Expert Opinion on Drug Safety最新文献

Background: Riociguat is a novel soluble guanylate cyclase stimulator approved for the treatment of pulmonary arterial hypertension (PAH). Despite its widespread use, there has been a lack of large-scale studies assessing the adverse events (AEs) associated with this medication.

Research design and methods: This study aimed to evaluate the AEs related to Riociguat by analyzing data from the FDA Adverse Event Reporting System (FAERS) from Q4 2013 to Q1 2024. A total of 12,149 AE reports were analyzed using four different disproportionality signal detection methodologies to identify significant AEs associated with Riociguat.

Results: The analysis revealed 117 preferred terms (PTs) with significant disproportionality signals across all four methods. Among these, common AEs included 'headache,' 'dizziness,' 'hypotension,' 'nausea,' 'fall,' and 'loss of consciousness.' Notably, several unexpected AEs, such as 'fatigue,' 'malaise,' 'asthenia,' 'feeling abnormal,' and 'pain in extremity,' were identified, which were not highlighted in the product's package insert. Additionally, gender-specific differences were observed in certain adverse events.

Conclusions: This study offers insights into Riociguat's side effects. Clinicians should monitor patients closely for unexpected symptoms like limb pain and fatigue, paying particular attention to male patients, as some AEs occur more frequently in this group.

Background: Luspatercept, approved for treating beta thalassemia, myelodysplastic syndromes (MDS) associated anemia, and MDS with ring sideroblasts or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis associated anemia, has uncertain long-term safety in large populations. This study analyzed adverse events (AEs) linked to luspatercept using data from the FDA Adverse Event Reporting System (FAERS) with data mining techniques.

Research design and methods: We collected and analyzed luspatercept-related reports from the FAERS database from the first quarter of 2022 through the first quarter of 2024. Disproportionality analysis was used in data mining to quantify luspatercept-related AE signals.

Results: A total of 46 AE signals were detected in 13 SOCs (system organ classes). In addition to the AEs identified during the clinical trial stage, this study also identified some unexpected and important AEs, such as product preparation error, prescribed overdose, product preparation issue, prescribed underdose, and acute hepatitis.

Conclusions: Our study provides a comprehensive description of the post-marketing safety of luspatercept and identifies new potential AEs. Healthcare workers must be vigilant in avoiding product preparation errors, an adverse event that highlights the need for enhanced training and the participation of pharmacists in assessing medication utilization scenarios.

Background: Tasimelteon is a novel dual melatonin receptor agonist approved for the treatment of non-24-hour sleep-wake disorder (N24HSWD). The purpose of this study was to provide a comprehensive analysis of post-marketing adverse events (AEs) for tasimelteon by analyzing the U.S. FDA Adverse Event Reporting System (FAERS) database.

Methods: Four algorithms are employed in this study to mine the significant signals: multi-item gamma poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), reporting odds ratio (ROR), and proportional reporting ratio (PRR).

Results: Tasimelteon was the primary suspected drug in 5,125 adverse event reports that were identified between the first quarter of 2014 and the first quarter of 2024. Significant system organ categories (SOC) included psychiatric disorders, general disorders and administration site conditions, and nervous system disorders. We not only confirmed the adverse reactions outlined in the prescribing information such as somnolence, nightmare or abnormal dreams, and inhibitory drug interaction, but also revealed new potential risks that were not documented, such as insomnia and sleep disorder.

Conclusions: This study revealed the characteristics of tasimelteon-associated adverse drug reactions, improved understanding of drug safety, and provided valuable signals for optimizing drug use regimens. Additional large-scale prospective studies remain necessary in the future.

Background: Blinatumomab, the first CD3/CD19 bispecific antibody, is FDA-approved for relapsed or refractory precursor B-cell acute lymphoblastic leukemia in adults and children. This study evaluates its safety profile through pharmacovigilance analysis of adverse events (AEs) reported in the FDA Adverse Event Reporting System (FAERS).

Method: We conducted a disproportionality analysis using four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Data from 2014Q1 to 2023Q4 were analyzed to identify safety signals related to blinatumomab, along with a stratification analysis to examine AE onset timing.

