-
BMC Pharmacology & Toxicology Nov 2023Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety...
BACKGROUND
Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety of pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain adverse events were present.
METHODS
In disproportionality analysis, four algorithms were employed to detect the signals of pertuzumab from the FAERS between 2012 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the potential and high-ROR (reporting odds ratio) signals of pertuzumab. We also collected the onset times of pertuzumab-associated AEs.
RESULTS
From January 2012 to December 2022, there are 39,190,598 AEs reported from the FAERS database, of which 14,707 AEs listed pertuzumab as the 'primary suspected (PS)' drug. A total of 115 (46 potential) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained. Finally, we detected that the pertuzumab-induced AEs occurred in 12 organ systems. For pertuzumab, unexpected and significant PTs of AEs were found, including but not limited to below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, and circulatory collapse. We found there were 9 strong signals (5 potential safety signals) and 68 medium intensity signals (21 potential safety signals) according to IC (information component). The potential strong signals (IC > 3.0) were myelosuppression, cardiotoxicity, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, and onychomadesis. Excluding unreported or unreasonable onset time reports, a total of 2016 AEs reported onset time and the median onset time was 117 days (4, 96), as median (Q1, Q3). Notably, most of the all AEs (n = 1133, 56%) and cardiac-related events (n = 405, 53%) all occurred within one month after pertuzumab therapy.
CONCLUSION
Analysis of FAERS data identified pertuzumab-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of pertuzumab. A significant association was detected between pertuzumab and some potential adverse events which should be regarded with some care. We have to pay attention to the first month after pertuzumab therapy and prepare emergency measures, especially for the elderly and patients with cardiovascular diseases.
Topics: Humans; Aged; Female; Cardiotoxicity; Adverse Drug Reaction Reporting Systems; Antibodies, Monoclonal, Humanized; Pharmacovigilance; Breast Neoplasms
PubMed: 37957717
DOI: 10.1186/s40360-023-00702-w -
Southern African Journal of Infectious... 2023The reporting of adverse drug reactions associated with drug-resistant tuberculosis (DR-TB) medication is important for pharmacovigilance, especially in high-burden...
BACKGROUND
The reporting of adverse drug reactions associated with drug-resistant tuberculosis (DR-TB) medication is important for pharmacovigilance, especially in high-burden countries such as South Africa. With DR-TB treatment being so dynamic, it is important to understand adverse event reporting practices at specialised facilities.
OBJECTIVES
The study aimed to understand the adverse drug reaction (ADR) reporting practices at DR-TB treatment facilities in South Africa.
METHOD
Interviews were conducted with healthcare workers at specialised DR-TB facilities. This was to collect data on demographics, pharmacovigilance training, and determine attitudes and practices towards reporting adverse events. A checklist was developed to review the most recent adverse event forms captured at the facility.
RESULTS
Most participants did not have adverse event reporting training since their initial training but were confident that they could complete a form themselves. Most participants could correctly identify the major adverse events associated with DR-TB medication, but some deemed non-adverse events as plausible. Adverse event report forms were not standardised with most participants deeming further training and regular feedback as reasons to report ADRs.
CONCLUSION
Standardisation of adverse event report forms used and the establishment of regular reporting will increase adverse event reporting at DR-TB facilities. Continuous training, empowerment and expansion of staff categories eligible to report adverse events will enhance and sustain such practice.
CONTRIBUTION
The study highlights challenges faced by healthcare professionals in reporting adverse events.
PubMed: 38223433
DOI: 10.4102/sajid.v38i1.564 -
OTO Open 2023Eustachian tube balloon dilation is a minimally invasive technique used to improve persistent Eustachian tube dysfunction. Currently, the US Food and Drug Administration...
OBJECTIVE
Eustachian tube balloon dilation is a minimally invasive technique used to improve persistent Eustachian tube dysfunction. Currently, the US Food and Drug Administration (FDA) has approved the use of balloon dilation devices produced by three manufacturers, but little is known about associated adverse events and subsequent management.
STUDY DESIGN
Case series.
SETTING
FDA Manufacturer and User Facility Device Experience (MAUDE) database.
METHODS
Reports submitted to the FDA using the MAUDE database searched from January 2000 to July 2022 were analyzed for adverse events and management.
