Spontaneous Adverse Event Reports Research Articles

Influence of loop diuretics on denosumab-induced hypocalcaemia in osteoporosis: a retrospective observational analysis

BackgroundWe examined whether denosumab-induced hypocalcaemia is evident in osteoporosis when given loop diuretics that promote urinary calcium excretion.MethodsJapanese Spontaneous Adverse Drug Event Reports was analyzed to examine signals for denosumab-induced hypocalcaemia co-administered loop diuretics. We retrospectively included osteoporotic patients to detect predictors for denosumab-induced hypocalcaemia (corrected calcium level < 8.5 mg/dL) using multivariate logistic regression analysis. We compared differences in corrected calcium levels (ΔCa = nadir-baseline).ResultsA significant signal for hypocalcaemia was detected (Reporting odds ratio = 865.8, 95% confidence interval [95% CI]: 596.8 to 1255.9, p < 0.0001). Among 164 patients (hypocalcaemia, 12%), loop diuretics have a significant association with hypocalcaemia (odds ratio [OR] = 6.410, 95% CI: 1.005 to 40.90, p = 0.0494). However, hypocalcaemia was found to be lower in high corrected calcium levels at baseline (OR = 0.032, 95% CI: 0.005 to 0.209, p < 0.0001) and calcium and vitamin D supplementation (OR = 0.285, 95% CI: 0.094 to 0.868, p = 0.0270). In the non-hypocalcaemia, ΔCa decreased significantly in the denosumab plus loop diuretics than in the denosumab alone (-0.9 [-1.3 to -0.7] mg/dL vs. -0.5 [-0.8 to -0.3] mg/dL, p = 0.0156). However, ΔCa remained comparable in the hypocalcaemia despite loop diuretics co-administration (-1.0 [-1.2 to -0.8] mg/dL vs. -0.8 [-1.5 to -0.7] mg/dL, p = 0.7904).ConclusionsLoop diuretics may predispose to developing denosumab-induced hypocalcaemia.

Regional diversity in drug-induced lung diseases among the USA, European Union, and Japan.

Drug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base. This retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and cytotoxic agents. Regional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418). The prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.

A Pharmacovigilance Study on Clozapine in the Food and Drug Administration Adverse Event Reporting System: A Regional Comparative Analysis.

This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration Adverse Event Reporting System (FAERS). We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate. However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemia/new onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis. Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation.

Disproportionality Analysis of Stomatitis Associated with Anticancer Drugs Using the Japanese Adverse Drug Event Report Database

Introduction: Anticancer drug-induced stomatitis can affect a patient’s quality of life and the continuation of drug treatment. Although there have been reports of the occurrence of stomatitis associated with anticancer agents in clinical trials, few Japanese participants have been enrolled in clinical trials and have not been sufficiently investigated. In addition, there has been little attention on research on anticancer drugs associated with stomatitis by patient stratification with different carcinogenic sites. Therefore, the aim of this study was to determine the disproportionality associated with stomatitis for various types of anticancer drugs in different types of cancer patients using the Japanese Adverse Drug Event Report (JADER) database. Methods: The aim of this study was to identify the disproportionality of stomatitis by analyzing the type of anticancer drug and cancer patients using the Japanese Pharmacovigilance Database. Data obtained from spontaneous reports of adverse events with more than 10 stomatitis outbreaks reported in the JADER database between April 2004 and March 2023 were analyzed. The safety signal for an adverse event was defined as the lower limit of the 95% confidence interval of the reported odds ratio of >1. Results: There were 6,178 reports of drugs associated with stomatitis. Among these, 41 drugs were suggested to be associated with stomatitis, and 41 drugs were detected as signals. These drugs were classified based on their efficacy: antipyrimidines (six drugs), folate metabolism antagonists (three drugs), alkylating agents (four drugs), platinum (three drugs), topoisomerase inhibitors (three drugs), microtubule inhibitors (three drugs), mammalian target of rapamycin (mTOR) inhibitors (two drugs), kinase inhibitors (seven drugs), anti-growth factor antibodies (five drugs) immune checkpoint inhibitors (one drug), and others (four drugs). Conclusion: The drugs that may be associated with stomatitis were cell cycle-dependent drugs, epidermal growth factor receptor-tyrosine kinase inhibitors, and mTOR inhibitors. Moreover, this study suggested that anti-growth factor antibodies and immune checkpoint inhibitors may be associated with stomatitis development.

Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitors and Hypothyroidism: An Analysis of the Japanese Pharmacovigilance Database.

Hypothyroidism induced by roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, was recently reported; however, information regarding roxadustat-associated hypothyroidism is still lacking. We explored the risk and time to onset of hypothyroidism associated with HIF-PH inhibitors using the Japanese Adverse Drug Event Report (JADER), a pharmacovigilance database. The participants of this study were registered in the JADER database between April 2004 and March 2023. The association between HIF-PH inhibitors and hypothyroidism was evaluated using the reporting odds ratio (ROR) and information component (IC). We also calculated the period from the start of drug administration to the onset of hypothyroidism and determined the onset pattern using Weibull distribution. Roxadustat had positive signals for hypothyroidism among the HIF-PH inhibitors based on the ROR [31.03, 95% confidence interval (CI)=27.81-34.62] and IC (4.51, 95%CI=4.36-4.67) values, and a strong relationship was confirmed. In addition, the median time to roxadustat-associated hypothyroidism onset was 92 days, and over 50% of cases occurred within 100 days of starting treatment. Furthermore, the onset pattern was an early failure type. There is a possible association between roxadustat and hypothyroidism. Therefore, enhanced thyroid function testing within 100 days of treatment initiation may help detect roxadustat-associated hypothyroidism. However, further research is required to confirm these findings, considering study limitations using databases of spontaneous adverse event reports.

Gender differences in spontaneous adverse event reports associated with zolpidem in South Korea, 2015-2019.

Study objectives: While zolpidem is considered as an example of a gender effect on drug response, there is insufficient evidence to reach a consensus. This study aimed to investigate gender differences in adverse events (AEs) of zolpidem. Methods: We estimated the difference between the reporting odds ratios (RORs) calculated in gender subgroups for the AEs signals detected in data mining using 2015-2019 Korea voluntary adverse drug events reporting system (KAERS) data. Different reporting risk by gender was evaluated by using the log RORs being significantly different by gender at the 5% significance level and the 95% confidence intervals of the gender ROR. Results: A total of 94 AE signals were detected. Among these, 35 signals showed significant disparities by gender at the 5% level or were detected only in one gender. When categorized by similarity of AEs, parasomnia including somnambulism and paroniria, and cardiovascular disorders including coronary thrombosis had higher reporting risks in women. Men were more likely to report cognitive disorders such as delirium, insomnia related disorders, and movement disorders. Among all AEs with gender differences in reporting risk, the difference in somnambulism was the most consistent and substantial. Conclusion: For several AEs associated with zolpidem, gender-based reporting disparities were evident. Notably, women exhibited a higher susbeptibility to somnambulism, potentially serious adverse effects of zolpidem. This underscores the need for further investigation into the underlying factors influencing these gender-specific reporting patterns.

Drug–drug interaction signals between loop diuretics and teicoplanin during acute kidney injury evaluated using Japanese spontaneous adverse drug event reports

Teicoplanin can cause acute kidney injury, but little is known about the risk of acute kidney injury when teicoplanin is co-administered with loop diuretics (a powerful diuresis), which can alter renal hemodynamics and glomerular filtration rate. We performed a signal detection analysis using a Japanese adverse event database to determine the additive impact of loop diuretics on acute kidney injury associated with teicoplanin. The dataset originated between April 2004 and August 2022. Disproportionality analysis was performed to detect the signals for acute kidney injury (the Standardized MedDRA Query) when co-administered teicoplanin or vancomycin (a positive control) with individual diuretics, including loop diuretics. Multivariate logistic regression analysis was tested to estimate the adjusted reporting odds ratio (aROR) and 95% confidence interval (95% CI). There were 147 and 515 events of acute kidney injury associated with teicoplanin and vancomycin, respectively. A significant positive signal for acute kidney injury when teicoplanin was co-administered with loop diuretics was present (aROR 4.83, 95% CI 3.52–6.61, p < 0.0001). Contrastingly, no significant signals were observed when vancomycin was co-administered with any diuretics. These findings suggest that co-administered loop diuretics may have an unfavorable effect on acute kidney injury while undertaking teicoplanin but not vancomycin.

META-INSTI: metabolic adverse events following integrase strand transfer inhibitor administration in spontaneous adverse event reports.

