Principal component analysis of antiseizure medication-induced hostility/aggression and factor analysis of levetiracetam using the food and drug administration adverse event reporting system.

The association between antiseizure medications (ASMs) and suicidality remains controversial. Analyses of additional datasets are needed to further elucidate the complex relationship between antiseizure medications and suicidality. The aim of this study was to compare the safety profile of newer ASMs with older ASMs through an analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with a focus on suicidality. We queried over 17 million reports in the FAERS database from 2012 to 2021 and identified cases involving ASMs. After removing incomplete and duplicate reports, the study cohort consisted of lacosamide (n = 7593), perampanel (n = 1813), clobazam (n = 3827), brivaracetam (n = 1166), and vigabatrin (n = 5293) compared with a control group of older ASMs (topiramate, lamotrigine, valproic acid, carbamazepine, levetiracetam; n = 71,535). Cases of suicidality (completed suicide, suicidal ideation, attempted suicide, suicidal behavior, suicidal depression) were identified in each group. Adjusted (age and sex) odds ratios (aOR) and associated 95% confidence intervals (CI) were calculated using logistic regression analysis for each new drug when compared with the control group of older ASM drugs. A total of 6309 cases of suicidality were identified among reports with ASMs. Most reports were sourced from healthcare professionals (5516, 87.4%). The proportion of reports involving suicidality were 210/7593 (2.8%) for lacosamide, 185/1813 (10.2%) for perampanel, 108/3827 (2.8%) for clobazam, 57/1166 (4.9%) for brivaracetam, 14/5293 (0.3%) for vigabatrin, and 5735/71,535 (8.0%) for older ASMs. Compared with older ASMs, the aOR for suicidality was 0.33 (95% CI 0.28-0.38) for lacosamide, 1.34 (95% CI 1.15-1.56) for perampanel, 0.35 (95% CI 0.29-0.43) for clobazam, 0.60 (95% CI 0.45-0.77) for brivaracetam, and 0.03 (95% CI 0.02-0.05) for vigabatrin. When compared with older ASMs, four newer ASMs (lacosamide, clobazam, brivaracetam, and vigabatrin) were found to have significantly lower odds of suicidality, while perampanel was found to significantly increase the odds of suicidality. Pronounced variability (greater than 30 fold) in the proportion of FAERS reports associated with suicidality among the drugs studied was identified. The results of this case control study of FDA adverse event reports spanning 10years and 6309 cases of suicidality expand our understanding of the safety profile of newer ASMs.

e18794 Background: Dysphonia is a rare and under-reported adverse event. It is associated with the use of several cancer drugs. Dysphonia has been included as possible side effect on packet insert (PI) for some medications, like regorafenib, lenvatinib and axitinib. However, dysphonia has not been reported on multiple other drugs. We aimed to conduct a more comprehensive study to generate signal for dysphonia as adverse effect of drugs used for oncologic indications. Methods: The United States Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database, a pharmacovigilance database, was used to extract data. All reported cases of dysphonia in the database were filtered for an indication of cancer. Descriptive analysis was conducted using SPSS 26. Results: Total 41840 cases of dysphonia were extracted from FAERS database. Out of these, cancer as an indication for medication use was noted in 2996 cases. Dysphonia was reported as side effect of 30 medications. Some of the most common medications were regorafenib (n=463), cabozantinib (290), lenvatinib (178), axitinib (176) and palbociclib (126) as noted in Table. Dysphonia was not listed as adverse reaction on PI for cabozantinib, palbociclib, sorafenib and oxaliplatin. However, it has been reported for regorafenib, lenvatinib and axitinib. Median age at diagnosis was 66 years (interquartile range 59-73). Dysphonia was reported more commonly in males (51.5%) as compared to females (46.2%). Reactions were reported to the FDA more commonly by consumers (53.3% cases) as compared to healthcare professionals (44.5% cases). Conclusions: This study demonstrates signal of developing dysphonia in patients receiving certain cancer directed medications based on FAERS database. It is worth noting that some of the suspect medications identified in this study do not have dysphonia listed as known adverse effect on accompanying package insert. Further studies need to be conducted to confirm if causal relationship exists between use of these drugs and development of dysphonia. Detailed description of five drugs used for oncologic indications with highest reported cases of dysphonia as adverse effect.[Table: see text]

