Zhang SH, Xu JZ, Zeng N
… +5 more, Xia ZY, Miao LT, Zhang C, Wang SG, Xia QD
Expert Opin Drug Saf
· 2025 Jun · PMID 40462621
·
Publisher ↗
OBJECTIVES: This study compares adverse events (AEs) of combined abiraterone acetate and olaparib treatment with their individual treatments for prostate cancer, focusing on safety profile differences and their clinical...OBJECTIVES: This study compares adverse events (AEs) of combined abiraterone acetate and olaparib treatment with their individual treatments for prostate cancer, focusing on safety profile differences and their clinical implications. METHODS: Data on AEs for abiraterone acetate and olaparib were extracted from the FDA Adverse Event Reporting System (FAERS) database between April 2011 and April 2024. The reporting odds ratio (ROR) was mainly utilized to analyze AEs and their preferred terms (PTs). RESULTS: A total of 32,745 AE reports for abiraterone acetate, 2493 for olaparib and 113 for combination therapy in males were identified. The combination therapy was associated with a higher risk of hematologic and lymphatic disorders and cardiovascular events compared to monotherapy. Notably, venous embolism and acute myocardial infarction showed significant ROR values in the combination therapy group. CONCLUSIONS: Combining abiraterone and olaparib increases risks of acute myocardial infarction, embolism, and pneumonitis over monotherapy. Though this combination improves survival, it demands vigilant patient monitoring and risk assessment. We recommend patients undergo serum lipid measurement, electrocardiograms, and cardiac and vascular ultrasounds to facilitate early detection and management of potential adverse effects. Additional research is needed to confirm these results and ensure the safe application of this drug combination.
Tao T, Du GL, Zhang ZJ
… +3 more, Luo ZY, Tang JF, Li X
Expert Opin Drug Saf
· 2025 May · PMID 40380893
·
Publisher ↗
OBJECTIVE: While extensive research has been conducted on isotretinoin's systemic side effects, studies focusing on its ocular side effects remain limited and often lack substantial sample sizes. To address this gap, we...OBJECTIVE: While extensive research has been conducted on isotretinoin's systemic side effects, studies focusing on its ocular side effects remain limited and often lack substantial sample sizes. To address this gap, we conducted a comprehensive investigation of isotretinoin-related ocular toxicity using data from the FAERS spanning 2004 to 2024. METHODS: After excluding duplicate and incomplete records from the FAERS database, we identified 760 eye-related adverse event reports from a total of 45,258 isotretinoin-related entries. We employed the Reporting Odds Ratio (ROR) method to assess the risk of ocular problems. Additionally, we examined the onset timing of eye toxicity. RESULTS: Among the 760 reports analyzed, dry eye emerged as the most frequently reported condition ( = 222), although it did not exhibit the strongest association. The ROR was observed for night blindness (ROR = 35.8, 95% CI = 29.66-43.21), indicating a significant risk. This finding underscores the need to focus on isotretinoin's impact on the retina and fundus, especially since night blindness and vision loss can manifest as early as the first day of treatment. CONCLUSION: These findings prompt new recommendations for safety monitoring by clinicians. However, additional clinical and fundamental research is essential to substantiate these observations and further elucidate the effects of isotretinoin on ocular health.
