Expert Opinion on Drug Safety最新文献

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: Tezepelumab is the first asthma biologic approved by the FDA that is not restricted by biomarker phenotypes. To date, there have been no studies reporting adverse events (AEs) associated with the real-world use of tezepelumab.

Research design and methods: This study included a comprehensive evaluation of AE reports related to tezepelumab since its approval (4th quarter of 2021 to 1st quarter of 2024) using the FAERS database, and compared with the currently reported clinical trial results (ClinicalTrials.gov).

Results: A total of 2153 reports of tezepelumab-related AEs were extracted. 256 preferred terms (PTs) of adverse reactions involving 27 system organ classes were identified. Significant AEs that were not reported on the drug label, such as 'dyspnea,' 'body temperature,' and 'tongue pruritus,' were reported. The median time to onset (TTO) of tezepelumab-related AEs was 35 days.The most frequent AEs in different sexes were 'arthralgia' and 'dyspnea,' with differences in signal strength ranking between the sexes.

Conclusions: This study represents the largest report to date on tezepelumab-related AEs, providing valuable insights into the potential side effects of tezepelumab. This work is crucial for the broader clinical application of this novel biologic and improving outcomes for patients with severe asthma.

Introduction: Atorvastatin, one of the most widely used drugs, has attracted controversy regarding its potential adverse reactions to acute kidney injury(AKI). This study aims to provide evidence in support of the safe use of atorvastatin.

Areas covered: Reports with atorvastatin as the primary suspect drug were extracted from the FDA Adverse Event Reporting System (FAERS) and categorized into five groups: general population, acute myocardial infarction (AMI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD). We conducted subgroup analyses by gender and age, using four standards-ROR, PRR, BCPNN, and EGBM-to perform disproportionality analysis and assess positive signals. Statistical analysis evaluated differences between the occurrence and non-occurrence of adverse drug reactions (ADRs), as well as differences between high and low induction time groups.

Expert opinion: In the general population, evidence for a positive AKI signal was insufficient. However, subgroup analysis showed risk in males and older individuals in AMI and IS populations, while younger age groups in T2DM showed positive signals. In the HLD population, evidence was insufficient across genders and ages. Atorvastatin is generally safe, but clinical vigilance for AKI is needed in T2DM, AMI, and IS populations, especially in those 65 and older.

Background: This study aimed to analyze adverse drug events (ADEs) of oseltamivir or baloxavir marboxil monotherapy using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, providing a valuable reference for clinical drug safety.

Research design and methods: FAERS data for oseltamivir and baloxavir marboxil from their market approval in the United States until the third quarter of 2023 were retrieved. Signal detection was performed using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods. ADEs were classified according to the System Organ Class (SOC) in the Medical Dictionary for Regulatory Activities (MedDRA) version 25.0.

Results: A total of 1,727 and 12,607 ADE reports were retrieved for baloxavir marboxil and oseltamivir, respectively, involving 17 and 26 SOC categories. Baloxavir marboxil demonstrated a strong association with ischemic colitis, melena, delirium febrile, enterocolitis, febrile convulsion, and altered state of consciousness. Oseltamivir exhibited a strong association with pathological personality, thinking abnormal, agitation, abnormal behavior, somnambulism, delirium febrile, and spinal cord hemorrhage.

Conclusions: When using oseltamivir and baloxavir marboxil clinically, attention should be paid not only to common ADEs but also to those not mentioned on the drug label.

Objective: This systematic review and meta-analysis aimed to identify and evaluate risk factors for bleeding in hospitalized patients receiving anticoagulation therapy.

Methods: Cochrane, Embase, and PubMed were searched from database inception until 20 November 2024, to identify studies exploring associations between risk factors and anticoagulation-related bleeding. Study quality was assessed using the PROBAST for risk assessment model studies and the QUIPS for prognostic factor studies. We rated the certainty of evidence for each factor using the GRADE framework. We calculated pooled odd ratios (ORs) with 95% Confidence interval [CI] using random-effects meta-analyses.

Results: This review included 29 studies, assessing 93 factors, 37 of which were associated with bleeding. We found high certainty evidence of an association between the bleeding risk and the following factors: gastrointestinal ulcers (OR 4.21, 95% CI 2.82-6.28), anemia (OR 3.24, 95% CI 2.08-5.06), medical procedures (OR 2.20, 95% CI 1.53-3.17), renal failure (OR 1.81, 95% CI 1.40-2.35), co-administration of antiplatelet agents (OR 1.78, 95% CI 1.48-2.14), concomitant use of bleeding-related drugs such as nonsteroidal anti-inflammatory drugs and corticosteroids (OR 2.67, 95% CI 2.13-3.33).

Conclusion: Our results highlight comorbidity and medication factors associated with in-hospital bleeding related to anticoagulants.

Study registration: PROSPERO CRD42025648123.

Objective: To analyze adverse events signals linked to dipyridamole using the FDA Adverse Event Reporting System, informing safety protocols for clinical use.

Methods: We retrospectively extracted AE reports linked to dipyridamole from the FAERS database, covering the period from Q1 2004 to Q4 2024. Signal detection was rigorously performed using a combination of statistical methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

Results: A total of 1235 patients experienced adverse events related to dipyridamole, with these events occurring 3371 times in total. The signal for Acquired von Willebrand's Disease emerged as particularly prominent, followed by Steal syndrome and Peritoneal hematoma. Additionally, signals indicating increased risks of pulmonary edema, myocardial ischemia and ischemic stroke were detected. Adverse events were common in patients aged ≥65 years, with the most prominent signal being Catheter site hematoma and Blood creatine phosphokinase MB increased. The combination of dipyridamole and other drugs was prone to bleeding adverse events, suggesting a multifaceted safety profile that warrants careful clinical consideration.

