Association Between Intravitreal Aflibercept and Serious Non-ocular Haemorrhage Compared with Intravitreal Ranibizumab: A Multicentre Observational Cohort Study
ConclusionNo association was identified between intravitreal aflibercept and non-ocular haemorrhage versus ranibizumab. A comparable risk for these intravitreal anti-VEGFs and intravitreal dexamethasone was observed. (Source: Drug Safety)
Source: Drug Safety - June 15, 2020 Category: Drugs & Pharmacology Source Type: research

Use of Social Media for Pharmacovigilance Activities: Key Findings and Recommendations from the Vigi4Med Project
The objective of this paper is to present the main findings and subsequent recommendations from the French research project Vigi4Med, which evaluated the use of social media, mainly web forums, for pharmacovigilance activities. This project included an analysis of the existing literature, which contributed to the recommendations presented herein. The recommendations are categorized into three categories: ethical (related to privacy, confidentiality, and follow-up), qualitative (related to the quality of the information), and quantitative (related to statistical analysis). We argue that the progress in information technolog...
Source: Drug Safety - June 15, 2020 Category: Drugs & Pharmacology Source Type: research

The Effect of Positively Framing Side-Effect Risk in Two Different Formats on Side-Effect Expectations, Informed Consent and Credibility: A Randomised Trial of 16- to 75-Year-Olds in England
ConclusionPositively framed PILs using natural frequencies significantly reduced side-effect expectations and provided the most accurate risk perceptions without impacting satisfaction or credibility. Replication is needed with patients prescribed new medication and those with lower educational status. (Source: Drug Safety)
Source: Drug Safety - June 15, 2020 Category: Drugs & Pharmacology Source Type: research

Thromboembolic Safety Reporting of Tofacitinib and Baricitinib: An Analysis of the WHO VigiBase
ConclusionThis study supports the current recommendation for cautious use of tofacitinib in patients with high thromboembolic risk. Moreover, with a similar patient profile and elevated reporting for baricitinib, a potential class effect of JAK inhibitors cannot be ruled out. (Source: Drug Safety)
Source: Drug Safety - June 11, 2020 Category: Drugs & Pharmacology Source Type: research

Does Ibuprofen Worsen COVID-19?
(Source: Drug Safety)
Source: Drug Safety - June 10, 2020 Category: Drugs & Pharmacology Source Type: research

Drug-Induced Liver Injury and COVID-19 Infection: The Rules Remain the Same
(Source: Drug Safety)
Source: Drug Safety - June 7, 2020 Category: Drugs & Pharmacology Source Type: research

Drug Safety in Geriatric Patients: Current Status and Proposed Way Forward
We present some proposals to overcome the barriers preventing the enrollment of frail elderly patients in clinical trials, and strategies for monitoring their therapy to minimize the risk of adverse reactions. Automated a lerts for drug and drug–disease interactions could help appropriate prescribing but should flag only clinically relevant interactions. Pharmaceutical forms should be designed to allow easy dose adjustment and, together with packaging and labeling, should account for the physical and cognitive limi tations of frail elderly patients. Aggregate pharmacovigilance reports should summarize the safety prof...
Source: Drug Safety - June 3, 2020 Category: Drugs & Pharmacology Source Type: research

Channeling Bias in the Analysis of Risk of Myocardial Infarction, Stroke, Gastrointestinal Bleeding, and Acute Renal Failure with the Use of Paracetamol Compared with Ibuprofen
ConclusionsFor paracetamol versus ibuprofen, when using LSPS methods in the CPRD, it is only possible to distinguish true effects if those effects are large (hazard ratio  >  2). Due to their smaller hazard ratios, the outcomes under study cannot be differentiated from null effects (represented by negative controls) even if there were a true effect. Based on these data, we conclude that we are unable to determine whether paracetamol is associated with an increased ris k of myocardial infarction, stroke, GI bleeding, and acute renal failure compared to ibuprofen, due to residual confounding. (Source: Drug Safety)
Source: Drug Safety - June 3, 2020 Category: Drugs & Pharmacology Source Type: research

