Comparative safety analysis of lacosamide and perampanel in epilepsy management: insights from FAERS database.

Background: Epilepsy is a chronic neurological condition requiring effective management with minimal adverse effects. Lacosamide (LCM) and Perampanel (PER), two promising treatments, have distinct profiles that merit comparative analysis to guide clinical decision-making. Methods: This study utilizes a pharmacovigilance analysis of adverse events reported in the FDA Adverse Event Reporting System database from Q1 2009 to Q3 2023. Employing disproportionality and Bayesian analyses, we assessed and compared the AE signals associated with LCM and PER to elucidate their safety profiles in epilepsy treatment. Results: The analysis included 12,576 AE reports for LCM and 2,703 for PER, highlighting a higher incidence of psychiatric disorders, including aggression with LCM, and a notable association of PER with psychiatric disorders such as psychotic disorders and dizziness. LCM showed a relatively safe profile during pregnancy, whereas PER's data suggested caution due to reported cases of suicidal ideation and attempts. Conclusion: This comprehensive evaluation underscores the importance of understanding the distinct AE profiles of LCM and PER in clinical practice, providing valuable insights for personalized epilepsy management. Future research with rigorous prospective designs is recommended to validate these findings and explore the mechanisms underlying the reported adverse events.

Assessment of safety profile of ivabradine in real-world scenario using FDA adverse event reporting system database.

BACKGROUND: Ivabradine is primarily indicated for patients with sinus rhythm and a heart rate ≥ 75 beats/min, who have NYHA class II-IV chronic heart failure with systolic dysfunction. There is currently a lack of large-scale, real-world studies concerning its drug adverse reactions. RESEARCH DESIGN & METHODS: This research assesses the side effects of ivabradine by analyzing reports of adverse events (AEs) from the FDA's Adverse Event Reporting System (FAERS) database. To evaluate the importance of these AEs, four sequential analytic strategies were utilized. RESULTS: In total, 2,701 ivabradine-related AE reports were identified in the FAERS database. We identified 26 ivabradine-induced AEs, each with more than 20 reports, including some significant AEs not mentioned on the product label. The timing of AEs was also analyzed, with the majority of AEs occurring within the first month of ivabradine use. Gender-specific analysis indicates that female have a higher risk of AEs, such as off-label use, tachycardia, drug effectiveness for unapproved indications, and rash compared to male. CONCLUSION: This study provides important information for maximizing the usage of ivabradine, increasing its efficacy, and reducing any possible negative effects. The actual clinical use of the medication will be greatly aided by this knowledge.

Exploring SGLT-2 inhibitors and sarcopenia in FAERS: a post-marketing surveillance study.

BACKGROUND: The sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) is associated with body weight loss but the composition of the losing weight remains unclear. RESEARCH DESIGN AND 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 SGLT-2i-associated musculoskeletal and connective tissue disorders AEs. RESULTS: The search retrieved a total of 3,206 cases of musculoskeletal and connective tissue disorder-related AEs during the reporting period. This included 1,061 cases for Canagliflozin, 1,052 cases for Dapagliflozin, 1,074 cases for Empagliflozin, and 19 cases for Ertugliflozin. Fifteen preferred terms (PTs) with significant disproportionality were retained. No musculoskeletal and connective tissue system-related AE signals were reported for Ertugliflozin. We identified a risk of muscle necrosis with Canagliflozin use, a risk of sarcopenia with Dapagliflozin use, and a chance of muscle atrophy with Dapagliflozin and Empagliflozin prescriptions. Most cases occurred within the first month after SGLT-2i initiation, and AEs can persist beyond 360 days of use. CONCLUSIONS: Our study identified potential new musculoskeletal and connective tissue disorder-related AE signals associated with SGLT-2 inhibitors.

Infection and infestation-related adverse events of biologics in psoriasis: insights from the food and drug administration adverse event reporting system (FAERS).

