Adverse Drug Reaction Profile Research Articles

Profile of adverse drug reactions reported via the Continuum+ platform: results from three-year regional follow-up

Profile of adverse drug reactions reported via the Continuum+ platform: results from three-year regional follow-up

Adverse drug reaction profile of third-generation smallpox vaccines used in France during the 2022 monkeypox epidemic.

Due to the start of the monkeypox epidemic in 2022, we retrospectively analyzed the adverse drug reactions (ADRs) reported in France after monkeypox vaccinations with the third-generation smallpox vaccine. Ninety-eight cases, representing 172 ADRs, were reported. ADRs were mostly expected reactogenicity reactions occurring within days after the first dose of vaccine and having a quick favorable outcome. Unexpected facial palsy and vaccination failure are discussed.

Non-Negative matrix factorization combined with kernel regression for the prediction of adverse drug reaction profiles

Abstract Motivation Post-market unexpected Adverse Drug Reactions (ADRs) are associated with significant costs, in both financial burden and human health. Due to the high cost and time required to run clinical trials, there is significant interest in accurate computational methods that can aid in the prediction of ADRs for new drugs. As a machine learning task, ADR prediction is made more challenging due to a high degree of class imbalance and existing methods do not successfully balance the requirement to detect the minority cases (true positives for ADR), as measured by the Area Under the Precision-Recall (AUPR) curve with the ability to separate true positives from true negatives (as measured by the Area Under the Receiver Operating Characteristic (AUROC) curve). Surprisingly, the performance of most existing methods is worse than a naïve method that attributes ADRs to drugs according to the frequency with which the ADR has been observed over all other drugs. The existing advanced methods applied do not lead to substantial gains in predictive performance. Results We designed a rigorous evaluation to provide an unbiased estimate of the performance of ADR prediction methods: Nested Cross-Validation and a hold-out set were adopted. Among the existing methods, Kernel Regression performed best in AUPR but had a disadvantage in AUROC, relative to other methods, including the naïve method. We proposed a novel method that combines Non-negative Matrix Factorization with Kernel Regression, called VKR. This novel approach matched or exceeded the performance of existing methods, overcoming the weakness of the existing methods. Availability Code and data are available on https://github.com/YezhaoZhong/VKR. Supplementary information Supplementary data are available at Bioinformatics online.

A RETROSPECTIVE ANALYSIS OF REPORTED CUTANEOUS ADVERSE DRUG REACTIONS IN A TERTIARY CARE TEACHING HOSPITAL

Objectives: Analysis of adverse drug reactions (ADR) reports enriches and updates physician’s awareness about the pattern of cutaneous adverse reactions in the population studied and may play an important role to envision the frequency of appearance of reactions to specific drugs and morphological designs. This study intends to portray the clinical profile and causative agents of dermal ADRs in our population. Methods: All the ADR reporting forms received from February 2021 to February 2023 were scrutinized, and forms with cutaneous ADRs (CADRs) were analyzed. The data about the history of drug intake, names of the drug taken, time lag of appearance of reaction, and clinical examination details were collected from the reports. Demography, prevalence, reaction time morphological pattern, and causative agents of CADRs were evaluated. Results: Among the CADRs, acute urticaria 53.4 was the most common followed by acute exanthematous reaction 35.8% and lichenoid drug eruption 3.8%. Among the drugs causing CADRs, antibiotics top the list with 47% followed by ATT at 29.7% and iron sucrose 12.9%. Among the antimicrobials, fluoroquinolones 48% top the list followed by cephalosporins 21.6% and penicillins and vancomycin each 8.3%. Conclusion: Physician’s knowledge about pattern and causative agents of CADR in the specific population can aid in prevention and early management of ADRs and thereby reducing hospitalization.

