UNASSIGNED: This study aims to evaluate the relationship between voriconazole (VRC) and central nervous system (CNS) toxicity based on the real world data.
UNASSIGNED: The reports of FAERS from January 2004 to March 2022 were included in our study. The CNS toxicity events were identified by using Medical Dictionary for Regulatory Activities terms. Reporting odds ratios corresponding 95% confidence intervals were employed to quantify the signals of VRC-associated CNS events.
UNASSIGNED: The overall RORs (95%CI) for psychiatric disorders, nervous system disorders and eye disorders were 1.84 (1.70, 2.00), 1.09 (1.01, 1.18) and 3.84 (3.48, 4.23), respectively (p＜0.05). The median time to the CNS events of VRC was 1(IQR 0-5) day. Top six signals were macular opacity, chloropsia, scintillating scotoma, toxic optic neuropathy, corneal bleeding and dyschromatopsia, all of them grouped as eye disorders. Compared with itraconazole, fluconazole, posaconazole and isavuconazole, VRC shows significantly relationship and higher incidence rate of psychiatric disorders, nervous system disorders and eye disorders, respectively (p＜0.05).
UNASSIGNED: VRC was significantly association with the CNS toxicity. Dosing adjustment, model based individualized treatment project and the therapeutic drug monitoring guided individualized medication regime could be the good strategies for the efficacy improving and the adverse events reducing of VRC.

UNASSIGNED: Sunitinib is approved for the treatment of metastatic renal cell carcinoma (mRCC), imatinib-resistant gastrointestinal stromal tumors (GIST), and advanced pancreatic neuroendocrine tumors (PNET). This study aims to investigate the safety profiles of sunitinib through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS).
UNASSIGNED: The individual case safety reports (ICSRs) on sunitinib from 2006 Q1 to 2024 Q1 were collected from the ASCII data packages in the Food and Drug Administration Adverse Event Reporting System (FAERS). After standardizing the data, a variety of disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed to identify the potential safety signals of sunitinib-associated AEs.
UNASSIGNED: A total of 35,923 ICSRs of sunitinib as the \"primary suspected\" drug were identified within the reporting period. The search detected 276 disproportionate preferred terms (PTs). The most common AEs, including diarrhea, asthenia, decreased appetite, hypertension, and dysgeusia, were consistent with the drug label and clinical trials. Unexpected significant AEs, such as uveal melanocytic proliferation, salivary gland fistula, yellow skin, eyelash discoloration, scrotal inflammation, were detected. The median onset time of sunitinib-related AEs was 57 days (interquartile range [IQR]16-170 days), with most of the ICSRs developing within the first month (n = 4,582, 39.73%) after sunitinib therapy as initiated.
UNASSIGNED: The results of our study were consistent with routine clinical observations, and some unexpected AEs signals were also identified for sunitinib, providing valuable evidence for the safe use of sunitinib in the real-world and contributing to the clinical monitoring and risk identification of sunitinib.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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 319, 517, 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.
UNASSIGNED: 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.

UNASSIGNED: Interleukin-6 (IL-6) monoclonal antibodies are commonly acknowledged for their efficacy in managing coronavirus disease 2019 (COVID-19); however, there remains a paucity of comprehensive studies on their potential adverse effects.
UNASSIGNED: This is a retrospective pharmacovigilance investigation. We employed FAERS using OpenVigil FDA to detect adverse reactions linked to the interleukin-6 antagonist tocilizumab and sarilumab.
UNASSIGNED: Completely 17,037,364 reports were collected from the FAERS database, with 67,976 reports identified as \'primary suspected (PS)\' adverse events (AEs) for tocilizumab, and 12,560 reports for sarilumab. AEs induced by both drugs involved 27 organ systems. 109 significant disproportionality preferred terms (PTs) of tocilizumab and 158 significant disproportionality PTs meeting the criteria of sarilumab across all four algorithms were retained simultaneously. A higher incidence of adverse reactions occurred in females aged 45-64 years, with a higher rate of subsequent hospitalization. Both drugs exhibited adverse reactions consistent with previously reported side effects, such as leukopenia, elevated liver enzymes, and hypercholesterolemia. Additionally, there was a strong correlation with gastrointestinal issues. Unexpected significant adverse events, including diabetes, fluctuations in blood pressure, drug ineffectiveness, malignancies, and disorders of the nervous system, were also observed. Gender and age differences existed in AEs signals related to IL-6RAs.
UNASSIGNED: Our study identified significant new AE signals for interleukin-6 receptor antagonists, potentially supporting clinical monitoring and risk identification for this class of drugs.