Liu Q, Sun S, Chu X
… +4 more, Li H, Zhang H, Li F, Song Y
Expert Opin Drug Saf
· 2025 May · PMID 40350711
·
Publisher ↗
BACKGROUND: Analgesics are widely used for pain management, yet their association with endocrine dysfunction remains understudied. This pharmacovigilance study analyzes endocrine-related adverse events (AEs) linked to an...BACKGROUND: Analgesics are widely used for pain management, yet their association with endocrine dysfunction remains understudied. This pharmacovigilance study analyzes endocrine-related adverse events (AEs) linked to analgesics, identifies high-risk populations, and explores mechanistic pathways. RESEARCH DESIGN AND METHODS: FAERS data (Q1 2004 to Q3 2023) were analyzed via OpenVigil 2.1 disproportionality analysis to assess analgesic-endocrine AE associations. Risk variations were evaluated through age/gender stratification, and molecular pathways were investigated via enrichment analysis. RESULTS: Opioids exhibited the strongest endocrine associations, particularly codeine with parathyroid injury (Reporting Odds Ratio [ROR]: 14.867, 95% Confidence interval [95% CI]: 12.336-17.918) and hypothalamic-pituitary injury (ROR: 3.197, 95% CI: 1.52-6.722), and methadone with testicular injury (ROR: 2.126, 95% CI: 1.446-3.126). Flurbiprofen (NSAIDs) exhibited pancreatic injury risk (ROR: 8.416, 95% CI: 5.187-13.656). Gabapentin/pregabalin showed no significant associations. Stratified analyses revealed elevated risks in females (e.g. codeine-parathyroid injury: ROR = 19.028 vs. non-significance in males) and in patients aged ≥ 60 years. Enrichment analysis implicated dysregulated hormone-metabolic pathways underlying tissue-specific injuries and pointed to disruption of several key signaling pathways. CONCLUSIONS: Specific analgesics (not all) are associated with endocrine risks, particularly in females and older adults, necessitating personalized monitoring despite limited dose-response data.
Su QY, Zhang JT, Gao HJ
… +5 more, Zhang Y, Luo J, Cao TY, Yang MY, Zhang SX
Expert Opin Drug Saf
· 2026 Jan · PMID 40347194
·
Publisher ↗
INTRODUCTION: Abatacept, a biological disease-modifying antirheumatic drug(bDMARD), has demonstrated unique and effective therapeutic properties for rheumatoid arthritis (RA). AREAS COVERED: This review offers an in-dept...INTRODUCTION: Abatacept, a biological disease-modifying antirheumatic drug(bDMARD), has demonstrated unique and effective therapeutic properties for rheumatoid arthritis (RA). AREAS COVERED: This review offers an in-depth examination of the mechanism by which abatacept exerts its effects in RA treatment and assesses its efficacy and safety based on a range of studies. We conducted a comprehensive search of PubMed, Embase databases, Web of Science, the Cochrane Library, MEDLINE, Wanfang Data, and CNKI from the time the databases were created until 30 July 2024. EXPERT OPINION: By modulating the CD28 and CD80/CD86 costimulatory signaling pathways, abatacept is instrumental in regulating immune cells and cytokines implicated in the pathogenesis RA. Longitudinal studies have highlighted its capacity to mitigate disease advancement and maintain joint functionality. The most frequently reported adverse effects associated with abatacept are headache, nausea, and upper respiratory tract infections, which are typically self-resolving. The incidence of serious infections was not high, mainly various types of bacterial pneumonia. Comparative safety analyses of abatacept with other DMARDs yield encouraging results. As our understanding of the mechanism of action of abatacept improves, we may be able to better identify appropriate biologic therapies and advanced combination therapies for RA patients and ultimately improve patient outcomes.
Expert Opin Drug Saf
· 2025 May · PMID 40324885
·
Publisher ↗
INTRODUCTION: To compare the risks of serious infections, herpes zoster (HZ), and opportunistic infections associated with Janus kinase (JAK) inhibitors versus placebo, tumor necrosis factor-α inhibitors (TNFi), methotre...INTRODUCTION: To compare the risks of serious infections, herpes zoster (HZ), and opportunistic infections associated with Janus kinase (JAK) inhibitors versus placebo, tumor necrosis factor-α inhibitors (TNFi), methotrexate (MTX), and among different JAK inhibitors. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science databases from their inception until 23 January 2024. Network meta-analysis estimated odds ratios for infections using restricted maximum likelihood models. RESULTS: Eighty randomized controlled trials were included with 40,460 patients. Part of JAK inhibitors including tofacitinib (5 mg [2.01; 95%CI, 1.25-3.23], 10 mg [1.84; 95%CI, 1.06-3.17]), baricitinib (4 mg [1.57; 95%CI, 1.05-2.35]), and upadacitinib (15 mg [1.55; 95%CI, 1.06-2.27], 30 mg [1.94; 95%CI, 1.26-2.98]), exhibited a significantly different risk of serious infections compared to placebo. Similarly, tofacitinib (10 mg), baricitinib (4 mg), upadacitinib (15 mg, 30 mg), abrocitinib (200 mg), and peficitinib (100 mg) showed a significantly different risk of HZ infection compared to placebo. Most JAK inhibitors didn't raise opportunistic infections risks vs. TNFi and MTX, and risks among JAK inhibitors weren't statistically significant. CONCLUSION: Attention should be paid to JAK inhibitor's types, dosages, and it is important to be aware of the risk of serious infections and HZ infections. Future long-term studies should be conducted. PROSPERO: CRD42024523067.
