European Journal Of Clinical Pharmacology[JOURNAL]
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200 papers
Impact of policy measures targeting benzodiazepines and Benzodiazepine-related drugs in Lithuania: interrupted time series analysis.
Lasys T, Essink SCM, Santa-Ana-Tellez Y … +6 more , Siiskonen SJ, Weir DL, Zomerdijk IM, Groenwold RHH, De Bruin ML, Gardarsdottir H
Eur J Clin Pharmacol · 2026 Feb · PMID 41649577 · Full text
PURPOSE: Prescribing recommendations, communication programmes, and mandatory electronic prescribing were implemented in Lithuania to promote responsible use of benzodiazepines and benzodiazepine-related drugs (BZRDs). W...
PURPOSE: Prescribing recommendations, communication programmes, and mandatory electronic prescribing were implemented in Lithuania to promote responsible use of benzodiazepines and benzodiazepine-related drugs (BZRDs). We assessed the impact of policy measures on benzodiazepine/BZRD prescribing patterns in Lithuania. METHODS: We analysed utilisation of oral benzodiazepines/BZRDs in Lithuania from 2018 to 2024, using national prescription data and wholesale medicines data. Benzodiazepines/BZRDs included (1) anxiolytic benzodiazepines; (2) hypnotic benzodiazepines; and (3) BZRDs. The policy intervention period spanned from November 1, 2020, to July 1, 2021. We used ARIMA models to assess monthly incidence, prevalence, and long-term use prevalence (≥ 180 days) per 1,000 inhabitants. Besides, the numbers of defined daily doses (DDDs) prescribed and sold to pharmacies per 1,000 inhabitants were studied. We estimated baseline slopes, step changes after implementation, and changes in slopes after implementation. RESULTS: In total, 717,590 patients received 6,974,059 prescriptions for benzodiazepines or BZRDs. Prior to implementing the policy measures, there were upward trends in incidence, prevalence, and long-term use prevalence across all classes. Following the implementation, monthly incidence stabilised and prevalence decelerated for anxiolytic benzodiazepines and BZRDs. The prevalence of hypnotic benzodiazepines showed a significant immediate reduction after implementation. Long-term use prevalence continued to increase for all benzodiazepine/BZRD classes after implementation of the policy. Before the policy measures were implemented, monthly DDDs sold to pharmacies were gradually declining for anxiolytic benzodiazepines, but were stable for other classes. In contrast, monthly DDDs prescribed were increasing across all classes. Following the policy measures, immediate reductions in DDDs sold to pharmacies were observed, without changes in slopes. The prescribed and sold DDDs converged after implementing the policy measures. CONCLUSION: From a public health perspective, the policy measures implemented in 2020 and 2021 had only a limited impact on the prescribing patterns of benzodiazepines and BZRDs in Lithuania. They continued to be used long-term, highlighting the persistence of potentially irrational prescribing.
Early albumin infusion and mortality in ICU patients with HFpEF: a target trial emulation study.
Wang Z, Li ML, Zhu NJ … +2 more , Fan TT, Zhang YM
Eur J Clin Pharmacol · 2026 Feb · PMID 41649576 · Publisher ↗
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a growing clinical challenge with limited treatment options. Hypoalbuminemia is common in HFpEF and associated with worse outcomes, yet the benefits o...
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a growing clinical challenge with limited treatment options. Hypoalbuminemia is common in HFpEF and associated with worse outcomes, yet the benefits of albumin infusion remain unclear. Due to practical limitations of randomized controlled trials (RCTs), we used Target Trial Emulation (TTE) to evaluate the effect of early albumin administration in this population. METHODS: We conducted a retrospective cohort study using the MIMIC-IV database, emulating an RCT to assess the effect of early albumin infusion (≥ 12.5 g within 24 h of Intensive Care Unit (ICU) admission) on 365-day mortality among ICU patients with HFpEF. A cloning-censoring-weighting approach was applied to simulate randomization and adjust for confounding and selection bias using inverse probability of treatment (IPTW) and censoring (IPCW) weights. A marginal weighted Cox model was fitted, and multiple sensitivity, subgroup, dose–response, and negative-control analyses were performed to assess robustness. RESULTS: A total of 7,269 ICU patients with HFpEF were included, of whom 807 (11.1%) received ≥ 12.5 g of albumin within 24 h. After weighting, early albumin administration was not associated with improved 365-day survival (HR 1.07, 95% CI 0.87–1.32). Exploratory subgroup analyses suggested a possible association between early albumin infusion and reduced mortality among patients with albumin > 3.5 g/dL (HR 0.52, 95% CI 0.28–0.95), with no corresponding signal in those ≤ 3.5 g/dL. Reinforcement analyses within the > 3.5 g/dL subgroup—including alternative exposure definitions, dose–response modeling, E-value assessment (E-value 3.27), and a negative-control outcome (ΔCreatinine)—supported that this subgroup-specific association was consistent, though exploratory. CONCLUSIONS: Early albumin infusion does not improve long-term survival in the overall ICU HFpEF population. A subgroup association was observed among patients with serum albumin > 3.5 g/dL; however, this finding is hypothesis-generating only and requires prospective validation. TRIAL REGISTRATION: Not applicable. This study is a retrospective observational study based on [MIMIC-IV database] and is not considered a clinical trial according to ICMJE criteria.
