European Journal of Clinical Pharmacology最新文献

{"title":"Unveiling cardiovascular and respiratory toxicities with monoclonal antibodies in multiple myeloma: disproportionality analysis from the FDA Adverse Event Reporting System.","authors":"Maria Antonietta Barbieri, Giulia Russo, Giuseppe Cicala, Giuseppe Andò, Tindara Franchina, Nicola Silvestris, Mariacarmela Santarpia, Edoardo Spina","doi":"10.1007/s00228-025-03824-8","DOIUrl":"10.1007/s00228-025-03824-8","url":null,"abstract":"<p><strong>Introduction: </strong>Monoclonal antibodies (mAbs) have revolutionized the treatment of multiple myeloma (MM), demonstrating remarkable effectiveness, despite potential adverse events (AEs). This study aims to identify unexpected signals of disproportionate reporting (SDRs) for cardiovascular (CV) and respiratory AEs associated with mAbs in MM treatment.</p><p><strong>Methods: </strong>From January 2015 to December 2023, reports involving suspected drugs (daratumumab, elotuzumab, elranatamab, isatuximab, belantamab mafodotin, teclistamab, and talquetamab) were analyzed in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Descriptive analysis was followed by disproportionality analyses first comparing mAbs to all other drugs (reference group, RG1), and subsequently conducting a sensitivity analysis against other MM drugs (RG2).</p><p><strong>Results: </strong>Out of 13,496,241 reports, 31,052 (0.2%) were associated with MM, with 6574 (0.1%) linked to CV and respiratory adverse events, primarily involving older population (n = 3441; 52.3%) and male (n = 3338; 50.8%) patients. Disproportionality analyses identified unexpected SDRs for daratumumab, including cardiac failure (n = 322; RG1: ROR = 4.74, CI 95% = 4.24-5.29; RG2: ROR = 4.42, 95% CI = 3.91-4.99), embolic and thrombotic event, such as pulmonary embolism (162; RG1: 2.44, 2.09-2.85), deep vein thrombosis (126; RG1: 2.95, 2.47-3.52), and respiratory failure (192; RG1: 4.06, 3.52-4.68; RG2: 4.2, 3.59-4.91). Isatuximab was linked to cardiac arrhythmia, such as atrial fibrillation (46; RG1: 2.54, 1.9-3.4; RG2: 1.35, 1.01-1.81), embolic and thrombotic event, including deep vein thrombosis (26; RG1: 2.93, 1.99-4.3) and pulmonary embolism (89; RG1: 6.56, 5.32-8.1; RG2: 2.93, 2.37-3.63). Elotuzumab showed also SDRs for atrial fibrillation (56; RG1: 3.68, 2.82-4.79; RG2: 1.96, 1.5-2.56) and deep vein thrombosis (41; RG1: 5.49, 4.03-7.47).</p><p><strong>Conclusion: </strong>Unexpected CV and respiratory AEs with clinical relevance not previously reported in literature have been identified underlining the importance of pharmacovigilance.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"755-770"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prescribing patterns of glucagon-like peptide-1 receptor agonists in the Swedish capital region-a register-based cross-sectional study.","authors":"Alice Fors, Tomas Forslund, Anders Sundström, Björn Wettermark","doi":"10.1007/s00228-025-03823-9","DOIUrl":"10.1007/s00228-025-03823-9","url":null,"abstract":"<p><strong>Purpose: </strong>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained considerable media attention, but there is limited knowledge about those receiving the drugs. This study aimed to assess demographic characteristics and previous diagnoses in patients dispensed GLP-1 RAs in Region Stockholm, Sweden, between 2019 and 2023, with a focus on off-label prescribing.</p><p><strong>Methods: </strong>This was a register-based cross-sectional study including all inhabitants in Region Stockholm, Sweden, who were dispensed a GLP-1 RA between 2019 and 2023. Patient characteristics were assessed through record linkage with administrative healthcare data on demographics, healthcare consultations, diagnoses, and other dispensed drugs.</p><p><strong>Results: </strong>The prevalence proportion of GLP-1 RA dispensations in Region Stockholm increased from 4.7 patients/1000 inhabitants in 2019 to 17.5 patients/1000 inhabitants in 2023, and the incidence proportion from 1.8 patients/1000 inhabitants in 2019 to 7.4 patients/1000 inhabitants in 2023. GLP-1 RAs have become more common among a younger and female population, with women constituting 47% of incident patients in 2019 compared to 53% in 2023. The most common diagnosis shifted from type 2 diabetes mellitus (T2DM) (82% in 2019) to obesity (47% in 2023). During the same period, obesity without T2DM notably increased from 10 to 31%. Almost one-third (31%) of all patients dispensed the drugs in 2023 had no recorded diagnosis of either diabetes or obesity, compared to 8% in 2019.</p><p><strong>Conclusion: </strong>This study showed an increase in the dispensation of GLP-1 RA, with characteristics of patients changing towards a higher degree of off-label use. The effectiveness and safety of the increasing prescriptions warrant future studies.