Global burden of vaccine-associated multiple sclerosis, 1967-2022: A comprehensive analysis of the international pharmacovigilance database.

Vaccine-associated multiple sclerosis (MS) is rare, with insufficient evidence from case reports. Given the scarcity of large-scale data investigating the association between vaccine administration and adverse events, we investigated the global burden of vaccine-associated MS and potential related vaccines from 1967 to 2022. Reports on vaccine-associated MS between 1967 and 2022 were obtained from the World Health Organization International Pharmacovigilance Database (total number of reports = 120 715 116). We evaluated global reports, reporting odds ratio (ROR), and information components (IC) to investigate associations between 19 vaccines and vaccine-associated MS across 156 countries and territories. We identified 8288 reports of vaccine-associated MS among 132 980 cases of all-cause MS. The cumulative number of reports on vaccine-associated MS gradually increased over time, with a substantial increase after 2020, owing to COVID-19 mRNA vaccine-associated MS. Vaccine-associated MS develops more frequently in males and adolescents. Nine vaccines were significantly associated with higher MS reporting, and the highest disproportional associations were observed for hepatitis B vaccines (ROR 19.82; IC025 4.18), followed by encephalitis (ROR 7.42; IC025 2.59), hepatitis A (ROR 4.46; IC025 1.95), and papillomavirus vaccines (ROR 4.45; IC025 2.01). Additionally, MS showed a significantly disproportionate signal for COVID-19 mRNA vaccines (ROR 1.55; IC025 0.52). Fatal clinical outcomes were reported in only 0.3% (21/8288) of all cases of vaccine-associated MS. Although various vaccines are potentially associated with increased risk of MS, we should be cautious about the increased risk of MS following vaccination, particularly hepatitis B and COVID-19 mRNA vaccines, and should consider the risk factors associated with vaccine-associated MS.

Pharmacovigilance Concept Knowledge, Perspectives and Attitudes: A Cross-Sectional Study Among Community Pharmacists.

The concept of pharmacovigilance (PV) is currently highlighted after emergency authorization and worldwide distribution of the urgently launched COVID-19 novel vaccinations. As they typically serve as the initial point of patient contact for medication-related issues, understanding the knowledge, perspectives, and attitudes of community pharmacists in PV and reporting adverse drug reactions (ADRs) is crucial to improving the healthcare system and public health policies. However, previous studies in Jordan have not focused entirely on community pharmacists. This study aimed to assess community pharmacists' knowledge, perspectives, and attitudes on PV and ADRs reporting in Jordan. The applied methodology in this study was based on a cross-sectional study design using a validated questionnaire distributed to a convenient sample of Jordanian community pharmacists. Seventeen questions were designed from different pieces of literature relating to knowledge, perspectives, and attitudes of PV among community pharmacists. Descriptive statistics (frequencies and percentages) were used to report the results data. The study questionnaire was completed by 180 of 325 community pharmacists willing to participate (a response rate of 55.4%). Of them (n = 132, 73%) were aware of the concept of PV. Additionally (n = 84, 47%) of the community pharmacists would use the concept and policy of PV in their everyday work. Nevertheless, only (n = 36, 20.0%) of the community pharmacists thought an ADR should be reported if seen, and approximately 120 pharmacists (67.0%) believed it was essential to report ADRs as patient health matters. Although community pharmacists in Jordan showed a considerable awareness level of PV, they demonstrated a low level of its application. Thus, ADR reporting is not considered a mainstay among them, and the implementation of PV is not yet addressed. The results from this study shed light on community pharmacists' perceptions and attitudes regarding ADR reporting and PV.

Cross-sectional study of pharmacovigilance knowledge, attitudes, and practices based on structural equation modeling and network analysis: a case study of healthcare personnel and the public in Yunnan Province.

