Expert Opinion on Drug Safety最新文献

Introduction: Breast cancer (BC) remains a prevalent and challenging malignancy among women, with significant advancements in treatment strategies over the past decades. Traditional chemotherapy has been progressively supplemented by newer modalities, including Antibody-Drug Conjugates (ADCs), Immunotherapy (IO), and Targeted Therapies (TT). Despite these advancements, there remains a critical need for strategies that maintain efficacy while minimizing toxicity.

Areas covered: This review delves into metronomic chemotherapy (MC), a novel approach involving the frequent administration of low-dose chemotherapy without prolonged breaks. We explore MC's impact across various breast cancer subtypes, such as Estrogen Receptor-Positive (ER+), HER2-Positive, and Triple-Negative Breast Cancer (TNBC). The literature reviewed highlights MC's mechanisms, including its anti-angiogenic, immunomodulatory, and antiproliferative effects, and its potential to improve treatment tolerability and address drug resistance.

Expert opinion: MC represents a promising adjunct to existing therapies, particularly in advanced or resistant cases. Its unique dosing schedule could offer sustained antitumor activity with reduced toxicity, making it a viable option for long-term management. However, further research is warranted to establish optimal dosing regimens, identify predictive biomarkers, and delineate its role within combination treatment strategies. Clarifying these aspects could refine MC's application, potentially reshaping treatment paradigms and enhancing patient outcomes in breast cancer management.

Introduction: Patient engagement in pharmacovigilance (PEP) has been shown to improve information on adverse drug reactions (ADRs), which may not be found in reports from healthcare professionals. This review shows that there is paucity of information on PEP in lower-middle-income countries (LMICs), particularly Africa. It provides insights into PEP in high-income countries (HICs) compared with Africa to help identify the disparities and system challenges in Africa.

Areas covered: We discussed the impact of PEP in HICs in comparison with Africa and incorporated two case studies: PEP in Ghana and medication error reporting in Africa using a scoping review. Recommendations were made to improve medication safety in Africa based on the identified disparities and system challenges.

Expert opinion: PEP is at an early stage in LMICs, particularly in Africa, with limited information available regarding patients' contributions to the safety of medicines. There should be further research into patients' roles in pharmacovigilance accompanied by advocacy efforts with policymakers, the development of sustainable funding strategies, benchmarking against experienced pharmacovigilance centers, and the use of technology to improve patient reporting.

Background: Tafasitamab is the first anti-CD19 monoclonal antibody approved for relapsed/refractory diffuse large B-cell lymphoma patients ineligible for autologous stem cell transplantation. The study was designed to evaluate tafasitamab-associated adverse events (AEs) by data mining the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Research design and methods: A disproportionality analysis was performed to assess the safety profile of tafasitamab based on the reports from the FAERS database between 2020Q3 and 2023Q3. Proportional reporting ratio (PRR) and empirical Bayesian geometric mean (EBGM) were used to identify the signals of AEs in patients receiving tafasitamab.

Results: A total of 529 reports with tafasitamab as the primary suspect drug were collected, including 1,262 AEs. Of these, 28 repeated AEs were identified using two algorithms. After excluding events unrelated to drug therapy, the top five repeated AEs by intensity ranking were cytopenia, immunosuppression, neutropenic sepsis, blood lactate dehydrogenase increased, and hematotoxicity. Unexpected significant AEs included polyneuropathy, splenomegaly, hemophagocytic lymphohistiocytosis, hypercalcemia, and ascites.

Conclusions: This study provides additional evidence for risk identification of tafasitamab in the real world, which could help clinicians and pharmacists increase vigilance and improve the safety of tafasitamab in clinical practice.

Background and aims: Data related to clinical characteristics and potential mechanisms of proton pump inhibitors (PPIs)-related liver injury are sparse, thus the purpose of this study is to summarize the clinical features and molecular mechanisms of PPIs-induced liver injury.

Methods: We collected case report on liver injury induced by PPIs in English and Chinese for retrospective analysis. Clinical and pathological data and outcomes were obtained and analyzed. Network pharmacology and molecular docking techniques were employed to examine the mechanism.