Clinico-Epidemiological Profile and Treatment Outcome of Severe Cutaneous Adverse Drug Reactions in the Paediatric Age Group of 0 to 18 Years: A Retrospective Cohort Study from Southern India

Introduction: The paediatric population is prone to developing cutaneous adverse drug reactions. However, the incidence of Severe Cutaneous Adverse Drug Reactions (SCAR) is rare in this age group, with few studies describing such reactions in detail. Aim: To describe the clinico-epidemiological factors, drug profile, laboratory parameters, and treatment outcomes of SCAR in children admitted to a tertiary care centre in South India. Materials and Methods: A retrospective cohort study was carried out over a 10-year period, including paediatric patients (0-18 years) admitted to Dermatology, Medicine, and Paediatric wards in the tertiary care centre. Demographic details, suspected drugs, comorbidities, personal and family history of drug reactions, physical examination, laboratory parameters, treatment received along with its duration, and the state of morbidity and mortality were recorded. SPSS version 18.0 was used for analysis. Descriptive statistics were used to summarise the demographics and clinical characteristics of the patients. Results: Among all the patients admitted with SCAR, 27 (15%) belonged to the paediatric age group. The median age was 15 years, and the female-to-male ratio was 1.25. Nineteen (70.3%) were diagnosed with Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), and eight (29.6%) were diagnosed with Drug Reaction with Eosinophilia and Systemic Symptom (DRESS). There were no cases of Acute Generalised Exanthematous Pustulosis (AGEP). The most common class of drugs implicated was antiepileptics (62.8%). Two patients (7%) had a family history of drug reactions. All patients had mucosal involvement. The majority of the children responded to intravenous steroids, and two required additional intravenous immunoglobulin injections for clinical improvement. All cases were cured with no mortality or long-term sequelae. Conclusion: The incidence of SCAR in the paediatric age group is significant. Anticonvulsants, particularly phenytoin, carbamazepine, and lamotrigine, need to be used with caution in this age group. Prompt diagnosis and treatment with systemic steroids can reduce mortality, morbidity, and long-term sequelae.

An open-label prospective observational study to evaluate the efficacy and safety of alternate day versus daily dosing of atorvastatin in patients of dyslipidemia

Background: Hypercholesterolemia is a main driver of atherosclerosis. Cholesterol-containing lipoproteins induce endothelial dysfunction and macrophage activation. Foam cell formation results from the uptake of cholesterol-containing lipoproteins by macrophages, it is an essential step in the initiation and progression of atherosclerosis. Aims and Objectives: To evaluate the efficacy and safety of alternate day versus daily dosing of atorvastatin in patients with dyslipidemia. Materials and Methods: This open-label, prospective, observational study was conducted on dyslipidemic patients who came into the medicine Outpatient Department of Dhanalakshmi Srinivasan Medical College and Hospital, Tamil Nadu. Approval for the study was taken from the Institutional Ethical Committee. The duration of the study was 3 months. The efficacy of atorvastatin was checked by noting their blood lipid profile status. Results: Out of 100 patients included in the study 79 completed the study whereas 21 patients were lost in follow-up, 42 patients were analyzed in daily dose (Group A), and 37 patients in alternate dose (Group B) of atorvastatin (20 mg). There was no statistically significant difference based on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels both prior and post-treatment in both the groups. Adverse drug reactions (ADR) profile showed a statistically significant difference between both the groups after treatment by atorvastatin (P=0.0001), with more ADRs noted in a daily dosing group. Conclusion: The results of this study show that alternate dosing of atorvastatin was better tolerated than daily dosing hence physicians can consider choosing an alternate day therapy to reduce pill burden on patients.

Adverse drug reactions seen in cancer patients undergoing palliative care treatment at a palliative care center in Alappuzha