Result: A total of 17,131 AE reports were retrieved from the FAERS database, with 6,266 indicating blinatumomab as the primary suspect. We identified 277 preferred terms (PTs) demonstrating significant disproportionality across all algorithms. Notably, unexpected AEs included Graft Versus Host Disease, myelosuppression, and hypokalaemia. Common AEs were consistent across gender and age groups, predominantly occurring within one month of treatment.

Conclusion: This pharmacovigilance study utilizing the FAERS database identified potential AE signals associated with blinatumomab, providing essential insights for its safe clinical use.

Background: Janus kinase inhibitors (JAKIs) have been approved for the treatment of rheumatoid arthritis (RA) for several years. A recent real-world study has shown the possibility of a relationship between the occurrence of ocular adverse events (OEs) and the use of JAKIs but failed to rule out whether those OEs are related to RA.

Research design and methods: A retrospective, pharmacovigilance study using the FDA Adverse Event Reporting System to evaluate OE reports following treatment with JAK inhibitors in patients with RA from Q1 2004 to Q1 2024.

Results: We identified 3226 cases associated with JAKIs and 24,158 cases associated with TNFIs. Most of the OEs are serious cases, the age distribution was similar but the sex distribution was not balanced. The OEs with top 10 ROR values in TNFIs had no detectable signal in JAKIs, and the time of onset of OEs also shows difference. Besides, far fewer OE were reported for baricitinib than for the other JAKIs.

Conclusions: Different types of JAKIs are associated with special types of OEs and differ in time of onset compared with TNF inhibitors. More rigorous trials should be conducted to better understand the risk factors in JAKIs-related OEs.

Background: Approved by the FDA in 2021, varenicline solution is the first nasal spray specifically designed to enhance basal tear film production for treating dry eye disease (DED). However, there is a lack of data comprehensively comparing its safety profile to conventional DED therapies. Herein, we assess whether ocular adverse events (AEs) are disproportionately reported with the real-world use of varenicline solution.

Research design and methods: This observational, population-based pharmacovigilance study analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS) data (inception-April 2024) using reporting odds ratio (ROR), with significance defined as a 95% CI lower bound > 1.0. Nasal saline and systane were the controls.

Results: A total of 1,125 AE reports were associated with varenicline solution. No disproportionate reporting of specific ocular AEs was observed when comparing varenicline solution with nasal saline. However, when compared with systane, varenicline solution showed higher odds of lacrimation (ROR = 2.18, 95%CI = 1.46-3.26, p < 0.0001), visual impairment (ROR = 2.27, 95%CI = 1.24-4.16, p = 0.0085), and photophobia (ROR = 7.50, 95%CI = 3.68-15.27, p < 0.0001).

Conclusions: Although a direct causal relationship for higher RORs cannot be established for varenicline solution compared to systane, our findings provide evidence for potential risk signals and highlight the crucial role of post-marketing pharmacovigilance in monitoring long-term safety.

Coronary Artery Disease (CAD) and Peripheral Artery Disease (PAD) are leading causes of death and illness worldwide. These conditions greatly impact the quality of life and increase the risk of serious cardiovascular and limb events (MACE and MALE). Even with advances in medical treatments, patients with chronic CAD and PAD still face a high risk of thrombotic events. Traditional anticoagulant therapies, such as warfarin combined with aspirin, have not effectively reduced cardiovascular events and often lead to major bleeding. Therefore, rivaroxaban, an oral factor Xa inhibitor, has emerged as a promising therapeutic agent. The COMPASS trial found that combining low-dose rivaroxaban with aspirin significantly reduces MACE and MALE in chronic CAD and PAD patients, though it also increases the risk of major bleeding. Additional studies, including COMPASS, LTOLE and VOYAGER PAD, have confirmed these results, demonstrating rivaroxaban's effectiveness and safety across different patient groups. It is important to note that the populations studied in these trials differ significantly, particularly regarding the heart failure population. Some patients, such as those with recent worsening chronic heart failure, do not benefit from rivaroxaban. Specifically, the COMMANDER HF trial found that in patients with chronic heart failure, reduced ejection fraction, and coronary artery disease who were not in atrial fibrillation, low-dose rivaroxaban did not significantly reduce the risk of death, myocardial infarction, or stroke compared to placebo. These distinct population characteristics highlight the importance of considering specific patient factors when interpreting the efficacy of rivaroxaban. Cost-effectiveness analyses from various healthcare systems show that rivaroxaban, especially when used with aspirin, is a cost-effective treatment for CAD and PAD patients. This review explores rivaroxaban's role in reducing MACE and MALE in CAD and PAD patients, discussing its pharmacology, uses, effectiveness, safety, and cost-efficiency. It also reviews recent research and recommendations for specific patient characteristics, offering a comprehensive overview and future perspectives on its role in managing cardiovascular diseasess.