Result: Twenty-three patients with PPIs-induced liver injury were enrolled. PPIs-induced liver injury is a rare adverse reaction, ranging from asymptomatic elevated transaminases to fulminant liver failure. Omeprazole was the drug with the highest number of associated reports. The most common symptom was fatigue. The most common liver injury pattern was hepatocellular injury. A total of 13 intersection targets of PPIs and liver injury were screened, and the top 10 targets were included, and the PI3K-Akt signaling pathway was significantly enriched. The results of molecular docking implied that the PPIs could combine well with key targets.

Conclusion: Patients receiving long-term treatment with PPIs should consider monitoring liver function. PPIs exhibit considerable capacity in liver injury via especially the PI3K-Akt signaling pathway.

Background: The increasing prevalence of statin use for cardiovascular disease management has raised concerns regarding their safety profile, particularly regarding the potential risk of diabetes. Our study aims to analyze diabetic adverse event reports related to statins using a large pharmacovigilance database to provide timely insights into this significant issue.

Methods: We analyzed data from the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023. Disproportionality analyses were performed to detect signals of diabetic adverse events associated with the three most commonly prescribed statins: atorvastatin, rosuvastatin, and simvastatin.

Results: We identified 11,364 cases of statin-related diabetic adverse events across the three statins. Disproportionality analyses revealed a significant association between these statins and four specific diabetic adverse events: type 2 diabetes mellitus, impaired glucose tolerance, diabetic neuropathy, and diabetic retinal edema. Notable sex differences emerged, with females exhibiting an overall significantly higher propensity for diabetes-related adverse events.

Conclusions: Our study is timely and relevant as it addresses growing concerns about the safety of widely prescribed statins and their association with diabetes. By highlighting these critical issues, the study seeks to contribute valuable insights to practitioners, ultimately guiding better clinical practices and enhancing pharmacovigilance efforts.

Background: Myocarditis is a rare but potentially life-threatening inflammation of the heart muscle that can be caused by various drugs. This study aimed to comprehensively evaluate the risk of drug-induced myocarditis using data from the FDA Adverse Event Reporting System (FAERS) database.

Methods: We queried the FAERS database for reports of myocarditis from Q1 2004 to Q4 2023. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were calculated to detect disproportionality signals for drugs associated with myocarditis.

Results: A total of 8,212 myocarditis-related reports were identified in the FAERS database. The most frequently reported drugs were clozapine (N = 1269), followed by nivolumab (N = 621), pembrolizumab (N = 358), mesalazine (252), and olanzapine (N = 191). Disproportionality analysis revealed strong signals for the top 50 drugs, including mesalazine (ROR 48.01, 95% CI 42.29-54.49), cemiplimab (ROR 38.84, 95% CI 26.71-56.47), clozapine (ROR 35.21, 95% CI 33.13-37.39), nivolumab (ROR 23.21, 95% CI 21.38-25.2), atezolizumab (ROR 20.75, 95% CI 17.91-24.05) and pembrolizumab (ROR 19.90, 95% CI 17.89-22.13).

Conclusions: Our findings suggest a potential risk of drug-induced myocarditis associated with various medications. Close monitoring for signs and symptoms of myocarditis is crucial, especially in patients with risk factors or those receiving these drugs. Further investigations are warranted to establish causality and identify risk factors.

Background: Thrombopoietin receptor agonists (TPO-RAs) are currently approved for the treatment of thrombocytopenia in different conditions. The relationship between TPO-RAs and thromboembolic events (TEEs) remains controversial.

Research design and methods: We extracted TPO-RAs adverse reaction reports after their marketing until now, using the FDA adverse event reporting system (FAERS). Positive signals were detected by reporting odds ratios (RORs). And the Weibull shape parameter test was utilized to analyze the time-to-onset profiles.

Result: Thromboembolic events accounted for 8.97% among TPO-RAs reports. Increased reporting of TEEs was related to TPO-RAs treatment compared with the entire FAERS database [ROR = 2.65 (2.56, 2.73)]. In addition, venous thrombotic events [ROR = 4.13 (3.92, 4.35)] were reported more frequently than arterial events ROR = 1.81 (1.7, 1.93)]. Age over 60 years [odds ratio (OR) = 1.10 (1.01, 1.20), p = 0.029] and weight over 80 kg [OR = 1.36 (1.17, 1.58), p < 0.001] of patients might have higher risk of TEEs during TPO-RAs therapy.