OBJECTIVE: The study aims to thoroughly assess the adverse events related to infections and infestations associated with biological agents used for psoriasis using the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database. METHODS: We analyzed FAERS data from the first quarter of 2004 to the fourth quarter of 2023. The study included TNF-α inhibitors (etanercept, infliximab, adalimumab), IL-12/23 inhibitors (ustekinumab), IL-23p19 inhibitors (guselkumab), and IL-17 inhibitors (secukinumab, ixekizumab). We used disproportionality analysis and Bayesian methods to quantify the related adverse event (AE) signals. RESULTS: Most AEs related to infections and infestations are already listed on the drug packaging labels. Notably, TNF-α inhibitors are associated with a significantly higher incidence of tuberculosis-related diseases compared to other biological agents. In contrast, IL-17 inhibitors show a greater variety and number of fungal infection-related AEs than their counterparts. Furthermore, our study has identified new potential AEs that require the attention of clinicians. CONCLUSION: In clinical practice, it is advisable to monitor the risks of infections and infestations in patients receiving biological agents for psoriasis to enable early detection and intervention. Our findings highlight the need for further epidemiological investigations to establish causality and guide clinical practice in managing these risks effectively.

Pancreatitis Associated With Teduglutide: A Disproportionality Analysis via the Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

Introduction Teduglutide is a glucagon-like peptide-2 analog that is indicated for the treatment of short bowel syndrome (SBS) by reducing patient dependence on parenteral support. Due to the rarity of SBS as well as the recent timeline of the adoption of teduglutide, the safety of teduglutide is relatively poorly understood. Several recent clinical case reports have highlighted elevated pancreatic enzymes and pancreatitis as a concerning complication of teduglutide. This prompts a systematic study of the association between pancreatitis and teduglutide. Methods This study conducts a case-control design disproportionality analysis by using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). Reports from the first quarter of 2020 through the first quarter of 2024 were retrieved from this database, and a disproportionality analysis was conducted. The analysis consisted of traditional methods of analyzing adverse drug events such as the reporting odds ratio (ROR) and proportional reporting ratio (PRR), as well as Bayesian methods such as the empirical Bayes geometric mean (EBGM) and information component (IC). A confidence interval for ROR and PRR that excludes a ratio of 1 or a confidence interval for IC that excludes a score of 0 was used as the criterion for a statistically significant association between pancreatitis risk and teduglutide use. Results Out of 11,696 reports of teduglutide adverse effects in over four years of adverse effects data drawn from the FAERS database, 79 cases of pancreatitis were identified. The disproportionality analysis revealed an ROR of 3.73 (95% CI (2.99, 4.66)), a PRR of 3.71 (95% CI (2.97, 4.63)), an EBGM of 3.70, and an IC of 1.84 (95% CI (1.51, 2.16)). All of these statistics indicate a statistically significant association between pancreatitis risk and teduglutide use. Conclusion The results reveal a statistically significant association between pancreatitis risk and teduglutide use. Our findings highlight the necessity for the careful monitoring of pancreatitis in patients undergoing teduglutide therapy going forward.

Adverse events associated with Azithromycin and clarithromycin in adults aged ≥65: a disproportionality analysis of the FDA adverse event reporting system (FAERS) database.

