Theranostics. 2025 Jan 1;15(1):52-67. doi: 10.7150/thno.100042. eCollection 2025.

ABSTRACT

Background: In oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC), frequent inadequate surgical margins highlight the importance of precise intraoperative identification and delineation of cancerous tissue for improving patient outcomes. Methods: A prospective, open-label, single-center, single dose, exploratory phase II clinical trial (EudraCT 2022-001361-12) to assess the efficacy of the novel uPAR-targeting near-infrared imaging agent, FG001, for intraoperative detection of OSCC and OPSCC. Macroscopic tumor detection was quantified with sensitivity and intraoperative tumor-to-background ratio (TBR). Microscopic tumor-specificity was assessed by analysis of morphological co-localization between tumor tissue, uPAR-expression, and optical signal. Blood samples were collected up to 44 hours post-injection to further characterize the pharmacokinetic profile of the agent. The trial was conducted with close safety monitoring. Results: Sixteen patients undergoing primary surgical resection were systemically administered 36 mg (n = 4), 16 mg (n = 8), or 4 mg (n = 4) of FG001 the evening prior to surgery. Intraoperatively, using a near-infrared imaging system, real-time optical imaging successfully identified all 16 tumors (sensitivity: 100%, mean TBR: 2.99 range: 2.02 - 3.95), and tumor-specificity was confirmed by histology. Clinical neck metastasis was detected with optical imaging. The maximal plasma concentrations were measured after 1 hour, and the half-life of FG001 was 12 hours. No drug-related or serious adverse events were observed. Conclusions: FG001 holds great potential for optical molecular imaging of OSCC and OPSCC. Further trials are warranted to explore FG001 for intraoperative margin delineation and as a decision-making tool.

PMID:39744227 | PMC:PMC11667226 | DOI:10.7150/thno.100042

Zhonghua Yan Ke Za Zhi. 2025 Jan 11;61(1):71-76. doi: 10.3760/cma.j.cn112142-20240117-00030.

ABSTRACT

Immune checkpoint inhibitors (ICI), as a new type of targeted therapeutic drugs, have demonstrated durable efficacy in cancer treatment. However, some patients receiving ICI treatment may be affected by immune-related adverse events (irAE). Compared with irAE in skin tissues, gastrointestinal system, etc., irAE in the neuro-ophthalmic efferent system are relatively rare. The reported irAE in the neuro-ophthalmic efferent system mainly include myasthenia gravis, orbital extraocular myositis, thyroid-associated ophthalmopathy-like conditions, internuclear ophthalmoplegia, Miller-Fisher syndrome, and cranial nerve adverse events. Exploring the possible mechanisms and potential intervention measures of irAE in the neuro-ophthalmic efferent system is crucial for predicting the risk of irAE in patients, formulating preventive measures, and implementing more effective clinical treatments. This review aims to summarize the occurrence mechanisms, clinical features, and prevention and treatment measures of irAE in the neuro-ophthalmic efferent system, so as to assist ophthalmologists and oncologists in the early diagnosis and management of such patients.

PMID:39743697 | DOI:10.3760/cma.j.cn112142-20240117-00030

Front Immunol. 2024 Dec 17;15:1455050. doi: 10.3389/fimmu.2024.1455050. eCollection 2024.

ABSTRACT

Biological drugs are extensively used to treat various inflammatory diseases, including psoriasis, atopic dermatitis (AD), and rheumatoid arthritis. While generally effective and safe, these therapies have been increasingly associated with secondary development of vitiligo, especially with anti-TNF α and anti-IL17 drugs. Dupilumab, an IL-4 receptor alpha antagonist used in moderate to severe AD, rarely induces vitiligo. This study reports two cases of new-onset vitiligo following dupilumab treatment for AD. The first case involves an 80-year-old male who developed vitiligo patches appeared on the chest, back, and lower limbs after 2 months of dupilumab therapy. Despite discontinuation of dupilumab, the vitiligo did not regress. The second case describes a 14-year-old female who experienced depigmentation on her forehead one month into dupilumab treatment, with partial improvement of vitiligo lesions over time despite continued therapy. This phenomenon may be due to dupilumab blocking type 2 inflammation, disrupting normal skin homeostasis, and exacerbating type 1 inflammation. These cases, supplemented with a literature review, highlight the potential for biologic drug-induced vitiligo and underscore the need for awareness of such adverse events in clinical practice. The mechanisms underlying this phenomenon likely involve disruption of the Th1/Th2/Th17 cytokine balance, suggesting that targeted therapies may inadvertently exacerbate type 1 inflammation, leading to vitiligo. With the rising use of biologics, clinicians should carefully consider the risk of vitiligo when prescribing these treatments.

