Reporting Odds Ratio Research Articles

The real-world safety of ticagrelor among older adults (above 75 years): a pharmacovigilance study from the FDA data

Abstract Introduction Potent P2Y12 inhibitors are recommended in conjunction with Aspirin for the treatment of acute coronary syndrome. Since Prasugrel is relatively contraindicated in patients older than 75 years, Ticagrelor remains the primary potent P2Y12 inhibitor option for this age group. However, its safety profile among older adults has not been adequately examined. Purpose To examine Ticagrelor safety profile among older adults (≥75 years) patients Methods We conducted a retrospective pharmacovigilance study utilizing the FDA Adverse Event Reporting System (FAERS) database. We employed disproportionality analysis comparing Ticagrelor to Clopidogrel. We evaluated the reporting of predefined adverse events (dyspnea, bradyarrhythmia, complete AV block [CAVB], intracranial hemorrhage, gastrointestinal hemorrhage, acute kidney injury [AKI], and gout) in adults (<75 years) and older adults (≥75 years). For each group, we calculated reporting odds ratio (ROR) and its 95% confidence interval and compared them by calculating P for interaction. Results The FAERS database encompassed 6,476 adverse event reports for Ticagrelor; 4,795 (74%) adults and 1,681 (26%) older adults. Among older adults and compared to Clopidogrel, Ticagrelor was not associated with an increased reporting for dyspnea (ROR 3.3 [2.7-3.9] vs. 3.9 [3.5-4.5]), bradyarrhythmia (ROR 4.1 [2.5 – 6.7] vs 5.4 [3.9 – 7.6]) intracranial hemorrhage (ROR 1.1 [0.7-1.7] vs. 1.1[0.8-1.5]), CAVB (ROR 11.5 [3.1–42.4] vs. ROR 27.8 [6.7-116.3]), and gout (ROR 3.8 [0.5-27] vs. 3.9 [2-7.5]). AKI was reported more frequently among older adults (ROR 2.3 [1.5-3.6] vs. 0.6 [0.4-0.9]). Ticagrelor was not associated with an increased reporting of GI hemorrhage. Conclusion According to the FAERS, Ticagrelor is generally safe for use in older adults (≥75 years) with no significant increase in the reporting of major adverse events compared to adults (<75 years), except for a higher reporting of AKI.

The effect of oral anticoagulants on the incidence of dementia in patients with atrial fibrillation: a systematic review and meta-analysis

Abstract Background Atrial fibrillation (AF) is a common cardiac arrhythmia, with dementia being an increasingly recognised complication of this. Treatment with oral anticoagulant (OAC) therapy may be protective in developing this complication. Purpose This meta-analysis aims to investigate the validity of this hypothesis, whilst additionally exploring the effect of specific OAC medication subtypes on the incidence of dementia. Methods A comprehensive search of MEDLINE and Embase for relevant studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. This included observational studies that reported odds ratio, risk ratio and hazard ratio for adult AF patients. Studies including patients with prior OAC use or prior history of dementia were excluded. Statistical analysis was performed using a random-effects model to calculate the pooled hazard ratio and their corresponding 95% confidence interval for all outcomes. Subgroup analyses were also performed according to the study design, presence of observational window, and prior history of stroke in patients. Results A total of 13 studies were included in the study. Although the heterogeneity was high in all comparisons, we demonstrated that OAC usage lowered the risk of developing dementia in AF patients when compared to the non-OAC cohort. Looking more specifically at medication subtypes, direct oral anticoagulants (DOACs) and vitamin K agonists (VKA) were both effective in reducing the likelihood of AF patients developing dementia when compared to non-OAC treatments. Conclusion Our meta-analysis confirms that administration of OAC and its subtypes (VKA and DOAC) are effective pharmacotherapies in managing dementia in patients with AF. These findings have important clinical implications for the management of AF patients and highlight the need for further investigation of the protective effects of OAC therapy on cognitive decline. Future research should explore the long-term effects of OAC therapy on cognitive function in AF patients.

Immune checkpoint inhibitor-associated bullous pemphigoid: Aretrospective and real-world study based on the United States Food and Drug Administration adverse event reporting system.

