International Journal of Clinical Pharmacy最新文献

Introduction: Ublituximab, a novel glycoengineered murine/human type Ⅰ chimeric IgG1-class monoclonal antibody targeting a unique CD20 epitope, is approved for the management of relapsing forms of multiple sclerosis in adults. While the safety and efficacy of ublituximab have been evaluated in several randomized clinical trials, real-world pharmacovigilance data remain limited.

Aim: This study aimed to evaluate the post-marketing adverse events (AEs) associated with ublituximab utilizing the FDA Adverse Event Reporting System (FAERS) database, thereby delineating the safety profile of ublituximab in the post-approval setting.

Method: The AE reports of ublituximab as the primary suspected drug from Q4 2022 to Q4 2024 were collected from the FAERS database. Disproportionality analysis, including the Reporting Odds Ratio, the Proportional Reporting Ratio, the Bayesian Confidence Propagation Neural Network, and the Multi-Item Gamma Poisson Shrinker, was performed to identify potential safety signals associated with ublituximab. Complementary analyses, comprising subgroup analysis, Weibull distribution, and sensitivity assessment, were conducted to characterize the ublituximab-associated AEs.

Results: A total of 1,190 reports encompassing 448 distinct AEs were collected. Known AEs that are consistent with the FDA label, such as infusion-related reactions (n = 591, ROR = 271.35, 95% CI 246.57-298.61) and infections (urinary tract infection: n = 28, ROR = 4.31, 95% CI 2.97-6.27; Respiratory tract infection: n = 8, ROR = 7.39, 95% CI 3.69-14.8), were reaffirmed, along with unexpected AEs like alopecia (n = 12, ROR = 2.06, 95% CI 1.17-3.64) and headache (n = 50, ROR = 2.55, 95% CI 1.93-3.38). The Weibull distribution characteristic of AEs is an early failure type, which indicates that vigilant monitoring in the initial treatment cycle is critical. Subgroup analyses revealed variations in the distribution across age and gender subgroups. Sensitivity analysis confirmed the consistency and robustness of the data.

Conclusion: This study provided preliminary insights into the post-marketing safety profile of ublituximab by confirming its known AEs and investigating unexpected AEs. These findings contribute to evidence-based risk minimization strategies and pharmacovigilance activities for ublituximab in clinical practice.

Introduction: Aplastic anemia is a rare but life-threatening disorder often triggered by drug exposure. Given its low incidence, identifying drug-associated risks requires large-scale real-world data. The FDA Adverse Event Reporting System (FAERS) is a valuable pharmacovigilance resource for detecting rare and serious drug reactions.

Aim: This study aimed to evaluate the association between a broad range of medications and the risk of drug-induced aplastic anemia using FAERS data obtained through disproportionality analysis, regression modeling, time-to-onset analysis, and predictive modeling.

Method: A retrospective pharmacovigilance study was conducted using FAERS reports from January 1, 2004, to December 31, 2024. Aplastic anemia cases were identified using five Preferred Terms from the Medical Dictionary for Regulatory Activities. Signal detection was performed using ROR, PRR, BCPNN, and MGPS. Logistic regression analyses with weighted LASSO variable selection identified the independent risk factors. A predictive model was developed and validated using receiver operating characteristic (ROC) curve analysis. Time-to-onset (TTO) and pharmacological classification were also conducted.

Results: A total of 4493 drug-related aplastic anemia cases were identified. Disproportionality analysis revealed 593 significant drugs, of which 16 met stringent inclusion criteria for multivariate analysis. Temozolomide was most frequent (n = 148), followed by methotrexate (n = 126), busulfan (n = 100), and linezolid (n = 90). Other common drugs included ribavirin, nivolumab, pembrolizumab, fludarabine, carboplatin, etoposide, and cyclophosphamide. Male sex was a significant risk factor (OR = 1.63), while older age (> 42 years) and higher weight (> 60 kg) were protective. The predictive model showed good discrimination (AUC = 0.777). Median TTO was 299 days, with most cases occurring within six months. The 16 implicated drugs fell into categories including antineoplastics, antibacterials, antivirals, antiepileptics, and antigout agents.