PMID:39742272 | PMC:PMC11685107 | DOI:10.3389/fimmu.2024.1455050

Front Immunol. 2024 Dec 17;15:1495137. doi: 10.3389/fimmu.2024.1495137. eCollection 2024.

ABSTRACT

INTRODUCTION: Antibody-drug conjugates (ADCs) are increasingly utilized in patients with solid tumors and hematologic malignancies. However, the adverse ocular toxicity induced by ADCs has not been comprehensively evaluated in real-world clinical settings.

METHODS: Data from April 2019 to March 2024 based on the FDA Adverse Event Reporting System (FAERS) were extracted and analyzed. Disproportionality analysis was used to evaluate the association between ADCs and ocular adverse events (AEs). The median time to onset (TTO) of various ADCs was compared.

RESULTS: A comprehensive analysis identified 2,686 ocular AEs associated with ADCs. Among these, Tisotumab vedotin had the most positive signals at the preferred terms (PTs) level, followed by trastuzumab emtansine and enfortumab vedotin. In contrast, gemtuzumab ozogamicin demonstrated minimal ocular toxicity signals. Cluster analysis revealed that ADC-related ocular toxicities predominantly manifested as corneal disorders or ocular neuromuscular disorders. The median onset of ocular toxicity varied considerably, with enfortumab vedotin showing the earliest median onset at 12.5 days.

CONCLUSIONS: Our study demonstrates the association between ADCs and ocular AEs based on real-world data, providing valuable guidance for clinicians when prescribing ADCs. And we found some important safety signals that have not been mentioned in the label or previous studies.

PMID:39742259 | PMC:PMC11685049 | DOI:10.3389/fimmu.2024.1495137

Ann Burns Fire Disasters. 2024 Dec 31;37(4):294-299. eCollection 2024 Dec.

ABSTRACT

The use of new oxygen supports associated to non-invasive respiratory strategies is well-established in clinical practice, especially after its extensive application in the management of Covid-19 respiratory failure. The use of high flow nasal cannula (HFNC) in patients undergoing procedural sedation and analgesia (PSA) is dramatically increasing. Enzymatic debridement in critical burn patients is a painful treatment that requires an optimal burn pain control protocol as well as a deep sedation for the entire duration of the procedure. Both hypnosis and opioid-analgesia may lead to significant respiratory depression. Fourteen patients undergoing enzymatic debridement under deep sedation have been included in this case study. All patients receiving oxygen through HFNC were evaluated. All patients underwent continuous monitoring of vital parameters, antithrombotic prophylaxis with low molecular weight heparins and fluid therapy calculated using the Parkland formula. Sedation was successful and well tolerated by all patients and physicians were able to carry out the enzymatic debridement procedure safely. No severe desaturation events were observed. Continuous monitoring of vital signs was carried out. Neither bradycardia events nor hypotensive or hypertensive events requiring treatment occurred. Enzymatic debridement procedures did not lead to any serious adverse events. Based on our experience, the administration of O2 by HFNC at an average concentration of 50% was proven safe and efficacious in the management of drug-induced respiratory depression.

PMID:39741773 | PMC:PMC11649166

BMC Ophthalmol. 2024 Dec 31;24(1):554. doi: 10.1186/s12886-024-03823-w.

ABSTRACT

BACKGROUND: Prostaglandin analogs are first-line treatments for open-angle glaucoma due to their proven efficacy in reducing intraocular pressure. Despite their topical administration, systemic adverse drug Events (ADEs) have been reported. This study investigates the systemic ADEs associated with topical prostaglandin analogs using the United States Food and Drug Administration (USFDA) Adverse Drug Event Reporting System (AERS) database.

