EudraVigilance Database Research Articles

Spontaneous Reporting to Regulatory Authorities of Suspected Adverse Drug Reactions to COVID-19 Vaccines Over Time: The Effect of Publicity.

IntroductionThe UK Medicines and Healthcare products Regulatory Agency (MHRA) has published frequent summaries of spontaneous reports of suspected adverse drug reactions (ADRs) (Yellow Cards) to vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The EudraVigilance database has provided similar data for the European Economic Area.ObjectiveOur objective was to characterize the evolution over time of spontaneous reports of suspected ADRs to coronavirus disease 2019 (COVID-19) vaccines and to observe the effect of a publicized reaction (cerebral venous and sinus thrombosis [CVST]) on reporting rates.MethodsWe used publicly available data on reports of suspected ADRs and doses of vaccine administered, published by the MHRA, EudraVigilance, and the European Centre for Disease Prevention and Control to calculate reporting rates.ResultsApproximately 4814 Yellow Card reports (23 fatal) per million doses of ChAdOx1 nCoV-19 (AstraZeneca) and 2890 (13 fatal) per million doses of tozinameran (Pfizer/BioNTech) have been lodged. Between 15 March and 31 October 2021, cumulative European reports of CVST rose from 0 to 443 (183 with thrombocytopenia, 72 fatal) with ChAdOx1 nCoV-19 and from 2 to 315 (9 with thrombocytopenia, 28 fatal) with tozinameran. European cases of retinal vein occlusion and thrombosis rose from 0 to 168 with ChAdOx1 nCoV-19 and from 1 to 220 with tozinameran; four of the ChAdOx1 nCoV-19 cases were associated with thrombocytopenia.ConclusionReports of fatal adverse reactions to coronavirus vaccines are very rare. Reports of CVST have been made in relation to both vaccines. Most were submitted after the reaction had been publicized. Thrombocytopenia occurred in a minority of cases. Reports linked both vaccines to cases of retinal vein thrombosis, just four cases with thrombocytopenia. This suggests two different mechanisms of thrombosis associated with the vaccines.

Cost-minimization and opportunity cost analysis of fully-liquid hexavalent and meningococcal vaccines in Spain

IntroductionSimplification of vaccine preparations saves time and reduces potential immunization errors. This study aimed to perform a cost-minimization analysis (CMA) and to assess the opportunity cost of fully-liquid versus non-fully liquid vaccines requiring reconstitution for the hexavalent (DTaP-IPV-HB-Hib) and MenACWY vaccines. MethodsA cost-minimization model based on the time required to prepare and administer vaccines, considering preparation errors, was developed. The number of administered hexavalent and MenACWY vaccines in one year was calculated, and the time required for the vaccination visit was obtained from a time-and-motion study. The percentage of preparation errors was obtained from the EUDRAVIGILANCE database. The vaccines unitary cost and nurse's salary were obtained from the Spanish Ministry of Health. Deterministic sensitivity analyses (scenarios and univariate) were performed. A panel multidisciplinary of experts was consulted to assess the opportunity cost associated with the use of fully-liquid vaccines. ResultsThe use of fully-liquid vaccines would save 62.92 healthcare-hours in one year per 100,000 inhabitants (41.68 and 21.23 healthcare-hours with the hexavalent and MenACWY vaccines, respectively), which translate into a expenditure reduction of € 2220.5 per 100,000 inhabitants. The deterministic analysis confirmed the robustness of these base-case results. The experts consulted concluded that improving parental health education during consultation would be the main action that could be implemented to employ the extra-time saved by healthcare professionals when fully-liquid vaccines are used. ConclusionsThe use of fully-liquid hexavalent and MenACWY vaccines instead of non-fully liquid presentations would reduce healthcare professionals' working hours that could be reinvested in improving the quality of the consultation.