Circadian considerations in antimicrobials.
Livieratos A, Grigoropoulos I, Tsiodras S
Eur J Clin Pharmacol · 2026 Feb · PMID 41649575 · Publisher ↗
PURPOSE: Circadian rhythms regulate key physiological processes, including metabolism, immune function, and organ perfusion, which can influence antimicrobial pharmacokinetics and, in turn, may indirectly shape pharmacod...
PURPOSE: Circadian rhythms regulate key physiological processes, including metabolism, immune function, and organ perfusion, which can influence antimicrobial pharmacokinetics and, in turn, may indirectly shape pharmacodynamic outcomes through changes in drug exposure or host immune responses. This review examines the evidence supporting circadian effects on antimicrobial efficacy and toxicity and evaluates the potential clinical relevance of time-of-day dosing. METHODS: We conducted a narrative review of 84 experimental and clinical studies published up to November 2025, identified through PubMed and Scopus. Eligible studies evaluated time-of-day or circadian effects on antimicrobial pharmacokinetics, safety, efficacy, or host immune response across major antibacterial, antiviral, antifungal, and antiparasitic drug classes. RESULTS: Circadian variation in gastric motility, hepatic metabolism, and renal clearance can alter antimicrobial exposure independent of dose. The most consistent circadian associations relate to toxicity: aminoglycoside and amphotericin B nephrotoxicity are more frequent with rest-phase dosing, while fluoroquinolone-associated QT prolongation is greater with afternoon administration, suggesting a relative safety advantage with morning dosing. Evidence for circadian modulation of antimicrobial efficacy is limited and heterogeneous, with observed effects more plausibly explained by variations in drug exposure, host immunity, or particularly in parasitic infections-pathogen developmental stage rather than intrinsic circadian changes in pathogen susceptibility. For many antivirals and antifungals, long half-lives and fixed dosing schedules minimize the clinical impact of dosing time. CONCLUSION: Overall, circadian regulation may influence antimicrobial pharmacology and toxicity in selected settings, although the available evidence is heterogeneous and clinical validation remains limited.
The phenprocoumon echo: Elevated INR risk after VKA reversal - A retrospective analysis of phenprocoumon and acenocoumarol in clinical practice in a Dutch teaching hospital.
Tijmensen-Reijers EMC, Saleh S, Griffioen-Keijzer A … +4 more , van Uden RCAE, Brijker F, Nierman MC, Becker ML
Eur J Clin Pharmacol · 2026 Feb · PMID 41649572 · Publisher ↗
INTRODUCTION: In case of excessively elevated INR values (INR > 6), major bleeding or emergency surgery, there is a need to reverse the anticoagulant effect of vitamin K antagonists (VKAs). Phenprocoumon’s longer half-li...
INTRODUCTION: In case of excessively elevated INR values (INR > 6), major bleeding or emergency surgery, there is a need to reverse the anticoagulant effect of vitamin K antagonists (VKAs). Phenprocoumon’s longer half-life poses greater challenges for reversal compared to acenocoumarol when using short-acting agents like phytomenadione and prothrombin complex concentrate (PCC). Data on supratherapeutic INR recurrence after reversal of both acenocoumarol and phenprocoumon remain limited. This study aims to compare the incidence of supratherapeutic INR following reversal with PCC and/or phytomenadione in patients using phenprocoumon versus acenocoumarol. METHODS: A retrospective observational study was conducted at Spaarne Gasthuis (Haarlem/ Hoofddorp, the Netherlands), analysing data from 2009 to 2024. Patients using acenocoumarol or phenprocoumon who achieved successful reversal (INR ≤ 2.0 within 48 h) with PCC and/or phytomenadione were included. Patients were followed from 48 h post-reversal until INR > 3.5, VKA resumption, discharge, death, or 14 days post-reversal. The primary outcome was the time to elevated INR (> 3.5). RESULTS: A total of 2,334 admissions were included. In 1,506 admissions, no INR was measured during follow-up. Phenprocoumon use was associated with a significantly higher risk of supratherapeutic INR after both PCC-based reversal (HR: 4.01, 95% CI: 1.41–15.30) and phytomenadione alone (HR: 3.71, 95% CI: 1.20-14.72). The risk was especially pronounced in patients with a baseline INR ≥ 6. CONCLUSION: Phenprocoumon use is associated with a higher risk of supratherapeutic INR elevation following reversal compared to acenocoumarol use. In patients with a baseline INR ≥ 6, almost all recurrences were in phenprocoumon users.
