Hum Vaccin Immunother. 2025 Dec;21(1):2452681. doi: 10.1080/21645515.2025.2452681. Epub 2025 Feb 2.

ABSTRACT

Chickenpox outbreaks frequently occur in collective settings such as kindergartens and schools, posing a significant threat to children's physical and mental health. This study aimed to evaluate the immunogenicity and safety of the freeze-dried live attenuated varicella vaccine (VarV) developed by Beijing Minhai Biotechnology Co. LTD. in healthy participants aged 1-12 years. In this phase III, single-center, randomized, double-blind, active-controlled trial,1,200 healthy participants randomly assigned in a 1:1 ratio to receive one dose of either the test vaccine or the active control vaccine. Venous blood samples were collected before vaccination and 42 days after vaccination, and the fluorescent antibody to membrane antigen (FAMA) assay was used to detect VZV antibody. Adverse events (AEs) observed within 42 days after vaccination and serious adverse events (SAEs) within six months after vaccination were recorded. The seroconversion rates in the test and control groups were 96.79% and 96.43%, respectively, with a difference of 0.36% (95% CI, -1.76%-2.48%). The geometric mean titers (GMTs) were 61.74 and 58.04, respectively, with a difference of 1.06 (95% CI, 0.92-1.23). The lower limits of the 95% CI for the differences in seroconversion rates and GMT ratios between the two groups were greater than their respective pre-set non-inferiority margins. The overall incidence of AEs (p = .0112) in the test group was significantly lower than that in the control group. The freeze-dried live attenuated VarV developed by Beijing Minhai Biotechnology Co. LTD. demonstrated good immunogenicity and higher safety compared to the active control vaccine in healthy participants aged 1-12 years.

PMID:39895085 | DOI:10.1080/21645515.2025.2452681

Hum Vaccin Immunother. 2025 Dec;21(1):2458948. doi: 10.1080/21645515.2025.2458948. Epub 2025 Feb 2.

ABSTRACT

The utilization of immune-checkpoint inhibitors (ICIs) in cancer immunotherapy frequently leads to the occurrence of immune-related adverse events (irAEs), making it generally not recommended for patients with preexisting autoimmune diseases. Hence, we conducted a meta-analysis on safety and efficacy of ICIs in cancer patients with preexisting autoimmune diseases to provide further insights. PubMed, EMBASE, and Cochrane Library were systematically searched until December 20, 2024. The main summary measures used were pooled rate and risk ratio (RR) with 95% confidential interval (CI), which were analyzed using R statistic software. A total of 52 articles were included in the study. When cancer patients with preexisting autoimmune diseases received ICIs treatment, the overall incidence was 0.610 (95% CI: 0.531-0.686) for any grade irAEs, 0.295 (95% CI: 0.248-0.343) for flares, 0.325 (95% CI: 0.258-0.396) for de novo irAEs, 0.238 (95% CI: 0.174-0.309) for grade ≥3 irAEs, and 0.143 (95% CI: 0.109-0.180) for discontinuation due to immunotoxicity. Compared with those without autoimmune diseases, cancer patients with autoimmune diseases experienced a higher risk of any-grade irAEs (RR: 1.23, 95% CI: 1.12-1.35) and discontinuation due to immunotoxicity (1.40, 95% CI: 1.11-1.78). However, no statistically significant differences were observed in the incidence of grade ≥3 irAEs, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between the two groups. During ICIs treatment, irAEs are common among cancer patients with autoimmune diseases, but severe irAEs is relatively low. ICIs are effective in this population, but should be strictly monitored when used to avoid immunotoxicity.

PMID:39894761 | DOI:10.1080/21645515.2025.2458948

Hum Vaccin Immunother. 2025 Dec;21(1):2458831. doi: 10.1080/21645515.2025.2458831. Epub 2025 Feb 2.