Background: This study focuses on understanding pharmacovigilance knowledge, attitudes, and practices (KAP) in Yunnan Province, employing Structural Equation Modeling (SEM) and network analysis. It aims to evaluate the interplay of these factors among healthcare personnel and the public, assessing the impact of demographic characteristics to inform policy and educational initiatives. Methods: A cross-sectional survey was conducted in Yunnan, targeting healthcare personnel and the public. Data collection was through questionnaires, with subsequent analysis involving correlation matrices, network visualization, and SEM. The data analysis utilized SPSS 27.0, AMOS 26.0, and Gephi software for network analysis. Results: This study evaluated pharmacovigilance KAP among 209 public participants and 823 healthcare personnel, uncovering significant differences. Public respondents scored averages of 4.62 ± 2.70 in knowledge, 31.99 ± 4.72 in attitudes, and 12.07 ± 4.96 in practices, while healthcare personnel scored 4.38 ± 3.06, 27.95 ± 3.34, and 7.75 ± 2.77, respectively. Statistically significant correlations across KAP elements were observed in both groups, highlighting the interconnectedness of these factors. Demographic influences were more pronounced among healthcare personnel, emphasizing the role of professional background in pharmacovigilance competency. Network analysis identified knowledge as a key influencer within the pharmacovigilance KAP network, suggesting targeted education as a vital strategy for enhancing pharmacovigilance engagement. Conclusion: The research reveals a less-than-ideal state of pharmacovigilance KAP among both healthcare personnel and the public in Yunnan, with significant differences between the two groups. SEM and network analysis confirmed a strong positive link among KAP components, moderated by demographics like age, occupation, and education level. These insights emphasize the need to enhance pharmacovigilance education and awareness, thereby promoting safer drug use.

Hemorrhage profile associated with immune checkpoint inhibitors: a systematic review and a real-world study based on the FAERS database.

OBJECTIVES: To investigate the risk of hemorrhage associated with Immune Checkpoint Inhibitors (ICIs) and characterize its clinical features. METHODS: We systematically reviewed randomized clinical trials (RCTs) of hemorrhage related to ICIs and calculated odds ratios (ORs) with 95% confidence intervals (CIs). Pharmacovigilance studies were conducted by collecting ICIs-related hemorrhage cases from the FAERS database and assessing disproportionalities by reporting odds ratios (RORs) and information components (ICs). RESULTS: A total of 79 RCTs involving 45,100 patients were finally included in the systematic review, with four published RCTs (n = 1965) and 75 unpublished RCTs (n = 43135). The primary analysis showed no significant difference in ICIs compared to the control group (OR 1.18 [95% CI 1.00-1.38], p = 0.05). In subgroup analyses, anti-PD-L1 combined with anti-CTLA-4 increased the risk of hemorrhage (OR 1.95, p = 0.03), and anti-CTLA-4 increased the risk of hemorrhage in the gastrointestinal system (OR 2.23, p = 0.04). 3555 cases of hemorrhage from the FAERS database were included in the disproportionate analysis, and the result suggested that ICIs increased the risk of hemorrhage (IC025 = 0.23). CONCLUSION: Our study suggests that ICIs increase the risk of hemorrhage, and in particular, anti-CTLA-4 significantly increases the risk of hemorrhage in the gastrointestinal system.

The OMOP common data model in Australian primary care data: Building a quality research ready harmonised dataset.

