Cardiovascular Complications of Modern Multiple Myeloma Therapy: Analysis of FDA Adverse Event Reporting System

Background: Multiple myeloma accounts for over 15% of hematological malignancies. In attempt to tackle this malady, the FDA approved four drugs in 2015 which has propagated further development of new anti-multiple myeloma since. However, the health safety of these new agents is still ill-defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs. Methods: We searched the cardiac adverse events of the newly approved FDA drugs since 2015 using the U.S. Food and Drug Administration Adverse Events Reporting System database. We calculated the reporting odds ratio (ROR) with 95% confidence for four drugs that have the highest incidence of cardiovascular adverse events. Results: Between 2015-2020, the FDA approved six novel agents for multiple myeloma which includes elotuzumab, Ixazomib, daratumumab, panobinostat, Isatuximab, and belantamab mafodotin. Among all these medications, elotuzumab, Ixazomib, daratumumab, and panobinostat showed the highest incidence of cardiovascular complications. After vetting all the cardiac adverse events, our analysis revealed that atrial fibrillation, heart failure, and coronary disease were the highest reported cardiac events with significant odds ratio. Conclusions: The newly approved multiple myeloma therapy (elotuzumab, Ixazomib, daratumumab, panobinostat) are significantly associated with cardiotoxicity. These results highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.

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Thrombocytopenia with Tedizolid and Linezolid

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01453-17 ◽

2017 ◽

Vol 62 (1) ◽

Cited By ~ 15

Author(s):

Erica Yookyung Lee ◽

Aisling R. Caffrey

Keyword(s):

Adverse Event ◽

Confidence Interval ◽

Drug Administration ◽

Odds Ratio ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Reporting Odds Ratio ◽

Event Reporting ◽

Using Data

ABSTRACT Several studies have suggested the risk of thrombocytopenia with tedizolid, a second-in-class oxazolidinone antibiotic (approved June 2014), is less than that observed with linezolid (first-in-class oxazolidinone). Using data from the Food and Drug Administration adverse event reporting system (July 2014 through December 2016), we observed significantly increased risks of thrombocytopenia of similar magnitudes with both antibiotics: linezolid reporting odds ratio [ROR], 37.9 (95% confidence interval [CI], 20.78 to 69.17); tedizolid ROR, 34.0 (95% CI, 4.67 to 247.30).

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Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System

Frontiers in Pharmacology ◽

10.3389/fphar.2021.720776 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaoyin Bai ◽

Shiyu Jiang ◽

Yangzhong Zhou ◽

Hongnan Zhen ◽

Junyi Ji ◽

...

Keyword(s):

Adverse Events ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

Reporting System ◽

Checkpoint Inhibitors ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Event Reporting ◽

Logistic Analysis ◽

The Us

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, immune-related adverse events (irAEs) in the gastrointestinal (GI) system commonly occur. In this study, data were obtained from the US Food and Drug Administration adverse event reporting system between July 2014 and December 2020. Colitis, hepatobiliary disorders, and pancreatitis were identified as irAEs in our study. Reporting odds ratio (ROR) with information components (IC) was adopted for disproportionate analysis. A total of 70,330 adverse events were reported during the selected period, 4,075 records of which were associated with ICIs. GI toxicities have been reportedly increased with ICI, with ROR025 of 17.2, 6.7, and 2.3 for colitis, hepatobiliary disorders, and pancreatitis, respectively. The risks of colitis, hepatobiliary disorders, and pancreatitis were higher with anti-CTLA-4 treatment than that with anti-PD-1 (ROR025 2.6, 1.3, and 1.1, respectively) or anti-PD-L1 treatment (ROR025 4.8, 1.3, and 1.3, respectively). Logistic analysis indicated that hepatobiliary disorders and pancreatitis more frequently occurred in female patients (adjusted odds ratio, 1.16 and 1.52; both p < 0.05). Consistently, polytherapy was a strong risk factor for colitis (adjusted odds ratio 2.52, p < 0.001), hepatobiliary disorders (adjusted odds ratio 2.50, p < 0.001), and pancreatitis (adjusted odds ratio 2.29, p < 0.001) according to multivariate logistic analysis. This pharmacovigilance analysis demonstrated an increased risk of all three GI irAEs associated with ICI therapies. The comparative analysis offered supportive insights on selecting GI irAEs for patients treated with ICIs.