ABSTRACT

To comprehensively assess the safety and difference of two types of EV71 vaccines: EV71-Vero, produced using Vero cells and EV71-H2, using human diploid cells. Our research included children of the recommended age who voluntarily received the EV71 vaccine in Hebei Province from 2019 to 2023. Detailed data on adverse events following immunization (AEFI) were collected, analyzed and compared for EV71-Vero and EV71-H2 vaccines. With 477 AEFI reported, the reported rate was 14.21 per 100,000 doses. Most cases occurred in infants under one year of age (45.91%). No significant differences in the AEFI reported rate were found between two types of EV71 vaccines across various demographic. However, a higher number of AEFI was reported in children under 1-year old following EV71-Vero compared to EV71-H2 with a reversal in 4-5 years- group (χ2 = 13.90, p = .01). The prognosis of cured took higher proportion for EV71-Vero than for EV71-H2 while inversely with improved outcome. The EV71 vaccine is advisable recommend to the appropriate age children to prevent EV7l infection. Both the EV71-Vero and EV71-H2 vaccines have good safety profiles. The reported AEFI, primarily high fever and allergic reactions, showed no significant differences in reported rates or case characteristics between the two types.

PMID:39894458 | DOI:10.1080/21645515.2025.2458831

Expert Opin Drug Saf. 2025 Feb 1. doi: 10.1080/14740338.2025.2461200. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to analyze adverse events (AEs)associated with naltrexone based on the FAERS database, providing a foundationfor its safety monitoring.

RESEARCH DESIGN AND METHODS: Disproportionality analysis methods,including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR),Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item GammaPoisson Shrinker (MGPS) algorithms, were employed to quantify signals ofnaltrexone-related AEs.

RESULTS: AEs related to naltrexone from the first quarter of 2013 to the fourth quarter of2023 were extracted from the FAERS database for detailed analysis. Among atotal of 41,757,311 reports 28,745 were directly associated with naltrexone,involving 27 organ systems. We identified 110 positive signals for AEsat the preferred term (PT) level using disproportionality analysis,whichincluded known AEs such as agitation, depressed mood, sleep disorder,tremor, delirium, and decreased libido. Additionally, our findings suggestedpotential risks of restless legs syndrome, eosinophilic pneumonia, andotolithiasis, which were not mentioned in the drug's label, therebysupplementing the existing safety information.

CONCLUSIONS: The analysis of the FAERS database identified AEsassociated with naltrexone, contributing to the awareness of clinicalpractitioners and pharmacists regarding the drug-related risk signals.Thisawareness facilitates timely preventive and therapeutic measures, ensuringpatient safety.

PMID:39893547 | DOI:10.1080/14740338.2025.2461200

Expert Opin Drug Saf. 2025 Feb 1. doi: 10.1080/14740338.2025.2460448. Online ahead of print.

ABSTRACT

BACKGROUND: Nasal septum perforation represents a significant clinical concern, with limited investigations into the role of medications in its etiology. This study utilizes the FDA Adverse Event Reporting System (FAERS) database to identify the drugs associated with nasal septum perforation and assess their risk.

RESEARCH DESIGN AND METHODS: This retrospective pharmacovigilance study analyzed drug-induced nasal septum perforation data from January 2004 to December 2023. Disproportionality analysis using reporting odds ratio (ROR) assessed drug associations with nasal septum perforation.

RESULTS: For 552 identified cases, the most commonly reported drugs were bevacizumab (n = 56), fluticasone propionate (n = 50), methotrexate (n = 34), hydrocodone and acetaminophen (n = 22), and paclitaxel (n = 17). Twenty-six drugs showed positive risk signals, with the top five being azelastine hydrochloride and fluticasone propionate (ROR = 173.82), beclomethasone dipropionate (ROR = 90.91), oxymetazoline (ROR = 53.77), desmopressin (ROR = 51.43), and leucovorin (ROR = 42.83). Intriguingly, 18 of these drugs did not list nasal septum perforation as a known side effect.

CONCLUSION: This study provides a comprehensive overview of drug-induced nasal septum perforation from a pharmacovigilance perspective, highlighting the need for further research to clarify these associations and update drug safety information to reduce patient risk.

PMID:39891519 | DOI:10.1080/14740338.2025.2460448

Medicine (Baltimore). 2025 Jan 31;104(5):e41460. doi: 10.1097/MD.0000000000041460.