Remimazolam vs. midazolam sedation in upper gastrointestinal endoscopy in adults ≥ 65 years: Randomized controlled trial.
Park JH, Noh CK, Lim SG … +3 more , Shin SJ, Lee KM, Lee GH
Eur J Clin Pharmacol · 2026 Feb · PMID 41649570 · Full text
PURPOSE: Safe and effective sedation are important factors when performing gastrointestinal endoscopy. However, clinicians should be cautious when using sedatives in older patients because of their decreased physiologica...
PURPOSE: Safe and effective sedation are important factors when performing gastrointestinal endoscopy. However, clinicians should be cautious when using sedatives in older patients because of their decreased physiological reserves. Remimazolam is an ultrashort active benzodiazepine that has attracted attention because of its efficacy. This study aimed to determine the safety and efficacy of remimazolam compared with midazolam as a sedative for diagnostic upper gastrointestinal endoscopy in older patients aged ≥ 65 years. METHODS: We randomly assigned patients aged ≥ 65 years who were scheduled for diagnostic upper gastrointestinal endoscopy. The average induction time, average recovery time, and side effect profile of patients who received remimazolam as a sedative were compared with those of patients who received midazolam. RESULTS: A total of 120 patients underwent randomization (60 in the remimazolam group and 60 in the midazolam group). Patients who received remimazolam had shorter average induction (mean ± standard deviation, 102.0 ± 77.2 s vs. 327.5 ± 125.3 s, p < 0.001) and recovery times (mean ± standard deviation, 5.8 ± 3.1 min vs. 13.4 ± 7.8 min, p < 0.001) than those who received midazolam. No significant difference in side effect profiles was observed between the groups. CONCLUSIONS: In performing upper gastrointestinal endoscopy in older patients, remimazolam can be a good alternative sedative to midazolam, whether used as monotherapy or in combination therapy.
A word on "Effects of drugs on the oxygen dissociation curve-a scoping review".
Rehman MU, Chola MH
Eur J Clin Pharmacol · 2026 Feb · PMID 41649567 · Publisher ↗
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Impact of eGFR estimation methods on drug dosing in pediatric ICU: a study of serum creatinine vs. cystatin C.
Samman A, Al-Jelaify M, Alsunaidi A … +3 more , Temsah MH, Alhasan KA, Alsultan A
Eur J Clin Pharmacol · 2026 Feb · PMID 41649566 · Publisher ↗
BACKGROUND AND OBJECTIVE: Serum creatinine (Scr)-based equations, particularly the Schwartz equation, are widely used to estimate glomerular filtration rate (eGFR) and guide drug dosing in pediatric intensive care unit (...
BACKGROUND AND OBJECTIVE: Serum creatinine (Scr)-based equations, particularly the Schwartz equation, are widely used to estimate glomerular filtration rate (eGFR) and guide drug dosing in pediatric intensive care unit (PICU) patients. However, Scr may be influenced by non-renal factors, potentially leading to inaccurate renal function assessment. Cystatin C–based equations like the Hoek equation may serve as a better tool to guide drug dosing in PICU patients. The objective of this study was to examine the concordance between eGFR estimated using the Schwartz and Hoek equations and to investigate its potential implications for drug dosing in PICU patients. METHODS: This was a prospective study of PICU patients aged 1 month to 14 years receiving renally eliminated antibiotics. eGFR was calculated using both the Schwartz and Hoek equations. Analyses included the mean relative difference, mean absolute relative difference, concordance rates within 10% and 30%, and classification into renal function categories: Participants were grouped by eGFR range: less than 50 ml/min/1.73m2, between 50 and 130 ml/min/1.73m2, and greater than 130 ml/min/1.73m2 ml/min/1.73m2 ml/min/1.73m2 ml/min/1.73m2. Agreement between the two estimation methods was further evaluated using Bland–Altman and scatter plots. RESULTS: A total of 65 pediatric patients were included in the study. The Schwartz equation overestimated estimated glomerular filtration rate compared to the Hoek equations, with a mean relative difference of 37.5% and mean absolute relative difference of 46.3%. Only 15% of patients had estimated glomerular filtration rate estimates within 10%, and 46% within 30% of each other. The renal function classification agreement between equations was 58%. Notably, the Schwartz equation categorized 48% of patients as having augmented renal clearance, compared to only 18% using the Hoek equation. CONCLUSIONS: There is significant discordance between serum creatinine and cystatin C based estimated glomerular filtration rate estimates in critically ill pediatric patients. The Schwartz equation frequently overestimates renal function, which may lead to inappropriate dosing. Greater adoption of cystatin C based methods in the PICU setting could improve the estimation of the GFR and drug dosing.
Artificial intelligence and machine learning for precision warfarin dosing: a comprehensive narrative review.