UNASSIGNED: Adverse events associated with dexmedetomidine were analyzed using data from the FDA\'s FAERS database, spanning from 2004 to the third quarter of 2023. This analysis serves as a foundation for monitoring dexmedetomidine\'s safety in clinical applications.
UNASSIGNED: Data on adverse events associated with dexmedetomidine were standardized and analyzed to identify clinical adverse events closely linked to its use. This analysis employed various signal quantification analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS).
UNASSIGNED: In the FAERS database, dexmedetomidine was identified as the primary suspect in 1,910 adverse events. Our analysis encompassed 26 organ system levels, from which we selected 346 relevant Preferred Terms (PTs) for further examination. Notably, adverse drug reactions such as diabetes insipidus, abnormal transcranial electrical motor evoked potential monitoring, acute motor axonal neuropathy, and trigeminal cardiac reflex were identified. These reactions are not explicitly mentioned in the drug\'s specification, indicating the emergence of new signals for adverse drug reactions.
UNASSIGNED: Data mining in the FAERS database has elucidated the characteristics of dexmedetomidine-related adverse drug reactions. This analysis enhances our understanding of dexmedetomidine\'s drug safety, aids in the clinical management of pharmacovigilance studies, and offers valuable insights for refining drug-use protocols.

UNASSIGNED: Current clinical trial data on PARP inhibitors (PARPis)-related acute renal failure (ARF) are not entirely representative of real-world situations. Therefore, in this study, the US Food and Drug Administration Adverse Event Reporting System (FAERS) was used to evaluate PARPis-related ARF.
UNASSIGNED: Data were obtained from 1 January 2015, to 30 September 2023. ARF event reports were analyzed based on four algorithms. The time-to-onset (TTO) and clinical outcomes of PARPis-associated ARF were assessed.
UNASSIGNED: The total included cases were 2726. Significant signals were observed for olaparib, niraparib, and rucaparib (reporting odds ratio (ROR): 1.62, 95% confidence interval (CI): 1.49-1.78, 1.25, 95% CI: 1.19-1.32 and 1.59, 95% CI: 1.47-1.72 respectively). The median TTO of ARF onset was 57, 36, and 85 days for olaparib, niraparib, and rucaparib, respectively. The proportion of deaths with olaparib (9.88%) was significantly higher than for niraparib (2.52%) and rucaparib (2.94%) (p < 0.005). The proportion of life-threatening adverse events associated with niraparib (4.89%) was significantly higher than for rucaparib (0.98%) (p < 0.005).
UNASSIGNED: ARF and PARPi were related, with the exception of talazoparib. More emphasis should be given to PARPis-related ARF due to the high proportion of serious AEs and delayed adverse reactions.

UNASSIGNED: To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy.
UNASSIGNED: Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals.
UNASSIGNED: Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the \"primary suspected (PS)\" ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation.
UNASSIGNED: Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).