BACKGROUND: Azithromycin and clarithromycin are commonly used to treat community-acquired pneumonia in adults aged ≥ 65, such as mycoplasma pneumonia. This study aims to evaluate adverse events (AEs) associated with azithromycin and clarithromycin in this age group by analyzing the FDA Adverse Event Reporting System (FAERS), providing insights for clinical use and management of AEs in this population. RESEARCH DESIGN AND METHODS: We retrieved reports of AEs related to azithromycin and clarithromycin from the FAERS database. Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Gamma Poisson Shrinkage (MGPS) to identify AEs associated with azithromycin and clarithromycin in adults aged ≥ 65. RESULTS: A total of 2,019 adverse event reports were retrieved for azithromycin, and 2,392 for clarithromycin. Off-label use (n = 349) and drug interactions (n = 487) were the most reported AEs in adults aged ≥ 65 for azithromycin and clarithromycin, respectively. Prolonged QT interval showed the strongest signal among AEs for azithromycin in this age group. Drug interaction-related medication errors had the strongest signal for clarithromycin. Seven signals not explicitly included in the azithromycin package insert were identified in adults aged ≥ 65. Fourteen signals not explicitly included in the clarithromycin package insert were identified. CONCLUSIONS: Among adults aged ≥ 65, cardiac-related adverse events are more closely associated with azithromycin than with clarithromycin. Conversely, AEs related to drug interactions and psychiatric symptoms are more associated with clarithromycin. Additionally, clinicians should be vigilant regarding AEs not specified in the package inserts. The findings of this study may help optimize the selection of azithromycin and clarithromycin based on patient circumstances and assist clinicians in focusing on relevant AEs for early intervention.

Risk analysis of enfortumab vedotin: A real-world approach based on the FAERS database.

Purpose: To analyze the risk of enfortumab vedotin (EV), a targeted therapy for advanced bladder cancer, using real-world data from the U.S. Food and Drug Administration's Federal Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using FAERS data from Q1 2020 to Q1 2024. Adverse drug events (ADEs) related to EV were identified and categorized according to the System Organ Classes (SOCs) and specific events. Statistical methods, such as the proportional reporting ratio, reporting odds ratio (ROR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean were used to detect safety signals. Results: Of the 7,449,181 FAERS case reports, 1,617 EV-related ADEs were identified, including 101 preferred terms and 22 SOCs. The key SOCs included skin and subcutaneous tissue, metabolic, and nutritional disorders. Rare ADEs, such as lichenoid keratosis (n = 4; ROR 26.89), small intestinal perforation (n = 3; ROR 24.51), pigmentation disorder (n = 9; ROR 18.16), and cholangitis (n = 8; ROR 17.48), showed significant disproportionality. Conclusion: While most findings aligned with the existing data, new signs such as lichenoid keratosis and small intestinal perforation were identified. Further studies are necessary to validate these findings and emphasize the need for the clinical monitoring of EV-related ADEs.

Pregnancy related adverse events and congenital disorders associated with fluoroquinolones: A real-world pharmacovigilance study of the FDA adverse event reporting system (FAERS).

Background: Fluoroquinolones, including ciprofloxacin, levofloxacin, and moxifloxacin, are extensively employed as broad-spectrum antibacterial agents. However, their use is discouraged during pregnancy due to potential adverse events (AEs). The aim of this study is to systematically investigate the association between fluoroquinolones (specifically ciprofloxacin, levofloxacin, and moxifloxacin) and AEs related to pregnancy, as well as their potential impact on congenital disorders. Methods: A disproportionality analysis was conducted utilizing FDA Adverse Event Reporting System (FAERS) data spanning from the first quarter of 2004 to September 2023. The objective was to identify potential AEs signatures associated with fluoroquinolones through conducting reporting odds ratios (RORs) and Bayesian confidence propagation neural networks (BCPNN). Assessing the potential risk of pregnancy-associated AEs involved comparing each fluoroquinolone with all other medications. Additionally, in-depth comparative analyses were carried out between various fluoroquinolones and a reference drug (azithromycin). Results: A total of 1159 cases were identified, involving AEs related to pregnancy and congenital disorders. Obvious disproportionate association of abortion spontaneous and other nine AEs was identified for fluoroquinolone during gestation. Upon comparison with all the other drugs, ciprofloxacin exhibited an elevated risk of spontaneous abortion, non-site specific bone disorders congenital and 10 other significant signals. Levofloxacin demonstrated an increased risk of congenital tongue disorders and three other significant signals. Moxifloxacin displayed a noteworthy signal indicating multiple congenital cardiac abnormalities. Conclusions: We present compelling evidence regarding pregnancy-related AEs and congenital disorders linked to fluoroquinolones. Considering perinatal and genotoxicity aspects, we explore whether levofloxacin or moxifloxacin might be preferable when fluoroquinolones are deemed necessary to balance the benefits of pregnant women and fetuses.