Background: Adverse drug reactions are a major contributor to morbidity and hospitalization in patients and have been held responsible for as much as 5% of hospital admissions. This is especially relevant in cancer patients undergoing palliative care because they often suffer from advanced/terminal cancer and the adverse drug reactions from the palliative care drugs can affect their remaining quality of life. Aim and Objectives: The aim of this study was to study the adverse drug reaction profile of palliative drugs used in cancer patients undergoing palliative care at the Pain and Palliative Care OPD and their association with gender, age, dose, and duration of opioid intake. Materials and Methods: After receiving permission from the Institutional Ethics Committee, TDMC Alappuzha, 138 eligible cancer patients receiving palliative care from the pain and palliative care OPD were included in the study. The necessary data were obtained through interviews with the patients, who had given their consent to the study and the information was used to fill a questionnaire. Results: Out of the 138 study participants, 96 were male and 42 were female. The age composition ranged from 35 years to 88 years of age. There were 30 diabetic patients, 28 hypertensive patients, and 13 patients with CAD. The most frequent adverse effects, seen within 2 weeks of a 5 mg dose oral morphine regimen, were nausea (58.26%), constipation (51.18%), vomiting (43.30%), insomnia (33.07%), sedation (31.49%), dry mouth (25.19%), abdominal discomfort (24.04%), edema (20.47%) and tremors (19.68%). Using the modified Naranjo algorithm, 12% of ADRs were doubtful, 40% of ADRs were possible, 32% of ADRs were probable, and 16% of ADRs were definite. Among male patients taking 5 mg oral morphine, the most frequent ADRs were nausea (56.25%), constipation (45.31%), vomiting (40.62%), insomnia (34.37%), sedation (26.56%), dry mouth (21.87%), abdominal discomfort (18.75%), and edema (17.18%). Among female patients, the most frequent ADRs were vomiting (58.62%), nausea (55.17%), constipation (55.17%), abdominal discomfort (34.48%), dry mouth (31.03%), insomnia (31.03%), tremors (31.03%), sedation (24.13%), edema (20.68%), and pruritus (20.68%). Almost no significant associations were seen w.r.t to age, dose, and duration of opioid intake. Conclusion: The study identified the adverse effects associated with palliative care and their relative incidence. It also attempted to derive a correlation between the incidence of adverse effects and the age and gender of patient, the dose, and duration of opioid use.

Adverse Drug Reactions in the Bipolar Disorder Patients Treated With Mood Stabilizers

Abstract Background: Bipolar disorder is a chronic illness requiring long-term use of mood stabilizers such as lithium and sodium valproate. The adverse drug reactions (ADRs) of these medicines can severely affect the quality of life of the patients. A comparative study of ADR profile of lithium and valproate in terms of prevalence, severity, and causality has not been done in the rural population of India. Methodology: A cross-sectional, observational study was done in the psychiatry outpatient department of a tertiary health care center. The bipolar disorder patients on lithium carbonate or divalproate monotherapy were chosen for documentation of ADRs after informed consent. The Naranjo causality algorithm and Modified Hartwig and Siegel scale for severity assessment were applied to all participants. The data obtained were statistically analyzed using Epi Info open-source software. Results: The study participants having mean age of 33.83 ± 12.02 years comprised nearly equal number of males and females. Tremors (19.4%), polyuria (11.5%), and polydipsia (11.2%) were the most common ADRs due to lithium, whereas nausea (12.6%), anorexia (10.6%), and sedation (9.1%) were more commonly seen in patients on valproate. Most of the ADRs had a mild severity and were categorized as possible in the Naranjo causality algorithm. Conclusion: Although ADRs are common in bipolar disorder patients treated with lithium or valproate, they are often mild and well tolerated by the patients.

Comparative effectiveness-safety of conventional versus newer antiepileptics in epileptic patients in a tertiary care hospital, India

<b>Background</b>: As initial monotherapy, individuals with epilepsy are treated with both conventional and newer antiepileptic drugs (AEDs). The differences in their relative effectiveness and safety as a group, however, have not been thoroughly studied.<br /> <b>Objective:</b> To evaluate and compare the effectiveness and safety of conventional and newer anti-epileptic drugs in epileptic patients.<br /> <b>Material and methods:</b> A prospective comparative study was done in 126 epileptic patients. Patients divided into two groups Group A and B of 63 each received conventional and newer antiepileptic drugs respectively. Patients were allocated the AED based on type of epilepsy, patient characteristics and drug characteristics by the treating physician. Patients maintained a seizure diary which they filled weekly and this seizure diary was evaluated at 6 weeks and 12 weeks of follow up. Patients were assessed for adverse drug reactions (ADRs) at 0, 6 and 12 weeks of follow up and also for spontaneous reported ADRs at any time during the study.<br /> <b>Results:</b> In both group A and group B, our study demonstrated that seizure freedom, seizure severity, and time before first seizure did not differ significantly (p>0.5). Except for cognitive dysfunction, impaired memory, and swollen gums, which were more frequent in the conventional anti-epileptics group, the ADR profiles of both group of medications were similar. Phenytoin was found to cause gum swelling and cognitive impairment. No subject experienced a serious adverse event.<br /> <b>Conclusion:</b> Newer Antiepileptics as monotherapy are equally efficacious as conventional antiepileptics but may offer a better safety profile to epileptic patients.