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COVID Vaccine and Cardiovascular Signals: An Analysis of Vaccine Adverse Event Reports (Preprint)

10.2196/preprints.30576 ◽

2021 ◽

Author(s):

Yiqing Zhao ◽

Michael Ison ◽

Yuan Luo

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Odds Ratio ◽

Spontaneous Reporting ◽

Reporting System ◽

Spontaneous Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Event Reporting ◽

High Odds

UNSTRUCTURED Adverse events (AEs) following COVID vaccination have been intensely monitored. In our study, we analyzed data from a spontaneous reporting system - Vaccine Adverse Event Reporting System and detected signals of AEs following administration of COVID vaccines. We identified several cardiovascular and inflammatory-related AEs that demonstrated high odds ratio. We demonstrated our system can serve as a complementary system to identify and monitor AEs outside of pre-defined outcomes routinely monitored by existing databases or projects.

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Ischemic cardiac events and other adverse events following ACAM2000® smallpox vaccine in the Vaccine Adverse Event Reporting System

Vaccine ◽

10.1016/j.vaccine.2014.06.034 ◽

2014 ◽

Vol 32 (37) ◽

pp. 4758-4765 ◽

Cited By ~ 3

Author(s):

Michael M. McNeil ◽

Maria Cano ◽

Elaine R. Miller ◽

Brett W. Petersen ◽

Renata J.M. Engler ◽

...

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Smallpox Vaccine ◽

Cardiac Events ◽

Event Reporting

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Medication Associated Salivary Gland Alterations– Assessment of risk

Journal of Indian Dental Association ◽

10.33882/jida.13.24723 ◽

2019 ◽

pp. 26-33

Author(s):

Rooban Thavarajah ◽

Elizabeth Joshua ◽

Umadevi Rao ◽

Kannan Ranganathan

Keyword(s):

Salivary Gland ◽

Adverse Events ◽

Odds Ratio ◽

Adverse Event Reporting System ◽

The United States ◽

Adverse Event Reporting ◽

Reporting Odds Ratio ◽

Chronic Medication ◽

Specific Description ◽

Salivary Gland Enlargement

Brief Background Medication Associated Salivary Gland Alterations (MASGA) are a common set of adverse events (AE) associated with many common medications. There are a few reports of the risk of MASGA with medication. Materials and Methods Using whole database approach, the Food and Drug Administration Adverse Event Reporting System (FAERS) of the United States of America was searched for MASGA. Common alterations and drugs associated were assessed for the Reporting Odds Ratio, as mentioned in pharmacovigilance researches. Results In the time phase considered, there were in all 16996785 AE reported in the FAERs database. Of this 68624 were related to MASGA with Dry Mouth and hypersecretion being most common. Anti-psychotic drugs predominated the hypersecretion spectrum with clozapine having a ROR of 58.04 followed by Haloperidol (25.29). Among the drugs that caused SG enlargement, potassium iodide (1335.32) and Oxyphenbutazone (696.58) had the highest ROR. Non-specific description of altered saliva was seen with high ROR in haloperidol and enoxaparin sodium (14.22). Summary and Conclusions Odds Ratio of drugs causing MASGA are. chronic medication such as those given for non-communicable, life style diseases and psychiatric medications known to cause MASGA. Key Words Salivary Alterations, Xerostomia, Salivary gland enlargement, Adverse Events, Pharmacovigilance

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Exploring pharmacogenetic difference using adverse event database: an example of clopidogrel and cardiovascular events

Pharmacogenomics ◽

10.2217/pgs-2020-0047 ◽

2020 ◽

Vol 21 (16) ◽

pp. 1157-1168

Author(s):

Kyung-In Joung ◽

Kwang Hyun Kim ◽

Cheng-Yang Hsieh ◽

Ju-Young Shin

Keyword(s):

Adverse Event ◽

Odds Ratio ◽

Cardiovascular Events ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Reporting Odds Ratio ◽

Event Reporting ◽

System Database ◽

System Data

Background: Poor clopidogrel metabolizers, carrying a cytochrome P450 2C19 loss-of-function allele, are more frequent among East Asians than Caucasians/White. Materials & methods: The Korea adverse event reporting system database and a case/noncase study design were used to examine the disproportionality of cardiovascular events following clopidogrel use. The US FDA’s adverse event reporting system database was also analyzed for comparison. Results: In the Korea adverse event reporting system data, the clopidogrel reporting odds ratio for cardiovascular events was 7.34, more than double that of ticagrelor. In the FDA’s adverse event reporting system data, the clopidogrel reporting odds ratio was 4.69, lower than that of ticagrelor. Adjustment for covariates did not change the trend. Conclusion: Considering the prevalence of poor clopidogrel metabolizers and the reported cardiovascular events among Koreans, rigorous clinical management is required for clopidogrel users.

