UNASSIGNED: Chimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients\' T cells to target tumors. Although significant therapeutic benefits have been observed, life-threatening adverse pulmonary events have been reported.
UNASSIGNED: Using SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration\'s Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs).
UNASSIGNED: The FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30 days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%).
UNASSIGNED: This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers.

UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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: Nusinersen is the first drug for precise targeted therapy of spinal muscular atrophy, a rare disease that occurs in one of 10,000 to 20,000 live births. Therefore, thorough and comprehensive reports on the safety of nusinersen in large, real-world populations are necessary. This study aimed to mine the adverse event (AE) signals related to nusinersen through the Food and Drug Administration Adverse Event Reporting System (FAERS) database.
METHODS: We extracted reports of AEs with nusinersen as the primary suspect from FAERS between December 2016 and March 2023. Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) were used for AE signal detection.
RESULTS: We extracted a total of 4807 suspected AE cases with nusinersen as the primary suspect from the FAERS database. Among them, 106 positive signals were obtained using the ROR and BCPNN. The highest frequency reported systemic organ class was general disorders and administration site conditions. Common clinical AEs of nusinersen were detected in the FAERS database, such as pneumonia, vomiting, back pain, headache, pyrexia, and post-lumbar puncture syndrome. In addition, we identified potential unexpected serious AEs through disproportionality analysis, including sepsis, seizure, epilepsy, brain injury, cardiorespiratory arrest, and cardiac arrest.
CONCLUSIONS: Analyzing large amounts of real-world data from the FAERS database, we identified potential new AEs of nusinersen by disproportionate analysis. It is advantageous for health care professionals and pharmacists to concentrate on effectively managing high-risk AEs of nusinersen, improve medication levels in clinical settings, and uphold patient medication safety.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified. Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14-90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78-6.02] vs. ROR 4.19 [95% CI, 3.56-4.91], p = 0.0147). Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.

UNASSIGNED: The purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.
UNASSIGNED: This study extracted reports received by the FAERS database from the first quarter of 2018 to the third quarter of 2023 for descriptive analysis and disproportionality analysis. Safety signal mining was conducted at the Preferred Term (PT) level and the System Organ Class (SOC) level using reporting odds ratio (ROR). The characteristics of the time-to-onset curves were analyzed using the Weibull Shape Parameter (WSP). The cumulative incidence of TTR inhibitors was evaluated using the Kaplan-Meier method. Subgroup analyses were conducted based on whether the reporter was a medical professional.
UNASSIGNED: A total of 3,459 reports of adverse events (AEs) caused by TTR inhibitors as the primary suspect (PS) drug were extracted. The top three reported AEs for patisiran were fatigue, asthenia, and fall, with the most unexpectedly strong association being nonspecific reaction. The top three reported AEs for vutrisiran were fall, pain in extremity and malaise, with the most unexpectedly strong association being subdural haematoma. The top three reported AEs for inotersen were platelet count decreased, blood creatinine increased, and fatigue, with the most unexpectedly strong association being blood albumin decreased. Vitamin A decreased, arthralgia, and dyspnea were the same AEs mentioned in the drug labels of all three drugs, while malaise and asthenia were the same unexpected significant signals. This study offers evidence of the variability in the onset time characteristics of AEs associated with TTR inhibitors, as well as evidence of differences in adverse event reporting between medical professionals and non-medical professionals.
UNASSIGNED: In summary, we compared the similarities and differences in drug safety of three TTR inhibitors in the real world using the FAERS database. The results indicate that not only do these three drugs share common AEs, but they also exhibit differences in drug safety profiles. This study contributes to enhancing the understanding of medical professionals regarding the safety of TTR inhibitors.

