scholarly journals Safety of BRAF+MEK Inhibitor Combinations: Severe Adverse Event Evaluation

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1650
Author(s):  
Tomer Meirson ◽  
Nethanel Asher ◽  
David Bomze ◽  
Gal Markel
Keyword(s):  
Adverse Event ◽  
Adverse Event Reporting System ◽  
Mek Inhibitor ◽  
Adverse Event Reporting ◽  
Stevens Johnson Syndrome ◽  
Reporting Odds Ratio ◽  
Serious Adverse Events ◽  
Johnson Syndrome ◽  
Increased Risk ◽  
Melanoma Patients

Aim: The selective BRAF and MEK inhibitors (BRAFi+MEKi) have substantially improved the survival of melanoma patients with BRAF V600 mutations. However, BRAFi+MEKi can also cause severe or fatal outcomes. We aimed to identify and compare serious adverse events (sAEs) that are significantly associated with BRAFi+MEKi. Methods: In this pharmacovigilance study, we reviewed FDA Adverse Event Reporting System (FAERS) data in order to detect sAE reporting in patients treated with the combination therapies vemurafenib+cobimetinib (V+C), dabrafenib+trametinib (D+T) and encorafenib+binimetinib (E+B). We evaluated the disproportionate reporting of BRAFi+MEKi-associated sAEs. Significant associations were further analyzed to identify combination-specific safety signals among BRAFi+MEKi. Results: From January 2018 through June 2019, we identified 11,721 sAE reports in patients receiving BRAFi+MEKi. Comparison of BRAFi+MEKi combinations demonstrates that skin toxicities, including Stevens–Johnson syndrome, were disproportionally reported using V+C, with an age-adjusted reporting odds ratio (adj. ROR) of 3.4 (95%CI, 2.9–4.0), whereas fever was most significantly associated with D+T treatment with an adj. ROR of 1.9 (95%CI, 1.5–2.4). Significant associations using E+B treatment include peripheral neuropathies (adj. ROR 2.7; 95%CI, 1.2–6.1) and renal disorders (adj. ROR 4.1; 95%CI, 1.3–12.5). Notably, we found an increase in the proportion of Guillain–Barré syndrome reports (adj. ROR 8.5; 95%CI, 2.1–35.0) in patients administered E+B. Conclusion: BRAFi+MEKi combinations share a similar safety profile attributed to class effects, yet concomitantly, these combinations display distinctive effects that can dramatically impact patients’ health. Owing to the limitations of pharmacovigilance studies, some findings warrant further validation. However, the possibility of an increased risk for these events should be considered in patient care.

scholarly journals Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data

Diagnostics ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 76 ◽  
Author(s):  
Theodoros G. Soldatos ◽  
Antonia Dimitrakopoulou-Strauss ◽  
Lionel Larribere ◽  
Jessica C. Hassel ◽  
Christos Sachpekidis
Keyword(s):  
Adverse Event ◽  
Metastatic Melanoma ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Adverse Event Data ◽  
Increased Risk ◽  
Post Marketing ◽  
Marketing Data ◽  
Melanoma Patients ◽  
Pathophysiologic Mechanisms

Recent studies suggest that combining nivolumab with ipilimumab is a more effective treatment for melanoma patients, compared to using ipilimumab or nivolumab alone. However, treatment with these immunotherapeutic agents is frequently associated with increased risk of toxicity, and (auto-) immune-related adverse events. The precise pathophysiologic mechanisms of these events are not yet clear, and evidence from clinical trials and translational studies remains limited. Our retrospective analysis of ~7700 metastatic melanoma patients treated with ipilimumab and/or nivolumab from the FDA Adverse Event Reporting System (FAERS) demonstrates that the identified immune-related reactions are specific to ipilimumab and/or nivolumab, and that when the two agents are administered together, their safety profile combines reactions from each drug alone. While more prospective studies are needed to characterize the safety of ipilimumab and nivolumab, the present work constitutes perhaps the first effort to examine the safety of these drugs and their combination based on computational evidence from real world post marketing data.

scholarly journals Assessment of the Potential Adverse Events Related to Ribavirin-Interferon Combination for Novel Coronavirus Therapy

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Wenya Shan ◽  
Dongsheng Hong ◽  
Jieqiang Zhu ◽  
Qingwei Zhao
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Drug Event ◽  
Reporting Odds Ratio ◽  
Serious Adverse Events ◽  
Bayesian Confidence Interval ◽  
Novel Coronavirus ◽  
Safety Signals