Yang JJ, Zhao H, Yan MM
… +4 more, Zheng X, Zhang Q, Chen HY, Qiu XY
Expert Opin Drug Saf
· 2025 May · PMID 40323709
·
Publisher ↗
BACKGROUND: Emerging studies have uncovered the innovative pharmacological characteristics of pioglitazone (PLZ). However, concerns regarding the potential link to an increased risk of bladder cancer (BC) had constrained...BACKGROUND: Emerging studies have uncovered the innovative pharmacological characteristics of pioglitazone (PLZ). However, concerns regarding the potential link to an increased risk of bladder cancer (BC) had constrained its clinical application. RESEARCH DESIGN AND METHODS: BC reports associated with PLZ and drug combinations containing PLZ from 1 January 2004 to 30 September 2024 were identified from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) method was applied to mine adverse drug event signals. RESULTS: Of 144 combinations, 15 showed an IC025 greater than 3, denoting a strong signal; 44 had an IC025 between 1.5 and 3, indicating moderate signal intensity; 36 had an IC025 between 0 and 1.5, pointing to a weak signal; and 49 had an IC025 less than 0, suggesting no apparent related signal. Importantly, the IC025 values for all drug combinations did not surpass the value observed when PLZ was used as monotherapy. CONCLUSIONS: Through comprehensive data mining, 14 PTs associated with BC were identified, indicating that specific medication combinations might mitigate the risk of PLZ-related BC. Our findings offer valuable insights for guiding decisions on PLZ combination therapies.
Meng P, Zhang Y, Zhao Q
… +2 more, Zhang H, Ruan Z
Expert Opin Drug Saf
· 2025 May · PMID 40321104
·
Publisher ↗
BACKGROUND: Non-infectious pneumonitis (NIP) is a severe adverse drug reaction. To better understand drug-induced NIP, improve patient safety, and inform clinical decision-making, this study aims to utilize the FDA Adver...BACKGROUND: Non-infectious pneumonitis (NIP) is a severe adverse drug reaction. To better understand drug-induced NIP, improve patient safety, and inform clinical decision-making, this study aims to utilize the FDA Adverse Event Reporting System (FAERS) database to evaluate the association between medications and NIP, identify potential risk factors, and offer clinical alerts. RESEARCH DESIGN AND METHODS: We reviewed the FAERS database from the 2004 through the second quarter of 2024. Using 'NIP' as the search term, we sorted, counted, and analyzed cases by generic drug name and trends of reports related to NIP submitted to FAERS database. We employed four statistical methods to identify drugs associated with the NIP. RESULTS: From 21,433,114 reported drug adverse events (AEs), 9,224 cases were classified as NIP. Our analysis identified 20 drugs associated with NIP, with the main categories being antineoplastic agents, antibiotics and immunosuppressants. Daptomycin, methotrexate, and tacrolimus had the highest NIP-related deaths. Trends in AEs reporting indicate that the drugs showing the fastest increase in NIP reports are daptomycin, methotrexate, sertraline, and amiodarone. CONCLUSION: These findings could assist clinicians in the early identification of drug-related NIP and provide valuable insights for future research into the mechanisms underlying drug-related NIP.