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

On April 18, 2024, the U.S. Food and Drug Administration officially required updating of the "boxed warning" for T cell malignancies for all chimeric antigen receptor T cell (CAR-T) therapies. Given the clinical significance of these therapies, a rigorous safety assessment is paramount. However, comprehensive real-world safety studies have been lacking for the newly marketed CAR-T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which target B cell maturation antigen, especially regarding the risk of secondary malignancies. Therefore, we aimed to thoroughly analyze the adverse events (AEs) information in the FDA Adverse Event Reporting System (FAERS) database to comprehensively understand the safety risks of ide-cel and cilta-cel. We extracted AE reports related to ide-cel and cilta-cel from the FAERS database (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.) from January 1, 2019 to December 31, 2023. Disproportionality analysis and Bayesian analysis were used to identify risk signals across subgroups and specific cases (including for death and secondary malignancies). Weibull distribution analysis was employed to determine the time to AE onset. A total of 695 AE reports for ide-cel and 848 for cilta-cel were included in the FAERS database. This analysis identified 81 positive signals for ide-cel and 74 for cilta-cel. Notably, comparisons with the drug labels revealed "unexpected signals," including febrile bone marrow aplasia (reporting odds ratio=69.10; confidence interval 39.12-122.03) and plasma cell myeloma (12.45; 8.18-18.95) for ide-cel, and increased serum ferritin (24.98; 8.0-77.58) and large intestine perforation (18.57; 5.98-57.69) for cilta-cel. Both drugs showed a higher AE incidence among male recipients and patients aged ≥65 years, although female recipients faced a greater risk. Most AEs occurred at the early stage of administration. However, secondary malignancies were detected for both drugs, primarily occurring one-year post-administration. This study provides a foundation for understanding the safety profile of CAR-T cell therapy, particularly in relation to the emergence of secondary malignancies. Such insights are helpful for clinical decision-making and the safe and effective utilization of these therapeutic agents.

Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

Background Tetracyclines are a class of antibacterial drugs commonly used in clinical practice, but there is no systematic analysis of the adverse effects (AEs) of these drugs. We performed such pharmacovigilance analyses using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore tetracycline-related AEs. Research design and methods We used the pharmacovigilance analysis tool Open Vigil 2.1 to access FAERS data and obtained AE reports from January 2004 to June 2023, including doxycycline, minocycline, tigecycline, omadacycline, sarecycline, and eravacycline as the top suspect drugs. The signal value of the AE of the analyzed drug was calculated by the reporting odds ratio (ROR). Results A total of 15,020 cases were identified by analyzing drugs. In terms of adverse signals, doxycycline caused gastrointestinal mucosal necrosis (ROR = 1699.652); minocycline was reported to cause bone hyperpigmentation (ROR = 30976.223); tigecycline is responsible for blood fibrinogen decreased (ROR = 1714.078). Conclusions AE reports of tetracycline drugs varied significantly. We found some AEs not mentioned in the instruction, such as the ototoxicity of tetracyclines. Doxycycline was associated with psychiatric side effects; minocycline presented in thyroid and skin tissue-associated tumors; abnormal signals were detected with eravacycline in the blood system.