A New Drug –Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study
ConclusionOur study identified a signal for the association hydroxychloroquine  + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone. (Source: Drug Safety)
Source: Drug Safety - June 2, 2020 Category: Drugs & Pharmacology Source Type: research

Remdesivir in Treatment of COVID-19: A Systematic Benefit –Risk Assessment
ConclusionsPreliminary clinical trial results suggest that there may be a favourable benefit –risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit–risk assessment. (Source: Drug Safety)
Source: Drug Safety - May 27, 2020 Category: Drugs & Pharmacology Source Type: research

Patient-Reported Burden of Adverse Drug Reactions Attributed to Biologics Used for Immune-Mediated Inflammatory Diseases
ConclusionsThe patient perspective gives important insights into the burden of ADRs experienced with biologics. This information could be used by healthcare professionals to optimise treatment with biologics. (Source: Drug Safety)
Source: Drug Safety - May 24, 2020 Category: Drugs & Pharmacology Source Type: research

Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety
ConclusionsWhile limited by the small number of pregnancies and related data from the cladribine clinical development program, highlighting the need for further study, the observations made in the present analysis were generally consistent with epidemiological data on pregnancy outcomes for the general population or women with multiple sclerosis. There were no congenital malformations in pregnancies that occurred during cladribine treatment or within 6  months after the last dose. As the data available for cladribine-exposed pregnancies in patients with multiple sclerosis are limited, a non-interventional post-authori...
Source: Drug Safety - May 22, 2020 Category: Drugs & Pharmacology Source Type: research

Information Visualization Platform for Postmarket Surveillance Decision Support
ConclusionsThe InfoViP system uses context-driven interactive visualizations and informatics tools to assist FDA SEs in synthesizing data from multiple sources for their case series analyses. (Source: Drug Safety)
Source: Drug Safety - May 21, 2020 Category: Drugs & Pharmacology Source Type: research

A Framework for Methodological Choice and Evidence Assessment for Studies Using External Comparators from Real-World Data
AbstractSeveral approaches have been proposed recently to accelerate the pathway from drug discovery to patient access. These include novel designs such as using controls external to the clinical trial where standard randomised controls are not feasible. In parallel, there has been rapid growth in the application of routinely collected healthcare ‘real-world’ data for post-market safety and effectiveness studies. Thus, using real-world data to establish an external comparator arm in clinical trials is a natural next step. Regulatory authorities have begun to endorse the use of external comparators in certain ci...
Source: Drug Safety - May 20, 2020 Category: Drugs & Pharmacology Source Type: research

Communicating Adverse Drug Reaction Insights Through Patient Organizations: Experiences from a Pilot Study in the Netherlands
ConclusionPatient organizations can help enable effective communication of adverse drug reactions to a relevant audience. The social media post generated more engagement than other communications from the patient organization, indicating a strong interest in this information. The additional patient experiences that were shared in the comments on social media further strengthened the original signal and its relevance to patients, creating an interesting feedback loop. The favourable experiences in this study support further consideration and exploration of this approach to communicate adverse drug reactions to patients. (Source: Drug Safety)
Source: Drug Safety - May 15, 2020 Category: Drugs & Pharmacology Source Type: research

Prospective Evaluation of Adverse Event Recognition Systems in Twitter: Results from the Web-RADR Project
ConclusionWe warn the community about a potentially large discrepancy between the expected performance of automated AE recognition systems based on published results and the actual observed performance on independent data. This study highlights the difficulty of implementing an all-purpose system for automatic adverse event recognition in Twitter, which could explain the lack of such systems in practical pharmacovigilance settings. Our recommendation is to use benchmark independent datasets, such as the WEB-RADR reference, to investigate the transferability of the adverse event recognition systems and ultimately enforce ri...
Source: Drug Safety - May 13, 2020 Category: Drugs & Pharmacology Source Type: research