This study aimed to describe bullous pemphigoid (BP) associated with immune checkpoint inhibitors (ICIs) reported in the United States Food and Drug Administration adverse event reporting system (FAERS). We obtained reports of ICI-associated BP from the first quarter of 2011 to the first quarter of 2024 in the FAERS database. The reporting odds ratio (ROR) method of the disproportionality analysis was performed to assess the potential risk for ICI-associated BP. We also described the clinical characteristics of ICI-associated BP and evaluated the time to onset (TTO) of BP developed after treatment with ICIs. Eight hundred and six cases of ICI-associated BP were gathered, in which 56.58% of the patients were aged 65 years or older. The majority of patients were male, accounting for 68.49% of all cases. The prevalent potential cancer type was skin cancer (31.64%). The results of the disproportionality analysis showed that males (ROR = 2.10 [1.78-2.49]), patients aged 65 or older (ROR = 2.13 [1.79-2.55]), and patients with skin cancer (ROR = 2.08 [1.80-2.43]) were more likely to develop ICI-associated BP. In comparison to cytotoxic T-lymphocyte-associated antigen 4 inhibitor and programmed cell death ligand 1 inhibitor, programmed cell death 1 inhibitor-associated BP has a higher risk of development (ROR = 24.45 [22.52-26.56]). ICI-associated BP had a median TTO of 204 days (interquartile range 57-426 days). ICI-associated BP is a rare but important immune-related adverse event. Our study provided helpful information to help medical professionals further understand ICI-associated BP.

Safety concerns of paternal drug exposure on fertility, pregnancy and offspring: An analysis based on the FDA adverse event reporting system.

Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce. To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health. Data from the FDA adverse event reporting system (FAERS) were analyzed (2010-2022). Disproportionality analyses were used to identify signals of each drug-adverse event pair associated with paternal drug exposure in a different hierarchical manner. Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam-small for dates baby and finasteride-cryptorchidism were particularly significant (reporting odds ratio, ROR>800, N>10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept-skeletal dysplasia, and tacrolimus-talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti-tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin. This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases-abortion, diazepam-small for date baby, finasteride-cryptorchidism, etoposide and cisplatin-13 trisomy.

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) for gemcitabine

ABSTRACT Background Gemcitabine is widely used in the treatment of various cancers. This study aims to evaluate gemcitabine-associated adverse events (AEs) using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Research design and methods We analyzed data spanning from January 2004 to June 2023. Employing reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms, we identified AEs with positive signals in patients administered gemcitabine. Results Out of 16,623,939 reports, 23,645 involved gemcitabine as the ‘primary suspected (PS)’ resulting in 74,306 AEs. Consistent with the reports in the specification and clinical trials, thrombocytopenia, pyrexia, neutropenia, and anemia were the most common AEs. Notably, our study identified some unexpected AEs such as abdominal pain, pleural effusion, ascites, and gastrointestinal hemorrhage, among others. The most significant SOC was ‘Blood and lymphatic system disorders’. The median onset time for gemcitabine-related AEs was 24 days (interquartile range [IQR] 6–82 days), with most cases occurring within the initial 30 days following gemcitabine administration. Conclusion Gemcitabine is associated with a broad spectrum of AEs affecting multiple organ systems, with a notable incidence of hospitalization. The study highlights both expected and unexpected AEs, which could enhance future clinical applications and safety of gemcitabine.

Hypocalcemia Event Associated with Denosumab: A Real-World Study from FDA Adverse Event Reporting System (FAERS) Database.