Pirozzi A, Hoyek C, Okano N
… +6 more, Abidoye O, Rimassa L, Sonbol MB, Uson Junior PLS, Bekaii-Saab T, Borad MJ
Expert Opin Drug Saf
· 2025 Dec · PMID 40307985
·
Publisher ↗
INTRODUCTION: Futibatinib is a small, potent, covalent, irreversible fibroblast growth factor receptor (FGFR) 1-4 inhibitor that has been added as a new standard of care for previously treated unresectable and/or advance...INTRODUCTION: Futibatinib is a small, potent, covalent, irreversible fibroblast growth factor receptor (FGFR) 1-4 inhibitor that has been added as a new standard of care for previously treated unresectable and/or advanced FGFR2 fusion/rearrangement-positive BTC. FGFR2 fusions/rearrangements play a key role in BTC survival, proliferation, invasion, and development of distant metastasis. The inhibition of this pathway is an important target in the treatment of BTC. AREAS COVERED: The article covers the development of futibatinib for the treatment of refractory unresectable/advanced BTC, its mechanism of action, and key pharmacodynamic/pharmacokinetic data with a focus on the safety profile. Data are based on published clinical trials, pooled analysis, and retrospective studies indexed in PubMed (2010-2024). EXPERT OPINION: Futibatinib is an FDA and EMA approved FGFR2 inhibitor for the treatment of patients with refractory BTC with FGFR2 fusions/rearrangements. Ongoing drug development strategies are centered on designing new FGFR2 fusion inhibitors able to overcome on-target and off-target resistances coupled with a high target selectivity to spare the most common treatment-related adverse events (hyperphosphatemia, stomatitis, alopecia, nail toxicity, skin reactions, eye toxicity).
Expert Opin Drug Saf
· 2025 Apr · PMID 40302414
·
Publisher ↗
BACKGROUND: The emergence of monoclonal antibodies has notably enhanced the outcomes for multiple myeloma. However, comprehensive assessment of monoclonal antibody-related pulmonary adverse events remains scarce. RESEARC...BACKGROUND: The emergence of monoclonal antibodies has notably enhanced the outcomes for multiple myeloma. However, comprehensive assessment of monoclonal antibody-related pulmonary adverse events remains scarce. RESEARCH DESIGN AND METHODS: This pharmacovigilance study analyzed adverse event data of monoclonal antibodies approved for myeloma from 1 January 2016, to 31 December 2023, using OpenVigil 2.1. Adverse event reports were classified based on the MedDRA v24.0 into five pulmonary SMQs: asthma/bronchospasm, infective pneumonia, interstitial lung disease, pulmonary hypertension, and respiratory failure. Disproportionality analyses were utilized to identify potential risk signals. RESULTS: A total of 8,043,250 reports were extracted. Male patients and those aged ≥ 65 years were predominant. Hospitalization and death were common outcomes. Elranatamab had the highest risk for infective pneumonia, elotuzumab had the highest risk for interstitial lung disease, and isatuximab had the highest risk for respiratory failure. Significant associations were discovered between pulmonary adverse events and all five monoclonal antibodies. Viral pneumonia was most prevalent with daratumumab, fungal pneumonia was predominant with elotuzumab, and bacterial pneumonia was predominant with isatuximab, teclistamab, and elranatamab. CONCLUSIONS: This study summarized significant pulmonary adverse event signals associated with monoclonal antibodies approved for myeloma, emphasizing the significance of monitoring interstitial lung disease, respiratory failure, and infective pneumonia.
