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Journal of Computer-aided Molecular... Dec 2023DrugCentral, accessible at https://drugcentral.org , is an open-access online drug information repository. It covers over 4950 drugs, incorporating structural,... (Review)
Review
DrugCentral, accessible at https://drugcentral.org , is an open-access online drug information repository. It covers over 4950 drugs, incorporating structural, physicochemical, and pharmacological details to support drug discovery, development, and repositioning. With around 20,000 bioactivity data points, manual curation enhances information from several major digital sources. Approximately 724 mechanism-of-action (MoA) targets offer updated drug target insights. The platform captures clinical data: over 14,300 on- and off-label uses, 27,000 contraindications, and around 340,000 adverse drug events from pharmacovigilance reports. DrugCentral encompasses information from molecular structures to marketed formulations, providing a comprehensive pharmaceutical reference. Users can easily navigate basic drug information and key features, making DrugCentral a versatile, unique resource. Furthermore, we present a use-case example where we utilize experimentally determined data from DrugCentral to support drug repurposing. A minimum activity threshold t should be considered against novel targets to repurpose a drug. Analyzing 1156 bioactivities for human MoA targets suggests a general threshold of 1 µM: t = 6 when expressed as - log[Activity(M)]). This applies to 87% of the drugs. Moreover, t can be refined empirically based on water solubility (S): t = 3 - logS, for logS < - 3. Alongside the drug repurposing classification scheme, which considers intellectual property rights, market exclusivity protections, and market accessibility, DrugCentral provides valuable data to prioritize candidates for drug repurposing programs efficiently.
Topics: Humans; Molecular Structure; Drug-Related Side Effects and Adverse Reactions; Drug Repositioning; Drug Discovery; Drug Delivery Systems
PubMed: 37707619
DOI: 10.1007/s10822-023-00529-x -
European Psychiatry : the Journal of... Nov 2023Recent reports of individuals experiencing suicidal and/or self-injurious behaviors while using liraglutide and semaglutide have heightened the concerns regarding...
BACKGROUND
Recent reports of individuals experiencing suicidal and/or self-injurious behaviors while using liraglutide and semaglutide have heightened the concerns regarding neuropsychiatric safety of Glucagon-like peptide-1 agonists (GLP-1RAs). As real-world evidence is very limited, we explored the association between GLP-1RA and suicide/self-injury by mining the FDA Adverse Event Reporting System (FAERS) database.
METHODS
The FAERS database was queried from 2005 Q2 to 2023 Q2. The Reporting Odds Ratio (ROR) and Empirical Bayes Geometric Mean (EBGM) were used to conduct the disproportionality analysis.
RESULTS
A total of 534 GLP-1RA-associated suicide/self-injury cases were reported in the FAERS during the study period. GLP-1RA did not cause a disproportionate increase in overall suicidal and self-injurious cases (ROR: 0.16, 95%CI 0.15-0.18, P < 0.001; EBGM05: 0.15). Stratified analyses found no safety signal of suicide/injury for GLP-1RA in both females and males. The ROR for suicide/self-injury with GLP-1RA was slightly elevated (ROR: 2.50, 95%CI 1.02-6.13, P = 0.05) in children, while the EBGM05 was < 2 in this population. No significant signal value was observed in other age groups. No over-reporting of suicide/self-injury was identified for GLP-1RA before or after the COVID-19 pandemic outbreak.
CONCLUSIONS
The cases of suicide or self-injury reported to FAERS do not indicate any overall safety signal attributable to GLP-1RA at this time. Subgroup analysis revealed a marginal elevation of ROR for suicide and self-injury with GLP-1RA in children, but no safety signal was detected by EBGM05 in this population. Further large-scale prospective investigations are still warranted to further confirm this finding.
Topics: Male; Female; Child; Humans; Glucagon-Like Peptide-1 Receptor Agonists; Pharmacovigilance; Bayes Theorem; Pandemics; Prospective Studies; Suicide
PubMed: 38031404
DOI: 10.1192/j.eurpsy.2023.2474 -
Therapie 2023Nirmatrelvir/ritonavir (Paxlovid®) is currently one of the few therapeutic options for coronavirus disease 2019 (COVID-19) curative treatment in non-oxygen-requiring...
INTRODUCTION
Nirmatrelvir/ritonavir (Paxlovid®) is currently one of the few therapeutic options for coronavirus disease 2019 (COVID-19) curative treatment in non-oxygen-requiring adult patients at-high risk of progressing to severe disease. This recently approved boosted antiviral therapy presents a significant risk of drug-drug interactions (DDI). As part of the enhanced surveillance program in France for COVID-19 drugs and vaccines, the French national pharmacovigilance database (BNPV [base nationale de pharmacovigilance]) was queried in order to better characterize the drug safety profile, with a special focus on DDI. The aim of the study was to describe the adverse drug reactions reported through the BNPV.
