Pharmacotherapy最新文献

{"title":"Evaluation of hyponatremia among older adults exposed to selective serotonin reuptake inhibitors and thiazide diuretics.","authors":"Trisha Matsuura, Abdelrahaman G Tawfik, Kenechukwu C Ben-Umeh, Philip D Hansten, Daniel C Malone","doi":"10.1002/phar.70004","DOIUrl":"10.1002/phar.70004","url":null,"abstract":"<p><strong>Objective: </strong>Hyponatremia is a common electrolyte disorder among older adults that can cause serious adverse effects. The purpose of this study was to assess the risk of hyponatremia with the concurrent use of selective serotonin reuptake inhibitors (SSRIs) and thiazide diuretics in an older population.</p><p><strong>Methods: </strong>Two retrospective nested case-control studies were conducted with exposure to an SSRI or a thiazide diuretic. Persons of interest were those enrolled in Medicare and who received parts A, B, and D benefits from 2017 to 2019 and who were receiving either an SSRI or thiazide diuretic. Cases were individuals with a diagnosis of hyponatremia. Controls had no documented history of hyponatremia. A logistic regression was conducted to determine the odds of hyponatremia.</p><p><strong>Results: </strong>Of the 551,298 patients receiving a SSRIs, the mean age was 77.8 years (Standard Deviation (SD) ± 8.0 years), 69% were female, and 91.23% were classified as White. We identified 701,007 individuals receiving a thiazide diuretic, with a mean age of 77.1 years (SD ± 7.2 years), 60.2% female, and 82.72% White. The prevalence of hyponatremia was 10.4% in patients taking thiazides alone and 9.0% in those taking SSRIs alone. On the other hand, patients on both medications had a hyponatremia prevalence of approximately 13.0%. Among SSRI users, the adjusted odds ratio (OR) of hyponatremia with concomitant use of thiazide diuretics was 1.24 (95% Confidence Interval (CI): 1.22-1.26). For thiazide users, the adjusted OR of hyponatremia with exposure to SSRIs was 1.27 (95% CI:1.24-1.29).</p><p><strong>Conclusion: </strong>The concurrent use of thiazide diuretics and SSRIs is associated with an increased risk of hyponatremia in older populations.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"169-176"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542944","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":"Establishing discordance rate of estimated glomerular filtration rate between serum creatinine-based calculations and cystatin-C-based calculations in critically ill patients.","authors":"Victoria L Williams, Anthony T Gerlach","doi":"10.1002/phar.70000","DOIUrl":"10.1002/phar.70000","url":null,"abstract":"<p><strong>Introduction: </strong>The use of serum creatinine (SCr) for drug dosing has significant limitations and is influenced by many non-kidney factors. Cystatin C (cysC) is an alternative or additional marker of kidney function that is less affected by non-kidney factors. Although cysC may be useful in hospitalized patients, the use of cysC to calculate drug dosing in critically ill patients has been incompletely investigated.</p><p><strong>Objective: </strong>The objective of this study was to determine the rate of discordance in estimated glomerular filtration rate (eGFR) between SCr-based calculations and SCr/cysC-based calculations that affect drug dosing in critically ill patients.</p><p><strong>Methods: </strong>This was a single-center, retrospective, observational cohort study at an academic medical center including critically ill adult patients admitted in 2023 with SCr and cysC ordered. Data were collected via chart review. Demographic data were analyzed via descriptive statistics. Discordance, defined as the percentage of times at which there is at least one discrepancy in kidney dosing for a medication using Cockcroft-Gault (CG) creatinine clearance versus Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR creatinine-cystatin C (eGFRcr-cys) equations, was analyzed via Wilcoxon matched pair signed ranked sum. eGFR calculations were normalized for patients' body surface area for comparison.</p><p><strong>Results: </strong>The study population included 232 patients (53.02% female; mean age 58.7 +/- 14.9 years; with 62.5% in medical, 23.28% in surgical, and 8.62% in neurological intensive care) with a median SCr of 0.94 mg/dL IQR [0.57-1.58] and median cysC of 1.92 mg/L IQR [1.27-2.77]. The median clearance rates were 68.5 mL/min (45.3-111.5) for CG and 53.9 mL/min (30.9-80.7) for CKD-EPI eGFRcr-cys; p < 0.001. The discordance rate across all study drugs was 32.3% (75/232). The four most common study drugs demonstrating discordance were cefepime 40.6% (52/128), vancomycin 38.3% (46/120), levetiracetam 35.1% (13/37), and piperacillin/tazobactam 11.6% (5/43).