Annals of Pharmacotherapy最新文献

{"title":"Systematic Literature Review of DOACs as Treatment for Confirmed or Suspected Heparin-Induced Thrombocytopenia (HIT).","authors":"Shoshana Steinmetz, Anastasiya Shor, Michelle Jakubovics","doi":"10.1177/10600280251322549","DOIUrl":"10.1177/10600280251322549","url":null,"abstract":"<p><strong>Objective: </strong>To analyze available literature on the use of direct oral anticoagulants (DOACs) in the treatment of confirmed or suspected heparin-induced thrombocytopenia (HIT).</p><p><strong>Data sources: </strong>PubMed and Embase databases were searched through December 16, 2024, to identify studies assessing DOAC use in the treatment of acute confirmed or suspected HIT.</p><p><strong>Study selection and data extraction: </strong>Included studies analyzed use of apixaban, dabigatran, edoxaban, or rivaroxaban in patients with confirmed or suspected HIT.</p><p><strong>Data synthesis: </strong>Ten studies including 275 patients met the inclusion criteria. Eight were retrospective cohort studies and 2 were prospective. No randomized control trials were identified. A 4Ts score was reported for 259 patients; an antibody immunoassay was reported for 149 patients; and a serotonin release assay was reported for 109 patients. Eight, 6, and 2 studies reported use of rivaroxaban, apixaban, and dabigatran, respectively. Thrombosis rates ranged from 0% to 8.3%, 0% to 13.7%, and 0% to 2.5% for rivaroxaban, apixaban, and dabigatran respectively. Major bleeding was reported in 1 patient receiving rivaroxaban.</p><p><strong>Relevance to patient care and clinical practice: </strong>The 2018 American Society of Hematology HIT guidelines conditionally recommend DOAC use due to very low certainty of effects. Direct oral anticoagulants (DOACs) are an attractive treatment option for acute HIT due to ease of administration and reduced need for monitoring. Analysis of the recently published relevant data can support and guide appropriate use of DOACs in these patients.</p><p><strong>Conclusions: </strong>This systematic review strengthens previously published evidence that DOACs are likely a safe and effective treatment for confirmed or suspected HIT. Study design, small study size, and varying diagnostic criteria reduce data certainty.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1015-1030"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xanomeline-Trospium: A Novel Therapeutic for the Treatment of Schizophrenia.","authors":"Olivia L Ramey, Armando Silva Almodóvar","doi":"10.1177/10600280251324642","DOIUrl":"10.1177/10600280251324642","url":null,"abstract":"<p><strong>Objective: </strong>This review describes a novel combination muscarinic agonist and antagonist, xanomeline-trospium, which was recently approved by the Food and Drug Administration (FDA) for schizophrenia. Efficacy and safety evidence from phase II and III clinical trials are reviewed.</p><p><strong>Data sources: </strong>The MEDLINE and EMBASE databases were searched in 2024; terms included \"xanomeline trospium\" OR \"xanomelinetrospium\" OR \"KarXT\" OR \"Cobenfy\" AND \"schizophrenia.\" The search was repeated in January 2025.</p><p><strong>Clinicaltrials: </strong>gov was used to review ongoing or unpublished studies.</p><p><strong>Study selection and data extraction: </strong>Human subject studies of xanomeline-trospium were included.</p><p><strong>Data synthesis: </strong>In phase III trials, xanomeline-trospium was superior to placebo for acute exacerbation of schizophrenia. EMERGENT-2 and EMERGENT-3 found patients improved by 9.6 and 8.4 points on the Positive and Negative Symptom Scale (PANSS), respectively, compared with placebo (95% confidence interval -13.9 to -5.2, <i>P</i> < 0.001 and -12.4 to -4.3, <i>P</i> < 0.001). Participants in EMERGENT-4, a long-term open-label extension study, who received the intervention in the randomized phases experienced a 9-point decrease in PANSS from the last result.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Xanomeline-trospium is a novel antipsychotic that is effective for treatment of schizophrenia and may have a favorable adverse effect profile in comparison with other antipsychotics due to its lack of dopamine receptor antagonism. Efficacy for improvement in negative symptoms and cognitive function in schizophrenia is promising.</p><p><strong>Conclusions: </strong>Xanomeline-trospium shows promising results for treatment of schizophrenia. Further studies with active comparators, larger sample sizes, and more patients with prominent negative symptoms are needed to corroborate efficacy and determine place in therapy.