RESULTS
A total of 13 adverse events were found in the database. Subcutaneous emphysema (n = 8) was the most common event. Other less frequent events included patulous Eustachian tube (n = 2), vascular dissection (n = 1), nasopharyngeal mucocele (n = 1), and tinnitus (n = 1). A majority of patients who experienced subcutaneous emphysema received antibiotics (n = 5) and were admitted to the hospital (n = 4). The patient with a carotid dissection 7 days postprocedure presented with a stroke and fully recovered after stent placement. There was limited preprocedure information in the MAUDE database. There were 2 patients who did not fully recover after a complication. Three patients underwent corrective surgical interventions. No one company had more associated adverse events reported.
CONCLUSION
Subcutaneous emphysema is the most common adverse event after Eustachian tube dilation. Further studies exploring potential balloon dilation adverse events to allow for better patient counseling are warranted.
PubMed: 37565059
DOI: 10.1002/oto2.70 -
Journal of Patient Safety Aug 2023A retrospective descriptive analysis of patient safety events related to COVID-19 was performed on data that were submitted in the Joint Patient Safety Event Reporting...
METHODS
A retrospective descriptive analysis of patient safety events related to COVID-19 was performed on data that were submitted in the Joint Patient Safety Event Reporting System and Root Cause Analysis databases to the VHA National Center for Patient Safety from March 2020 to February 2021. Events were coded for type of event, location, and cause of event.
RESULTS
Delays in care and staff/patients exposed to COVID-19 were the most common types of patient safety events, followed by COVID-19-positive patients eloping, laboratory processing errors, and one wrong procedure. The most frequently cited locations where events took place were emergency departments, medical units, community living centers, and intensive care units. Confusion over procedures, care not provided because of COVID-19, and failure to identify COVID-positive patient before they exposed others to COVID were the most common causes for patient safety events.
DISCUSSION
Our results are similar to other studies of patient safety during the first year of the COVID-19 pandemic. Based on these results, we recommend the following: (1) focus on patient safety culture, leadership, and governance; (2) proactively develop competency checklists, cognitive aids, and other tools for healthcare staff who are working in new or unfamiliar clinical settings; (3) augment or enhance communication efforts with patient safety huddles or briefings at all levels within a healthcare organization to proactively uncover risk and mitigate fear by explaining changes in policies and procedures; and (4) maximize the use of quality and patient safety experts who are knowledgeable in system and human factor theories as well as change management to assist in redesigning clinical workflows and processes.
Topics: Humans; COVID-19; Patient Safety; Pandemics; Retrospective Studies; Safety Management
PubMed: 37125700
DOI: 10.1097/PTS.0000000000001129 -
The Annals of Pharmacotherapy Feb 2024Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical...
BACKGROUND
Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo.
OBJECTIVE
Our study's aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19.
METHOD
We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with "Covid-19" excluded.
RESULTS
A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively.
CONCLUSIONS AND RELEVANCE
This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.
Topics: Humans; SARS-CoV-2; COVID-19; Retrospective Studies; Ritonavir; Dysgeusia; Pharmacovigilance; Antiviral Agents
PubMed: 37144730
DOI: 10.1177/10600280231169256 -
Journal of Clinical Pharmacology Oct 2023Patients with impaired left ventricular (LV) function can develop LV thrombus, a potentially life-threatening condition due to risk of stroke and embolization.... (Review)
Review
Patients with impaired left ventricular (LV) function can develop LV thrombus, a potentially life-threatening condition due to risk of stroke and embolization. Conventional treatment with vitamin K antagonists (VKAs; e.g., warfarin) puts patients at risk of bleeding, and the use of direct oral anticoagulants (DOACs) appears promising, although data are scant. We searched the published English language literature for randomized controlled trials (RCTs) comparing DOACs with VKAs in LV thrombus. End points were failure to resolve, thromboembolic events (stroke, embolism), bleeding, or any adverse event (composite of thromboembolism or bleeding), or all-cause death. Data were pooled and analyzed in hierarchical Bayesian models. In three eligible RCTs, 141 patients were studied during an average of 4.6 months (53.8 patient-years; n = 71 assigned to DOAC, n = 70 assigned to VKA). A similar number of patients in each treatment arm demonstrated failure to resolve (DOAC: 14/71 vs. VKA: 15/70) and death events (3/71 vs. 4/70). However, patients on DOACs suffered fewer strokes/thromboembolic events (1/71 vs. 7/70; log odds ratio [OR], -2.02 [95% credible interval (CI ), -4.53 to -0.31]) and fewer bleeding events (2/71 vs. 9/70; log OR, -1.62 [CI , -3.43 to -0.26]), leading to fewer patients on DOACs with any adverse event versus VKAs (3/71 vs. 16/70; log OR, -1.93 [CI , -3.33 to -0.75]). In conclusion, pooled analysis of RCT data favors DOACs over VKAs in patients with LV thrombus in terms of both efficacy and safety.