METHODS: The USFDA AERS database was queried for reports on prostaglandin analogs from March 2004 to March 2024 in this retrospective pharmacovigilance study. Data were deduplicated and analyzed using disproportionality analysis with both frequentist and Bayesian approaches. Reports on systemic ADEs where topical prostaglandin analogs were the primary suspect were included. Statistical analysis was performed using descriptive statistics and the chi-square test for categorical variables.

RESULTS: A total of 30,853 reports were analyzed, predominantly involving latanoprost and bimatoprost, with most patients being elderly and female. In general, hypersensitivity reactions were the most common systemic adverse events reported with prostaglandin analogs. Varied systemic adverse events were observed within the class as latanoprost was linked to conditions like angina pectoris, atrial tachycardia and Meniere's disease, bimatoprost to lentigo maligna melanoma, and tafluprost to labyrinthitis and skin discoloration. Notably, tafluprost had a significantly higher occurrence of death compared to other prostaglandin analogs, yet the causal relationship has not been established for this association due to unavailability of critical data on temporality and potential confounders including concomitant diseases/drugs and severity of the disease.

CONCLUSION: Prostaglandin analogs are associated with systemic ADEs, particularly in elderly and female patients. The most reported systemic adverse event was hypersensitivity reactions for the class and cardiac events for latanoprost. Tafluprost was observed with higher mortality statistically, yet causal relationship could not be established in the absence of details on the potential confounders. The findings emphasize the need for continuous monitoring of adverse reactions, and consideration of patient-specific factors when prescribing these medications.

PMID:39741235 | DOI:10.1186/s12886-024-03823-w

BMJ Open. 2024 Dec 31;14(12):e088389. doi: 10.1136/bmjopen-2024-088389.

ABSTRACT

INTRODUCTION: Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings.

METHODS: This is an observational cohort study with a nested case-control study. We enrolled consecutive patients who had been initiated on TPT using the 3HP regimen. These are followed up biweekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2, AADAC and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes.

ANALYSIS: The safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. χ2 tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modelling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.

ETHICS AND DISSEMINATION: Ethical approval of this study inclusive of all the appropriate documents was obtained from the Infectious Diseases Institute Research and Ethics Committee and the Uganda National Council of Science and Technology. The study adheres to legal, ethical and Good Clinical Practice (GCP) guidelines. Deidentified genotype data from 300 patients will be shared after publication. The protocol and phenotype data will be publicly accessible. Abstracts will be submitted to conferences, and a manuscript will be published poststudy.

PMID:39740953 | DOI:10.1136/bmjopen-2024-088389

In Vivo. 2025 Jan-Feb;39(1):433-439. doi: 10.21873/invivo.13846.

ABSTRACT

BACKGROUND/AIM: The use of hypnotic drugs can lead to accidents and injuries. However, few reports have shown their association with these events after adjusting for many concomitant medications. This study aimed to determine whether the use of hypnotic drugs was associated with accidents and injuries.

PATIENTS AND METHODS: Using the Japanese Adverse Event Reporting Database, 772,387 reports published between September 2023 and April 2004 were analyzed. Reporting odds ratios (RORs) and 95% confidence intervals (CIs) for accidents and injuries associated with each hypnotic drug were calculated after adjusting for potential confounders.

RESULTS: Of the total, 12,484 reports indicated association of hypnotic drugs with accidents and injuries. The use of each hypnotic drug was associated with accidents, injuries, and other adverse events. However, a multivariate analysis adjusted for age, sex, reporting year, and concomitant medications showed a considerable decrease in ROR for melatonin receptor agonists (adjusted ROR=1.26; 95%CI=1.03-1.55) and dual orexin receptor antagonists (DORAs) (adjusted ROR=1.04; 95%CI=0.86-1.25). Particularly in DORAs, a loss of signal for accidents and injuries was observed.

CONCLUSION: The risk of accidents and injuries may vary with hypnotic drug use; however, DORAs may be less frequently associated with these events. The results of this study provide useful information for the selection of hypnotic drugs.

PMID:39740920 | DOI:10.21873/invivo.13846

In Vivo. 2025 Jan-Feb;39(1):346-352. doi: 10.21873/invivo.13834.