Denosumab is widely used for osteoporosis and cancer treatment. However, hypocalcemia induced by denosumab is a frequent adverse event. The objective of this study is to comprehensively investigate the safety signals and the occurrence of hypocalcemia in real-world patient cases reported through the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Reports from January 1, 2017 to December 31, 2021 were extracted from the FAERS. Only cases of hypocalcemia suspected to denosumab were eligible in pharmacovigilance study. Denosumab-related hypocalcemia safety signal were identified to characterize their clinical features. A safety signal for hypocalcemia was evaluated using reporting odds ratios (ROR). Among the 102,413 cases related to denosumab, 1042 cases were reported with denosumab-related hypocalcemia. The affected patients were mainly elderly (median age 70years) and male (n = 568, 63.5%). In available data, the median onset time of 23 (range 0-1601) days. Most patients required drug interruption (n = 226, 72.9%) and can achieve a recovered-resolved state (n = 318, 62.1%). For the whole database, denosumab exhibited a safety signal for hypocalcemia (ROR = 14.09, 95% Cl 13.18, 15.06). In the sensitivity analyses, denosumab also showed a safety signal for hypocalcemia in cancer (ROR = 21.28, 95% Cl 18.79, 24.11) and osteoporosis (ROR = 9.29, 95% Cl 6.80, 12.59). Compared with bisphosphonates, denosumab still has safety signal for hypocalcemia (ROR = 1.88, 95% Cl 1.67, 2.11). This pharmacovigilance database analysis indicates a high safety signal for hypocalcemia associated with denosumab, particularly in cancer patients.

Real-world analysis of levetiracetam-associated rhabdomyolysis: insights from the FDA adverse event reporting system

ABSTRACT Background Levetiracetam, a widely prescribed antiseizure medication, is recognized for its broad-spectrum efficacy, good tolerability, and minimal drug interactions. This study examines the association between levetiracetam and rhabdomyolysis, utilizing real-world data from the FDA Adverse Event Reporting System (FAERS) database to further elucidate its safety profile. Methods This study extracted adverse events related to levetiracetam from the FAERS database (Q1 2013 to Q1 2024). Four types of disproportionality analysis identified rhabdomyolysis as a significant adverse even. Logistic regression assessed risk factors, including gender, age, and severity. A Gaussian Mixture Model analyzed the time-to-onset distribution of rhabdomyolysis, while the impact of concomitant medications on its risk was evaluated using Reporting Odds Ratio (ROR). Results Levetiracetam significantly increased rhabdomyolysis risk (ROR = 13.5). Males showed a higher incidence (OR = 2.60). Most adverse events occurred within the first 30 days, with a bimodal onset distribution. Co-administration of antibiotics, antipsychotics, and PPIs elevated the risk while other antiseizure medications did not. Conclusion This study found a significant association between levetiracetam and the risk of rhabdomyolysis, highlighting the need for increased clinical vigilance in this patient population. Future research should focus on elucidating the underlying mechanisms and optimizing clinical guidelines.

Safety assessment of sapropterin dihydrochloride: real-world adverse event analysis based on the FDA adverse event reporting system (FAERS)

ObjectiveSapropterin dihydrochloride is the first drug for the therapy of phenylketonuria, which is a rare disease that occurs one of 10,000–15,000 newborns. As a result, detailed and comprehensive reports on the safety of sapropterin in large, real-world populations are required. The purpose of this study is to undertake a complete analysis of sapropterin’s adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) database.MethodsWe retrieved reports of adverse events with sapropterin as the principal suspect from FAERS between the first quarter of 2008 and the first quarter of 2024. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) were utilized to detect AE signals.ResultsThe study collected 4,953 suspected AE cases from the FAERS database, with sapropterin as the major suspect. A total of 130 positive signals were obtained utilizing the ROR, PRP, and BCPNN. The FAERS database revealed that common clinical AEs of sapropterin included vomiting, upper respiratory infection, rhinorrhea, and a reduction in amino acid concentrations. Furthermore, we detected probable unexpected adverse events (AEs) using disproportionality analysis, including gastroesophageal reflux disease, flatulence, influenza, ear infection, viral infection, pharyngitis streptococcal, spontaneous abortion, and nephrolithiasis.ConclusionBy analyzing huge amounts of real-world data from the FAERS database, we found potential novel AEs of sapropterin using disproportionate analysis. It is advantageous for healthcare professionals and pharmacists to focus on efficiently managing sapropterin’s high-risk adverse events, improving drug levels in clinical settings, and ensuring patient medication safety.