Comparative Analysis of Adverse Drug Reactions (ADRs) between COVID-19 Vaccines and Established Vaccines: A CDC VAERS Database Analysis

Background: COVID-19 vaccines have been developed rapidly to combat the pandemic, but vaccine hesitancy remains a challenge due to concerns about adverse drug reactions (ADRs). This study aimed to compare the ADR profiles of COVID-19 vaccines with established vaccines and investigate differences between adults and children.
 Methods: A retrospective observational study used the VAERS database to analyze ADR reports from January 2021 to December 2022 in the United States. Top ten common ADRs and seven severe ADRs associated with COVID-19 vaccines were studied using the Evans Criteria.
 Results: Among the common ADRs, only dyspnea showed disproportionate reporting in COVID-19 vaccines. Severe ADRs, including myocarditis, pneumonia, and cerebrovascular accidents, were disproportionately reported. Age-stratified analysis revealed myocarditis disproportionately reported in both adults and children.
 Conclusions: This study provides a comprehensive comparison of ADRs between COVID-19 vaccines and established vaccines. Although some severe ADRs were disproportionately reported, further evaluation is required to establish any causal relationships with COVID-19 vaccine. Continuous monitoring of ADRs is crucial for vaccine safety.

Iopromide safety assessment in a radiology department: A seven-year retrospective characterization of adverse events.

Since the mid-20th century, contrast agents have been widely used in radiology due to their ability to provide high-definition radiographic images and greater precision in diagnostic exams. Different types of contrast agents are used in image diagnosis, namely radiological media. Despite being considered safe, there are still uncertainties about their safety profile, interactions, and incidence of adverse drug reactions in real-world settings. To characterise the pattern of adverse events, during 7 years, in a radiology unit. We performed a retrospective observational and descriptive study at an Image Center in Portugal between August 2012 and October 2019. A total of 77,449 computed tomography (CT) were registered, and from those 15,640 cases of iopromide were used as a contrast agent. The authors have accessed, under the authorization, the data of adverse events and procedures after the event. Most of the hypersensitivity events were immediate or with a short time of onset, with the majority of cases developing events with skin involvement and mild degree, where the most common events were papules (n =60), pruritus (n =42), erythema (n =27) and urticaria (n =14). Severe events, including hypersensitivity, were mainly represented by vomiting (n =11), stridor (n =8), breathing difficulties (n =7) and syncope (n =3). Abdominal-pelvic CT exam presented a higher frequency of adverse events. Despite all the current information about iopromide usage, the utilization of this agent is not abstent of risks and its safety profile not fully established. Most frequent symptoms were local, as skin adverse events, including papules, pruritus and erythema. Common medications used to treat or control adverse events were frequently hydrocortisone, clemastine and methylprednisolone.

Temporal profile of adverse drug reactions and associated clinical factors: a prospective observational study in a neonatal intensive care unit

ObjectiveAlthough adverse drug reactions (ADRs) are quite common in hospitalised neonates, pharmacovigilance activities in this public are still incipient. This study aims to characterise ADRs in neonates in a neonatal...

Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database.