UNASSIGNED: Our study aims to characterize the ocular safety profiles of phosphodiesterase type 5 (PDE5) inhibitors and explore the differences among different PDE5 inhibitors.
UNASSIGNED: We analyzed reports on ocular adverse events associated with sildenafil, vardenafil and tadalafil submitted to the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the first quarter of 2023. Disproportionality analysis was conducted to evaluate reporting risk profiles.
UNASSIGNED: Among 61,211 reports qualifying for analysis, 5,127 involved sildenafil, 832 vardenafil, and 3,733 tadalafil. All PDE5 inhibitors showed increased reporting odds ratios (ROR) for ocular adverse events, with vardenafil highest (ROR 4.47) followed by sildenafil and tadalafil. Key ocular adverse events included cyanopsia, optic ischemic neuropathy, visual field defects, unilateral blindness and blindness. Sildenafil showed the highest disproportionality for cyanopsia (ROR 1148.11) while vardenafil and tadalafil showed the highest disproportionality for optic ischemic neuropathy. Time-to-onset analysis also revealed significant differences, with sildenafil having a later median time-to-onset compared to vardenafil and tadalafil.
UNASSIGNED: This comprehensive pharmacovigilance study reveals distinct patterns of ocular adverse events associated with PDE5 inhibitors. These findings contribute to a better understanding of the safety profiles of PDE5 inhibitors and may guide healthcare professionals in clinical decision-making.

Niraparib plays a crucial role in the treatment of ovarian cancer. A comprehensive understanding of the incidence and risk of hypertension associated with niraparib would be of vital importance to healthcare practitioners.
In this study, an observational, retrospective, pharmacovigilance study was conducted based on the FDA Adverse Event Reporting System (FAERS) database. Cases of hypertension related to niraparib were extracted for disproportionality analysis from the first quarter (Q1) of 2017 to Q1 of 2023. Moreover, a separate meta-analysis was performed using the randomized controlled trials (RCTs) on niraparib for cancer treatment published in PubMed, Embase, and Web of Science from inception to May 31st, 2023. The primary outcomes were the incidence and risk of hypertension associated with niraparib.
In the FAERS, 1196 hypertension cases were found to be related to niraparib treatment. Notably, niraparib exhibited the highest level of disproportionality, as indicated by a reporting odds ratio (ROR) of 2.85 (95% CI, 2.69-3.01), suggesting a greater likelihood of causing hypertension compared to other poly-ADP-ribose polymerase (PARP) inhibitors (P < 0.01). Our safety meta-analysis included five pivotal RCTs of niraparib that reported hypertension. In comparison to placebo treatment, the meta-analysis demonstrated a significant increase in the risk of hypertension with niraparib (OR 2.84 [95% CI, 2.17-3.72], P < 0.01), with no heterogeneity observed among the studies (I2 = 0%, χ2 = 2.02, P = 0.73). The incidence of niraparib-induced hypertension was determined to be 16.9% (95% CI, 14.9-18.9; I2 = 34%).
These findings suggest that hypertension is a distinctive adverse event associated with niraparib compared to other PARP inhibitors. Niraparib significantly increases the risk of hypertension that needs early recognition and management in clinical medication.

Recent reports of individuals experiencing suicidal and/or self-injurious behaviors while using liraglutide and semaglutide have heightened the concerns regarding neuropsychiatric safety of Glucagon-like peptide-1 agonists (GLP-1RAs). As real-world evidence is very limited, we explored the association between GLP-1RA and suicide/self-injury by mining the FDA Adverse Event Reporting System (FAERS) database.
The FAERS database was queried from 2005 Q2 to 2023 Q2. The Reporting Odds Ratio (ROR) and Empirical Bayes Geometric Mean (EBGM) were used to conduct the disproportionality analysis.
A total of 534 GLP-1RA-associated suicide/self-injury cases were reported in the FAERS during the study period. GLP-1RA did not cause a disproportionate increase in overall suicidal and self-injurious cases (ROR: 0.16, 95%CI 0.15-0.18, P < 0.001; EBGM05: 0.15). Stratified analyses found no safety signal of suicide/injury for GLP-1RA in both females and males. The ROR for suicide/self-injury with GLP-1RA was slightly elevated (ROR: 2.50, 95%CI 1.02-6.13, P = 0.05) in children, while the EBGM05 was < 2 in this population. No significant signal value was observed in other age groups. No over-reporting of suicide/self-injury was identified for GLP-1RA before or after the COVID-19 pandemic outbreak.
The cases of suicide or self-injury reported to FAERS do not indicate any overall safety signal attributable to GLP-1RA at this time. Subgroup analysis revealed a marginal elevation of ROR for suicide and self-injury with GLP-1RA in children, but no safety signal was detected by EBGM05 in this population. Further large-scale prospective investigations are still warranted to further confirm this finding.

