Dataset Information

Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug-gene Interaction Network.

ABSTRACT: Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food and Drug Administration Adverse Event Reporting System (FAERS). Furthermore, we elucidated the potential toxicological mechanisms of montelukast-associated neuropsychiatric AEs through functional enrichment analysis of human genes interacting with montelukast. The reporting odds ratios of suicidal ideation and depression in the system organ class of psychiatric disorders were 21.5 (95% confidence interval (CI): 20.3-22.9) and 8.2 (95% CI: 7.8-8.7), respectively. We explored 1,144 human genes that directly or indirectly interact with montelukast. The molecular complex detection (MCODE) plug-in of Cytoscape detected 14 clusters. Functional analysis indicated that several genes were significantly enriched in the biological processes of "neuroactive ligand-receptor interaction." "Mood disorders" and "major depressive disorder" were significant disease terms related to montelukast. Our retrospective analysis based on the FAERS demonstrated a significant association between montelukast and neuropsychiatric AEs. Functional enrichment analysis of montelukast-associated genes related to neuropsychiatric symptoms warrant further research on the underlying pharmacological mechanisms.

SUBMITTER: Umetsu R

PROVIDER: S-EPMC8720925 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug-gene Interaction Network.

Umetsu Ryogo R Tanaka Mizuki M Nakayama Yoko Y Kato Yamato Y Ueda Natsumi N Nishibata Yuri Y Hasegawa Shiori S Matsumoto Kiyoka K Takeyama Noriaki N Iguchi Kazuhiro K Tanaka Hiroyuki H Hinoi Eiichi E Inagaki Naoki N Inden Masatoshi M Muto Yoshinori Y Nakamura Mitsuhiro M

Frontiers in pharmacology 20211220

Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food and Drug Administration Adverse Event Reporting System (FAERS). Furthermore, we elucidated the potential toxicological mechanisms of montelukast-associated neuropsychiatric AEs through functional enri ...[more]

PMID: 34987393

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Project description:BackgroundCapecitabine, a prodrug of 5-fluorouracil, is extensively utilized for the treatment of metastatic breast cancer, colorectal cancer, and gastric cancer. Nevertheless, there exist limitations in comprehending adverse reactions (AEs) in clinical practice. In this study, we investigated the distribution of AEs associated with capecitabine and explored potential rare adverse reactions by mining the Food and Drug Administration Adverse Event Reporting System (FAERS).ObjectivesOur research aimed to explore the spectrum of AEs associated with capecitabine, including both documented and potential events, to provide a comprehensive understanding of the drug's safety profile and guide clinical practice. At the same time, it provides a new direction for further research on AEs associated with capecitabine in the future.DesignWe collected capecitabine-related adverse reactions from the FAERS and standardized the classification of AEs using the Medical Dictionary for Regulatory Activities 26.0. Four statistical schemes were used to analyze the obtained standardized signals.MethodsWe collected AEs reported for capecitabine from the FAERS between 2004 and 2023. To ensure standardized data, the collected reports related to capecitabine-associated adverse events were categorized using the preferred terms (PTs) and system organ classes (SOCs) classifications provided by the Medical Dictionary for Regulatory Activities 26.0. Statistical analysis involved the utilization of reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. Four statistical schemes were employed to analyze the adverse reactions associated with capecitabine. A positive signal was considered when all four schemes indicated an association with the adverse event.ResultsWe collected a total of 45,011 AEs associated with the use of capecitabine from the database, covering 27 SOCs from 2004 to 2023. The nine SOC categories with the highest number of events were identified, which include gastrointestinal disorders; general disorders and administration site conditions; skin and subcutaneous tissue disorders; nervous system disorders; investigations, injury, poisoning, and procedural complications; blood and lymphatic system disorders; metabolism and nutrition disorders; infections and infestations; and neoplasms benign, malignant, and unspecified (including cysts and polyps). Among these 27 SOCs, we identified seven SOCs that met the signal value criteria. Notably, we discovered AEs not mentioned in the instructions, including intestinal obstruction in gastrointestinal disorders, penetrating aortic ulcer in cardiac disorders, and non-cirrhotic portal hypertension in hepatobiliary disorders, all of which exhibited signals. Furthermore, 40.1% of AEs associated with the use of capecitabine occurred within the first 30 days.ConclusionOur study conducted a comprehensive analysis of capecitabine's AEs using the FAERS database. We identified previously unreported AEs, mitigating the risk for patients and ensuring safe drug administration.