Metabolic effects of integrase strand transfer inhibitors (INSTIs) have been reported. The FDA Adverse Event Reporting System (FAERS) is a publicly available database that captures spontaneously reported adverse events. The objective of this study was to evaluate the relationship between INSTIs and metabolic adverse events using the FAERS database. FAERS data were queried from quarter 4 of 2007 through quarter 4 of 2019 and limited to adults. The Standardized MedDRA Query for 'hyperglycaemia/new-onset diabetes mellitus' (H/DM) was used to identify metabolic adverse events of interest. Weight gain was analysed as a separate event. Reporting odds ratios (RORs) and 95% CIs were calculated for the INSTI class and individual agents. Over 10.1 million FAERS reports were identified. Any INSTI was mentioned as a primary and/or secondary suspect agent in 18,400 (0.18%) reports (bictegravir: 1414 [0.01%]; dolutegravir: 7840 [0.08%]; elvitegravir: 4034 [0.04%]; raltegravir: 5551 [0.05%]). RORs (95% CI) for H/DM and weight gain for any INSTI were 1.20 (1.15-1.27) and 2.16 (1.96-2.38). For individual agents, RORs (95% CI) for H/DM and weight gain were as follows: bictegravir, 1.23 (1.10-1.37) and 6.82 (5.50-8.41); dolutegravir, 1.28 (1.19-1.39) and 1.86 (1.58-2.18); elvitegravir, 0.76 (0.56-1.02) and 1.63 (1.37-1.92); and raltegravir, 1.00 (0.90-1.11) and 3.29 (2.77-3.91). H/DM was noted in 159 bictegravir and 712 dolutegravir reports. Overall, H/DM was associated with bictegravir and dolutegravir and weight gain with all INSTIs. Clinicians should know the potential relationship between INSTIs and metabolic effects and institute appropriate monitoring. META-INSTI: Metabolic Adverse Events Following Integrase Strand Transfer Inhibitor Administration in Spontaneous Adverse Event Reports. Platform Presentation. ID Week. Virtual 2020.

Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis.

The safety of tofacitinib in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) has been demonstrated in clinical studies of≤ 4 and 9.5years, respectively. Post-marketing surveillance (PMS) data for tofacitinib from spontaneous and voluntary adverse event (AE) reports have been published for RA, but not PsA. To inform the real-world safety profile of tofacitinib in PsA, we evaluated AE reports submitted to the Pfizer safety database (including RA data for context). Endpoints included AEs, serious AEs (SAEs), AEs of special interest (AESIs; serious infections, herpes zoster, cardiovascular events, malignancies, venous thromboembolism), and fatal cases. Exposure was estimated using IQVIA global commercial sales data. Number, frequency, and reporting rates (RRs; number of events/100 patient-years' [PY] exposure) were summarized by indication and formulation (immediate release [IR] 5 or 10mg twice daily], modified release [MR] 11mg once daily, or all tofacitinib). The data-collection period differed by indication (PsA: 14December2017 [US approval, IR/MR]to6November2021; RA: 6November2012 [US approval, IR]to6November2021; MR approval, 24February2016). A total of 73,525 case reports were reviewed (PsA = 5394/RA = 68,131), with 20,706/439,370 PY (PsA/RA) ofexposure. More AEs were reported for IR versus MR (IR/MR: PsA = 8349/7602; RA = 137,476/82,153). RRs for AEs (IR/MR: PsA = 59.6/113.4; RA = 44.0/64.8) and SAEs (PsA = 8.1/13.6; RA = 8.0/9.5) were higher with MR versus IR. AE RRs (RA) in the first 4years after IR approval were 95.9 (IR; 49,439 PY) and 147.0 (MR; 2000 PY). Frequency of SAEs, AESIs, and fatal cases was mostly similar across formulations and indications. The most frequently-reported AE Preferred Terms (PsA/RA) included drug ineffective (20.0%/17.8%), pain (9.7%/10.6%), condition aggravated (9.9%/10.5%), headache (8.8%/7.9%) and, for PsA, off-label use (10.5%/3.4%). Tofacitinib PMS safety data from submitted AE reports were consistent between PsA and RA, and aligned with its known safety profile. Exposure data (lower MR versus IR; estimation from commercial sales data), reporting bias, reporter identity, and regional differences in formulation use limit interpretation.

