Bruton\'s tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of B-cell lymphomas. However, safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy. A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment. A multidisciplinary consensus working group was established, comprising 35 members from the fields of hematology, cardiovascular disease, cardio-oncology, clinical pharmacy, and evidence-based medicine. This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method. The Joanna Briggs Institute Critical Appraisal (JBI) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used to rate the quality of evidence and grade the strength of recommendations, respectively. This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains, including the management of common adverse drug events such as bleeding, cardiovascular events, and hematological toxicity, as well as the management of drug-drug interactions and guidance for special populations. This multidisciplinary expert consensus could contribute to promoting a multi-dimensional, comprehensive and standardized management of BTKis.

UNASSIGNED: Compartment syndrome is an uncommon but life-threatening condition. No study has comprehensively compared compartment syndrome (CS) association with available drugs. The objective of this study was to estimate the association between CS and drugs using the FDA Adverse Event Report System (FAERS).
UNASSIGNED: FAERS reports from the first quarter of 2004 to the third quarter of 2023 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CS cases. Reporting odds ratio (ROR), corresponding to 95% confidence intervals (95% CI) were calculated to detect a positive signal.
UNASSIGNED: A total of 2197 reports were considered in the study after the inclusion criteria were applied. Totally 100 drugs were found to be associated with CS. The median time for drug-associated CS was 45 days.
UNASSIGNED: By analyzing the FAERS database, the study revealed that certain drugs are significantly associated with compartment syndrome. Further studies are needed to verify whether these drugs are associated with such a risk.

BACKGROUND: Bempedoic acid exhibits promising potential in hyperlipidemia therapy and preventing cardiovascular events. However, investigations into its adverse drug reactions remain scant. This study seeks to utilize data mining techniques with the FDA Adverse Event Reporting System (FAERS) database to assess adverse drug events (ADEs) linked to bempedoic acid.
METHODS: Based on the drug\'s market release timeline, we extracted data from the FAERS database covering the fourth quarter of 2020 through the fourth quarter of 2023 for disproportionality analysis.
RESULTS: This study gathered a total of 5,797,543 adverse event case reports, of which 735 were linked to bempedoic acid. These reports covered 19 System Organ Classes (SOCs) and 22 Preferred Terms (PTs). Predominantly, the musculoskeletal and nervous systems were implicated in these adverse events. By conducting PT-level screening, various signals for ADEs were detected, including myalgia (ROR 30.33, PRR 28.51, IC 4.83, EBGM 28.47), arthralgia (n = 34, ROR 6.34, PRR 6.09, IC 2.61, EBGM 6.09), tendon disorders (ROR 99.57, PRR 98.75, IC 6.62, EBGM 98.28), and dizziness (ROR 3.18, PRR 3.13, IC 1.65, EBGM 3.13). Particularly noteworthy was the hypertensive crisis (ROR 28.63, PRR 28.51, IC 4.83, EBGM 28.47), which exhibited a robust signal strength, an observation previously unreported in clinical studies and drug labeling.
CONCLUSIONS: While our results are largely consistent with the drug\'s specifications, several new adverse reaction signals, such as hypertensive crisis, have not been previously documented. Therefore, further investigations are necessary to assess these unlabeled adverse reactions, offering crucial support for the clinical utilization of bempedoic acid.

BACKGROUND: Adverse drug events (ADEs) represent challenges affecting Africa\'s healthcare systems owing to the increased healthcare expenditure and negative health outcomes of ADEs.
OBJECTIVE: We aimed to systematically review published studies on ADEs and synthesize the existing evidence of ADE prevalence in Africa.
METHODS: Studies reporting on ADE occurrence in African settings and published from Jan 1, 2000 to Oct 1, 2023 were identified by searching PubMed, EBSCO, Science Direct, and Web of Science. Studies that either articulately investigated ADEs caused by clinical condition (such as HIV patients) or ADEs caused by exposure to specific drug(s) (such as antibiotics) were considered specific and the remaining were general. Grouped ADE prevalence rates were described using median and interquartile range (IQR). PROSPERO registration (CRD42022374095).
RESULTS: We included 78 observational studies from 15 African countries that investigated the prevalence of ADEs leading to hospital admissions (17 studies), developed during hospitalizations (30 studies), and captured in the outpatient departments (38 studies) or communities (4 studies). Twelve studies included multiple settings. The median prevalence of ADE during hospitalization was 7.8% (IQR: 4.2-21.4%) and 74.2% (IQR: 54.1-90.7%) in general and specific patients, respectively. The ADE-related fatality rate was 0.1% and 1.3% in general and specific patients. The overall median prevalence of ADEs leading to hospital admissions was 6.0% (IQR: 1.5-9.0%); in general, patients and the median prevalence of ADEs in the outpatient and community settings were 22.9% (IQR: 14.6-56.1%) and 32.6% (IQR: 26.0-41.3%), respectively, with a median of 43.5% (IQR: 16.3-59.0%) and 12.4% (IQR: 7.1-28.1%) of ADEs being preventable in general and specific patients, respectively.
CONCLUSIONS: The prevalence of ADEs was significant in both hospital and community settings in Africa. A high ADE prevalence was observed in specific patients, emphasizing important areas for improvement, particularly in at-risk patient groups (e.g., pediatrics, HIV, and TB patients) in various settings. Due to limited studies conducted in the community setting, future research in this setting is encouraged.