ABSTRACT

BACKGROUND/AIM: Despite the seriousness of lung adverse events (AEs) associated with lenvatinib, comprehensive data on these events remain limited. This study was conducted to examine the disproportionality, time to onset, incidence rates, and outcomes of lenvatinib-associated lung AEs using the Japanese Adverse Drug Event Report database.

PATIENTS AND METHODS: We analysed data for the period from April 2004 to May 2023. Data on lung AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Weibull distribution parameters were also calculated.

RESULTS: Among the 2,230,863 reports analysed, 7,684 reports of AEs associated with lenvatinib were identified, including 380 lung AEs. Signals were detected for three lung AEs: tracheal fistula, tracheo-oesophageal fistula, and tracheal haemorrhage. Fatal outcomes were observed for tracheal fistula and tracheal haemorrhage. A histogram of median times to onset indicated that lung AEs associated with lenvatinib occurred 15-111 days after administration. Weibull distributions showed that the incidence of these AEs remained constant throughout the exposure period (random failure type).

CONCLUSION: The present study highlights post-marketing AEs associated with lenvatinib, with a particular focus on lung AEs. Tracheal fistula and tracheal haemorrhage were identified as AEs with potentially serious outcomes following lenvatinib administration. Monitoring patients for early signs of these AEs is important not only at treatment initiation, but also throughout the entire course of therapy.

PMID:39740919 | DOI:10.21873/invivo.13834

In Vivo. 2025 Jan-Feb;39(1):396-403. doi: 10.21873/invivo.13841.

ABSTRACT

BACKGROUND/AIM: Nintedanib may cause adverse events such as elevated liver enzyme levels, diarrhea, and decreased appetite. These adverse events should be managed appropriately as they affect the quality of life of patients. This study has aimed to analyze patient characteristics and time-to-onset of adverse events caused by nintedanib using the Japanese Adverse Drug Event Report (JADER) database.

PATIENTS AND METHODS: Data from April 2004 to June 2023 were extracted from the JADER database and the patient characteristics of nintedanib administration were evaluated using reported odds ratio (ROR) and 95% confidence interval (95%CI). The data were analyzed for time-to-onset and patient characteristics such as age, sex, body mass index (BMI), and the presence or absence of prednisolone.

RESULTS: The JADER database included 1,419 adverse event reports in which nintedanib was suspected. The number (%) and ROR of adverse events known to occur with the use of nintedanib were 72 (5.07%) cases of decreased appetite [ROR=7.09 (95%CI=5.59-8.99)], and 79 (5.57%) cases of diarrhea [ROR=6.52 (5.19-8.18)]. The median days until onset were 19.5 (IQR=6.25-50.5) days for hepatotoxicity, 119.5 (IQR=24.5-258.5) days for diarrhea, and 131.5 (IQR=20.5-334.5) days for decreased appetite.

CONCLUSION: Nintedanib is more likely to cause elevated liver enzyme levels, diarrhea, and decreased appetite than other drugs. These events occurred within approximately 3-4 months. The concomitant use of prednisolone may also be associated with gastrointestinal hemorrhage.

PMID:39740899 | DOI:10.21873/invivo.13841

In Vivo. 2025 Jan-Feb;39(1):360-366. doi: 10.21873/invivo.13836.

ABSTRACT

BACKGROUND/AIM: Despite the seriousness of lung adverse events (AEs) associated with sorafenib, comprehensive data are limited. This study was conducted to examine the disproportionality, times to onset, incidence rates, and outcomes of sorafenib-associated lung AEs, using the Japanese Adverse Drug Event Report database.

PATIENTS AND METHODS: Data for the period between April 2004 and May 2023 were analyzed. Data on lung AEs were extracted, and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs).

RESULTS: A total of 2,230,863 reports were analyzed, and 8,374 reports of AEs associated with sorafenib, including 381 lung AEs, were identified. Signals were detected for two lung AEs: metastases to the lung and tracheal hemorrhage. Fatal outcomes were observed for both AEs. Histograms of the median times to onset of the two detected lung AE signals showed that AEs occurred from 49 to 275 days after sorafenib administration. Weibull distributions showed that the incidences of these AEs occurred constantly throughout the exposure period (random failure type).