ABSTRACT

The present study aims to evaluate the adverse events associated with Capmatinib using real-world data, providing a reference basis for its rational use in clinical practice. Relevant data from the Food and Drug Administration adverse event reporting system database was mined. Next, reporting odds ratio and Bayesian confidence propagation neural network method were used to analyze real-world adverse events associated with Capmatinib. The study revealed significant adverse event signals of Capmatinib, primarily involving general disorders and administration site conditions, cardiac disorders, gastrointestinal disorders, respiratory, thoracic and mediastinal disorders, neoplasms benign, malignant and unspecified (including cysts and polyps) and investigations, among others. A total of 79 signals were identified, with 13 of them not mentioned in the drug's specifications. Taken together, our comprehensive analysis of the Food and Drug Administration adverse event reporting system database enhances the understanding of Capmatinib's safety profile, thereby contributing to informed decision-making in its clinical application and facilitating the timely management of associated adverse reactions.

PMID:39889151 | DOI:10.1097/MD.0000000000041460

PLoS One. 2025 Jan 31;20(1):e0303130. doi: 10.1371/journal.pone.0303130. eCollection 2025.

ABSTRACT

OBJECTIVE: To evaluate the effect and safety of sclerotherapy in patients with difficult-to-resect venous malformations treated with ethanolamine oleate.

DESIGN AND SETTING: This investigator-initiated clinical trial employed a multicenter, single-arm design and was conducted in Japan.

PATIENTS: Overall, 44 patients with difficult-to-resect venous malformations were categorized into two cohorts: 22 patients with cystic-type malformations and 22 patients with diffuse-type malformations, including children (<15 years old).

INTERVENTIONS: Adult patients received injections of 5% ethanolamine oleate solution, double diluted with contrast or normal saline, with a maximum dose of 0.4 mL/kg. The same method of administration was used for children (<15 years old). The maximum volume of the prepared solution in one treatment was 30 mL.

EVALUATION METHODS: Treatment effect was assessed by evaluating the difference in lesion volume using magnetic resonance imaging as a primary endpoint and differences in pain using a visual analog scale as a key secondary endpoint.

RESULTS: Among the 45 patients who consented, one was excluded owing to potential intracranial involvement of venous malformations during screening. Regarding the primary outcome, 26 of 44 patients (59.1%, 95% confidence interval: 44.41-72.31%) achieved ≥ 20% reduction in malformation volume, with 16 patients having cystic lesions (72.7%, 51.85-86.85%) and 10 patients having diffuse lesions (45.5%, 26.92-65.34%). Both cohorts showed significant improvement in self-reported pain scores associated with lesions 3 months post-sclerotherapy. No death or serious adverse events occurred. Hemoglobinuria was observed in 23 patients (52%), a known drug-related adverse event. Prompt initiation of haptoglobin therapy led to full recovery within a month for these patients.

CONCLUSIONS: Ethanolamine oleate shows potential as a therapeutic sclerosing agent for patients with difficult-to-resect venous malformations.

PMID:39888898 | DOI:10.1371/journal.pone.0303130

Expert Opin Drug Saf. 2025 Jan 31. doi: 10.1080/14740338.2024.2446414. Online ahead of print.

ABSTRACT

OBJECTIVES: Medroxyprogesterone acetate (MPA), a steroid progesterone, is widely used to treat endometriosis, menstrual disorders, and uterine bleeding in clinical practice. However, the safety profile of MPA requires comprehensive evaluation.

METHODS: This study performed a retrospective analysis using real-world data extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Case reports from 2003 to 2023 were analyzed using methods like reporting advantage ratio (ROR), proportional report ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and empirical Bayes geometric mean (EBGM).

RESULTS: In the case reports spanning from 2003 to 2023, showed 26,437 adverse events (AEs) related to MPA, mostly in females (25,639). Disproportionality analysis identified 116 ADRs across 19 system organ class (SOC) levels, including expected AEs like 'female breast cancer'(n = 8717) and 'ovarian cancer' (n = 459). Unexpected AEs, such as 'acquired diaphragmatic eventration'(n = 3), were also noted.