Expert Opin Drug Saf
· 2025 May · PMID 40302219
·
Publisher ↗
BACKGROUND: Limited data have raised concerns about an increased risk of thromboembolic adverse events in atrial fibrillation (AF) patients co-treated with factor Xa-inhibiting direct oral anticoagulants (FXa-DOACs) and...BACKGROUND: Limited data have raised concerns about an increased risk of thromboembolic adverse events in atrial fibrillation (AF) patients co-treated with factor Xa-inhibiting direct oral anticoagulants (FXa-DOACs) and anti-seizure medications (ASMs). However, evidence regarding this association remains controversial. OBJECTIVES: This study aims to investigate the impact of ASMs on the reporting of thromboembolic events in FXa-DOAC-treated patients. METHODS: This study analyzed data from the FDA Adverse Event Reporting System (FAERS) between 2011Q3 and 2024Q1 using the weighted composite score integrated by four pharmacovigilance signals [reporting odds ratio (ROR), Empirical Bayes Geometric Mean (EBGM), additive model and multiplicative model]. RESULTS: A total of 177 cases of thromboembolic events were identified in patients using combined FXa-DOACs and ASMs. Levetiracetam together with FXa-DOACs was associated with an increased risk of thromboembolic events, particularly apixaban (ROR: 2.29, 95%CI 1.56-3.38; EBGM05:1.32; additive model:0.14 > 0; multiplicative mode: 2.47 > 1;composite score:1) and rivaroxaban (ROR:3.81, 95% CI 2.77-5.26; EBGM05:1.99; additive model:0.13; multiplicative model:1.71; composite score:1). Valproic acid was associated with thromboembolic risk when with rivaroxaban (ROR:4.80, 95%CI 2.50-9.19; EBGM05:1.64; additive model:0.29; multiplicative model:8.48; composite score:1). CONCLUSION: This study suggests that the concomitant use of levetiracetam and valproic acid with FXa-DOACs is associated with an increased risk of thromboembolic events.
Sittiphan S, Lim A, Dureh N
… +3 more, Shah S, Tanchanarat A, Khurram H
Expert Opin Drug Saf
· 2025 May · PMID 40292767
·
Publisher ↗
BACKGROUND: Adverse drug reactions (ADRs), which can occur in any drug class and are one of the leading causes of morbidity and hospitalization around the world, remain a public health concern. This study aimed to explor...BACKGROUND: Adverse drug reactions (ADRs), which can occur in any drug class and are one of the leading causes of morbidity and hospitalization around the world, remain a public health concern. This study aimed to explore the distribution and patterns of anti-infective-induced ADRs in Thailand. RESEARCH DESIGN AND METHODS: The national database of anti-infective-induced ADRs from January 2012 to December 2021 in the 77 provinces of Thailand. After the pre-processing, frequencies and percentages were used to examine the distribution of the ADRs. The chi-square test was used for measuring association for anti-infective-induced ADRs. RESULTS: A total of 82,333 anti-infective-induced ADR reports were recorded from 2012-2021 in the 77 provinces of Thailand. The most commonly reported ADRs were in Central Thailand (29.0%), followed by the Northeast (25.9%). Most of the patients were females aged 20-39. Antibiotics categorized by chemical structure, cephalosporin (28.0%) and penicillin (23.4%), were the most common anti-infective drug-induced ADRs. Dose frequency and ADR onset were statistically associated with therapeutic drug class, anti-infective group, and disease (p-value < 0.05). CONCLUSIONS: The results of this study will enable healthcare professionals to prioritize groups and policymakers to make effective ADR prevention policies to reduce the risk and improve patient safety.
