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OBJECTIVES: Adverse drug reactions (ADRs) are among the leading standalone causes of morbidity and hospitalisation and contribute substantially to an increase in healthcare expenditure. Repeat ADR events, although difficult to quantify, are a recognised problem that lead to preventable suffering for the patient. The current approaches for the prevention of ADR recurrence in low/middle-income countries range from inefficient to non-existent. There is very little literature that focuses on the preventability of ADRs in such settings. This study aimed to develop the ADR Alert Card, an economical innovation designed as a stop gap in preventing ADR recurrence, and to evaluate its utility by validating the system through input from medical professionals. METHODS: The ADR Alert Card was validated and registered with the Copyrights Office of the Government of India. To obtain the opinion of healthcare professionals and gauge the status quo in prevention of ADR recurrence, we conducted an online descriptive cross-sectional study over a period of 6 months. RESULTS: The survey received 218 responses. Demographics varied, ranging across different healthcare specialties and years of experience. Our study found that existing practice in ADR recurrence prevention was inadequate, and most healthcare workers were unaware of an alternative approach. Unique solutions were provided by the respondents, with the majority favouring a card format for preventing recurrence. CONCLUSIONS: After being introduced to the ADR Alert Card, there was an overwhelming consensus on the utility and practicality of this card in preventing ADR recurrence.

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Budd-Chiari syndrome (BCS) is a rare disease characterised by an obstruction in the hepatic venous outflow. We describe two cases of patients hospitalised a few days after tozinameran vaccination. Liver tests and medical imaging were carried out, and BCS was diagnosed. After treatment including anticoagulant therapy, the first patient improved clinically, unlike the second patient with persistent hepatic thrombosis. According to the WHO-UMC causality assessment system, the vaccine's share was assessed as 'probable' for the first patient as BCS occurred during anticoagulant therapy, and 'possible' for the second patient as no other aetiology was found. Further epidemiological studies are needed to confirm or refute the causal relationship between BCS and tozinameran vaccination.

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This study aimed to investigate the current knowledge and experiences of consumers in Australia on adverse drug reaction (ADR) reporting and their reasons for reporting or not reporting ADRs, with a focus on the use of digital tools for ADR reporting. METHODS: A cross-sectional online survey was conducted among adults who had taken medicine in Australia. A structured questionnaire with multiple choice or Likert scale responses with an option for participants to provide free-text responses and pretested for face validity was used. Consumer characteristics, knowledge, and ADR reporting practices were analyzed using descriptive statistics and the chi-square test or Fisher's exact test. RESULTS: A total of 544 survey responses were included in the analysis. The majority of respondents were women (68%), and 22% were aged between 65 and 74 years. Fifty-eight percent (n = 317) of respondents knew that they could report ADRs to either the Therapeutic Goods Administration (TGA), state or territory government health department, or healthcare professionals. Three-quarters (n = 405) of respondents stated that they had experienced an ADR; of these, 36% reported an ADR to either the TGA, state or territory government health department, or healthcare professionals. Among those who reported ADRs, 58% were unaware that they could use digital tools to report ADRs. The main reason for not reporting was that they did not think the ADR was serious enough to report (39%). CONCLUSION: Over half of consumers knew that they could report ADR; however, improved consumer awareness about using digital tools for ADR reporting and increased ADR reporting is needed.

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OBJECTIVE: Several medications are associated with delirium; however, studies with adequate statistical power are limited, and it is difficult to determine the effects of the various concomitant medications used in clinical practice. Therefore, in this study, we aimed to comprehensively evaluate the safety signals of delirium-associated drugs using a spontaneous adverse event reporting system. METHOD: The JAPIC AERS (Food and Drug Administration Adverse Event Reporting System pre-processed by the Japan Pharmaceutical Information Center) was used for the analysis in this pharmacovigilance study. The reporting odds ratio (ROR) for delirium was adjusted for using multivariate logistic regression analysis with sex, age, indication, and melatonin receptor agonist use, and 22 drug categories were targeted as covariates. RESULTS: After excluding patients with missing information, 7,527,568 patients were included in the study. Delirium signals were detected even after adjusting for covariates in 17 drug categories, including benzodiazepines (adjusted ROR, 1.76; 95% confidence interval [CI], 1.64-1.89), opioids (adjusted ROR, 4.42; 95% CI, 4.21-4.64), and tricyclic antidepressants (adjusted ROR, 2.44; 95% CI, 2.20-2.71). CONCLUSIONS: These findings suggest that many drug classes, such as benzodiazepines, are independent risk factors for delirium and strengthen the evidence of an association between delirium and medications.