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"937-950"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Nervous System Disorders: A Systematic Review and Meta-Analysis\".","authors":"Rachana Mehta, Shubham Kumar, Ranjana Sah","doi":"10.1177/10600280251330967","DOIUrl":"10.1177/10600280251330967","url":null,"abstract":"","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"962-963"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Acute Respiratory Failure Associated With Trimethoprim/Sulfamethoxazole Among Adolescent and Young Adults: An Active Comparator-Restricted Disproportionality Analysis From the FDA Adverse Event Reporting System (FAERS) Database.","authors":"Fatemeh Ahmadi, Niaz Chalabianloo, Eric McArthur, Mohammad Ali Omrani, Sheikh S Abdullah, Facundo Garcia-Bournissen, Flory T Muanda","doi":"10.1177/10600280251320690","DOIUrl":"10.1177/10600280251320690","url":null,"abstract":"<p><strong>Background: </strong>The US Food and Drug Administration (FDA) has raised concerns about a potential link between trimethoprim/sulfamethoxazole (TMP-SMX) and an increased risk of acute respiratory failure/acute respiratory distress syndrome (ARF/ARDS) in healthy adolescents and young adults.</p><p><strong>Objective: </strong>To assess the association between TMP-SMX and the risk of ARF/ARDS using data from the FDA Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>We analyzed adverse drug events (ADEs) reported in FAERS from January 1, 2004, to December 31, 2023. We focused on reports where TMP-SMX, amoxicillin-clavulanic acid, or azithromycin were the primary suspect drugs for ADEs in individuals aged 10 to 24 years. The outcomes of interest-ARF/ARDS-were identified using MedDRA-preferred terms. We used an active comparator-restricted disproportionality analysis (ACR-DA) to estimate the reporting odds ratio (ROR) and 95% confidence interval (CI), adjusting for age, sex, acne, and urinary tract infections. Bayesian Confidence Propagation Neural Networks (BCPNN) were used to calculate the Information Components (IC₀₂₅). Due to the amount of missing information, a case-by-case analysis could not be performed.</p><p><strong>Results: </strong>3171 ICSRs (810 for TMP-SMX, 1617 for azithromycin, and 744 for amoxicillin-clavulanic acid) were included in the study. ACR-DA showed an unadjusted 8-fold increase in the reports of ARF/ARDS with TMP-SMX compared with azithromycin (unadjusted ROR, 7.98; 95% CI, 4.09 to 15.60) and an adjusted 3-fold increase after adjustment for age, sex, acne, and urinary tract infection (adjusted ROR, 2.80; 95% CI, 1.28 to 6.11). BCPNN analysis confirmed significant disproportionality (IC₀₂₅, 0.75). No cases of ARF/ARDS were reported for amoxicillin-clavulanic acid.</p><p><strong>Conclusion and relevance: </strong>TMP-SMX may increase the risk of ARF/ARDS, requiring further validation in larger pharmacoepidemiological studies. Our findings lay the groundwork for future research to further investigate the safety profile of TMP-SMX in adolescent populations. If confirmed, prescribers should exercise greater caution when prescribing TMP-SMX to adolescents and young adults.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"904-911"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seladelpar for the Treatment of Primary Biliary Cholangitis.","authors":"Adonice P Khoury, Jason Powell","doi":"10.1177/10600280251320069","DOIUrl":"10.1177/10600280251320069","url":null,"abstract":"<p><strong>Objective: </strong>To review the published data including the pharmacology, efficacy, and safety of seladelpar, a peroxisome proliferator-activated receptor delta (PPARδ) agonist leading to the Food and Drug Administration (FDA) accelerated approval for the treatment of primary biliary cholangitis (PBC).</p><p><strong>Data sources: </strong>A PubMed (January 1, 1985 to January 27, 2025) literature search was performed using the terms seladelpar, MBX-8025, peroxisome proliferator-activated receptor agonist, and PBC. Other data sources included Google Scholar and the National Institutes of Health Clinical Trials Registry.</p><p><strong>Study selection and data extraction: </strong>All English-language literature evaluating the pharmacology, pharmacokinetics, safety, and efficacy of seladelpar in the treatment of PBC was reviewed.