Topics: Humans; Warfarin; Randomized Controlled Trials as Topic; Anticoagulants; Hemorrhage; Stroke; Thrombosis; Administration, Oral
PubMed: 37139934
DOI: 10.1002/jcph.2267 -
Current Eye Research Sep 2023The current study seeks to investigate the association between lacrimal disorders and the use of docetaxel and paclitaxel.
PURPOSE
The current study seeks to investigate the association between lacrimal disorders and the use of docetaxel and paclitaxel.
METHODS
A disproportionality analysis was conducted using the United States FDA Adverse Event Reporting System (FAERS). All adverse event reports containing the term docetaxel or paclitaxel were selected. Lacrimal adverse events were identified using the lacrimal disorders Standardized MedDRA Query (SMQ), which includes disorders that affect lacrimal gland and drainage system including blockage of nasolacrimal duct, occlusion/stenosis of punctum, lacrimal gland neoplasms, and inflammations and infections.
RESULTS
The proportionate reporting ratio (PRR) comparing lacrimal events among docetaxel to paclitaxel users was 2.47 (95% CI, 2.03-3.02). With respect to specific lacrimal events, dacryostenosis (PRR 19.54 [95% CI, 7.19-53.13]), increased lacrimation (PRR 3.2 [95% CI, 2.42-4.23]), lacrimation disorder ( = 0.02), and xeropthalmia reports ( > 0.001) were significantly more common.
CONCLUSIONS
The growing body of epidemiologic, clinical, and pathophysiologic research supports the case that docetaxel leads to adverse lacrimal events in certain patients and should be taken into consideration when oncologists consider docetaxel vs. paclitaxel.
Topics: Humans; United States; Docetaxel; Taxoids; Paclitaxel; Lacrimal Apparatus Diseases
PubMed: 37232564
DOI: 10.1080/02713683.2023.2219041 -
European Journal of Internal Medicine Aug 2023Renin-angiotensin-aldosterone system inhibitors (RAASi) are commonly used medications. Renal adverse events associated with RAASi are hyperkalemia and acute kidney...
BACKGROUND
Renin-angiotensin-aldosterone system inhibitors (RAASi) are commonly used medications. Renal adverse events associated with RAASi are hyperkalemia and acute kidney injury. We aimed to evaluate the performance of machine learning (ML) algorithms in order to define event associated features and predict RAASi associated renal adverse events.
MATERIALS AND METHODS
Data of patients recruited from five internal medicine and cardiology outpatient clinics were evaluated retrospectively. Clinical, laboratory, and medication data were acquired via electronic medical records. Dataset balancing and feature selection for machine learning algorithms were performed. Random forest (RF), k-nearest neighbor (kNN), naïve Bayes (NB), extreme gradient boosting (xGB), support vector machine (SVM), neural network (NN), and logistic regression (LR) were used to create a prediction model.
RESULTS
409 patients were included, and 50 renal adverse events occurred. The most important features predicting the renal adverse events were the index K and glucose levels, as well as having uncontrolled diabetes mellitus. Thiazides reduced RAASi associated hyperkalemia. kNN, RF, xGB and NN algorithms have the highest and similar AUC (≥ 98%), recall (≥ 94%), specifity (≥ 97%), precision (≥ 92%), accuracy (≥ 96%) and F1 statistics (≥ 94%) performance metrics for prediction.
CONCLUSION
RAASi associated renal adverse events can be predicted prior to medication initiation by machine learning algorithms. Further prospective studies with large patient numbers are needed to create scoring systems as well as for their validation.