CONCLUSION: This study focused on lung AEs associated with sorafenib, highlighting serious outcomes such as lung metastases and tracheal hemorrhage. Continuous monitoring for these AEs is crucial from treatment initiation through the entire therapy course.

PMID:39740895 | DOI:10.21873/invivo.13836

PLoS One. 2024 Dec 31;19(12):e0316573. doi: 10.1371/journal.pone.0316573. eCollection 2024.

ABSTRACT

Nirmatrelvir/Ritonavir, acting as an effective agent against COVID-19, has achieved considerable results in clinical studies in terms of drug efficacy. However, there is little research about its medication safety. Based on the FDA adverse event reporting system (FAERS) database, this study aims to mine the adverse reaction signals of the latest major recommended drug Nirmatrelvir/Ritonavir for the antiviral treatment of COVID-19, so as to provide a basis for safe and rational drug use. The reporting odds ratio (ROR) was used to explore the adverse event report data of all COVID-19 emergency use authorization (EUA) products in the FAERS database with the deadline of third quarter of 2023. In the analysis, 135427 adverse drug event (ADE) reports were found, and 35250 ADEs were reported with Nirmatrelvir/Ritonavir as the primary suspected drug, which was involved in multiple system. There was a high signal intensity of dysgeusia (ROR = 72.98), diarrhea (ROR = 3.03) and headache (ROR = 1.25), which was compatible with the adverse reactions recorded in the manual for Nirmatrelvir/Ritonavir. In addition, it was suggested that Nirmatrelvir/Ritonavir might cause pale-colored stools (ROR = 45.53), chromaturia (ROR = 3.07), yellow skin (ROR = 3.62), tongue coating (ROR = 35.55) and other new adverse reactions (not included in the instructions manual for Nirmatrelvir/Ritonavir). The ADEs of Nirmatrelvir/Ritonavir that are not in the instructions and are highly relevant in the real world are supplemented, prompting clinical attention to the ADEs of the drug, and providing a theoretical basis for the safe and effective application of the drug.

PMID:39739861 | DOI:10.1371/journal.pone.0316573

J Cardiovasc Pharmacol. 2024 Dec 31. doi: 10.1097/FJC.0000000000001662. Online ahead of print.

ABSTRACT

It is unclear whether drugs other than warfarin can cause spontaneous gastrointestinal intraluminal hematomas (SGIH). This study aimed to investigate the drugs that induced SGIH based on the FDA Adverse Event Reporting System (FAERS) data. A retrospective pharmacovigilance study was conducted. The disproportionality analysis was performed to assess the reports of drug-induced SGIH from the first quarter of 2004 to the fourth quarter of 2023. Logistics regression analysis was used to explore drug-related SGIH risk factors. Weibull distribution was applied for the onset time of SGIH. A total of 116 drugs associated with SGIH have been reported in the FAERS database. After removing duplicates, 88 unique drugs involving 210 patients were identified. These drugs can be broadly classified into four categories: (1) anticoagulants, (2) new direct oral anticoagulants, (3) antiplatelet agents, and (4) others. The first group is dominated by warfarin (59/210), while the second group, rivaroxaban, accounts for the most significant proportion (9/210). As for the third group, aspirin is the dominant drug (16/210), and for the fourth group, drugs that cause thrombocytopenia are dominant. The median number of reported cases was 11.5 per year, accounting for a median percentage of 0.0094% of all adverse events related to target drugs. The median time to drug-related SGIH onset was 12.5 days (interquartile range 1-220.25 days). When patients on the related drugs present with corresponding abdominal symptoms, it is crucial to consider the differential diagnosis of SGIH despite its low incidence.

PMID:39739309 | DOI:10.1097/FJC.0000000000001662

Adv Ther. 2024 Dec 30. doi: 10.1007/s12325-024-03073-8. Online ahead of print.

ABSTRACT

INTRODUCTION: This study evaluated the safety and tolerability of fezolinetant in women with vasomotor symptoms (VMS) due to menopause in a pooled analysis of data from three 52-week phase 3 studies (SKYLIGHT 1, 2, and 4).

