Food And Drug Administration Adverse Event Reporting System Database Research Articles

Bleeding Complications in Vancomycin-Induced Thrombocytopenia: A Real-world Postmarketing Pharmacovigilance Analysis

PurposeVancomycin and linezolid are first-line drugs used for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin is well known as the best alternative drug when linezolid-induced thrombocytopenia occurs. However, several cases with vancomycin-induced thrombocytopenia, especially with bleeding complications, have been reported recently, which has attracted attention. The objective of this study is to assess the potential relevance between vancomycin and bleeding complications in thrombocytopenia. MethodsThis is a real-world pharmacovigilance study conducted in October 2022 using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We performed a disproportional analysis to assess the risk of bleeding complications in vancomycin-induced thrombocytopenia by calculating reporting odds ratios (RORs) and information components (ICs), with a weak signal defined as a lower limit of the IC 95% CI of 0 to 1.5, a middle signal defined as a lower limit of the IC 95% CI of 1.5 to 3.0, and a strong signal defined as a lower limit of the IC 95% CI of >3.0. FindingsThere were 21,854 cases in the FAERS database that listed vancomycin as a suspected drug from quarter 1 of 2004 to quarter 2 of 2022. There were 800 cases of vancomycin-induced thrombocytopenia and 125 cases of bleeding complications in vancomycin-induced thrombocytopenia. Teicoplanin, tigecycline, and vancomycin (3 middle signals) were sequentially less associated with thrombocytopenia than linezolid (strong signal). However, bleeding complications in thrombocytopenia were significant associated with vancomycin (ROR = 9.641; 95% CI, 8.105–11.468; IC = 3.184; 95% CI, 2.929–3.440 [middle signal]), followed by linezolid (ROR = 9.350; 95% CI, 7.318–11.947; IC = 3.106; 95% CI, 2.745–3.466 [middle signal]), teicoplanin (ROR = 6.399; 95% CI, 2.869–14.272; IC = 2.059; 95% CI, 0.881–3.283 [weak signal]), and daptomycin (ROR = 2.784; 95% CI, 1.496–5.180; IC = 1.287; 95% CI, 0.374–2.201 [weak signal]). Tigecycline and daptomycin were the least likely anti-MRSA drug to cause thrombocytopenia (middle signal and weak signal, respectively) and bleeding complications in thrombocytopenia (no signal and weak signal, respectively). Middle signals of bleeding complication in vancomycin-induced thrombocytopenia were found in all group except those <45 to ≥80 years of age (weak signal). ImplicationsBleeding complications in thrombocytopenia were significantly associated with vancomycin use, and the risk was highest among all the anti-MRSA drugs. Physicians should be aware of this possible serious adverse reaction.

Weight gain, gender, and antipsychotics: a disproportionality analysis of the FDA Adverse Event Reporting System database (FAERS)

ABSTRACT Introduction Side effects are a very important aspect of antipsychotic treatments. Weight gain is an important side effect that jeopardizes the uninterrupted therapy administration, especially in patients with psychiatric conditions. This case-non-case pharmacovigilance study aims at investigating in a real-world adverse event reporting system whether several antipsychotics increase the risk of weight gain reporting, and the differences among men and women as far as weight gain as a reported adverse event is concerned. Areas covered Adverse event reports submitted to the FDA Adverse Event Reporting System of the Food and Drug Administration of the United States (FAERS) of 24 major antipsychotics were extracted, cleaned, and analyzed to determine which of these drugs were correlated with weight gain. The Reported Odds Ratio (ROR) and the adjusted Reported Odds Ratio (aROR) were calculated for each antipsychotic using logistic regression models. Demographics like age, gender, and concomitant insulin use were taken into consideration for each drug. Expert opinion Women had a statistically significant increase in weight gain reporting compared to men, while the men's group was associated with a reduced weight gain reporting in every antipsychotics in the logistic regression analyses. Out of the 24 antipsychotics included in our analysis, Aripiprazole, Brexpiprazole, Olanzapine, and Haloperidol had statistically significantly more weight increase reporting compared to the others.