Background:This research aims to explore and compare the signals of rhabdomyolysis from the use of Proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods:Rhabdomyolysis and related terms submitted between 2013 and 2021 were retrieved from the FAERS database. The data were analyzed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayes Geometric Mean (EBGM) and the information component (IC). The signals of rhabdomyolysis associated with PPIs use were detected in both 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) utilizers and non-utilizers.Results:A total of 7,963,090 reports were retrieved and analyzed. Fifty-seven reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association. The ROR was 2.5 (95% confidence interval [CI] 1.9–3.2) for PPIs in non-statin-included reports and 2 (95% CI: 1.5–2.6) for PPIs in statin-included reports.Conclusion:Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports compared to statin-included reports.Plain Language SummaryPlain language summaryProton Pump Inhibitors and rhabdomyolysis riskBackground: The FDA created the FDA Adverse Event Reporting System (FAERS) database to support post-marketing surveillance programs. The FAERS is a computerized database with more than nine million adverse event reports, including all reports from 1969 to the present. This research aims to explore and compare the signals of rhabdomyolysis from the use of proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Research design and methods: We retrieved rhabdomyolysis and related terms submitted between 2013 and 2021 from the FAERS database. Then, we analyzed the data that we found. We detected the signals of rhabdomyolysis associated with PPIs use in both statins utilizers and non-utilizers.Results: We retrieved and analyzed a total of 7,963,090 reports. We found 57 reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association.Conclusion: Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports than in statin-included reports.

Taxane drugs are essential chemotherapeutic agents in the clinical management of various solid tumors; however, their associated psychiatric adverse effects and underlying mechanisms remain insufficiently explored. This study aims to assess the association between taxane drugs and psychiatric adverse events (pAEs) and to investigate their potential biological mechanisms. The association between taxane drugs and pAEs was analyzed using the reporting odds ratio (ROR) method based on data from the Food and Drug Administration Adverse Event Reporting System (FAERS) (2013-2023) and the World Health Organization's global pharmacovigilance database (Vigibase database). Tumor-bearing mouse models treated with taxane drugs were developed, and RNA sequencing was conducted to examine the underlying molecular mechanisms. Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate the activity of relevant pathways. A total of 10,132 cases and 10,525 cases of pAEs associated with taxane drugs were identified in the FAERS and Vigibase databases, respectively. Nine significant taxane-related psychiatric adverse events (TX-related pAEs) were identified, with emotional distress showing the strongest signal. Subgroup analysis indicated that women (RORFAERS = 15.244), individuals younger than 45 years (RORFAERS = 17.849), and breast cancer patients exhibited a higher risk. Mechanistic studies revealed four significantly associated signaling pathways: cobalamin metabolic process, regulation of response to oxidative stress, G protein-coupled receptor signaling, and nitric oxide-mediated signal transduction. This study is the first to systematically assess taxane drug-associated pAEs, elucidating the characteristics of high-risk populations and underlying molecular mechanisms, thereby offering valuable insights for clinical drug safety and personalized treatment.

Clarithromycin is a widely used antibiotic, but its safety profile, particularly in different age groups, remains inadequately explored. This study aims to characterize and illustrate the features of clarithromycin-related adverse events (AEs) across different age groups using the FDA Adverse Event Reporting System (FAERS) database, providing a reference for the clinical detection, prevention, and management of AEs in various age groups. A disproportionality analysis was performed using data from the FAERS database. The study included all AE reports related to clarithromycin, stratified by age groups. Disproportionality analysis was conducted using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multiple gamma Poisson shrinkers. Statistical analyses included descriptive statistics and Chi-square tests. A total of 7319 reports of clarithromycin AEs were retrieved from the FAERS database. Vomiting, diarrhea, drug interactions, and drug interactions were reported most frequently in the age groups 0-17, 18-44, 45-64, and ⩾65 years, respectively. Abnormal product taste, taste disorder, and medication errors related to drug interactions specified in the package insert were the strongest signals in the age groups 0-17, 18-44, 45-64, and ⩾65 years, respectively. A total of 41 Preferred Terms signals were not explicitly included in the clarithromycin package insert and were mainly associated with psychiatric disorders, skin and subcutaneous tissue disorders, and gastrointestinal disorders, among others. Specific signals for age differences were identified, with 18 signals being age-specific, including 3 in children and 15 in elderly individuals. The safety profile of clarithromycin varies across age groups. In children, it is mainly associated with vomiting, hypersensitivity, and dyspnea, while in adults, psychiatric AEs are more common. In the elderly, clarithromycin should be used cautiously, with attention to drug interactions.