COVID-19 mRNA vaccination is associated with IgA nephropathy: an analysis of the Japanese adverse drug event report database.

Purpose: Coronavirus disease 2019 (COVID-19) mRNA vaccines are used worldwide to prevent severe symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IgA nephropathy (IgAN) is the most common form of glomerular injury after COVID-19 vaccination; however, because of the low frequency of such events, only a few reports have been published. A large pharmacovigilance database of real-world spontaneous adverse event (AE) reports is essential for evaluating the drug-associated safety signals regarding rare AEs. Herein, we aimed to investigate the frequency of IgAN after the COVID-19 vaccination, using the Japanese Adverse Drug Event Report (JADER) database. Methods: Data on drug-associated AEs reported between April 2004 and May 2022 were obtained from the JADER database on the Pharmaceuticals and Medical Devices Agency website. To evaluate the safety signals for the targeted AEs, reporting odds ratios (RORs), information components (ICs), and their 95% confidence intervals (CIs) were calculated using two-by-two contingency tables. Results: A total of 697,885 cases were included in the analysis. Safety signals were detected for IgAN (ROR: 6.49, 95% CI: 4.38-9.61; IC: 2.27, 95% CI: 1.70-2.83). Of 30 cases for IgAN associated with COVID-19 mRNA vaccines, 16 had information available on time to onset. Of the 16 cases, 11 occurred ≤2days after vaccination, and two occurred >28days after vaccination. Conclusion: These results suggest that, compared with other drugs, COVID-19 vaccination is associated with a higher frequency of IgAN. Monitoring of gross hematuria following COVID-19 vaccination should be needed.

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System

ABSTRACT Background In this study, we fill this gap in knowledge by updating the safety profile of ubrogepant and rimegepant via disproportionality analysis in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a US-based database registering spontaneous reports. Research design and methods ASCII files of quarterly extraction of FAERS data were downloaded from the FDA website up to the 3rd quarter (Q3) of 2021 (last accessed 03/02/2022). Disproportionality analysis was done using the Reporting Odds Ratio (ROR) as a disproportionality measure. RORs of all AEs related to ubrogepant and rimegepant in FAERS were calculated in comparison with those related to erenumab. Drug-event pairs with a frequency ≤ 2, were removed according to European Medicine Agency (EMA)’s procedures. Results In total, 2010 and 3691 individual case safety reports (ICSRs) recorded in FAERS reported ubrogepant and rimegepant, respectively, as suspect drugs. Ten disproportionality signals for ubrogepant and 25 disproportionality signals for rimegepant were identified; these were mostly related to psychiatric, neurological, gastrointestinal, skin, vascular, and infectious type of adverse events. Conclusions New safety aspects related to the treatment of ubrogepant and rimegepant using disproportionality analysis from spontaneous reporting databases were identified. Further studies are needed to confirm these findings.

Adverse Events of Traditional Medicines and Herbal Products in The Thai Health Product Vigilance Center Database and The Ayurved Clinic of Applied Thai Traditional Medicine, Siriraj Hospital

Objective: The aim of this study was to categorize adverse events (AEs) and symptoms related to traditional medicines (TMs) and herbal products (HPs) using the Thai Vigibase program (TVP). Materials and Methods: TVP collected spontaneous AE reports including causality assessment of medical products in Thailand. For prospective data, Naranjo’s algorithm (NJA) was used to determine the level of causality. Results: There were a total of 1,133 AE case reports extracted from TVP and featured 1,229 TMs/HPs (310 TMs/HPs names) and 1,592 symptoms (204 symptom names). Andrographis paniculata was the product most frequently linked to AEs, with six cases of confirmed urticaria, 37 probable cases, and 24 possible causalities, 15 patients were given 23 TMs/HPs and this related to 33 AEs. The Ya Hom No.24 Tablets had the most reported AEs at 17.4% with only one causality, which was most probably linked to chest burning pain. There was also one case of herbal decoction relieving menopausal symptoms that was certainly related to chest fullness, feeling hot and cold, suffocation feeling, and sweating increase. Ayurved Siriraj Brand Ya Lom No.65 Pills, also reported one case that was linked to fatigue and drowsiness. Conclusion: Reports from both data sources found a similar pattern in AE type and TMs/HPs. Naranjo’s algorithm might be one of useful tools to help assess the causality between TMs/HPs and AEs. The results of this study serve as a good reference for causality between TMs/HPs and their AEs for all Thai traditional medicine practitioners.

