Adverse Event Reporting System Research Articles

Adverse Events Associated with Antivirals for COVID-19: An Analysis Based on FDA Adverse Event Reporting System (FAERS).

The COVID-19 pandemic has called for the rapid development and use of antiviral drugs to effectively control the disease. Nirmatrelvir/Ritonavir (Paxlovid), Molnupiravir, and Remdesivir have been pivotal in therapeutic approaches, although they raise concerns regarding adverse drug reactions (ADRs). This study aimed to thoroughly assess the ADRs associated with these drugs by utilizing the Adverse Event Reporting System (FAERS) database of the Food and Drug Administration (FDA). ADR reports for Paxlovid, Molnupiravir, and Remdesivir throughout the period of January 2022 to May 2023 were extracted and classified according to the severity, type of reaction, and demographic variables. Reporting Odds Ratios (RORs) with 95% confidence intervals were calculated to evaluate the relationship between antiviral medications and various ADRs. The study established notable correlations between Paxlovid and the recurrence of the disease (40.08%) and dysgeusia (16.29%). Molnupiravir was linked to gastrointestinal (16.73%) and skin reactions (9.47%), while Remdesivir had impairments in the liver (25.21%) and kidneys (13.34%). ADRs were more commonly observed in female patients treated with Paxlovid (57.95%) and Molnupiravir (49.40%), whereas Remdesivir ADRs were mostly reported in males (58.56%). Paxlovid and Remdesivir ADRs were frequently reported in adults between the ages of 18 and 64 (46.01% and 45.01%), while Molnupiravir ADRs were more common in older individuals aged 65 to 85 (40.38%). This thorough assessment emphasizes the importance of careful surveillance and control of ADRs linked to COVID-19 antiviral therapies. It is essential to customize treatments by considering specific patient histories, particularly for pre-existing diseases.

Drug-induced Parkinson-like events: a real-world study from 2004 to the first quarter of 2024 based on FAERS.

Timely identification of drug-induced Parkinson-like events is essential to improve clinical management and enhance patients' quality of life. However, there is a significant lack of studies addressing these events in real-world settings. To bridge this gap, we analyzed adverse event (AE) reports related to Parkinson-like events from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the first quarter of 2024. Our objective was to summarize a list of potential drugs at high risk for Parkinson-like events and their corresponding proportions of AE reports. As a result, a total of 54,639 AE reports linked to Parkinson-like events involving 1,224 drugs were identified. Among these, carbidopa/levodopa exhibited the highest number of reports, followed by baclofen and pimavanserin. The most frequently reported drug class was antiparkinsonian drugs and psycholeptics, followed by psychoanaleptics. Using two disproportionate analysis methods, the reporting odds ratio and proportional reporting ratio, we found that 136 drugs exhibited positive results in both methods, while 1,063 drugs did not show any positive signals. This study provides a comprehensive pharmacovigilance analysis of drugs associated with Parkinson-like events, aiming to promote rational drug use and inform clinical practice.

A Real-World Pharmacovigilance Study of FDA Adverse Event Reporting System Events for Obeticholic Acid.

Based on the Adverse Event Reporting System (FAERS) data from the US FDA, this study mined the adverse drug reactions of obeticholic acid (OCA) in the real world and provided reference for clinical safe drug use. Adverse event reports for OCA from the second quarter of 2016 to the third quarter of 2023 were extracted. The analysis for adverse reaction signal detection was conducted using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. A total of 5661 OCA-related adverse event reports were collected, and 105 OCA-related adverse reaction signals were obtained, involving 14 systems, among which 46 new signals were not previously mentioned in the product labeling. Severe adverse event of OCA accounted for a relatively high proportion (1445 cases, 25.53%), among which the number of hospitalization reports was the largest (1042 cases, 18.41%). The top five adverse events were pruritus, fatigue, constipation, elevated blood alkaline phosphatase, and abdominal distention. The top five adverse reaction signals intensity were abnormal blood alkaline phosphatase, abnormal ratio of albumin globulin, spider nevus, combined with abnormal bilirubin, and γ-abnormal glutamyl transferase. Based on the pharmacovigilance study of the FAERS database, it is necessary to strengthen the clinical medication monitoring of OCA, so as to provide reference for effective pharmaceutical monitoring and rational clinical medication.