Vancomycin and linezolid are first-line drugs used for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin is well known as the best alternative drug when linezolid-induced thrombocytopenia occurs. However, several cases with vancomycin-induced thrombocytopenia, especially with bleeding complications, have been reported recently, which has attracted attention. The objective of this study is to assess the potential relevance between vancomycin and bleeding complications in thrombocytopenia.
This is a real-world pharmacovigilance study conducted in October 2022 using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We performed a disproportional analysis to assess the risk of bleeding complications in vancomycin-induced thrombocytopenia by calculating reporting odds ratios (RORs) and information components (ICs), with a weak signal defined as a lower limit of the IC 95% CI of 0 to 1.5, a middle signal defined as a lower limit of the IC 95% CI of 1.5 to 3.0, and a strong signal defined as a lower limit of the IC 95% CI of >3.0.
There were 21,854 cases in the FAERS database that listed vancomycin as a suspected drug from quarter 1 of 2004 to quarter 2 of 2022. There were 800 cases of vancomycin-induced thrombocytopenia and 125 cases of bleeding complications in vancomycin-induced thrombocytopenia. Teicoplanin, tigecycline, and vancomycin (3 middle signals) were sequentially less associated with thrombocytopenia than linezolid (strong signal). However, bleeding complications in thrombocytopenia were significant associated with vancomycin (ROR = 9.641; 95% CI, 8.105-11.468; IC = 3.184; 95% CI, 2.929-3.440 [middle signal]), followed by linezolid (ROR = 9.350; 95% CI, 7.318-11.947; IC = 3.106; 95% CI, 2.745-3.466 [middle signal]), teicoplanin (ROR = 6.399; 95% CI, 2.869-14.272; IC = 2.059; 95% CI, 0.881-3.283 [weak signal]), and daptomycin (ROR = 2.784; 95% CI, 1.496-5.180; IC = 1.287; 95% CI, 0.374-2.201 [weak signal]). Tigecycline and daptomycin were the least likely anti-MRSA drug to cause thrombocytopenia (middle signal and weak signal, respectively) and bleeding complications in thrombocytopenia (no signal and weak signal, respectively). Middle signals of bleeding complication in vancomycin-induced thrombocytopenia were found in all group except those <45 to ≥80 years of age (weak signal).
Bleeding complications in thrombocytopenia were significantly associated with vancomycin use, and the risk was highest among all the anti-MRSA drugs. Physicians should be aware of this possible serious adverse reaction.

UNASSIGNED: We analyze and identify the signals of gender differences in adverse events (ADEs) related to Osimertinib and provide reference for clinical implementation of individualized drug use.
UNASSIGNED: ADE reports of Osimertinib received from FAERS database from the first quarter of 2016 to the fourth quarter of 2022 were extracted. Reporting odds ratio (ROR) data analysis strategy was used for mining of signal strength that represents gender differences in ADEs related to Osimertinib.
UNASSIGNED: The number of Osimertinib ADE reports included in the analysis was 7968 in females and 7570 in males, respectively. According to ROR, men were more likely to develop pneumonia aspiration, lung infection, interstitial lung disease, pulmonary toxicity, dyspnea, ventricular extrasystoles, and pulmonary thrombosis, while women were more likely to develop cardiac failure congestive, stomatitis, diarrhea, muscle spasms, nail disorder, onycholysis, skin disorder, dry skin, and rash.
UNASSIGNED: Gender differences existed in ADE signals related to Osimertinib. The higher risk of ADEs in male patients was lung diseases that seem more serious than those nail toxicities or skin problems that occurred in female patients. In order to ensure the safety of medication, we should be alert to the differences between different genders and take corresponding preventive measures to reduce the occurrence of serious ADEs.