Conclusions: These findings underscore the need for tailored safety monitoring strategies and more nuanced risk-benefit assessments in the clinical use of dipyridamole.

Background: Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment but can induce thyroid dysfunction. While the incidence of ICI-induced thyroid dysfunction (ICI-TD) has been studied, the timing of onset, particularly in relation to sex differences, remains underexplored.

Research design and methods: We assessed time to onset of thyroid dysfunction caused by nivolumab, pembrolizumab, and ipilimumab using the Japanese Adverse Drug Event Report (JADER) database. Cases were identified using standardized MedDRA queries. Reporting odds ratios and 95% confidence intervals were calculated. Time-to-onset analysis used the Weibull shape parameter and Mann-Whitney U-test, stratified by sex.

Results: Among 914,713 reports, 2468 nivolumab, 3030 pembrolizumab, and 1457 ipilimumab cases of suspected ICI-TD were found. All ICIs detected positive signals. Median onset times for hyperthyroidism were 42, 33 and 44.5 days, for nivolumab, pembrolizumab, and ipilimumab, respectively; hypothyroidism onset times were 85, 60 and 65 days, respectively. Onset time was consistently shorter in females than males. The Weibull analysis indicated a wear-out failure type, except for pembrolizumab-induced hypothyroidism, which showed a random failure type.

Conclusions: ICI-TD occurs earlier in female patients. This finding highlights the need for sex-specific monitoring to optimize early detection and management of thyroid-related adverse events in patients receiving ICIs.

Introduction: The study aimed to comprehensively evaluate the role of direct oral anticoagulants (DOACs) combined with antiplatelet therapy (APT) in acute coronary syndrome (ACS) patients and those with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) or complicating ACS.

Methods: Data were pooled using the Mantel - Haenszel random-effect models. The risk ratio (RR) value and 95% confidence intervals (CI) calculated were applied to dichotomous outcomes.

Results: In 38,170 ACS patients from 11 studies, DOACs combined with APT significantly reduced major adverse cardiovascular events (MACEs), stent thrombosis (ST), ischemic stroke and all-cause death, accompanied by increased bleeding risks compared with control groups. Among 11,175 participants from 6 studies involving AF patients undergoing PCI or complicating ACS, DOACs plus APT markedly reduced bleeding risksin various definitions, with no significant difference in efficacy outcomes compared with control groups.

Conclusions: The combination of DOACs and APT requires a tailored approach. For ACS patients, therapy should center on balancing ischemic and bleeding risks, favoring those at high ischemic risk but low or manageable bleeding risk. In contrast, for AF patients undergoing PCI or complicating ACS, the regimen is aimed at risk minimization and is most suitable for patients in whom this is the primary concern.Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42025645639.

Introduction: This meta-analysis evaluated the efficacy and safety of naldemedine for treating opioid-induced constipation (OIC) in non-cancer patients, focusing on SBM, serious TEAEs, GI side effects, opioid withdrawal, and other adverse events (AEs).

Methods: A systematic review was conducted using PubMed, ScienceDirect, CINAHL, and the Cochrane Library. Two reviewers independently screened studies, extracted data, and assess methodological quality. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A random-effects model was applied to analyze outcomes using Review Manager 5.3.

Results: Eight RCTs from six studies were included, with 3879 patients in the intervention group and 3868 in the control group. Naldemedine significantly increased the incidence of serious TEAEs (RR = 1.07; 95% CI: 1.00-1.14, p < 0.05), drug-related adverse events (RR = 1.44, 95% CI: 1.26-1.65, p < 0.05), GI adverse events (RR = 1.61, 95% CI: 1.40-1.86, p < 0.0), and opioid withdrawal-related events (RR = 1.65, 95% CI: 1.42-1.91, p < 0.05). Specific AEs include abdominal pain (RR = 3.71, CI: 2.87-3.71, p < 0.01), nausea (RR = 1.51, CI: 1.38-1.65, p < 0.01), and diarrhea (RR = 2.57, CI: 2.08-3.16, p < 0.01) were also significantly higher in the naldemedine group.

Conclusions: Naldemedine 0.2 mg is effective for treating OIC in non-cancer patients and is generally well tolerated, with primarily mild-moderate AEs. Further studies should explore long-term safety and comparisons with other PAMORAs.This review was registered in the PROSPERO databases (CRD42023472575).

Objective: The study endeavors to elucidate AE signals associated with zanubrutinib data from the WHO-VigiAccess and FAERS databases. The aim is to furnish robust scientific evidence to inform clinical practice and regulatory decisions.

Methods: We meticulously extracted all AE breports tied to zanubrutinib from the both databases, encompassing the period from the drug's market introduction until 30 April 2024. Retrospective quantitative analysis employing ROR, PRR, and BCPNN methodologies were utilized to analysis.

Results: The investigation unveiled 1,304 reports from WHO-VigiAccess and 1,141 reports from FAERS related to zanubrutinib. Among the top 30 reported PTs in both databases, those not recorded in the drug label included pyrexia, dizziness, and death. In the FAERS database, signals for zanubrutinib were detected across 19 SOCs. Systems not covered in the drug label included reproductive system and breast disorders, metabolism and nutrition disorders, ear and labyrinth disorders, among others. Unmentioned signals included intestinal perforation, onychoclasis, night sweats, etc.

Conclusion: This study confirms common AEs of zanubrutinib and identifies new ones, highlighting the need for careful monitoring and personalized treatment. It also emphasizes the importance of ongoing drug safety surveillance and patient management to maximize therapeutic benefits and minimize risks.