Analysis of Predictors of Adverse Events and Mortality Risk Associated With IL‐6 Inhibitors: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database

Aim: This study aimed to investigate post‐marketing adverse events (AEs) of interleukin‐6 (IL‐6) inhibitors, and to explore risk factors for death.Method: Disproportionality analyses were conducted on adverse event cases of IL‐6 inhibitors reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the time of drug launch until the fourth quarter of 2023. Univariate and multivariate logistic regression analyses were carried out utilizing patient‐related clinical information, and prediction models for IL‐6 inhibitor‐related mortality risk were developed by incorporating patient age and weight factors.Results: A total of 63,445 reports were retrieved, with the majority of known age groups falling between 18 and 64 years. Most reports were submitted by consumers and physicians, predominantly from the United States. Tocilizumab was associated with AEs such as drug intolerance and infection, while sarilumab showed symptoms of pain and condition aggravated. Siltuximab was linked to disease progression and thrombocytopenia. The median time to AEs with IL‐6 inhibitors was 74 days (interquartile range [IQR] 10‐311), mostly occurring within 1 month. Factors such as age, propionic acid derivative, infections and infestations, nervous system disorders, and immune system disorders were independent risk factors for deaths related to IL‐6 inhibitor use (p < 0.05). The mortality risk prediction model demonstrated good discriminatory power and clinical applicability in both the training set (AUC 0.6968) and the validation set (AUC 0.7502).Conclusion: Our postmarketing pharmacovigilance analysis revealed the types and incidence of AEs related to IL‐6 inhibitors. Column line diagrams may be useful for clinical assessment of the occurrence of death and have high clinical utility.

Hepatic adverse events associated with ketamine and esketamine: A population-based disproportionality analysis.

To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine. We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders. Formulations of ketamine and esketamine were evaluated for the proportionality of reporting for each hepatobiliary disorder parameter using the reporting odds ratio (ROR). We also estimated the lower limits of 95 % confidence intervals of information components (IC025) to determine whether the association was significant. Acetaminophen was used as the positive reference agent and lithium as the neutral reference agent. We observed disproportionately lower reporting of hepatitis, liver disorder, liver injury, drug-induced liver injury, hepatic failure, and acute hepatic failure for ketamine compared to acetaminophen. Additionally, we observed disproportionately higher reporting of hepatic function abnormalities and hepatic cytolysis for ketamine compared to acetaminophen. For esketamine, we did not find disproportionate reporting of any hepatobiliary toxicity relative to acetaminophen. However, for ketamine, there was disproportionate lower reporting of hepatic function abnormalities, liver disorder and hepatic cirrhosis. In contrast, for esketamine, there was disproportionately higher reporting of hepatic failure. Although causality has not been established, the data support recommendations for periodic monitoring of liver function tests, as well as clinical surveillance for stigmata of hepatobiliary disease in individuals receiving chronic exposure to ketamine and esketamine.