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"739-753"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the comprehensive factors influencing tacrolimus pharmacokinetics in early renal transplant recipients: A population pharmacokinetic analysis.","authors":"Yan Zhang, Ling Xue, Linkun Hu, Liangliang Wang, Hao Pan, Yuxin Lin, Xiaoliang Ding, Yuhua Huang, Liyan Miao","doi":"10.1007/s00228-025-03825-7","DOIUrl":"10.1007/s00228-025-03825-7","url":null,"abstract":"<p><strong>Purpose: </strong>To establish a population pharmacokinetic (PopPK) model of tacrolimus in the early stages after renal transplantation and evaluate the model's predictive performance with external data.</p><p><strong>Methods: </strong>Intravenous and oral tacrolimus were administered to 302 renal transplant recipients in the early posttransplantation stages. Related data were obtained from the electronic medical records. Single nucleotide polymorphisms in genes associated with tacrolimus pharmacokinetics were tested. The data were analyzed by NONMEM. The external data from 153 patients were subsequently used to evaluate model extrapolation.</p><p><strong>Results: </strong>A one-compartment model was used to determine tacrolimus pharmacokinetics. The estimated clearance (CL), volume of distribution (V) and bioavailability (F) of tacrolimus were 4.91 L/h, 77 L and 26.5%, respectively. CL and V decreased with increasing hematocrit. CL and F decreased with increasing operation time. Diltiazem and Wuzhi capsule resulted in 28.4% and 43.9% decreases in the CL, respectively. Omeprazole or esomeprazole resulted in a 9% increase in F. The value of F for patients expressing CYP3A5 was 36.6% lower than that for the patients who did not express CYP3A5. The evaluation of external data revealed that the proportion of individual prediction error within 20% of the observed tacrolimus concentration was greater than 77.3%.</p><p><strong>Conclusions: </strong>A PopPK model for tacrolimus was established for early renal transplantation. CYP3A5 was a significant covariate for F. Fat-free mass was the best predictor of the influence of body size on CL and V. The model could be extrapolated to stable renal transplant recipients.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"785-799"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facilitators and barriers to generic and biosimilar medications in the Middle East and North Africa: insights from physicians and pharmacists-a systematic review.","authors":"Kefah Ali Alqawasmeh, Thomas Mason, Abigail Morris, Wael Hafez, Thekra Hasan, Sondos Taher, Rania Al Dweik","doi":"10.1007/s00228-025-03819-5","DOIUrl":"10.1007/s00228-025-03819-5","url":null,"abstract":"<p><strong>Background: </strong>The adoption of generic and biosimilar medications is crucial for improving healthcare accessibility and cost savings in the Middle East and North Africa (MENA) region. Understanding the factors that influence their acceptance is crucial for developing effective strategies for promoting their use.</p><p><strong>Purpose: </strong>This systematic review aimed to examine the facilitators and barriers identified by healthcare professionals while prescribing and dispensing generic and biosimilar medications in the MENA region, focusing on their perceptions, knowledge, and attitudes.</p><p><strong>Methods: </strong>Following Cochrane guidelines and the \"Guidance on the Conduct of Narrative Synthesis in Systematic Reviews,\" a comprehensive search of electronic databases and grey literature was conducted from 2012 to 2024. Studies assessing physicians' and pharmacists' perspectives on generics and biosimilars in the MENA region were included. Quality appraisal was performed using a standardized tool, the mixed methods appraisal tool (MMAT). The findings were synthesized using a descriptive analysis.</p><p><strong>Results: </strong>Of the 3570 screened citations, 39 met the inclusion criteria. Among them, 25 studies addressed facilitators and barriers to adopting generic medications, whereas 15 focused on biosimilars. Facilitators of generic medications included understanding the use of generics as cost-effective substitutes, supportive government policies, generic medication awareness, and pharmacists' empowerment to substitute medications. Barriers included knowledge gaps leading to distrust in efficacy and safety, the influence of pharmaceutical companies, cultural biases favoring brand name drugs, regulatory challenges, low consumer awareness, and concerns about pharmacists' profitability. Facilitators for biosimilars were mostly similar to generics, with an added emphasis on access benefit recognition when using biosimilars. Unique barriers included concerns about the lack of long-term safety data, hesitancy toward non-medical switching, and nocebo effect concerns. The quality assessment indicated that most studies were of moderate quality, with limitations such as sample size and representativeness, validity of the measurement tools, and potential biases of the researchers.