</p><p><strong>Conclusion: </strong>Clinically significant discordance exists between SCr and SCr/cysC-based estimates of kidney function. This study established a discordance rate, as defined by drug dosing, of 32.3% in adult patients admitted to the ICU.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"161-168"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410012","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":"Cross-titration from risperidone to clozapine utilizing clozapine serum concentrations: A case report.","authors":"Nicolette Centanni, Kayla Garvey, Elizabeth Mullany, Stephanie Nichols","doi":"10.1002/phar.4649","DOIUrl":"10.1002/phar.4649","url":null,"abstract":"<p><strong>Introduction: </strong>Clozapine and risperidone are second-generation antipsychotics used in the treatment of schizophrenia. There are no guidelines on cross-titration of antipsychotics and, additionally, there is a paucity of published data to support the potential utility of using serum drug levels to guide dosing in these situations.</p><p><strong>Case report: </strong>A 68-year-old female patient with a history of schizophrenia, taking risperidone and fluoxetine, and a recent diagnosis of Parkinson's disease was admitted to the hospital after a fall at home. During the patient's hospital stay, utilizing serum clozapine levels as guidance, the patient was cross-titrated from risperidone 12 mg daily to a final dose of clozapine 75 mg daily over the span of 17 days, in the setting of multiple possible drug-drug interactions.</p><p><strong>Discussion: </strong>There is no evidence-based guidance on transitioning patients from one antipsychotic to another especially in the setting of drug-drug interactions. In this case, the patient was successfully transitioned from risperidone to clozapine using serum clozapine levels and clinical status to guide decision-making.</p><p><strong>Conclusions: </strong>Utilizing serum clozapine levels may be helpful in guiding dose changes during antipsychotic cross-titration, especially when multiple drug interactions are involved.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"187-190"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009649","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":"GLP-1RA-induced delays in gastrointestinal motility: Predicted effects on coadministered drug absorption by PBPK analysis.","authors":"Levi Hooper, Shuhan Liu, Manjunath P Pai","doi":"10.1002/phar.70007","DOIUrl":"https://doi.org/10.1002/phar.70007","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are breakthrough medicines for obesity treatment and have rapidly gained widespread clinical application. Although GLP-1RAs are generally not associated with drug-drug interactions (DDIs) via drug metabolism or transporter pathways, their effects on reduced gastrointestinal (GI) motility could influence the pharmacokinetics of coadministered oral medications.</p><p><strong>Objectives: </strong>This study uses physiologically based pharmacokinetic (PBPK) modeling to evaluate the DDI potential of GLP-1RA-induced GI motility delays.</p><p><strong>Methods: </strong>Using Certara's Simcyp™ Simulator V23, we modeled the pharmacokinetics of atorvastatin, metformin, metoprolol, ethinyl estradiol, and digoxin in a virtual cohort of obese adults (n = 1000). GLP-1RA-related gastric emptying delays were simulated based on capsule endoscopy data from liraglutide-treated patients. Results were compared with clinical data from semaglutide and liraglutide users. Additionally, exploratory analyses were conducted on frequently coadministered drugs identified from the 2022 Medical Expenditure Panel Survey, including rosuvastatin and dabigatran.</p><p><strong>Results: </strong>GLP-1RA-induced gastric emptying delays led to increased area under the concentration-time curve (AUC) and prolonged time to maximum concentration (Tmax) for several medications. The model outputs for rosuvastatin, valsartan, and dabigatran indicate increases in AUC by 64%, 90%, and 205%, respectively. Dabigatran, a narrow therapeutic index anticoagulant, exhibited the most significant changes, raising potential concerns of higher drug exposure.