UNASSIGNED: In clinical practice, observations have been made regarding bladder and urethral symptoms (BUS), notably urinary frequency and urgency, among patients prescribed the anti-seizure medication (ASM) lacosamide. However, the precise association between ASMs and BUS events in real-world settings remains elusive.
UNASSIGNED: Data from the FDA Adverse Event Reporting System (FAERS) database were employed and the analysis focused on ASMs-associated BUS events utilizing disproportionality analysis methods, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). Furthermore, co-administration, time to onset of ASMs-associated BUS events, and severity assessments were conducted.
UNASSIGNED: Several ASMs demonstrated statistically meaningful associations with BUS signals, notably ezogabine, valproic acid/valproate sodium, and clorazepate (p < 0.05). And ASMs-associated BUS events predominantly occurred within the first week and persisted for more than 180 days afterward. Diazepam, gabapentin, and brivaracetam exhibited distinct risk profiles for severe BUS events compared to valproic acid/sodium valproate (p < 0.05). And the nomogram constructed in this study exhibited robust predictive performance.
UNASSIGNED: This study yields valuable insights into the association between ASMs and BUS events, but several limitations warrant consideration. Nonetheless, these findings emphasize the significance of vigilance and proactive management of ASMs-associated BUS events.

UNASSIGNED: This study aims to analyze adverse drug events (ADEs) associated with cenobamate from the FAERS database, covering the third quarter of 2020 to the second quarter of 2023.
UNASSIGNED: Data related to cenobamate-associated ADEs from the third quarter of 2020 to the second quarter of 2023 were collected. After standardizing the data, various signal quantification techniques, including ROR, MHRA, BCPNN, and MGPS, were employed for analysis.
UNASSIGNED: Among 2535 ADE reports where cenobamate was the primary suspected drug, 94 adverse reactions involving 11 different System Organ Class (SOC) categories were identified through the application of four signal quantification techniques. More specifically, neurological disorders and injuries resultant from complications are frequent adverse reactions associated with cenobamate.
UNASSIGNED: Our research findings align with established results, affirming the favorable safety profile of cenobamate. Effective prevention of adverse reactions induced by cenobamate can be achieved through the establishment of efficient blood concentration monitoring and dose adjustments.

BACKGROUND: Developments in anesthetic pharmacology have been aiming at minimizing physiological disturbance in addition to maintaining and improving titrateability, recovery profile, and patient experience. Remimazolam, a GABAAlpha receptor agonist, is a new intravenous anesthetic agent which has recently been approved for use. This analysis aimed to systematically compare the adverse drug events reported with the newly approved remimazolam in comparison to propofol for general anesthesia (GA) in patients undergoing surgery.
METHODS: Electronic databases were searched from 15 May to 20 December 2023 for relevant publications which compared the outcomes reported with the newly approved remimazolam versus propofol in patients undergoing surgery. Relevant reported adverse drug events were the endpoints of this study. The statistical analysis was carried out using the latest version of the RevMan software. Data analysis was represented by risk ratio (RR) with 95% confidence intervals (CI).
RESULTS: Sixteen studies with a total number of 1897 participants were included in this analysis; 1104 participants received remimazolam and 793 participants received propofol. The risks for hypotension (RR 0.50, 95% CI 0.43-0.58; P = 0.00001), hypoxemia (RR 0.43, 95% CI 0.19-0.99; P = 0.05), bradycardia (RR 0.53, 95% CI 0.36-0.78; P = 0.001), pain at injection site (RR 0.07, 95% CI 0.01-0.56; P = 0.01), and total adverse events (RR 0.33, 95% CI 0.24-0.47; P = 0.00001) were significantly lower with remimazolam. However, no significant differences were observed in terms of postoperative nausea and vomiting (RR 0.98, 95% CI 0.66-1.46; P = 0.93), dizziness (RR 0.42, 95% CI 0.11-1.57; P = 0.20), psychiatric symptoms (RR 1.09, 95% CI 0.45-2.67; P = 0.85), and respiratory depression (RR 0.81, 95% CI 0.24-2.76; P = 0.74).
CONCLUSIONS: Our current analysis showed that the newly approved remimazolam was apparently associated with significantly fewer adverse drug events in comparison to propofol for GA in patients undergoing surgery. Therefore, this new drug should be further studied and more research with larger population sizes should be carried out to confirm this hypothesis.

