Expert Opinion on Drug Safety最新文献

Background: Vancomycin-induced acute kidney injury (VI-AKI) is one of its serious adverse reactions. The purpose of this study is to discuss the risk factors for VI-AKI in overweight patients and construct a clinical prediction model based on the results of the analysis.

Methods: Multivariable logistic regression analysis was used to identify risk factors for VI-AKI and constructed nomogram models. The performance of the nomogram was evaluated based on the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA).

Result: Cancer (OR 4.186, 95% CI 1.473-11.896), vancomycin trough concentration >20.0 μg/mL (OR 6.251, 95% CI 2.275-17.180), concomitant furosemide (OR 2.722, 95% CI 1.071-6.919) and vasoactive agent (OR 2.824, 95% CI 1.086-7.340) were independent risk factors for VI-AKI. The AUC of the nomogram validation cohorts were 0.807 (95% CI 0.785-0.846). The calibration curve revealed that the predicted outcome was in agreement with the actual observations. Finally, the DCA curves showed that the nomogram had a good clinical applicability value.

Conclusion: There are four independent risk factors for the occurrence of VI-AKI in overweight patients, and the nomogram prediction model has good predictive ability, which can provide reference for clinical decision-making.

Background: Sugammadex is a novel agent that reverses neuromuscular blockade during general anesthesia. Recent case reports have raised concerns regarding potential cardiac adverse events (CAEs). However, no large-scale real-world studies have yet evaluated the potential link between sugammadex and CAEs.

Research design and methods: Data from the FDA Adverse Event Reporting System were obtained. The association between sugammadex and CAE was evaluated using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. Serious outcomes resulting from sugammadex-related CAEs were assessed, and complications associated with CAEs were evaluated.

Results: Nineteen CAEs were identified and classified into two categories: cardiac arrhythmias and coronary artery disorders. The most frequent CAEs were bradycardia (n = 202), cardiac arrest (n = 119), tachycardia (n = 30), and Kounis syndrome (n = 22). Subgroup analysis based on age, sex, and weight revealed parallel findings. The CAEs most likely to result in serious consequences were pulseless electrical activity and cardiac arrest. The most common concurrent adverse effects with CAEs were hypotension (n = 51), anaphylactic reactions (n = 46), and anaphylactic shock (n = 23).

Conclusion: This study suggests a potential link between sugammadex and CAEs, highlighting the need for careful monitoring and personalized risk assessment, especially in patients with cardiovascular risk factors.

Background: Angiotensin receptor blockers (ARBs) are widely used for treating hypertension and heart failure. Angioedema has been reported as a controversial adverse effect of ARBs and the evidence on individual ARB risks is limited. This study aimed to assess signals of angioedema with different ARBs using the US FDA Adverse Event Reporting System (AERS) database.

Research design and methods: Reports of angioedema from 2004 to 2024 in AERS with an ARB as the primary suspect were extracted using Medical Dictionary for Regulatory Activities queries. Disproportionality analyses including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker were conducted to identify safety signals for individual ARBs.

Results: A total of 3,683 unique reports met the selection criteria. Irbesartan and losartan generated signals in all statistical measures, followed by telmisartan and candesartan in some measures. Valsartan had the highest report count. Most reports reported hospitalization, prolonged hospitalization or life-threatening outcomes consequent to angioedema.

Conclusion: This pharmacovigilance study using AERS highlights potential higher risks of angioedema with losartan and irbesartan compared to other ARBs, warranting validation through prospective epidemiological studies to characterize individual ARB safety profiles.

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.