Sorafenib safety evaluation: Real-world analysis of adverse events from the FAERS database.

Background: Sorafenib 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. Objective: By 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. Methods: Collect 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. Results: Among 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. Conclusion: Sorafenib 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.

Postmarketing adverse events of tamoxifen in male and female patients with breast cancer.

Tamoxifen (TAM), a selective estrogen receptor (ER) modulator, has received approval for use in patients with breast cancer (BC) exhibiting positive ER expression. Given the widespread clinical use of TAM, a comprehensive real-world study of its adverse events (AEs) is warranted. The database for analysis, sourced from the Food and Drug Administration Adverse Event Reporting System (FAERS), covers the period from the first quarter of 2014 to the third quarter of 2023. A disproportionality analysis was conducted to quantify the correlation between TAM and AEs. Subgroup analyses were performed to identify differences between BC AEs in males and females receiving TAM, aiming to assess the risk factors of male BC AEs. Total 4890 reports indicated BC, with 91 and 4190 specifically linked to AEs in male and female patients with BC, respectively. Male-specific AE was libido decreased (reporting odds ratio [ROR]: 43.33), and female-specific AE was uterine disease, including sarcoma uterus (ROR: 519.51), endometrial cancer (ROR: 131.26), uterine polyp (ROR: 40.83), endometriosis (ROR: 11.39), among others. A notably higher risk of AEs in male patients with BC was observed in individuals aged >65 years (χ2 = 20.83, p < .001). Male patients with BC had a relatively higher risk of hospitalization (χ2 = 4.83, p = .03) and a lower risk of deaths (χ2 = 5.32, p = .02). Theses finding may assist healthcare professionals in recognizing the TAM-associated AEs and understanding gender differences, potentially improving safety in clinical applications.

Insights from pharmacovigilance and pharmacodynamics on cardiovascular safety signals of NSAIDs.

Background and Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat fever, pain, and inflammation. Concerns regarding their cardiovascular safety have been raised. However, the underlying mechanism behind these events remains unknown. We aim to investigate the cardiovascular safety signals and receptor mechanisms of NSAIDs, employing a comprehensive approach that integrates pharmacovigilance and pharmacodynamics. Methods: This study utilized a pharmacovigilance-pharmacodynamic approach to evaluate the cardiovascular safety of NSAIDs and explore potential receptor mechanisms involved. Data were analyzed using the OpenVigil 2.1 web application, which grants access to the FDA Adverse Event Reporting System (FAERS) database, in conjunction with the BindingDB database, which provides target information on the pharmacodynamic properties of NSAIDs. Disproportionality analysis employing the Empirical Bayes Geometric Mean (EBGM) and Reporting Odds Ratio (ROR) methods was conducted to identify signals for reporting cardiovascular-related adverse drug events (ADEs) associated with 13 NSAIDs. This analysis encompassed three System Organ Classes (SOCs) associated with the cardiovascular system: blood and lymphatic system disorders, cardiac disorders, and vascular disorders. The primary targets were identified through the receptor-NSAID interaction network. Ordinary least squares (OLS) regression models explored the relationship between pharmacovigilance signals and receptor occupancy rate. Results: A total of 201,231 reports of cardiovascular-related ADEs were identified among the 13 NSAIDs. Dizziness, anemia, and hypertension were the most frequently reported Preferred Terms (PTs). Overall, nimesulide and parecoxib exhibited the strongest signal strengths of ADEs at SOC levels related to the cardiovascular system. On the other hand, our data presented naproxen and diclofenac as drugs of comparatively low signal strength. Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were identified as central targets. OLS regression analysis revealed that the normalized occupancy rate for either COX-1 or COX-2 was significantly inversely correlated with the log-transformed signal measures for blood and lymphatic system disorders and vascular disorders, and positively correlated with cardiac disorders and vascular disorders, respectively. This suggests that higher COX-2 receptor occupancy is associated with an increased cardiovascular risk from NSAIDs. Conclusion: Cardiovascular safety of NSAIDs may depend on pharmacodynamic properties, specifically, the percentage of the occupied cyclooxygenase isoenzymes. More studies are needed to explore these relations and improve the prescription process.