BACKGROUND: The use of routinely collected health data for secondary research purposes is increasingly recognised as a methodology that advances medical research, improves patient outcomes, and guides policy. This secondary data, as found in electronic medical records (EMRs), can be optimised through conversion into a uniform data structure to enable analysis alongside other comparable health metric datasets. This can be achieved with the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM), which employs a standardised vocabulary to facilitate systematic analysis across various observational databases. The concept behind the OMOP-CDM is the conversion of data into a common format through the harmonisation of terminologies, vocabularies, and coding schemes within a unique repository. The OMOP model enhances research capacity through the development of shared analytic and prediction techniques; pharmacovigilance for the active surveillance of drug safety; and 'validation' analyses across multiple institutions across Australia, the United States, Europe, and the Asia Pacific. In this research, we aim to investigate the use of the open-source OMOP-CDM in the PATRON primary care data repository. METHODS: We used standard structured query language (SQL) to construct, extract, transform, and load scripts to convert the data to the OMOP-CDM. The process of mapping distinct free-text terms extracted from various EMRs presented a substantial challenge, as many terms could not be automatically matched to standard vocabularies through direct text comparison. This resulted in a number of terms that required manual assignment. To address this issue, we implemented a strategy where our clinical mappers were instructed to focus only on terms that appeared with sufficient frequency. We established a specific threshold value for each domain, ensuring that more than 95% of all records were linked to an approved vocabulary like SNOMED once appropriate mapping was completed. To assess the data quality of the resultant OMOP dataset we utilised the OHDSI Data Quality Dashboard (DQD) to evaluate the plausibility, conformity, and comprehensiveness of the data in the PATRON repository according to the Kahn framework. RESULTS: Across three primary care EMR systems we converted data on 2.03 million active patients to version 5.4 of the OMOP common data model. The DQD assessment involved a total of 3,570 individual evaluations. Each evaluation compared the outcome against a predefined threshold. A 'FAIL' occurred when the percentage of non-compliant rows exceeded the specified threshold value. In this assessment of the primary care OMOP database described here, we achieved an overall pass rate of 97%. CONCLUSION: The OMOP CDM's widespread international use, support, and training provides a well-established pathway for data standardisation in collaborative research. Its compatibility allows the sharing of analysis packages across local and international research groups, which facilitates rapid and reproducible data comparisons. A suite of open-source tools, including the OHDSI Data Quality Dashboard (Version 1.4.1), supports the model. Its simplicity and standards-based approach facilitates adoption and integration into existing data processes.

Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Electrolyte disorders induced by six multikinase inhibitors therapy for renal cell carcinoma: a large-scale pharmacovigilance analysis.

To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders' adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45-64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65-74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events.

The association of hypophysitis with immune checkpoint inhibitors use: Gaining insight through the FDA pharmacovigilance database.

The use of immune checkpoint inhibitor (ICI) marked a revolutionary change in cancer treatment and opened new avenues for cancer therapy, but ICI can also trigger immune-related adverse events (irAEs). Here, we investigated the publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insight into the possible association between immune checkpoint inhibitors and hypophysitis. Data on adverse events (AEs) due to hypophysitisfor nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected from the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, and the signals for hypophysitis associated with the four drugs were examined using the reporting odds ratio (ROR) method. The number of reported hypophysitis events ≥ 3 and the lower limit of the 95% confidence interval (CI) of the ROR > 1 were considered positive for hypophysitis signals. A total of 1252 AE reports of hypophysitis associated with nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected, including 419, 149, 643, and 41 cases, respectively. The RORs of hypophysitis were 289.58 (95% CI 258.49-324.40), 171.74 (95% CI 144.91-203.54), 2248.57 (95% CI 2025.31-2496.45), and 97.29 (95% CI 71.28-132.79), respectively. All four drugs were statistically correlated with the target AE, with the correlation being, in descending order, ipilimumab, nivolumab, pembrolizumab, and atezolizumab. Nivolumab, pembrolizumab, ipilimumab, and atezolizumab have all been associated with hypophysitis, which can negatively impact quality of life, and early recognition and management of immune checkpoint inhibitor-related hypophysitis is critical.

Low albumin combined with low-molecular-weight heparin as risk factors for liver injury using azvudine: Evidence from an analysis of COVID-19 patients in a national prospective pharmacovigilance database.

OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.

Hemorrhage induced by antithrombotic agents: new insights from a real-world pharmacovigilance study.

BACKGROUND: Hemorrhage represents the most common and serious side effect of antithrombotic agents. Many studies have compared the risk of bleeding between different antithrombotic agents, but analysis of time-to-onset for hemorrhage induced by these drugs is yet sparse. METHODS: We conducted a retrospective study based on the adverse drug reaction reports on antithrombotic agents collected by the Henan Adverse Drug Reaction Monitoring Center. We assessed the reporting odds ratio to determine the disproportionate reporting signals for bleeding and the Weibull shape parameter was used to evaluate the time-to-onset data. RESULTS: In the signal detection, crude low molecular weight heparin-hemorrhage was found as a positive signal. The hemorrhage for most antithrombotic agents was random failure profiles. In particular, the hazard of hemorrhage decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole. CONCLUSION: We found that the risk of bleeding in patients taking Crude low molecular weight heparins was significantly higher compared to other antithrombotic agents, but with a small magnificence, which may be attributed to the severely irrational use of this medication under improper management. Statistics in days, results showed that the risk of bleeding decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole.