Pathophysiology of Drug-Induced Hypomagnesaemia
AbstractMagnesium (Mg2+) is the second most abundant intracellular and fourth extracellular cation found in the body and is involved in a wide range of functions in the human cell and human physiology. Its role in most of the enzyme processes (ATP-ases) —stabilisation of nucleic acids (DNA, RNA), regulation of calcium and potassium ion channels, proliferation, glucose metabolism and apoptosis—make it one of the most important cations in the cell. Three pathogenetic mechanisms are mainly implicated in the development of hypomagnesaemia: reduced food intake, decreased intestinal absorption and increased renal exc...
Source: Drug Safety - May 11, 2020 Category: Drugs & Pharmacology Source Type: research

Combining Social Media and FDA Adverse Event Reporting System to Detect Adverse Drug Reactions
ConclusionThe accuracy of signal detection using social media can be improved by combining signals with those from SRSs. However, the combined system cannot achieve better AUC performance than data from FAERS alone, which may indicate that Twitter data are not ready to be integrated into a purely data-driven combination system. (Source: Drug Safety)
Source: Drug Safety - May 7, 2020 Category: Drugs & Pharmacology Source Type: research

The Role of Pharmacovigilance and ISoP During the Global COVID-19 Pandemic
(Source: Drug Safety)
Source: Drug Safety - May 6, 2020 Category: Drugs & Pharmacology Source Type: research

Critical Assessment of Pharmacokinetic Drug –Drug Interaction Potential of Tofacitinib, Baricitinib and Upadacitinib, the Three Approved Janus Kinase Inhibitors for Rheumatoid Arthritis Treatment
AbstractThe introduction of novel, small-molecule Janus kinase inhibitors namely tofacitinib, baricitinib and upadacitinib has provided an alternative treatment option for patients with rheumatoid arthritis outside of traditional drugs and expensive biologics. This review aimed to critically assess the drug –drug interaction potential of tofacitinib, baricitinib and upadacitinib and provide a balanced perspective for choosing the most appropriate Janus kinase inhibitor based on the needs of patients with rheumatoid arthritis including co-medications and renal/hepatic impairment status. Based on the c ritical assessme...
Source: Drug Safety - May 3, 2020 Category: Drugs & Pharmacology Source Type: research

Effect of Bempedoic Acid on Serum Uric Acid and Related Outcomes: A Systematic Review and Meta-analysis of the available Phase 2 and Phase 3 Clinical Studies
AbstractIntroductionBempedoic acid (ETC-1002) is a first-in-class lipid-lowering agent recently approved by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for commercialization.ObjectiveThe aim was to assess, through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies, the effect of treatment with bempedoic acid on serum uric acid (SUA) concentration. Secondary outcomes were treatment-related variations in creatinine serum level and incidence of gout.MethodsA systematic literature search in SCOPUS, PubMed Medline,...
Source: Drug Safety - April 30, 2020 Category: Drugs & Pharmacology Source Type: research

Oxycodone, Hydromorphone, and the Risk of Suicide: A Retrospective Population-Based Case –Control Study
ConclusionsWhile preliminary, these findings support the possibility that some high-potency opioids might independently influence the risk of suicide in susceptible individuals. (Source: Drug Safety)
Source: Drug Safety - April 22, 2020 Category: Drugs & Pharmacology Source Type: research

The International Society of Pharmacovigilance (ISoP) Special Interest Group on Herbal and Traditional Medicines: Towards Progress in Pharmacovigilance for Herbal and Traditional Medicines and Other “Natural Health” Products
(Source: Drug Safety)
Source: Drug Safety - April 22, 2020 Category: Drugs & Pharmacology Source Type: research

