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Therapie 2022Protein kinase inhibitors experienced their advent in the 2000s. Their market introduction made it possible to constitute a class of targeted therapies administered... (Review)
Review
Protein kinase inhibitors experienced their advent in the 2000s. Their market introduction made it possible to constitute a class of targeted therapies administered orally. This name was chosen to mark a break with conventional chemotherapy drugs, but it is important to stress that these are multi-target drugs with complex affinity profiles. Adverse effects can be explained by direct interactions with their targets of interest, chosen for their indications (on-target) but also interactions with other targets (off-target). The adverse effect profiles of these drugs are therefore varied and it is possible to identify common profiles related to inhibitions of common targets. Identification of these targets has improved the global understanding of the pathophysiological mechanisms underlying the onset of adverse drug reactions as well as of the related diseases, and makes it possible to predict the adverse effect profile of new protein kinase inhibitors based on their affinities. In this review, we describe the main adverse drug reactions associated with protein kinase inhibitors, their frequency and their plausible mechanisms of action.
Topics: Adverse Drug Reaction Reporting Systems; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacovigilance; Protein Kinase Inhibitors
PubMed: 34895753
DOI: 10.1016/j.therap.2021.11.004 -
Drug Safety Jan 2021Pharmaceutical legislation provides a legal framework to ensure the safe and effective use of medicines. This framework requires national regulatory authorities (NRAs)... (Review)
Review
Pharmaceutical legislation provides a legal framework to ensure the safe and effective use of medicines. This framework requires national regulatory authorities (NRAs) to establish and maintain a pharmacovigilance system (PV system) stating and enforcing the regulatory commitments that key stakeholders, including marketing authorisation holders (MAHs), are required to fulfil. In recent years, national legislative bodies and NRAs across the world have issued a significant amount of legislation and guidance enforcing the obligation to perform pharmacovigilance activities. In countries where the NRA is a member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), safety management requirements are generally consistent with ICH guidelines. In a number of countries beyond this scope, requirements may deviate from internationally agreed standards, adding a substantial complexity and increasing burden on the stakeholders involved, whilst the benefit for patients' safety may not be evident. Committed to fulfilling safety-regulatory obligations in any country where a product licence is held, global pharmaceutical companies have accumulated a broad and deep experience acquired whilst meeting the expectations of a large array of diverse PV systems across the world. These range from sub-optimal frameworks, according to the World Health Organization (WHO) Global Benchmarking Tool, to highly effective resource-optimised PV systems. In order to support countries creating or further developing their PV systems, especially where infrastructure and resources are limited, the European Federation of Pharmaceutical Industries and Associations (EFPIA) International Pharmacovigilance Group (IPVG) has developed consensus recommendations consistent with harmonised standards for the development and step-wise implementation of key PV system components. These recommendations endorsed by the EFPIA membership constitute the focus of this review article.
Topics: Consensus; Drug Industry; Humans; Patient Safety; Pharmacovigilance; World Health Organization
PubMed: 33289904
DOI: 10.1007/s40264-020-01008-0 -
Trends in Pharmacological Sciences Jun 2022Researchers, regulatory agencies, and the pharmaceutical industry are moving towards precision pharmacovigilance as a comprehensive framework for drug safety assessment,... (Review)
Review
Researchers, regulatory agencies, and the pharmaceutical industry are moving towards precision pharmacovigilance as a comprehensive framework for drug safety assessment, at the service of the individual patient, by clustering specific risk groups in different databases. This article explores its implementation by focusing on: (i) designing a new data collection infrastructure, (ii) exploring new computational methods suitable for drug safety data, and (iii) providing a computer-aided framework for distributed clinical decisions with the aim of compiling a personalized information leaflet with specific reference to a drug's risks and adverse drug reactions. These goals can be achieved by using 'smart hospitals' as the principal data sources and by employing methods of precision medicine and medical statistics to supplement current public health decisions.
Topics: Adverse Drug Reaction Reporting Systems; Data Collection; Drug Industry; Drug-Related Side Effects and Adverse Reactions; Hospitals; Humans; Pharmacovigilance
PubMed: 35490032
DOI: 10.1016/j.tips.2022.03.009 -
Sultan Qaboos University Medical Journal May 2021
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Oman; Pharmacovigilance
PubMed: 34221460
DOI: 10.18295/squmj.2021.21.02.001 -
Drug Safety May 2022Authors' views on the role of artificial intelligence and machine learning in pharmacovigilance. (MP4 139807 kb).