Expert Opin Drug Saf
· 2025 May · PMID 40289838
·
Publisher ↗
BACKGROUND: First-generation KRAS inhibitors, sotorasib and adagrasib, are approved for treating non-small cell lung cancer and colorectal cancer with specific KRAS mutations. This study analyzed data from FAERS database...BACKGROUND: First-generation KRAS inhibitors, sotorasib and adagrasib, are approved for treating non-small cell lung cancer and colorectal cancer with specific KRAS mutations. This study analyzed data from FAERS database to evaluate adverse events (AEs) associated with KRAS inhibitors. RESEARCH DESIGN AND METHODS: Four disproportionality analysis methods were applied to measure risk signals: reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS) algorithms. RESULTS: Between Q2 2021 and Q1 2024, 5,580 AEs in 2,958 reports on sotorasib or adagrasib were identified. Most patients were 45 and above, with a median age of 67. After meeting four algorithms' criteria, sotorasib and adagrasib retained 43 and 18 disproportionate priority items (PTs), respectively. Common AEs were diarrhea, hepatotoxicity, and pneumonitis. Unexpected important AEs included pericardial effusion, colitis, and pancreatitis associated with sotorasib; seizure, encephalopathy, unresponsiveness to stimuli and disorientation with adagrasib. Most AEs emerged within the first month of treatment. The median time to onset was 50 days for sotorasib and 21 days for adagrasib. CONCLUSIONS: Our research revealed potential new AE signals and provided a comprehensive safety profile of KRAS inhibitors, emphasizing the importance of careful monitoring and supportive care.
Cui L, Guo D, Zhu M
… +3 more, Wang T, Gao A, Xiao J
Expert Opin Drug Saf
· 2025 May · PMID 40286279
·
Publisher ↗
BACKGROUND: To investigate the incidence and clinical characteristics of drug-induced movement disorders(DIMDs)in a large group of hospitalized patients. RESEARCH DESIGN AND METHODS: A retrospective study was conducted a...BACKGROUND: To investigate the incidence and clinical characteristics of drug-induced movement disorders(DIMDs)in a large group of hospitalized patients. RESEARCH DESIGN AND METHODS: A retrospective study was conducted among hospitalized patients in 2022, utilizing the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II). After the operation and manual selection, DIMDs cases were identified for analysis of incidence, associated drugs, and clinical characteristics. RESULTS: Among 102,914 hospitalized patients, 504 cases were identified as DIMDs, with an incidence of 0.49%. There were more males than females.Most patients were over 65 years old.A total of 158 associated drugs across 15 classes were identified, with the top three classes being antibiotics(12.10%), antiepileptics(8.13%), and calcium channel blockers (7.14%).The top three drugs were sodium valproate(1.67%),meropenem(0.58%)and pregabalin (0.55%).The clinical manifestations were primarily shakiness, tremor and tic. Different manifestations are difficult to distinguish.It's necessary to make a thorough record and consult specialists. CONCLUSION: For the first time, this study found that the incidence of DIMDs in hospitalized patients in general hospitals was 0.49%, occurs occasionally. Clinicians should pay close attention to the manifestations and identification of involuntary movements. Enhanced monitoring is recommended when using valproate, meropenem and pregabalin.
McCall KL, Mastro Dwyer KA, Casey RT
… +5 more, Samana TN, Sulicz EK, Tso SY, Yalanzhi ER, Piper BJ
Expert Opin Drug Saf
· 2026 Mar · PMID 40285721
·
Publisher ↗
BACKGROUND: This study evaluated the safety of compounded glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared to non-compounded formulations using the U.S. FDA Adverse Event Reporting System (FAERS). RESEARCH...BACKGROUND: This study evaluated the safety of compounded glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared to non-compounded formulations using the U.S. FDA Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: A retrospective analysis of FAERS from 2018 to 2024 examined adverse events (AEs), medication errors, and product quality issues for liraglutide, semaglutide, and tirzepatide. Reporting odds ratios (RORs) with 95% confidence intervals were calculated with adjustment using logistic regression. RESULTS: Of the 81,078 GLP-1 RA reports in the FAERS database, 707 involved compounded products. Compounded formulations demonstrated higher RORs for abdominal pain (2.84 [2.29, 3.49]), diarrhea (1.59 [1.25, 1.99]), nausea (1.27 [1.05, 1.52]), suicidality (6.34, [4.32, 8.99]), and cholecystitis (3.39, [1.61, 6.31]). Compounded products showed higher RORs of preparation errors (48.92 [12.63, 189.6]), prescribing errors (4.46, [2.49, 7.98]), contamination (19.00, [4.24, 85.03]), and compounding/manufacturing issues (8.51, [5.17, 14.0]), while lower odds of administration (0.29 [0.16, 0.53]) and dosing errors (0.24, [0.17, 0.32]). The hospitalization odds were higher for compounded products (2.35 [1.94, 2.83]). CONCLUSIONS: Compounded GLP-1 RAs may be associated with a higher odds of AEs, safety concerns, and product quality issues compared to non-compounded products. These findings underscore the importance of cautious prescribing, rigorous quality standards, and enhanced patient monitoring.