Conclusion: This study identified key drugs and patient factors associated with aplastic anemia, providing a data-driven framework for pharmacovigilance. These findings support early detection and informed clinical and regulatory decision making, but prospective studies are required to confirm causality and refine individualized risk predictions.

Introduction: Approximately one-third of patients with minor ischemic stroke (MIS) and transient ischemic attack (TIA) fail to achieve functional independence due to stroke progression or recurrent stroke. Identifying effective secondary prevention strategies is crucial to reduce morbidity, mortality, and disability.

Aim: This systematic review and network meta-analysis aimed to evaluate the effectiveness and safety of various antiplatelet therapies using network meta-analysis and to identify the optimal treatment option for patients with MIS or high-risk TIA.

Method: Studies were retrieved from PubMed, Embase, Web of Science, and Cochrane Library from inception to August 29, 2024. Randomized controlled trials (RCTs) and observational studies comparing antiplatelet treatments for MIS or high-risk TIA were included through consensus. The primary outcome was recurrent strokes. The secondary outcomes included recurrent ischemic strokes and a composite outcome combining ischemic stroke, myocardial infarction, and vascular death. The safety outcomes included intracerebral hemorrhage (ICH), any bleeding events, and all-cause mortality. Treatments were ranked based on the surface under the cumulative rank curve (SUCRA).

Results: Nineteen studies, including 12 RCTs and seven observational studies with 90,483 patients, were analyzed. Compared with aspirin or other mono antiplatelet therapies, both dual antiplatelet therapies of clopidogrel plus aspirin and ticagrelor plus aspirin reduced the risk of recurrent strokes, recurrent ischemic strokes, and the composite outcome without increasing the risk of ICH or all-cause mortality. However, ticagrelor plus aspirin significantly increased the risk of any bleeding. This treatment had the highest SUCRA score (0.97) for the primary outcome and the lowest (0.01) for any bleeding.

Conclusion: Based on the combined results of effectiveness and safety, clopidogrel plus aspirin may be the optimal choice. However, for patients with a low bleeding risk, ticagrelor plus aspirin serves as an appropriate alternative.

Introduction: Antimicrobial stewardship (AMS) education plays a vital role in addressing antimicrobial resistance (AMR), yet its long-term impact on behavior and clinical outcomes remains underexplored. Educational interventions are often assessed through knowledge-based outcomes, with limited evaluation of sustained practice changes or patient-level results, and standardized higher-level outcome measures across diverse healthcare settings.

Aim: This scoping review aimed to map pre-post AMS healthcare educational interventions using the Kirkpatrick Model, evaluating their effectiveness across its four levels: reaction, learning, behavior, and results. The goal was to identify trends, highlight gaps, and provide insight into reported outcomes, delivery methods, and evaluation tools, supporting future research and strengthening the evidence base for AMS education.

Method: This review followed the Joanna Briggs Institute framework. A literature search of nine databases identified studies from 2010 to 2024. Eligible studies included pre-post AMS educational interventions targeting undergraduate students and healthcare professionals (HCPs) and reporting outcomes which were subsequently mapped by the reviewers to the Kirkpatrick Model. Data were categorized by target population, delivery format, and evaluation tools. Narrative synthesis was used to describe trends and relationships.

Results: Studies targeted HCPs such as physicians, pharmacists, nurses, and dental professionals, and undergraduate students in pharmacy, medicine, nursing, and dentistry. Sixty-three studies were included. Outcomes were distributed across Level 1 (Reaction) (n = 46, 24%), Level 2 (Learning) (n = 51, 27%), Level 3 (Behavior) (n = 50, 26%), and Level 4 (Results) (n = 45, 23%). While n = 24 (38%) assessed all four levels, another n = 24 (38%) reported mixed or partial levels. Face-to-face or online-only formats achieved Levels 1 and 2. Whereas blended or workplace-integrated interventions more often demonstrated behavior change and clinical outcomes (Levels 3 and 4). Longitudinal follow-up and mixed evaluation tools (e.g., surveys, chart reviews, interviews) supported higher-level impacts. Pharmacy-led, interdisciplinary, and contextually tailored interventions mapped to all levels.