METHOD
All nirmatrelvir/ritonavir reports validated in the BNPV from the first authorization in France (January, 20th 2022) to December, 3rd 2022 (date of the query) were considered. An analysis of the scientific literature (PubMed®) and from the WHO pharmacovigilance database (Vigibase) was also performed.
RESULTS
Over this period (11 months), 228 reports (40% of serious reports) were registered with a sex ratio of 1.9 female/1 male and a mean age of 66 years old. DDI reports account for more than 13% of reports (n=30) and were mainly related to immunosuppressive drugs overexposure (n=16). A total of 10/228 reports with fatal outcomes were reported in complex clinical settings. The main reported unexpected adverse drug reaction (ADRs) were high blood pressure (n=7), confusion (n=5), acute kidney injuries (AKI, n=7) and various skin reactions (n=22). Apart from situations of disease recurrence (not found in this analysis), data from Pubmed® and Vigibase also reported the above-mentioned events of interest.
CONCLUSION
Overall, this analysis shows that nirmatrelvir/ritonavir safety profile was conform to current summary of product characteristics (SmPC). The main concern was the risk of DDI. Therefore, SmPC and expert recommendations should be systematically consulted before initiation of this antiviral, which is particularly indicated in polypharmacy patients. A case-by-case multidisciplinary approach including a clinical pharmacologist is required in these complex situations. Blood pressure elevation, confusion, cutaneous reactions and AKIs were the main unexpected ADRs of interest to follow, but need to be confirmed with a qualitative approach over time and new reports.
PubMed: 37012153
DOI: 10.1016/j.therap.2023.03.001 -
Therapeutic Advances in Drug Safety 2023An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings is the lack of adequate funds to establish a functional National...
BACKGROUND
An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings is the lack of adequate funds to establish a functional National Pharmacovigilance System. Consequently, the crucial function of monitoring and ensuring the availability of safe medicines in these settings cannot be guaranteed considering the peculiarities of diseases and medicines used.
OBJECTIVES
The objective of this paper is to provide an overview as to the availability of potential sources of funds, which could be explored to ensure Medicine Safety and to proffer a potential framework likely to ensure sustainable funding of PV in Africa.
METHODS/PROCESSES
The process of developing this framework entailed a review of PV financing in some developed economies, a landscape study of funding of PV in some African countries, an in-depth understanding of the PV system and the organisational structure and nexus between the regulatory agencies and National Pharmacovigilance Centre. Critical points for consideration included the sources of funds, revenue pool, the disbursement of funds, budgeting and expenditure profile and the legal framework. Consultative meetings, webinars and interviews with experts were carried out.
RESULTS
The findings showed that most of the PV systems were mainly integrated into the regulatory agencies regarding operational and fiscal governance with few facilities being independent of the regulatory agencies. The main source of funding was from the government with significant donor funding which is ad hoc and non-sustainable. Several potential sources were identified but yet to be exploited. There were no legal provisions for PV financing. A framework likely to ensure sustainable PV financing is suggested to capture all available sources of funding, mine the potential sources providing a sizeable pool of revenue to address its activities and enabling legal framework which will engender autonomy. Furthermore, it will address the nexus between the regulatory agencies and the PV outfits, thus enabling appropriate share of resources and blockage of diversions.
CONCLUSION
In all, addressing the various elements identified in this study and providing the legal provisions which guarantees some degree of autonomy will provide a sustainable mechanism for PV funding in the resource-limited setting of Africa.
PubMed: 37529763
DOI: 10.1177/20420986231188836 -
European Neuropsychopharmacology : the... May 2024The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA).
Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis.
INTRODUCTION
The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA).
AIM
The aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators.
METHODS
Descriptive and pharmacovigilance disproportionality analyses was performed.
RESULTS
A total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 'serious' cases related to selected ADRs were registered during 2005-2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide).
DISCUSSION
Suicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations.
CONCLUSIONS
With the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Pharmacovigilance; Male; Female; Suicidal Ideation; Adult; Middle Aged; Self-Injurious Behavior; Anti-Obesity Agents; Adverse Drug Reaction Reporting Systems; Metformin; Weight Loss; Aged; Liraglutide; Orlistat; Hypoglycemic Agents; Exenatide; Young Adult; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38508100
DOI: 10.1016/j.euroneuro.2024.02.003 -
Journal of Clinical Medicine Jul 2023Concerns remain regarding the rare cardiovascular adverse events, myocarditis and pericarditis (myo/pericarditis), particularly in younger individuals following mRNA...