Cost-minimization and opportunity cost analysis of fully-liquid hexavalent and meningococcal vaccines in Spain

IntroductionSimplification of vaccine preparations saves time and reduces potential immunization errors. This study aimed to perform a cost-minimization analysis (CMA) and to assess the opportunity cost of fully-liquid versus non-fully liquid vaccines requiring reconstitution for the hexavalent (DTaP-IPV-HB-Hib) and MenACWY vaccines. MethodsA cost-minimization model based on the time required to prepare and administer vaccines, considering preparation errors, was developed. The number of administered hexavalent and MenACWY vaccines in one year was calculated, and the time required for the vaccination visit was obtained from a time-and-motion study. The percentage of preparation errors was obtained from the EUDRAVIGILANCE database. The vaccines unitary cost and nurse's salary were obtained from the Spanish Ministry of Health. Deterministic sensitivity analyses (scenarios and univariate) were performed. A panel multidisciplinary of experts was consulted to assess the opportunity cost associated with the use of fully-liquid vaccines. ResultsThe use of fully-liquid vaccines would save 62.92 healthcare-hours in one year per 100,000 inhabitants (41.68 and 21.23 healthcare-hours with the hexavalent and MenACWY vaccines, respectively), which translate into a expenditure reduction of € 2220.5 per 100,000 inhabitants. The deterministic analysis confirmed the robustness of these base-case results. The experts consulted concluded that improving parental health education during consultation would be the main action that could be implemented to employ the extra-time saved by healthcare professionals when fully-liquid vaccines are used. ConclusionsThe use of fully-liquid hexavalent and MenACWY vaccines instead of non-fully liquid presentations would reduce healthcare professionals' working hours that could be reinvested in improving the quality of the consultation.

Subacute thyroiditis and COVID-19 vaccines: a case/non-case study.

PurposeSome case reports have suggested a possible association between COVID-19 vaccines and subacute thyroiditis (SAT), however, to our knowledge, no study has analyzed this possible relationship. This study aimed to analyze whether a disproportionate number of cases of SAT were reported in the EudraVigilance database for four COVID-19 vaccines (BNT162b2, mRNA-1273 ChAdOx1-S or Ad26.COV2.S).MethodsA case/non-case study was conducted to assess the association between SAT and COVID-19 vaccines, calculating the reporting odds ratios (RORs) up to December 2, 2021. Cases were selected using the preferred term ‘subacute thyroiditis’. First, cases involving COVID-19 vaccines were compared with those involving all other drugs. Secondly, the RORs for COVID-19 vaccines compared with other viral vaccines (overall and influenza vaccines only) were obtained.ResultsUntil December 2, 2021, of 1,221,582 spontaneous cases of adverse reactions with the four vaccines, we found 162 SAT cases: BNT162b2 (n = 103), mRNA-1273 (n = 27), ChAdOx1-S (n = 31) and Ad26.COV2.S (n = 1). SAT cases were found to be reported more frequently in association with BNT162b2, mRNA-1273, and ChAdOx1-S vaccines than with other drugs. Moreover, we found a signal of disproportionate reporting for SAT with BNT162b2 and mRNA-1273 vaccines comparing with other viral vaccines (BNT162b2 ROR 3.58, 95% CI 1.92–6.66; mRNA-1273 ROR 3.44, 95% CI 1.71–6.94). However, this association was absent when these COVID-19 vaccines were compared with influenza vaccines.ConclusionsIn EudraVigilance, SAT is relatively more frequently reported in association with mRNA COVID-19 vaccines than with other viral vaccines. Well designed observational studies are needed to confirm these results.

Neues aus dem RABBIT-Register

Seit 2001 rekrutieren Rheumatolog:innen deutschlandweit Patient:innen mit rheumatoider Arthritis in das Biologikaregister RABBIT, um die Langzeitsicherheit und -wirksamkeit moderner antirheumatischer Therapien zu untersuchen. In den vergangenen 20 Jahren wurden mehr als 20.000 Patient:innen in die prospektive Kohortenstudie eingeschlossen. In diesem Beitrag fassen wir aktuelle Forschungsergebnisse der Jahre 2020 und 2021 zusammen; dabei stehen Sicherheitsaspekte, Einflussfaktoren auf die Therapiewirksamkeit und patientenberichtete Outcomes im Fokus. Mit Herpes zoster, Fazialisparese und Psoriasis wurden verschiedene unerwünschte Ereignisse untersucht, die entweder als Sicherheitssignal aus klinischen Studien oder durch die EudraVigilance-Datenbank gemeldet wurden oder als paradoxe Reaktion unter medikamentöser Behandlung aufgetreten sind. Für diese Ereignisse wurde der Einfluss der biologischen DMARD(„disease-modifying antirheumatic drug“)-Therapie analysiert. In der Publikation zu Herpes zoster berücksichtigten wir auch die medikamentöse Behandlung mit Januskinaseinhibitoren. Starkes Übergewicht kann den Erfolg einer Therapie beeinflussen. Hier gibt es geschlechtsspezifische Unterschiede, und auch das Wirkprinzip einer Therapie entscheidet, ob eine Adipositas das Therapieansprechen reduziert. Die Mehrheit der in RABBIT beobachteten Patient:innen ist nach 1 Jahr Behandlung mit der erhaltenen Therapie zufrieden. Wir konnten zeigen, welche Faktoren die Zufriedenheit mit der Wirksamkeit und der Sicherheit der Behandlung begünstigen oder aber negativ beeinflussen. Diese Übersichtsarbeit zeigt, dass Langzeitbeobachtungsstudien wie das RABBIT-Register auch nach 2 Dekaden der Datenerhebung zum Verständnis von Therapierisiken beiträgt sowie Faktoren identifiziert, die die Wirkung der Therapien beeinflussen können.

