Expert Opinion on Drug Safety最新文献

Background: The aim of this study was to explore the risk of severe cutaneous adverse reactions (SCARs) caused by different antifungal drugs in the real world.

Methods: We extracted the data from the FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2022 and performed disproportionality analyses to characterize the signal differences of antifungal agents-related SCARs.

Results: A total of 952 antifungals-related SCARs were identified. Antifungal drugs-related SCARs were more common in the 18-64 age group than other groups, and five agents were detected significant SCAR signals in this age group. Among these antifungals, fluconazole had the strongest associations with the SCARs, and showed significant SCAR signals at all age stages. Six antifungals showed a significant association with SCARs under disproportionality. The reporting odds ratios (RORs) and the 95% confidence intervals (95% CI) for six antifungals were as follows: fluconazole (9.50, 8.62-10.47), caspofungin (8.92, 7.29-10.91), itraconazole (3.48, 2.78-4.35), amphotericin B (2.73, 2.20-3.39), micafungin (2.62, 1.85-3.71) and voriconazole (2.50, 2.12-2.94).

Conclusions: The data mining of FAERS demonstrated that antifungal drugs were significantly associated with SCARs, which reminded clinicians to continue monitoring patients who are at risk of developing SCARs with the use of these drugs.

Background: Aducanumab, a monoclonal antibody, received approval for the treatment of Alzheimer's disease in 2021. However, it remains controversial over the security of this drug. In this study, aducanumab-related adverse events (AEs) were evaluated through data mining based on the FDA Adverse Event Reporting System (FAERS) database.

Research design and methods: The AE reports induced by aducanumab as the primary suspected drug were extracted from the FAERS database. The clinical characteristics of aducanumab-associated reports were analyzed. The potential new AE signals of aducanumab were explored using four disproportionality analysis methods. Furthermore, the difference in aducanumab-associated AE signals was investigated concerning sex, age, weight, dose, onset time, and continent.

Results: In total, 328 reports and 793 AEs associated with aducanumab were identified. Six new AEs were identified. No significant sex and weight difference in aducanumab-related signals was found. Notably, nervous system disorders, especially 'amyloid related imaging abnormality-edema/effusion' and 'amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits,' were more frequently to be reported within 121-240 days, particularly in Europe.

Conclusions: This study contributes real-world evidence regarding the safety of aducanumab.

Background: Polatuzumab vedotin is the first antibody-drug conjugate approved by the US Food and Drug Administration (FDA) for patients with diffuse large B-cell lymphoma. This study evaluated adverse events (AEs) associated with polatuzumab vedotin by data mining of the FDA Adverse Event Reporting System (FAERS).

Methods: This study included AEs registered in FAERS between 2019 Q2 and 2023 Q2. Four algorithms were used to quantify the signals of polatuzumab vedotin-associated AEs, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker.

Results: A total of 7,609,450 reports were collected from the FAERS database, and 1,388 reports of polatuzumab vedotin were identified as primary suspected AEs. Polatuzumab vedotin-associated AEs involved 26 organ systems. According to the four algorithms, 108 significant disproportionality AEs were retained simultaneously. Unexpected significant AEs included gastrointestinal hemorrhage, ileus, gastrointestinal perforation, cholecystitis, hypogammaglobulinemia, hepatitis B reactivation, hypercalcemia, hydronephrosis, cystitis hemorrhagic, interstitial lung disease, and thrombophlebitis. The median time to onset of polatuzumab vedotin-associated AEs was 20 (interquartile range 4-56) days.

Conclusions: Our study identified significant new AE signals for polatuzumab vedotin through real-world disproportionality analysis data and may provide additional evidence for risk identification of polatuzumab vedotin.

Background: Polymyxins have been regarded as last-line treatment for multidrug-resistant gram-negative bacterial infections. Nonetheless, concerns regarding toxicity persist. This study aimed to explore and compare potential adverse events (AEs) between colistin and polymyxin B (PMB).

Methods: Polymyxins-related AEs were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System between 2004 and 2022. Potential signals were estimated by the reporting odds ratio (ROR), and subgroup analyses were preformed to adjust for potential factors in AEs with significant disproportionality.