A pharmacovigilance study of adverse event profiles and haemorrhagic safety of bevacizumab based on the FAERS database

ABSTRACT Background Bevacizumab is used for the treatment of advanced malignant tumors; it acts by inhibiting angiogenesis. This study aimed to examine adverse events (AEs) of bevacizumab, especially hemorrhage, using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Research Design and Methods The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to analyze the AEs of bevacizumab using FAERS registration data from January 2004 to September 2022. Clinical information regarding hemorrhagic signals was further analyzed. Results The number of bevacizumab-associated AE reports was 96,477. Our study found that 892 significant preferred terms (PTs) were spread throughout 25 organ systems. The system organ classes (SOCs) focus on general disorders, administration site conditions, blood and lymphatic system disorders, injury, poisoning, and procedural complications. A total of 2,847 bevacizumab-related hemorrhage cases were reported, and 37 hemorrhagic signals were identified. Hemorrhagic signals were focused on SOC levels in vascular, gastrointestinal, and nervous system disorders. Colorectal, lung, and breast cancers are the three most common malignancies associated with BV-induced hemorrhage. Conclusion The AE report from the present study confirms the majority of label information for bevacizumab, while also identifying new AEs. In addition, this was a large descriptive study of bevacizumab-induced hemorrhage.

A real-world pharmacovigilance study of abaloparatide based on the FDA Adverse Event Reporting System (FAERS).

We investigated 33,480(0.14%) ABL-related adverse events (AEs) through data mining of Food and Drug Administration Adverse Event Reporting System (FAERS) retrospectively. Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed to quantify the signals of ABL-related AEs from 2017Quarter2 to 2022.Serious and non-serious cases were compared by Mann-Whitney U test or Chi-squared (χ2) test. We collected 8,470,497 reports from the FAERS database, including 11,487 reports defined ABL as the primary suspected (PS) drug. Additionally, 36.16% of the reports were submitted by healthcare professionals (n=4154), compared to 62.26% reported by consumers (n=7140). A total 99 signals simultaneously conforming to four algorithms were detected, among which, 35 signals were identified as unexpected signals. Such as growing pains (n=13), waist circumference increased (n=21), sensory disturbance (n=103), tinnitus (n=65), visual acuity reduced (n=54), blood alkaline phosphatase increased (n=61), and hair growth abnormal (n=13). Patient age (p < 0.001) might be associated with an increased risk of AEs severity. The most common timeframe for AE occurrence was 0-7 days. Our study provided a deeper and broader understanding of abaloparatide's safety profiles, which would help healthcare professionals to mitigate the risk of AEs in clinical practice, a low number of unexpected AEs supporting ongoing additional pharmacovigilance.

A real-world pharmacovigilance analysis of FDA adverse event reporting system database for upadacitinib.

Objective: To mine the adverse drug event (ADE) signals of upadacitinib based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to provide a reference for the safe clinical use of the drug. Methods: The ADE data for upadacitinib from Q1 2004 to Q1 2023 in the FAERS database were retrieved, and data mining was performed using the reporting odds ratio and proportional reporting ratio. Results: A total of 21,213 ADE reports for the primary suspect drug upadacitinib were obtained, involving 444 ADEs. Patients aged ≥60years (21.48%) and female (70.11%) patients were at a higher risk of ADEs with upadacitinib. After data cleaning, 182 ADE signals from 19 system organ classes (SOCs) were obtained. Six of these SOCs that occurred more frequently and were not mentioned in the drug labeling information included renal and urinary system (1.09%), reproductive and breast diseases (1.14%), ear and labyrinth disorders (0.57%), psychiatric disease (0.57%), blood and lymphatic system disorders (0.57%), and endocrine disorders (0.57%). The top ten most frequent ADE signals reported for upadacitinib were mainly related to: infections and infestations (7), investigations (2), and skin and subcutaneous tissue disorders (1). The top 10 ADEs in signal intensity ranking were lip neoplasm, ureteral neoplasm, eczema herpeticum, vulvar dysplasia, mediastinum neoplasm, eosinopenia, herpes zoster cutaneous disseminated, eye ulcer, acne cystic, and Moraxella infection. The top 10 high-frequency events leading to serious adverse events were urinary tract infection (2.74%), herpes zoster (1.63%), diverticulitis (1.19%), bronchitis (0.68%), nasopharyngitis (0.68%), localised infection (0.66%), nephrolithiasis (0.66%), pulmonary thrombosis (0.66%), blood cholesterol increased (0.55%), and Pneumocystis jirovecii pneumonia (0.53%). Conclusion: Clinicians should be vigilant to upadacitinib-induced events in systems not covered in the drug labeling information and to new and highly signaled ADEs to ensure the safe and effective use of upadacitinib.