</p><p><strong>Conclusion: </strong>Significant knowledge gaps regarding regulatory approval, safety, and efficacy hinder the adoption of generic drugs and biosimilars in MENA. Targeted educational initiatives at the regulatory and payer levels are essential for bridging these gaps, enhancing awareness, and fostering acceptance. Implementing comprehensive educational programs for physicians and pharmacists is crucial to support the transition toward the greater use of generics and biosimilars.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"647-665"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative review of the placebo effect: historical roots, current applications, and emerging insights.","authors":"Cagri Ozpolat, Yagmur Okcay, Kemal Gokhan Ulusoy, Oğuzhan Yildiz","doi":"10.1007/s00228-025-03818-6","DOIUrl":"10.1007/s00228-025-03818-6","url":null,"abstract":"<p><strong>Purpose: </strong>Placebo is a term to define physiologically inactive compounds used in treatment that causes physical and emotional changes. The placebo effect, driven by expectation and conditioning, plays a significant role in various conditions like pain, depression, and Parkinson's disease, while the nocebo effect can hinder treatment outcomes. Understanding mechanisms such as neuromodulation and genetics has gained importance in modern medicine. This review aims to explore the clinical relevance of placebo responses, particularly in neuropsychiatric disorders, and their potential in personalized medicine. By integrating placebo research into healthcare, it highlights opportunities to enhance treatment efficacy, improve patient well-being, and reduce reliance on pharmacological interventions.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar databases. Recent studies were reviewed to evaluate placebo effects, and the variability of the placebo response in neuropsychiatric disorders was summarized.</p><p><strong>Results: </strong>Placebo effects significantly impact treatment outcomes across various conditions, including Parkinson's disease, depression, pain syndromes, and epilepsy. The mechanisms involve neurobiological and psychological factors, with evidence suggesting that placebo interventions can modulate neurotransmitter activity and improve patient well-being.</p><p><strong>Conclusion: </strong>Integrating placebo research into clinical practice may enhance treatment outcomes, reduce drug dependency, and support personalized medicine by tailoring interventions to individual placebo responsiveness. Understanding placebo and nocebo mechanisms can optimize therapeutic strategies while minimizing unnecessary pharmacological treatments.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"625-645"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of cigarette smoking on drugs' metabolism and effects: a systematic review.","authors":"Stefano Zanni, Jole Del Prete, Alessandra Capogrossi, Giuseppe Papapietro, Angela Del Cimmuto, Sergio Gazzanelli, Andrea Caronna, Carmela Protano","doi":"10.1007/s00228-025-03817-7","DOIUrl":"10.1007/s00228-025-03817-7","url":null,"abstract":"<p><strong>Purpose: </strong>Cigarette smoke continues to be widely used around the world and it contains several substances that can affect the pharmacokinetics and/or pharmacodynamics of medications, altering their safety and effectiveness. The aim of this systematic review was to summarize the scientific evidence regarding possible changes in the pharmacokinetics and/or pharmacodynamics of drugs induced by cigarette smoking, possible mechanisms of action and related effects.</p><p><strong>Methods: </strong>The systematic review was performed according to the PRISMA Statement and the protocol was registered on the PROSPERO platform (CRD42023477784). Pubmed, Scopus, Web of Science databases were used. We considered observational, semi-experimental or experimental studies written in English and published between January 1, 2000, and November 13, 2024, focused on smoking subjects (healthy volunteers or patients) receiving any kind of medication. Data regarding possible modifications in drugs' pharmacokinetics and/or pharmacodynamics induced by cigarette smoking were assessed. The quality of observational studies and experimental studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale and the Jadad Scale, respectively.