Expert Opinion on Drug Safety最新文献

Background: Previous studies have documented an increased risk of pulmonary embolism (PE) in patients with schizophrenia taking antipsychotics (APs). However, specific data from real-world studies remain limited. This study aims to investigate the potential relationship between APs and PE.

Research design and methods: In the Food and Drug Administration Adverse Event Reporting System (FAERS), from the first quarter of 2018 to the first quarter of 2023, all PE cases suspected of being induced by APs were collected for disproportionality analysis, and the reporting odds ratio (ROR) was used to evaluate associations. Mortality, life-threatening events, and hospitalizations were also analyzed for each APs.

Results: A total of 1,676 cases of PE related to APs were included. APs were significantly associated with PE (ROR 2.00, 1.91-2.10), including chlorpromazine (n = 41), haloperidol (n = 164), loxapine (n = 37), olanzapine (n = 461), paliperidone (n = 161), quetiapine (n = 526), risperidone (n = 274), aripiprazole (n = 254), and clozapine (n = 234). The median onset time of PE was 29 days. Among all cases, 347 (20.7%) resulted in death, with haloperidol (53.2%) having a higher mortality rate than other APs.

Conclusions: APs may increase the risk of PE in patients with schizophrenia.

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.

Background: The use of proteasome inhibitors (PIs), namely Bortezomib and Carfilzomib, revolutionized multiple myeloma (MM) treatment. Understanding their distinct adverse event (AE) profiles aids in tailored treatment plans.

Research design and methods: We analyzed FDA Adverse Event Reporting System (FAERS) data (Q1 2012-Q4 2023) for Bortezomib and Carfilzomib, utilizing reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN).

Results: FAERS yielded 19,720 Bortezomib and 12,252 Carfilzomib AE reports. Males aged 45-65 exhibited higher AE susceptibility. Common AE systems included Infections, Nervous System Disorders, Blood Disorders, General Disorders, Cardiac Disorders, and Renal Disorders. New Bortezomib signals were sepsis and colitis. Carfilzomib exhibited elevated cardiac and renal toxicity but reduced peripheral neuropathy and thrombocytopenia.

Conclusions: FAERS analysis revealed new AE signals (sepsis, colitis) for Bortezomib and highlighted Carfilzomib's heightened cardiac and renal risks compared to Bortezomib. Balancing PIs' benefits and risks is crucial for clinical decision-making.

Background: Teriparatide is widely used for osteoporosis treatment in various patients, but its safety profile is not fully documented. This study analyzes the FDA pharmacovigilance database to assess teriparatide's safety.

Research design and methods: Data from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2023 were extracted and analyzed for disproportionality between teriparatide and adverse effects (AE).

Results: A total of 66,991 AE reports identified teriparatide as the principal suspect medication, aggregating to 222,116 individual AEs. Notably, healthcare professionals authored 16.1% of these reports (n = 10,809), whereas consumers accounted for the majority with 81.3% (n = 54,474). Teriparatide revealed a marked association with an increased propensity for musculoskeletal and connective tissue disorders (ROR,3.95; 95% CI, 3.91-3.99) at the System Organ Class (SOC) level. Concurrently, 199 preferred terms (PTs) displayed significant disproportionality across all four employed algorithms.

Conclusions: Our study confirms several well-known adverse drug reactions and identifies potential safety issues associated with teriparatide treatment. This contributes to a deeper understanding of the complex relationship between adverse reactions and teriparatide. These findings emphasize the importance of continuous monitoring and ongoing surveillance to promptly identify and effectively manage adverse reactions, thereby enhancing overall patient safety and well-being.

Introduction: The rivastigmine transdermal patch was developed to provide similar efficacy to oral rivastigmine in the treatment of Alzheimer's disease (AD), but with improved tolerability.

Areas covered: Randomized clinical trials and observational studies reporting on the tolerability of the rivastigmine transdermal patch in patients with AD, identified through a systematic literature search.

Expert opinion: Rivastigmine was the first cholinesterase inhibitor for which a transdermal formulation was developed; consequently, there is a substantial body of evidence on its efficacy and tolerability. The incidence of gastrointestinal AEs is markedly reduced with the transdermal patch compared with oral rivastigmine, while the efficacy of the patch remains similar to that of the oral formulation. Application site reactions are generally mild and do not cause much discomfort for the patient, and the risk of can be reduced by simple measures such as site rotation and good skin care. Tolerability of the patch improves over time, including at the highest dose level. Overall, the available evidence supports transdermal rivastigmine being generally well tolerated at doses up to 13.3 mg/24 h in patients with AD.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are widely used, but may lead to significant serum creatinine elevation ( > 30%), posing a risk of acute kidney injury.