</p><p><strong>Conclusions: </strong>PBPK modeling suggests that GLP-1RAs can influence the pharmacokinetics of oral medications by delaying gastric emptying, potentially leading to clinically relevant DDIs. While further clinical validation and pharmacovigilance is needed, these findings highlight the importance of PBPK tools in predicting and potentially mitigating risks associated with GLP-1RA use.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483888","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":"Changes in serum potassium in people with type 2 diabetes taking sodium-glucose co-transporter-2 inhibitors.","authors":"Kellye Eagan, Charlotte Bolch, Elizabeth Van Dril, Christie Schumacher","doi":"10.1002/phar.70006","DOIUrl":"https://doi.org/10.1002/phar.70006","url":null,"abstract":"<p><strong>Study objective: </strong>The primary objective of this study was to determine if there was a significant change in potassium levels with sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy in people with type 2 diabetes (T2D). A co-primary objective was to evaluate which factors may predispose a patient to changes in potassium levels.</p><p><strong>Design: </strong>Multicenter retrospective cohort chart review.</p><p><strong>Data source: </strong>Study patients were identified through an electronic medical record-generated report if they had T2D and were prescribed an SGLT2 inhibitor from January 2013 to September 2019.</p><p><strong>Patients: </strong>Patients were included if they had T2D, were receiving care at Advocate Medical Group, and were confirmed to have taken one of the four SGLT2 inhibitors available at the time of study approval, canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin, for at least 7 days. Patients were excluded if they did not have a basic metabolic panel or comprehensive metabolic panel recorded 1 year prior to or 6 months after SGLT2 inhibitor therapy initiation.</p><p><strong>Results: </strong>Data extraction from the electronic medical record identified 6425 patients receiving an SGLT2 inhibitor, of which 1926 met inclusion criteria. The SGLT2 inhibitor most prescribed was canagliflozin (43.7%), followed by empagliflozin (36.9%) and dapagliflozin (19.4%). Concomitant baseline medications were thiazide diuretics (27.5%); angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors (72.1%); and/or mineralocorticoid receptor antagonists (27.2%). A statistically significant change in potassium levels was found with dapagliflozin (p = 0.018); albeit not clinically significant. No other statistically significant changes or patterns were identified. The overall mean change in serum potassium from baseline was 0.021 mmol/L within 3 months; 0.007 mmol/L from 3 to 5.9 months; -0.017 mmol/L within 6-12 months; and 0.004 mmol/L after more than 12 months.</p><p><strong>Conclusions: </strong>No clinically significant increase or decrease in potassium levels was observed upon initiation of SGLT2 inhibitor therapy in patients with T2D. This was consistent across background medication use and patient-specific factors. Baseline potassium should not be a factor in initiating SGLT2 inhibitor therapy, if clinically indicated, in patients with T2D.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483887","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":"Comment on \"Use of proton pump inhibitors and risk of severe COVID-19: A case-control study in United States Medicare beneficiaries\".","authors":"Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan, Kaeshaelya Thiruchelvam","doi":"10.1002/phar.70002","DOIUrl":"https://doi.org/10.1002/phar.70002","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441254","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":"Comment on \"Intravenous ketamine successfully treats treatment-resistant catatonia in schizophrenia: A case report\".","authors":"João Gama Marques, Josef Finsterer","doi":"10.1002/phar.4647","DOIUrl":"https://doi.org/10.1002/phar.4647","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"45 2","pages":"145-146"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410016","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":"Associating regulatory actions on diclofenac use with Danish trends in utilization by route of administration 1999-2023.","authors":"Anna Emilie Møller, Anne Bech-Drewes, Lotte Rasmussen, Søren Friis, Morten Schmidt","doi":"10.1002/phar.4643","DOIUrl":"10.1002/phar.4643","url":null,"abstract":"<p><strong>Aims: </strong>With the growing evidence of cardiovascular risks associated with diclofenac use, regulatory measures governing its application and sales have intensified since 2008. We evaluated the association between central regulatory actions and trends in diclofenac use in Denmark from 1999 to 2023, according to different dosage forms and routes of administration.