Expert Opin Drug Saf
· 2025 Apr · PMID 40285682
·
Publisher ↗
BACKGROUND: Colistin, a last-resort antimicrobial, is often used in combination with other drugs to treat multidrug-resistant infections, but its nephrotoxic potential raises concerns, especially in combination therapies...BACKGROUND: Colistin, a last-resort antimicrobial, is often used in combination with other drugs to treat multidrug-resistant infections, but its nephrotoxic potential raises concerns, especially in combination therapies. RESEARCH DESIGN AND METHODS: A retrospective analysis was performed on 29,163,222 reports from the USFDA Adverse Event Reporting System (AERS), identifying 125 reports meeting inclusion criteria for acute renal failure (ARF) associated with colistin-antimicrobial combinations. Disproportionality analysis using frequentists and Bayesian techniques were employed to evaluate ARF risk. Drug interaction and clinical outcomes were assessed using the Interaction-Adjusted SignalScores (INTSS) and mortality data, respectively. RESULTS: The results showed significantly higher ARF risk for colistin combinations with ceftazidime, vancomycin, meropenem, and tigecycline, with particularly strong signals observed for colistin-ceftazidime combinations, corroborated by INTSS. Mortality rates were paradoxically higher in patients receiving colistin without nephrotoxic antimicrobials. Comprehensive signal detection metrics highlighted a consistent ARF risk for several other antimicrobial combinations. Clinical outcomes analysis revealed a complex relationship between combination therapy choices and patient mortality. CONCLUSION: Colistin combinations with certain antimicrobials, especially ceftazidime, vancomycin, and tigecycline, carry significantly higher nephrotoxicity risks, warranting careful clinical consideration. Rigorous renal monitoring protocols are essential in managing these therapies, particularly in critically ill patients.
Luo Z, Zhang M, Liang W
… +8 more, Hu M, Jiang Y, Lei X, Wang Z, Zhu J, Du Y, Liu Y, Yang C
Expert Opin Drug Saf
· 2025 Apr · PMID 40266634
·
Publisher ↗
BACKGROUND: To assess lurasidone's real-world safety via retrospective analysis of post-marketing adverse reactions. RESEARCH DESIGN AND METHODS: Signal mining was carried out by retrieving the adverse events (AEs) assoc...BACKGROUND: To assess lurasidone's real-world safety via retrospective analysis of post-marketing adverse reactions. RESEARCH DESIGN AND METHODS: Signal mining was carried out by retrieving the adverse events (AEs) associated with lurasidone from the FDA Adverse Event Reporting System (FAERS) database spanning from the first quarter of 2011 to the fourth quarter of 2023. Disproportionality analyses including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and empirical Bayesian geometric mean (EBGM) were used to assess the presence of significant associations between lurasidone and AEs. RESULTS: From the 10,176,406 reports collected in the FAERS database, a total of 12,451 reports of lurasidone-related AEs were identified, which focused on Psychiatric disorders ( = 8950), notably, akathisia and parkinsonian rest tremor are strongly associated with lurasidone; Breast engorgement, galactorrhea, breast discharge, and umbilical cord around neck and new ocular AEs including oculogyric crisis, excessive eye blinking, and blepharospasm, have not been mentioned in the specification. The most common and most severe PT reported was off-label use, followed by suicidal ideation. CONCLUSIONS: This study reveals known and unexpected AEs about lurasidone, related to the eye, lactating women and life-threatening threats, and underscores the need for ongoing post-marketing surveillance of lurasidone.