Shamohammadi M, Nazari MA, Mirkalaie SMM … +5 more , Dowlat BF, Hoseini D, Garavand AA, Javid S, Hosseini K
Eur J Clin Pharmacol · 2026 Feb · PMID 41649565 · Publisher ↗
BACKGROUND: Warfarin remains one of the most widely used anticoagulants; however, its narrow therapeutic index means that even small dosing deviations can result in thromboembolic or bleeding events, necessitating close...
BACKGROUND: Warfarin remains one of the most widely used anticoagulants; however, its narrow therapeutic index means that even small dosing deviations can result in thromboembolic or bleeding events, necessitating close monitoring and strict control of the international normalized ratio (INR). MAIN BODY: Although traditional warfarin dosing algorithms incorporating CYP2C9 and VKORC1 genotypes improve upon fixed-dose regimens, they explain less than 50% of dose variability and perform inconsistently across populations. These limitations underscore the need for more adaptive and precise dosing methodologies. Artificial intelligence (AI) and machine learning (ML) have been recognized as powerful approaches to advance warfarin dose individualization. This narrative review synthesizes literature on machine learning approaches to warfarin dosing, including support vector regression, neural networks, ensemble models, and reinforcement learning, with a focus on predictive performance and clinical relevance. Overall, the literature indicates that ML-based warfarin dosing models may improve prediction of the therapeutic warfarin dose and regulation of INR levels compared with traditional clinical and pharmacogenetic interventions. However, many published models are constrained by small sample sizes and limited external validation, reducing generalizability. Methodological heterogeneity and inconsistent reporting further underscore persistent gaps in the evidence base. CONCLUSION: AI and ML approaches have shown potential advantages over clinical and pharmacogenetic dosing methods for warfarin, with some studies reporting lower prediction errors and improved therapeutic INR control. However, further studies are needed to draw definitive conclusions about their comparative effectiveness.
Relating consequential falls to individual and combinations of prescription medication use in Swedish older adults.
Peterson DS, Johansson L, Westerlind B … +2 more , Lopes de Oliveira T, Finkel D
Eur J Clin Pharmacol · 2026 Feb · PMID 41649547 · Full text
PURPOSE: We assessed the relationship between prescription of medications (both individually and in combination) and consequential falls. METHODS: Medication prescription and prospectively registered falls over 2.5 years...
PURPOSE: We assessed the relationship between prescription of medications (both individually and in combination) and consequential falls. METHODS: Medication prescription and prospectively registered falls over 2.5 years were extracted from 441 participants within a Swedish National Quality Register. Conditional generalized estimating equations, considering dependence of longitudinal data as a cluster to correct confidence intervals, were used to relate medications (individual and in combination) and falls. RESULTS: Regarding individual-medications, Angiotensin II receptor blockers and diuretics (C09DA) were significantly related to incidence of consequential falls (p = 0.022). Six drug combinations significantly related to fall incidence. Most frequently, falls were observed when platelet aggregation inhibitors (B01AC) were prescribed with C09DA, opioids (N02AA), or blood glucose lowering drugs (biguanides, A10BA). DISCUSSION: Caution should be taken when prescribing cardiovascular medications. Further, prescription of platelet aggregation inhibitors could increase the incidence of a negative outcome of a fall when prescribed in people at risk for falls.
Assessing patient risk, benefit, and outcomes in drug development: a decade of sorafenib clinical trials.
Corwin L, George J, Paul E … +11 more , Smith T, Hughes GK, McIntire R, Gardner B, Peña A, Ladd C, Minley K, Riley K, Haslam A, Prasad V, Vassar M
Eur J Clin Pharmacol · 2026 Feb · PMID 41649539 · Publisher ↗
BACKGROUND: Pharmaceutical companies frequently explore previously approved cancer drugs for new indications, which may expose trial participants to uncertain benefit and potential harm. Sorafenib has been investigated a...
BACKGROUND: Pharmaceutical companies frequently explore previously approved cancer drugs for new indications, which may expose trial participants to uncertain benefit and potential harm. Sorafenib has been investigated across numerous cancer types despite limited evidence supporting many off-label uses. This study evaluates sorafenib’s reported risk–benefit profile in clinical trials published during the past decade. OBJECTIVE: To assess the portfolio of sorafenib trials by examining reported efficacy and safety outcomes over the last ten years. METHODS: A literature search of bibliographic databases was conducted on May 25, 2023, to identify adult clinical trials evaluating sorafenib’s antitumor activity. Eligible studies were published within the prior decade and reported objective response criteria. Screening and data extraction were performed in duplicate. Extracted variables included trial characteristics, objective response rate (ORR), grade 3–5 adverse event (AE) rates, median progression-free survival, and median overall survival. Primary endpoints were categorized as positive, negative, or indeterminate based on author-defined criteria. RESULTS: Since sorafenib’s most recent FDA approval in 2013, investigators have examined its activity in more than 32 off-label indications. Across 154 trials, 12,226 participants were evaluable for AE grading, with 11,003 grade 3–5 AEs reported. Cumulative trends demonstrated persistently low ORR and increasing cumulative rates of severe AEs over time across off-label indications. CONCLUSION: This descriptive portfolio review highlights that, across published trials of sorafenib monotherapy in non-FDA-approved indications, reported objective responses were infrequent while severe AEs were common. These findings underscore the importance of transparent reporting and careful consideration of the existing evidence base when designing or interpreting future sorafenib trials in off-label settings. Key words: Sorafenib, Off-label indications, Risk-benefit analysis, Clinical trial portfolio, Adverse events
Efficacy and safety of treatments for atopic dermatitis: a model based meta-analysis of randomized controlled trials.