DPP-4 Inhibitors in Combination with Lipid-Lowering Agents and Risk of Serious Muscular Injury: A Nested Case-Control Study in a Nationwide Cohort of Patients with Type 2 Diabetes Mellitus
ConclusionIn this study, DPP-4 inhibitor use was not associated with an increased risk of serious muscular injury among patients with type 2 diabetes mellitus using statins or fibrates. (Source: Drug Safety)
Source: Drug Safety - April 17, 2020 Category: Drugs & Pharmacology Source Type: research

Should Patients Receiving ACE Inhibitors or Angiotensin Receptor Blockers be Switched to Other Antihypertensive Drugs to Prevent or Improve Prognosis of Novel Coronavirus Disease 2019 (COVID-19)?
(Source: Drug Safety)
Source: Drug Safety - April 16, 2020 Category: Drugs & Pharmacology Source Type: research

Erice Call for Change: Utilising Patient Experiences to Enhance the Quality and Safety of Healthcare
AbstractThis ‘Erice Call for Change’ is a report from a group of experts, patients and patient representatives who met in Erice in September 2019 following previous similar meetings after the original Erice Declaration (1996). The aim of the meeting was to discuss the challenge of causal complexity and indiv idual variation in modern healthcare. The group’s concern was the impact that new clinical decision-making tools, based on statistical correlations in large databases, could have on individual patient care if they replace other types of clinical investigation and knowledge. The group calls for a c han...
Source: Drug Safety - April 14, 2020 Category: Drugs & Pharmacology Source Type: research

Evidence of Clinically Meaningful Drug –Drug Interaction With Concomitant Use of Colchicine and Clarithromycin
ConclusionClinical manifestations of colchicine –clarithromycin interaction may resemble other systemic diseases and may be life threatening. Understanding this clinically meaningful interaction can help clinicians avoid unsafe medication combinations. (Source: Drug Safety)
Source: Drug Safety - April 8, 2020 Category: Drugs & Pharmacology Source Type: research

Chloroquine for COVID-19 Infection
(Source: Drug Safety)
Source: Drug Safety - April 6, 2020 Category: Drugs & Pharmacology Source Type: research

Comment on ‘Reported Severe Hypersensitivity Reactions after Intravenous Iron Administration in the European Economic Area (EEA) Before and After Implementation of Risk Minimization Measures’
(Source: Drug Safety)
Source: Drug Safety - April 5, 2020 Category: Drugs & Pharmacology Source Type: research

A Disproportionality Analysis of the Adverse Drug Events Associated with Lurasidone in Paediatric Patients Using the US FDA Adverse Event Reporting System (FAERS)
(Source: Drug Safety)
Source: Drug Safety - April 3, 2020 Category: Drugs & Pharmacology Source Type: research

Systemic Adverse Events Associated with Compounded Topical Pain Products
(Source: Drug Safety)
Source: Drug Safety - April 3, 2020 Category: Drugs & Pharmacology Source Type: research

Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab
AbstractEosinophils play a pivotal role in the inflammatory pathology of asthma and have been the target of new biologic treatments for patients with eosinophilic asthma. Given the central role of interleukin (IL)-5 in the eosinophil lifecycle, several therapies directed against the IL-5 pathway have been developed, including the anti-IL-5 antibodies mepolizumab and reslizumab and the IL-5 receptor α (IL-5Rα)–directed cytolytic antibody benralizumab. Eosinophil-depleting therapies represent a relatively new class of asthma treatment, and it is important to understand their long-term efficacy and safety. E...
Source: Drug Safety - April 1, 2020 Category: Drugs & Pharmacology Source Type: research

Enhancing Pharmacovigilance in Sub-Saharan Africa Through Training and Mentoring: A GSK Pilot Initiative in Malawi
ConclusionRegular PV training and mentoring of HCPs were effective in enhancing passive safety surveillance in Malawi, but the transmission of reports to the national PV centre requires further improvement.Plain Language SummaryWhen a medicine or vaccine is made available for use, healthcare organisations maintain regular surveillance to confirm that the medicinal product is safe and effective. The efficiency of this surveillance depends mainly on the healthcare system and medical practices in place in each country. An important element is an effective procedure for identifying and reporting any unwanted medical occurrence...
Source: Drug Safety - March 31, 2020 Category: Drugs & Pharmacology Source Type: research