Poly (ADP-Ribose) polymerase inhibitors (PARPi) have emerged as a targeted therapy in cancer treatment with promising results in various types of cancer. This work aims to investigate the profile of adverse drug reactions (ADRs) associated with PARPi through the reports provided by the Eudravigilance (EV) database. We also intend to analyze the potential association of peripheral neuropathy to PARPi. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. A total of 12,762 ICSRs were collected from the EV database. Serious cases of nervous system disorders were analyzed providing strong evidence that peripheral neuropathy was reported in a higher frequency in patients treated with niraparib. Most cases reported a not recovered/not resolved outcome and involved drug withdrawal. However, several studies suggest that PARPi attenuate chemotherapy-induced painful neuropathy. Unexpected ADRs such as peripheral neuropathy may also occur, mostly in patients taking niraparib. Further pharmacovigilance studies should be conducted in this area to clarify with more precision the toxicity profile of these drugs.

Analysis of Clinical Profile of Adverse Drug Reactions among Hiv Positive Patients on Antiretroviral Therapy

Analysis of Clinical Profile of Adverse Drug Reactions among Hiv Positive Patients on Antiretroviral Therapy

A prospective observational study to evaluate the safety of COVID-19 mRNA vaccines administered to Qatar Rehabilitation Institute patients.

The safety of the COVID-19 mRNA vaccine in the outpatient setting has been extensively studied; however, there need to be more reports that specifically assess their safety in the inpatient population. It is hence imperative to explore the adverse drug reaction (ADR) profile in this population and monitor the progression of these ADRs in a hospital setting. This provides a unique opportunity to closely observe patients to ensure no side effects go undiagnosed. This study aims to explore and quantify the incidence and severity of ADRs in patients who have received the COVID-19 vaccine during their stay in the rehabilitation facility. This is a prospective observational study, which included adult patients admitted to the rehabilitation facility who were deemed eligible to receive the COVID-19 vaccine during their hospital stay. Data were collected by the investigators from June 2021 to May 2022 at 24 hours, 48 hours, and 7 days post-vaccination. A piloted data collection tool was utilized. Thirty-five patients met the inclusion criteria. Pain at the injection site was the most commonly reported local ADR, while headache was the most frequent systemic ADR. The majority of the reported ADRs were mild to moderate in nature, with only one severe reaction detected. Although no statistical significance was noted among the variables, common patterns were identified, such as a higher occurrence of fever at 24 hours after the second dose as opposed to the first dose. Close monitoring of the included study subjects did not reveal any unanticipated ADRs or an increase in ADRs susceptibility and severity compared to the general population. This study supports the initiation of vaccination campaigns in inpatient rehabilitation settings. This approach would offer the advantage of gaining full immunity and reducing the risk of contracting COVID-19 infection and complications once discharged.

French pharmacovigilance survey of casirivimab - imdevimab monoclonal antibodies in coronavirus disease (COVID-19)

Casirivimab and imdevimab (Ronapreve®) are two recombinant human monoclonal antibodies (mAbs) that bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, preventing the virus from entering cells. In March 2021, this drug was granted emergency use authorisation (EUA) in France for early treatment of COVID-19 in patients at increased risk of progression to severe COVID-19. In August/September 2021, the indication was expanded to COVID-19 prevention (pre- or post-exposure prophylaxis) and treatment of hospitalised patients requiring non-invasive oxygen therapy. The aim of the study was to better describe the adverse drug reaction (ADR) profile and detect safety signals of this new drug used in COVID-19 treatment. We described ADR profile with casirivimab/imdevimab reported as suspect/interacting drug to the French pharmacovigilance network and the pharmaceutical company between 17/03/2021 and 30/06/2022. Data presented correspond to the 2 periods of the pharmacovigilance survey: the first carried out by the pharmaceutical company for curative and prophylactic uses and the second by Toulouse university regional pharmacovigilance center (RPVC). A total of 384 reports were analysed and 256 were "serious". ADR profile was comparable between the 2 periods and between curative and prophylactic use, corresponding to expected ADRs such as infusion-related reactions and hypersensitivity, inefficiencies or worsened infections and deaths. Two potential pharmacovigilance signals were also studied: acute pulmonary oedemas and sudden deaths. No pharmacovigilance signal emerged from this 15 months French pharmacovigilance survey. Moreover data from published studies are also reassuring. This pharmacovigilance survey was the first one for the new version of EUA and with a new ADR reporting process i.e. declaration to the RPVC instead of the pharmaceutical company. Casirivimab/imdevimab is no longer used in France today but we continue to monitor this drug for any future evidence of resurgent activity on a new variant of Sars-CoV-2.