Zhang L, Gong Y, Gu X … +7 more , Liu Y, Chen M, Yi Q, Jia J, Li L, Xu L, Zheng Q
Eur J Clin Pharmacol · 2026 Jan · PMID 41618061 · Publisher ↗
PURPOSE: We aimed to quantitatively compare the efficacy and safety of currently marketed Atopic Dermatitis (AD) therapies and placebo in AD patients, providing evidence-based guidance for clinical treatment selection. M...
PURPOSE: We aimed to quantitatively compare the efficacy and safety of currently marketed Atopic Dermatitis (AD) therapies and placebo in AD patients, providing evidence-based guidance for clinical treatment selection. METHODS: Randomized controlled trials (RCTs), drug labels, and regulatory review documents related to AD treatments and placebo were retrieved from PubMed, FDA, EMA, NMPA, and PMDA databases from inception to July 11, 2023. The response rates of Eczema Area and Severity Index (EASI) 75, clear (0) or almost clear (1) with a ≥ 2-point improvement in Investigator's Global Assessment (IGA) including validated IGA (vIGA) (hereinafter referred to as IGA), EASI 90 and ≥ 4-point improvement in Pruritus Numerical Rating Scale (PP-NRS4) were used as the efficacy index. Time-effect models were subsequently established using a model-based meta-analysis (MBMA). For treatments not suitable for MBMA or subgroup analyses stratified by disease severity and age groups, meta-analyses were conducted. Safety outcomes were compared via pooled analysis. RESULTS: A total of 274 articles and 4 FDA review documents were identified, with 77 studies and 2 FDA reviews ultimately included (total sample size: 20,262). Results showed that all topical and systemic medications demonstrated superior efficacy (EASI 75 response rate) to placebo. Among topical treatments, methylprednisolone showed the highest efficacy. For non-steroidal topicals, ruxolitinib cream exhibited the best efficacy, followed by tacrolimus ointment and difamilast ointment. Among systemic treatments, upadacitinib demonstrated the highest efficacy, followed by abrocitinib, with dupilumab ranking third as the most effective biologic. Baricitinib showed relatively lower efficacy. Biologics exhibited slower onset compared to other treatments. Safety analysis revealed higher overall adverse event incidence with systemic treatments versus topical treatments. CONCLUSION: MBMA was conducted for the time courses of several efficacy index. In conclusion, results showed that there is still a lack of treatment methods that balance efficacy, safety and speed of onset. The results of this MBMA can be used as a reference for optimizing clinical medication and provide a basis for decision-making in the future development of new AD drugs.
Correction to: Adherence to psychotropic medication in completed suicide in Sweden 2006-2013: a forensic-toxicological matched case-control study.
Forsman J, Taipale H, Masterman T … +2 more , Tiihonen J, Tanskanen A
Eur J Clin Pharmacol · 2026 Jan · PMID 41593397 · Full text
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The effectiveness and safety of oral anticoagulation therapy in patients undergoing transcatheter aortic valve replacement: a systematic review/meta-analysis.
Zhou Q, Liu X, Liu S … +4 more , Yang X, Wu Y, Tao Y, Wei M
Eur J Clin Pharmacol · 2026 Jan · PMID 41571953 · Publisher ↗
BACKGROUND: Patients undergoing transcatheter aortic valve replacement (TAVR) often require anticoagulation therapy due to various comorbidities. However, the decision to continue anticoagulation therapy during the TAVR...