Background: While vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKIs) are known to cause adverse events like cardiotoxicity and haematotoxicity, their impact on liver injury remains understudied. This study evaluates the association between VEGFR-TKIs and liver injury using data from the FDA Adverse Event Reporting System (FAERS) database from 2006 to 2024.

Research design and methods: Nine VEGFR-TKIs (Axitinib, Vandetanib, Cabozantinib, Lenvatinib, Pazopanib, Ponatinib, Regorafenib, Sunitinib, Sorafenib) were analyzed. Disproportionality and Bayesian analyses identified cases of VEGFR-TKI-induced liver injury, assessing onset time, mortality, and hospitalization rates.

Results: 8,619 cases of liver injury were identified. Pazopanib had the highest association with liver injury (reporting odds ratio 3.9). The median onset of liver injury was 21 days. Mortality was 28.5%, with Sorafenib linked to the highest mortality (48.6%). Lenvatinib had the highest hospitalization rate (56%).

Conclusion: VEGFR-TKIs are associated with liver injury. Close monitoring is required to mitigate the risks of hospitalization and early mortality during treatment.

Background: Selinexor is approved for the treatment of relapsed or refractory multiple myeloma. However, a comprehensive understanding of adverse events associated with selinexor is lacking.

Methods: Clinical trials of selinexor in patients with multiple myeloma were reviewed. We investigated selinexor-related adverse events through data of the US Food and Drug Administration Adverse Event Reporting System (FAERS). The disproportionality analysis was conducted. Four algorithms were employed to evaluate the signals of adverse events. The adverse effects of selinexor combined with dexamethasone were compared with bortezomib and dexamethasone. Sensitivity analysis was performed to exclude consumer-reported adverse events. The onset of adverse reactions were calculated.

Results: A total of 1,698 reports related with selinexor from FAERS were identified. 6 significant system organ class and 42 significant preferred terms (PTs) were found. Unexpected significant adverse events including mania, acute kidney injury, orthostatic hypotension, and embolisms were identified. 14 PTs reported significant signals in treatment of selinexor combined dexamethasone compared with traditional treatment of bortezomib and dexamethasone. 45.2% of adverse events occurred within the first month of starting selinexor.

Conclusions: Comprehensive analyses of selinexor related adverse events are helpful for clinical detection of adverse events and timely intervention, advancing selinexor's therapeutic progress in future treatment.

Objectives: This study aimed to describe the pulmonary toxicity of cyclin-dependent kinase 4/6 inhibitors (CDK 4/6 inhibitors) (palbociclib, ribociclib, and abemaciclib) in patients being treated for breast cancer using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Research design and methods: Disproportionality analysis was performed to assess pulmonary toxicity associated with CDK 4/6 inhibitors. Clinical characteristics, onset time, sensitivity analysis, subgroup analyses, drug combinations, comorbidities, and co-reported events were performed.

Results: Out of 83,505 CDK 4/6 inhibitor-related adverse events (AEs) documented in the FAERS database during the study period, 437 cases of pneumonitis, 555 cases of pulmonary edema, and 181 cases of pulmonary thrombosis related to CDK 4/6 inhibitors were analyzed. Pneumonitis and pulmonary thrombosis had the strongest signal strength in abemaciclib; pulmonary edema had the strongest signal strength in ribociclib. The median latency for pneumonitis, pulmonary edema, and pulmonary thrombosis was 66-173.5 days, 27-131 days, and 68-279 days, respectively. Pulmonary toxicity is statistically significant disproportionality in females as well as in patients over 60 years old.

Conclusion: Abemaciclib was most strongly associated with pneumonitis and pulmonary thrombosis. Ribociclib was most strongly associated with pulmonary edema. The correlation with pulmonary toxicity was, in descending order, abemaciclib, ribociclib, and palbociclib.