Hematological and Other Cancers in People Using Clozapine: Analysis of Australian Spontaneous Reports Between 1995 and 2020.

Recent observational study evidence suggests that clozapine, unlike other antipsychotics, may be associated with a small increased risk of hematological malignancy. This study described characteristics of hematological and other cancers in those taking clozapine reported to the Australian Therapeutic Goods Administration. We analyzed public case reports for "clozapine," "Clozaril," or "Clopine" from January 1995 to December 2020 classified as "neoplasm benign, malignant and unspecified" by the Australian Therapeutic Goods Administration. Data on age, sex, dose, clozapine start and cessation dates, Medical Dictionary for Regulatory Activities reaction terms, and date of cancer were extracted. Overall, 384 spontaneous reports of cancers in people taking clozapine were analyzed. The mean age of patients was 53.9 years (SD, 11.4 years), and 224 (58.3%) were male. The most frequent cancers were hematological (n = 104 [27.1%]), lung (n = 50 [13.0%]), breast (n = 37 [9.6%]), and colorectal (n = 28 [7.3%]). The outcome was fatal for 33.9% of cancer reports. Lymphoma comprised 72.1% of all hematological cancers (mean patient age, 52.1 years; SD, 11.6 years). The median daily dose of clozapine at the time of hematological cancer report was 400 mg (interquartile range, 300-543.8 mg), and the median duration of clozapine use before hematological cancer diagnosis was 7.0 years (interquartile range, 2.8-13.2 years). Lymphoma and other hematological cancers are overrepresented in spontaneous adverse event reports compared with other cancer types. Clinicians should be aware of the possible association with hematological cancers and monitor for and report any hematological cancers identified. Future studies should examine histology of lymphomas in people using clozapine and corresponding blood level of clozapine.

Drug repositioning prediction for psoriasis using the adverse event reporting database.

Inverse signals produced from disproportional analyses using spontaneous drug adverse event reports can be used for drug repositioning purposes. The purpose of this study is to predict drug candidates using a computational method that integrates reported drug adverse event data, disease-specific gene expression profiles, and drug-induced gene expression profiles. Drug and adverse events from 2015 through 2020 were downloaded from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR), information component (IC) and empirical Bayes geometric mean (EBGM) were used to calculate the inverse signals. Psoriasis was selected as the target disease. Disease specific gene expression profiles were obtained by the meta-analysis of the Gene Expression Omnibus (GEO). The reverse gene expression scores were calculated using the Library of Integrated Network-based Cellular Signatures (LINCS) and their correlations with the inverse signals were obtained. Reversal genes and the candidate compounds were identified. Additionally, these correlations were validated using the relationship between the reverse gene expression scores and the half-maximal inhibitory concentration (IC50) values from the Chemical European Molecular Biology Laboratory (ChEMBL). Inverse signals produced from a disproportional analysis can be used for drug repositioning and to predict drug candidates against psoriasis.