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.

Angiotensin Receptor Blocker-Related Sprue-like Enteropathy: Review of Food and Drug Administration Adverse Event Reporting System.

Sprue-like enteropathy (SE) related to olmesartan use was first reported in 2012. In 2017, the manufacturer of Benicar paid $300 million for 2300 claims for olmesartan-related SE. A study in 2019 suggested that SE was related to olmesartan and with the possibility of angiotensin receptor blocker (ARB) class effect. To further characterize this condition, our group examined reports of ARB-related SE to Food and Drug Administration Adverse Event Reporting System (FAERS). All reports of ARB-related SE from January 2017 to December 2021 were downloaded from the FAERS database. Gastrointestinal adverse events including SE were reviewed. Reporter categories included physicians, pharmacists, other health care professionals, consumers, and attorneys. A total of 106 590 reports of ARB-related adverse effects were analyzed. Sprue-like enteropathy was identified in 4337 cases (4.1% of total reports). Of these, 4240 cases (98.0%) of ARB-related SE were reported in patients using products with olmesartan, and 97 cases of SE were reported for all other ARBs (eprosartan, losartan, telmisartan, irbesartan, valsartan, and candesartan). Reports of olmesartan-related SE increased rapidly in 2017, continued at a high rate in 2018 and 2019, and essentially stopped in 2020 and 2021. Reports to FAERS for ARB-related SE are mostly related to olmesartan. There was a steep decline in reports of olmesartan-related SE following the lawsuit with potential of lawyer interference. There are reports of SE related to ARBs other than olmesartan, with increased physician awareness and the potential to discover a class effect with future studies.

Causes of Drug-Induced Severe Cutaneous Adverse Reaction Epidermal Necrolysis (EN): An Analysis Using FDA Adverse Event Reporting System (FAERS) Database.

The purpose of the study is to analyze FAERS data to identify drugs associated with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), determine demographics, drug classes involved, most likely resulted in death, and highlight emerging trends in SJS/TEN reactions. We reviewed the publicly available FAERS database from 2004-2021. Using search terms "Stevens-Johnson syndrome" or "Toxic epidermal necrolysis", we identified the reports of SJS/TEN or SJS/TEN followed by death that might associated with specific drugs. Then the amounts and trends were counted analyzed. During the study period of 2004-2021, the Food and Drug Administration (FDA) received a total of 14,363,139 reports of adverse reactions, among which 24,976 were linked to SJS or TEN. After excluding the cases with incomplete or insufficient information on age, gender, or country of origin, the median median age of patients was 53.82 (IQR = 57.52), the females accounted for 56.59% (12,827 cases) and 8,507 (38.34%) originated in the United States. The top 50 drugs were associated with 15,149 cases (60.65%). The subsequent fatal outcome occurring in 4878 out of 24,976 cases (19.53%). Top 3 drug classes associated with SJS/TEN in FAERS were antiepileptics, non-steroidal anti-inflammatory drugs (NSAIDs) and others. Top drug classes associated with SJS/TEN deaths were antineoplastic agents and cephalosporins. Linear regression showed that the annual percentage of monoclonal antibody-related SJS/TEN reactions increased at an average rate of 0.25% (95% confidence interval: 0.18, 0.32) from 0.00% in 2004 to 4.79% in 2021, faster than any other drug class except antigout drug (allopurinol). By using the publicly available FAERS data, we have identified some important themes and trends in drug-related SJS/TEN reactions. Monoclonal antibodies and proton pump inhibitors are drugs with emerging trends causing SJS/TEN. Additionally, cephalosporin antibiotics have a higher mortality rate following SJS/TEN.