BACKGROUND: Patients undergoing transcatheter aortic valve replacement (TAVR) often require anticoagulation therapy due to various comorbidities. However, the decision to continue anticoagulation therapy during the TAVR perioperative period and the optimal regimen for postoperative anticoagulation therapy remain debatable. METHODS: We searched the PubMed, EMBASE, MEDLINE, and Cochrane Library databases from their date of establishment to September 2024. We evaluated the choice of anticoagulation regimen in the TAVR perioperative and postoperative period. The primary outcomes were stroke, major bleeding, all-cause death, and net adverse clinical events (NACEs). The secondary outcomes were any bleeding, life-threatening bleeding, thrombotic events, and cardiovascular death. We conducted a meta-analysis with a RR and 95% CI. We performed subgroup analyses based on the follow-up duration, study design, and whether oral antiplatelet drugs (OAP) were used. RESULTS: We compared four studies with peri-procedural continuation or discontinuation of oral anticoagulants (OACs). We did not observe a difference between the two groups with major bleeding, stroke, all-cause death, and NACEs (P > 0.05). Seventeen studies compared the effects of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) after TAVR. The risk of NACEs (RR: 0.84, 95% CI :0.71-0.99, P = 0.04) and cardiovascular death (RR: 0.78, 95% CI: 0.69-0.87, P < 0.0001) was significantly lower in the DOACs than in the VKAs, but there were no statistically significant differences between the two groups with other outcomes. In the subgroup analysis, the beneficial effects of DOACs on NACEs were observed in the early postoperative (P < 0.05). During the long-term follow-up time after TAVR, DOACs had a lower risk of all-cause mortality and cardiovascular death compared to VKAs (P < 0.05), but an increased risk of any bleeding (P < 0.05). In RCTs, the risk of any bleeding owing to DOACs was higher (P < 0.05). In cohort studies, DOACs led to lower NACEs and cardiovascular death (P < 0.05). When administered in combination with OAP drugs, DOACs posed a lower risk for cardiovascular death and all-cause death than VKAs (P < 0.05). If not administered in combination with OAP drugs, DOACs posed a lower risk for all-cause death (P < 0.05). CONCLUSION: In patients undergoing TAVR with established indications for OACs, periprocedural continuation of OACs may offer comparable clinical outcomes to temporary discontinuation. Furthermore, DOACs after TAVR appear to be associated with more favorable clinical outcomes than VKAs, although this benefit must be weighed against a potentially increased risk of bleeding. Further large-scale RCTs are warranted to validate these findings.
Trimetazidine and allopurinol for the prevention of Contrast-associated acute kidney injury in elective percutaneous coronary intervention: a randomized controlled trial.
Ali NO, Bazan NS, Mowafy HH … +2 more , Abdelrahim MEA, Harb HS
Eur J Clin Pharmacol · 2026 Jan · PMID 41566038 · Full text
PURPOSE: Contrast-associated acute kidney injury (CA-AKI) is a significant concern following percutaneous coronary intervention (PCI). This study assessed whether adding trimetazidine (TMZ) or TMZ/allopurinol to standard...
PURPOSE: Contrast-associated acute kidney injury (CA-AKI) is a significant concern following percutaneous coronary intervention (PCI). This study assessed whether adding trimetazidine (TMZ) or TMZ/allopurinol to standard hydration reduces CA-AKI among elective PCI patients. METHODS: 129 patients undergoing elective PCI were randomized into three groups: Group 1 received (IV isotonic saline + TMZ + allopurinol), Group 2 received (IV isotonic saline + TMZ), and Group 3 (control) received (IV isotonic saline only). The primary outcome was the incidence of CA-AKI at 24- and 48-hour post-PCI. Risk was stratified using the Mehran and the Age, Creatinine, and Ejection Fraction (ACEF) scores. RESULTS: Group 1 demonstrated a non-significant reduction in CA-AKI incidence compared with Groups 2 and 3 (24 h: 4.65%, 4.55%, and 9.52%; 48 h: 16.28%, 20.45%, and 28.57%; p > 0.05). All patients were classified as low-moderate risk by ACEF and Mehran scores, neither of which predicted CA-AKI. At 48 h, SGLT2 inhibitors users demonstrated a smaller rise in creatinine compared with non-users (-0.04 ± 0.158 mg/dL vs. 0.096 ± 0.237 mg/dL, p < 0.05), as did DPP-4 inhibitor users (-0.05 ± 0.217 mg/dL vs. +0.098 ± 0.237 mg/dL, p < 0.05). Diuretics were associated with greater increases (p < 0.05). CONCLUSION: The TMZ-allopurinol combination showed a favorable but non-significant trend toward reducing CA-AKI, while ACEF and Mehran scores demonstrated limited predictive value. Improved risk-stratification tools and larger studies in higher-risk patients are needed. SGLT2 and DPP-4 inhibitors showed smaller creatinine increases, suggesting possible nephroprotection, but this remains exploratory.
Letter to the editor: Severe myasthenic crises following infiltration of amide local anesthetics in a patient with myasthenia gravis: an unusual adverse reaction.
Bouaziz I, Atheymen R, Sahnoun R … +4 more , Ksouda K, Affes H, Hammami S, Zghal K
Eur J Clin Pharmacol · 2026 Jan · PMID 41565840 · Publisher ↗
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Prescribed drugs and comorbidities as risk factors for Torsades de Pointes arrhythmia: a Swedish population-based cohort study.