Comparison of adverse events of poly adenosine diphosphate ribose polymerase inhibitors in patients with ovarian cancer using the United States Food and Drug Administration Adverse Event Reporting System

ABSTRACT Background Olaparib, niraparib, and rucaparib are the three primary poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors that are currently available in the market. Previous studies indicate different incidences of adverse events based on the PARP inhibitor or country. Research design and methods This study used data from the United States Food and Drug Administration Adverse Event Reporting System collected between January 2018 and December 2023. The data analyzed in this study involved patients receiving PARP inhibitors for treating ovarian cancer. A comparative analysis of the three PARP inhibitors was conducted using the reporting odds ratio (ROR) and the adjusted ROR (aROR) controlling for patient background differences. Results The aROR for niraparib was significant at > 1.000, including platelet count decreased (p < 0.001) and thrombocytopenia (p < 0.001) when olaparib was set as the reference. Conversely, the aROR for niraparib was significant at < 1.000, including anemia (p < 0.001). Additionally, significant differences were observed in various adverse events for rucaparib. Moreover, significant differences were observed when comparing between countries. Conclusions This study indicates that the types of adverse events may vary by PARP inhibitor and by country. These results will be beneficial in clinical practice.

Risk factors for acute appendicitis among adult patients with indeterminate ultrasound.

Abdominal ultrasound is used for diagnosing appendicitis in patients with right lower quadrant abdominal pain. Between 45 and 82% of radiology performed ultrasounds are indeterminate for appendicitis and computed tomography is required for diagnostic confirmation. Our study aims to determine predictors to rule out appendicitis when ultrasound is indeterminate. We performed a health records review of adult emergency department (ED) patients presenting with symptoms suspicious for appendicitis and indeterminate ultrasound to two academic EDs between June 2019 and July 2020. The outcome was appendicitis diagnosis within 30days of the index ED visit. We used multivariable logistic regression, identifying a cut-off threshold for continuous variables with cubic spline, and chose the parsimonious model to develop a binary decision rule. We report Odds ratios (OR) and diagnostic performance with 95% confidence intervals (CI). Overall, 463 patients (mean age 30.3years (SD 10.5years), 74.9% female) were included. Appendicitis was diagnosed in 45 patients (9.7% [95% CI 7.2-12.8%]). After ultrasound, computed tomography was performed in 227 patients (49.0%) and 39 patients (17.2%) were diagnosed with appendicitis. Among the 236 patients who did not have a subsequent computed tomography, 6 (2.6%) patients had appendicitis. Neutrophil count > 5.5 × 109/L (OR 1.21 [95% CI 1.12-1.30]) and secondary signs of inflammation on ultrasound (OR 2.16 [1.07-4.37]) were associated with a higher likelihood of appendicitis (C-statistic 0.77 [95% CI 0.70-0.84]). The absence of both predictors had a sensitivity of 88.9% (95% CI 76.0-96.3%), specificity of 45.7% (95% CI 40.8-50.6%) and a negative predictive value of 0.97 (95% CI 0.94-0.99) to rule out appendicitis. For patients suspected of appendicitis and indeterminate ultrasound, the absence of an elevated neutrophil count and secondary signs of inflammation are associated with a low probability of appendicitis.

Safety of dapagliflozin and empagliflozin in cases with diabetes mellitus or/and heart failure: a retrospective pharmacovigilance study conducted on the eudravigilance database.

Dapagliflozin and empagliflozin are sodium-glucose cotransporter-2 (SGLT2) inhibitors initially approved for the treatment of type 2 diabetes mellitus (DM), and later for heart failure (HF). Considering this differential therapeutic use, we decided to evaluate cases related to these agents by comparing those with DM, HF, or both (DM and HF). A retrospective, pharmacovigilance study was conducted by using data contained in the EudraVigilance from January 1st, 2021, to December 31st, 2023. Cases were classified into those with DM, HF, or both diseases. The Reporting Odds Ratio (ROR), and its 95% confidence interval (95%CI) were computed to compare the reporting probability of the four most reported adverse events. The following comparisons were performed: DM vs. HF; both DM and HF vs. HF; both DM and HF vs. DM. Analyses were adjusted for age, sex, and time between the approval date of the SGLT2 inhibitor and the reporting date. A total of 14,594 (50.5%) cases were classifiable for DM (N = 11,962; 82.0%), HF (N = 2,100; 14.4%), or both DM and HF (N = 532; 3.64%). The empagliflozin was the most reported SGLT2 inhibitor (60.1%), and only 15 cases (0.1%) reported both empagliflozin and dapagliflozin. Cases with DM and both DM and HF were associated with a higher reporting probability of ketoacidosis (ROR: 5.95, 95%CI: 4.87-7.26; ROR: 3.05, 95%CI: 2.27-4.09) and Fournier's gangrene (ROR: 2.30, 95%CI: 1.65-3.20; ROR: 2.30, 95%CI: 1.38-3.82) than HF. These results were also confirmed by adjusted analyses. We found that ketoacidosis and Fournier's gangrene had a higher reporting in cases with DM. Further studies are warranted.