Data mining and safety analysis of traditional immunosuppressive drugs: a pharmacovigilance investigation based on the FAERS database.

OBJECTIVE: The purpose of this study aimed to explore the new and serious adverse events(AEs) of Tacrolimus(FK506), cyclosporine(CsA), azathioprine(AZA), mycophenolate mofetil(MMF), cyclophosphamide(CTX) and methotrexate(MTX), which have not been concerned. METHODS: The FAERS data from January 2016 and December 2022 were selected for disproportionality analysis to discover the potential risks of traditional immunosuppressive drugs. RESULTS: Compared with CsA, FK506 has more frequent transplant rejection, and is more related to renal impairment, COVID-19, cytomegalovirus infection and aspergillus infection. However, CsA has a high infection-related fatality rate. In addition, we also found some serious and rare AE in other drugs which were rarely reported in previous studies. For example, AZA is closely related to hepatosplenic T-cell lymphoma with high fatality rate and MTX is strongly related to hypofibrinogenemia. CONCLUSION: The AEs report on this study confirmed that the results were basically consistent with the previous studies, but there were also some important safety signals that were inconsistent with or not mentioned in previous published studies. EXPERT OPINION: The opinion section discusses some of the limitations and shortcomings, proposing the areas where more effort should be invested in order to improve the safety of immunosuppressive drugs.

Adverse Events Following COVID-19 Vaccination in Adolescents: Insights From Pharmacovigilance Study of VigiBase.

BACKGROUND: During coronavirus disease 2019 (COVID-19) pandemic, several COVID-19 vaccines were licensed with fast-track procedures. Although these vaccines have demonstrated high immunogenicity, there has been concerns on the serious adverse events (AEs) following COVID-19 vaccination among adolescents. We aimed to analyze comparative safety of COVID-19 vaccination in adolescents. METHODS: In this pharmacovigilance study, we performed a disproportionality analysis using VigiBase, the World Health Organization's global individual case safety report (ICSR) database. To compare serious AEs reported following COVID-19 vaccines vs. all other vaccines in adolescents aged 12-17 years, ICSRs following any vaccines on adolescents aged 12-17 years were included, defining cases as reports with the AEs of interest, with all other AEs as non-cases. The AEs of interest were myocarditis/pericarditis, multisystem inflammatory syndrome/Kawasaki disease (MIS/KD), anaphylaxis, Guillain-Barré syndrome (GBS), and immune thrombocytopenia (ITP). We conducted a disproportionality analysis to estimate reporting odds ratio (ROR) with 95% confidence interval (CI) for each AE of interest, adjusted for sex by using logistic regression. RESULTS: Of 99,735 AE reports after vaccination in adolescents, 80,018 reports were from COVID-19 vaccinated adolescents (52.9% females; 56.3% America). The AEs of interest were predominantly reported as serious AE (76.1%) with mRNA vaccines (99.4%). Generally, higher reporting odds for the AEs were identified following COVID-19 vaccination in adolescents; myocarditis/pericarditis (2,829 reports for the COVID-19 vaccine vs. 35 for all other vaccines, adjusted ROR [aROR], 19.61; 95% CI, 14.05-27.39), and MIS/KD (104 vs. 6, aROR, 4.33; 95% CI, 1.89-9.88). The reporting odds for anaphylaxis (515 vs. 165, aROR, 0.86; 95% CI, 0.72-1.02), GBS (94 vs. 40, aROR, 0.64; 95% CI, 0.44-0.92) and ITP (52 vs. 12, aROR, 1.12; 95% CI, 0.59-2.09) were not significantly higher following COVID-19 vaccination. CONCLUSION: In this study, there were disproportionate reporting of immune-related AEs following COVID-19 vaccination. While awaiting definitive evidence, there is a need to closely monitor for any signs of immune-related AEs following COVID-19 vaccination among adolescents.