Authors' views on the role of artificial intelligence and machine learning in pharmacovigilance. (MP4 139807 kb).
Topics: Artificial Intelligence; Humans; Machine Learning; Pharmacovigilance
PubMed: 35579805
DOI: 10.1007/s40264-022-01177-0 -
BMJ Open Sep 2023The slow progress of pharmacovigilance (PV) in low-income and middle-income countries (LMIC) raises questions about core challenges on the growth of PV, and the... (Review)
Review
OBJECTIVES
The slow progress of pharmacovigilance (PV) in low-income and middle-income countries (LMIC) raises questions about core challenges on the growth of PV, and the appropriateness of strategies used so far to develop PV. Therefore, this scoping review aims to describe strategies and interventions to strengthen PV in LMIC and to propose recommendations for future investments in PV capacity building.
INCLUSION CRITERIA
Publications included were primary studies, articles, policy and guideline papers, describing interventions to strengthen PV in LMIC.
METHODS
The review was conducted following the Joanna Briggs Institute (JBI) guidelines on conducting scoping reviews. Literature searches were performed in MEDLINE, EMBASE, Web of Science, PDQ-evidence, CINAHL and other relevant websites from January 1990 to January 2021. Two reviewers independently screened titles, abstracts and full texts. One reviewer performed data extraction and descriptive analysis, which were reviewed by two other reviewers.
RESULTS
10 922 unique titles were screened and 152 were eligible for full text review. Of these, 57 and an additional 13 reports from grey literature fulfilled eligibility criteria for inclusion in the review. These were grouped into two categories: (1) Interventions aimed at increasing PV knowledge and adverse drug reactions (ADR) reporting (45 papers), primarily education of healthcare professionals (HCP), alone or in combination with other interventions such as mobile and electronic reporting and (2) Interventions aimed at strengthening various components of the national PV system (25 papers), describing strategies or mixed interventions implemented at the national level, targeting different components of the national PV system.
CONCLUSIONS
Results of this review suggest that educating HCP on ADR reporting is the most common approach to build PV capacity in LMIC. Though important, education alone is insufficient and should ideally be organised within the holistic framework of strengthening national PV systems, with a focus on also building capacity for advanced activities such as signal detection.
Topics: Humans; Developing Countries; Pharmacovigilance; Educational Status; Academies and Institutes; Capacity Building; Drug-Related Side Effects and Adverse Reactions
PubMed: 37709326
DOI: 10.1136/bmjopen-2022-071079 -
Zhongguo Fei Ai Za Zhi = Chinese... Jul 2022In 2019, Drug Administration Law of China was first time proposed that the country should establish pharmacovigilance system. In 2021, the first Pharmacovigilance...
In 2019, Drug Administration Law of China was first time proposed that the country should establish pharmacovigilance system. In 2021, the first Pharmacovigilance Quality Management Standard of China was released. The proposal and implementation of pharmacovigilance were the initial stage in China, and it needed to improve the aspects of pharmacovigilance include institution, monitoring mechanism and database construction. The number of new diagnosed cancer patients in China ranked first in the world. In recent years, the marketing speed of novel antitumor drugs was accelerated, and there were many clinical trials. Therefore, antitumor pharmacovigilance was imperative. In this article, we summarized pharmacovigilance of the origin, clinical practice objectives, procedures, methods. We described the difficulties in antitumor pharmacovigilance and current characteristics of pharmacovigilance in China, aiming to provide reference for the development of antitumor pharmacovigilance. .
Topics: China; Humans; Lung Neoplasms; Pharmacovigilance
PubMed: 35899454
DOI: 10.3779/j.issn.1009-3419.2022.101.33 -
Drug Safety May 2022Monitoring adverse drug events or pharmacovigilance has been promoted by the World Health Organization to assure the safety of medicines through a timely and reliable... (Review)
Review
Monitoring adverse drug events or pharmacovigilance has been promoted by the World Health Organization to assure the safety of medicines through a timely and reliable information exchange regarding drug safety issues. We aim to discuss the application of machine learning methods as well as causal inference paradigms in pharmacovigilance. We first reviewed data sources for pharmacovigilance. Then, we examined traditional causal inference paradigms, their applications in pharmacovigilance, and how machine learning methods and causal inference paradigms were integrated to enhance the performance of traditional causal inference paradigms. Finally, we summarized issues with currently mainstream correlation-based machine learning models and how the machine learning community has tried to address these issues by incorporating causal inference paradigms. Our literature search revealed that most existing data sources and tasks for pharmacovigilance were not designed for causal inference. Additionally, pharmacovigilance was lagging in adopting machine learning-causal inference integrated models. We highlight several currently trending directions or gaps to integrate causal inference with machine learning in pharmacovigilance research. Finally, our literature search revealed that the adoption of causal paradigms can mitigate known issues with machine learning models. We foresee that the pharmacovigilance domain can benefit from the progress in the machine learning field.