Research design and methods: A retrospective analysis was conducted using data from 3,720 hospitalized patients who received SGLT2i between 2014 and 2023. Patients were divided into two groups based on creatinine elevation ( > 30%). Univariate and multivariate logistic regression analyses were performed to identify risk factors, and a predictive model was constructed. The dataset of 1,040 patients from 2024 serves as validation data.

Results: Significant serum creatinine elevation ( > 30%) occurred in 6.67% of patients. Multivariate analysis identified nine risk factors: female sex, age ≥70 years, elevated admission serum creatinine, low admission plasma albumin, heart failure, and concomitant use of nephrotoxic antimicrobials, biologics, diuretics, or antiarrhythmic drugs. The predictive model demonstrated good discrimination (area under curve: 0.815) and calibration (p = 0.717), with consistent performance in the validation cohort (area under curve: 0.777).

Conclusions: This study developed a reliable predictive model, highlighting key risk factors. The model can assist clinicians in early identification and monitoring of patients at risk, potentially reducing adverse renal outcomes and hospital stays. Further prospective studies are needed to validate and refine the model.

Introduction: Monoclonal antibodies (mAbs) targeting CD20 used in patients with multiple sclerosis (MS) can cause hypogammaglobulinemia, increasing the risk of infections. We aim to identify the proportion of individuals developing these events during the treatment with an anti-CD20 mAb.

Methods: A systematic review of observational studies was conducted from 2014 to 2024. Studies involving patients with MS, receiving anti-CD20 mAbs, evaluating outcomes related to hypogammaglobulinemia and/or infections were included. A random effect meta-analysis approach was used.

Results: 55 articles were selected for meta-analysis, covering a population of 14,548 MS patients. Overall, rituximab exhibited a higher prevalence of hypogammaglobulinemia [11%; 95% Confidence Interval (CI): 0.08 to 0.15], infections of any grade (25%; 95%CI: 0.18 to 0.32), genito-urinary infections (9%;95%CI: 0.05 to 0.12), while ocrelizumab exhibited a higher prevalence of serious infections (6%; 95%CI: 0.03 to 0.09) and respiratory infections (12%; 95%CI: 0.07 to 0.17). The paucity of data for ofatumumab and ublituximab highlights a research gap. The proportion of these AEs increase with treatment duration. Substantial heterogeneity was identified in all analyses. The quality of included studies was mainly classified as poor.

Conclusions: Monitoring and educating patients on anti-CD20 mAb is fundamental to quickly identifying adverse events and minimizing clinical risks.

Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42024617575.

Introduction: Most of the new agents in cancer therapy (referred to as targeted therapies in the paper) come to the market with limited and preliminary data concerning activity and tolerance. Although better tolerated than classical chemotherapy, safety issues of targeted agents must not be underestimated.

Areas covered: The aim of this mini review is to present some pharmacological specifities of targeted anticancer agents and to examine tolerance challenges observed after approval through some examples. References were identified through searches of PubMed for articles published up to March 2025 using the term postmarketing safety AND anticancer agent. Relevant articles were also searched for in high impact journals and specialty journals.

Expert opinion: Considering the clinical immaturity of targeted agents at their launch, partly due to expedited approvals, the new mechanisms of cell killing and the novel technologies of manufacturing, the postmarketing safety surveillance is a critical feature to secure their use. Pharmacoepidemiologic studies based on electronic health-based data will help to identify emergent and late safety events and to investigate their etiology along with predisposition factors. Work is also needed to elucidate the sex differences in toxicity of targeted therapies and to harmonize withdrawal decisions of drug regulatory agencies for safety reasons.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are frequently linked to gastrointestinal immune-related adverse events, which can severely affect patient outcomes.

Research design and methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (2011-2024). Disproportionality analyses (ROR, PRR, BCPNN, MGPS) identified gastrointestinal adverse events (AEs) associated with ICIs across pan-cancer populations, while multivariable logistic regression and Bayesian network modeling were used to examine influencing factors.

Results: A total of 85 distinct gastrointestinal toxicities were identified and categorized as ICI-related gastrointestinal AEs (GI AEs). Substantial variation in ICI-related GI AE profiles was observed across different ICI regimens, with anti-CTLA-4 demonstrating the highest toxicity (ROR = 17.76 [16.88-18.68]). Logistic regression and Bayesian network analyses indicated that disease stage, concurrent targeted therapies, and ICI type significantly influenced the risk of developing ICI-related GI AEs. Patients with gastric variceal hemorrhage exhibited the highest mortality rate (63.64%).

Conclusions: Our pharmacovigilance analysis reveals a high risk of gastrointestinal adverse events with ICI therapy, especially anti-CTLA-4. Stage IV disease, concurrent targeted therapies, and anti-CTLA-4 therapy or combination therapy further increase this risk, highlighting the need for personalized treatment strategies.