Evaluating the impact of loperamide on irinotecan-induced adverse events: a disproportionality analysis of data from the World Health Organization pharmacovigilance database (VigiBase).

SN-38, the active metabolite of irinotecan, may cause adverse events necessitating treatment discontinuation and management. Diarrhea, which is treated with loperamide, is one such event. However, loperamide may delay SN-38 elimination, causing more adverse events. Therefore, understanding the adverse events caused by symptomatic drugs is crucial for safe drug therapy. This study aimed to assess the association between loperamide and irinotecan-induced adverse events. We analyzed data up to December 2022 from VigiBase, the World Health Organization's adverse event database. The study used reporting odds ratios (RORs) to evaluate the associations between concomitant medications and irinotecan-induced adverse events. Fisher's exact probability test was used to analyze the adverse events. Logistic regression analysis was performed to identify associated adverse event signals. Of the 32,520,983 cases analyzed, 57,454 involved the use of irinotecan. Among these, 1589 (2.8%) patients were co-treated with loperamide. Signals for neutropenia (ROR 1.37, 95% confidence interval (CI) 1.20-1.57, p < 0.001), anemia (ROR 1.81, 95% CI 1.43-2.30, p < 0.001), and alopecia (ROR 1.89, 95% CI 1.30-2.74, p < 0.01) were detected with concomitant loperamide. Multivariate logistic regression analysis confirmed that concomitant loperamide use was associated with signals for neutropenia, anemia, and alopecia. Our results suggest that loperamide increases the risk of irinotecan-induced adverse events and enhances irinotecan toxicity. The study methodology may be useful for predicting adverse event risk when choosing symptomatic therapy drugs during irinotecan use.

The Association Between Dextromethorphan/Bupropion with Alcohol and Substance Misuse: Reports to the Food and Drug Administration Adverse Event Reporting System (FAERS).

Dextromethorphan/bupropion (DXM/BUP) received Food and Drug Administration (FDA) approval for the treatment of adults with major depressive disorder (MDD) in August 2022. This combination is not known to have abuse liability and is not currently scheduled by the Drug Enforcement Administration (DEA). Notwithstanding, dextromethorphan is a drug of abuse. Herein, we sought to determine whether DXM/BUP has alcohol and/or substance misuse liability. We evaluated spontaneous reports of terms such as "alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse" in the FDA Adverse Event Reporting System (FAERS). The FAERS is a spontaneous reporting database of adverse events submitted to the FDA. We performed a comparative assessment of the alcohol and/or substance misuse liability of DXM/BUP since its market authorization in August 2022, using acetaminophen as the control. Dextromethorphan served as the upper-bound reference point. Our findings showed that, since August 2022, dextromethorphan had a significant reporting odds ratio (ROR) for "drug abuse." In contrast, DXM/BUP did not have a significant ROR for any of the categories of alcohol and/or substance misuse evaluated. Limitations of our findings derive largely from the limitations of the FAERS and its data capture method. The absence of alcohol or substance misuse reported to the FAERS with DXM/BUP accords with the lack of evidence of abuse liability prior to FDA approval and its non-scheduling by the DEA.

Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration

BackgroundCompared to alternative weight-loss strategies and medications, semaglutide stands out for its convenience and efficacy, resulting in a significant increase in prescriptions and raising public safety concerns. Furthermore, the safety profiles of its oral and subcutaneous formulations require further examination.ObjectiveOur goal is to investigate the potential safety risks associated with semaglutide by analyzing data from the FAERS database and social media. Additionally, we aim to compare the adverse drug reaction (ADR) signals between the oral and subcutaneous administration routes of semaglutide.MethodsWe collected semaglutide-related reports from the FAERS database spanning Q1 2018 to Q2 2023, and patient reviews on WebMD and AskaPatient up to 20 July 2023. Following data extraction and cleansing, we conducted descriptive analyses of demographic characteristics. Subsequently, we calculated adverse drug reaction (ADR) signals using the reporting odds ratio (ROR).ResultsWe identified 19,289 and 422 semaglutide-related adverse drug events (ADEs) reported in the FAERS database and online patient reviews, respectively. Gastrointestinal disorders emerged as the most commonly reported System Organ Class (SOC) in both datasets. Predominant Preferred Terms (PTs) included nausea, vomiting, and diarrhea. Serious outcomes constituted 3.07% and 2.25% of all cases for oral and subcutaneous semaglutide, respectively. At the SOC level, gastrointestinal disorders accounted for 30.19% of total ADEs in oral semaglutide, slightly surpassing the 27.76% in subcutaneous semaglutide. The median onset for gastrointestinal PTs was 4 days in both oral (Q1: 1, Q3: 32) and subcutaneous (Q1: 1, Q3: 35) formulations. Noteworthy, new serious adverse event (AE) signals were identified, including hemorrhagic diarrhea (ROR: 3.69), hepatic pain (ROR: 4.20), abnormal hormone levels (ROR: 6.51), and pancreatic failure (ROR: 36.34) in subcutaneous semaglutide, and Dupuytren’s contracture (ROR: 46.85) in oral semaglutide.ConclusionOur study delineates the safety profile of semaglutide using data from the FAERS database and social media. And identified novel ADR signals specific to oral and subcutaneous forms of semaglutide.

Cardiovascular adverse events associated with triptans for treatment of migraine: a pharmacovigilance study of the FDA adverse event reporting system (FAERS).

The purpose of this study was to determine the relationship between triptans (sumatriptan, rizatriptan, and zolmitriptan) and cardiovascular (CV) adverse events with data from the FDA Adverse Event Reporting System (FAERS). FAERS database was used to collect data on triptans from 1997 to 2023. Disproportionality methods were utilized to quantify triptan-associated CV events and to identify the potential risk. The reporting odds ratio was used to identify the risk signals. CV outcomes related to age, sex, clinical results, and other factors were also examined for triptans; 820 reports involving the triptans were recognized as CV adverse events out of total of 12 699 reports that were gathered from on FAERS database. Women reported more CV adverse events with rizatriptan and zolmitriptan as compared to men. The CV adverse event risk was highest among individuals aged 18-64. Clinical outcome analysis showed that sumatriptan carries a higher CV risk than rizatriptan and zolmitriptan, and most deaths and serious cases have been documented for sumatriptan. The patients prescribed sumatriptan or zolmitriptan were at a higher risk of reporting CV events for chest pain and chest discomfort, compared to rizatriptan. This finding may provide support for the clinical observation and risk evaluation of triptan treatment.

Adverse events analysis of Relugolix (Orgovyx®) for prostate cancer based on the FDA Adverse Event Reporting System (FAERS).

Due to the limitations of clinical trials, some delayed and rare adverse events (AEs) may remain undetected, and safety information can be supplemented through post-market data analysis. This study aims to comprehensively analyze the AEs associated with Relugolix (Orgovyx®) using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Relugolix (Orgovyx®) therapy. Data of Relugolix (Orgovyx®) were collected from the FAERS database covering the period from the fourth quarter of 2020 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), Bayesian analysis confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) to detect positive signals. Totally, 5,382,189 reports were collected from the FAERS database, 4,397 reports of Relugolix (Orgovyx®) were identified as the 'primary suspected (PS)' AEs. Relugolix (Orgovyx®) induced AEs occurred in 26 organ systems. 58 significant disproportionality preferred terms (PTs) satisfying with the four algorithms were retained at the same time. Unexpected significant AEs such as Pollakiuria, and Prostatic specific antigen increased also occur. The median time of onset was 60 days. The majority of the AEs occurred within the first 30 days after Relugolix (Orgovyx®) initiation. Common AEs included Hot flush, Fatigue, Asthenia, Constipation, and Myalgia. These AEs should be focused on when using the drug to avoid serious consequences. In addition, the study results also suggested that the drug may exist Pollakiuria, Prostatic specific antigen increased and other AEs not mentioned in the manual, to supplement the AEs in the manual. This study is helpful for clinicians and pharmacists to improve their understanding of Relugolix (Orgovyx®) related AEs, and take timely prevention and treatment measures to ensure drug safety for patients.