CONCLUSION: Our study identifies potential new and unexpected ADR signals linked to MPA, which align with clinical observations. Additional research is necessary to confirm these associations and address previously unrecognized safety concerns. This research provides a novel and distinctive approach to exploring drug-related AEs.

PMID:39888632 | DOI:10.1080/14740338.2024.2446414

Int J Clin Pharm. 2025 Jan 31. doi: 10.1007/s11096-025-01867-6. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-induced hypofibrinogenemia has received increasing scrutiny; however, the specific drugs involved remain poorly characterized. Hypofibrinogenemia can have significant clinical implications, including increased bleeding risks.

AIM: This study aimed to utilize the FDA Adverse Event Reporting System (FAERS) to identify and analyze drugs frequently implicated in drug-induced hypofibrinogenemia.

METHOD: A disproportionality analysis was conducted using FAERS data from January 2004 to March 2024. Various statistical tools were used, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio, Medicines and Healthcare Products Regulatory Agency metrics, and Bayesian confidence propagation neural network.

RESULTS: The analysis included 17,627,340 cases involving 52,373,206 adverse events, with 1,661 cases identified as hypofibrinogenemia. The top five drugs associated with hypofibrinogenemia by case number were methotrexate (124 cases), tigecycline (119 cases), tocilizumab (100 cases), pegaspargase (83 cases), and alteplase (57 cases). The drugs ranked by signal strength based on ROR included eravacycline (ROR 2173.84, 95% CI 1208.80-3909.30), tigecycline (ROR 747.34, 95% CI 619.03-902.24), crotalidae polyvalent immune Fab (ROR 407.67, 95% CI 291.07-570.99), pegaspargase (ROR 216.06, 95% CI 173.15-269.61), and asparaginase (ROR 184.93, 95% CI 132.18-258.72).

CONCLUSION: This analysis of FAERS data identified 52 drugs associated with hypofibrinogenemia, most (88.5%) of which do not mention this risk in their prescribing information. These findings demonstrate the need for the monitoring of blood fibrinogen and may serve as a reference for the explore of the characteristics and underlying mechanism of drug-induced hypofibrinogenemia in the real world.

PMID:39888490 | DOI:10.1007/s11096-025-01867-6

J Int AIDS Soc. 2025 Feb;28(2):e26414. doi: 10.1002/jia2.26414.

ABSTRACT

INTRODUCTION: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was efficacious and well tolerated in children/adolescents with HIV (aged ≥6 years, weighing ≥25 kg) in a Phase 2/3 study. Here, we report data from children aged ≥2 years and weighing ≥14-<25 kg.

METHODS: This is an analysis of data from the youngest cohort in an open-label, multicentre, multi-cohort, single-group, international study of children/adolescents with HIV. Participants in this cohort were children aged ≥2 years, weighing ≥14-<25 kg at screening and able to swallow tablets, on stable antiretroviral therapy with virologic suppression (HIV-1 RNA <50 copies/ml for ≥6 consecutive months) and a CD4 count ≥400 cells/µl. Eligible participants received low-dose E/C/F/TAF (90/90/120/6 mg) once daily through Week 48. The study included pharmacokinetic evaluation of the low-dose E/C/F/TAF tablet at Week 2. Safety, efficacy, palatability and acceptability were also evaluated.

RESULTS: Between 16 January and 25 November 2019, 27 participants were enrolled with a median (quartile [Q]1, Q3) age of 6 (4, 8) years, body weight of 19.3 (17.0, 20.5) kg, CD4 count of 1061 (895, 1315) cells/µl and CD4 cell percentage of 37.4 (30.6, 40.3). Most (92.6%) participants acquired HIV through vertical transmission. On 6 October 2020 (data-cut), median (Q1, Q3) exposure to E/C/F/TAF was 48.3 (48.0, 60.1) weeks. Pharmacokinetic parameters were within the safe and efficacious range of previous data in adult and paediatric populations. Drug-related treatment-emergent adverse events occurred in 4/27 (15%) participants. There were no Grade 3/4 adverse events, or adverse events leading to E/C/F/TAF discontinuation. One participant experienced a serious treatment-emergent adverse event (Grade 2 pneumonia not considered E/C/F/TAF related). Virologic suppression (US FDA Snapshot algorithm) was maintained by 26/27 (96%) participants at Weeks 24 and 48. At Week 48, most children reported positive palatability (84.6%) and acceptability (96.2%).