</p><p><strong>Results: </strong>In total, 37 studies were included, and 31 of them showed relevant modifications in the pharmacokinetics or effects of the drugs in smokers compared to non-smokers. Most of the included studies (n = 20) investigated drugs for psychiatric or neurological disorders, showing a reduction in plasma concentration or an increase in drug clearance in smokers as well as antibiotics metronidazole and cycloserine. Besides, seven articles focused on anticancer drugs indicating an increase in drug metabolism. The remaining articles reported effects of smoking on the metabolism of other drugs, such as cardiovascular drugs, phosphodiesterase 5 inhibitors, local anesthetics and medications for musculoskeletal or chronic obstructive pulmonary diseases. Induction of the cytochrome enzyme CYP1A2 is the most common mechanism mediating the reduction of drug concentrations by cigarette smoking.</p><p><strong>Conclusion: </strong>The results indicate an increased risk of therapeutic failure for smokers and represent further motivation to encourage smoking cessation or attention in formulating personalized therapy.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"667-695"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of surrogate endpoints in phase III randomized control trials of advanced hepatocellular carcinoma treated with immune checkpoint inhibitors.","authors":"Ke Jiang, Miaowen Liu, Xiao Zhao, Shutong Wang, Yunyan Ling, Liangliang Qiao, Jianfei Tu, Zhenwei Peng","doi":"10.1007/s00228-025-03820-y","DOIUrl":"10.1007/s00228-025-03820-y","url":null,"abstract":"<p><strong>Purpose: </strong>Overall survival (OS) is recommended as a gold standard endpoint but has some limitations. We aimed to finding more effective surrogate endpoints for advanced hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>Three online databases were searched for randomized control trials (RCTs) on HCC, published between January 2015 and July 2023, that evaluated ICIs and reported progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and OS. The correlation between the potential surrogate endpoints and OS was evaluated at the trial, arm, and patient levels. The prediction models were validated in single-arm or non-RCTs. Individual data were collected from a real-world (RW) cohort with advanced HCC underwent ICI monotherapy at three tertiary medical centers in China.</p><p><strong>Results: </strong>Ten RCTs (6023 participants) with 11 comparisons were included. PFS had a moderately significant association with OS (R² = 0.50, p = 0.014). ORR, DCR, and OS showed weak correlations. On limiting the analysis to ICI monotherapy studies, the correlations of OS with PFS became stronger (R² = 0.85, p = 0.02). The RW cohort also verified that PFS was closely related to OS when patient received with ICI monotherapy.</p><p><strong>Conclusion: </strong>PFS are recommended as surrogate markers in patients with advanced HCC treated with ICI monotherapy.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"727-737"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of direct oral anticoagulants and their relation to bleeding.","authors":"Sofia Attelind, Niclas Eriksson, Mia Wadelius, Pär Hallberg","doi":"10.1007/s00228-025-03821-x","DOIUrl":"10.1007/s00228-025-03821-x","url":null,"abstract":"<p><strong>Purpose: </strong>Direct oral anticoagulants (DOACs) are used to prevent and treat thromboembolic events in adults. We aimed to investigate whether pharmacogenomic variation contributes to the risk of bleeding during DOAC treatment.</p><p><strong>Methods: </strong>Cases were recruited from reports of bleeding sent to the Swedish Medical Products Agency (n = 129, 60% men, 93% Swedish, 89% on factor Xa inhibitors) and compared with population controls (n = 4891) and a subset matched for exposure to DOACs (n = 353). We performed a genome-wide association study, with analyses of candidate single nucleotide polymorphisms (SNPs) and candidate gene set analyses.</p><p><strong>Results: </strong>Forty-four cases had major, 37 minor, and 48 clinically relevant non-major (CRNM) bleeding. When cases were compared with matched controls, BAIAP2L2 rs142001534 was significantly associated with any bleeding and major/CRNM bleeding (P = 4.66 × 10^-8 and P = 3.28 × 10^-8, respectively). The candidate SNP CYP3A5 rs776746 was significantly associated with major and major/CRNM bleeding (P = 0.00020 and P = 0.00025, respectively), and ABCG2 rs2231142 was nominally associated with any bleeding (P = 0.01499). Rare coding variants in the candidate gene VWF were significantly associated with any bleeding (P = 0.00296).</p><p><strong>Conclusion: </strong>BAIAP2L2, CYP3A5, ABCG2, and VWF may be associated with bleeding in DOAC-treated patients. The risk estimates of the candidate variants in CYP3A5 and ABCG2 were in the same direction as in previous studies. The Von Willebrand Factor gene (VWF) is linked to hereditary bleeding disorders, while there is no previous evidence of bleeding associated with BAIAP2L2.