Topics: Humans; Renin-Angiotensin System; Hyperkalemia; Angiotensin-Converting Enzyme Inhibitors; Prospective Studies; Retrospective Studies; Bayes Theorem; Algorithms; Machine Learning
PubMed: 37217407
DOI: 10.1016/j.ejim.2023.05.021 -
Indian Journal of Psychological Medicine Jan 2024United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse... (Review)
Review
BACKGROUND AND OBJECTIVE
United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse events (weight gain) in adult patients with schizophrenia and bipolar disorder. To opine about the safety and efficacy of OLZSAM, authors performed a systematic review and meta-analysis to convene justifiable evidence.
METHODS
A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, from inception to September 2022, with the keywords: 'olanzapine and samidorphan' and schizophrenia; and "ALKS3831" and "lybalvi." Clinical trials published in English that analyzed the efficacy and safety of OLZSAM were included. The significant outcomes included in this study were change from baseline (CFB) in Positive and Negative Syndrome Scale (PANSS) at the end of the study, the proportion of patients with weight gain at the end of the study, the proportion of patients with at least one adverse event, and the incidence of drug discontinuation due to adverse events.
RESULTS
The change in PANSS score at the end of the study was comparable among groups receiving OLZSAM and olanzapine alone: standardized mean difference (SMD) = 0.04; 95% CI = -0.09 to 0.17; = 0.57. The OLZSAM group reported less incidence of weight gain: risk ratio (RR) = 0.91; 95% CI = 0.62-1.34; = 0.63, and any adverse event: RR = 0.99; 95% CI = 0.90-1.09; = 0.81. Drug discontinuation incidence was higher in the OLZSAM group: RR = 1.22; 95% CI = 0.84-1.79; = 0.30.
CONCLUSIONS
The combination OLZSAM showed comparable efficacy to olanzapine alone in schizophrenia patients, with relatively less incidence of weight gain and adverse events; however, the drug discontinuation due to adverse events was more in the OLZSAM group.
PubMed: 38524957
DOI: 10.1177/02537176231201326 -
JACC. Cardiovascular Interventions Jul 2023Prior studies have found that female patients have worse outcomes following high-risk percutaneous coronary intervention (HRPCI). (Observational Study)
Observational Study
BACKGROUND
Prior studies have found that female patients have worse outcomes following high-risk percutaneous coronary intervention (HRPCI).
OBJECTIVES
The authors sought to evaluate sex-based differences in patient and procedural characteristics, clinical outcomes, and safety of Impella-supported HRPCI in the PROTECT III study.
METHODS
We evaluated sex-based differences in the PROTECT III study; a prospective, multicenter, observational study of patients undergoing Impella-supported HRPCI. The primary outcome was 90-day major adverse cardiac and cerebrovascular events (MACCE)-the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization.
RESULTS
From March 2017 to March 2020, 1,237 patients (27% female) were enrolled. Female patients were older, more often Black, more often anemic, and had more prior strokes and worse renal function, but higher ejection fractions compared to male patients. Preprocedural SYNTAX score was similar between sexes (28.0 ± 12.3). Female patients were more likely to present with acute myocardial infarction (40.7% vs 33.2%; P = 0.02) and more often had femoral access used for PCI and nonfemoral access used for Impella device implantation. Female patients had higher rates of immediate PCI-related coronary complications (4.2% vs 2.1%; P = 0.004) and a greater drop in SYNTAX score post-procedure (-22.6 vs -21.0; P = 0.04). There were no sex differences in 90-day MACCE, vascular complications requiring surgery, major bleeding, or acute limb ischemia. After adjustment using propensity matching and multivariable regression, immediate PCI-related complications was the only safety or clinical outcome that was significantly different by sex.
CONCLUSIONS
In this study, rates of 90-day MACCE compared favorably to prior cohorts of HRPCI patients and there was no significant sex differences. (The PROTECT III Study is a substudy of The Global cVAD Study [cVAD]; NCT04136392).
Topics: Humans; Male; Female; Coronary Artery Disease; Percutaneous Coronary Intervention; Prospective Studies; Treatment Outcome; Myocardial Infarction; Stroke; Risk Factors
PubMed: 37409991
DOI: 10.1016/j.jcin.2023.04.036