Aim and background: This study attempted to identify similarities and differences in adverse events (AEs) between human epidermal growth factor receptor 2 (HER2) inhibitors, especially those related to hemorrhagic events and nervous system disorders. Methods: This study summarized the types, frequencies, and system organ classes (SOCs) of AEs of HER2 inhibitors. The US Food and Drug Administration Adverse Event Reporting System (FAERS) data from January 2004 through March 2022 was collected and analyzed. Disproportionality analyses were conducted to detect AEs signals for every HER2 inhibitor. The chi-square test, Wilcoxon test, and descriptive analysis were used to compare the differences of AEs for specific SOCs or drugs. Results: A total of 47,899 AE reports were obtained for eight HER2 inhibitors. Trastuzumab-related AEs were reported in the highest number and combination of regimens. In monotherapy, trastuzumab had the highest reported rate of cardiac disorders-related AEs (24.0%). However, small-molecule drugs exceeded other drugs in the reported rates of AEs related to gastrointestinal disorders, metabolism and nutrition disorders. The highest reported rates of respiratory disorders (47.3%) and hematologic disorders (22.4%) were associated with treatment with trastuzumab deruxtecan (T-DXd). Patients treated with trastuzumab emtansine (TDM-1) had the highest reported rate (7.28%) of hemorrhagic events, especially intracranial haemorrhage events. In addition, patients treated with TDM-1 with concomitant thrombocytopenia were likely to experience hemorrhagic events compared to other HER2 inhibitors (p < 0.001). The median time to onset of intracranial haemorrhage associated with trastuzumab (0.5 months) and TDM-1 (0.75 months) was short. However, there was no significant difference in median time to onset intracranial haemorrhage between patients in different age groups or with different outcomes. Disproportionality analysis results reveal that cerebral haemorrhage is a positive signal associated with T-DXd and TDM-1. In addition, tucatinib was the drug with the highest rate of reported nervous system disorders (31.38%). Memory impairment (83 cases) is a positive signal for tucatinib. Conclusion: The types and reporting rates of AEs associated with different HER2 inhibitors vary across multiple systems. In addition, hemorrhagic events concomitant with TDM-1 treatment and nervous system disorders concomitant with tucatinib treatment may be worthy of attention.

UNASSIGNED: Despite potential benefits and widespread prescription of aspirin among chronic obstructive pulmonary disease (COPD) patients, limited research has investigated its adverse effects (AEs) in COPD population.
UNASSIGNED: We conducted a retrospective analysis of adverse drug events (ADEs) reported in the US Food and Drug Administration Adverse Event Reporting System (FAERS) between Q1 2013 and Q2 2022. COPD patients were categorized into two groups based on aspirin use. ADEs related to aspirin use were identified using combined reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) methods.
UNASSIGNED: A total of 56,660 ADEs reports associated with COPD patients were included in the study. Among these reports, 144 adverse events were linked to aspirin use in COPD patients, including fatigue (4.12%), diarrhea (3.13%), dyspnea exertional (2.03%), rhinorrhea (1.99%), weight increased (1.89%) and vomiting (1.84%), muscle spasms (1.79%), cardiac disorder (1.74%), heart rate increased (1.69%) and peripheral swelling (1.59%). Subgroup analysis indicates that age and gender might affect the AEs frequency in COPD patients using aspirin.
UNASSIGNED: Our findings identify 10 most frequently reported ADEs associated with aspirin use in COPD patients, thus offer valuable insights into the AEs of aspirin for safer clinical utilization in COPD management.

OBJECTIVE: The association between proton-pump inhibitors (PPIs) and rhabdomyolysis were unclear. The aim of this study was to explore and systematically analyze the potential link between five PPIs and the rhabdomyolysis events using the FDA Adverse Event Reporting System (FAERS) database.
METHODS: Suspected rhabdomyolysis events associated with PPIs were identified by data mining with the reporting odds ratio (ROR), proportional reporting ratio (PRR), the information component (IC), and Empirical Bayes Geometric Mean (EBGM). Demographic information, drug administration, and outcomes of PPI-induced rhabdomyolysis events were also analyzed.
RESULTS: There were 3311 reports associated with PPI-induced rhabdomyolysis that were identified. After removing duplicates, 1899 cases were determined to contain complete patient demographic data. The average age was 65 ± 18 year and 57% were male. Omeprazole and pantoprazole had the same largest percentage of reports. Lansoprazole had the highest ROR index of 12.67, followed by esomeprazole (11.18), omeprazole (10.27), rabeprazole (10.06), and pantoprazole (9.24). PRR, IC, and EBGM showed similar patterns. This suggested that lansoprazole exhibited the strongest correlation with rhabdomyolysis. In rhabdomyolysis events, PPIs were mainly \"concomitant\" (>60%), and only a few cases were \"primary suspects\" (<15%). Rabeprazole showed the lowest death rate while lansoprazole showed the highest.
CONCLUSIONS: The study suggested that significant rhabdomyolysis signals were associated with PPIs. Further research should be performed in drug safety evaluation for a more comprehensive association.