Age-Stratified Risk of Cerebral Venous Sinus Thrombosis After SARS-CoV-2 Vaccination.

Cerebral venous sinus thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) vaccination. Estimated background rate of CVST with thrombocytopenia is 0.1 per million per month. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination. We estimated the absolute risk of CVST with and without thrombocytopenia within 28 days of a first dose of 4 SARS-CoV-2 vaccinations using data from the European Medicines Agency's EudraVigilance database (until June 13, 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries, we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category. The absolute risk of CVST within 28 days of first-dose vaccination was 7.5 (95% confidence interval [CI] 6.9-8.3), 0.7 (95% CI 0.2-2.4), 0.6 (95% CI 0.5-0.7), and 0.6 (95% CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95% CI 3.9-4.9), 0.7 (95% CI 0.2-2.4), 0.0 (95% CI 0.0-0.1), and 0.0 (95% CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the absolute risk of CVST, both with and without thrombocytopenia, was the highest in the 18- to 24-year-old group (7.3 per million, 95% CI 2.8-18.8 and 3.7 per million, 95% CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia in ChAdOx1 nCov-19 recipients was the lowest in the age group ≥70 years (0.2, 95% CI 0.0-1.3). Age <60 years compared to ≥60 years was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79, 95% CI 2.98-11.24, p < 0.001). The risk of CVST with thrombocytopenia within 28 days of first-dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S compared with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of SARS-CoV-2 mRNA vaccines.

The Impact of Mandatory Reporting of Non-Serious Safety Reports to EudraVigilance on the Detection of Adverse Reactions

Introduction and ObjectiveEuropean Union legislation has mandated the submission of European Economic Area non-serious reports to the EudraVigilance database since November 2017. As spontaneous reports of suspected adverse reactions to medicines represent a key source of safety signals, the European Medicines Agency has undertaken this work to assess the effects of this requirement on the characteristics of the reports submitted to EudraVigilance and on the detection of adverse drug reactions through routine analyses of the database.MethodsChanges in the numbers of serious and non-serious reports transmitted to EudraVigilance were examined over the period during which the legislation was implemented. The numbers and nature of potential safety signals emerging from established statistical algorithms used at the European Medicines Agency applied either to only the serious reports or to all reports in EudraVigilance were compared.ResultsUp to November 2017, less than 25% of European Economic Area reports in EudraVigilance were classified as non-serious, since than this figure was slightly above 60%. This change accompanied an increase in the total number of reports received. Addition of non-serious reports to the signal detection process resulted in a small overall increase in signals of disproportionate reporting with some new signals of disproportionate reporting appearing and some existing signals of disproportionate reporting disappearing; the sensitivity of the signal detection system was slightly increased and the proportion of signals of disproportionate reporting that corresponded to known adverse drug reactions (a measure of efficiency) was unchanged.ConclusionsThe change in legislation has led to a small increase in sensitivity, without affecting the efficiency of the routine statistical measures used. The number of non-serious reports as a proportion of reports in EudraVigilance is likely to increase over time and further monitoring of the impact on signal detection is required. Further work is also required on the qualitative impact of non-serious reports on the nature of signals detected and on their evaluation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01137-0.

Thrombotic Adverse Events Reported for Moderna, Pfizer and Oxford-AstraZeneca COVID-19 Vaccines: Comparison of Occurrence and Clinical Outcomes in the EudraVigilance Database.