571. A Report of the Postmarketing Spontaneous Safety Data over 24 Years for GSK’s Measles-Mumps-Rubella (MMR) Vaccine

Abstract Background GSK’s measles-mumps-rubella (MMR) vaccine is indicated for active immunization of individuals aged 12 months and older against these 3 serious illnesses. It is licensed in &amp;gt; 100 countries worldwide not including the US. In clinical trials, it elicited robust immune responses in children and was well tolerated. Monitoring the vaccine’s real-world safety profile in the general population continues, and rapid collection of data on its real-world use is a strength of passive safety surveillance. We provide an overview of the postmarketing spontaneous safety data over 24 years for GSK’s MMR vaccine. Methods Spontaneous adverse events (AE) reports following vaccination with GSK’s MMR vaccine were collected from GSK’s Global Safety Database from 4-December-1997 until 1-March-2022. Annual reporting trends for pyrexia, rashes (commonly reported in the pediatric population), and events of clinical interest like febrile convulsions and neurological conditions were analyzed from 1998 until 2021. The patient exposure was estimated by the number of doses distributed (DD). Results Over the reviewed period, ∼445 million doses of GSK’s MMR vaccine were distributed worldwide, and 29,504 cases were spontaneously reported (rate: 6.63 cases reported/100,000 DD). Of all spontaneous AE reports, 9,960 (33.76%) were considered as serious. For the period analyzed, pyrexia and rash were the most frequently reported AEs following vaccination with GSK’s MMR vaccine (Table). Reports of febrile convulsions had a mean frequency of 0.27 cases/100,000 DD (Table); reports of neurological conditions (encephalitis and/or panencephalitis and/or meningitis and/or meningism) had a mean frequency of 0.07 cases/100,000 DD (Table) and did not show a trend of increased incidence over time. Conclusion The postmarketing safety data analyzed showed that the safety profile of GSK’s MMR vaccine is consistent with that observed in clinical trials and remains supportive of its overall safety profile in routine use. GSK continues monitoring the safety of its MMR vaccine. Funding GlaxoSmithKline Biologicals SA Acknowledgment: Adina Truta/Julie Mellery provided medical writing/editorial support (Modis c/o GSK) Disclosures Tina Singh, MD physician, GSK: Employee of the GSK group of companies and having restricted GSK shares in the GSK group of companies Giacomo Casabona, MD, GSK: I’m an employee of the GSK group of companies and shareholder in the GSK group of companies Remon Abu-Elyazeed, MD, PhD, GSK: Employee of the GSK group of companies and having GSK stocks in the GSK group of companies Volker Vetter, MD, GSK: I’m an employee of the GSK group of companies and hold shares in the GSK group of companies Fanny Hergibo, Pharm.D., GSK: Employee of the GSK group of companies.

Stimulated Reporting of Adverse Events Following Immunization with COVID-19 Vaccines.

In India, up until December 2021, Covishield and Covaxin vaccines against COVID-19 were being used for mass vaccination programs. In view of the urgency of fighting the ongoing pandemic, many vaccines have been granted emergency use approval while phase 2/3 clinical trials were still underway. Even for vaccines that have completed phase 3 trials, safety data may not be comprehensive. This retrospective observational study was conducted at a designated Regional Training Centre for Pharmacovigilance cum Adverse Drug Reaction Monitoring Centre (AMC) under the Pharmacovigilance Programme of India. The data sources were stimulated spontaneous reports of Adverse Events Following Immunization (AEFI) due to the COVID-19 vaccines from 10 January to 31 December 2021. A total of 51,010 COVID vaccine doses were administered during the study period. There were 330 AEFI reported (AEFI rate: 0.65%). Six AEFI were serious events among which three were Adverse Events of Special Interest. The majority of the AEFI were systemic, reported after the first dose, and with an onset between 1 and 24 h after vaccination. On comparing Covishield and Covaxin, there were no statistically significant differences in the AEFI reported with either vaccine in terms of gender, seriousness, lag period, duration, recovery, causality, treatment received for AEFI, presence of co-morbidity, or history of COVID-19 infection. Overall, the rates of AEFI was uncommon, and serious AEFI were rare with both Covishield and Covaxin, with a higher rate after the first dose. Whether immunological tolerance or allayed anxiety was responsible for the lower AEFI risk with the second dose remains to be investigated.

Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects.

Interstitial lung disease (ILD), as an adverse effect of certain drugs, leads to inflammation and damage in the walls of the alveoli, making it difficult for the alveoli to take up oxygen. Interstitial pneumonia with no identifiable cause is called idiopathic interstitial pneumonia (IIP), and, among the major IIPs, idiopathic pulmonary fibrosis (IPF) is diagnosed in about half of patients. Current treatment options are limited, among which the antifibrotic drugs nintedanib (Ofev) and pirfenidone (Pirespa) are the first-line drugs. In this study, we investigated the incidence of ILD possibly caused by antifibrotic agents using data from the Japanese Adverse Drug Event Report (JADER) database, a database of spontaneous adverse event reports published by the Pharmaceuticals and Medical Devices Agency (PMDA), and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), published by the FDA. We used the FAERS and JADER to detect the signals of adverse events on the basis of reporting odds ratios. The relationship between indications and adverse events was clarified by separating indications and adverse events using the spontaneous adverse event reporting database with novel drug involvement. Regarding the involvement of nintedanib and pirfenidone in the development of ILD, JADER and FAERS showed signals for both nintedanib and pirfenidone as suspect drugs, and no signals for nintedanib or pirfenidone as concomitant drug interactions were detected. We highlight this because there are only a few effective drugs for IPF, and effective and safe drug therapies should be implemented by taking into consideration drug-induced ILD.