Andersson ML, Fastbom J, Danielsson B … +3 more , Wikström E, Dahl ML, Nowinski K
Eur J Clin Pharmacol · 2026 Jan · PMID 41553550 · Full text
PURPOSE: Drug-induced long QT interval syndrome (LQTS) is a risk for Torsade de Pointes (TdP) arrhythmia. The purpose was to investigate patients diagnosed with TdP in relation to dispensed risk drugs, the presence of co...
PURPOSE: Drug-induced long QT interval syndrome (LQTS) is a risk for Torsade de Pointes (TdP) arrhythmia. The purpose was to investigate patients diagnosed with TdP in relation to dispensed risk drugs, the presence of comorbidities, and sex-differences. METHODS: All patients with a first episode of a registered TdP diagnosis in the National Patient Register between 2006 and 2018 were included in this register-based cohort study. Comorbidities within five years and medications dispensed within 90 days prior to TdP diagnosis were retrieved. Drugs were classified for their risk to cause TdP ("risk drugs") using two different Clinical Decision Support Systems (CredibleMeds and Janusmed). RESULTS: The cohort consisted of 762 patients (50% females) with TdP, median age 72 years. A majority (59%) were dispensed at least one risk drug and 338 patients (44%) had at least one risk diagnosis for TdP. Concomitant use of several risk drugs was common. Prior to TdP, 558 patients (73%) had at least one risk diagnosis and/or were dispensed at least one risk drug. More females than males used antidepressants (26% vs 12%, p < 0.01) although the total use of risk drugs were similar in females compared to males. More males than females had risk diagnoses for TdP (53% vs. 36%, p < 0.004). CONCLUSION: A majority of patients with TdP had been dispensed risk drugs and/or had risk diagnoses. Sex-differences in dispensed drugs and risk diagnoses were identified. Prescription drugs, underlying risk diagnoses and sex should be incorporated into the risk assessment for TdP.
Effects of ABC transporter polymorphism on the pharmacokinetics of pentoxifylline and its active metabolites in healthy Chinese subjects.
Guo L, Sun X, Qiu B … +3 more , Bai W, Du Y, Song H
Eur J Clin Pharmacol · 2026 Jan · PMID 41553547 · Publisher ↗
PURPOSE: The objective of this study was to evaluate the influence of genetic polymorphisms in drug transporters on the pharmacokinetics of pentoxifylline (PTX) and its key active metabolites in a healthy Chinese populat...
PURPOSE: The objective of this study was to evaluate the influence of genetic polymorphisms in drug transporters on the pharmacokinetics of pentoxifylline (PTX) and its key active metabolites in a healthy Chinese population. SUBJECTS AND METHODS: Forty-six healthy Chinese volunteers were enrolled and took oral administration of 400 mg pentoxifylline. Plasma concentrations of PTX and its active metabolites (M1 and M5) were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Genotyping of ABCB1 (3435C>T, 1236C>T, 2677G>T/A), ABCG2 (421C>A, 34G>A), and ABCC2 (-24C>T, 1249G>A, 3972C>T) was performed using the SnapShot technique. RESULTS: Under fasting conditions, subjects carrying the ABCB1 3435C/T genotype demonstrated a significantly lower AUC (P < 0.05, Bonferroni-corrected) and a higher CL/F (P < 0.01, Bonferroni-corrected) of PTX compared to those carrying the ABCB1 3435C/C genotype. Furthermore, carriers of the ABCB1 3435C/T genotype exhibited a significantly higher metabolic conversion rate to M5 (P < 0.05, Bonferroni-corrected). Similarly, subjects with the ABCB1 2677(A/A+A/T) genotypes also showed a higher M5 conversion rate (P < 0.05, Bonferroni-corrected). CONCLUSION: The ABCB1 3435C>T and 2677G>T/A polymorphisms are associated with variations in the pharmacokinetics of PTX and its active metabolites.
A review of current therapeutics for psoriasis: Systemic and topical use of non-biological drugs.
Gün E, Sevgi S, Demirçi B … +4 more , Arıca İE, Helvacı G, Büyüktaş A, Sezen SF
Eur J Clin Pharmacol · 2026 Jan · PMID 41553544 · Publisher ↗
PURPOSE: Psoriasis is a chronic, immune-mediated inflammatory disease characterized by dysregulated cytokine signaling, keratinocyte hyperproliferation, and recurrent relapses requiring sustained management. Although bio...