Vaccination against COVID-19 is the cornerstone of controlling and mitigating the ongoing pandemic. Thrombotic adverse events linked to Moderna, Pfizer and the Oxford-AstraZeneca vaccine have been documented and described as extremely rare. While the Oxford-AstraZeneca vaccine has received much of the attention, the other vaccines should not go unchallenged. This study aimed to determine the frequency of reported thrombotic adverse events and clinical outcomes for these three COVID-19 vaccines, namely, Moderna, Pfizer and Oxford-AstraZeneca. A retrospective descriptive analysis was conducted of spontaneous reports for Moderna, Pfizer and Oxford-AstraZeneca COVID-19 vaccines submitted to the EudraVigilance database in the period from 17 February to 14 June 2021. There were 729,496 adverse events for the three vaccines, of which 3420 were thrombotic, mainly Oxford-AstraZeneca (n = 1988; 58.1%) followed by Pfizer (n = 1096; 32.0%) and Moderna (n = 336; 9.8%). As serious adverse events, there were 705 reports of pulmonary embolism for the three vaccines, of which 130 reports (18.4%) were for Moderna, 226 reports (32.1%) for Pfizer and 349 (49.5%) for Oxford-AstraZeneca vaccines. The occurrence of pulmonary embolism is significantly associated with a fatal outcome (p ≤ 0.001). Sixty-three fatalities were recorded (n = 63/3420; 1.8%), of which Moderna (n = 6), Pfizer (n = 25) and Oxford-AstraZeneca (n = 32).

Crystal nephropathy and amoxicillin: insights from international spontaneous reporting systems.

A substantial increase in amoxicillin-induced crystal nephropathy was recently reported in France. Our study aims to further characterize this safety issue from a worldwide perspective. We queried both the FDA Adverse Event Reporting System (FAERS) and the Eudravigilance databases, and performed disproportionality analysis, selecting only adverse events (AEs) related to crystal nephropathy where amoxicillin or amoxicillin/clavulanic acid were reported as suspect. In FAERS, the reporting odds ratios were calculated and deemed significant by the lower limit of the 95% confidence interval (LL95%CI) > 1, selecting all other drugs/events recorded in FAERS as comparator. Deduplication followed by case-by-case assessment and comparison between French and non-French cases were also performed in both databases. Overall, 57,754 and 84,764 AE reports with amoxicillin or amoxicillin/clavulanic acid were recorded in FAERS and Eudravigilance, respectively, with France accounting for 18.7% and 22.0% of cases. Specific AEs of interest were retrieved in 144 and 239 cases, respectively. Increased reporting was found in FAERS for crystalluria (N = 99; LL95%CI 53.18), crystal nephropathy (24; 27.01), medication crystal in urine present (9; 92.00), crystal urine (8; 11.90), and crystal urine present (4; 1.57). In FAERS and Eudravigilance databases, reports were classified as serious in 98.8% and 91.2% of cases, respectively. Acute kidney injury (AKI) was found in 81.2% and 71.1% of patients. Amoxicillin was mainly given intravenously, and a dose ≥ 12g/day was administered in 50.0% and 19.7% of cases in the FAERS and Eudravigilance databases, respectively. Although causal association cannot be firmly inferred, a consistent signal of crystal nephropathy with amoxicillin emerged, especially in France. Clinicians should monitor patients for possible early AKI onset, especially when dealing with intravenous administration of daily doses > 12g.

Comparison of adverse drug reactions among four COVID‐19 vaccines in Europe using the EudraVigilance database: Thrombosis at unusual sites