VigiBase Pharmacovigilance Studies on Antidepressant-Related Adverse Reactions: A Scoping Review.

VigiBase, the World Health Organization's collaborative global pharmaco-vigilance database, provides storage for millions of adverse drug reaction (ADR) reports. Pharmacovigilance scientists use the database to detect signals, assess, and understand trends in ADRs so that potential harms can be communicated. A search for pharmacovigilance studies on psychotropic-related ADR reports published over the past 5 years in VigiBase identified the majority to be antipsychotic-related ADRs, and within the antipsychotic class, clozapine-related. The nine antidepressant-related ADR reports were reviewed in more detail and provide an example of how the science of pharmacovigilance identifies and communicates medication risks. [Journal of Psychosocial Nursing and Mental Health Services, 62(3), 7-10.].

Artificial intelligence-powered pharmacovigilance: A review of machine and deep learning in clinical text-based adverse drug event detection for benchmark datasets.

OBJECTIVE: The primary objective of this review is to investigate the effectiveness of machine learning and deep learning methodologies in the context of extracting adverse drug events (ADEs) from clinical benchmark datasets. We conduct an in-depth analysis, aiming to compare the merits and drawbacks of both machine learning and deep learning techniques, particularly within the framework of named-entity recognition (NER) and relation classification (RC) tasks related to ADE extraction. Additionally, our focus extends to the examination of specific features and their impact on the overall performance of these methodologies. In a broader perspective, our research extends to ADE extraction from various sources, including biomedical literature, social media data, and drug labels, removing the limitation to exclusively machine learning or deep learning methods. METHODS: We conducted an extensive literature review on PubMed using the query "(((machine learning [Medical Subject Headings (MeSH) Terms]) OR (deep learning [MeSH Terms])) AND (adverse drug event [MeSH Terms])) AND (extraction)", and supplemented this with a snowballing approach to review 275 references sourced from retrieved articles. RESULTS: In our analysis, we included twelve articles for review. For the NER task, deep learning models outperformed machine learning models. In the RC task, gradient Boosting, multilayer perceptron and random forest models excelled. The Bidirectional Encoder Representations from Transformers (BERT) model consistently achieved the best performance in the end-to-end task. Future efforts in the end-to-end task should prioritize improving NER accuracy, especially for 'ADE' and 'Reason'. CONCLUSION: These findings hold significant implications for advancing the field of ADE extraction and pharmacovigilance, ultimately contributing to improved drug safety monitoring and healthcare outcomes.

Collaboration within the global vaccine safety surveillance ecosystem during the COVID-19 pandemic: lessons learnt and key recommendations from the COVAX Vaccine Safety Working Group.

This analysis describes the successes, challenges and opportunities to improve global vaccine safety surveillance as observed by the Vaccine Safety Working Group from its role as a platform of exchange for stakeholders responsible for monitoring the safety of vaccines distributed through the COVAX mechanism. Three key elements considered to be essential for ongoing and future pandemic preparedness for vaccine developers in their interaction with other members of the vaccine safety ecosystem are (1) the availability of infrastructure and capacity for active vaccine safety surveillance in low-income and middle-income countries (LMICs), including the advancement of concepts of safety surveillance and risk management to vaccine developers and manufacturers from LMICs; (2) more comprehensive mechanisms to ensure timely exchange of vaccine safety data and/or knowledge gaps between public health authorities and vaccine developers and manufacturers; and (3) further implementation of the concept of regulatory reliance in pharmacovigilance. These aims would both conserve valuable resources and allow for more equitable access to vaccine safety information and for benefit/risk decision-making.