CONCLUSIONS: These data support the use of single-tablet E/C/F/TAF (90/90/120/6 mg) regimen for the treatment of HIV in children aged ≥2 years and weighing ≥14-<25 kg.

CLINICAL TRIAL NUMBER: NCT01854775.

PMID:39888251 | DOI:10.1002/jia2.26414

BMC Pharmacol Toxicol. 2025 Jan 30;26(1):23. doi: 10.1186/s40360-025-00856-9.

ABSTRACT

PURPOSE: This study aims to assess the risks associated with drug-induced macular edema and to examine the epidemiological characteristics of this condition.

METHODS: This study analyzed data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2004 to June 2024 to conduct a disproportionality analysis identifying drugs with positive signals of drug-induced ME. Additionally, the onset time of ME associated with these drugs was examined.

RESULTS: In the FAERS database, a total of 490 drugs were reported to pose a risk of drug-induced ME. Disproportional analysis and screening further identified 8 drugs that significantly increased this risk. Among these, one is ophthalmic drugs, including Latanoprost (ROR = 5.51), and ten are non-ophthalmic drugs, including Cefuroxime (ROR = 75.93), Fingolimod (ROR = 30.69), and Siponimod (ROR = 20.51).

CONCLUSIONS: This study utilizes the FAERS database to investigate potential associations between drug use and the occurrence of ME, rapidly identify drugs that may induce the condition, and propose research strategies. These findings hold significant value for guiding clinical medication practices.

PMID:39885611 | DOI:10.1186/s40360-025-00856-9

J Pharm Health Care Sci. 2025 Jan 31;11(1):8. doi: 10.1186/s40780-025-00413-w.

ABSTRACT

BACKGROUND: The Anticholinergic Risk Scale and Total Anticholinergic Load were developed to assess the risks associated with anticholinergic drugs. Recently, the Japan Anticholinergic Risk Scale was introduced; however, the total anticholinergic load for adverse events has not been clarified, and the criteria for risk assessment in clinical practice have not been established. In this study, we used data from the Japanese Adverse Drug Event Report (JADER) database provided by the Pharmaceuticals and Medical Devices Agency to determine the total anticholinergic load associated with reported adverse events related to anticholinergic syndrome.

METHODS: Using JADER data from April 2004 to September 2023, we investigated the association between drugs included in the J-ARS and adverse events related to anticholinergic syndrome. In addition, we calculated the total anticholinergic load for each case involving a drug recorded in the JADER database and compared it with other adverse events associated with anticholinergic effects.

RESULTS: Based on the JADER data, we observed an association between anticholinergic syndrome-related adverse events and the drugs listed in the J-ARS, confirming the feasibility of calculating the total anticholinergic drug burden for each case. In the group reporting anticholinergic syndrome-related adverse events, the mean ± standard deviation of the total anticholinergic load was 4.20 ± 3.09.

CONCLUSIONS: The mean total anticholinergic load of anticholinergic syndrome-related adverse events obtained from the JADER database in this study supports the development of a comprehensive risk assessment of anticholinergic drugs in clinical practice.

PMID:39885610 | DOI:10.1186/s40780-025-00413-w

BMC Pharmacol Toxicol. 2025 Jan 30;26(1):24. doi: 10.1186/s40360-025-00858-7.

ABSTRACT

BACKGROUND: A number of pharmaceuticals, including antidepressants and antiepileptics, have a strong correlation with suicide risk. However, it is not entirely clear which of these medications are more strongly associated with suicide-related behaviors.