Project description:Omalizumab is a biologic agent used in the management of allergic conditions, including asthma and urticaria. Although the efficacy of omalizumab has been well established, its safety profile is primarily derived from clinical trials with limited sample sizes. To conduct a comprehensive evaluation of its safety in larger populations, this study conducted an extensive analysis of data sourced from the America Food and Drug Administration's Adverse Event Reporting System (FAERS), with the aim of elucidating adverse drug events associated with omalizumab in real-world settings. We extracted reports of adverse events associated with omalizumab from the FAERS database covering the period from the first quarter of 2004 to the second quarter of 2024. We assessed the significance of the association between omalizumab and adverse events using four distinct methods of disproportionality analysis. Furthermore, we analyzed adverse events across gender and age subgroups. We identified a total of 49,456 adverse event reports linked to omalizumab and pinpointed 357 adverse events related to omalizumab within 27 system organ classes. These adverse events encompassed several commonly reported reactions documented in the product labeling, including anaphylactic reactions (ROR: 17.28, 95%CI:16.62-17.96) and asthma (ROR:19.24, 95%CI:18.74-19.76), alongside unlisted reactions such as asthmatic crisis (ROR: 47.3, 95%CI: 43-52.03), lower respiratory tract congestion (ROR: 35.68, 95%CI: 30.42-41.84). Furthermore, the results of our analysis indicated that omalizumab-related adverse events displayed significant gender and age disparities. The median time to onset for all documented adverse events was approximately 145 days, with a substantial proportion occurring after one year of treatment. This study not only offers a significant reference for optimizing the utilization of omalizumab, enhancing its efficacy while minimizing potential side effects, but also facilitates the safe application and broader implementation of omalizumab in clinical practice.

Project description:Introduction: Linezolid is an oxazolidinone antibiotic that is active against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups. Results: A total of 11,176 reports of linezolid as the "primary suspected" drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia (n = 1,139, ROR 21.98), anaemia (n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis (n = 90, ROR 4.33), and electrocardiogram QT prolonged (n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs (n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment (n = 46). Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings.

Project description:ObjectiveThis study aimed to understand how people living with drug-resistant focal epilepsy (DRE) navigate through lines of antiseizure medications (ASM) and experience adverse events (AEs) in the real-world setting in the United States.MethodsA retrospective study was conducted with medical chart data from clinical practices in the United States. Eligible adults had a confirmed diagnosis of DRE and initiated a third-line ASM therapy between January 2013 and January 2020 (i.e., the index date). Subjects must have medical history data available for ≥1 year prior to (the baseline) and ≥2 years after the index date (the follow-up). Treatment patterns were captured from first to fourth lines. After the emergence of drug resistance, time to ASM discontinuation, reasons for discontinuation, AE experience and AE management were reported separately during third and fourth lines of treatment and beyond.ResultsThe study included a total of 345 individuals, with an average (standard deviation) age of 23.9 (11.9) years at first diagnosis. All individuals had at least three lines of ASMs with first and second lines during baseline, and third line during follow-up. The first line for most individuals was monotherapy. As individuals progressed through additional lines of ASM therapy, they were more likely to receive polytherapy. The regimens were more individualized after meeting drug resistance criteria. The top reasons for discontinuing were uncontrolled seizure and/or intolerance/AEs for both third and subsequent lines. More than a third of individuals experienced at least one AE. Among those with at least one AE, many individuals had to manage these AEs with dose adjustment (39.4%), discontinuation of offending ASM (37.9%), de novo pharmacotherapy (25.8%), emergency room visit (13.6%), and hospitalization (12.1%).SignificanceThis study demonstrated that individuals living with DRE experience significant AEs, and many of these AEs lead to treatment disruption and significant healthcare resource utilization.Plain language summaryThis study examined how individuals with focal epilepsy are treated across various clinics in United States and reported the adverse events these individuals experienced during treatment, along with the consequence associated with these adverse events. We found that as individuals progressed through additional treatments, they were more and more likely to receive more than one antiseizure medication, and a significant portion of individuals experienced at least one adverse event, often manifested as headache, somnolence, dizziness, and fatigue.

