JAPhA Pharmacotherapy最新文献

{"title":"Impact of glucagon-like peptide-1 receptor agonist or glucagon-like peptide-1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonists After bariatric surgery in the veteran population","authors":"Sara Corum,&nbsp;Timothy Morgan,&nbsp;Ashley Thomas","doi":"10.1016/j.japhar.2025.100020","DOIUrl":"10.1016/j.japhar.2025.100020","url":null,"abstract":"<div><h3>Background</h3><div>Obesity is a progressive chronic disease that increases the risk of metabolic complications. Bariatric surgery is recommended alongside comprehensive lifestyle interventions for patients with a body mass index (BMI) of &gt; 40 kg/m², BMI of &gt; 35 kg/m² with obesity-related comorbidities, or BMI of &gt; 30 kg/m² with a history of type 2 diabetes mellitus (T2DM). Bariatric procedures result in weight loss and improved metabolic outcomes, although weight regain can occur after surgery. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and GLP-1 RA/glucose-dependent insulinotropic polypeptide receptor agonists (GIP RAs) have emerged as effective injectable therapies for weight loss and management of obesity-related comorbidities.</div></div><div><h3>Objective</h3><div>This project evaluated the efficacy and tolerability of GLP-1 RA and GLP-1 RA/GIP RA therapy after bariatric surgery.</div></div><div><h3>Methods</h3><div>This single-center, retrospective project included patients who underwent bariatric surgery, were initiated on GLP-1 RA or GLP-1/GIP RA at least 1 year after surgery, and were on therapy for at least 6 months. The primary outcome was the percentage change in body weight from initiation of therapy to 6 months after. Secondary outcomes included the percentage of patients achieving ≥ 5%, ≥ 10%, or ≥ 15% reduction in weight; time from bariatric surgery to therapy initiation; discontinuation or dose reduction of therapy; and weight change comparison between patients with a history of T2DM and not enrolled in a weight loss clinic compared with those enrolled in a weight loss clinic.</div></div><div><h3>Results</h3><div>Fifty patients met the inclusion criteria. The mean percentage weight change at 6 months was −8.4%. For percentage weight reduction, 16 patients achieved ≥ 5%, 13 achieved ≥ 10%, and 7 achieved ≥ 15%. Median time from surgery to initiation of therapy was 111 months. Adverse events occurred in 3 patients (6%).</div></div><div><h3>Conclusion</h3><div>Overall, in patients receiving GLP-1 RA at least 1 year after bariatric surgery, additional weight loss was observed with minimal reported adverse events.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 4","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing intraoperative administration of long-acting bupivacaine, multimodal cocktails, and local anesthetics for postoperative pain management","authors":"Gabriella A. Perez,&nbsp;Alexander D. Schroeder,&nbsp;Daniel R. Fassett,&nbsp;Matthew W. Todd,&nbsp;Leilanie Y. Crespo Hernández,&nbsp;Francisco G. Perez Diaz,&nbsp;Oscar Santalo","doi":"10.1016/j.japhar.2025.100019","DOIUrl":"10.1016/j.japhar.2025.100019","url":null,"abstract":"<div><h3>Background</h3><div>Liposomal bupivacaine (LB) has gained popularity for its reported analgesic effects lasting up to 72 hours. However, multimodal local anesthetic cocktails (MCs) may offer comparable pain control with potential cost savings and opioid-sparing benefits.</div></div><div><h3>Objectives</h3><div>This study compared postoperative pain outcomes with LB versus MCs such as ropivacaine-epinephrine-clonidine-ketorolac, bupivacaine-epinephrine-dexamethasone, bupivacaine-meloxicam, and traditional local anesthetics (LAs) such as lidocaine and bupivacaine.</div></div><div><h3>Setting and participants</h3><div>This retrospective, observational study included patients who underwent outpatient and inpatient procedures between August 1, 2023, and January 31, 2024.</div></div><div><h3>Outcome measures</h3><div>The primary outcome was postoperative day (POD) 2 pain scores. Secondary outcomes included total morphine milliequivalents (MMEs) administered within 72 hours and projected cost savings. Participants were excluded if they were younger than 18 years, lacked documented pain scores or MME data, had a history of chronic pain, or were pregnant.