Neuropsychiatric adverse events associated with Glucagon-like peptide-1 receptor agonists: a pharmacovigilance analysis of the FDA Adverse Event Reporting System database.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used due to their profound efficacy in glycemic control and weight management. Real-world observations have revealed potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs. This study aimed to comprehensively investigate and characterize these neuropsychiatric AEs with GLP-1RAs. We analyzed GLP-1RA adverse reaction reports using the FDA Adverse Event Reporting System database. Disproportionality analysis using reporting odds ratio (ROR) identified eight categories of neuropsychiatric AEs associated with GLP-1RAs. We conducted descriptive and time-to-onset (TTO) analyses and explored neuropsychiatric AE signals among individual GLP-1RAs for weight loss and diabetes mellitus (DM) indications. We identified 25,110 cases of GLP-1RA-related neuropsychiatric AEs. GLP-1RAs showed an association with headache (ROR 1.74, 95% confidence interval [CI] 1.65-1.84), migraine (ROR 1.28, 95%CI 1.06-1.55), and olfactory and sensory nerve abnormalities (ROR 2.44, 95%CI 1.83-3.25; ROR 1.69, 95%CI 1.54-1.85). Semaglutide showed a moderate suicide-related AEs signal in the weight loss population (ROR 2.55, 95%CI 1.97-3.31). The median TTO was 16days (interquartile range: 3-66days). In this study, we identified eight potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs and, for the first time, detected positive signals for migraine, olfactory abnormalities, and sensory abnormalities. We also observed positive suicide-related signals of semaglutide, in weight loss population. This study provides a reliable basis for further investigation of GLP-1RA-related neuropsychiatric AEs. However, as an exploratory study, our findings require confirmation through large-scale prospective studies.

Drug Interaction of SGLT2Is and ARNI on Acute Kidney Injury: A Real-World Pharmacovigilance Analysis Through the FAERS.

Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and angiotensin receptor-neprilysin inhibitor (ARNI) may cause potential renal damage, the combined impact of SGLT2Is and ARNI on acute kidney injury (AKI) remains unclear. This pharmacovigilance study conducted a disproportionality analysis using reports from the FDA Adverse Event Reporting System database. The reporting odds ratio was used as an estimate for detecting AKI signal. A total of 659,573 reports on at least 1 glucose-lowering drug and/or ARNI were obtained. Of the 413 reports on cotherapy of SGLT2Is and ARNI, 99 (24.0%) reports mentioned AKI. Overall, the AKI reporting rate significantly increased in cotherapy (adjusted reporting odds ratio, 95% confidence interval: 8.04, 6.20-10.42, P < 0.001), with a stronger AKI signal in cotherapy of canagliflozin and ARNI (16.82, 3.75-75.57, P < 0.001). Specifically, no increased AKI signal was detected in patients with heart failure (HF) receiving cotherapy after adjustment for sex and age (HF: 1.27, 0.89-1.80, P = 0.189; HF plus diabetes: 2.08, 0.99-4.40, P = 0.055; or HF plus hypertension: 1.69, 0.53-5.35, P = 0.376), whereas enhanced AKI signals were detected in patients with diabetes (20.57, 11.93-35.46, P < 0.001), hypertension (4.30, 1.98-9.37, P < 0.001), or diabetes plus hypertension (5.44, 1.92-15.43, P = 0.001). This study reveals that superimposed renal impairment results from cotherapy with SGLT2Is and ARNI. It is necessary to be vigilant that the elderly patients with diabetes, hypertension, or chronic kidney disease are more susceptible to AKI, especially if they likewise receive diuretics. When cotherapy is unavoidable, early monitoring of renal function, blood volume, and blood pressure is excessively crucial. However, it is relatively safe in patients with HF.

Post-marketing safety surveillance for the recombinant zoster vaccine (Shingrix), vaccine adverse event reporting system, United States, October 2017-April 2024.