Analysis of pulmonary adverse events associated with immune checkpoint inhibitors based on FAERS and VigiBase database.

Comment on “Low dose oral minoxidil for treating alopecia: A 3-year North American retrospective case series”: Adding further evidence about side effects

Triazole antifungals are widely used as broad-spectrum antifungal activity; however, there are many undetected and unreported adverse events (AEs). Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021 were selected for disproportionality analysis to assess the connection between antifungal triazoles, and AEs and important medical events (IMEs). A total of 22,566 records associated with triazole antifungals were identified, with 9584 triazole antifungal-IME pairs. The following system organ classes (SOCs) appeared as significant signals: 'Endocrine disorders' [reported odds ratio (ROR) = 167.94], 'Metabolism and nutrition disorders' (ROR = 46.30), and 'Skin and subcutaneous tissue disorders' (ROR = 21.37). Strong signals were observed with respiratory failure, rash, hepatic function abnormal, and hypokalemia. Uncommon security signals included a change in the QT interval, neurotoxicity, pseudoaldosteronism, and hallucinations. Various triazole antifungals cause AEs of different types and intensities of association. Our results are broadly consistent with prescribing information and previous studies; however, additional pharmacoepidemiological studies are required to verify AEs with modest incidence but high signal. A study on the adverse effects of triazole antifungals Introduction: The triazole antifungals we studied include fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole. Triazole antifungals are widely used as broad-spectrum antifungals; however, there are many undetected and unreported adverse events (AEs).Materials and Methods: The Food and Drug Administration Adverse Event Reporting System (FAERS) database contains AEs reported to the FDA by different countries regarding post-marketing drugs. Through the FAERS database, we retrieved a total of 22,566 AE reports related to triazole antifungals. We not only counted information about patients' gender, age, weight, reporting country, outcome indicators, and indications but also analyzed the system organ classes (SOCs) of AEs, and the number of reported drug-related AEs and the degree of relevance.Results: We found a total of 22,566 records related to triazole antifungal agents, of which 9584 reports made important medical events (IMEs) about triazole antifungal agents, which are serious AEs. The following SOCs appear as important signals: 'endocrine disorders', 'metabolic and nutritional disorders', and 'skin and subcutaneous tissue disorders'. Triazole antifungals produce AEs, such as respiratory failure, rash, hepatic function abnormal, and hypokalemia. They also produce uncommon AEs, including changes in the QT interval, neurotoxicity, pseudoaldosteronism, and hallucinations.Conclusion: By analyzing data from the FAERS database, we identified more AEs associated with these five triazole antifungals than were indicated in the instructions and our findings provide additional insight into triazole-related AEs to inform clinicians before and during treatment.

Background: The U.S. Food and Drug Administration Adverse Event Reporting System, FAERS, contains information on adverse events and medication error reports submitted to the FDA through the MedWatch program. Opioid use has been linked to a significant number of adverse events reported in the FAERS database. The focus of this research  was to determine the frequency counts and related deaths of opioid drug names in the FAERS database. Methods: Drug information was obtained from the database's DRUG and OUTCOME files. Morphine, fentanyl, oxycodone, hydrocodone, tramadol, hydromorphone, methadone, codeine, oxymorphone, meperidine, propoxyphene, diphenoxylate, and heroin were among the drugs discovered. The MySQL database management system was used to determine the frequency counts and concomitant deaths of opioid drug names. Results: Fifteen different opioid drugs were linked to ADEs, including death, in the FAERS database, with three drugs (oxycodone, hydrocodone, and fentanyl) accounting for more than half of the reports. The highest frequency count value for oxycodone was 158,181, representing approximately 20.2 percent of the opioid frequency counts. Dextromethorphan had the lowest frequency count value of 2,161, accounting for approximately 0.3 percent of the total. The opioid with the highest proportion of deaths to drug count was heroin (71.8%), followed by dextromethorphan (55.6%), methadone (37.2%), morphine (26.8%), and propoxyphene (23.7%). Conclusion: The FAERS database is an important source for detecting and reporting Adverse Drug Events (ADEs), particularly those involving opioids and related drugs. Estimating the true incidence of ADEs for this class of drugs in the general population remains challenging.