Reassessment of pioglitazone and bladder cancer based on FAERS database.

BACKGROUND: The association between pioglitazone (PLZ) and bladder cancer (BC) remains controversial in several randomized control trials, meta-analyses of multiple prospective studies, and large-scale observational studies. RESEARCH DESIGN AND METHODS: Adverse event (AE) data from 1 January 2004 to 31 March 2024 were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis were applied to quantify the signals of PLZ related BC. RESULTS: In total, 17,627,524 AE reports were recorded in the FAERS database, of which 1366 were PLZ-related BCs. More male than female patients were reported. The median age of patients was 70 years old. The peak in the annual report occurred in 2011. A total of 602 AEs reported time to onset (TTO) and the median TTO was 1023 days. In this study, BC and BC recurrence were strong signal, whereas BC stage 0 (with cancer in situ), stage ii and iii were weak signals. CONCLUSIONS: This study comprehensively demostrated the PLZ-induced risk of BC in patients with diabetes mellitus using the FAERS database. The results demonstrated that the patients treated with PLZ were more likely to develop BC. The male and aging attributed more cases to BC-related reports of PLZ treated patients.

Post-marketing safety of tralokinumab: a real-world pharmacovigilance study based on the FDA adverse event reporting system.

BACKGROUND: Tralokinumab is a fully human IgG4 monoclonal antibody targeting IL-13, used for treating atopic dermatitis. This study analyzed tralokinumab-related adverse drug events by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database to provide a safety reference for clinical application. METHODS: Adverse drug event reports from Q1 2022 to Q2 2024 were extracted from the FAERS database. After standardizing the data, various signal detection methods were used for analysis, including ROR, PRR, BCPNN, and MGPS. RESULTS: A total of 1,820 reports of adverse events (AEs) with tralokinumab as the primary suspected drug were identified. 70 preferred terms (PTs) met the criteria across four signal detection methods, involving 11 system organ classes (SOCs). These included known adverse reactions like conjunctivitis and injection site reactions, and signals not previously reported in clinical trials, such as eye pruritus, dry eye, eye swelling, pneumonia pneumococcal, and cutaneous T-cell lymphoma. Most AEs occurred within one month of initiating tralokinumab treatment. CONCLUSIONS: Based on the FAERS database, this study comprehensively and systematically analyzed AE signals in tralokinumab treatment. The results enhance the understanding of tralokinumab's safety and serve as valuable references for reducing the risk of adverse reactions during clinical use.

Adverse event profiles of drug-induced decreased libido: an assessment of the US food and drug administration Adverse Event Reporting System.

BACKGROUND: Drug-induced decreased libido significantly affects the quality of life and relationships of patients. However, no comprehensive study has examined the relationship between drugs and libido. This study assessed drug-induced decreased libido by mining data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: Adverse drug event (ADE) reports from the first quarter of 2004 to the fourth quarter of 2023 in FAERS were collected and screened for reports of decreased libido and were subjected to medication signal mining by using the disproportionality analysis. RESULTS: Overall 10,773 ADE reports were obtained. Thirty-three of the top 50 drugs with the highest frequency of ADE reports did not mention the risk of reduced libido in their instructions. Fifty-eight drugs showed potential decreased libido risk based on the disproportionality analysis, with 40 of the drugs not mentioning the risk of reduced libido in their instructions. Of these 40 drugs, drugs used in genito urinary and sex hormones and nervous system were the drug class with the greatest number of ADE reports. CONCLUSION: A data mining exercise using FAERS for drugs that cause decreased libido has identified 40 drugs with new signals of adverse effects that should be closely monitored in medical practice.