METHODS: SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies where women (≥ 40 to ≤ 65 years), with moderate to severe VMS (minimum average ≥ 7 hot flashes/day) were randomized to once-daily placebo, fezolinetant 30 mg or 45 mg. After 12 weeks, those on placebo were re-randomized to fezolinetant 30 mg or 45 mg, while those on fezolinetant continued on their assigned dose for 40 weeks. SKYLIGHT 4 was a placebo-controlled, double-blind, 52-week safety study. Safety was assessed by frequency of treatment-emergent adverse events (TEAEs) and endometrial events. TEAEs of special interest included liver test elevations and endometrial hyperplasia or cancer or disordered proliferative endometrium.

RESULTS: Totals of 952 participants receiving placebo, 1100 receiving fezolinetant 45 mg, and 1103 receiving fezolinetant 30 mg took ≥ 1 dose of study medication. TEAEs occurred in 55.3%, 62.9%, and 65.4%, respectively; exposure-adjusted results were consistent with these results. Most frequent TEAEs in fezolinetant-treated participants included upper respiratory tract infection (7.7-8.3%), headache (6.8-8.2%), coronavirus disease 2019 (5.8-6.1%), back pain (3.1-3.7%), arthralgia (2.9-3.2%), diarrhea (2.3-3.2%), urinary tract infection (2.9-3.4%), and insomnia (2.0-3.0%). The incidence of drug-related serious TEAEs and associated treatment withdrawals was low. Elevations in liver transaminases occurred in 1.5-2.3% of fezolinetant-treated participants, were typically asymptomatic and transient, resolved on treatment or discontinuation, with no evidence of severe drug-induced liver injury (Hy's law). Endometrial safety results were well within US Food and Drug Administration criteria. Analysis of benign and non-benign neoplasm controlled for exposure demonstrated no increased risk versus placebo.

CONCLUSION: Pooled data confirm the safety and tolerability of fezolinetant over 52 weeks.

TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT04003155, NCT04003142, and NCT04003389. Graphical abstract available for this article.

PMID:39739195 | DOI:10.1007/s12325-024-03073-8

Front Immunol. 2024 Dec 16;15:1490334. doi: 10.3389/fimmu.2024.1490334. eCollection 2024.

ABSTRACT

BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS) is a life-threatening severe cutaneous adverse reaction.

OBJECTIVE: This study aims to study fatal DRESS cases using FAERS database and systematic review.

METHODS: Data of the FDA Adverse Event Reporting System (FAERS) database were extracted and manipulated. Articles from Pubmed, Embase and CINAHL databases were screened.

RESULTS: 0.13% of the adverse events submitted to FAERS was identified as DRESS and the percentage of fatal cases was up to 6.62%. The top five drugs calculated to induce DRESS with the highest number of reported cases were allopurinol, lamotrigine, vancomycin, amoxicillin and carbamazepine. The top five drugs statistically related to fatal outcome with the highest number of reported cases were allopurinol, vancomycin, trimethoprim, sulfamethoxazole and lamotrigine. Skin manifestations remained the main reason for admission and the average time from dose to rash onset was 27.19 days. The most commonly cited culprit medication type were antibiotics (50.00%), anti-gout agents (15.38%) and anti-epileptic drug (11.54%).

CONCLUSIONS: We discussed fatal cases of DRESS through FAERS system and case reports, hoping to raise awareness when using relevant drugs.

PMID:39737180 | PMC:PMC11683082 | DOI:10.3389/fimmu.2024.1490334

CJC Open. 2024 Sep 12;6(12):1527-1533. doi: 10.1016/j.cjco.2024.09.003. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Antiplatelet drugs, such as clopidogrel, ticagrelor, prasugrel, and acetylsalicylic acid, may be associated with a risk of adverse events (AEs). Vanessa's Law was enacted to strengthen regulations to protect Canadians from drug-related side effects (with mandatory reporting of serious adverse events [SAEs]).

OBJECTIVE: To determine whether Vanessa's Law has led to an increase in SAE reporting among antiplatelet users.