PURPOSE: Psoriasis is a chronic, immune-mediated inflammatory disease characterized by dysregulated cytokine signaling, keratinocyte hyperproliferation, and recurrent relapses requiring sustained management. Although biologic agents have transformed treatment by selectively targeting IL-17, IL-23, and TNF-α pathways, important limitations persist, including high costs, limited accessibility, treatment failures, and insufficient long-term safety data. Therefore, topical therapies and non-biologic small-molecule systemic agents remain essential, particularly for mild-to-moderate disease and for patients ineligible for biologic therapy. This review provides an integrative assessment of established and emerging topical and non-biologic systemic treatments. METHODS: A systematic search of PubMed® and ClinicalTrials.gov with 'psoriasis, topical therapies, clinical trials, systemic therapy' keywords, identified several small-molecule classes in active clinical development, including JAK/TYK2 inhibitors, PDE-4 inhibitors, AhR modulators, A3AR agonists, RORγt and ROCK2 inhibitors, S1P1 modulators, and IRAK4/RIPK1 inhibitors. RESULTS: Among these, oral TYK2 inhibitors have shown the most consistent late-phase success, offering superior PASI responses, rapid onset of action, and favorable emerging long-term safety profiles. Early-phase studies of other targets report promising reductions in inflammatory biomarkers and lesion severity, though interpretation remains limited by small cohorts, short follow-up, and the lack of head-to-head comparisons. Topical therapies, especially corticosteroids, remain foundational first-line options and valuable adjuncts to systemic regimens. While topical JAK inhibitors have generated interest in clinical trials, their clinical efficacy has not paralleled the superior outcomes achieved with oral JAK/TYK2 inhibitors. CONCLUSION: Overall, current evidence suggests that targeted non-biologic small molecules are gaining importance as scalable, patient-friendly alternatives to biologics. Their optimal placement within future treatment algorithms will depend on long-term safety data, comparative clinical trials, biomarker-guided patient selection, and cost-effectiveness analyses.
Clozapine and Mirabegron, a case report of drug-drug interaction with severe consequences in a geriatric patient.
Guerin C, Auty C, Pierre M … +3 more , Delamillieure P, Meurant A, Fedrizzi S
Eur J Clin Pharmacol · 2026 Jan · PMID 41553535 · Publisher ↗
We report a rare but clinically significant drug-drug interaction between clozapine and mirabegron in a 63-year-old man with schizophrenia. The patient presented with repeated falls, drowsiness and balance disorders foll...
We report a rare but clinically significant drug-drug interaction between clozapine and mirabegron in a 63-year-old man with schizophrenia. The patient presented with repeated falls, drowsiness and balance disorders following initiation of mirabegron for overactive bladder. Clozapine plasma levels progressively exceeded the therapeutic range. Dose reduction of clozapine restored concentrations to target levels and improved mobility and alertness, with only one fall reported after adjustment. This case highlights a probable pharmacokinetic interaction through mirabegron's moderate inhibition of CYP2D6, contributing to clozapine overdose. Only one similar case has previously been published. Clinicians should be aware of this interaction, especially in older patients with polypharmacy. Monitoring clozapine concentrations after introduction of clozapine's cytochrome inhibitors is recommended to prevent dose-dependent adverse effects such as sedation and falls, particularly in vulnerable populations such as older patients.
Potentially inappropriate medications related to two-year progression of mild cognitive impairment and dementia.
Kersten H, Barca ML, Eldholm RS … +6 more , Persson K, Thomasgaard L, Jaioun K, Saltvedt I, Selbaek G, Engedal K
Eur J Clin Pharmacol · 2026 Jan · PMID 41553533 · Full text
PURPOSE: To document use and impact of potentially inappropriate medications on two-year progression of dementia in individuals with cognitive declines. METHODS: A retrospective study of 397 patients with Mild Cognitive...
PURPOSE: To document use and impact of potentially inappropriate medications on two-year progression of dementia in individuals with cognitive declines. METHODS: A retrospective study of 397 patients with Mild Cognitive Impairment (MCI) or dementia diagnosed and followed-up in outpatient memory clinics in Norway during 2009 − 18. Beers (2019)- and STOPP-2 criteria were used to identify Potentially Inappropriate Medications (PIMcogs) in individuals with cognitive impairments at baseline and two-year-follow-up. PIMcog use in terms of dementia severity, cognitive function, and neuropsychiatric and depressive symptoms were analyzed in regression models. RESULTS: The prevalence of PIMcogs increased from 16% at baseline to 23% at follow-up. PIMcog users were more likely to be women (63.5%), and they used more drugs, with a median of 5 drugs at baseline and 4 drugs at follow-up, compared to non-users who had a median of 3 used drugs at both time points. PIMcog users had higher median Neuropsychiatric Inventory severity sum scores (6 [3.0–11.0] versus 4.0 [2.0–7.0]) and median Cornell Scale for Depression in Dementia scores (6.5 [3.0–11.0] versus 4.0 [1.0–7.0]) compared to non-users at follow-up (p ≤ 0.002). PIMcog users exhibited more severe dementia, with a Clinical Dementia Rate-Sum of Boxes (CDR-SB) score of 7.0 (4.0–13.0) compared to 6.0 (3.5–10.0) in non-users. The median annual increase in CDR-SB was one unit, and PIMcog use at follow-up was significantly associated with more rapid progression of dementia severity. CONCLUSION: Faster dementia progression was documented among PIMcog users although, the prevalence of PIMcogs was generally low in Norwegian memory clinic patients with cognitive impairments.
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