Expert Opinion on Drug Safety最新文献

Background: Letairis (ambrisentan), an endothelin receptor antagonist (ERA), is a critical medication for pulmonary arterial hypertension (PAH). Despite its efficacy, its safety profile is under scrutiny, warranting a detailed analysis.

Research design and methods: This study leveraged the FDA Adverse Event Reporting System (FAERS) from Q1 2007 to Q4 2023, focusing on Letairis as the primary suspect in adverse events. Employing advanced data mining techniques, such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), the study aimed to uncover safety signals.

Results: A total of 43,774 cases were identified, with Letairis implicated in 16,038,963 adverse event reports. There was a notable predominance of female patients (75.30%), with a median age around 64 years. Severe outcomes, including hospitalization (51.63%) and fatalities (20.44%), were prevalent. Signal strength analysis highlighted concerns in infections and infestations, as well as cardiac disorders.

Conclusion: The analysis underscores the need for vigilant pharmacovigilance and highlights Letairis's potential to induce serious AEs, particularly in female and elderly populations. These findings are instrumental in guiding clinical practice and future drug safety assessments.

Introduction: Atorvastatin, one of the most widely used drugs, has attracted controversy regarding its potential adverse reactions to acute kidney injury(AKI). This study aims to provide evidence in support of the safe use of atorvastatin.

Areas covered: Using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2024), we extracted reports where atorvastatin was the primary suspect and categorized them into five populations: the general population, acute myocardial infarction (AMI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD). We performed subgroup analyses by gender and age strata within these populations, assessing positive signals through disproportionality analysis using four criteria: Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EGBM). The statistical analysis evaluated differences between adverse drug reaction (ADR) occurrence and nonoccurrence, as well as between high and low induction time groups.

Expert opinion: In the general population, evidence for a positive signal of AKI was insufficient. However, the sub-group analysis revealed a risk in males, with older individuals more often affected in both AMI and IS populations. In T2DM, positive signals were evident in younger age groups. For the HLD population, evidence of a positive AKI signal was insufficient across gender and age strata. Overall, atorvastatin is generally safe, but clinical vigilance for AKI is warranted in T2DM, AMI, and IS populations, particularly in older adults (65+ years).

Objective: The study endeavors to elucidate AE signals associated with zanubrutinib data from the WHO-VigiAccess and FAERS databases. The aim is to furnish robust scientific evidence to inform clinical practice and regulatory decisions.

Methods: We meticulously extracted all AE breports tied to zanubrutinib from the both databases, encompassing the period from the drug's market introduction until 30 April 2024. Retrospective quantitative analysis employing ROR, PRR, and BCPNN methodologies were utilized to analysis.

Results: The investigation unveiled 1,304 reports from WHO-VigiAccess and 1,141 reports from FAERS related to zanubrutinib. Among the top 30 reported PTs in both databases, those not recorded in the drug label included pyrexia, dizziness, and death. In the FAERS database, signals for zanubrutinib were detected across 19 SOCs. Systems not covered in the drug label included reproductive system and breast disorders, metabolism and nutrition disorders, ear and labyrinth disorders, among others. Unmentioned signals included intestinal perforation, onychoclasis, night sweats, etc.

Conclusion: This study confirms common AEs of zanubrutinib and identifies new ones, highlighting the need for careful monitoring and personalized treatment. It also emphasizes the importance of ongoing drug safety surveillance and patient management to maximize therapeutic benefits and minimize risks.

Background: Multidrug-resistant (MDR) infections pose a global public health crisis with significant mortality and economic burdens. Combination of polymyxins and vancomycin has shown effectiveness against MDR infections. However, their combined nephrotoxicity complicates clinical use. Given these concerns, we conducted a pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) to assess the nephrotoxicity of combinations of polymyxins and vancomycin compared to monotherapy.

Research design and methods: In this retrospective study, data from FAERS reports (2012 Q4 to 2023 Q2) were deduplicated and analyzed for adverse events (AEs) related to vancomycin, polymyxin B, and colistin. Disproportionality analyses were performed to evaluate the association between drugs and nephrotoxicity.