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PURPOSE: This study aimed to perform a nationwide analysis of medication errors (MEs) from hospitals using national reporting system data and to compare the ME patterns among different age groups. METHODS: We analyzed medication-related incidents in acute care hospitals reported to the Korean Patient Safety Reporting and Learning System (KOPS), which is a patient safety reporting system, from July 2016 to December 2020. The stages of the medication use process, type of errors, medication class involved in MEs, and degree of harm were analyzed. RESULTS: Among a total of 5071 medication-related incidents, 37.7% (1911 cases) were incidents that caused patient harm and 1.2% caused long-term, permanent, and fatal harm. The proportion of medication-related incidents that resulted in harm was the highest among the <1-year-old age group (67 cases, 51.5%), followed by the elderly (≥ 65 years) (828 cases, 40.9%). The cases leading to patient death were most frequently reported in patients aged ≥65 years. Medication-related incidents occurred mainly in the administration stage (2954 cases, 58.3%), and wrong dose was the most frequently reported ME type. The most prevalent medication class occurring in the 20-64-year age group (256 cases, 11.7%) was 'antibacterials for systemic use', whereas 'contrast media' (236 cases, 11.6%) and 'blood substitutes and perfusion solutions' (98 cases, 19.3%) were the most prevalent drug classes in the ≥65- and <20-year-old age groups, respectively. CONCLUSIONS: It is necessary to establish guidelines for the prevention of medication-related incidents according to the medication use process and patient age group.

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PURPOSE: This study investigates the clinical impact of electronic patient-reported outcome (ePRO) monitoring apps/web interfaces, aimed at symptom-management, in cancer patients undergoing outpatient systemic antineoplastic treatment. Additionally, it explores the advantages offered by these applications, including their functionalities and healthcare team-initiated follow-up programmes. METHODS: A systematic literature review was conducted using a predefined search strategy in MEDLINE. Inclusion criteria encompassed primary studies assessing symptom burden through at-home ePRO surveys in adult cancer patients receiving outpatient systemic antineoplastic treatment, whenever health outcomes were evaluated. Exclusion criteria excluded telemedicine-based interventions other than ePRO questionnaires and non-primary articles or study protocols. To evaluate the potential bias in the included studies, an exhaustive quality assessment was conducted, as an additional inclusion filter. RESULTS: Among 246 identified articles, 227 were excluded for non-compliance with inclusion/exclusion criteria. Of the remaining 19 articles, only eight met the rigorous validity assessment and were included for detailed examination and data extraction, presented in attached tables. CONCLUSION: This review provides compelling evidence of ePRO monitoring's positive clinical impact across diverse cancer settings, encompassing various cancer types, including early and metastatic stages. These systems are crucial in enabling timely interventions and reducing communication barriers, among other functionalities. While areas for future ePRO innovation are identified, the primary limitation lies in comparing clinical outcomes of reviewed articles, due to scale variability and study population heterogeneity. To conclude, our results reaffirm the transformative potential of ePRO apps in oncology and their pivotal role in shaping the future of cancer care.