Pharmacokinetics and pharmacogenomics of clozapine in an ancestrally diverse sample: a longitudinal analysis and genome-wide association study using UK clinical monitoring data

The antipsychotic, clozapine, is the only licensed drug against the treatment-resistant symptoms that affect 20-30% of people with schizophrenia. Clozapine is markedly underprescribed, partly because of concerns about its narrow therapeutic range and adverse drug reaction profile. Both concerns are linked to drug metabolism, which varies across populations globally and is partly genetically determined. Our study aimed to use a cross-ancestry genome-wide association study (GWAS) design to investigate variations in clozapine metabolism within and between genetically inferred ancestral backgrounds, to discover genomic associations to clozapine plasma concentrations, and to assess the effects of pharmacogenomic predictors across different ancestries. In this GWAS, we analysed data from the UK Zaponex Treatment Access System clozapine monitoring service as part of the CLOZUK study. We included all available individuals with clozapine pharmacokinetic assays requested by their clinicians. We excluded people younger than 18 years, or whose records contained clerical errors, or with blood drawn 6-24 h after dose, a clozapine or norclozapine concentration less than 50 ng/mL, a clozapine concentration of more than 2000 ng/mL, a clozapine-to-norclozapine ratio outside of the 0·5-3·0 interval, or a clozapine dose of more than 900 mg/day. Using genomic information, we identified five biogeographical ancestries: European, sub-Saharan African, north African, southwest Asian, and east Asian. We did pharmacokinetic modelling, a GWAS, and a polygenic risk score association analysis using longitudinal regression analysis with three primary outcome variables: two metabolite plasma concentrations (clozapine and norclozapine) and the clozapine-to-norclozapine ratio. 19 096 pharmacokinetic assays were available for 4760 individuals in the CLOZUK study. After data quality control, 4495 individuals (3268 [72·7%] male and 1227 [27·3%] female; mean age 42·19 years [range 18-85]) linked to 16 068 assays were included in this study. We found a faster average clozapine metabolism in people of sub-Saharan African ancestry than in those of European ancestry. By contrast, individuals with east Asian or southwest Asian ancestry were more likely to be slow clozapine metabolisers than those with European ancestry. Eight pharmacogenomic loci were identified in the GWAS, seven with significant effects in non-European groups. Polygenic scores generated from these loci were associated with clozapine outcome variables in the whole sample and within individual ancestries; the maximum variance explained was 7·26% for the metabolic ratio. Longitudinal cross-ancestry GWAS can discover pharmacogenomic markers of clozapine metabolism that, individually or as polygenic scores, have consistent effects across ancestries. Our findings suggest that ancestral differences in clozapine metabolism could be considered for optimising clozapine prescription protocols for diverse populations. UK Academy of Medical Sciences, UK Medical Research Council, and European Commission.

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database

ABSTRACT Background Semaglutide is a Glucagon-like peptide-1 receptor agonist used in the second-line treatment of poorly controlled type 2 diabetes and can be used in monotherapy or associated with other oral antidiabetics or even insulin, increasing the effectiveness of the treatment. This work aims to analyze the profile of adverse drug reactions reported for semaglutide in Eudravigilance. Research design and methods Data on Individual Cases Safety Reports were obtained from the database of the centralized European spontaneous reporting system Eudravigilance by accessing www.adrreports.eu. (1 December 2021). Results It is possible to observe a high prevalence of gastrointestinal disorders (N = 3502, 53.2%). The most severe reported cases were primarily gastrointestinal disorders, metabolic, and nutritional disorders, eye disorders, renal and urinary disorders and cardiac disorders, with an evident higher prevalence of adverse gastrointestinal events both in oral and injectable dosage form (N = 133, 50.0% vs N = 588, 47.2%, respectively). Through a comparative analysis, semaglutide had a greater number of reported gastrointestinal adverse events compared to sitagliptin and empaglifozin (p < 0.00001). Conclusions Semaglutide has a good safety profile, however the definition of subgroups within the type 2 diabetes population who are particularly prone to develop serious adverse event when treated with GLP-1 RAs is crucial.

Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms.

There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety concerns arise regarding adverse drug reactions in specific subpopulations. The aim of this study was to investigate the safety of intravenous ketamine treatment in relation to dissociative and psychotic measures in TRD inpatients with Major Depressive Disorder (MDD) and Bipolar depression (BP) with comorbidities. In total, 49 inpatients with MDD or BP were treated with ketamine following the registered naturalistic observational protocol in a tertiary reference unit for mood disorders (NCT04226963). This dataset represents an intermittent analysis of an observational study performed for interim modeling of observational learning. The observations were applied to the inhomogeneous TRD population in a single site with no blinding and were limited to acute administration. The presence of epilepsy was significantly associated with an elevation in the BPRS over time (p = 0.008). Psychotic symptomatology with BPRS scores for comorbid conditions excluding epilepsy turned out to be insignificant (p = 0.198) regardless of the diagnosis. However, for a subgroup of patients with epilepsy (n = 6), a substantial fluctuation was seen across all administrations in the time course of the study. The study results contribute to the literature on the safety and tolerability profile of CNS adverse drug reactions in short-term treatment with intravenous ketamine as an add-on intervention to current standard-of-care psychotropic medication in TRD-MDD and TRD-BP inpatients with comorbidities. The careful consideration of comorbidities and concomitant medication is needed with ketamine administration along with close-clinical supervision at every visit.

Pharmacovigilance follow-up of patients in the context of the COVID-19 pandemic

In the context of COVID-19 pandemic, a national pharmacovigilance survey was set up in March 2020. The purpose of this survey was to ensure continuous monitoring of adverse drug reactions (ADRs) in patients with COVID-19, not only related to the drugs used in this indication but also related to all drugs administered to these patients or suspected of having promoted the infection. This descriptive study was based on data extracted from the French Pharmacovigilance Database from 1 January 2020 to 30 September 2021. Misuse was also analysed through the MESANGE project. The ADRs were classified according to three groups: "drugs used to treat COVID-19", "other drugs administered to COVID-19 positive patients" and "drugs suspected of having promoted COVID-19". The data were also presented according to 2 periods (period one was from January to June 2020 and period two from July 2020 onwards). Among 2189 included cases, 67.1% were serious. Cases were mainly related to "other drugs administrated to COVID-19 positive patients" (58.5%) followed by "drugs used to treat COVID-19" (33.7%) and "drugs suspected of having promoted COVID-19" (7.8%). Drugs used to treat COVID-19 and their main safety profile were different depending on the period: mostly hydroxychloroquine (51%) with heart injury and lopinavir/ritonavir (42%) with liver injury for the first period, and dexamethasone (46%) with hyperglycemia and tocilizumab (28%) with liver injury for the second period. The drugs suspected of worsening COVID-19 differed in both periods especially for non-steroidal anti-inflammatory drugs mainly reported in period 1 (41.5% versus 8.2% in period 2). Other immunosuppressive drugs were in the majority in the second period (85.7%), with mainly methotrexate (15.3%), anti-CD20 (15.3%) and anti-TNF alpha (10.5%). No confirmed safety signal was identified among other drugs administered to patients with COVID-19. The profile of ADRs and suspected drugs was similar between the 2 periods. The study of misuse in outpatient settings identified in both periods mainly hydroxychloroquine, azithromycin, ivermectin and zinc±vitamin C. This survey, based on real-time pharmacological and medical assessment of ADRs and weekly meetings in a specific national committee, made it possible to identify relevant safety signals which contribute to patient care with no delay. The main safety signal highlighted was serious cardiac damage under hydroxychloroquine, alone or combined with azithromycin and also with lopinavir/ritonavir. This signal has contributed to the evolution of the recommendations for these 2 drugs. The methodology of this survey has been taken over and is still going on for the pharmacovigilance monitoring of vaccines against COVID-19, for monoclonal antibodies used against COVID-19 and also for Paxlovid® (nirmatrelvir/ritonavir) which benefit from dedicated surveys.