OBJECTIVE: This study aims to elucidate the drugs responsible for drug-associated suicidal ideation or self-injurious, recognizing the severe consequences associated with such outcomes. However, it is not entirely clear which specific medications are associated with higher levels of suicide-related behavior. Real-world data from the FDA adverse event reporting system database were analyzed to identify medications correlated with suicidal ideation or self-injurious.

METHODS: The reporting intensity of the High-Level Term "suicidal ideation or self-injurious behavior" and its Preferred Terms across distinct categories was assessed using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR).

RESULTS: We identified the top 20 drugs with the highest reporting frequencies, spanning sedative-hypnotics, antidepressants, antipsychotics, antiepileptics, antihypertensives, antipyretic/analgesic drugs, and antihyperglycemic drugs. Ranking these medications according to ROR, the top five medications with ROR values related to suicidal ideation or self-injurious were alprazolam, zolpidem, amphetamine, quetiapine, and fluoxetine. Further analysis showed that suicide-related adverse events were more frequently reported in females. Antiepileptics had the highest frequency of reported adverse events in the 51-55 year age group, compared to 16-20 years for antidepressants and 46-50 years for sedative-hypnotics.

CONCLUSION: Our study provides valuable information for clinical drug selection by presenting a potential list of medication classes commonly associated with drug-associated suicidal ideation or self-injurious behavior. We observed a large number of adverse event reports of suicidal ideation with duloxetine and relatively few reports of suicide attempts. Acetaminophen and amlodipine had substantial adverse event reports of completed suicides, but may not be associated with drug-induced suicidal behavior. On the other hand, some drugs mentioned in this study, such as quetiapine, aripiprazole, and lamotrigine, are recommended to be used after assessing the risk level of suicide in patients.

PMID:39885564 | DOI:10.1186/s40360-025-00858-7

Drug Ther Bull. 2025 Jan 30:dtb-2025-000006. doi: 10.1136/dtb.2025.000006. Online ahead of print.

NO ABSTRACT

PMID:39884824 | DOI:10.1136/dtb.2025.000006

Lupus Sci Med. 2025 Jan 30;12(1):e001362. doi: 10.1136/lupus-2024-001362.

ABSTRACT

OBJECTIVES: Patients with SLE take multiple medications. Within a large prospective longitudinal SLE cohort, we characterised medication-related hospitalisations and their preventability.

METHODS: We identified consecutive admissions to our tertiary hospitals between 2015 and 2020. Two independent adjudicators evaluated if medication-related events contributed to the hospitalisation, considering (1) adverse drug events (ADEs) and (2) events from medication non-adherence, using the Leape and Bates method. We classified ADEs as potentially preventable/ameliorable if we identified modifiable factors. Logistic regressions with generalised estimating equations evaluated associations between participant characteristics and medication-related hospitalisations, accounting for repeat hospitalisations within the same participant.

RESULTS: We studied 68 hospitalisations among 45 participants (91% female). At first hospitalisation, the median age was 38 years (IQR 26.5-53.0) and median SLE duration was 12 years (IQR 5.5-19.5). One or more ADEs contributed to 20 (29%) hospitalisations (11/23 (48%) ADEs being preventable/ameliorable), and SLE flares associated with medication non-adherence contributed to 7 (10%) hospitalisations. Adjusting for age and sex, current prednisone use (adjusted OR (aOR) 3.7, 95% CI 1.1 to 13.0) or ≥1 current immunosuppressant (aOR 11.5, 95% CI 2.7 to 50.0), renal involvement at SLE diagnosis (aOR 6.5, 95% CI 2.7 to 15.7) and polypharmacy (≥5 medications; aOR 11.3, 95% CI 1.2 to 103.8) were associated with having an ADE-related (vs non-ADE) hospitalisation. Age at SLE diagnosis<18 years (OR 5.9, 95% CI 1.3 to 26.6) was associated with hospitalisation for a flare related to non-adherence.

CONCLUSION: Forty per cent of SLE hospitalisations were medication-related, while half were potentially preventable/ameliorable. Renal involvement, polypharmacy, prednisone and immunosuppressant use were associated with hospitalisation related to an ADE, highlighting a vulnerable group.