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OBJECTIVES: Drug shortages are of increasing concern to worldwide public health. The consequences of drug shortages for patient safety have been little studied, especially from a pharmacovigilance point of view. In this context, the network of French pharmacovigilance centres conducted the CIRUPT study (Conséquences Iatrogènes des RUPTures de stock/iatrogenic consequences of drug shortages) based on a prospective campaign of adverse effects occurring in the context of drug shortage notifications. METHODS: All notifications involving a shortage drug submitted to the French pharmacovigilance centres between 1 January 2020 and 30 June 2021 were collected and registered in the French national pharmacovigilance database with the standardised high level term 'product supply and availability issues' and with predefined keywords in the narrative section. RESULTS: 224 cases were included, involving mainly adverse drug reactions (ADRs) (n=131/224, 59%) and medication errors (n=51/224, 23%); 29% of the cases were serious. The most represented classes of shortage drugs were: vaccines (n=78/224, 35%); drugs for acid-related disorders (H2-receptor antagonists) (n=27/224, 12%); antineoplastic agents (n=17/224, 8%); and antiepileptics (n=15/224, 7%). In 82% of cases, the involved shortage drug was the subject of information delivered to health professionals by the National Agency for the Safety of Medicines and Health Products. Drug shortages were associated with an ADR related to replacement drugs in 59% (n=131/224) of the cases, drug inefficacy in 18% (n=41/224), and/or an aggravation of the underlying disease in 11% (n=25/224). CONCLUSIONS: From a pharmacovigilance point of view, a large diversity of anatomical therapeutic classes is involved and the risk related to drug shortages is not limited to drugs registered on 'major therapeutic interest or essential drug' lists. Information from health agencies is not sufficient to avoid the risks, and further strategies should be developed.

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BACKGROUND: People with gender dysphoria are treated with hormone therapy for gender reassignment. The indication of this therapy was initially for the opposite sex, and information on potential adverse drug reaction (ADR) is lacking. OBJECTIVE: To describe ADR associated with gender transition medication in transgender individuals reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Data from the FAERS database up to June 2023 were examined, focusing on reports of gender transition medication use in the context of gender dysphoria. The ADRs were categorized using the Medical Dictionary for Regulatory Activities at both Preferred Term and System Organ Class (SOC) levels. Descriptive statistics summarized report counts, medication types, indications, and ADR severity. RESULTS: For individuals assigned female at birth undergoing gender transition to male (transgender men), 82 reports (230 ADRs) were analyzed, with an average age of 29.5 years. Transgender hormonal therapy was cited in 72% of reports, predominantly from the United States (67.1%). A striking 88% were categorized as serious ADRs, primarily SOC injury, poisoning, and procedural complications (26.5%), followed by psychiatric disorders (14.8%) and nervous system disorders (12.2%). Among those assigned sex male at birth transitioning to female (transgender women) (81 reports, 237 ADRs), mean age was 33.3 years, with 58% indicating use for gender dysphoria. A significant proportion (53.6%) were serious ADRs, primarily SOC: injury, poisoning, and procedural complications (26.6%). CONCLUSIONS AND RELEVANCE: The FAERS data reveal significant ADRs in transgender individuals using hormone therapy, sometimes unintended for their recipient gender. Population-level studies are crucial to enhance transgender health care. Spontaneous surveillance databases like FAERS illuminate off-label ADRs, urging health care providers to approach hormone therapies with informed caution.

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La vacunación de la gripe en embarazadas muestra una clara relación beneficio/riesgo. En la actualidad se están desarrollando vacunas contra la gripe utilizando nuevas plataformas. Es imprescindible analizar la seguridad de estas nuevas vacunas en este grupo poblacional, infrarrepresentado en los ensayos clínicos. En la temporada 2019-2020 se aconsejó una vacuna obtenida en cultivo celular a las embarazadas en 2comunidades autónomas. Se recogió información de los centros de vacunación y de farmacovigilancia de ambas comunidades. La tasa de notificación de casos de acontecimientos adversos tras la vacunación en embarazadas fue de 4,02/100.000 dosis administradas y, en mujeres de 18 a 64 años no embarazadas, de 5,9/100.000 dosis administradas. La tasa de acontecimientos adversos notificados fue de 8,04 y 17,74, respectivamente. No se notificaron abortos espontáneos, prematuridad ni malformaciones fetales. Este análisis señala la seguridad en embarazadas de la vacuna de la gripe obtenida de cultivos celulares.(AU)