BackgroundReal‐world experience with adenoviral vector vaccines against COVID‐19 raised some safety concerns. Cases of cerebral vein thrombosis (CVT) associated with thrombocytopenia have been observed after the first dose of the adenoviral vector vaccines CHADOX1 NCOV‐19 and AD26.COV2.S. ObjectivesTo assess the reporting rate of CVT as adverse drug reaction (ADR) for the COVID‐19 vaccines authorized in Europe. Patients and MethodsThis observational study assessed the CVT reporting rate attributed to four COVID‐19 vaccines authorized in Europe, namely Tozinameran (Pfizer‐Biontech), CX‐024414 (Moderna), CHADOX1 NCOV‐19 (AstraZeneca), and AD26.COV2.S (Janssen). Data on thrombotic ADRs reported on EudraVigilance database between January 1, 2021 and July 30, 2021, were collected. ADRs referring to CVT were identified. The reporting rate of CVT was expressed as 1 million individual vaccinated‐days with 95% confidence interval. Finally, an observed‐to‐expected (OE) analysis was performed. ResultsThe reporting rate of CVT per 1 million person vaccinated‐days was 1.92 (95% confidence interval [CI], 1.71–2.12) for Tozinameran, 5.63 (95% CI, 4.74–6.64) for CX‐024414, 21.60 (95% CI, 20.16–23.11) for CHADOX1 NCOV‐19, and 11.48 (95% CI, 9.57–13.67) for AD26.COV2.S. CVT occurred alongside thrombocytopenia for the four vaccines. The OE ratio was greater than one for all four vaccines, both with the lowest and the highest CVT background incidence. ConclusionsThis report on EudraVigilance data strengthens anecdotal findings on CVT following COVID‐19 vaccinations. Although the European Medicines Agency released an alert only for CHADOX1 NCOV‐19 and AD26.COV2.S, Tozinameran and CX‐024414 also are complicated by CVT, albeit to lesser extent.

SC37 - Sexual adverse events-related to dutasteride e finasteride: analysis of real-life data from Eudra-Vigilance database

SC37 - Sexual adverse events-related to dutasteride e finasteride: analysis of real-life data from Eudra-Vigilance database

Declining mortality of cerebral venous sinus thrombosis with thrombocytopenia after SARS-CoV-2 vaccination.

Background and purposeHigh mortality rates have been reported in patients with cerebral venous sinus thrombosis (CVST) due to vaccine‐induced immune thrombotic thrombocytopenia (VITT) after vaccination with adenoviral vector SARS‐CoV‐2 vaccines. The aim of this study was to evaluate whether the mortality of patients with CVST‐VITT has decreased over time.MethodsThe EudraVigilance database of the European Medicines Agency was used to identify cases of CVST with concomitant thrombocytopenia occurring within 28 days of SARS‐CoV‐2 vaccination. Vaccines were grouped based on vaccine type (adenoviral or mRNA). Cases with CVST onset until 28 March were compared to cases after 28 March 2021, which was the day when the first scientific paper on VITT was published.ResultsIn total, 270 cases of CVST with thrombocytopenia were identified, of which 266 (99%) occurred after adenoviral vector SARS‐CoV‐2 vaccination (ChAdOx1 nCoV‐19, n = 243; Ad26.COV2.S, n = 23). The reported mortality amongst adenoviral cases with onset up to 28 March 2021 was 47/99 (47%, 95% confidence interval 37%–58%) compared to 36/167 (22%, 95% confidence interval 16%–29%) in cases with onset after 28 March (p < 0.001). None of the four cases of CVST with thrombocytopenia occurring after mRNA vaccination died.ConclusionThe reported mortality of CVST with thrombocytopenia after vaccination with adenoviral vector‐based SARS‐CoV‐2 vaccines has significantly decreased over time, which may indicate a beneficial effect of earlier recognition and/or improved treatment on outcome after VITT.

Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European Medicines Agency.

Background and purposeCerebral venous sinus thrombosis (CVST) has been described after vaccination against SARS‐CoV‐2. The clinical characteristics of 213 post‐vaccination CVST cases notified to the European Medicines Agency are reported.MethodsData on adverse drug reactions after SARS‐CoV‐2 vaccination notified until 8 April 2021 under the Medical Dictionary for Regulatory Activities Term ‘Central nervous system vascular disorders’ were obtained from the EudraVigilance database. Post‐vaccination CVST was compared with 100 European patients with CVST from before the COVID‐19 pandemic derived from the International CVST Consortium.ResultsIn all, 213 CVST cases were identified: 187 after AstraZeneca/Oxford (ChAdOx1 nCov‐19) vaccination and 26 after a messenger RNA (mRNA) vaccination (25 with Pfizer/BioNTech, BNT162b2, and one with Moderna, mRNA‐1273). Thrombocytopenia was reported in 107/187 CVST cases (57%, 95% confidence interval [CI] 50%–64%) in the ChAdOx1 nCov‐19 group, in none in the mRNA vaccine group (0%, 95% CI 0%–13%) and in 7/100 (7%, 95% CI 3%–14%) in the pre‐COVID‐19 group. In the ChAdOx1 nCov‐19 group, 39 (21%) reported COVID‐19 polymerase chain reaction tests were performed within 30 days of CVST symptom onset, and all were negative. Of the 117 patients with a reported outcome in the ChAdOx1 nCov‐19 group, 44 (38%, 95% CI 29%–47%) had died, compared to 2/10 (20%, 95% CI 6%–51%) in the mRNA vaccine group and 3/100 (3%, 95% CI 1%–8%) in the pre‐COVID‐19 group. Mortality amongst patients with thrombocytopenia in the ChAdOx1 nCov‐19 group was 49% (95% CI 39%–60%).ConclusionsCerebral venous sinus thrombosis occurring after ChAdOx1 nCov‐19 vaccination has a clinical profile distinct from CVST unrelated to vaccination. Only CVST after ChAdOx1 nCov‐19 vaccination was associated with thrombocytopenia.

