Clozapine and hematologic adverse reactions: Impact of the Risk Evaluation and Mitigation Strategy program

Abstract Introduction In October 2015, the Food and Drug Administration (FDA) instituted an update to the mandatory Risk Evaluation and Mitigation Strategy (REMS) program for clozapine to improve safety monitoring of hematologic events. However, the impact of the clozapine REMS program on reporting of hematologic adverse events has not been quantified. Methods We assessed adverse event reports for agranulocytosis, granulocytopenia, leukopenia, and neutropenia from the FDA Adverse Event Reporting System (FAERS) for a 1-year time period before (October 2014 to September 2015, pre-REMS) and after (October 2015 to September 2016, post-REMS) the implementation of the clozapine REMS program. The AERSMine platform was used to capture historical effect estimates (October 2004 to September 2014). Reporting odds ratios (ROR), proportional reporting ratios (PRR), and corresponding Taylor series 95% confidence intervals (CIs) were calculated for hematologic events with clozapine compared with all other medications using OpenEpi. Results Reporting rates for agranulocytosis, granulocytopenia, leukopenia, and neutropenia with clozapine all increased from the pre-REMS to post-REMS time frames, ranging from a 2-fold increase with leukopenia to a 40-fold increase with neutropenia; the composite measure of all hematologic reports had a 12-fold increase. During the post-REMS time frame, the ROR increased by 1691% (111.4, 95% CI 100.6-123.4) compared with the pre-REMS time frame (7.1, 95% CI 5.2-9.6), and the PRR increased by 1280% (83.1, 95% CI 76.8-90.0 vs 6.9, 95% CI 5.1-9.4) for the composite outcome. Discussion We observed significant increases in reports of hematologic adverse events with clozapine after the introduction of the clozapine REMS program. Future research should explore the impact of the less stringent exclusionary and discontinuation criteria on utilization (eg, expanded access) and clinical outcomes (eg, treatment effectiveness and adverse events).

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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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The Irish National Adverse Event Study-2 (INAES-2): longitudinal trends in adverse event rates in the Irish healthcare system

BMJ Quality & Safety ◽

10.1136/bmjqs-2020-011122 ◽

2021 ◽

pp. bmjqs-2020-011122 ◽

Cited By ~ 1

Author(s):

Warren Connolly ◽

Natasha Rafter ◽

Ronan M Conroy ◽

Cornelia Stuart ◽

Anne Hickey ◽

...

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Positive Impact ◽

Retrospective Chart Review ◽

Published Data ◽

National Programmes ◽

Event Rates ◽

Hospital Associated Infections ◽

Design And Methods ◽

The Impact

ObjectivesTo quantify the prevalence and nature of adverse events in acute Irish hospitals in 2015 and to assess the impact of the National Clinical Programmes and the National Clinical Guidelines on the prevalence of adverse events by comparing these results with the previously published data from 2009.Design and methodsA retrospective chart review of 1605 admissions to eight Irish hospitals in 2015, using identical methods to those used in 2009.ResultsThe percentage of admissions associated with one or more adverse events was unchanged (p=0.48) at 14% (95% CI=10.4% to 18.4%) in 2015 compared with 12.2% (95% CI=9.5% to 15.5%) in 2009. Similarly, the prevalence of preventable adverse events was unchanged (p=0.3) at 7.4% (95% CI=5.3% to 10.5%) in 2015 compared with 9.1% (95% CI=6.9% to 11.9%) in 2009. The incidence densities of preventable adverse events were 5.6 adverse events per 100 admissions (95% CI=3.4 to 8.0) in 2015 and 7.7 adverse events per 100 admissions (95% CI=5.8 to 9.6) in 2009 (p=0.23). However, the percentage of preventable adverse events due to hospital-associated infections decreased to 22.2% (95% CI=15.2% to 31.1%) in 2015 from 33.1% (95% CI=25.6% to 41.6%) in 2009 (p=0.01).ConclusionAdverse event rates remained stable between 2009 and 2015. The percentage of preventable adverse events related to hospital-associated infection decreased, which may represent a positive impact of the related national programmes and guidelines.

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Adverse events following adenovirus type 4 and type 7 vaccine, live, oral in the Vaccine Adverse Event Reporting System (VAERS), United States, October 2011–July 2018

Vaccine ◽

10.1016/j.vaccine.2019.08.087 ◽

2019 ◽

Vol 37 (44) ◽

pp. 6760-6767 ◽

Cited By ~ 2

Author(s):

Michael M. McNeil ◽

Iwona Paradowska-Stankiewicz ◽

Elaine R. Miller ◽

Paige L. Marquez ◽

Srihari Seshadri ◽

...

Keyword(s):

United States ◽

Adverse Event ◽

Adverse Events ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adenovirus Type ◽

Adverse Event Reporting ◽

Event Reporting

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Descriptive epidemiology of adverse events after immunization: Reports to the Vaccine Adverse Event Reporting System (VAERS), 1991-1994

The Journal of Pediatrics ◽

10.1016/s0022-3476(97)70056-8 ◽

1997 ◽

Vol 131 (4) ◽

pp. 529-535 ◽

Cited By ~ 32

Author(s):

M.Miles Braun ◽

Susan S. Ellenberg

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Descriptive Epidemiology ◽

Event Reporting

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Safety of SGLT2 Inhibitors: A Pharmacovigilance Study From 2015 to 2020 Based on FDA Adverse Event Report System Database

10.22541/au.162109370.02304837/v1 ◽

2021 ◽

Author(s):

Xiang Zhou ◽

Xiaofei Ye ◽

Yinghong Zhai ◽

Fangyuan Hu ◽

Yongqing Gao ◽

...

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Diabetic Ketoacidosis ◽

Adverse Event Reporting System ◽

Kidney Injury ◽

Adverse Event Reporting ◽

Adverse Event Report ◽

System Database ◽

Report System ◽

Euglycemic Diabetic Ketoacidosis

Aim: With the widespread use of SGLT2i, various adverse events (AEs) have been reported. This study aimed to describe the distribution of SGLT2i-related AEs in different systems, quantify the association of important medical events (IMEs) and SGLT2i regimens, and build a signal profile of SGLT2i- induced IMEs. Methods: Data from 2015 Q1 to 2020 Q4 in the FDA Adverse Event Reporting System database (FAERS) were selected to conduct disproportionality analysis. Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to evaluate the correlation between SGLT2i and IMEs. The lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed a signal. For ROR, it was defined a signal if ROR025 over one, with at least 3 cases. Results: A total of 45,771,436 records were involved, including 111,564 records related to SGLT2i, with 38,366 records of SGLT2i-induced IMEs. Overall, SGLT2i was significantly associated with IMEs (IC=0.36, 95% CI: 0.35-0.38; ROR=1.44, 95% CI: 1.42-1.46). Most SGLT2i-related adverse events occurred in monotherapy (92.93%). Diabetic ketoacidosis was the most IMEs. Specifically, acute osteomyelitis has the strongest signal of all SGLT2i (IC025=7.83), and it was unique to canagliflozin. Diabetic ketoacidosis, acute kidney injury, ketoacidosis, Fournier’s gangrene, and euglycemic diabetic ketoacidosis were common to the four FDA-approved SGLT2i. Conclusion: Our study demonstrated that different SGLT2i regimens lead to different important adverse events, but there are overlapping events. Early identification and management of SGLT2i-associated IMEs are essential for clinical practice.

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