Conclusion: AMS education often leads to short-term learning gains, but fewer interventions achieve sustained behavior change or measurable clinical outcomes. Blended and practice-integrated formats, paired with long-term evaluation, are key to realizing the full potential of AMS education. Embedding such approaches in undergraduate and professional programs can better prepare the future HCPs to address AMR effectively.

Introduction: Polypharmacy and potentially inappropriate medications (PIMs) are common among terminally ill older people and often persist until death, undermining comfort-focused care. While deprescribing is an effective strategy to optimise medicines use at the end of life, its timing is crucial. Delaying deprescribing until after hospice admission may diminish opportunities for comprehensive medication review during hospital-based care, when a full multidisciplinary team (MDT) and complete clinical records are available. Timely deprescribing during the final days of hospital-based care before hospice transition may better align pharmacotherapy with end-of-life goals and facilitate transition.

Aim: This study aimed to evaluate the impact of an MDT-led intervention delivered during the final days of hospital-based care before hospice transition on medication burden, PIM use, and symptom control prescribing.

Method: This retrospective cohort study was conducted at a Jordanian tertiary hospital. Patients aged ≥ 65 years with life-limiting illnesses who were transitioned to hospice care between January and December 2022 were included. Medication data were extracted at baseline (seven days before MDT review) and post-intervention (in the final 24 h of hospital-based care). Deprescribing was categorised as proactive (planned discontinuation to prevent future harm) or reactive (triggered by an immediate clinical issue). Medication appropriateness was assessed using STOPPFrail version 2. Regimen complexity was evaluated using the Medication Regimen Complexity Index (MRCI).

Results: Among 165 patients, polypharmacy (use of ≥ five medications) prevalence declined from 63.0% to 14.5% (P < 0.001), and the proportion receiving ≥ one PIM decreased from 91.6% to 34.0% (P < 0.001). The mean number of chronic medications declined by 4.5 (± 3.2), and MRCI scores decreased by 4.8 points (P < 0.001). Of 736 medications discontinued, 65.9% were proactively deprescribed. Use of symptom control medications, particularly opioids, increased significantly (from 5 to 64 prescriptions; P < 0.001). Regression analysis identified baseline polypharmacy, high MRCI, and dyslipidaemia as predictors of greater PIM reduction.

Conclusion: MDT-led deprescribing, implemented during the final days of hospital-based care before hospice transition, was associated with reduced medication burden and PIM use, alongside increased symptom-focused prescribing. These findings support the integration of structured, proactive deprescribing into hospital-based care to improve medication safety, enhance patient comfort, and facilitate continuity across care settings.

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) is an aggressive disease with a poor prognosis. Current treatment guidelines recommend combining androgen receptor axis-targeted therapies (ARATs) with androgen deprivation therapy (ADT) for mHSPC. While individual ARATs have shown success, few studies directly compare their effects.

Aim: To compare the safety and clinical outcomes of abiraterone acetate (abiraterone) and apalutamide in chemotherapy-naïve mHSPC patients, focusing on prostate-specific antigen (PSA) kinetics, safety, and survival outcomes.

Method: A retrospective, single-centre study included 107 chemotherapy-naïve mHSPC patients treated with abiraterone or apalutamide plus ADT. PSA levels were measured at baseline and during treatment. Primary outcomes were PSA progression-free survival (PSA-PFS) and overall survival (OS). Adverse events were recorded. Inverse probability treatment weighting adjusted baseline differences.

Results: Median PSA-PFS significantly favoured apalutamide (log-rank p = 0.015). Achieving PSA ≤ 0.02 ng/mL was strongly associated with delayed progression (HR 0.07, 95% CI 0.02-0.28; p < 0.001). OS did not differ significantly between groups (p = 0.504). Apalutamide achieved lower median nadir PSA (0.02 ng/mL vs. 0.23 ng/mL, p < 0.001) and shorter mean time to nadir (4.5 vs. 7.2 months, p = 0.001), with more patients reaching ultralow PSA levels (≤ 0.02 ng/mL) during follow-up. Adverse events occurred more frequently with apalutamide (71.2% vs. 46.5%, p = 0.015), with fatigue and rash being the most common.

