Dataset Information

Cardiac Events Potentially Associated to Remdesivir: An Analysis from the European Spontaneous Adverse Event Reporting System.

ABSTRACT: Remdesivir was recommended for hospitalized patients with COVID-19. As already reported in the Summary of Product Characteristics, most of remdesivir's safety concerns are hepatoxicity and nephrotoxicity related. However, some cases have raised concerns regarding the potential cardiac events associated with remdesivir; therefore, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency requested to investigate all available data. Therefore, we analyzed all Individual Case Safety Reports (ICSRs) collected in the EudraVigilance database focusing on cardiac adverse events. From April to December 2020, 1375 ICSRs related to remdesivir were retrieved from EudraVigilance, of which 863 (62.8%) were related to male and (43.3%) adult patients. A total of 82.2% of all AEs (N = 2604) was serious and one third of the total ICSRs (N = 416, 30.3%) had a fatal outcome. The most frequently reported events referred to hepatic/hepatobiliary disorders (19.4%,), renal and urinary disorders (11.1%) and cardiac events (8.4%). Among 221 cardiac ICSRs, 69 reported fatal outcomes. Other drugs for cardiovascular disorders were reported as suspected/concomitant together with remdesivir in 166 ICSRs (75.1%), 62 of which were fatal. Moreover, the mean time to overall cardiac event was 3.3 days (±2.2). Finally, disproportionality analysis showed a two-fold increased risk of reporting a cardiac adverse event associated with remdesivir compared to both hydroxychloroquine and azithromycin. This study showed that remdesivir could be associated to risk of cardiac events, suggesting a potential safety signal which has not been completely evaluated yet. Further studies are needed to confirm these findings.

SUBMITTER: Rafaniello C

PROVIDER: S-EPMC8308754 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTaxanes are an essential class of antineoplastic agents used to treat various cancers and are a fundamental cause of hypersensitivity reactions. In addition, other adverse events, such as bone marrow toxicity and peripheral neuropathy, can lead to chemotherapy discontinuation. This study aimed to evaluate the safety of taxanes in the real world.MethodsTaxane-associated adverse events were identified by the Medical Dictionary for Regulatory Activities Preferred Terms and analyzed and compared by mining the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database from January 2004 to December 2019. Reported adverse events, such as hypersensitivity reaction, bone marrow toxicity, and peripheral neuropathy, were analyzed with the following signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), and logistic regression methods. Adverse outcome events and death outcome rates were compared between different taxane groups using Pearson's χ2 test, whereas significance was determined at P < 0.05 with a 95% confidence interval (CI).ResultsA total of 966 reports of hypersensitivity reactions, 1109 reports of bone marrow toxicity, and 1374 reports of peripheral neuropathy were analyzed. Compared with paclitaxel and docetaxel, bone marrow toxicity following the use of nab-paclitaxel had the highest ROR of 6.45 (95% two-sided CI, 6.05-6.88), PRR of 5.66, (χ2 = 4342.98), information component of 2.50 (95% one-sided CI = 2.34), and empirical Bayes geometric mean of 5.64 (95% one-sided CI = 5.34). Peripheral neuropathy following the use of nab-paclitaxel showed a higher ROR of 12.78 (95% two-sided CI, 11.55-14.14), PRR of 12.16 (χ2 = 4060.88), information component of 3.59 (95% one-sided CI = 3.25), and empirical Bayes geometric mean of 12.07 (95% one-sided CI = 11.09).ConclusionsThe results showed that bone marrow toxicity and peripheral neuropathy were the major adverse events induced by taxanes. Nab-paclitaxel exhibited the highest potential for taxane-associated adverse events. Further research in the future is warranted to explain taxane-associated adverse effects in real-world circumstances.

Project description:Data regarding the safety of anti-vascular endothelial growth factor (anti-VEGF) treatment is limited.To compare the adverse events (AEs) induced by aflibercept and ranibizumab using a spontaneous reporting system and determine the signals.We used data from the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD), collected between 2007 and 2016. Differences in patient demographics, report type, reporter, causality, and serious-AEs between aflibercept and ranibizumab were compared. Metrics including proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC), were used to compare signals with the AEs on the drug labels in the United States of America and Korea. Logistic regression analysis was performed to identify AEs that are more likely to occur with drug use.A total of 32 aflibercept and 103 ranibizumab cases of AEs were identified. The proportion of AEs that were reported voluntarily was higher with aflibercept (50.5%) use than ranibizumab (4.9%), whereas the AEs reported by post-marketing surveillance were higher with ranibizumab (46.6%) use than aflibercept (31.3%). The percentage of AEs in patients >60 years old, reports by consumers, and the ratio of SAEs to AEs associated with aflibercept (84. %, 9.4%, and 75.0%, respectively) were higher than those of ranibizumab (77.7%, 1.9%, and 19.4%, respectively). The number of newly detected AEs after aflibercept and ranibizumab treatment was 3 and 8, respectively. Among these, conjunctivitis and medicine ineffective were not included on the aflibercept and ranibizumab labels, respectively. Endophthalmitis (OR 6.96, 95% CI 2.74-17.73) was more likely to be reported in patients with aflibercept than in patients without aflibercept, whereas medicine ineffective (OR 18.49, 95% CI 2.39-143.29) and retinal disorder (OR 7.03, 95% CI 1.60-30.96) were more likely to be reported in patients with ranibizumab than in patients without ranibizumab.New signals have been identified for aflibercept and ranibizumab. Further research is necessary to evaluate the causality of AEs that were detected as signals in this study.

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Cardiac Events Potentially Associated to Remdesivir: An Analysis from the European Spontaneous Adverse Event Reporting System.

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