scholarly journals Gender Differences in Adverse Drug Events of Hydroxychloroquine: Analysis of Spontaneous Reports Submitted to FAERS

2021 ◽  
Author(s):  
Huan-huan JI ◽  
Lin SONG ◽  
Yun-tao JIA
Keyword(s):  
Gender Differences ◽  
Adverse Drug Events ◽  
Adverse Event Reporting System ◽  
Safety Data ◽  
Adverse Event Reporting ◽  
Drug Event ◽  
System Organ Class ◽  
Reporting Odds Ratio ◽  
Disproportionality Analysis ◽  
Spontaneous Reports

Abstract Background Several studies have investigated gender as a risk factor for the occurrence of adverse drug events (ADEs) and found that females are more likely to experience ADEs than male. Today, there is a poor knowledge about gender differences in safety profile of ADEs to hydroxychloroquine (HCQ). Identifying those gender differences in ADEs could reduce the experience of ADEs for patients with HCQ. Therefore, the aim of this explorative study was to investigate whether differences exist in reported ADEs of HCQ for male and female in the database of FDA Adverse Event Reporting System (FAERS). Methods We performed a descriptive gender-related analysis and disproportionality analysis of HCQ safety data, obtained from the FAERS. Reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated to quantify the signals of gender differences for specific drug-event combinations at system organ class (SOC) and preferred term (PT) level. Results Disproportionality analysis indicated that 8 SOCs with 12 ADEs were statistically significantly more reported in female than male, including electrocardiogram Qt prolonged, retinal toxicity, musculoskeletal disorder, hypersensitivity, anaphylactic reaction, among others, and 5 SOCs with 11 ADEs were reported more in male than female, including cardiac failure, renal failure, completed suicidal, photosensitivity reaction. Common adverse events are similar between female and male. However, serious ADEs were more frequently reported in males. Conclusions Therefore, the recognition of gender differences in ADEs may be helpful in prescribing medications, e.g. greater caution should be taken when prescribing HCQ to female with conduction disorder.

scholarly journals Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
Yong Zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Safety Issues

Abstract Background Immune checkpoint inhibitors-induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADEs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCPNN) method was the strongest. Conclusion The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which were consistent with the results of previous clinical trials and could provide a reference for clinical workers when using ICIs.

scholarly journals Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

2020 ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
yong zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Safety Issues

Abstract Background: Immune checkpoint inhibitors induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods: We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADRs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results: Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCNPP) method was the strongest. Conclusion: The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which are consistent with the results of previous clinical trials and can provide a reference for clinical workers when using ICIs.

scholarly journals Pharmacovigilance Assessment of Drug-Induced Acute Pancreatitis Using a Spontaneous Reporting Database

2019 ◽  
Vol 38 (6) ◽  
pp. 487-492 ◽  
Author(s):  
Iku Niinomi ◽  
Keiko Hosohata ◽  
Saki Oyama ◽  
Ayaka Inada ◽  
Tomohito Wakabayashi ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Odds Ratio ◽  
Spontaneous Reporting ◽  
Adverse Drug Events ◽  
Drug Event ◽  
Reporting Odds Ratio ◽  
Event Report ◽  
Disproportionality Analysis ◽  
Drug Induced ◽  
Spontaneous Reporting Database

Background: Acute pancreatitis (AP) is associated with risks of morbidity and mortality. The incidence of AP recently increased compared to that traditionally reported in the literature. Objective: The purpose of this study was to evaluate the possible association between AP and drugs using the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database of adverse drug events. Methods: Adverse event reports submitted to the JADER database between 2004 and 2017 were analyzed. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence intervals for signal detection. Results: A total of 3,443 reports (0.17% of all adverse events) were identified as drug-induced AP, in which 431 different drugs were involved. Acute pancreatitis was frequently reported in men (58.5%) in their 60s (19.1%); 40.6% developed AP within 4 weeks after the treatment. Among the most frequently reported drugs, signals were detected for prednisolone, ribavirin, sitagliptin, mesalazine, tacrolimus, and l-asparaginase, which are well-known causes of AP. Telaprevir, donepezil, and ustekinumab also generated signals. As for drugs with high RORs, l-asparaginase and alogliptin were noteworthy. Conclusion: Most of the identified drugs were already known to induce AP, but the likelihood of the reporting of AP varied among the drugs. Our results should raise physicians’ awareness of drugs associated with AP, but further investigation of these medications is warranted.