Drug-Induced QT Prolongation and Torsade de Pointes in Spontaneous Adverse Event Reporting: A Retrospective Analysis Using the Japanese Adverse Drug Event Report Database (2004-2021).

Drugs with new mechanisms of action are continually being developed, but it is difficult to capture whether a drug induces QT prolongation/torsade de pointes (TdP) in preclinical and preapproval clinical trials. To evaluate drugs associated with drug-induced QT prolongation/TdP using a real-world database in Japan. A search was performed in the Japanese Adverse Drug Event Report (JADER) database for QT prolongation and TdP. The reporting odds ratio (ROR) was calculated to identify potential drug-induced QT prolongation/TdP association. Among the reported 4,326,484 data entries, 3410 patients exhibited QT prolongation/TdP (2707 with QT prolongation, 703 with TdP) with the suspected drugs. Of these patients, 53.9% were females. The highest occurrence was in the 70- to 79-year-old age group (24.7%). The most common types of drugs involved were cardiovascular drugs, central nervous system (CNS) drugs, anticancer drugs, and anti-infective drugs; the rate of overdose was reportedly very low at 1.6%. The highest adjusted RORs were observed for nifekalant (351.41, 95% confidence interval (CI) 235.85-523.59), followed by vandetanib (182.55, 95% CI 108.11-308.24), evocalcet (181.59, 95% CI 132.96-248.01), bepridil (160.37, 95% CI 138.17-186.13), diarsenic trioxide (79.43, 95% CI 63.98-98.62), and guanfacine (78.29, 95% CI 58.51-104.74). Among the drugs launched in Japan during the last decade, vandetanib had the highest adjusted RORs. This study using the JADER database showed that antiarrhythmic drugs, calcium-sensing receptor agonists, small-molecule targeted anticancer drugs, and CNS drugs are associated with QT prolongation/TdP. Further pharmacoepidemiological studies, such as cohort studies using large databases, are needed to prove these causal relationships.

Spontaneous Adverse Event Reporting by COVID-19 Vaccinated Healthcare Professionals Through an Electronic Form Implemented by the Hospital Pharmacy.

Aim: Implementation of a web-form based pharmacovigilance plan for the spontaneous notification of adverse events to the Comirnaty® COVID-19 vaccine during its administration to hospital healthcare professionals. Methods: An electronic pharmacovigilance form was developed containing 8 pre-defined event options, an open answer option for the description of other events and/or symptoms, and a question about the overall intensity of symptoms. The adverse events reports were standardized according to physiological and pathological condition. Results: A total of 4119 adverse events notifications were obtained with a 45% rate of electronic notification. The most clinically relevant events reported were:tachycardia (n = 19), dyspnea (n = 7), chest pain (n = 6), facial/labial edema (n = 6), lipothymia (n = 5), bronchospasm (n = 2), herpetic infection (n = 2), vasculitis (n = 2), arrhythmia (n = 1), difficult to control arterial hypertension (n = 1), gastritis (n = 1), and spontaneous abortion (n = 1). Regarding the intensity of symptoms (n = 2928), 70.0% were reported as mild, 25.8% as moderate, and 4.27% as severe, with higher intensity in the second dose compared to first dose. The highest frequency of severe events were reported in the groups from 40 to 59 years in both vaccination periods. During the vaccination process, no hospitalizations and no deaths were notified and/or recorded. Conclusion: In this real world study, comparing with Comirnaty clinical trials program, it was observed a higher frequency of adenomegaly and gastrointestinal disorders. Noteworthy, the notification of a case of miscarriage. The use of hospital pharmacy pharmacovigilance electronic forms, seemed to be relevant to notification adherence and to obtain a greater and faster knowledge of COVID-19 vaccine safety profile.

EPH139 COVID-19 Vaccine Related Adverse Events in a Population Aged 5–17 Years: A Study of Reports from the VAERS Database

Evaluating the side effects of COVID-19 vaccines and educating the public about their occurrence may dispel concerns and promote higher vaccination rates. This study focuses on the safety of COVID-19 vaccines approved in the U.S. for children between 5 and 17 years of age by considering spontaneous reports of adverse events from the Vaccine Adverse Event Reporting System (VAERS) database.