A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic Anemia in the FDA Adverse Event Reporting System.

Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term "anaemias haemolytic immune" according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.

Cardiac arrhythmias associated with anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) may provoke cardiac arrhythmias. We conducted this pharmacovigilance analysis to research cardiac arrhythmias associated with ALK-TKIs using the Food and Drug Administration Adverse Event Reporting System (FAERS). Research design and methods The first ALK-TKI, named crizotinib, was approved by the Food and Drug Administration (FDA) on 26 August 2011 for the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). We evaluated ALK-TKIs-induced cardiac arrhythmias, by using the reporting odds ratio (ROR) and information component (IC) for mining the adverse event report signals in the FAERS database between January 2016 and June 2022. Results We identified a total of 362 ALK-TKIs-related cardiac arrhythmia reports which appeared to influence more men (64.44%) than women (30.76%), with a median age of 68 (interquartile range [IQR] 7–74) years. Compared with the full database, ALK-TKIs were detected with pharmacovigilance of cardiac arrhythmias (ROR025 = 1.26, IC025 = 0.26). Crizotinib and alectinib were found to be related to higher reporting of arrhythmias. The median time to onset (TTO) among five ALK-TKI therapies was significantly different (p = 0.044). Conclusion ALK-TKIs present different frequencies of cardiac arrhythmias reporting, with only crizotinib and alectinib producing positive signals in high-level group term (HLGT) level arrhythmia. The time interval between the initial of drug treatment to the onset of arrhythmia varies greatly and cannot be predicted.

Purine antimetabolites associated Pneumocystis jirovecii pneumonia.

To detect the possible safety signal of purine antimetabolites associated with Pneumocystis jirovecii pneumonia through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database. A case/non-case retrospective disproportionality analysis was performed in the publicly available FAERS database using AERSmine (2004Q1-2021Q3). Four models were developed to explore the signal strength of PAs among different populations with possible confounding factors. Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) was used as the data mining algorithm for the analysis. A value of ROR-1.96SE > 1 and PRR ≥ 2 with an associated X2 value of 4 or more was considered the threshold for a signal. A total of 7073 reports associated with Pneumocystis jirovecii pneumonia were present in the database, of which 899 reports were associated with purine antimetabolites. A crude signal strength of ROR 15.76(14.70-16.91) was obtained for purine antimetabolites associated PJP, with the highest signal strength reported with fludarabine and thioguanine [ROR 19.63(17.42-22.13); 19.45(13.21-28.63)]. Stratifying the cases based on autoimmune disorders and the cancer population revealed an ROR of 3.33(2.46-4.50) and 2.93(2.26-3.79) respectively. The highest risk of PJP with use of PAs was observed amongst children with a higher risk of nearly 2 times than the adult population [ROR 11.57(9.16-14.62)]. Our study provided evidence on the occurrence of PJP with the use of purine antimetabolites among the autoimmune and cancer population. We identified signals for PJP with azathioprine, mercaptopurine, thioguanine, cladribine, fludarabine, and clofarabine. More research with a superior epidemiological study design of a defined population is required to validate these findings.