PMID:39884714 | DOI:10.1136/lupus-2024-001362

Age Ageing. 2025 Jan 6;54(1):afaf008. doi: 10.1093/ageing/afaf008.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet they carry a unique spectrum of immune-related adverse events (irAEs). Given the ageing global population and the underrepresentation of older adults in clinical trials for ICIs, we investigated the occurrence and characteristics of irAEs in older versus younger adults as well as among different age subsets within the older adult population.

METHODS: We analysed the U.S. Food and Drug Administration Adverse Event Reporting System database reports from 2015 to 2023, focusing on ICIs. We categorised irAEs into 11 distinct types and performed descriptive and multivariate analyses to compare the prevalence and clinical characteristics of irAEs across different age groups, adjusting for potential confounding factors.

RESULTS: Among 47 513 patients aged 18-100 reporting irAEs, the 65-74 and 75-84 age groups had significantly increased risks compared to 18-64 (OR 1.13, 95% CI [1.09-1.18]; 1.15 [1.1-1.21]). Cardiovascular irAEs rose with age, peaking at 75-84, while endocrine irAEs decreased. Hepatobiliary, gastrointestinal and ocular irAEs decreased with age, but renal and musculoskeletal irAEs increased, showing higher risks in older adults. Serious outcomes slightly decreased in the 85+ group, while the proportion of deaths increased with age.

CONCLUSION: We discuss the potential changes in the immune system contributing to the decreased prevalence of irAEs in the oldest age group. Additionally, conservative treatment approaches and underreporting of irAEs in older patients may influence these findings. Our findings highlight the need for personalised decision-making for ICI therapies, considering performance status and comorbidities rather than age alone.

PMID:39883592 | DOI:10.1093/ageing/afaf008

Ther Adv Drug Saf. 2025 Jan 29;16:20420986241310685. doi: 10.1177/20420986241310685. eCollection 2025.

ABSTRACT

In 2019, intranasal esketamine gained approval as a promising therapy for those individuals grappling with treatment-resistant depression. Both clinical trials and real-world studies have underscored its efficacy in alleviating and remitting depressive symptoms, with sustained benefits observed for nearly 4.5 years. As the S-enantiomer of ketamine, esketamine's dosing guidelines and strict medical supervision stem from prior research on ketamine's use in depression and history as a recreational drug. Despite initial concerns, long-term clinical studies have not documented instances of abuse, misuse, addiction or withdrawal, and the same was found in case reports or subsamples of high-risk populations with comorbidities such as substance use disorder or alcohol use disorder. Esketamine has proven to be safe and well tolerated without fostering new-onset substance use in vulnerable groups. Real-world studies reinforced these observations, reporting no adverse events (AEs) related to pharmacological interactions of esketamine with any other substance, and no new-onset drug or alcohol misuse, craving, misuse or diversion of use. Reports of esketamine craving remain rare, with only one case report documented in 2022. Most drug-related AEs reported in pharmacovigilance databases are those identified in the product's technical data sheet and with known reported frequency. More importantly, no register of illicit acquisition of esketamine or its tampering for obtaining ketamine or other altered products was found in our search. Overall, our review confirms esketamine's safety across diverse patient populations, reassuring its responsible use and the scarcity of reports of abuse or misuse since its introduction to the market.

PMID:39882342 | PMC:PMC11776012 | DOI:10.1177/20420986241310685

Front Pharmacol. 2025 Jan 15;15:1523136. doi: 10.3389/fphar.2024.1523136. eCollection 2024.

ABSTRACT

OBJECTIVE: Although there are certain drug categories associated with heart failure (HF), most of the associated risks are unclear. We investigated the top drugs associated with HF and acute HF (AHF) reported in the FDA Adverse Event Reporting System (FAERS).

METHODS: We reviewed publicly available FAERS databases from 2004 to 2023. Using the search terms "cardiac failure" or "cardiac failure acute" and classifying cases by drug name, we processed and analyzed drug reports related to HF or AHF.