Recombinant zoster vaccine (RZV), received its first marketing authorization in October 2017 to prevent herpes zoster and its complications in older adults. The purpose of this study was to provide comprehensively worldwide post-marketing safety information about RZV using data from the Vaccine Adverse Event Reporting System (VAERS). We searched for and analyzed adverse event (AE) reports of RZV submitted to U.S. VAERS between October 20, 2017 and April 26, 2024. Descriptive analyses included sex, age, time-to-onset, seriousness, most commonly reported AEs, AE of special interest, and cause of death. The empirical Bayesian data mining was employed to identify potential disproportionalities in reporting. During the study period, 1,279,596 AE reports for vaccines were received by VAERS after excluding any duplicates, including 66,849 reports specifically related to RZV. Most reports were classified as non-serious (97.3%). Among reports with age or sex reported, individuals were mainly 50-79years (71.2%) and females (63.1%). The most commonly reported AEs included injection site reactions, pyrexia, chills, headache and fatigue. A total of 86 reports documenting deaths were identified following RZV vaccination. In addition to cardiovascular events and falls, Guillain-Barre syndrome was the most common cause of death. The median TTO for RZV-related AEs was 1day in all cohort groups over 50years old. The safety profile of RZV, based on the large sample post-marketing use, was reassuring and consistent with that observed in clinical trials. Further studies are needed to continue generating real-world safety data and further characterize RZV-AE pairs systematically.

Drug-induced dementia: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database.

Dementia is a serious adverse event (AE) that requires attention in clinical practice. However, information on drug-induced dementia is limited. The U.S. FDA Adverse Event Reporting System (FAERS) serves as an important resource for identifying real-world adverse drug reactions and safety signals. This study aimed to use FAERS data to identify drugs associated with increased dementia risk. A secondary analysis of the FAERS database was conducted using disproportionality analysis methods. We reviewed dementia-related reports in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023, used the Medical Dictionary for Regulatory Activity to identify dementia cases and summarized the corresponding list of potential medications, counted the dementia-causing medication classes with the highest frequency of reports, and disaggregated all medications. The study identified 31,881 dementia-related AEs in the FAERS database, with an increasing trend over time, particularly among females and individuals over 65. Apixaban had the most reports (1631). Disproportionality analyses revealed that rivastigmine, nicergoline, aducanumab, amlodipine/atorvastatin, and dihydroergometrine had the highest risk, based on reporting odds ratio, proportional reporting ratio, and information component. Only valproate and tramadol among the top 50 drugs included a potential dementia risk in their package inserts. This study identified a list of medications associated with dementia risk, many of which lack dementia warnings on their labels. Increased monitoring is necessary for high-risk individuals, and further research is required to clarify these associations and improve patient safety.

Cardiovascular and Metabolic Adverse Events of Endocrine Therapies in Women with Breast Cancer: A Disproportionality Analysis of Reports in the FDA Adverse Event Reporting System

ABSTRACTIntroductionEmerging evidence suggests potential cardiovascular toxicities from oral endocrine therapies (ETs); however, results are conflicting. This study comprehensively examined adverse reactions of ETs and investigated cardiovascular and metabolic safety signals within the FDA Adverse Event Reporting System (FAERS).MethodsReports in the FAERS through December 2023 were analyzed for documented reactions to tamoxifen, letrozole, anastrozole, and exemestane in female breast cancer patients. Standardized queries were used to identify cases of cardiovascular (myocardial infarction, heart failure, arrhythmia, stroke) and metabolic (hypertension, dyslipidemia, hyperglycemia) disorders. Descriptive and disproportionality analyses were performed to assess reports and detect safety signals.ResultsAmong 14,327 unique ET‐related reports, arthralgia (n = 1873 events) was the most prevalent reaction. We identified 2170 cardiovascular and 2252 metabolic events associated with ETs. Letrozole had the highest reporting rate of cardiac arrhythmia (7.7%) and showed positive signals for both arrhythmia (reporting odds ratio [ROR] = 2.2; 95% confidence interval [CI]: 1.8–2.5) and myocardial infarction (ROR = 1.9; 95% CI: 1.4–2.6). We also observed a significantly increased risk of heart failure with letrozole (ROR = 1.3; 95% CI: 1.1–1.6) and stroke with tamoxifen (ROR = 1.7; 95% CI: 1.5–2.1). Only anastrozole was significantly associated with metabolic dysfunctions with a notable hyperglycemia reporting rate of 12.2%.ConclusionOur findings provide valuable evidence on common reactions as well as controversial cardiovascular and metabolic abnormalities associated with the real‐world use of ETs for breast cancer. Ongoing benefit–risk assessment and close monitoring of cardiac function during treatment, particularly in high‐risk women, are warranted to optimize cancer outcomes while minimizing cardiovascular injury.