Post-Marketing Safety Concerns with Upadacitinib: A Disproportionality Analysis of the FDA Adverse Event Reporting system

ABSTRACT Background Upadacitinib was approved to treat rheumatoid arthritis, psoriasis, ulcerative colitis, ankylosing spondylitis, and atopic dermatitis. This study assessed the adverse events (AEs) associated with upadacitinib by mining data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of upadacitinib-associated AEs. Results A total of 3,837,420 reports of AEs were collected from the FAERS database, of which 4494 reports were identified with upadacitinib as the “primary suspect (PS)”. Upadacitinib-induced AEs occurrence targeted 27 system organ clases (SOCs). A total of 200 significant disproportionality PTs conforming to the four algorithms were simultaneously retained. Unexpected significant AEs, such as arthralgia, musculoskeletal stiffness, diverticulitis, and cataract might also occur. The median onset time of upadacitinib-associated AEs was 65 days (interquartile range [IQR] 21–182 days), and most of the onsets occurred within the first 1, 2, 3, and 4 months after initiation of upadacitinib. Conclusion This study found potential new AEs signals and might provide important support for clinical monitoring and risk identification of upadacitinib.

Investigating the risk of deep vein thrombosis with JAK inhibitors: a disproportionality analysis using FDA Adverse Event Reporting System Database (FAERS)

ABSTRACT Background Janus kinase (JAK) inhibitors are immune-modulating medications used to treat conditions including rheumatoid arthritis, COVID-19, ulcerative colitis, atopic dermatitis, myelofibrosis, and polycythemia Vera. However, these medications have been associated with higher incidence of deep vein thrombosis. The objective of this study was to investigate potential safety signals for DVT associated with JAK inhibitors using disproportionality analysis from the FDA Adverse Event Reporting System (FAERS) database. Research design and methods The authors retrospectively investigated case/non-case analysis using Openvigil 2.1-MedDRA-v24 (2004Q1 to 2022Q4). The preferred term used was ‘deep vein thrombosis,’ and the drugs included were baricitinib, tofacitinib, and upadacitinib. Reporting odds ratio, proportional reporting ratio, and information component were used to detect signals. Results Overall 114,005 AE reports related to JAK inhibitors were identified, of which 647 reports (baricitinib − 169, tofacitinib − 425, and upadacitinib − 53) associated with DVT were obtained from FAERS. On analysis, baricitinib and tofacitinib had greater signal strength for age group of 65–100 years and all three had the highest signal strength for male gender. Conclusions Our study identified signals for DVT with baricitinib, tofacitinib, and upadacitinib. Further research using well-designed epidemiological data is needed to validate these results.

Adverse events of guselkumab in the real world: emerging signals to target preventive strategies from the FDA adverse event reporting system

ABSTRACT Background Guselkumab is an IL−23 inhibitor widely used for the treatment of moderate-to-severe plaque psoriasis. Our study aimed to characterize the profile of adverse events (AEs) associated with guselkumab from the FDA adverse event reporting system (FAERS). Methods Disproportionality analysis including the proportional reporting ratio (PRR), the reporting odds ratio (ROR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms were used to assess the signals of guselkumab related AE. Results A total of 22,950,014 reports were collected from the FAERS database, of which 24,312 reports regarding guselkumab as the ‘primary suspected (PS)’ AEs were identified. AEs induced by guselkumab were distributed in 27 organ systems. In this study, 205 significant disproportionality preferred terms (PTs) that matched four algorithms simultaneously were obtained for analysis. Unexpected significant AEs such as onychomadesis, malignant melanoma in situ, endometrial cancer, and erectile dysfunction were observed. Conclusion The clinical observed AEs, along with potential new AE signals associated with guselkumab were identified based on the analysis of FAERS data, which could provide valuable evidence for clinical monitoring, risk identification, and further safety studies of identification.

Real-world safety profile of riluzole: a systematic analysis of data from the FAERS database and case reports