</p><p><strong>Methods and results: </strong>Data on diclofenac sales in Denmark from 1999 to 2023 were retrieved from the publicly available web database MEDSTAT, based on the Danish Register of Medicinal Products Statistics. The annual sales of various diclofenac dosage forms, including systemic (tablets, modified-release dosage forms, and suppositories) and topical (nonspecific and ophthalmic) dosage forms, were calculated and displayed by sales unit. From 1999 to 2008, sales of all systemically administered diclofenac forms increased: tablets by 51% (2000-2008), modified-release dosage forms by 40% (2003-2007), and suppositories by 44% (1999-2008). Thereafter, sales of tablets declined by 86% and modified-release dosage forms by 90% through 2023. The sales of suppositories declined somewhat lesser, by 34%, during 2008 to 2018 and then increased by 67% through 2023. Sales of nonspecific topical diclofenac increased by several thousandfold from 2005, although with brief periods of decline.</p><p><strong>Conclusion: </strong>Sales of systemically administered diclofenac dosage forms, particularly tablets and modified-release drugs, declined by approximately 90% from about 2008 to 2023, indicating compliance with Danish and international regulatory actions. Conversely, sales of topically administered diclofenac increased heavily from 2005 to 2023, denoting a policy-driven shift toward these lower risk dosage forms.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"104-110"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915448","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":"Response to comment on \"Intravenous ketamine successfully treats treatment-resistant catatonia in schizophrenia: A case report\".","authors":"Atif Siddiqui","doi":"10.1002/phar.4645","DOIUrl":"https://doi.org/10.1002/phar.4645","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"45 2","pages":"147-148"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410018","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":"Disease-modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications.","authors":"Erika L Hellenbart, Heather J Ipema, Mary C Rodriguez-Ziccardi, Hema Krishna, Robert J DiDomenico","doi":"10.1002/phar.4639","DOIUrl":"10.1002/phar.4639","url":null,"abstract":"<p><p>Transthyretin amyloidosis (ATTR) is a rare disease that results in amyloid fibril misfolding and deposition in multiple organs, including the heart, leading to the development of ATTR cardiomyopathy (ATTR-CM), which is associated with poor outcomes. In the last decade, several disease-modifying medications are in advanced stages of clinical development or have been approved to treat ATTR-CM. The purpose of this review is to critically evaluate clinical trial data investigating the use of approved and investigational medications for the treatment of ATTR-CM. We performed a comprehensive literature search via PubMed and EMBASE to identify randomized controlled trials evaluating medications for the treatment of ATTR-CM published through August 2024. This narrative review describes the pathophysiology of ATTR-CM, highlights important screening and diagnostic work-up, and summarizes the existing clinical evidence resulting from our literature search. Several classes of disease-modifying medications are in development for ATTR-CM. The tetramer stabilizers and transthyretin silencers have proven to be the most effective therapies to date. Tafamidis and acoramidis are currently approved for ATTR-CM while vutrisiran approval for ATTR-CM may be forthcoming. Other disease-modifying medication classes in development include antisense oligonucleotides, gene editing therapies, and monoclonal antibodies. However, several unmet needs exist including the lack of cost-effectiveness due to the extremely high acquisition costs of these medications. Disease-modifying medications approved and in development to treat ATTR-CM offer hope for patients with this disease, but their lack of affordability is the biggest barrier to their use.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"124-144"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877615","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}