Análisis de las notificaciones de úlceras cutáneas inducidas por medicamentos en España / Analysis of notifications of drug-induced skin ulcers in Spain

Las úlceras cutáneas son un serio problema de salud, el cual tiene repercusiones socioeconómicas y laborales muy importantes con una elevada tendencia a la cronicidad y recidiva, estimándose que hasta el 50% de ellas permanecerán activas entre 6 meses y un año. Objetivo: Estudio del papel de los medicamentos en la etiología de las úlceras cutáneas. Material y método: Estudio de todas las notificaciones espontáneas relativas a úlceras cutáneas que constan en la base de datos del Sistema Español de Farmacovigilancia de medicamentos de uso humano.Resultados: Se identificaron 292 notificaciones en las que constaban sospechas de reacción adversa a medicamentos (RAM) del tipo lesión ulcerosa relacionadas con el consumo de medicamentos. Estaban implicados 369 medicamentos que suponen 427 principios activos. Las úlceras fundamentalmente aparecían en mujeres con una media de edad de 56,6 años. Los medicamentos sospechosos más frecuentemente notificados fueron los iSGLT-2, vacunas frente al COVID-19, metotrexato, hidroxicarbamida, trimetropim-sulfametoxazol, foscarnet trisódico hexahidrato, ribavirina, docetaxel, acenocumarol e imiquimod y asociación de lidocaína Hcl-pentosano polisulfato sodio-triamcinolona acetónido. Discusión: Numerosos medicamentos tienen como reacción adversa la aparición de úlceras. No debería descartarse esta posibilidad ante la aparición de una lesión cutánea nueva tras la administración de un nuevo medicamento dado que el 25% de las RAM eran desconocidas en el momento de su notificación, como eran los casos de úlceras asociadas a los i-SGLT2 y a las vacunas contra el COVID al inicio de su comercialización; sin embargo, gracias al hecho de seguir notificando las sospechas de RAM, se crearon alertas sanitarias advirtiendo de este hecho y es por ello que aconsejamos seguir notificando cualquier sospecha de RAM a los sistemas regionales de farmacovigilancia.(AU)

Skin ulcers are a serious health problem with significant socioeconomic and labour repercussions and a high tendency to chronicity and recurrence; approximately, up to 50% remain active between six months to one year. Aim: To study the role of drugs in the aetiology of skin ulcers. Material and method: A comprehensive study of all spontaneous reports related to skin ulcers that appear in the Spanish Pharmacovigilance System of Medicines for Human Use database. Results: A total of 292 reports were identified containing suspected adverse drug reactions (ADRs) of ulcer lesion type. Three hundred sixty-nine medications with 427 active ingredients were identified. The ulcers appeared mainly in women with a mean age of 56.6 years. The most frequently reported suspected drugs were SGLT-2, vaccines against COVID-19, methotrexate, hydroxycarbamide, trimethoprim-sulfamethoxazole, foscarnet trisodium hexahydrate, ribavirin, docetaxel, acenocumarol and imiquimod, and the combination of lidocaine Hcl-pentosan polysulfate sodium-triamcinolone acetonide. Discussion: Numerous medications may cause ulcers as an adverse reaction. This possibility should not be ruled out when a new skin lesion appears after the administration of new drugs since 25% of the ADRs were unknown at the time of their notification, as were the cases of ulcers associated with i-SGLT2 and vaccines against COVID at the beginning of their commercialization. However, informative health alerts can be generated by continuously notifying suspected ADRs, so we strongly advise reporting any suspected ADRs to the regional pharmacovigilance system.(AU)

Evaluation of Kosovo pharmacists’ knowledge of tamoxifen-induced psychiatric disorders in comparison with reported side effects in the WHO pharmacovigilance database