BACKGROUND: Anaplastic lymphoma kinase (ALK) has been to be involved in the uptake and regulation of dopamine 2 receptor (D2R), a G protein-coupled receptor expressed in various brain regions. Therefore, it is crucial to understand the relationship between ALK inhibitors and seizures is an important issue. This study investigated the relationship between ALK inhibitors and seizures.
METHODS: This study investigated the relationship between ALK inhibitors and seizures through a disproportionality analysis using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The target drugs were the ALK inhibitors crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The seizures covered were defined high-level group term (HLGT): \"Seizures (incl. subtype)\" including high-level term (HLT): \"seizures and seizure disorders NEC.\" This study used the information component (IC), a signal score, as a Bayesian statistical method for disproportionality analysis. The signal detection criteria used in this study were the same as those reported previously: a lower limit of 95% credible interval (CrI) for IC >0.
RESULTS: The signal scores of \'\"seizures and seizure disorders not elsewhere classified (NEC)\" \"for each ALK inhibitor were crizotinib (IC: -0.00052, 95% CrI: -0.38-0.27), ceritinib (IC: 1.18, 95% CrI: 0.68-1.54), alectinib (IC: 0.68, 95% CrI: 0.19-1.02), brigatinib (IC: 1.04, 95% CrI: 0.32-1.54), and lorlatinib (IC: 0.82, 95% CrI: 0.11-1.32). On the other hand, \"generalized tonic-clonic seizures,\" \"partial simple seizures NEC,\" \"absence seizures,\" and \"partial complex seizures\" had no or few reported cases, and no signal was detected.
CONCLUSIONS: To our knowledge, this is the first report to evaluate the relationship between ALK inhibitors and seizures using post-marketing surveillance data. These results suggest that ceritinib, alectinib, brigatinib, and lorlatinib, which are highly brain-migrating drugs, are associated with seizures.

UNASSIGNED: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are one of the most commonly used drugs for type 2 diabetes mellitus. Clinical guidelines recommend GLP-1 RAs as an adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, and obesity. The weight loss observed in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment.
UNASSIGNED: Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled boxed warning for the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of the most recent postmarketing safety data was warranted to quantify thyroid hyperplasia and neoplasm instances.
UNASSIGNED: GLP-1 RA patient reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System database were analyzed using reporting odds ratios and 95% CIs.
UNASSIGNED: In this study, we analyzed over 18 million reports from the US FDA Adverse Event Reporting System and provided evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA monotherapy when compared to patients taking sodium-glucose cotransporter-2 (SGLT-2) inhibitor monotherapy.
UNASSIGNED: GLP-1 RAs, regardless of indication, are associated with an over 10-fold increase in thyroid neoplasm and hyperplasia adverse event reporting when compared to SGLT-2 inhibitors.

OBJECTIVE: To describe reported cases of prolonged or relapsed ketoacidosis (KA) in adults with type 2 diabetes receiving treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors.
METHODS: We performed a search of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and medical literature, to identify our case series and to characterize cases of prolonged KA, relapsed KA, or persistent ketonemia, persistent ketonuria and/or persistent glucosuria in adults receiving SGLT2 inhibitors.
RESULTS: The FDA identified 29 unique cases of prolonged or relapsed KA, as well as related terms persistent ketonemia, persistent ketonuria, and persistent glucosuria, in patients receiving SGLT2 inhibitors through July 26, 2022. The patients ranged in age from 26 to 85 years. Treatment duration of KA ranged from 3 to 20 days. There were 7 cases of relapsed KA when insulin was reduced or transitioned to subcutaneous route. Arterial pH value was 7.0 or below in 4 patients, and the median pH was 7.1. Associated factors for prolonged or relapsed KA included surgery, decreased caloric intake, and ketogenic/carbohydrate restricted diet. A total of 62% of the patients were taking 3 or more glycemic control medications including the SGLT2 inhibitor. All patients with sufficient follow-up information recovered.
CONCLUSIONS: Although KA is a well-known risk associated with SGLT2 inhibitors, this case series demonstrated the potential for prolonged or recurrent KA events with serious outcomes. These cases informed updates to FDA\'s prescribing information to inform prescribers of this risk.