Project description:BACKGROUND:Immune-checkpoint inhibitors (ICIs) emerged as a novel class of drugs for the treatment of a broad spectrum of malignancies. ICIs can produce durable antitumor responses but they are also associated with immune-related adverse events (irAEs). Endocrinopathies have reported as one of the most common irAEs of ICIs. METHODS:This study aimed to quantify association of endocrine adverse events (AEs) and ICI therapy and also to characterize the profiles of ICI-related endocrine complications from real-world practice. Data from the first quarter of 2014 to first quarter of 2019 in FDA Adverse Event Reporting System (FAERS) database were gathered to conduct disproportionality analysis. The definition of endocrine AEs relied on the preferred terms (PTs) provided by the Medical Dictionary for Regulatory Activities (MedDRA). Two signal indices based on statistical shrinkage transformation, reporting odds ratios (ROR) and information component (IC), were used to evaluate correlations between ICIs and endocrine events. For ROR, it was defined a signal if the lower limit of the 95% confidence interval (ROR025) more than one, with at least 3 cases. For IC, lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed statistically significant. RESULTS:A total of 29,294,336 records were involved, among these 6260 records related to endocrine AEs after ICIs treatment were identified. In general, male had a slightly lower reporting frequencies for ICIs-related endocrinopathies compared with female but not significant (ROR = 0.98 95%CI: 0.93-1.04) and the difference varied in several common endocrine AEs. Notably, in general, ICI drugs were significantly associated with over-reporting frequencies of endocrine complications, corresponding to IC025 = 2.49 and ROR025 = 5.99. For monotherapy, three strategies (anti-PD-1, anti-PD-L1 and anti-CTLA-4) were all associated with significant increasing endocrine events. Different reporting frequencies emerged when anti-CTLA-4 therapy was compared with anti-PD-1/PD-L1 medications for endocrine toxicities, corresponding to ROR = 1.68 (95%CI 1.55-1.83), ROR = 2.54 (95%CI 2.20-2.93), respectively. Combination therapy was associated with higher risk of endocrinopathies compared with monotherapy (ROR = 2.00, 95%CI 1.89-2.11). When further analysis, the spectrum of endocrine AEs differed in immunotherapy regimens. Hypothyroidism (N = 885,14.14%), adrenal insufficiency(N = 730,11.66%), hypophysitis (N = 688,10.99%) and hyperthyroidism (N = 472,7.54%) were top 4 ranked endocrine events after ICI therapy and their reporting frequency also differed in ICI immunotherapies. CONCLUSION:Our pharmacovigilance analysis shows a high reporting frequency of endocrine AEs provoked by ICI monotherapy (especially anti-CTLA-4 therapy) and further reinforced by combination therapy. In addition, treatment with different ICI immunotherapies may result in a unique and distinct profile of endocrinopathies. Early recognition and management of ICI-related endocrine irAEs is of vital importance in clinical practice.

Project description:BackgroundSorafenib is approved for the targeted therapy of cancers such as liver cancer and renal cancer. Given its widespread use, drug-related adverse events have received attention, and the post-marketing regulatory link is crucial.ObjectiveBy using the FAERS database to mine the adverse events (AEs) related to sorafenib, comparing the association intensity of key AEs, and exploring potential drug-related AEs, it provides a reference for clinical medication.MethodsCollect ADE data related to sorafenib in the FAERS database from 2006 to 2023. Standardize the data, and map adverse events to system organ classes and preferred terms. Analyze using various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS.ResultsAmong 18,520 adverse event reports (AERs) where sorafenib was the primary suspected drug, a total of 390 preferred terms (PTs) of adverse reactions were identified, covering 24 different system organ classes (SOCs). Specifically, the adverse events of sorafenib mainly involve the digestive system, skin and subcutaneous tissue, as well as non-specific physical discomfort including infection and injury. Among them, digestive system symptoms and skin toxicity are typical adverse reactions of sorafenib. We also observed uncommon but clearly strong AE signals, such as chloracne (n = 3, ROR 1756.39, PRR 1756.32, IC 8.78, EBGM 439.83), low-differentiated thyroid cancer (n = 4, ROR 585.47, PRR 585.44, IC 8.2, EBGM 293.22). It is worth noting that palmar-plantar erythrodysaesthesia syndrome (n = 2109, ROR 73.98, PRR 72.03, IC 6.01, EBGM 64.25) and hepatic encephalopathy (n = 457, ROR 37.44, PRR 37.23, IC 5.13, EBGM 35.07) have a higher incidence and signal intensity. In addition, we also observed some adverse events not mentioned in the official drug instructions, such as vitamin K deficiency or increased protein induced by antagonist II (PIVKA-II), abnormal alpha-fetoprotein, tumor metastasis, and splenic atrophy.ConclusionSorafenib carries the risk of various adverse reactions while providing therapeutic effects. In clinical applications, physicians should closely monitor the occurrence of digestive system reactions, skin lesions, endocrine system lesions, as well as injuries, infections, and other events.

Dataset Information

Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug-gene Interaction Network.

Publications

Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug-gene Interaction Network.

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