A real-world pharmacovigilance analysis of potential ototoxicity associated with sacubitril/valsartan based on FDA Adverse Event Reporting System (FAERS)

Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, is widely used to treat heart failure. Despite its efficacy, sacubitril/valsartan inevitably causes adverse events such as hypotension, renal dysfunction, hyperkalemia, and angioedema. Sacubitril/valsartan-associated ototoxicity is often underreported in clinical studies and real-world settings. This study aimed to systematically characterize ototoxicity profiles using post-marketing data. Disproportionality analysis was performed using the Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2015 to 2023. The reporting odds ratio (ROR) and information components (IC) were used to detect potential ototoxicity associated with sacubitril/valsartan. Significant signals were defined as ROR025 > 1 and IC025 > 0 in at least three reports. From 272,790 reports on sacubitril/valsartan and 10,798 (4.0%) reports on ototoxicity, sacubitril/valsartan and ototoxicity showed significant association (IC025 = 1.57; ROR025 = 2.99). Dizziness, hypoacusis, balance disorder, and deafness were detected as positive signals; hypoacusis was the strongest (IC025 = 3.21; ROR025 = 9.29). Median time to onset was 45 (10–99) days, and 62.4% of ototoxicity events occurred within 90 days of sacubitril/valsartan administration. Hospitalization accounted for 32.5% of ototoxic outcomes, while life-threatening events, death, and disabling accounted for only 3.9%, 3.4%, and 2.0%, respectively. Sacubitril/valsartan treatment increased ototoxicity risks. Therefore, promptly identifying and treating sacubitril/valsartan-related ototoxicity is critical.

Pharmacologically induced autoimmune encephalitis—disproportionality analysis utilizing FAERS database

ABSTRACT Background Autoimmune encephalitis (AE) is a neuroimmune disorder that presents significant diagnostic challenges. The FDA Adverse Event Reporting System (FAERS) database can help explore the relationship between drugs and AE, but comprehensive studies are lacking. This study aims to analyze the association between drugs and AE using the FAERS database, providing insights for clinical practice and pharmacovigilance. Research Design and Methods Adverse event reports in the FAERS database were analyzed, focusing on the incidence of drug-induced AE, as well as characteristics such as gender and age. Multiple statistical methods were employed to assess the association between drugs and adverse reactions. Results The study revealed that drug-induced AE predominantly occurred in individuals aged 41 and above, with a higher prevalence among female patients. Nivolumab and pembrolizumab were among the drugs most frequently reported for adverse drug reactions. However, only a minority of drug labels mentioned these adverse reactions. Conclusion This study underscores the potential risk of drug-induced AE, advocating for close monitoring in clinical practice. Further epidemiological investigations are warranted to elucidate the exact relationship between drugs and these disorders. While the FAERS database provides crucial leads for such research, additional studies and validation are necessary.

Detection of risk signals for ustekinumab in the real world using the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background Ustekinumab is a fully human interleukin-12/23 (p40) inhibitor used to treat immune-mediated diseases. However, the limitations of clinical trials and the expanding target population necessitate an update on the ustekinumab-associated adverse events (AEs). We conducted signal mining for ustekinumab-related AEs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Research Design and Methods AE reports were collected from 2009 Q3 to 2024 Q1. Four disproportionality analysis algorithms – reporting odds ratio, medicines and healthcare products regulatory agency, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker – were used to quantify the signals of ustekinumab. Results During this period 69,345 AE reports associated with ustekinumab were collected, and ustekinumab was identified as the primary suspect. Overall, 319 signals involving 15 system organ classes were identified, and 111 signals had a medium or strong value for IC025. Of them, 67 were classified as important medical events. Squamous cell carcinoma, pertussis, vulval abscess, breast abscess, and fistula exhibited higher signal intensities. Conclusions Our study identified the risk signals for ustekinumab using real-world data and provides further evidence to support its rational use. Due to the limitations of FAERS, further studies are warranted to verify these findings.