Abemaciclib increases the risk of venous thromboembolism in breast cancer: Integrate meta-analysis, pharmacovigilance database analysis, and in vitro validation.

BACKGROUND: Recently, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have emerged as a novel treatment strategy for breast cancer. However, increasing reports of CDK4/6i-associated venous thromboembolism (VTE) have garnered attention. This study assessed CDK4/6i-associated VTE in breast cancer, and examined the effect of CDK4/6i on platelet/coagulation function for the first time in vitro. METHODS: PubMed and Embase databases were searched for studies published from the establishment of the database to December 31, 2022 for randomized controlled trials (RCTs) and real-world studies of CDK4/6i in patients with breast cancer, and the data obtained from the included studies were used for meta-analysis. A disproportionality analysis by extracting adverse drug reaction signals of CDK4/6i-associated VTE from the FDA Adverse Event Reporting System (FAERS) database was also conducted. Additionally, the in vitro effect of CDK4/6i on platelet function was assessed based on platelet aggregation tests and flow cytometry, and coagulation function was assessed based on the blood clotting function test. FINDINGS: A total of 16,903 patients in 13 RCTs and 6,490 patients in 9 real-world studies were included in the meta-analysis. In RCTs, VTE occurred in 193 (2.1 %) and 55 (0.7 %) patients in the CDK4/6i and control groups, respectively. In real-world studies, the aggregate incidence rate of VTE was 4.2 % (95 % CI: 2.1, 6.3). The meta-analysis of RCTs revealed that abemaciclib (Odds ratio [OR]: 4.40 [95 % CI: 2.74,7.05], p < 0.001) and palbociclib (OR: 2.35 [95 % CI: 1.34, 4.12], p < 0.01) significantly increased the risk of VTE in patients with breast cancer compared to placebo. FAERS database analysis revealed that abemaciclib (reporting odds ratio [ROR]: 1.63 [95 % CI: 1.36, 1.97]; IC025: 0.67) and ribociclib (ROR: 1.17 [95 % CI: 1.0, 1.39]; IC025: 0.18) demonstrated a significantly increased signal of VTE. Similarly, findings from in vitro experiments demonstrated that abemaciclib enhanced agonist-induced platelet activation, especially when collagen was used as the inducer, and this effect became more prominent with increasing its concentration. INTERPRETATION: Use of abemaciclib may increase the risk of VTE in patients with breast cancer, which may be partially attributed to the effect of abemaciclib on platelet function. Close monitoring of VTE occurrence is highly recommended while using abemaciclib, especially in patients at a high risk of VTE.

A real-world disproportionality analysis of baloxavir marboxil: post-marketing pharmacovigilance data.

OBJECTIVE: Baloxavir marboxil (hereafter referred to as baloxavir) is the only cap-dependent endonuclease inhiabitor approved for the treatment and prevention of influenza. However, as a new drug marketed in 2018, the long-term safety of baloxavir in large sample population was unclear. This study aims to evaluate baloxavir-associated adverse events (AEs) through data mining of the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS). METHODS: Disproportionality analysis was conducted to assess the association between baloxavir and its AEs. Data were collected from FAERS from March 2018 to June 2023. After standardizing the data, signal quantification techniques including ROR, PRR, BCPNN and MGPS were used for analysis. RESULTS: A total of 49 significant baloxavir-related preferred terms (PTs) in 20 system organ classes (SOCs) were identified in our data analysis. Compared to baloxavir's FDA label, some new PTs emerged, with the top 10 being pneumonia, loss of consciousness, rhabdomyolysis, seizure, altered state of consciousness, hepatic function abnormal, delirium, depressed level of consciousness, encephalopathy and cardio-respiratory arrest. CONCLUSION: In clinical application of baloxavir, attention should be paid to the new AE signals in addition to the those recorded in the labels, so as to ensure the safety of the patients.