</p><p><strong>Data synthesis: </strong>Seladelpar is the first PPARδ agonist in the treatment of PBC that has shown a significant reduction across biochemical response, alkaline phosphatase (ALP) normalization, and pruritus as compared to placebo while demonstrating safety and tolerability.Relevance to patient care and clinical practice in comparison to existing drugs:While existing drug treatments for PBC are efficacious, there remains an unmet need due to an incomplete biochemical response in many patients. Patients frequently suffer from symptoms, including pruritus, impacting their quality of life. Seladelpar could have a beneficial role in PBC as add-on therapy in improving biochemical response as well as alleviating pruritus.</p><p><strong>Conclusion: </strong>Seladelpar is a safe and effective treatment for PBC and fills a significant unmet need. Seladelpar's clinical benefit predicted by improvement in surrogate endpoints may need confirmation for traditional FDA approval.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"951-958"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Comment on \"Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Nervous System Disorders: A Systematic Review and Meta-Analysis\".","authors":"Bo Xu, Jiecan Zhou","doi":"10.1177/10600280251330966","DOIUrl":"10.1177/10600280251330966","url":null,"abstract":"","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"964"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis Comparing Metolazone Versus Intravenous Chlorothiazide in Patients With Acute Decompensated Heart Failure.","authors":"Kazuhiko Kido, Mikiko Shimizu, Tsuyoshi Shiga, Masayuki Hashiguchi","doi":"10.1177/10600280251325250","DOIUrl":"10.1177/10600280251325250","url":null,"abstract":"","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"959-961"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of GLP-1 Receptor Agonists in Metabolic Associated Steatotic Liver Disease.","authors":"Klaudia Nowak, Krzysztof Łupina, Anna Romac, Aleksandra Kalisz, Łucja Ilkiewicz, Jakub Janczura","doi":"10.1177/10600280251322002","DOIUrl":"10.1177/10600280251322002","url":null,"abstract":"<p><strong>Objective: </strong>To summarize the current knowledge on the therapeutic potential of GLP-1 receptor agonists in managing metabolic associated steatotic liver disease (MASLD).</p><p><strong>Data sources: </strong>A literature review was conducted using the search terms <i>GLP-1 agonists</i>, <i>MASLD</i>, <i>NAFLD</i>, <i>nonalcoholic fatty liver disease</i>, <i>treatment</i>, and <i>therapy</i> on PubMed (from January 1, 2019, through February 1, 2025), National Institutes of Health (NIH) (from January 1, 2019, through February 1, 2025), Scopus (from January 1, 2019, through February 1, 2025), and the World Health Organization (WHO) data.</p><p><strong>Study selection and data extraction: </strong>All relevant clinical trials, review articles, package inserts, and guidelines evaluating clinically relevant evidence regarding the therapeutic potential of GLP-1 agonists in MASLD were considered for inclusion.</p><p><strong>Data synthesis: </strong>GLP-1 RAs have shown promising results in MASLD treatment. Semaglutide has demonstrated efficacy in reducing liver fat content, inflammation, and fibrosis, with clinical trials indicating improvements in hepatic biomarkers and cardiometabolic risk factors. Similarly, tirzepatide has been associated with substantial weight loss and significant reductions in liver fat and fibrosis markers. Both agents exert their effects through mechanisms involving improved insulin sensitivity, reduced lipid accumulation, and attenuation of hepatic inflammation.</p><p><strong>Relevance to patient care and clinical practice: </strong>Given the high prevalence of MASLD in patients with obesity and type 2 diabetes, tirzepatide and semaglutide could play a critical role in clinical practice by addressing multiple facets of the disease. Both agents have shown potential in reducing liver fat, improving hepatic biomarkers, and mitigating cardiometabolic risks, which are leading causes of morbidity and mortality in MASLD patients. Incorporating these therapies into MASLD treatment guidelines could significantly enhance patient outcomes by targeting both liver-related and systemic complications of the disease.</p><p><strong>Conclusions: </strong>GLP1 RAs show great potential in managing MASLD by promoting weight loss, improving glycemic control, and reducing liver inflammation.