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"771-783"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiretroviral drug exposure in pregnancy and risk of congenital anomalies: a European case/non-case malformed study.","authors":"Laura Saint-Lary, Anna-Belle Beau, Agnès Sommet, Valériane Leroy, Maria Loane, Clara Cavero-Carbonell, Ester Garne, Jonathan Hoareau, Anna Latos Bielenska, Isabelle Monier, Vera Nelen, Amanda J Neville, Mary O'Mahony, Isabelle Perthus, Anna Pierini, Anke Rissmann, Florence Rouget, Joanna Sichitiu, David Tucker, Helen Dolk, Christine Damase-Michel","doi":"10.1007/s00228-025-03814-w","DOIUrl":"10.1007/s00228-025-03814-w","url":null,"abstract":"<p><strong>Purpose: </strong>Antiretroviral drugs are recommended during pregnancy to achieve HIV viral suppression and reduce mother-to-child transmission. Congenital anomaly signals were reported after fetal exposure to antiretroviral drugs in several studies warranting further investigation. We aimed to evaluate the risk of congenital anomalies after fetal exposure to antiretroviral drugs using the European congenital anomaly registry data.</p><p><strong>Methods: </strong>A case/non-case study was performed, using the EUROmediCAT central database. All the congenital anomalies, exposed to any antiretroviral drugs, were included from 1995 to 2019. We explored each signal identified from the literature for associations between congenital anomalies and specific antiretroviral exposures. We compared antiretroviral exposure between the signal anomalies (cases) and all other malformed registrations (controls). Reporting odds ratio (ROR) and their 95% confidence intervals were estimated and adjusted for registry and maternal age.</p><p><strong>Results: </strong>Between 1995 and 2019, 173 cases of congenital anomalies were observed after any exposure to antiretroviral drugs. The signal previously identified in the literature between congenital heart defects and exposure to zidovudine was confirmed in the main analysis (aROR 3.66 [1.63-8.23]). Other signals identified in the literature were not confirmed, although two cases of hypospadias and two cases of limb defects were reported after zidovudine and atazanavir exposure, respectively. The signal detection analysis did not reveal any new signal after applying the Bonferroni correction.</p><p><strong>Conclusions: </strong>Our study does not reveal new signals but confirms the previously identified signal between congenital heart defects and fetal exposure to zidovudine. The physio-pathological hypothesis induced by zidovudine exposure should be explored in future studies.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"697-709"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the implementation of pharmacogenetic testing in Belgium.","authors":"Jolyce Bourgeois, Elena Costa, Carl Devos, Janis Luyten, Sien Ombelet, Nancy Thiry, Frank Hulstaert","doi":"10.1007/s00228-025-03816-8","DOIUrl":"10.1007/s00228-025-03816-8","url":null,"abstract":"<p><strong>Purpose: </strong>Although already a lot of research has been done on pharmacogenetic tests to inform the choice and/or dosing of medicines, the implementation and clinical uptake remain limited. This study assessed the implementation of pharmacogenetic (PGx) testing on a national scale by analyzing access to and volumes of reimbursed PGx.</p><p><strong>Methods: </strong>The use of pharmacogenetic tests was examined via a cross-sectional online survey among the Belgian laboratories, collecting data on PGx targets, testing volumes and technologies used. The focus was on reimbursed tests. Additional data were sourced from the national reimbursement database to describe uptake of testing per medication.</p><p><strong>Results: </strong>The uptake of PGx testing in Belgium varied by medication, with significant implementation for fluoropyrimidines, abacavir, and thiopurines. DPYD gene testing was the most frequently performed PGx test, due to endorsed (inter)national guidelines. Reimbursement rules shape access to PGx, with the majority of PGx tests performed in dedicated centers for human genetics (CHG). Access to HLA laboratories for HLA targets was not optimal and some laboratories without a CHG also included constitutional PGx targets in somatic oncology panels.</p><p><strong>Conclusion: </strong>This nationwide study demonstrates that in a country where the prescribers have access to a relatively extensive list of reimbursable PGx tests, the implementation of PGx testing is shaped by the presence of endorsed evidence-based clinical practice guidelines, as well as organizational and logistical factors.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"711-718"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}