Adverse Drug Events in the Prevention and Treatment of COVID-19: A Data Mining Study on FDA Adverse Event Reporting System (FAERS) (Preprint)

2021 ◽  
Author(s):  
Qiang Guo ◽  
Shaojun Duan ◽  
Yaxi Liu ◽  
Yinxia Yuan
Keyword(s):  
Data Mining ◽  
Adverse Event ◽  
Adverse Drug Events ◽  
Reporting System ◽  
Proportional Reporting Ratio ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Drug Event ◽  
Event Reporting ◽  
Prevention And Treatment

BACKGROUND In the emergency situation of COVID-19, off-label therapies and newly developed vaccines may bring the patients adverse drug event (ADE) risks. Data mining based on spontaneous reporting systems (SRSs) is a promising and efficient way to detect potential ADEs so as to help health professionals and patients get rid of these risks. OBJECTIVE This pharmacovigilance study aimed to investigate the ADEs of “Hot Drugs” in COVID-19 prevention and treatment based on the data of the US Food and Drug Administration (FDA) adverse event reporting system (FAERS). METHODS FAERS ADE reports associated with COVID-19 from the 2nd quarter of 2020 to the 2nd quarter of 2021 were retrieved with “Hot Drugs” and frequent ADEs recognized. A combination of support, proportional reporting ratio (PRR) and Chi-square (2) test was applied to detect significant “Hot Drug” & ADE signals by Python programming language on Jupyter notebook. RESULTS 13,178 COVID-19 cases were retrieved with 18 “Hot Drugs” and 312 frequent ADEs on “Preferred Term” (PT) level. 18  312 = 5,616 “Drug & ADE” candidates were formed for further data mining. The algorithm finally produced 219 significant ADE signals associated with 17 “Hot Drugs”and 124 ADEs.Some unexpected ADE signals were observed for chloroquine, ritonavir, tocilizumab, Oxford/AstraZeneca COVID-19 Vaccine and Moderna COVID-19 Vaccine. CONCLUSIONS Data mining is a promising and efficient way to assist pharmacovigilance work and the result of this paper could help timely recognize ADEs in the prevention and treatment of COVID-19.

scholarly journals Disproportionality Analysis of Safety with Nafcillin and Oxacillin with the FDA Adverse Event Reporting System (FAERS)

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Tristan T. Timbrook ◽  
Lydia McKay ◽  
Jesse D. Sutton ◽  
Emily S. Spivak
Keyword(s):  
Adverse Event ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Lower Proportion ◽  
Reporting Odds Ratio ◽  
Disproportionality Analysis ◽  
Event Reporting ◽  
Content Type ◽  
Failure Reporting

ABSTRACT Antistaphylococcal penicillins such as nafcillin and oxacillin are among the first choices of treatment for severe invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections, although there has been limited safety evaluations between individual agents. Using the FDA Adverse Event Reports System (FAERS), oxacillin was observed to have a lower proportion of reports of acute renal failure (reporting odds ratio [ROR], 5.3 [95% confidence interval {CI}, 3.1 to 9.3] versus 21.3 [95% CI, 15.8 to 28.6], respectively) and hypokalemia (ROR, 0.7 [95% CI, 0.1 to 4.8] versus 11.4 [95% CI, 7.1 to 18.3], respectively) than nafcillin.