Results: Analysis of 3,915 records involving 718 patients revealed a higher disproportionality of renal and urinary disorders (ROR 1.62, 95% CI 1.01-2.59) and acute kidney injury (ROR 1.75, 95% CI 1.07-2.87) with colistin treatment. Conversely, colistin exhibited a lower risk for neurotoxicity (ROR 0.47, 95% CI 0.30-0.73). Seven cases of skin hyperpigmentation were reported with PMB, whereas none were reported with colistin. Over 80% of cases involving polymyxin-related AEs occurred during the first two weeks of therapies, with a median onset time of 4.5 days.

Conclusions: Patients received colistin displayed a higher potential risk of nephrotoxicity but a lower risk of neurotoxicity. Clinicians should be vigilant in monitoring the AEs of hyperpigmentation disorders induced by PMB.

Objective: Our objective was to develop a machine learning model capable of predicting irrational medical prescriptions precisely within orthopedic perioperative patients.

Methods: A dataset comprising 3047 instances of suspected irrational medication prescriptions was collected from a sample of 1318 orthopedic perioperative patients from April 2019 to March 2022. Four machine learning models were employed to forecast irrational prescriptions, following which, the performance of each model was meticulously assessed. Subsequently, a thorough variable importance analysis was conducted on the model that performed the best predictive capabilities. Thereafter, the efficacy of integrating this optimal model into the existing audit prescription process was rigorously evaluated.

Results: Of the models utilized in this study, the RF model yielded the highest AUC of 92%, whereas the NB model presented the lowest AUC of 68%. Also, the RF model boasted the most robust performance in terms of PPV, reaching 82.4%, and NPV, reaching 86.6%. The ANN and the XGBoost model were neck and neck, with the ANN slightly edging out with a higher PPV of 95.9%, while the XGBoost model boasted an impressive NPV of 98.2%. The RF model singled out the following five factors as the most influential in predicting irrational prescriptions: the type of drug, the type of surgery, the number of comorbidities, the date of surgery after hospitalization, as well as the associated hospital and drug costs.

Conclusion: The RF model showcased significantly high level of proficiency in predicting irrational prescriptions among orthopedic perioperative patients, outperforming other models by a considerable margin. It effectively enhanced the efficiency of pharmacist interventions, displaying outstanding performance in assisting pharmacists to intervene with irrational prescriptions.

Objective: The FDA Adverse Event Reporting System (FAERS) was used to mine and evaluate adverse events (AEs) associated with cyclin-dependent kinase (CDK) 4/6 inhibitors, thereby providing a reference for clinical rational drug use.

Methods: AE data related to CDK4/6 inhibitors from the first quarter of 2015 to the first quarter of 2023 were acquired from FAERS, while the signal mining was processed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method.

Results: The number of AE reports for CDK4/6 inhibitors was, respectively, 132,494 for palbociclib, 56,151 for ribociclib, and 7,014 for abemaciclib. The corresponding numbers of AE signals were 322,522, and 59, with the number of involved System Organ Class (SOC) being 23, 23, and 15, mainly involving blood and lymphatic system disorders, respiratory, thoracic and mediastinal disorders, hepatobiliary disorders, skin and subcutaneous tissue disorders, etc.

Conclusion: CDK4/6 inhibitors could lead to pulmonary toxicity, myelosuppression, skin reactions, etc. Special attention should be paid to abemaciclib for interstitial lung disease (ILD), erythema multiforme, and thrombosis risk; ribociclib for cardiac toxicity, hepatotoxicity, and musculoskeletal toxicity; palbociclib for neurocognitive impairment and osteonecrosis of the jaw.

Introduction: Statins are well established as the first-line treatment to reduce low-density-lipoprotein cholesterol (LDL-C) and cardiovascular (CV) events, but some patients are unable to tolerate effective doses or sometimes any dose of statins and alternative treatments may be required.

Areas covered: In this review we summarize the relevant published literature obtained from a PubMed search on the safety of statin alternatives for the treatment of hypercholesterolemia.