</div></div><div><h3>Results</h3><div>Of 27,878 patients, 265 were evaluated, and 174 met the inclusion criteria. Fifty-one received LB, 73 received MCs, and 50 received LAs. POD 2 pain scores for the LB, MC, and LA groups were not statistically different (<em>P</em> = 0.41), with averages of 4.69, 5.05, and 4.42, respectively. Total MMEs were also similar across groups, with a median total of 48.53, 51.16, and 40.10 for LB, MCs, and LAs, respectively (<em>P</em> = 0.58). Our cost analysis projected annualized savings of approximately $2.8 million and average patient savings of $46,500 per surgical procedure.</div></div><div><h3>Conclusion</h3><div>These findings suggest that MCs are a cost-effective alternative to LB with comparable analgesic effects.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 3","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world safety profile of lecanemab: A disproportionality analysis of adverse events in the FDA adverse event reporting system","authors":"Jayoung Han,&nbsp;Yuan Fang,&nbsp;Nicole Campbell","doi":"10.1016/j.japhar.2025.100015","DOIUrl":"10.1016/j.japhar.2025.100015","url":null,"abstract":"<div><h3>Background</h3><div>Lecanemab, an antiamyloid monoclonal antibody, has emerged as a treatment option for Alzheimer disease. However, there is a pressing need for real-world evidence to inform clinical practice, particularly regarding its safety profile.</div></div><div><h3>Objectives</h3><div>This study aimed to analyze adverse events (AEs) associated with lecanemab using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.</div></div><div><h3>Methods</h3><div>All cases reporting AEs were included if reported during the study period, from January 1, 2023, to June 30, 2024, during which a total of 1,307,937 cases were reported in the FAERS database. A disproportionality analysis was conducted to assess adverse reactions associated with lecanemab. Reporting odds ratios (RORs) with 95% CIs were extracted from OpenVigil 2.1-MedDRA-v24 for lecanemab-related events.</div></div><div><h3>Results</h3><div>The analysis identified a total of 1679 AEs associated with lecanemab during the study period. The strongest safety signal was observed for amyloid-related imaging abnormalities (ARIAs), particularly ARIA with hemosiderin deposits in the brain parenchyma or on the pial surface (microhemorrhages, ROR 11,221.5 [95% CI 5706.2–22,067.5]) and ARIA with brain edema or sulcal effusion (edema/effusion, ROR 8927.3 [95% CI 5243.6–15,199.1]). Other notable AEs included infusion-related reactions (ROR 24.9 [95% CI 18.9–32.8]), headache (ROR 10.2 [95% CI 8.6–12.2]), and confusional states (ROR 15.0 [95% CI 11.4–19.7]).</div></div><div><h3>Conclusion</h3><div>This study underscores the importance of vigilant monitoring for ARIA and other neurologic and psychiatric AEs associated with lecanemab in real-world clinical settings. The findings highlight the need for ongoing postmarket surveillance to ensure patient safety and guide clinical decision making.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 2","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the safety of daptomycin coadministered with statin medications","authors":"Tyler M. Mitzner,&nbsp;Michael McCormick,&nbsp;Krissy M. Lentz,&nbsp;Ryan Tomlin,&nbsp;Kyle J. Schmidt,&nbsp;Lisa E. Dumkow","doi":"10.1016/j.japhar.2025.100017","DOIUrl":"10.1016/j.japhar.2025.100017","url":null,"abstract":"<div><h3>Background</h3><div>Conflicting clinical evidence and prescribing recommendations exist regarding the safety of daptomycin when coadministered with statin medications. In addition, recommendations to hold statins during daptomycin therapy do not account for atherosclerotic cardiovascular disease (ASCVD) risk. Because of this, the practice of holding or continuing statins during daptomycin therapy is variable among providers.</div></div><div><h3>Objectives</h3><div>This study aimed to compare the musculoskeletal and cardiovascular safety of daptomycin and statin coadministration versus monotherapy and assess the appropriateness of monitoring during daptomycin infusion therapy, including creatine kinase (CK) and musculoskeletal symptoms, and the resumption of statins held during daptomycin therapy.