BackgroundTemozolomidee (TMZ) is an alkylating antitumor drug used in the treatment of glioblastoma and anaplastic astrocytoma. It is often combined with radiotherapy and has cytotoxic effects on tumor cells. Although temozolomidee has a certain efficacy in the treatment of brain malignancies, its numerous adverse effects (AEs) suggest that its safety needs to be thoroughly evaluated.MethodsBased on data from the FDA Adverse Event Reporting System (FAERS) database, a retrospective pharmacovigilance study was conducted to evaluate temozolomide-related adverse events. Methods for identifying temozolomide-related AEs signals include taking a case/non-case approach. Specific detection algorithms also include report Odds ratio (ROR), Proportional Report ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item Gamma-Poisson constrictor (MGPS).ResultsAmong 48,766,547 FAERS reports, 13,608 TMZ-related AEs were identified. Males (53.66%) and patients aged ≥45 years predominated. The most frequent outcomes were hospitalization (35.76%), death (22.79%), and serious AEs (34.24%). Hematologic toxicities dominated, with “blood and lymphatic system disorders” showing the strongest signal (ROR 5.94, 95% CI: 5.73–6.15; PRR 5.48). Notable PTs included *petechiae* (ROR 9.87), *hemiparesis* (ROR 9.36), and *platelet count decreased* (ROR 8.61). Unexpected AEs, such as *pulmonary embolism* (ROR 4.96) and *Pneumocystis jirovecii pneumonia* (ROR 7.09), were identified. Renal/metabolic disorders (e.g., hypernatremia) and neurotoxic events (e.g., seizures, ROR 6.19) also demonstrated significant signals.ConclusionThis large-scale analysis highlights TMZ’s association with severe hematologic, thromboembolic, and opportunistic infection-related AEs in real-world settings. While expected toxicities (e.g., myelosuppression) were confirmed, novel signals like pulmonary embolism and neurotoxicity warrant further investigation. Clinicians should prioritize hematologic monitoring, thromboprophylaxis in high-risk patients, and *Pneumocystis* prophylaxis during corticosteroid co-administration. Future studies should validate these signals through prospective trials and mechanistic research to optimize TMZ’s risk-benefit profile in glioma therapy.

Background This study aimed to measure and present a comprehensive overview of the association of antipsychotic drugs and venous thromboembolism (VTE) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Method: All VTE cases treated with antipsychotic drugs as primary suspected medicines were extracted from the FAERS database from 2004 to 2021. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results In the FAERS system, 4,455 VTE cases associated with antipsychotics were identified. The VTE signal was detected with olanzapine, haloperidol, paliperidone, and quetiapine. The RORs and 95% confidence intervals (95% CI) of olanzapine, haloperidol, paliperidone, and quetiapine were (ROR = 2.53 95% Cl 2.38–2.69 IC = 1.31 95% Cl 1.11–1.52), (ROR = 2.17 95% Cl 1.91–2.46 IC = 1.1 95% Cl 0.66–1.52), (ROR = 1.6 95% Cl 1.4–1.83 IC = 0.67 95% Cl 0.22–1.11), and (ROR = 1.37 95% Cl 1.28–1.47 IC = 0.45 95% Cl 0.23–0.67). Pulmonary embolism occurred in more than 50% of VTE events (2760 cases, 52.84%). Conclusion The data mining of FAERS suggested an association between VTE and antipsychotic drugs, which reminds medical workers to pay attention to the serious adverse drug effects of antipsychotic drugs leading to venous thromboembolism.