ABSTRACT Background The study aims to obtain the safety profile of riluzole in the real world and provide reference for clinical drug applications. Research design and methods Proportional reporting ratio (PRR) was used to detect riluzole adverse drug reactions (ADRs) from the data between the first quarter of 2004 and the third quarter of 2022 in the FDA adverse event reporting system database (FAERS). Case reports of riluzole published in PubMed, Embase, and Web of Science before November 2022 were reviewed, and patient’s data were extracted. Results FAERS analysis identified 86 ADRs. Gastrointestinal system disorders and respiratory, thoracic, and mediastinal disorders account for 12 of the top 20 most frequent ADRs. Similarly, 9 of the 20 highest PRR ADRs were gastrointestinal system disorders and respiratory, thoracic, and mediastinal disorders. Twenty-two published riluzole-associated cases were identified in the literature. Respiratory, thoracic, and mediastinal disorders were the most commonly reported cases (n = 9), followed by gastrointestinal disorders, pancreatitis (n = 5). Conclusions Strong ADRs between riluzole and pancreatitis were identified, which reminds clinicians to monitor patients carefully. For patients with respiratory symptoms, clinicians should pay attention to distinguish the cause of their occurrence, and take appropriate measures. Beware that riluzole may increase the risk of inflammatory reactions and inappropriate vasopressin secretion and hyponatremia due to respiratory failure.

Safety profile of vascular endothelial growth factor receptor tyrosine-kinase inhibitors in pediatrics: a pharmacovigilance disproportionality analysis.

Introduction: existing research on children consists primarily of phase I/II clinical trials for VEGFR-TKI. System reports of safety on the use of VEGFR-TKI in pediatrics are lacking. Aim: to investigate the safety profiles of VEGFR-TKI in pediatrics via the FDA Adverse Event Reporting System (FAERS). Method: data regarding VEGFR-TKIs were extracted from the FAERS between 2004Q1 to 2022Q3 and categorized by the Medical Dictionary for Regulatory Activities (MedDRA). Population characteristics were analyzed, and reporting odds ratio (ROR) was performed to identify risk signals associated with VEGFR-TKI. Results: 53,921 cases containing 561 children were identified in the database from 18 May 2005, to 30 September 2022. Among those in the system organ class, skin, subcutaneous tissue disorders, and blood and lymphatic system disorders in pediatrics contributed to over 140 cases. Palmar-plantar eythrodysesthesia syndrome (PPES) in VEGFR-TKI presented the most significant 340.9 (95% 229.2-507.0). And pneumothorax also gave a high reporting odds ratio of 48.9 (95% 34.7-68.9). For a specific drug, musculoskeletal pain gave a ROR of 78.5 (95% 24.4-252.6) in cabozantinib and oesophagitis in lenvatinib with a ROR of 95.2 (95% 29.5-306.9). Additionally, hypothyroidism presented a high signal, especially sunitinib, with a ROR of 107.8 (95% 37.6-308.7). Conclusion: the present study explored the safety profile of VEGFR-TKI in pediatrics using the FAERS database. Multiple skin and subcutaneous tissue disorders, as well as blood and lymphatic system disorders, were common VEGFR-TKI-related AEs in system organ class. No serious hepatobiliary AEs were detected. For the specific AEs, PPES and pneumothorax were VEGFR-TKI-related AEs that presented significantly higher signals than those in the general population.

Mining and analysis of adverse drug reactions associated with perampanel based on FAERS database

IntroductionPerampanel (PER) is a non-competitive AMPA glutamate receptor antagonist used as an anti-seizure medication. Large post-marketing databases are still lacking for safety analysis of the new generation of anti-seizure medications. Based on the FDA's adverse event reporting system (FAERS) database, this study aimed to investigate, assess, and offer evidence for the safety of PER to support clinical decision-making. MethodsPerampanel-related adverse reaction signals were mined using the reporting odds ratio (ROR), medicines and healthcare products regulatory agency (MHRA), and Bayesian confidence propagation neural network (BCPNN). The rate and occurrence of reported adverse responses were examined. ResultsWith the three methodologies used in combination, 83 signals mostly related to psychosis and different nervous system disorders were detected. Among them, suicide behavior, respiratory depression, hepatotoxicity, cognitive impairment, and other possible novel signals warranted consideration. Further examination of the age and gender differences in the detected signals revealed that elderly patients should be closely monitored for any change in consciousness and the occurrence of movement disorders; male patients should be observed for negative mental reactions like a personal attack and homicidal ideation; and female patients should be watched for the occurrence of negative reactions in memory, weight, vision, liver function, and other specific areas. ConclusionsThis study found that PER had the risk of causing suicide behavior, respiratory depression, hepatotoxicity, and cognitive impairment among other adverse effects. When used clinically, PER should be closely monitored for the occurrence of adverse effects on mental health and behavior. However, these results should be interpreted with caution.