Influenza vaccination in pregnant women shows a clear benefit/risk ratio. Influenza vaccines are currently being developed using new platforms. It is essential to analyze the safety of these new vaccines in this population group, underrepresented in clinical trials. In the 2019-2020 season, a vaccine obtained in cell culture was recommended to pregnant women in 2autonomous communities. Information is collected from the vaccination and pharmacovigilance centers of both communities. The reporting rate of adverse events after vaccination in pregnant women was 4.02/100,000 doses administered, and in non-pregnant women aged 18-64 years it was 5.9/100,000 doses administered. The rate of adverse events reported was 8.04 and 17.74, respectively. No spontaneous abortions, prematurity or fetal malformations were reported. This analysis suggests the safety in pregnant women of the influenza vaccine obtained from cell cultures.(AU)

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OBJECTIVE: To evaluate the risk of myasthenia gravis (MG) associated with immune checkpoint inhibitors (ICI). METHODS: Adverse event (AE) reports related to MG, myasthenic syndrome, and MG crisis for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab in the US FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q3 2022 were collected. The proportional reporting odds ratio (PRR) method was used to evaluate the correlation between the six drugs and the three AEs. Statistical significance was defined as having reports ≥3, PRR ≥ 2, and chi-square (χ2 ) ≥ 4. RESULTS: A total of 36, 78, 276, 380, 5, and 53 AE reports were collected for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For myasthenic syndrome, the PRR values reflecting the correlation with the drugs were 27.83 (χ2 = 102.66), 26.20 (χ2 = 235.67), 44.17 (χ2 = 1313.98), 32.09 (χ2 = 1229.54), 21.31 (χ2 = 151.15), and 0 for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG, the PRR values reflecting the correlation with the drugs were 24.21 (χ2 = 682.04), 18.34 (χ2 = 900.27), 39.32 (χ2 = 7945.15), 26.93 (χ2 = 6636.45), 14.73 (χ2 = 566.47), and 15.69 (χ2 = 54.77) for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG crisis, there were no data for durvalumab, atezolizumab, avelumab, and ipilimumab; the PRR values reflecting the correlation with the drugs were 16.54 (χ2 = 225.23) and 9.20 (χ2 = 119.14) for pembrolizumab and nivolumab, respectively. All six drugs were statistically correlated with their corresponding AEs. CONCLUSIONS: ICI may lead to ICIs-associated MG during therapy. Analysis of FAERS data identified signals for AEs of MG with ICI regimens. Practitioners should consider the factors that may increase the likelihood of MG. The findings support a continued surveillance and risk factor identification.

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Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04-53.00), leukopenia (4.04, 95%CI 3.52-4.64), and thrombocytopenia (4.01, 95%CI 3.19-5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia.

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This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs.

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A man with diffuse large B-cell lymphoma in the nasal cavity was treated with sindilizumab, an immune checkpoint inhibitor, combined with local radiotherapy for multiple nodules of the left upper arm. After a single administration of sindilizumab and 10 radiotherapy treatments, the patient presented with liver dysfunction. Liver function tests showed that the levels of transaminases had increased abnormally and deteriorated though with intense treatment. His bilirubin level was also increased with obvious yellow staining of the skin and sclera. The patient was considered to have severe immune-mediated hepatitis (IMH) caused by sindilizumab combined with local radiotherapy. His liver function did not improve and he died of organ failure. This is a case of rare liver failure which was considered to be IMH induced by synergistic treatment with immune checkpoint therapy and radiotherapy.