Topics: Causality; Drug-Related Side Effects and Adverse Reactions; Humans; Machine Learning; Models, Theoretical; Pharmacovigilance
PubMed: 35579811
DOI: 10.1007/s40264-022-01155-6 -
Annals of the American Thoracic Society Aug 2021Pulmonary hypertension (PH) has been described in patients treated with leflunomide. To assess the association between leflunomide and PH. We identified incident...
Pulmonary hypertension (PH) has been described in patients treated with leflunomide. To assess the association between leflunomide and PH. We identified incident cases of PH in patients treated with leflunomide from the French PH Registry and through the pharmacoVIGIlAnce in Pulmonary ArTerial Hypertension (VIGIAPATH) program between September 1999 to December 2019. PH etiology, clinical, functional, radiologic, and hemodynamic characteristics were reviewed at baseline and follow-up. A pharmacovigilance disproportionality analysis using the World Health Organization's global database was conducted. We then investigated the effect of leflunomide on human pulmonary endothelial cells. Data are expressed as median (min-max). Twenty-eight patients treated with leflunomide before PH diagnosis was identified. A total of 21 (75%) had another risk factor for PH and 2 had two risk factors. The median time between leflunomide initiation and PH diagnosis was 32 months (1-120). Right heart catheterization confirmed precapillary PH with a cardiac index of 2.37 L⋅min ⋅m (1.19-3.1) and elevated pulmonary vascular resistance at 9.63 Wood Units (3.6-22.1) without nitric oxide reversibility. Five patients (17.9%) had no other risk factor for PH besides exposure to leflunomide. No significant hemodynamic improvement was observed after leflunomide withdrawal. The pharmacovigilance disproportionality analysis using the World Health Organization's database revealed a significant overrepresentation of leflunomide among reported pulmonary arterial hypertension-adverse drug reactions. studies showed the dose-dependent toxicity of leflunomide on human pulmonary endothelial cells. PH associated with leflunomide is rare and usually associated with other risk factors. The pharmacovigilance analysis suggests an association reinforced by experimental data.
Topics: Cardiac Catheterization; Endothelial Cells; Humans; Hypertension, Pulmonary; Leflunomide; Lung; Pharmacovigilance
PubMed: 33502958
DOI: 10.1513/AnnalsATS.202008-913OC -
Drug Safety Dec 2020This review summarizes current evidence on the abuse and misuse of the gabapentinoids pregabalin and gabapentin. Pharmacovigilance studies, register-based studies,... (Review)
Review
This review summarizes current evidence on the abuse and misuse of the gabapentinoids pregabalin and gabapentin. Pharmacovigilance studies, register-based studies, surveys, clinical toxicology studies, and forensic toxicology studies were identified and scrutinized with the goal to define the problem, identify risk factors, and discuss possible methods to reduce the potential for abuse and misuse. Studies found that gabapentinoids are abused and misused and that individuals with a history of psychiatric disorders or substance use disorder seem to be at high risk. Moreover, some evidence supports the notion that patients with opioid use disorders may be at an increased risk of abusing gabapentinoids. Available evidence also suggests that abuse and misuse are more frequent in users of pregabalin compared with users of gabapentin. Health professionals and prescribers should be aware of the risk for misuse of pregabalin and gabapentin, which eventually could lead to abuse, substance dependence, and intoxications. Prescribing to patients belonging to risk populations such as those with psychiatric disorders or substance use disorder should be avoided if possible and, if prescribed, signs of misuse and abuse should be monitored.
Topics: Gabapentin; Humans; Pharmacovigilance; Prescription Drug Misuse; Risk Factors; Substance-Related Disorders
PubMed: 32857333
DOI: 10.1007/s40264-020-00985-6