Concerns remain regarding the rare cardiovascular adverse events, myocarditis and pericarditis (myo/pericarditis), particularly in younger individuals following mRNA COVID-19 vaccination. Our study aimed to comprehensively assess potential safety signals related to these cardiac events following the primary and booster doses, with a specific focus on younger populations, including children as young as 6 months of age. Using the Vaccine Adverse Events Reporting System (VAERS), the United States national passive surveillance system, we conducted a retrospective pharmacovigilance study analyzing spontaneous reports of myo/pericarditis. We employed both frequentist and Bayesian methods and conducted subgroup analyses by age, sex, and vaccine dose. We observed a higher reporting rate of myo/pericarditis following the primary vaccine series, particularly in males and mainly after the second dose. However, booster doses demonstrated a lower number of reported cases, with no significant signals detected after the fourth or fifth doses. In children and young adults, we observed notable age and sex differences in the reporting of myo/pericarditis cases. Males in the 12-17 and 18-24-year-old age groups had the highest number of cases, with significant signals for both males and females after the second dose. We also identified an increased reporting for a spectrum of cardiovascular symptoms such as chest pain and dyspnea, which increased with age, and were reported more frequently than myo/pericarditis. The present study identified signals of myo/pericarditis and related cardiovascular symptoms after mRNA COVID-19 vaccination, especially among children and adolescents. These findings underline the importance for continued vaccine surveillance and the need for further studies to confirm these results and to determine their clinical implications in public health decision-making, especially for younger populations.
PubMed: 37568373
DOI: 10.3390/jcm12154971 -
Journal of Cancer 2023Trastuzumab emtansine(T-DM1) and trastuzumab deruxtecan (T-DXd, formerly DS-8201a), the human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate...
Trastuzumab emtansine(T-DM1) and trastuzumab deruxtecan (T-DXd, formerly DS-8201a), the human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC), are commonly used in metastatic breast cancer. However, their real-world safety profile has not been adequately compared. We aimed to investigate the adverse event (AE) profile of T-DM1 and T-DXd reported by the US Food and Drug Administration Adverse Event Reporting System (FAERS). All indications were searched for T-DM1 and T-DXd, as primary suspected drugs, from FAERS data (January 2004 to June 2023). Disproportionality analyses were performed by reporting odds ratios (ROR) and proportional reporting ratio (PRR). The odds ratio (OR) of fatal AEs associated with T-DM1 and T-DXd under different exposure factors were performed by univariate and multivariate logistical regression analysis. 3723 and 2045 reports of T-DM1 and T-DXd were submitted to FAERS. Finally, 94 and 61 significant signals for T-DM1 and T-DXd were systematically analyzed. The valid AEs with the highest frequency and the strongest signal intensity for T-DM1 were platelet count decreased (n=108) and hepatopulmonary syndrome (ROR=680.42), respectively. Interstitial lung disease (n=262, ROR=82.55) and pneumonitis (n=89, ROR = 48.34) showed both high frequency and strong signal intensity for T-DXd. The proportion of AEs in each SOC system was different. T-DM1 had a greater proportion of valid AEs in the nervous system, musculoskeletal system, hepatobiliary system, ocular system, cardiac system and hematologic system(<0.05). T-DXd had a greater proportion of valid AEs in the skin disorders, respiratory system, infestations, general system and gastrointestinal system(<0.05). Furthermore, the analysis of fatal AEs in four systems revealed that T-DXd exhibited a significantly higher proportion of fatal outcomes in the hematologic and respiratory system compared to T-DM1. Conversely, T-DM1 had a significantly higher proportion of fatal outcomes in the hepatobiliary system. Neither T-DM1 nor T-DXd exhibited a high mortality ratio in the cardiac system. Logistic regression analysis indicated that advanced age (≥65 years) and male gender were identified as independent risk factors of fatal AEs for both T-DM1 and T-DXd. Additionally, the drug combination therapy, particularly with a CYP3A4 inhibitor, was found to be a risk factor for fatal AEs specifically related to T-DXd. Hematological and respiratory toxicity of T-DXd and hepatobiliary toxicity of T-DM1 exhibited a high incidence of fatal outcomes. It is crucial to identify high-risk factors and enhance the monitoring of AEs during clinical application.
PubMed: 37928419
DOI: 10.7150/jca.86746 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2023The purpose of the current study was to evaluate the general public knowledge, attitudes, and practice regarding Adverse Drug Reactions (ADRs) reporting and...
OBJECTIVES
The purpose of the current study was to evaluate the general public knowledge, attitudes, and practice regarding Adverse Drug Reactions (ADRs) reporting and pharmacovigilance in Jordan.
METHODS
A cross-sectional study was conducted between July 16, 2022, and July 30, 2022, in Jordan. During the study period, an electronic survey consisting of 4 sections was administered to a convenience sample of Jordanians (aged 18 or above) using 2 social media platforms (Facebook and WhatsApp). Logistic regression analysis was used to screen the predictors of ADRs reporting by the participants.