Adverse drug reaction signals mining comparison of amiodarone and dronedarone: a pharmacovigilance study based on FAERS

BackgroundAmiodarone and dronedarone are both class III antiarrhythmic medications used to treat arrhythmias. The objective of this study was to enhance the current understanding of adverse drug reaction (ADR) associated with amiodarone and dronedarone by employing data mining methods on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), and providing a reference for safe and reasonable clinical use.MethodsThe ADR records were selected by searching the FAERS database from 2011 Q3 to 2023 Q3. The disproportionality analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were used to detect signals of amiodarone-related and dronedarone-related ADRs. The ADR profiles of amiodarone and dronedarone categorized by organ toxicity were compared through the Z-test and the Fisher exact test.Results9,295 reports specifically mentioned the use of amiodarone and 2,485 reports mentioned the use of dronedarone among 9,972,109 reports, with the majority of ADRs occurring in males over 60 years old. The United States was responsible for the highest proportion of reported ADRs. Significant system organ classes (SOC) for both included Cardiac disorders, Respiratory, thoracic and mediastinal disorders, and Investigations, etc. At the preferred terms (PTs) level, the more frequent ADR signals for amiodarone were drug interaction (n = 856), hyperthyroidism (n = 758), and dyspnoea (n = 607), while dronedarone were atrial fibrillation (n = 371), dyspnoea (n = 204), and blood creatinine increased (n = 123). Notably, unexpected ADRs, including electrocardiogram T wave alternans (n = 16; EBGM05 = 231.27), accessory cardiac pathway (n = 11; EBGM05 = 140), thyroiditis (n = 178; EBGM05 = 125.91) for amiodarone, and cardiac ablation (n = 11; EBGM05 = 31.86), cardioversion (n = 7; EBGM05 = 22.69), and dysphagia (n = 47; EBGM05 = 3.6) for dronedarone, were uncovered in the instructions. The analysis also revealed significant differences in the ADR profiles of amiodarone and dronedarone, with dronedarone showing higher proportions of cardiac toxicity but lower thyroid toxicity compared to amiodarone.ConclusionThese findings underscore the significance of vigilantly monitoring and comprehending the potential risks linked to the use of amiodarone and dronedarone. New ADRs discovered and clear ADR profiles of amiodarone and dronedarone enhance a thorough understanding of these drugs, which is essential for clinicians to ensure safe use of amiodarone and dronedarone.

Cardiovascular adverse events associated with norepinephrine-dopamine reuptake inhibitors: a pharmacovigilance study of the FDA Adverse Event Reporting System.

Norepinephrine-dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivity disorder, and depression. Cardiovascular adverse events have been reported to the FDA despite their effectiveness. This pharmacovigilance study analyzed cardiovascular adverse events associated with NDRIs using the FDA Adverse Event Reporting System data from January 2004 to December 2021. A retrospective analysis of adverse event reports was conducted, employing time-trend analysis and disproportionality evaluation to assess cardiovascular risks. Bupropion had the greatest reported odds ratios (RORs) for tachycardia (ROR=4.2, 95% CI: 4.0-4.4) and hypertension (ROR=3.5, 95% CI: 3.3-3.7), while methylphenidate showed greater ROR for arrhythmias (ROR=2.8, 95% CI: 2.6-3.0) and palpitations (ROR=3.1, 95% CI: 2.9-3.3). Reboxetine had signals for palpitations (ROR=3.0, 95% CI: 2.8-3.2) and myocardial infarction (ROR=2.7, 95% CI: 2.5-2.9), whereas atomoxetine revealed signals for hypertension (ROR=2.9, 95% CI: 2.7-3.1) and syncope (ROR=2.5, 95% CI: 2.3-2.7). Time-trend analysis revealed temporal variability in the cardiovascular risks connected with NDRIs. Our research elucidates cardiovascular safety profiles for NDRIs, highlighting the necessity for continuous pharmacovigilance. The observed variations in adverse events emphasize the need for ongoing surveillance to mitigate potential cardiovascular risks and enhance patient safety and treatment outcomes.