Expert opinion: The main alternatives to statins are ezetimibe, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab, alirocumab, and inclisiran, and the recently approved bempedoic acid. These have all shown an excellent safety profile and have not been associated with skeletal muscle symptoms or with increased risk of new onset diabetes and they have no major drug interactions. The injectable PCSK9 inhibitors are associated with a small increase in injection site reactions which are usually of mild or moderate intensity. Bempedoic acid is associated with a small increase in plasma uric acid and slightly increased frequency of episodes of gout in susceptible subjects. The cost and availability and the degree of lowering of LDL-C required are more likely to determine the choice of statin alternatives than the safety issues.

Introduction: Metformin has been part of treatment algorithms for type 2 diabetes mellitus (T2DM) for decades. While it has formal approval in the U.S.A. for treatment of T2DM, it is used off-label in gestational diabetes mellitus (GDM), polycystic ovarian syndrome (PCOS), and ovarian hyperstimulation prevention. Its role as an insulin sensitizer has made it an attractive therapeutic to address the insulin resistance seen in these syndromes. In 2022, the European Union approved metformin as the only oral antidiabetic medication for diabetes in pregnancy. While its safety and benefits for the mother are well documented, it does cross the placenta with plasma concentrations comparable between mother and child at delivery.

Areas covered: This special report will focus on major randomized control trials investigating metformin use in pregnancies impacted by PCOS, GDM, T2DM, and obesity and their offspring follow-up trials.

Expert opinion: For the mother, metformin can be beneficial, with reduction in insulin therapeutic burden, weight gain, hypoglycemia and in certain situations, pre-eclampsia. For the neonate, benefits may include reduction in hypoglycemia and no increased risk of congenital anomalies. It is the long-term data in the offspring that remains unknown with some areas of concerns (SGA, altered anthropometrics) requiring continued research.

Background: Isocitrate dehydrogenase (IDH) inhibitors hold promise for IDH-mutated cancer patients and demonstrated favorable clinical efficacy. Nonetheless, a comprehensive understanding of the associated toxicities of IDH inhibitors remains notably lacking.

Research design and methods: This pharmacovigilance analysis utilized the FDA Adverse Event Reporting System (FAERS) database to assess notable adverse events (AEs) attributed to IDH inhibitors (enasidenib and ivosidenib) from January 2018 to December 2023.

Results: In the FAERS database, 2,905 enasidenib-associated and 1,289 ivosidenib-related AEs records were identified, respectively. The toxicity profiles of IDH1 and IDH2 inhibitors exhibited notable similarities. The most commonly significant system-organ classes induced by IDH inhibitors encompassed general disorders and administration site conditions, investigations, gastrointestinal disorders, and infections and infestations. The most common AEs included nausea, fatigue, diarrhea, decreased appetite, decreased platelet count, fever, pneumonia, weakness, sepsis, constipation, vomiting, rash, and reduced hemoglobin levels. Notably, temporal analysis of AEs shows enasidenib and ivosidenib have median onset times of 137 and 75 days, with distinct initial peak frequencies.

Conclusion: The reversible nature of the toxicities associated with IDH inhibitors underscores their promise as a therapeutic agent with a favorable safety profile.

Background: Drug-induced delirium is known risk factors associated with increased morbidity and mortality in older patients. The objective was to evaluate the risk of drug-related delirium in older patients based on the FDA Adverse Event Reporting System (FAERS).

Research design and methods: Delirium reports in older patients (age ≥65) extracted from the FAERS database using Open Vigil 2.1. The reported odds ratio and the proportional reported ratio were calculated to detect the adverse reaction signal of delirium. Combined with published evidence, suspected drugs were categorized as known, possible, or new potential delirium-risk-increasing drugs.

Results: Of the 130,885 reports (including 28,850 delirium events and 1,857 drugs) analyzed for this study, 314 positive signal drugs were detected. Positive signal drugs are mainly concentrated on the drug of nervous system, cardiovascular system , alimentary tract and metabolism and anti-infectives for systemic use. Of the positive signal drugs, 26.11% (82/314) were known delirium-risk increasing drugs, 44.90% (141/314) were possible and 28.98% (91/314) were new potential.

Conclusion: Drug-induced delirium risk is prevalent in older patients, according to the FAERS. The risk level of drug-induced delirium should be taken into account to optimize drug therapy in clinical practice.