Drug Safety Issues Covered by Lay Media: A Cohort Study of Direct Healthcare Provider Communications Sent between 2001 and 2015 in The Netherlands
ConclusionsNewspapers covered a small proportion of DHPC safety issues only. Most drugs mentioned in DHPCs were covered in social media. Coverage in both media were higher for drugs without a specialist indication. (Source: Drug Safety)
Source: Drug Safety - March 23, 2020 Category: Drugs & Pharmacology Source Type: research

Rates and Costs of Dispensing Naloxone to Patients at High Risk for Opioid Overdose in the United States, 2014 –2018
ConclusionsRates of dispensing naloxone to high risk patients were extremely low, and prescription costs varied greatly. Since improving naloxone ’s affordability may increase access, whether naloxone’s high cost is associated with low dispensing rates should be evaluated. (Source: Drug Safety)
Source: Drug Safety - March 15, 2020 Category: Drugs & Pharmacology Source Type: research

Patterns of Inpatient Antibiotic Use Among Public Hospitals in Hong Kong from 2000 to 2015
ConclusionsWe found that the overall volume of antibiotic use increased between 2000 and 2015. The rise in the dispensing of carbapenems in our study is concerning. The significant change in tetracycline use after being recommended as one of the preferred regimens demonstrated that the change in the clinical practice guideline had an immediate effect on the antibiotic prescribing practice in Hong Kong public hospitals. (Source: Drug Safety)
Source: Drug Safety - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

ISoP Fellowships: Recognising Contributions to the Goals of ISoP
(Source: Drug Safety)
Source: Drug Safety - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Fluoroquinolone-Induced Photosensitivity: A Chemical Fragment-Based Approach by a Case/Non-case Study in VigiBase ®
ConclusionThis study confirms the high reporting rate of photosensitivity adverse effects for sparfloxacin from real-world data. Moreover, our data suggest more photosensitivity adverse effects reporting for fluoroquinolones with a halogen at their 8th position. (Source: Drug Safety)
Source: Drug Safety - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Prevalence and Nature of Medication Errors and Medication-Related Harm Following Discharge from Hospital to Community Settings: A Systematic Review
ConclusionsThis is the first systematic review to explore the prevalence and nature of medication errors and adverse drug events following hospital discharge. Targets for future work have been identified. (Source: Drug Safety)
Source: Drug Safety - March 2, 2020 Category: Drugs & Pharmacology Source Type: research

Identifying Drugs Inducing Prematurity by Mining Claims Data with High-Dimensional Confounder Score Strategies
ConclusionsMining complex healthcare databases with statistical methods from the high-dimensional inference field may improve signal detection in pregnant women. (Source: Drug Safety)
Source: Drug Safety - March 1, 2020 Category: Drugs & Pharmacology Source Type: research

Leveraging Human Genetics to Identify Safety Signals Prior to Drug Marketing Approval and Clinical Use
ConclusionsBy connecting and integrating in vivo and in silico data, SA-PheWAS offers an opportunity to supplement current methods for predicting or confirming safety signals associated with therapeutic agents. (Source: Drug Safety)
Source: Drug Safety - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

Sex Differences in Adverse Drug Reactions of Metformin: A Longitudinal Survey Study
This study has a longitudinal design using data about patients initiating metformin collected by the Dutch National Pharmacovigilance Center Lareb through their Intensive Monitoring program. Patients were asked to complete a web-based questionnaire six times after initiation (i.e., at 2  weeks, 6 weeks and at 3, 6, 9, and 12 months). The outcome variables were the proportion of patients reporting any ADR (primary) and the dose of metformin (secondary). Sex differences in the proportions of ADRs and in the dose were tested at each assessment using Pearson Chi-Squared tests and Wi lcoxon rank-sum tests, respec...
Source: Drug Safety - February 10, 2020 Category: Drugs & Pharmacology Source Type: research