Hepatitis B reactivation in patients with multiple myeloma treated with anti-CD38 monoclonal antibody-based therapies: a pharmacovigilance analysis.

Daratumumab and isatuximab are anti-CD38 monoclonal antibodies indicated for the treatment of multiple myeloma. These agents can increase the risk of infectious complications, including viral infections. Cases of hepatitis B virus (HBV) reactivation have been reported in the literature in patients receiving anti-CD38 monoclonal antibody-based therapies. The objective of this analysis was to determine if the association between anti-CD38 monoclonal antibody exposure and the development of hepatitis B reactivation had a detectable reporting signal in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). We conducted a post marketing pharmacovigilance analysis by querying the FAERS for reports of HBV reactivation with daratumumab or isatuximab exposure reported between 2015 and 2022. Disproportionality signal analysis was conducted by calculating reporting odds ratios (RORs). Sixteen cases of hepatitis B virus reactivation were reported in the FAERS database among patients receiving daratumumab or isatuximab reported between 2015 and 2022. The ROR for HBV reactivation was statistically significant for both daratumumab (ROR 4.76, 95% CI 2.76-8.22) and isatuximab (ROR 9.31, 95% CI 3.00-28.92). Overall, our analysis demonstrates a significant reporting signal for HBV reactivation with daratumumab and isatuximab.

A real-world pharmacovigilance study of severe cutaneous adverse reactions associated with antiepileptic drug combination therapy: data mining of FDA adverse event reporting system

ABSTRACT Background The aim of this study was to evaluate the association between antiepileptic drug combination regimens and severe cutaneous adverse reactions (SCAR). Research design and methods We gathered cases indication with epilepsy based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2021. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results Out of 128,262 reports were collected from the FAERS database, 104,278 cases were in the antiepileptic drugs group, and 23,984 cases were in the other primary suspected drugs group. A total of 20 combination regimens were associated with increased association of SCAR, top five of them were topiramate-phenytoin (ROR 57.62, 95% CI 30.93–107.34), lamotrigine-valproic acid (ROR 52.93, 95% CI 47.09–59.49), diazepam-phenobarbital (ROR 39.61, 95% CI 20.01–78.38), zonisamide-valproic acid (ROR 36.57, 95% CI 19.16–69.80), lamotrigine-diazepam (ROR 35.22, 95% CI 15.70–79.00). Conclusion The antiepileptic agent combinations may increase the incidence of SCAR and should be carefully evaluated in clinical practice. It is recommended to choose the combination regimens which have lower SCAR reporting rate for patients.

A real-world data analysis of acetylsalicylic acid in FDA Adverse Event Reporting System (FAERS) database

ABSTRACT Background Acetylsalicylic acid (Aspirin), one of the oldest medicines, is widely used in various clinical fields. However, numerous adverse events (AEs) have been reported. In this study, we aimed to investigate adverse drug reactions (ADRs) of aspirin using real-worlddata from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods We assessed the disproportionality of aspirin-related AEs by calculating measures such as reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagationneural network (BCPNN), and Gamma-Poisson Shrinker (GPS). Results Out of 7,510,564 casereports in the FAERS database, 18644 reports of aspirin as the ‘primary suspected (PS)’ AEs were recorded. Disproportionality analyses identified 493 aspirin-related preferred terms (PTs) across 25 organ systems. Notably, unexpected significant AEs such as pallor (p=5.66E–33), dependence (p=6.45E–67), and compartment syndrome (p=1.95E–28) were observed, which were not mentioned in the drug’s instructions. Conclusion Our findings align with clinical observations, highlighting potential new and unexpected ADR signals associated with aspirin. Further prospective clinical studies are necessary to confirm and elucidate the relationship between aspirin and these ADRs. This study offers a fresh and unique perspective for studying drug-AEs.