Background: Tamoxifen is a widely prescribed selective estrogen receptor modulator (SERM) used for the treatment and prevention of hormone receptor-positive breast cancer. While tamoxifen has proven effective in lowering the chance of cancer recurrence, current data point to a possible link between tamoxifen treatment and unfavorable psychological consequences. Objective: In this study, the World Health Organization (WHO) pharmacovigilance database will be analyzed to determine the frequency and kind of psychiatric disorders linked to the use of the tamoxifen as well as Kosovo pharmacists’ awareness of these reported adverse effects. Methods: The WHO pharmacovigilance database, VigiBase, was queried for adverse drug reaction reports related to tamoxifen use between 1978 and 2022. A cross-sectional survey of 70 community pharmacies operating in Kosovo was conducted as part of the data collection between January 1 and March 1, 2023, with the goal of comparison. Results: The search of VigiBase yielded a total of 1746 reported cases of psychiatric disorders. The data were further classified based on the type of psychiatric adverse effect, including depressive disorders, anxiety disorders, cognitive impairment, and other psychiatric symptoms. Depressive disorders were the most frequently reported adverse event, accounting for 30% of the cases. Anxiety disorders and sleeps disorders were also prevalent, comprising 11% and 7% of the reported cases, respectively. Other psychiatric symptoms such as mood swings, insomnia, and confusion were observed in 32% of the cases. In Kosovo, 30% of pharmacist’s linked tamoxifen with depression, 25% with anxiety, 56% with sleep disorders, 53% insomnia, and 18% confusion. Conclusions: Based on the WHO pharmacovigilance database and knowledge of Kosovo pharmacists for these documented adverse effects, this study analyzes tamoxifen-induced psychiatric disorders... (AU)

Exploration of adverse events associated with risdiplam use: Retrospective cases from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Risdiplam is a new drug for treating spinal muscular atrophy (SMA). However, pharmacovigilance analyses are necessary to objectively evaluate its safety-a crucial step in preventing severe adverse events (AEs). Accordingly, the primary objective of the current study was to examine the AEs associated with risdiplam use based on real-world data obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. More specifically, we examined incidents reported between the third quarter of 2020 and the second quarter of 2023. The imbalance of risdiplam-related AEs was evaluated by computing the reporting odds ratio. A total of 5,406,334 reports were thoroughly reviewed. By removing duplicate reports, we identified 1588 reports in which risdiplam was the main suspected drug whose use was accompanied by 3470 associated AEs. Among the included AEs, 703 were categorized as serious and 885 as non-serious. Risdiplam use induced AEs across 18 organ systems, resulting in 130 positive signals. Notably, we detected new AE signals, including cardiac arrest, nephrolithiasis, tachycardia, loss of libido, and elevated hepatic enzyme activities; however, no ophthalmologic toxicity was reported. Although these new adverse reaction signals associated with risdiplam have been defined, long-term clinical studies are needed to confirm these findings. Nevertheless, our findings provide a valuable reference for improving the clinical management of SMA.

Medications Mostly Associated With Ejaculatory Disorders: Assessment of the Eudra-Vigilance and Food and Drug Administration Pharmacovigilance Databases Entries.

OBJECTIVE: To identify which medications are mostly associated with ejaculatory disorders through a disproportionality analysis. METHODS: The Food and Drug Administration Adverse Event Reporting System (FDA-FAERS) and the Eudra-Vigilance (EV) database were queried to identify medications more commonly associated to ejaculatory disorders from September 10, 2012 to June 1, 2023. Proportional Reported Ratios (PRRs) were computed for all the selected drugs. RESULTS: Overall, 7404 reports of ejaculatory disorders reports were identified, and of these, 6854 cases (92.6%) were attributed to ten specific medications. On FDA-FAERS and EV databases, Paroxetine and Tamsulosin were the main responsible of delayed ejaculation (103/448 events, 23.0%) and retrograde ejaculation (366/1033 events, 35.4%), respectively. Finasteride was mostly related to painful ejaculation and ejaculation failure, with 150 events (7.8%) and 735 events (38.4%) respectively. Within the group of high-risk medications, Sildenafil presented higher risk of ejaculatory disorders than Tadalafil (PRR=5.85 (95%CI 5.09-6.78), P < .01). CONCLUSION: Ten drugs were recognized to display significant reporting levels of ejaculatory disorders. Among them, Finasteride and Sildenafil were responsible for the most reports in FDA-FAERS and in EV databases, respectively. Physicians should thoroughly counsel patients treated with these drugs about the risk of ejaculatory disorders. Further integration into clinical trials is needed to enhance the applicability and significance of these results.