Conclusion: Apalutamide demonstrated deeper and more sustained PSA reductions, translating into delayed disease progression compared to abiraterone. Both treatments were generally well tolerated, though adverse events were more prevalent with apalutamide.

Background: Glucagon-like peptide 1 (GLP-1) analogues are a class of medications that stimulate glucose-dependent insulin release and slow gastric emptying. With the increasing use of GLP-1 analogues, concerns about potential psychiatric adverse events (AEs) remain under-explored.

Aim: This pharmacovigilance study aimed to investigate the prevalence of psychiatric AEs associated with currently available GLP-1 analogues by analysing publicly available national datasets from the US (FAERS), Canada (CVAROD) and Australia (DAEN).

Method: Psychiatric AE reports were extracted from all three databases for all approved GLP-1 analogues. A disproportionality analysis was conducted to calculate reporting odds ratios (RORs) and 95% confidence intervals (CIs) for psychiatric AEs of interest.

Results: Significant associations were identified when multiple databases reported elevated RORs. Semaglutide was associated with depressive symptoms (FAERS, ROR = 6.24 CI 4.49-8.69), panic attacks (FAERS, ROR = 1.46 CI 1.16-1.82) and suicidal ideation (FAERS, ROR = 2.58 CI 2.31-2.88). Liraglutide was linked to depression (CVAROD, ROR = 1.68 CI 1.12-2.51), while dulaglutide showed positive associations with eating disorders (FAERS, ROR = 1.47 CI 1.26-1.71) and insomnia (FAERS, ROR = 2.93 CI 2.35-3.66).

Conclusion: GLP-1 analogues, particularly semaglutide and liraglutide, are associated with significant psychiatric AEs, especially depression and suicidal ideation. Further studies are required to understand the mechanisms underlying these associations, particularly in patients with pre-existing psychiatric conditions.

Introduction: To improve access to innovative medications, the Chinese government introduced a dual-channel policy, allowing community pharmacies to dispense innovative drugs listed in the National Reimbursement Drug List of the national healthcare security system. However, research on how community pharmacies interpret and respond to these policies remains limited.

Aim: To investigate community pharmacy manager/ pharmacist perceptions of and responses to the dual-channel policy, with a focus on improving accessibility and the rational use of innovative drugs for patients in China.

Method: A qualitative research design, involving semi-structured interviews, was conducted in Jiangsu Province, China. The interview guide was developed to address key domains relevant to community and licensed pharmacists. The participants were recruited through purposive and snowball sampling to ensure diverse perspectives. The interviews were audio-recorded, transcribed, and analyzed using the framework method. NVivo software was used for coding and theme development, until theoretical saturation was achieved.

Results: The participants viewed the dual-channel policy as an opportunity to expand business operations and enhance market competitiveness. However, they also identified several challenges, including space and storage constraints, regional inconsistencies in electronic prescription systems, limited influence on hospital prescription flows, selective partnerships with pharmaceutical companies, and elevated service expectations from patients. In response, pharmacies have implemented a range of hardware-focused strategies, such as upgrading service areas, integrating insurance billing systems, and developing patient management platforms, as well as soft competence strategies, including pharmacist training on innovative drugs and disease knowledge, interpretation of reimbursement policies, and emergency response preparedness.

Conclusion: This study demonstrates that participation in a dual-channel policy is widely perceived by community pharmacies as a strategic opportunity, despite the associated operational and systemic challenges. Proactive engagement with the policy not only strengthened their competitive positioning but also contributed to improved pharmaceutical services and patient care outcomes.

Introduction: Mitomycin, a cytotoxic antitumor antibiotic, has been approved for the treatment of low-grade upper tract urothelial carcinoma (UTUC) and non-muscle invasive bladder cancer (NMIBC). It is also used off-label in ophthalmic procedures and gastrointestinal malignancies. Although the efficacy of mitomycin is well recognized, its safety profile, particularly regarding rare or serious adverse events (AEs), remains insufficiently characterized in large real-world populations.