Part 2: Drug Interactions Involving Cannabis Products in Persons Aged 18 and Over: A Summary of Published Case Reports and Analysis of the FDA Adverse Event Reporting System.

The increasing utilization of cannabis products combined with lack of data regarding potential cannabis-prescription drug interactions is concerning. This study aimed to review published case reports and FDA Adverse Event Reporting System (FAERS) spontaneous reports to assess cannabis-drug interactions in persons aged 18 and over. A literature search identified 20 case reports that were each assessed for drug interaction causality using the Drug Interaction Probability Scale. Data collected from the FAERS revealed a greater proportion of reports mentioning serious outcomes, including death, when cannabis was used concomitantly with controlled substances compared to noncontrolled substances. Fisher's exact test showed a statistically significant difference between the controlled and noncontrolled groups (p = 0.043). Overall, these findings emphasize the need for additional research and vigilant monitoring of cannabis use when combined with other medications.

Concomitant use of sodium-glucose co-transporter 2 inhibitors and metformin and the risk of osteomyelitis reporting: a disproportionality analysis based on FAERS database

ABSTRACT Background Recent clinical case reports have generated controversy concerning the adverse events (AEs) of amputation linked to sodium-glucose co-transporter 2 inhibitors (SGLT2i). We assessed the risk of osteomyelitis AE reporting linked to SGLT2i or SGLT2i-metformin co-medication. Research design and methods Investigated the FDA Adverse Event Reporting System for osteomyelitis-related AEs associated with SGLT2i or SGLT2i-metformin co-medication from 2013q2 to 2023q1. Comprehensive disproportionality analysis and Bayesian confidence propagation methods were used to detect safe signals. The additive interaction model, multiplicative interaction model, and Ω shrinkage measure were employed to explore the latent interactions between SGLT2i and metformin. A Venn diagram was utilized to estimate the coincidence of related osteomyelitis and amputation. Results Among 2,569 SGLT2i-associated osteomyelitis reports, we identified 2,509 related to canagliflozin (ROR 104.47; PRR 99.70, χ2 = 214840.90; EBGM05 = 84.38; IC025 = 4.78) and 103 related to the SGLT2i-metformin compound. Drug-drug interaction detection revealed a negative correlation (RERI=-21.73, eβ3 = 0.699, Ω025=-1.370). The coincidence of osteomyelitis and amputation linked to SGLT2i（2,672 vs. 3,548）was 2,150(80%) by Venn diagram. Conclusions This study showed an increased risk of SGLT2i-associated osteomyelitis, focusing on canagliflozin, and presented a potential association between amputation and osteomyelitis, providing a reference for the clinical practice of diabetes with SGLT2i medication.

Fulminant type 1 diabetes mellitus: a neglected but high-risk adverse event associated with immune checkpoint inhibitors.

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment but is associated with fulminant type 1 diabetes mellitus (FT1DM). Our study aims to investigate the association between ICI therapy and FT1DM using the FDA Adverse Event Reporting System (FAERS) database. We conducted a retrospective analysis from the first quarter of 2004 to the first quarter of 2023. The disproportionality analysis incorporating the reporting odds ratio (ROR) and information component (IC) was performed to assess the magnitude of the adverse event signal between ICIs and FT1DM. A total of 520 cases of FT1DM were identified in association with ICI therapy, representing 75.9% of all FT1DM cases reported in the FAERS database. Descriptive analyses revealed a predominance in males (60.2%) and the elderly (70.6%). The median time to onset was 69 days and 337 patients (64.81%) were hospitalized while 35 (6.73%) cases resulted in death. Disproportionality analysis showed a strong signal for FT1DM with ICI treatment (ROR 438.84) versus other drugs. These findings provide compelling evidence linking ICI therapy to the development of FT1DM, underscoring the need for clinical vigilance and early intervention strategies to optimize patient outcomes while leveraging the remarkable therapeutic potential of cancer immunotherapy.