Results: A total of 9,796,784 adverse event reports, including 73,009 reports associated with nephrotoxicity, were included. All three drugs showed significant associations with nephrotoxicity. In combination therapy, polymyxin B-vancomycin exhibited a stronger association with nephrotoxicity compared to monotherapy, whereas colistin-vancomycin demonstrated a lower association with nephrotoxicity than colistin monotherapy.

Conclusions: This study found that combining vancomycin with colistin alleviated colistin-induced nephrotoxicity, while combining vancomycin with polymyxin B worsened polymyxin B-induced nephrotoxicity.

Background: Dapagliflozin prevents myocardial dysfunction in chronic kidney disease patients regardless of residual kidney function. We hypothesized that this effect is extensible also to patients on dialysis.

Research design and methods: The DARE-ESKD-2 is an ongoing, single-center, open-label randomized clinical trial designed to determine the effects of adding dapagliflozin to standard treatment on myocardial function and structure. Eligible patients were adults on a regular dialysis scheme for more than 3 months. Pregnancy, liver failure, allergy to the investigational drug, and prior use of SGLT2i were exclusion criteria. Participants were randomized in a 1:1 ratio to dapagliflozin or standard treatment groups for 24-weeks. The primary goal is to compare the change in NT-proBNP levels between study arms, and secondary goals include comparing the between-group difference in left ventricle global longitudinal strain, indexed mass, ejection fraction, and E/e` ratio, and on symptoms scale and 6-minute walk test distance. An exploratory analysis will evaluate changes in body composition and bone densitometry.

Results: The trial has finished the enrollment of 80 patients, who are currently being followed-up.

Conclusions: This trial will provide novel data on myocardial effects of SGLT2i in dialysis recipients. Results from this study may provide evidence to support SGLT2i use in ESKD.

Background: This study aimed to provide an overview of gastrointestinal (GI) adverse events associated with immune checkpoint inhibitors (ICIs) using two pharmacovigilance databases, EudraVigilance and VigiAccess.

Research design and methods: Data was collected from the date of ICI's marketing authorization until 30 November 2023. Reporting odds ratio (ROR) was used as a measure of ADR reporting disproportionality for signal detection.

Results: Overall, across both databases, EudraVigilance and VigiAccess, a total of 76,606 ADR reports were analyzed. In EudraVigilance, colitis (12,581) and diarrhea (12,108) were the most reported GI adverse events, with similar findings in VigiAccess. Furthermore, in both databases, the most ADR reports were associated with nivolumab and pembrolizumab. Durvalumab (ROR:3.96,95%CI:3.65-4.28), ipilimumab (ROR:1.95,95%CI:1.89-2.01), nivolumab (ROR:1.05,95%CI:1.02-1.07), and atezolizumab (ROR:1.04,95%CI:1.01-1.07) demonstrated higher risks of GI events compared to other ICIs. EudraVigilance analysis identified dysphagia, ascites, hematochezia, and gastroesophageal reflux disease as potential signals associated with ICI therapy. Majority of ADR reports (87.2%) comprised serious GI adverse events, a portion of which was associated with fatal outcomes (14.5%). Atezolizumab (14.9%) and pembrolizumab (11.9%) were linked to a higher incidence of fatal outcomes compared to other ICIs.

Conclusion: The differential risk profiles of ICIs-associated-GI adverse events underscore the importance of personalized therapy in oncology.

Background: Rufinamide (RUF) is an antiepileptic drug recently introduced for managing seizures in Lennox-Gastaut syndrome (LGS), but its adverse reactions are not well understood. This study aims to evaluate RUF's safety profile using data from the FDA Adverse Event Reporting System (FAERS).

Methods: Disproportionality analysis was conducted to assess RUF-associated adverse drug events (ADEs), using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-Poisson shrinker (MGPS).

Results: We collected 338 ADE reports related to RUF. Nervous system disorders were the most frequently reported signals, and several new ADEs were detected, including atonic seizures, sudden unexplained death in epilepsy, seizure clusters, multi-drug resistance, and Stevens-Johnson syndrome. Nearly half of the ADEs in pediatric patients were psychological or neurological. Disproportionality analysis within 4 weeks of treatment showed high RORs for QT shortening, sudden death, and atonic seizures.

Conclusions: Our study revealed prospective signals of new ADEs linked to RUF as well as revealed that both prescribers and patients were more conscious of the risks involved in its clinical use.