Real-world large sample assessment of drug-related dry eye risk: Based on the FDA adverse event reporting system database.

PURPOSE AND DESIGN: This study aimed to evaluate the risk of drug-related dry eye using real-world data, underscoring the significance of tracing pharmacological etiology for distinct clinical types of dry eye. METHODS: Analyzing adverse event reports in the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to September 2023, we employed disproportionality analysis and the Bayesian confidence propagation neural network algorithm. The analysis involved categorizing drugs causing dry eye, assessing risk levels, and conducting segmental assessments based on the time of onset of drug-related dry eye adverse reactions. RESULTS: In the FAERS database, adverse reactions related to dry eye were linked to 1160 drugs. Disproportionality analysis identified 33 drugs with significant risk, notably in ophthalmic (brimonidine, bimatoprost), oncology (tisotumab vedotin, erdafitinib), and other medications (isotretinoin, oxymetazoline). The top three drugs with the highest risk of drug-related dry eye are isotretinoin (Bayesian confidence propagation neural network (BCPNN) = 6.88), tisotumab vedotin (BCPNN = 6.88), and brimonidine (BCPNN = 6.77). Among different categories of drugs, respiratory medications have the shortest mean onset time for drug-related dry eye, averaging 50.99 days. The prevalence skewed towards females (69.9 %), particularly in menopausal and elderly individuals (45-70 years old, mean age 54.7 ± 18.2). Reports of drug-related dry eye adverse reactions showed an annual increase. CONCLUSION: Informed clinical decision-making is crucial for preventing drug-related dry eye. Assessing the risk of dry eyes associated with both local and systemic medications helps optimize treatment and provide necessary cautionary information.

High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database.

BACKGROUND: Cetirizine and Loratadine are the two best-selling second-generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions. METHODS: ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs. RESULTS: A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle-aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n = 326, ROR 6.75), sneezing (n = 251, ROR 15.24), and nasal congestion (n = 185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n = 2556, ROR 10.52 vs. Loratadine, n = 1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n = 233, ROR 3.3), while Loratadine was associated with nervousness (n = 145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n = 138, ROR 8.13), potentially leading to serious adverse consequences. CONCLUSION: Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

Neratinib safety evaluation: real-world adverse event analysis from the FAERS database.

Aims: Neratinib has emerged as significant theraputic option for breast cancer treatment. However, despite its approval, numerous adverse drug events (ADEs) associated to it remain unrecognized and unreported. This study aims to mine and analyze the signals of ADEs related to neratinib from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, providing insights for safe and rational clinical use of drug. Methods: All the neratinib-related ADEs data were collected from FAERS database from the third quarter (Q3) of 2017 to the fourth quarter (Q4) of 2023. After standardizing the data, 4 disproportionality methods were used to assess the correlation between neratinib and ADEs. Results: Of the 1,544 ADEs implicating neratinib as the primary suspected drug, a combined total of 48 preferred terms (PTs) and 10 system organ classes (SOCs) showed significant disproportionality accross all four algorithms simultaneously. These SOCs included gastrointestinal disorders (n = 2,564, ROR 7.14), general disorders and administration site conditions (n = 958, ROR 0.77) and injury poisoning and procedural complications (n = 474, ROR 0.58) among others. Upon comparison with the neratinib manual, 34 ADEs not documented in the manual were found at the PT level. Conclusion: Our study provide new real-world evidence for drug safety information of neratinib. While the majority of our findings were aligned with the information provided in the manual. We identified additional ADEs not previously documented. Consequently, further studies are needed to validate unreported ADEs to ensure the efficacy and safety of neratinib for patients.