Cardiac Events Potentially Associated to Remdesivir: An Analysis from the European Spontaneous Adverse Event Reporting System.

Remdesivir was recommended for hospitalized patients with COVID-19. As already reported in the Summary of Product Characteristics, most of remdesivir’s safety concerns are hepatoxicity and nephrotoxicity related. However, some cases have raised concerns regarding the potential cardiac events associated with remdesivir; therefore, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency requested to investigate all available data. Therefore, we analyzed all Individual Case Safety Reports (ICSRs) collected in the EudraVigilance database focusing on cardiac adverse events. From April to December 2020, 1375 ICSRs related to remdesivir were retrieved from EudraVigilance, of which 863 (62.8%) were related to male and (43.3%) adult patients. A total of 82.2% of all AEs (N = 2604) was serious and one third of the total ICSRs (N = 416, 30.3%) had a fatal outcome. The most frequently reported events referred to hepatic/hepatobiliary disorders (19.4%,), renal and urinary disorders (11.1%) and cardiac events (8.4%). Among 221 cardiac ICSRs, 69 reported fatal outcomes. Other drugs for cardiovascular disorders were reported as suspected/concomitant together with remdesivir in 166 ICSRs (75.1%), 62 of which were fatal. Moreover, the mean time to overall cardiac event was 3.3 days (±2.2). Finally, disproportionality analysis showed a two-fold increased risk of reporting a cardiac adverse event associated with remdesivir compared to both hydroxychloroquine and azithromycin. This study showed that remdesivir could be associated to risk of cardiac events, suggesting a potential safety signal which has not been completely evaluated yet. Further studies are needed to confirm these findings.

P0638 - Overall Adverse events of drugs for metastatic renal cell carcinoma: Real world reporting patterns from eudra vigilance database

P0638 - Overall Adverse events of drugs for metastatic renal cell carcinoma: Real world reporting patterns from eudra vigilance database

P0033 - Sexual adverse events-related to dutasteride e finasteride: Analysis of real-life data from EudraVigilance database

P0033 - Sexual adverse events-related to dutasteride e finasteride: Analysis of real-life data from EudraVigilance database

Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine Reported to EudraVigilance Database.

The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early in December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford–AstraZeneca vaccine amid reports of blood clot events and the death of a vaccinated person, despite the European Medicines Agency (EMA) and the World Health Organization’s assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with the Oxford–AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports, of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to pulmonary embolism; one fatality to thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events The EMA’s Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients’ characteristics and comorbidities, may enable assessment of the causality with higher specificity.

Neuroleptic malignant syndrome associated with second-generation antipsychotics (SGA): An analysis of reported cases in eudravigilance database, 2017-2020