RESULTS
A total of 441 participants completed the survey. The majority of the participants (67.6%) were females, 53.1% between 26 and 45 years old. Almost all participants (96.3%) were always aware of the indication of the medications they take, the time and frequency (87.8%), and the duration of medications (84.4%). Nearly one-third of the participants (37.4%) asked about their medications' ADRs. However, the drug information leaflet was the most frequently used source of ADR information (33.3%). The majority of responders believed that both healthcare providers and consumers should report ADRs (93.4% and 80.3%, respectively). Only one-quarter of respondents (27.2%) believed that consumers could directly report ADRs through the Jordan pharmacovigilance program. The majority of patients who had experienced ADRs (70.3%) were aware that ADRs should be reported, and among them, 91.9% had reported the ADRs to healthcare providers. Furthermore, few participants (8.1%) reported it to the Jordan National Pharmacovigilance Centre (JNCP). Linear regression revealed that none of the demographic characteristics (age, gender, education, job, and social status) were affecting public reporting practice of the ADRs (P > 0.05 for all).
CONCLUSION
Respondents showed fair knowledge about adverse drug reactions and their reporting. However, there is a need to initiate educational activities and intervention programs to raise awareness about the JNPC, which will have a positive impact on public health and ensure safe medication use in Jordan.
PubMed: 37273263
DOI: 10.1016/j.jsps.2023.05.016 -
Orphanet Journal of Rare Diseases Sep 2023The aims of this paper is to search and explore publications in the field of pharmacovigilance for rare diseases and to visualize general information, research hotspots,... (Review)
Review
OBJECTIVES
The aims of this paper is to search and explore publications in the field of pharmacovigilance for rare diseases and to visualize general information, research hotspots, frontiers and future trends in the field using the bibliometric tool CiteSpace to provide evidence-based evidence for scholars.
METHODS
We searched the Web of Science Core Collection (WoSCC) for studies related to pharmacovigilance for rare diseases, spanning January 1, 1997-October 25, 2022. CiteSpace software was utilized to discuss countries/regions, institutions, authors, journals, and keywords.
RESULTS
After screening, a total of 599 valid publications were included in this study, with a significant upward trend in the number of publications. These studies were from 68 countries/regions with the United States and the United Kingdom making the largest contributions to the field. 4,806 research scholars from 493 institutions conducted studies on pharmacovigilance for rare diseases. Harvard University and University of California were the top two productive institutions in the research field. He Dian of the Affiliated Hospital of Guizhou Medical University and Peter G.M. Mol of the University of Groningen, The Netherlands, were the two most prolific researchers. The Cochrane Database of Systematic Reviews and the New England Journal of Medicine were the journals with the highest number of articles and co-citation frequency respectively. Clinical trial, therapy and adverse event were the top three most cited keywords.
CONCLUSIONS
Based on keywords co-occurrence analysis, four research topics were identified: orphan drug clinical trials, postmarketing ADR surveillance for orphan drugs, rare diseases and orphan drug management, and diagnosis and treatment of rare diseases. Immune-related adverse reactions and benefit-risk assessment of enzyme replacement therapy were at the forefront of research in this field. Treatment outcomes, early diagnosis and natural history studies of rare diseases may become hotspots for future research.
Topics: Male; Humans; Rare Diseases; Pharmacovigilance; Systematic Reviews as Topic; Bibliometrics; Databases, Factual
PubMed: 37752556
DOI: 10.1186/s13023-023-02915-y -
Therapeutic Advances in Drug Safety 2023The relatively new discipline of pharmacovigilance (PV) aims to monitor the safety of drugs throughout their evolution and is essential to discovering new drug risks.... (Review)
Review
The relatively new discipline of pharmacovigilance (PV) aims to monitor the safety of drugs throughout their evolution and is essential to discovering new drug risks. Due to their specific and complex physiology, children, pregnant women, and elderly adults are more prone to adverse drug reactions (ADRs). Additionally, the lack of clinical trial data exacerbates the challenges faced with pharmacotherapy in these populations. Elderly patients tend to have multiple comorbidities often requiring more extensive medication, which adds additional challenges for healthcare professionals (HCPs) in delivering safe and effective pharmacotherapy. Clinical trials often have inherent limitations, including insufficient sample size and limited duration of research; as some ADRs are attributed to long-term use of a drug, these may go undetected during the course of the trial. Therefore, the implementation of PV is key to insuring the safe and effective use of drugs in special populations. We conducted a thorough review of the scientific literature on PV systems across the European Union, the United States, and China. Our review focused on basic physiological characteristics, drug use, and PV for specific populations (children, pregnant women, and the elderly). This article aims to provide a reference for the development of follow-up policies and improvement of existing policies as well as provide insight into drug safety with respect to patients of special populations.
PubMed: 37780667
DOI: 10.1177/20420986231200746