Conclusion: Evidence from the real world suggested that TPO-RAs were associated with higher incidence of TEEs, particularly venous thrombosis. The risk of TPO-RAs-associated TEEs mostly happened in the early stages of treatment and decreased over time.

Objective: To assess the efficacy and safety of aripiprazole, bromocriptine, and cabergoline in the treatment of hyperprolactinemia (HPRL) using network meta-analysis.

Method: We searched PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and China Biology Medicine disc (CBMdisc) for randomized controlled trials (RCTs). The quality of the included studies was assessed using the Cochrane risk-of-bias tool, and data were analyzed using RevMan 5.4, R 4.3.3, and Stata 17.

Results: 44 RCTs involving a total of 3886 patients were finally included. The results showed that at 12 week of treatment, cabergoline plus conventional therapy had optimal efficacy in reducing prolactin (PRL) levels. Cabergoline plus conventional therapy was most effective in reducing PRL levels in patients with non-drug-induced HPRL. Aripiprazole plus conventional therapy had optimal efficacy in reducing PRL levels in patients with antipsychotics-induced or antidepressant-induced HPRL. Bromocriptine was the most efficacious intervention in improving estrogen (E₂) levels.

Conclusion: Three dopamine receptor agonists (DAs) have different advantages in improving serum PRL and E₂ levels in HPRL patients.

Prospero id: CRD42024510695.

Introduction: Vanishing bile duct syndrome (VBDS) is a potentially fatal adverse reaction triggered by certain medications. The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and VBDS is based on case reports. We explored the reporting prevalence and evaluated the clinical features of NSAID-related VBDS.

Research design and methods: Adverse event reports of VBDS associated with NSAIDs from 2004 to 2023 in the FAERS database were retrieved, and disproportionality analyses were conducted to detect risk signals. Case reports from 2000 to 2023 on NSAID-induced VBDS were retrieved for retrospective analysis.

Results: We obtained 87 VBDS reports from the FAERS database. Ibuprofen had the greatest proportion of VBDS (63.2%), while loxoprofen had the highest positive signal value. Sixteen case reports showed evidence of VBDS, with 37.5% of children. The median age was 29 years; typical initial symptoms included rash (60.0%), jaundice (53.3%), fatigue/asthenia (33.3%), and SJS/TEN (53.3%). The median onset time of VBDS was 4 weeks. All cases had abnormal liver function tests, with the median level of TBIL being 20.0 mg/dl. The overall prognosis is poor, with 50% of patients achieving clinical remission.

Conclusion: Four NSAID agents had significant reporting associations with VBDS. Prescribers should be more aware of this risk and identify signs/symptoms earlier.

Background: CAR-T-associated neurotoxicity is extremely frequent with highly variable clinical presentation.

Research design and methods: Disproportionality analysis was conducted leveraging the FDA Adverse Event Reporting System (FAERS), covering the period from 1 January 2017, through 31 March 2023. The reporting odds ratio (ROR) and the information component (IC) were utilized to assess the adverse signals in total/individual CAR-T product. The lower limit of the ROR and IC 95% confidence interval (ROR₀₂₅ and IC₀₂₅) both exceeding threshold value (1 and 0, respectively) was considered a significant signal.

Results: Of the 60, 730 records associated with CAR-T, 11, 037 (18.17%) pertained to neurological events. Tisagenlecleucel exhibited the highest percentage of death (38.02%) and life-threatening (12.90%) outcomes. Notably, it also displayed the broadest distribution of neurotoxicity. Additionally, distinct adverse signals unique to individual CAR-T products were identified. For instance, paraparesis, cerebral hemorrhage, impaired pupillary reflex, Guillain-Barre syndrome, brain death following tisagenlecleucel; dysarthria, orthostatic hypotension, and spinal cord edema after axicabtagene; parkinsonism, Bell's palsy, and cranial nerve paralysis post ciltacabtagene.

Conclusions: Axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel exhibited increased odds of neurotoxicity, with some discrepancies in their characteristics, profiles, and severity.