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Introduction: Post-marketing identification and report of unknown adverse drug reactions (ADRs) are crucial for patient safety. However, complete information on unknown ADRs seldom is available at the time of spontaneous ADR reports and this can hamper their contribution to the pharmacovigilance system. Methods: In order to characterize the seriousness and outcome of unknown ADRs at the time of report and at follow-up, and analyze their contribution to generate pharmacovigilance regulatory actions, a retrospective observational study of those identified in the spontaneous ADR reports of patients assisted at a hospital (January, 2016-December, 2021) was carried out. Information on demographic, clinical and complementary tests was retrieved from patients' hospital medical records. To evaluate the contribution to pharmacovigilance system we reviewed the European Union SmPCs, the list of the pharmacovigilance signals discussed by the Pharmacovigilance Risk Assessment Committee, and its recommendations reports on safety signals. Results: A total of 15.2% of the spontaneous reported cases during the study contained at least one unknown drug-ADR pair. After exclusions, 295 unknown drug-ADR pairs were included, within them the most frequently affected organs or systems were: skin and subcutaneous tissue (34, 11.5%), hepatobiliary disorders (28, 9.5%), cardiac disorders (28, 9.5%) and central nervous system disorders (27, 9.2%). The most frequent ADRs were pemphigus (7, 2.4%), and cytolytic hepatitis, sudden death, cutaneous vasculitis and fetal growth restriction with 6 (2%) each. Vaccines such as covid-19 and pneumococcus (68, 21.3%), antineoplastics such as paclitaxel, trastuzumab and vincristine (39, 12.2%) and immunosuppressants such as methotrexate and tocilizumab (35, 11%) were the most frequent drug subgroups involved. Sudden death due to hydroxychloroquine alone or in combination (4, 1.4%) and hypertransaminasemia by vincristine (n = 3, 1%) were the most frequent unknown drug-ADR pairs. A total of 269 (91.2%) of them were serious. Complementary tests were performed in 82.7% of unknown-ADR pairs and helped to reinforce their association in 18.3% of them. A total of 18 (6.1%) unknown drug-ADR pairs were evaluated by the EMA, in 8 (2.7%) the information was added to the drug's SmPC and in 1 case the risk prevention material was updated. Conclusion: Identification and follow-up of unknown ADRs can be of great relevance for patient safety and for the enrichment of the pharmacovigilance system.

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Objective: Between 2012 and 2017, the U.S. Food and Drug Administration (FDA) approved 10 antidiabetic indicated therapies. Due to the limited literature on voluntarily reported safety outcomes for recently approved antidiabetic drugs, this study investigated adverse drug reactions (ADRs) reported in the FDA Adverse Event Reporting System (FAERS). Research Design and Methods: A disproportionality analysis of spontaneously reported ADRs was conducted. FAERS reports from January 1, 2012 to March 31, 2022 were compiled, allowing a 5-year buffer following drug approval in 2017. Reporting odds ratios were calculated for the top 10 ADRs, comparing new diabetic agents to the other approved drugs in their therapeutic class. Results: 127,525 reports were identified for newly approved antidiabetic medications listed as the primary suspect (PS). For sodium-glucose co-transporter-2 (SGLT-2) inhibitors, the odds of blood glucose increased, nausea, and dizziness being reported was greater for empagliflozin. Dapagliflozin was associated with greater reports of weight decreased. Canagliflozin was found to have a disproportionally higher number of reports for diabetic ketoacidosis, toe amputation, acute kidney injury, fungal infections, and osteomyelitis. Assessing glucagon-like peptide-1 (GLP-1) receptor agonists, dulaglutide and semaglutide were associated with greater reports of gastrointestinal adverse drug reactions. Exenatide was disproportionally associated with injection site reactions and pancreatic carcinoma reports. Conclusion: Pharmacovigilance studies utilizing a large publicly available dataset allow an essential opportunity to evaluate the safety profile of antidiabetic drugs utilized in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved antidiabetic medications to determine causality.

Adverse drug reactions reported for antidiabetic medications Introduction: This study investigated the trends in voluntary reporting of adverse drug reactions for recently approved antidiabetic medications. Methods: Data from the FDA Adverse Events Reporting System were evaluated. The top 10 adverse drug reactions were compared between antidiabetic medications in the same therapeutic class. Results: We identified 127,525 adverse drug reaction reports for the newer approved antidiabetic medications. For SGLT-2 inhibitors, empagliflozin was associated with greater reports of blood glucose increase, nausea, and dizziness; weight decreased was reported more often for dapagliflozin; and diabetic ketoacidosis, toe amputation, acute kidney injury, fungal infections, and osteomyelitis were reported more commonly for canagliflozin. Assessing GLP-1 receptor agonists, the odds of gastrointestinal adverse drug reactions being reported was greater for dulaglutide and semaglutide. Exenatide was disproportionally associated with injection site reactions and pancreatic carcinoma reports. Conclusion: Medication safety studies using a large publicly available dataset allows an essential opportunity to evaluate the safety profile of antidiabetic drugs in the real-world setting. Additional research is needed to determine if the reported safety concerns for recently approved antidiabetic medications to determine causality.