METHODS: This descriptive retrospective study was conducted from January, 2018-December, 2021. Included are 260 adult antiplatelet users (cohorts: 2018 [n = 64]; 2019 [n = 79]; 2020 [n = 73]; 2021 [n = 44]) hospitalized at the Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval. The main diagnostic of hospitalization was coded using the International Classification of Diseases,10th revision, Canadian version, and data related to demographic characteristics, hospitalization length-of-stay, drugs administered, and AEs were extracted.

RESULTS: The 260 antiplatelet users were hospitalized mainly for diseases of the circulatory system (codes [I00-I99]; 2018, 75 %; 2019, 71 %; 2020, 71 %; 2021, 77 %) or diseases of the respiratory system (codes [J00-J99]; 2018, 6 %; 2019, 8 %; 2020, 4 %; 2021, 7 %). The median age was 70 years. The median duration of hospital stay was 3 days. Among the 1395 AEs recorded during the study, 12 % were SAEs. None of the SAEs (or AEs) was reported to Health Canada, either before or after Vanessa's Law implementation.

CONCLUSIONS: These results provide the first picture of reporting trends for SAEs among antiplatelet users in Canada. Investigation of the underreporting of SAEs is needed, as the implementation of a mandatory policy does not seem to have had a favourable impact.

CLINICAL TRIAL REGISTRATION: 135263.

PMID:39735944 | PMC:PMC11681356 | DOI:10.1016/j.cjco.2024.09.003

World J Gastroenterol. 2024 Dec 28;30(48):5152-5161. doi: 10.3748/wjg.v30.i48.5152.

ABSTRACT

BACKGROUND: For the treatment of gastritis, rebamipide, a mucoprotective agent, and nizatidine, a gastric acid suppressant, are commonly employed individually.

AIM: To compare the efficacy of Mucotra® SR (rebamipide 150 mg) and Axid® (nizatidine 150 mg) combination therapy with the sole administration of Axid® in managing erosive gastritis.

METHODS: A total of 260 patients diagnosed with endoscopically confirmed erosive gastritis were enrolled in this open-label, multicenter, randomized, phase 4 clinical trial, allocating them into two groups: Rebamipide/nizatidine combination twice daily vs nizatidine twice daily for 2 weeks. The full-analysis set analysis encompassed 239 patients (rebamipide/nizatidine, n = 121; nizatidine, n = 118), while the per-protocol analysis included 218 patients (n = 110 vs 108). Post-treatment assessments comprised primary (erosion improvement rate) and secondary (erosion and edema cure rates, erythema improvement rates, hemorrhage, and gastrointestinal symptoms) endpoints. Furthermore, drug-related adverse effects were evaluated.

RESULTS: Primary efficacy assessment showed a statistically significant improvement rate in mucosal erosions in the combination group compared to the control group in the full-analysis set (rebamipide/nizatidine 62.0%, nizatidine 49.2%, P = 0.046), with a similar trend noted in the per-protocol analysis (62.7% vs 50.0%, P = 0.058). Both groups were effective in curing erosion and edema and improvement of bleeding, erythema, and gastrointestinal symptoms, whereas no inter-group differences were noted. When confined to the participants with gastritis symptoms, improvement of erosion was more optimal in the combination group (63.0% vs 49.5%, P = 0.046). No adverse events related to the drugs were observed.

CONCLUSION: Rebamipide/nizatidine combination is effective in treatment of erosive gastritis.

PMID:39735267 | PMC:PMC11612702 | DOI:10.3748/wjg.v30.i48.5152

Cureus. 2024 Nov 28;16(11):e74677. doi: 10.7759/cureus.74677. eCollection 2024 Nov.

ABSTRACT

Olanzapine, a second-generation antipsychotic widely used for schizophrenia, is primarily known for its efficacy in managing both positive and negative symptoms. While its metabolic side effects are well-documented, hematologic complications such as thrombocytopenia are rare and often underrecognized. A 30-year-old Middle Eastern male with a longstanding history of schizophrenia developed persistent thrombocytopenia after several years of olanzapine use, with platelet counts consistently below the normal range. Despite being asymptomatic for bleeding or bruising, his platelet decline necessitated treatment adjustments. Cross-tapering olanzapine with other antipsychotics initially failed due to psychiatric relapse, but the introduction of aripiprazole alongside olanzapine tapering successfully improved platelet counts while maintaining psychiatric stability. The successful use of aripiprazole in this case represents a novel therapeutic approach, addressing antipsychotic-induced thrombocytopenia without compromising psychiatric outcomes. This case underscores the rare but significant risk of olanzapine-induced thrombocytopenia and highlights the need for vigilant hematologic monitoring during long-term antipsychotic therapy, even in asymptomatic patients or those with low baseline platelet count or concomitant blood dyscrasias.