scholarly journals Real-world Safety Profile of Darunavir and its Boosted Agents: An Analysis of FDA Adverse Event Reporting System Database

2021 ◽  
Author(s):  
Xiaojiang Tian ◽  
Yao Yao ◽  
Guanglin He ◽  
Yuntao Jia ◽  
Kejing Wang ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Drug Events ◽  
Reporting System ◽  
Proportional Reporting Ratio ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Exfoliative Dermatitis ◽  
Adverse Pregnancy

Abstract This current investigation was aimed to generate signals for adverse drug events of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All adverse event (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), 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 10756 AE reports were identified commonly observed in cardiovascular, endocrine, musculoskeletal, gastrointestinal, hepatobiliary, 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 associated with multiple adverse pregnancy conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.

scholarly journals Development of a Network-Based Signal Detection Tool: The COVID-19 Adversome in the FDA Adverse Event Reporting System

2021 ◽  
Vol 12 ◽  
Author(s):  
Michele Fusaroli ◽  
Emanuel Raschi ◽  
Milo Gatti ◽  
Fabrizio De Ponti ◽  
Elisabetta Poluzzi
Keyword(s):  
Adverse Event ◽  
Signal Detection ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Vein Thrombosis ◽  
Spontaneous Reports ◽  
Effective Signal

Introduction: The analysis of pharmacovigilance databases is crucial for the safety profiling of new and repurposed drugs, especially in the COVID-19 era. Traditional pharmacovigilance analyses–based on disproportionality approaches–cannot usually account for the complexity of spontaneous reports often with multiple concomitant drugs and events. We propose a network-based approach on co-reported events to help assessing disproportionalities and to effectively and timely identify disease-, comorbidity- and drug-related syndromes, especially in a rapidly changing low-resources environment such as that of COVID-19.Materials and Methods: Reports on medications administered for COVID-19 were extracted from the FDA Adverse Event Reporting System quarterly data (January–September 2020) and queried for disproportionalities (Reporting Odds Ratio corrected for multiple comparisons). A network (the Adversome) was estimated considering events as nodes and conditional co-reporting as links. Communities of significantly co-reported events were identified. All data and scripts employed are available in a public repository.Results: Among the 7,082 COVID-19 reports extracted, the seven most frequently suspected drugs (remdesivir, hydroxychloroquine, azithromycin, tocilizumab, lopinavir/ritonavir, sarilumab, and ethanol) have shown disproportionalities with 54 events. Of interest, myasthenia gravis with hydroxychloroquine, and cerebrovascular vein thrombosis with azithromycin. Automatic clustering identified 13 communities, including a methanol-related neurotoxicity associated with alcohol-based hand-sanitizers and a long QT/hepatotoxicity cluster associated with azithromycin, hydroxychloroquine and lopinavir-ritonavir interactions.Conclusion: Findings from the Adversome detect plausible new signals and iatrogenic syndromes. Our network approach complements traditional pharmacovigilance analyses, and may represent a more effective signal detection technique to guide clinical recommendations by regulators and specific follow-up confirmatory studies.

scholarly journals Immune Checkpoint Inhibitors-related Myocarditis in Patients With Cancer: an Analysis of International Spontaneous Reporting Systems

2020 ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
yong zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Toxic Effects ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Post Marketing

Abstract Background:Immune checkpoint inhibitors induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of PD-1, PD-L1 and CTLA-4 inhibitors by mining the real-world data reported in two international pharmacovigilance databases.Methods: We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADRs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014, to December 31, 2019, and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining methods were used to detect the signal of five fatal toxic effects caused by ICIs.Results: Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADEwasipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Elderly patients and male patients were more likely to develop ICIs-related myocarditis.The results of signal detection showed that the risk of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCNPP)method was the strongest.Conclusion:The findings of this study showed the risk of developing myocarditis and other fatal ADRs when using ICIs, which are consistent with the results of previous clinical trials and can provide a reference for clinical workers when using ICIs.

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