Bres V, Ben Fadhel N, Trouillet R
… +3 more, Broc G, Chiriac A, Faillie JL
Expert Opin Drug Saf
· 2025 Apr · PMID 40265270
·
Publisher ↗
BACKGROUND: Allergy-like symptoms after COVID-19 vaccination are frequently reported, though true allergic reactions are rare. Clinical trials suggest many reported symptoms may reflect nocebo effects. This study aimed t...BACKGROUND: Allergy-like symptoms after COVID-19 vaccination are frequently reported, though true allergic reactions are rare. Clinical trials suggest many reported symptoms may reflect nocebo effects. This study aimed to characterize nocebo responses and identify associated factors. RESEARCH DESIGN AND METHODS: A case-control study was conducted using pharmacovigilance records and a cross-sectional questionnaire. Cases were defined as patients reporting allergy-like symptoms without anaphylaxis; controls reported reactogenicity or localized reactions. Data on demographics, medical history, vaccinations, and psychological factors were analyzed using multivariate logistic regression to identify risk factors associated with nocebo effects. RESULTS: Among 1038 participants, 320 were nocebo cases and 718 were controls. Cases frequently reported cutaneous (71.8%) and respiratory (38.8%) symptoms, with 43.4% occurring after the first dose. Nocebo responses were positively associated with a history of allergy (OR 1.78, 95% CI: 1.32-2.4) and COMIRNATY vaccine (OR 1.60, 95% CI: 1.20-2.14), and negatively correlated with perceived vaccine effectiveness (OR 0.93, 95% CI: 0.88-0.98). CONCLUSIONS: The nocebo effect appears to differ by vaccine type and is more common in individuals with a history of allergy and lower perceived vaccine effectiveness. While further research is needed to validate these findings, this underscores the importance of clear, evidence-based communication to reduce nocebo responses.
Al Aamer K, Al Sulaiman K, Aljuhani O
… +20 more, Alshehri S, Alshehri AM, Aldawood L, AlQurashi A, Aloufi K, Kassem L, Nazel S, Albarqi K, Alsaeedi AS, Alonazi S, Alqahtani A, Alhmoud M, Aljohani M, Bahri QA, Alanazi A, Jassar S, Alnasser B, Alqadi R, Alqumia A, Al-Dorzi HM
Expert Opin Drug Saf
· 2025 Apr · PMID 40263941
·
Publisher ↗
BACKGROUND: Evidence is limited on the utilization of the Medication Regimen Complexity - Intensive Care Unit (MRC-ICU) scores for predicting clinical outcomes in critically ill patients. Therefore, this study aims to ex...BACKGROUND: Evidence is limited on the utilization of the Medication Regimen Complexity - Intensive Care Unit (MRC-ICU) scores for predicting clinical outcomes in critically ill patients. Therefore, this study aims to examine the impact of the MRC-ICU score on clinical outcomes for critically ill patients. RESEARCH DESIGN AND METHODS: A single-center retrospective cohort study included adult ICU patients admitted for >72 hours between January and December 2021. Patients were categorized into two groups based on MRC-ICU scores assessed within 24 hours of ICU admission. The primary endpoint was the Multiorgan Dysfunction (MOD) score at 72 hours of ICU admission. Other clinical outcomes were considered secondary. RESULTS: Of the 1406 patients included, 718 had an MRC-ICU score of nine or higher. Patients with MRC-ICU scores ≥9 had significantly higher MOD scores at 72 hours (median 5 vs 3, < 0.001), longer hospital LOS, and higher mortality rates in crude analyses. Regression analysis showed a significant association between MRC-ICU score and MOD score at day 3 of ICU admission (coefficient: 0.49, 95% CI 0.07 to 0.92, = 0.02). However, no significant differences were observed with ICU-LOS, vasopressor-free days, or mortality. CONCLUSIONS: Higher MRC-ICU scores might be linked to worse clinical outcomes, including greater organ dysfunction, and longer hospital stay.