PMID:39735128 | PMC:PMC11681948 | DOI:10.7759/cureus.74677

Front Pharmacol. 2024 Dec 13;15:1480269. doi: 10.3389/fphar.2024.1480269. eCollection 2024.

ABSTRACT

INTRODUCTION: Retinal vein occlusion (RVO) often causes irreversible visual impairment, making early prevention crucial. This study aims to identify associations between different medications and RVO and provide information for clinical practice.

METHOD: This study included reports of RVO from the FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2023. The reported drugs were analyzed for adverse drug reaction (ADR) signals using four disproportionality algorithms. Kaplan-Meier curves and median time to onset were used to evaluate the drugs.

RESULTS: From 2004 to 2023, the FAERS database recorded 6,151 reports associated with RVO. Disproportionality analyses identified 25 drugs significantly associated with RVO. Mirabegron showed the highest risk signal, followed by Raloxifene, Tadalafil, Fingolimod, and Bimatoprost. These high-risk drugs are distributed across different therapeutic areas, including urogenital system and sex hormones, ophthalmic drugs, nervous system drugs, musculoskeletal system drugs, anti-tumor and immune-modulating drugs, and anti-parasitic drugs. Specific drug targets such as adrenergic receptor agonists, hormone regulators, and PDE5 inhibitors were identified as high risk. Ophthalmic drugs exhibited the longest median time to adverse ocular reactions at 532.01 days, followed by anti-parasitic drugs, nervous system drugs, urogenital system and sex hormone drugs, anti-tumor and immune-modulating drugs, and musculoskeletal system drugs.

CONCLUSION: This study provides an overview of drug-induced RVO, identifying potential culprit drugs and their distribution characteristics. These findings enhance understanding of medication safety and help optimize clinical practice.

PMID:39734405 | PMC:PMC11671269 | DOI:10.3389/fphar.2024.1480269

Respir Med. 2024 Dec 27:107924. doi: 10.1016/j.rmed.2024.107924. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The association between interstitial lung abnormalities (ILA) and various conditions and diseases, including drug-related pneumonitis (DRP), has been reported. However, the association of the presence of ILA with developing DRP in patients undergoing cytotoxic agent-based chemotherapy, one of the standard treatments for malignancies, remains unclear. This warrants urgent investigation.

METHODS: We included consecutive patients diagnosed with malignancy and treated with cytotoxic agents with/without immune checkpoint inhibitors (ICIs). We used Gray's method and multivariate Fine-Gray sub-distribution hazards analysis to evaluate the cumulative incidence of DRP (common terminology criteria for adverse events grade of ≥3) and the association between ILA and DRP development, respectively.

RESULTS: Among 786 patients, 58 (7.3%) demonstrated ILA. Patients with ILA were older, predominantly male, and reported a higher smoking history compared to those without ILA. The 90-day cumulative incidence of cytotoxic agent-induced DRP with/without ICIs was significantly higher in patients with ILA than in those without ILA (6.0% vs. 1.2%, p = 0.006). Multivariate analysis, adjusted for age, sex, and smoking history, revealed that ILA was associated with an increased risk of developing DRP due to cytotoxic agents with/without ICIs (hazard ratio [HR] 3.11, 95% confidence interval [CI]: 1.06-9.14, p = 0.039) and cytotoxic agents alone (HR: 5.53, 95% CI: 1.55-19.7, p = 0.008).

CONCLUSIONS: The presence of ILA is associated with an increased risk of developing DRP in patients undergoing cytotoxic agent-based chemotherapy. Therefore, evaluating the presence of ILA before determining chemotherapy regimens that include cytotoxic agents is recommended.

PMID:39733813 | DOI:10.1016/j.rmed.2024.107924