RESULTS: From 2004 to 2023, 17,379,609 adverse drug events were reported by FAERS, of which 240,050 (1.38%) were reported as HF. Among those with HF, the male-to-female ratio was 0.94% and 52.37% were >65 years old; 46.2% were from the United States. There were 5,971 patients with AHF. We identified 38 drugs and 13 drug classes with a potential high risk of causing HF, and 41 drugs and 19 drug classes were associated with AHF. The median onset times of HF and AHF were 83 days (IQR: 11-416) and 49 days (IQR: 8-259), respectively. The Weibull shape parameter (WSP) test showed early failure-type profile characteristics.

CONCLUSION: This study highlights key drugs associated with drug-induced HF and AHF, emphasizing the importance of early risk assessment and close monitoring, particularly during the initial stages of treatment. These findings contribute to a better understanding of drug-induced HF and provide a basis for future research on its underlying mechanisms.

PMID:39881876 | PMC:PMC11775474 | DOI:10.3389/fphar.2024.1523136

Int Med Case Rep J. 2025 Jan 25;18:163-171. doi: 10.2147/IMCRJ.S488796. eCollection 2025.

ABSTRACT

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered in all age groups due to their effectiveness in reducing fever, relieving pain, and reducing inflammation. However, they have also been identified as the second most common cause of drug-induced hypersensitivity reactions, after beta-lactam antibiotics. Adverse reactions to NSAIDs can range from expected pharmacological side effects such as gastritis to severe allergies, including anaphylaxis. It is important to distinguish true hypersensitivity reactions from other side effects to ensure proper management and patient safety. Four patients aged 35-60 years were treated with NSAIDs for pain management and subsequently developed hypersensitivity reactions to NSAIDs such as ketorolac, ketoprofen, and diclofenac sodium in the type of allergic reactions such as NSAIDs-induced urticaria/angioedema (NIUA). This case series provides valuable insights into the clinical presentations and potential mechanisms of NSAID hypersensitivity in the documented cases in one of the hospitals in Indonesia. It highlights important areas for future investigation, including the need for larger, controlled studies to better understand incidence, risk factors, and generalizability to broader populations.

PMID:39881781 | PMC:PMC11776529 | DOI:10.2147/IMCRJ.S488796

BMC Cancer. 2025 Jan 29;25(1):170. doi: 10.1186/s12885-025-13432-5.

ABSTRACT

BACKGROUND: The integration of immune checkpoint inhibitors (ICIs) into routine gynecologic cancer treatment requires a thorough understanding of how to manage immune-related adverse events (irAEs) to ensure patient safety. However, reports on real-world clinical experience in the management of ICIs in gynecologic oncology are very limited. The aim of this survey was to provide a real-world overview of the experiences and the current state of irAE management of ICIs in Germany, Switzerland, and Austria.

METHODS: We designed a questionnaire consisting of 34 items focused on physicans' clinical experiences with ICIs and their management of irAEs. The survey was distributed between October 2022 and May 2023 to medical professionals with experience in the field of gynecologic oncology.

RESULTS: A total of 221 gynecologists participated in the study. Most respondents (n = 130, 59.1%) were primarily engaged in gynecologic oncology at the time of the survey, with an average of ten years of clinical experience. Individual experiences with regard to irAEs varied significantly. When asked which irAEs they had observed "frequently" or "very frequently", respondents most commonly reported thyroiditis (37.2%), followed by skin reactions (23.6%), and pneumonitis (10.6%). A total of n = 16 (7.4%) reported at least one death of a patient due to irAEs. Feeling "unconfident" or "very unconfident" about managing irAEs was reported by 35.6% (n = 78). With regard to clinical management of adverse events after discontinuation of treatment, 32.4% (n = 68) ceased to inquire about irAEs after six months.

CONCLUSION: The results of this survey provide valuable insights into physicians' real-world experiences with irAEs associated with ICI treatment. Dealing with serious immune-related and potentially life-threatening side effects has become a routine aspect of clinical practice. Many physicians, however, express a lack of sufficient familiarity with irAEs and their management. Therefore, it is essential to improve medical education, specialized oncological training, and close interdisciplinary collaboration to improve patient care.

PMID:39881252 | DOI:10.1186/s12885-025-13432-5