Purpose. We aimed to analyze and evaluate the safety signals of ribavirin-interferon combination through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide reference for the rationale use of these agents in the management of relevant toxicities emerging in patients with novel coronavirus pneumonia (COVID-19). Methods. Reports to the FAERS from 1 January 2004 to 8 March 2020 were analyzed. The proportion of report ratio (PRR), reporting odds ratio (ROR), and Bayesian confidence interval progressive neural network (BCPNN) method were used to detect the safety signals. Results. A total of 55 safety signals were detected from the top 250 adverse event reactions in 2200 reports, but 19 signals were not included in the drug labels. All the detected adverse event reactions were associated with 13 System Organ Classes (SOC), such as gastrointestinal, blood and lymph, hepatobiliary, endocrine, and various nervous systems. The most frequent adverse events were analyzed, and the results showed that females were more likely to suffer from anemia, vomiting, neutropenia, diarrhea, and insomnia. Conclusion. The ADE (adverse drug event) signal detection based on FAERS is helpful to clarify the potential adverse events related to ribavirin-interferon combination for novel coronavirus therapy; clinicians should pay attention to the adverse reactions of gastrointestinal and blood systems, closely monitor the fluctuations of the platelet count, and carry out necessary mental health interventions to avoid serious adverse events.

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

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.

scholarly journals Thrombocytopenia with Tedizolid and Linezolid

2017 ◽  
Vol 62 (1) ◽  
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).

Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database

2020 ◽  
pp. 135245852094998
Author(s):  
Natalia Gonzalez Caldito ◽  
Afsaneh Shirani ◽  
Amber Salter ◽  
Olaf Stuve
Keyword(s):  
Adverse Event ◽  
B Cell ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Event Reporting ◽  
Oral Herpes ◽  
Anti Cd20 ◽  
Related Reaction

Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared. Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug–AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR025) exceeded 1. Results: There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug–AE association for rituximab and ocrelizumab were ear pruritus (ROR025: 47.53) and oral herpes (ROR025: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively). Conclusion: This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies.

scholarly journals 1977. Comparing Acute Kidney Injury Risk among Antibiotic Classes: A Study of the FDA Adverse Event Reporting System (FAERS)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S662-S662
Author(s):  
Taylor M Patek ◽  
Chengwen Teng ◽  
Kaitlin E Kennedy ◽  
Christopher R Frei
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Event ◽  
Injury Risk ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Kidney Injury ◽  
Adverse Event Reporting ◽  
Drug Event ◽  
Event Reporting ◽  
Increased Risk

Abstract Background A recent article published in 2018 studied the FDA Adverse Event Reporting System (FAERS) and listed the most common medications associated with acute kidney injury (AKI) based on number of AKI reports. In regards to antibiotics, the study only ranked vancomycin, fluoroquinolones, penicillin combinations, and trimethoprim–sulfamethoxazole as having a significant association with AKI. The objective of this study was to evaluate those and additional antibiotic classes using FAERS, and to compare their risk associated with this adverse drug event. Methods FAERS reports from January 1, 2015 to December 31, 2017 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify AKI cases. Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95% CI) for the association between antibiotics and AKI were calculated. An association was considered statistically significant when the lower limit of the 95% CI was greater than 1.0. Results A total of 2,042,801 reports (including 20,138 acute kidney injury reports) were considered, after inclusion criteria were applied. Colistin had the greatest proportion of AKI reports, representing 25% of all colistin reports. Acute kidney injury RORs (95% CI) for antibiotics were (in descending order): colistin 33.10 (21.24–51.56), aminoglycosides 17.41 (14.49–20.90), vancomycin 15.28 (13.82–16.90), trimethoprim-sulfamethoxazole 13.72 (11.94–15.76), penicillin combinations 7.95 (7.09–8.91), clindamycin 6.46 (5.18–8.04), cephalosporins 6.07 (5.23–7.05), daptomycin 6.07 (4.61–7.99), macrolides 3.60 (3.04–4.26), linezolid 3.48 (2.54–4.77), carbapenems 3.31 (2.58–4.25), metronidazole 2.55 (1.94–3.36), tetracyclines 1.73 (1.26–2.36), and fluoroquinolones 1.71 (1.49–1.97). Conclusion This study found 17 classes of antibiotics and combinations that were significantly associated with AKI compared with four antibiotics that were mentioned in a recently published article looking at drug-associated AKI. While this study confirmed previous literature of certain antibiotics associated with increased risk of AKI, it also compared antibiotics within classes and provided additional insight regarding which antibiotics had the highest associated risk of an AKI. Disclosures All authors: No reported disclosures.

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