A Retrospective Observational Study of Adverse Drug Reactions (ADR) Reported to ADR Monitoring Centre from 2010 to 2020.

Adverse Drug Reactions (ADR) are one of the essential causes of hospital admissions and pose a significant clinical and economic burden on the healthcare system. The Adverse Drug Reaction Monitoring Centre (AMC) in JIPMER functioning under the Pharmacovigilance Programme of India (PvPI) plays a vital role in ensuring medication safety by routinely detecting and monitoring ADRs. Hence, this study aimed to assess the characteristics of ADR reported from 2010 to 2020 in AMC JIPMER and to detect signals, if any. To study the characteristics of Adverse Drug Reactions (ADR) reported to a regional ADR monitoring center from 2010 to 2020 and to detect signals of disproportionate reporting (SDRs) if any from the reported ADRs. A total of 6007 ADR reports with a single suspect drug were included for analysis from 2010 to 2020. The characteristics of these reports, including patient's age and gender, Number and percentage of ADRs, the causality of ADR using WHO UMC (World Health Organization-Uppsala Monitoring Scale), the seriousness of the ADR, and outcome were collected from the ADR reports. MedDRA (Medical Dictionary for Regulatory Activities) Preferred Terms (PT) were used to classify adverse drug reactions. Causality analysis using the Naranjo Algorithm and Preventability using Modified Schumock and Thornton criteria were performed for the ADRs. The number and percentage of severe ADRs were analyzed. The System Organ class of all the ADRs was enumerated. ADRs not mentioned in the US FDA (United States Food and Drug Administration) product label (unlabelled reactions) were documented. Unlabeled reactions with ≥3 ADR reports were included for signal detection by disproportionality analysis. Antineoplastic drugs, followed by antimicrobials, anticonvulsants, Anti snake venom, and NSAID were the most common drugs implicated in ADRs. Skin and subcutaneous tissue disorders were the most common System Organ Class (SOC) involved in the ADRs. Among the 6007 reports, 19.2% were serious ADRs. Most of the ADR reports were of possible causality followed by probable and certain as per WHO UMC and Naranjo causality scales. Only ten ADRs were preventable and one reaction (Tamoxifen-induced neuropathy) was eligible for signal detection. Disproportionality analysis using a 2x2 contingency table showed insignificant signal detection using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). Analysis of ADRs from an ADR Monitoring center functioning in a tertiary care hospital shows antineoplastic drugs to be the most common drugs associated with adverse drug reactions, with rash being the most common adverse effect. The majority of the ADRs were not preventable. No Signals of Disproportionate Reporting (SDR) were detected in our study.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: A replication study using reports to the World Health Organization pharmacovigilance database (VigiBase®)

IntroductionReports of suicidality associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been reported to the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). We previously reported an increased reporting odds ratio (ROR) of some measures of suicidality with semaglutide and liraglutide using the FDA Adverse Event Reporting System (FAERS). Notwithstanding the increased ROR, causality between GLP-1 RAs exposure and any aspect of suicidality is not established. Research design and methodsThe analysis herein aims to extend a previous analysis of the FAERS by evaluating the ROR for suicidality reported to the World Health Organization (WHO) Pharmacovigilance Database (VigiBase). We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports. As per our previous report, the ROR was considered significant when the lower limit of the 95 % confidence (CI) was >1.0. ResultsWe searched VigiBase reports from inception to January 2024. The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25). For “depression/suicidal”, the ROR was significantly increased for semaglutide (14.74) and liraglutide (5.86); and for suicidal behaviour, the ROR was significantly increased for semaglutide (6.52) and liraglutide (3.90). However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15). For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008). ConclusionUnlike our previous report with FAERS, a mixed pattern of ROR emerged in the WHO VigiBase with respect to suicidality and exposure to select GLP-RAs. Causation between GLP-1 RA exposure and suicidality (either increased or decreased) cannot be ascertained from ROR data.