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Adverse outcomes associated with the treatment of Toxoplasma infections

Scientific Reports ◽

10.1038/s41598-020-80569-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ahmed M. Shammaa ◽

Thomas G. Powell ◽

Imaan Benmerzouga

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Real World ◽

Odds Ratio ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Adverse Outcomes ◽

Reporting Odds Ratio ◽

Real World Data ◽

Suspect Drug

AbstractAdverse outcomes associated with the treatment of Toxoplasma gondii infections in patients with various health backgrounds have not been characterized. The aim of this study was to identify the adverse outcomes and adverse events associated with the current clinical treatments of Toxoplama gondii infections using real world data reported to the FDA adverse event reporting system (FAERS). Data submitted to FAERS between 2013 and 2019 was retrieved and analyzed. Reporting odds ratio of death was calculated for the drugs having ≥ 25 reports of adverse outcomes. The adverse event profiles for the same drugs were analyzed and the reporting odds ratio was calculated relative to all other drugs used in the treatment of Toxoplasma infections. There were 503 cases reporting the treatment of Toxoplasma infections in the FAERS database. Death (DE) was the adverse outcome in 102 reports, of which 23 (22.5%) anti-Toxoplasma drugs were listed as the primary suspect drug (PS). Clindamycin (2.04; 1.07–3.90) followed by pyrimethamine (1.53; 0.99–2.36) were the most likely to be associated with death. Adverse events analysis suggest that sulfonamides formulations may have a less favorable safety profile. Our study represents the first real-world analysis of adverse outcomes and events associated with the treatment of Toxoplasma infections. Our findings support the need to better understand the current first-line agents for Toxoplasma infections, in addition to underscoring the need to identify safer regimens.

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Novel Adverse Events of Iloperidone: A Disproportionality Analysis in US Food and Drug Administration Adverse Event Reporting System (FAERS) Database

Current Drug Safety ◽

10.2174/1574886313666181026100000 ◽

2019 ◽

Vol 14 (1) ◽

pp. 21-26 ◽

Cited By ~ 2

Author(s):

Viswam Subeesh ◽

Eswaran Maheswari ◽

Hemendra Singh ◽

Thomas Elsa Beulah ◽

Ann Mary Swaroop

Keyword(s):

Data Mining ◽

Adverse Event ◽

Adverse Events ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Disproportionality Analysis ◽

Positive Signal ◽

Data Mining Algorithms ◽

Mining Algorithms

Background: The signal is defined as “reported information on a possible causal relationship between an adverse event and a drug, of which the relationship is unknown or incompletely documented previously”. Objective: To detect novel adverse events of iloperidone by disproportionality analysis in FDA database of Adverse Event Reporting System (FAERS) using Data Mining Algorithms (DMAs). Methodology: The US FAERS database consists of 1028 iloperidone associated Drug Event Combinations (DECs) which were reported from 2010 Q1 to 2016 Q3. We consider DECs for disproportionality analysis only if a minimum of ten reports are present in database for the given adverse event and which were not detected earlier (in clinical trials). Two data mining algorithms, namely, Reporting Odds Ratio (ROR) and Information Component (IC) were applied retrospectively in the aforementioned time period. A value of ROR-1.96SE>1 and IC- 2SD>0 were considered as the threshold for positive signal. Results: The mean age of the patients of iloperidone associated events was found to be 44years [95% CI: 36-51], nevertheless age was not mentioned in twenty-one reports. The data mining algorithms exhibited positive signal for akathisia (ROR-1.96SE=43.15, IC-2SD=2.99), dyskinesia (21.24, 3.06), peripheral oedema (6.67,1.08), priapism (425.7,9.09) and sexual dysfunction (26.6-1.5) upon analysis as those were well above the pre-set threshold. Conclusion: Iloperidone associated five potential signals were generated by data mining in the FDA AERS database. The result requires an integration of further clinical surveillance for the quantification and validation of possible risks for the adverse events reported of iloperidone.

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Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database

Scientific Reports ◽

10.1038/s41598-021-91549-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xiaojiang Tian ◽

Yao Yao ◽

Guanglin He ◽

Yuntao Jia ◽

Kejing Wang ◽

...

Keyword(s):

Data Mining ◽

Adverse Event ◽

Reporting System ◽

Proportional Reporting Ratio ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Reporting Odds Ratio ◽

Systematic Analysis ◽

Event Reporting ◽

Exfoliative Dermatitis

AbstractThis current investigation was aimed to generate signals for adverse events (AEs) of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All AE reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10,756 reports were identified commonly observed in hepatobiliary, endocrine, cardiovascular, musculoskeletal, gastrointestinal, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be possibly associated with multiple adverse pregnant conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.

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