Aim: This study aimed to evaluate mitomycin-associated AEs through comprehensive analysis of two major global pharmacovigilance databases, with the goal of identifying high-risk organ systems and specific AE signals requiring increased clinical awareness.

Method: AE data were retrieved from the FDA Adverse Event Reporting System (FAERS) covering Q1 2004 to Q3 2024. Data were deduplicated and standardized according to MedDRA terminology. Complementary data were collected from the World Health Organization VigiAccess database. Disproportionality analysis was performed using four signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The time-to-onset of adverse events was analyzed using non-parametric statistical methods.

Results: A total of 1461 mitomycin-related reports, comprising 3652 AEs, were identified in the FAERS database. Notably, strong safety signals have emerged at the system organ class (SOC) level for eye, renal and urinary, blood and lymphatic system, and skin and subcutaneous tissue disorders. At the preferred term (PT) level, high disproportionality values were observed for serious events, such as scleral thinning (OR = 7129.60, 95% CI 4576.64-11,106.7) and bladder perforation (OR = 1585.69, 95% CI 1111.91-2261.33). Over two-thirds of AEs occurred within 30 days of drug administration, although 68.93% of the reports lacked valid onset-time data. The VigiAccess findings corroborated the SOC trends observed in FAERS.

Conclusion: Mitomycin is associated with a broad range of organ-specific toxicities, many of which occur early in the treatment course and may have serious clinical consequences. This study highlights the need for early risk identification, individualized monitoring strategies, and greater pharmacovigilance in populations treated with mitomycin. These findings provide an important foundation for optimizing the safe and effective use of mitomycin in oncology and in other therapeutic settings.

Introduction: Proton pump inhibitors (PPIs) are widely prescribed as acid-suppressive agents; however, their use during pregnancy remains controversial. Although generally considered safe, omeprazole is classified as Food and Drug Administration (FDA) pregnancy category C, whereas other PPIs are classified as category B, raising concerns regarding potential maternal and fetal risks. Clarifying the safety profile during pregnancy is critical to inform clinical decision making.

Aim: This study aimed to evaluate pregnancy-related adverse event (AE) signals associated with omeprazole, esomeprazole, lansoprazole, rabeprazole, and pantoprazole using data from the US FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q1 2025.

Method: A total of 625,127 AE reports listing PPIs as primary suspect drugs were retrieved, among which 1,099 pregnancy-related reports were identified. Signal detection employs two disproportionality algorithms: the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN). Each PPI was compared with all other drugs in the database, all other PPIs, and ranitidine, a comparator that is considered relatively safe during pregnancy.

Results: Disproportionality signals for pregnancy-related AEs associated with PPIs included premature labor, low birth weight, fetal growth restriction (FGR), abortion, fetal macrosomia, pregnancy on contraception, morning sickness, pre-eclampsia, and hemorrhagic complications. Compared with all the other drugs, omeprazole showed notable signals of postpartum hemorrhage (ROR: 3.14, 95% CI 1.63-6.04; E(IC): 1.36, IC025:0.45), FGR (ROR: 2.14, 95% CI 1.52-3.01; E(IC): 1.046, IC025:0.55), and pre-eclampsia (ROR: 1.95, 95% CI 1.27-3; E(IC): 0.9, IC025:0.28). These associations persisted when compared with other PPIs or ranitidine. Pantoprazole showed consistent risk signal trends, such as premature labor (ROR: 1.48, 95% CI 1.26-1.74; E(IC): 0.56, IC025:0.32), low birth weight babies (ROR: 2.08, 95% CI 1.56-2.76; E(IC): 1.02, IC025:0.6), and morning sickness (ROR: 3.9, 95% CI 1.75-8.7; E(IC): 1.46, IC025:0.36).

Conclusion: This study detected potential disproportionality signals, suggesting an association between PPIs use during pregnancy and reported AEs. Certain signals appeared to be drug-specific rather than class-specific, such as omeprazole for postpartum hemorrhage and preeclampsia, lansoprazole for pregnancy on contraceptives, and pantoprazole for morning sickness. However, these findings should be regarded as exploratory and hypothesis generating, warranting cautious interpretation and confirmation through rigorously designed epidemiological and clinical studies.