Safety assessment of deutetrabenazine: real-world adverse event analysis from the FAERS database

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.

Adverse event of ruxolitinib cream: a real-world analysis based on FDA adverse event reporting system from 2021 to 2024

ABSTRACT Background Ruxolitinib cream, a topical Janus kinase (JAK) inhibitor, is a widely used treatment for various dermatological diseases. This study employs the FDA Adverse Event Reporting System (FAERS) database to examine adverse events (AEs) associated with ruxolitinib cream. Methods This study employed disproportionate analysis methods, including reported odds ratio and proportional reporting ratio, to collate AEs reported from the fourth quarter of 2021 to the first quarter of 2024. Results After data processing, 803 reports involving ruxolitinib cream were analyzed. Statistically significant signals were identified for 4 system organ classes (SOCs) and 29 preferred terms (PTs). The most notable signal observed in the SOCs was associated with skin and subcutaneous tissue disorders. For PTs, the AEs observed included clinical symptoms such as pruritus, skin irritation, and burning sensations, as well as signs such as rash, scratching, erythema, and dry skin. Additionally, other observed AEs included diseases such as acne, drug hypersensitivity, and herpes zoster. Conclusions This study offers insights into the safety of ruxolitinib cream, improving understanding of its AEs and guiding safer clinical practices. However, the FAERS database lacks data on AE severity and the ability to establish causality, requiring further research to clarify mechanisms behind certain AEs.

Adverse drug events associated with metreleptin administration: a real-world pharmacovigilance study from 2014 to 2024 using the FAERS database

ABSTRACT Background This study analyzed adverse drug event (ADE) signals associated with metreleptin using the FDA Adverse Event Reporting System (FAERS) to provide insights for safe clinical use. Research design and methods Data from 1 January 2014, to 31 March 2024, were extracted. Signal intensity for adverse events was assessed using reporting odds ratio (ROR), Medicines and Healthcare Products Regulatory Agency (MHRA), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods. Time-to-onset (TTO) correlations were evaluated using the Weibull shape parameter (WSP). Logistic regression identified potential hospitalization risk factors. Results 4,000 ADE reports were identified, with 1,025 significant events mainly involving females (66.73%) and reported by healthcare professionals (67.80%), primarily from the United States (84.10%). 101 preferred term (PT) signals were confirmed by all methods, with 57 PTs not listed on the drug label. Overall TTO was 547 days (IQR: 113–1325), with gastrointestinal disorders and investigations as hospitalization risk factors. Conclusions This study provides critical insights into the TTO of ADEs related to metreleptin, informing safe clinical application and emphasizing the importance of monitoring potential side effects.

A real‑world pharmacovigilance study of raloxifene based on the FDA adverse event reporting system (FAERS)

ABSTRACT Background Raloxifene was approved for the treatment of postmenopausal osteoporosis; however, its safety profile remains inadequately understood. This study aimed to evaluate the safety signals associated with raloxifene. Research design and methods Adverse events (AEs) related to raloxifene, spanning from the first quarter of 2004 to the fourth quarter of 2023, were extracted from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was conducted using several methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Results The analysis yielded 7 229 reports related to raloxifene across 19 277 AEs. A total of 217 significantly disproportionate signals were identified, including muscle spasms and hot flashes. Notably, the study also uncovered novel AEs, including eye conditions like cataracts and macular degeneration, as well as gynecological issues like uterine polyps and hemorrhage. Additionally, the analysis confirmed that pulmonary embolism and deep vein thrombosis were the two most prevalent thromboembolic AEs. Conclusion Our study reaffirmed some existing safety information regarding raloxifene while also unveiling novel risk signals. The findings provided crucial insights to enhance the rational use of the drug and inform safety regulatory strategies.