Benzodiazepine Use and Risk of Acute Angle-Closure Glaucoma: A Population-Based Case-Crossover Study
ConclusionWe found that BZD use was associated with AACG risk in the Korean population. Clinicians should carefully monitor the occurrence of visual disturbance in BZD-treated patients. (Source: Drug Safety)
Source: Drug Safety - February 6, 2020 Category: Drugs & Pharmacology Source Type: research

Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase ®
This study aims to quantify the redundancy among the three databases when characterized by two disproportionality-based analyses (DPA).MethodsSDRs for 100 selected products were identified with two sets of thresholds (standard EudraVigilance SDR criteria for all vs Bayesian approach for FAERS and VigiBase®). Per product and database, the presence or absence of SDRs was determined and compared. Adverse events were considered at three levels: MedDRA® Preferred Term (PT), High Level Term (HLT), and HLT combined with Standardized MedDRA® Query (SMQ). Redundancy was measured in terms of recall (SDRs in EVDAS divided...
Source: Drug Safety - February 3, 2020 Category: Drugs & Pharmacology Source Type: research

Quality of Reporting on the Evaluation of Risk Minimization Programs: A Systematic Review
ConclusionsGaps in reporting of risk minimization program evaluation studies were identified. Addressing gaps will help build the evidence base regarding risk minimization initiatives, as well as ensure that programs are maximally effective and minimally burdensome on the healthcare system, and do not unduly interfere with patient access to the medicine. (Source: Drug Safety)
Source: Drug Safety - February 3, 2020 Category: Drugs & Pharmacology Source Type: research

Disproportionality Analysis for Pharmacovigilance Signal Detection in Small Databases or Subsets: Recommendations for Limiting False-Positive Associations
This study aims to investigate the relationship between database size and robustness of disproportionality analysis, with regards to limiting spurious associations.MethodsThree types of subsets were created from the global database VigiBase: random subsets (500 replicates each of 11 fixed subset sizes between 250 and 100,000 reports), country-specific subsets (all 131 countries available in the original VigiBase extract) and subsets based on the Anatomical Therapeutic Chemical classification. For each subset, a spuriousness rate was computed as the ratio between the number of drug –event combinations highlighted by d...
Source: Drug Safety - January 31, 2020 Category: Drugs & Pharmacology Source Type: research

An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis across Phase III and Long-Term Extension Studies with Comparison to Real-World Observational Data
ConclusionIn patients with PsA, tofacitinib had a safety profile similar to that of other systemic therapies in real-world settings, except for the risk of HZ, a known risk of tofacitinib.Trial RegistrationClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364. (Source: Drug Safety)
Source: Drug Safety - January 30, 2020 Category: Drugs & Pharmacology Source Type: research

Adverse Events in Twitter-Development of a Benchmark Reference Dataset: Results from IMI WEB-RADR
ConclusionsA manually curated benchmark reference dataset based on Twitter data has been created and is made available to the research community to evaluate the performance of automated methods and systems for adverse event recognition in unstructured free-text information. (Source: Drug Safety)
Source: Drug Safety - January 28, 2020 Category: Drugs & Pharmacology Source Type: research

Authors ’ Reply to Uysal and Colleagues’ Comment on: “Evaluation of Potential Drug–Drug Interactions in Adults in the Intensive Care Unit: A Systematic Review and Meta-Analysis”
(Source: Drug Safety)
Source: Drug Safety - January 28, 2020 Category: Drugs & Pharmacology Source Type: research

Comment on “Evaluation of Potential Drug–Drug Interactions in Adults in the Intensive Care Unit: A Systematic Review and Meta-analysis”
(Source: Drug Safety)
Source: Drug Safety - January 28, 2020 Category: Drugs & Pharmacology Source Type: research