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included patients who were prescribed a statin medication and daptomycin therapy. The primary outcome was to compare daptomycin discontinuation owing to suspected musculoskeletal toxicity between patients who had their statin held and received daptomycin monotherapy (monotherapy group) and those who received daptomycin coadministered with statins (coadministered group). Secondary outcomes included evaluating CK monitoring practices, ASCVD events, and the resumption of held statins at the completion of daptomycin therapy.</div></div><div><h3>Results</h3><div>A total of 74 patients were included (monotherapy, n = 64; coadministered, n = 10). No statistically significant differences were observed between the 2 groups regarding daptomycin discontinuation owing to suspected musculoskeletal toxicity (6.3% monotherapy vs. 10% coadministered, <em>P</em> = 0.527). One patient in the monotherapy group had an ASCVD event during daptomycin therapy; none occurred within the coadministered group. Within the monotherapy group, 9 patients (14.1%) did not have documentation of statin resumption and 22 (34.4%) saw a delay of 4 or more weeks in statin resumption after daptomycin completion.</div></div><div><h3>Conclusion</h3><div>Patients who received daptomycin coadministration with statin therapy did not experience more musculoskeletal toxicity than patients who received daptomycin monotherapy. Owing to the risk of ASCVD events and potential for errors and delays in resumption, statins should be continued during daptomycin therapy, especially in high-risk patients.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 2","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overall survival of patients over 65 years old with lung cancer receiving programmed death-1 inhibitors and antibiotics","authors":"Valerie S. Hughes,&nbsp;Eric J. Vick,&nbsp;Rowena Schwartz,&nbsp;Roman Jandarov,&nbsp;Jeff J. Guo,&nbsp;Alex C. Lin,&nbsp;Ana L. Hincapie","doi":"10.1016/j.japhar.2025.100012","DOIUrl":"10.1016/j.japhar.2025.100012","url":null,"abstract":"<div><h3>Background</h3><div>Programmed death-1 (PD-1) inhibitors have advanced treatment of patients with non–small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, and other cancers. Lung cancer is commonly diagnosed at the advanced stage in an older adult patient population; therefore, many contributing factors can influence the treatment response. Not all patients respond to PD-1 treatment and even less is known for aging patients with comorbidities, altered gut microbiome, and multiple concomitant medications.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate overall survival (OS) in older adult patients with lung cancer receiving PD-1 inhibitors and medications known to affect the gut microbiome.</div></div><div><h3>Methods</h3><div>Surveillance, Epidemiology, and End Results–Medicare is a database that links tumor registry data with Medicare enrollment and claims files. The study cohort was determined based on lung cancer histology, claims for nivolumab or pembrolizumab, and continuous enrollment. Oral antibiotic (Ab) claims were identified in the Part D file and assigned to 14-, 30-, or 60-day comparison groups. Patient characteristics between PD-1 and Ab exposure at 14, 30, and 60 days were assessed by chi-square test. The association between OS and Ab was analyzed using the Cox proportional hazards model and Kaplan-Meier curves.</div></div><div><h3>Results</h3><div>We identified 3445 patients who had lung cancer and received PD-1 inhibitors from 2014 to 2017. Of those patients, 1702 (49%) received an oral Ab within 60 days of starting the PD-1 therapy. Ab use during the initiation of PD-1 treatment was associated with shorter OS when given within 60 days of initiation of treatment (hazard ratio 1.273 [95% confidence interval 1.104–1.469], <em>P</em> = 0.0009) than patients with no Ab claim within 180 days of index.</div></div><div><h3>Conclusion</h3><div>Utilization of immunotherapy is increasing in the Medicare population and these patients commonly have age-related changes to the immune systems and microbiome. These results provide OS estimates for older adult patients with lung cancer treated with PD-1 and receiving medications known to alter important gut microbiome diversity. The complex interactions of the immune system, microbiome, and immunotherapy response are key for the effective treatment of patients with NSCLC.