IntroductionAntipsychotic drugs are the cornerstone of the pharmacological treatment of psychotic disorders; however, even with Second-generation antipsychotics (SGA), adverse effects continue to be extremely accentuated and the treatment effectiveness is compromised by low adherence of the patient.ObjectivesTaking into consideration the importance of adverse effects for psychotic therapeutics, this study aims to analyze the adverse effect of the Neuroleptic Malignant Syndrome (NMS) reported in EudraVigilance Database, associated with 3 widely used SGA, Risperidone, Quetiapine, and Clozapine.MethodsThe EudraVigilance Database was analyzed from 09/01/2017 to 31/10/2020 about NMS, associated with Risperidone, Quetiapine, and Clozapine. NMS is the second most reported adverse effect inside the Nervous System Disorders SOC (System Organ Class). There were just considered NMS as suspected adverse effect.ResultsIt was observed a general tendency of reduction of NMS reports from 2017 to 2020 (most of them performed by healthcare professionals). Risperidone presented the highest level of reports during this period (more than 350), followed by Quetiapine and Clozapine. The NMS reports were predominantly referred to the male sex, from 18 to 64 years old. Risperidone presented the lowest number of fatal cases of NMS (1), in contrast with 3 reported with Quetiapine and Clozapine. A significant number of patients with Schizophrenia recovered from NMS.ConclusionsIt is important to do clinical monitoring of the NMS, because it is rare, although it has life-threatening consequences. Pharmacovigilance databases are important tools to evaluate the safety of drugs and it must be more widely and efficiently promoted for healthcare and patients use.DisclosureNo significant relationships.

Analysis of the reporting of adverse drug reactions in children and adolescents in Germany in the time period from 2000 to 2019.

The objective of this study was to analyse reports on adverse drug reactions (ADRs) from Germany in the particularly vulnerable patient group of children and adolescents. Reporting characteristics, demographic parameters and off-label use were examined among others. The ratio of ADR reports per number of German inhabitants and the ratio of ADR reports per number of German inhabitants exposed to drugs were calculated and compared. These parameters were examined to derive trends in reporting of ADRs. 20,854 spontaneous ADR reports for the age group 0–17 years were identified in the European ADR database EudraVigilance for the time period 01.01.2000–28.02.2019 and analysed with regard to the aforementioned criteria. 86.5% (18,036/20,854) of the ADR reports originated from Healthcare Professionals and 12.2% (2,546/20,854) from non-Healthcare Professionals. 74.4% (15,522/20,854) of the ADR reports were classified as serious. The proportion of ADR reports per age group was 11.8% (0–1 month), 11.0% (2 months—1 year), 7.4% (2–3 years), 9.3% (4–6 years), 25.8% (7–12 years), and 34.8% (13–17 years) years, respectively. Male sex slightly dominated (51.2% vs. 44.8% females). Only 3.5% of the ADR reports reported off-label use. The annual number of ADR reports increased since 2000, even if set in context with the number of inhabitants and assumed drug-exposed inhabitants. The pediatric population declined in the study period which argues against its prominent role for the increase in the total number of ADR reports. Instead, among others, changes in reporting obligations may apply. The high proportion of serious ADR reports underlines the importance of pediatric drug safety.

Can Treatment with Venetoclax for Chronic Lymphocytic Leukemia (CLL) Result In Autoimmune Hemolytic Anemia?

Patient: Female, 62-year-oldFinal Diagnosis: Autoimmune hemolytic anemiaSymptoms: AnemiaMedication:—Clinical Procedure: —Specialty: HematologyObjective:Unusual clinical courseBackground:Chronic lymphocytic leukemia (CLL) is a hematological disease characterized by the clonal proliferation and accumulation of neoplastic B lymphocytes in the blood, bone marrow, lymph nodes, and spleen. Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic anemia in which the destruction of erythrocytes is helped by anti-erythrocyte auto-antibodies. This has a controversial effect on the clinical outcome and survival of patients with CLL. Venetoclax, a second-generation BH3 mimetic compound, is one of the new therapies that has been approved for the treatment of CLL. Venetoclax disrupts the antiapoptotic signaling through BCL2. Common adverse events associated with venetoclax include neutropenia, thrombocytopenia, and diarrhea. This case report describes a patient with CLL who developed AIHA when treated with venetoclax.Case Report:A patient of 62-year-old woman, who was treated with multiple lines of therapy, presented autoimmune hemolytic anemia after treatment with venetoclax. The anemia was resolved after holding venetoclax and being treated with rituximab. In January 2019, there were reports of 7 patients developing AIHA related to veneto-clax therapy in Europe, according to the EudraVigilance database. How venetoclax can cause AIHA is not completely clear. This complication can happen when the erythrocyte antigen is altered by the drug that can produce antibodies. The other described mechanism is the binding of the drug with erythrocytes, which leads to production of an immune response.Conclusions:Although AIHA can be a complication of CLL, it may be caused by treatment with venetoclax. That may be confirmed after eliminating other causes.