Bevacizumab (2.77%; ROR: 7.95 [6.54, 9.66]; P < 0.05), Cytarabine (2.77%; ROR: 15.43 [12.70, 18.76]; P < 0.05), and Cisplatin (2.48%; ROR: 10.84 [8.82, 13.32]; P < 0.05). Conclusion: Docetaxel was the most reported cause of drug-induced intestinal necrosis (3.6% of all reports), while Cytarabine had the highest ROR (15.43) amongst the most frequently reported drugs. A high degree of suspicion should be employed when patients present with warning symptoms after a recent change in medications. Such patients should discontinue these medications when possible, and immediate supportive care should be instituted.

Capmatinib was approved by the US Food and Drug Administration (FDA) in 2020 for the treatment of non-small cell lung cancer with MET exon 14 mutation (METex14). Real-world studies on the safety of Capmatinib are still lacking. The aim of this study was to explore the significant adverse drug reactions (ADRs) associated with Capmatinib through the FDA Adverse Event Reporting System (FAERS) database. We employed the reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and the Empirical Bayes Geometric Mean (EBGM) as primary algorithms for the disproportionality analysis. Adverse events (AEs) were classified as adverse drug reactions (ADRs) solely upon fulfillment of criteria across all four algorithms. In our study, there were 1767 cases explicitly attributed to Capmatinib. A total of 38 ADRs in preferred terms (PTs) level in 14 system-organ categories (SOCs) were identified after filtering. Notably, unexpected SOC "Ear and labyrinth disorders" and PTs "hypoacusis" and "deafness" were identified, without being specified in the drug label. Our study identified unexpected ADRs associated with Capmatinib, with a focus on ototoxicity-related events, underscoring the need for enhanced clinical monitoring and further investigation into the underlying mechanisms.

Lutetium-177(177Lu)–PSMA-617 has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Our main objective is to elucidate the association between 177Lu-PSMA-617 and reported adverse events (AEs) in the FDA Adverse Event Reporting System (FAERS) database. Relevant information regarding 177Lu-PSMA-617 usage and reports of AEs was extracted from the FAERS database. The Empirical Bayes Geometric Mean (EBGM), Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN) with their 95% confidence intervals (CI) were calculated using four algorithms of disproportionality analysis. The pharmacovigilance signals deemed significant across the four algorithms were considered associated with drug use. We collected 6266 unique reports related to 177Lu-PSMA-617 usage from the FAERS database. Compared to other drugs, 177Lu-PSMA-617 usage was associated with a higher risk of anemia, platelet count decreased, and pancytopenia. In addition to hematologic AEs, consistent high signals were observed for AEs such as dry mouth, laboratory test abnormal, and general physical health deterioration. The analysis based on mCRPC treatment drugs showed that full blood count decreased, general physical health deterioration, and laboratory test abnormal continued to exhibit significant signals. Furthermore, the number of AEs reports for 177Lu-PSMA-617 decreased over time, with most reports occurring within one month after drug administration. Our study compiled AEs associated with 177Lu-PSMA-617 in real-world drug usage and highlighted its propensity for specific AEs in the context of mCRPC treatment. These findings will contribute to enhancing our clinical experience with this medication.

Purpose Emerging evidence suggests rosacea as a recognizable adverse event during dupilumab therapy. This study aimed to investigate the potential association between dupilumab and rosacea using pharmacovigilance data and to characterize the clinical features of dupilumab-associated rosacea (DAR) through a review of reported cases. Materials and methods We utilized the FDA Adverse Event Reporting System (FAERS) database (2017–2024) to identify disproportionality signals using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayesian Geometric Mean (EBGM). To contextualize these findings, we performed a focused narrative review of 8 publications comprising 10 DAR cases with extractable individual data. Results A significant disproportionality signal was identified across all four methods (ROR 3.873; PRR 3.872; IC 1.865 with IC025 1.653; EBGM 3.642), with reports predominantly in adults and females. In the case review, a consistent phenotype emerged: papulopustules on persistent centrofacial erythema with frequent burning; facial predominance with occasional extension to neck, scalp, or upper trunk; frequent Demodex detection by scraping, KOH, or in vivo imaging; and occasional granulomatous histology. Onset ranged from approximately 2 weeks to 21 months, including one post-discontinuation case. Most patients improved with rosacea-directed therapy (topical ivermectin or metronidazole; anti-inflammatory-dose doxycycline). However, dechallenge or rechallenge patterns and the need for dose-interval extension, temporary interruption, or switching biologic (e.g., lebrikizumab, upadacitinib) in a subset support a drug-related pattern at the reporting level. Conclusions DAR represents a distinct clinical entity from dupilumab-associated head and neck dermatitis, which is eczematous and typically responds to antifungals or calcineurin inhibitors. While disproportionality signals indicate association rather than incidence or causality and are subject to reporting bias, clinicians should be aware of this potential adverse event to ensure appropriate management.