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"928-936"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse Reactions by Radiopharmaceuticals: Retrospective Analysis of the Portuguese National Pharmacovigilance System.","authors":"Sara Martins, Ângelo Jesus, Ricardo Andrade, Mariana Rocha, Ana Martín-Suarez","doi":"10.1177/10600280251316542","DOIUrl":"10.1177/10600280251316542","url":null,"abstract":"<p><strong>Background: </strong>Radiopharmaceuticals are essential in the field of nuclear medicine, but like any other medicinal product, radiopharmaceuticals can potentially cause adverse reactions in patients.</p><p><strong>Objective: </strong>To describe the adverse reactions to radiopharmaceuticals reported to the Portuguese National Pharmacovigilance System (SNF).</p><p><strong>Methods: </strong>We performed a retrospective, observational study by examining individual case safety reports (ICSRs) provided by the SNF related to all radiopharmaceuticals commercially available in Portugal from 2010 to 2023.</p><p><strong>Results: </strong>The SNF received a total of 84 ICSRs. These reports resulted in a total of 224 adverse drug reactions (ADR), which involved a total of 15 different radiopharmaceuticals. The mean age of patients was 61.9 years old. Twenty-one different system organ classes (SOCs) were identified, with the most prevalent situations being \"Gastrointestinal Disorders\" (18.3%; n = 41) followed by \"General disorders and administration site conditions\" (16.5%; n = 37), \"Skin and subcutaneous tissue disorders\" (11.2%; n = 25) and \"Blood and lymphatic system disorders\" (10.3%; n = 23). Fifty-seven reports (67.85%) showed at least 1 serious ADR. Most notified radiopharmaceuticals were, respectively, radium-223 (n = 36, 41.4%), lutetium-177 oxotreotide (n = 12, 13.8%) and iodide-131 (n = 9, 10.3%).</p><p><strong>Conclusion and relevance: </strong>Although the number of notifications is limited, these findings provide valuable insights into the types and frequencies of adverse reactions associated with radiopharmaceuticals used in Portugal between 2010 and 2023. The data highlight the importance of continued pharmacovigilance efforts to monitor the safety of these specialized medical products and inform clinical decision-making.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"919-927"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective Analysis of Tacrolimus Levels: The First 56 Days Following Allogeneic Hematopoietic Stem Cell Transplant and Patient Outcomes.","authors":"Kateryna Kovalenko, Joseph Bubalo, Jennifer Saultz, Pavani Malla","doi":"10.1177/10600280251321324","DOIUrl":"10.1177/10600280251321324","url":null,"abstract":"<p><strong>Background: </strong>Despite prophylaxis, acute graft-versus-host disease (aGVHD) occurs in up to 40% to 60% of patients undergoing an allogeneic hematopoietic stem cell transplantation (alloHSCT). Tacrolimus remains a common GVHD prophylactic medication used in combination with mycophenolate or methotrexate.</p><p><strong>Objective: </strong>The purpose of this study was to compare tacrolimus levels up to day +56 to clinical outcomes in patients who underwent alloHSCT.</p><p><strong>Methods: </strong>This was a retrospective cohort study of adult patients who underwent alloHSCT between January 2009 and April 2019 at Oregon Health and Science University (OHSU) Hospital. A logistic regression analysis was performed using SAS software to evaluate the association between tacrolimus concentration range and the GVHD grade outcome.</p><p><strong>Results: </strong>There were 295 patients included in the study. The median patient age was 53 years (range 18-72), the majority were males (55%), with a median comorbidity index of 2 (range 0-9). Most patients received peripheral blood stem cell transplant (95%). The median tacrolimus levels were divided into 4 groups: (1) between 3.8 and 4.9 ng/mL, (2) 5.0 and 7.9 ng/mL, (3) 8.0 and 9.9 ng/mL, and (4) 10.0 and 10.7 ng/mL in 8 (2.7%), 206 (69.8%), 71 (24.1%), and 10 (3.4%) of patients, respectively. The odds ratio of 0.193 (95% confidence interval [CI]: 0.045-0.836) suggested that patients in the tacrolimus 8 to 12 ng/mL range were approximately 80.5% less likely to have grade 3 to 4 aGVHD compared to those in the 5 to 8 ng/mL range.</p><p><strong>Conclusion and relevance: </strong>Overall, we found that higher levels of tacrolimus (range 8-12 ng/mL) in the first 8 weeks post-transplant were associated with improved outcomes without increased rate of relapse.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"912-918"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}