Background: Azithromycin and clarithromycin are commonly used to treat community-acquired pneumonia in adults aged ≥ 65, such as mycoplasma pneumonia. This study aims to evaluate adverse events (AEs) associated with azithromycin and clarithromycin in this age group by analyzing the FDA Adverse Event Reporting System (FAERS), providing insights for clinical use and management of AEs in this population.

Research design and methods: We retrieved reports of AEs related to azithromycin and clarithromycin from the FAERS database. Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Gamma Poisson Shrinkage (MGPS) to identify AEs associated with azithromycin and clarithromycin in adults aged ≥ 65.

Results: A total of 2,019 adverse event reports were retrieved for azithromycin, and 2,392 for clarithromycin. Off-label use (n = 349) and drug interactions (n = 487) were the most reported AEs in adults aged ≥ 65 for azithromycin and clarithromycin, respectively. Prolonged QT interval showed the strongest signal among AEs for azithromycin in this age group. Drug interaction-related medication errors had the strongest signal for clarithromycin. Seven signals not explicitly included in the azithromycin package insert were identified in adults aged ≥ 65. Fourteen signals not explicitly included in the clarithromycin package insert were identified.

Conclusions: Among adults aged ≥ 65, cardiac-related adverse events are more closely associated with azithromycin than with clarithromycin. Conversely, AEs related to drug interactions and psychiatric symptoms are more associated with clarithromycin. Additionally, clinicians should be vigilant regarding AEs not specified in the package inserts. The findings of this study may help optimize the selection of azithromycin and clarithromycin based on patient circumstances and assist clinicians in focusing on relevant AEs for early intervention.

Background: Anti-herpesvirus drug safety profiles have not been systematically compared. Understanding variations in adverse events (AEs) could provide reference for rational clinical use.

Methods: We collected data on acyclovir, ganciclovir, valaciclovir, and foscarnet from the FDA Adverse Event Reporting System (FAERS) database from Q1 2004 to Q3 2023. Disproportionality analyses were conducted to evaluate the risk of AEs.

Results: All drugs exhibited significant associations with hematotoxicity, with ganciclovir and foscarnet being more myelosuppressive. The correlation with renal impairment ranked as follows: foscarnet, ganciclovir, valaciclovir, and acyclovir (ROR = 16.72, 7.06, 3.51, and 2.02, respectively). Regarding hepatotoxicity, ganciclovir was associated with acute-on-chronic liver failure (ROR = 52.83), and foscarnet was associated with fulminant hepatitis (ROR = 49.91). In the nervous system, acyclovir showed the highest intensity of neurotoxicity (ROR = 14.95). Valaciclovir ranked first in toxic encephalopathy (ROR = 64.70). Foscarnet showed the highest intensity of status epilepticus (ROR = 6.45). Besides, acyclovir showed the strongest association with severe cutaneous adverse reactions (SCARs).

Conclusions: Our study revealed differences in safety profiles of four anti-herpesvirus medications. Ganciclovir exhibited the highest risk of hematotoxicity but appeared relatively safe in seizures and SCARs. Foscarnet was more likely to induce nephrotoxicity, seizures, and electrolyte imbalances than others. Acyclovir and valaciclovir were strongly associated with plasmacytosis, neurotoxicity, and SCARs.

Objective: This study analyzed the signal mining of adverse events caused by finerenone based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) and evaluated the drug's safety to provide a reference for the safe administration of this medication in medical institutions.

Methods: FAERS data from the third quarter of 2021 to the fourth quarter of 2023 were used, and the adverse event codes of the Medical Dictionary for Regulatory Activities were compared. After the data were processed, adverse event reports that featured finerenone as the most suspected drug were extracted.

Results: A total of 905 reported cases of adverse events including finerenone as the first suspected drug were extracted. The ratio of male to female patients was 1.25, and most were aged 65-85 years (30.1%). The adverse events that were reported more frequently with positive signals were decreased glomerular filtration rate, hyperkalemia, increased blood creatinine, and dizziness. The adverse events that were concentrated on in investigations were metabolism and nutrition disorders and diseases of the renal and urinary system.

Conclusions: Our study identified significant novel adverse events (AEs) signals for finerenone that could provide support for clinical monitoring of and risk identification for finerenone.