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 1","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alignment of counseling around topical steroids will improve morbidity associated with lichen sclerosus","authors":"Margaret E. Greer,&nbsp;Paras P. Vakharia,&nbsp;Melissa M. Mauskar","doi":"10.1016/j.japhar.2025.100010","DOIUrl":"10.1016/j.japhar.2025.100010","url":null,"abstract":"<div><div>Ultrapotent topical steroids are the first-line treatment for lichen sclerosus, a chronic inflammatory disease that most commonly affects the genital and anal regions. Lichen sclerosus can cause profound morbidity and can progress to squamous cell carcinoma. Therefore, treatment is essential to mitigate these complications. Despite the accessibility, relative affordability, and safety profiles of topical steroids, many clinicians, pharmacists, and patients are hesitant to use them. This paper outlines the importance of chronic steroid use for managing lichen sclerosus to prevent disease sequelae and aims to educate readers on ways physicians and pharmacists can mitigate steroid phobia.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"1 4","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guidance on calculating doses of antineoplastic agents for transgender and gender-expansive patients taking gender-affirming hormone therapy","authors":"Andréa C. LeVoir,&nbsp;Erica C. Stumpf,&nbsp;Wiktoria Bogdanska,&nbsp;Maly Fenelus,&nbsp;Ilya G. Glezerman,&nbsp;Lubaina Presswala,&nbsp;Boglarka Gyurkocza,&nbsp;Koshy Alexander,&nbsp;Kelly Haviland","doi":"10.1016/j.japhar.2024.100009","DOIUrl":"10.1016/j.japhar.2024.100009","url":null,"abstract":"<div><h3>Background</h3><div>There is currently no formal guidance for calculating chemotherapy in transgender and gender-expansive patients taking gender-affirming hormone therapy (GAHT). It is necessary to develop a method that ensures that chemotherapy dosing and treatment are both safe and effective in this population.</div></div><div><h3>Objectives</h3><div>To identify guidance for clinicians to evaluate renal function to determine appropriate chemotherapy doses in transgender and gender-expansive adult patients taking GAHT.</div></div><div><h3>Methods</h3><div>The Lesbian, Gay, Bisexual, Transgender, Queer, and Intersex (LGBTQI+) Clinical Advisory Committee at a large comprehensive cancer center conducted an unstructured review in PubMed to identify current literature surrounding chemotherapy and medication dosing in patients taking GAHT.</div></div><div><h3>Results</h3><div>The use of sex assigned at birth-dependent methods to define renal dosing may not be accurate for transgender and gender-expansive patients. Based on the limited published literature, a multidisciplinary team developed guidance on calculating chemotherapy dosing in patients who are taking GAHT. Gaps not addressed by available literature were evaluated by a panel of experts, and their recommendations were included.</div></div><div><h3>Conclusion</h3><div>A guideline was produced based on the available data; however, additional research is needed to better define the physiologic changes that occur with GAHT and how those changes affect renal function and current surrogates that are used to estimate renal function.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"1 4","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143242616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of prolonged thrice-weekly high-dose daptomycin in a hemodialysis patient with prosthetic valve endocarditis","authors":"Michael Bosco,&nbsp;Nadeem Baalbaki","doi":"10.1016/j.japhar.2024.100008","DOIUrl":"10.1016/j.japhar.2024.100008","url":null,"abstract":"<div><h3>Background</h3><p>Daptomycin (DAP) is a cyclic lipopeptide antibiotic with in vitro, concentration-dependent bactericidal activity against many clinically relevant gram-positive organisms including <em>Staphylococcus</em> spp. and <em>Enterococcus</em> spp. High-dose DAP (i.e., &gt; 9 mg/kg) has been associated with improved survival outcomes in patients with invasive enterococci infections. Although generally well tolerated, DAP is associated with myopathy and rhabdomyolysis. Limited data regarding the safety of high-dose DAP in hemodialysis (HD) patients, especially with doses ≥ 12 mg/kg, are available. Here, we describe the safety outcomes in a HD patient who received prolonged, thrice-weekly, high-dose DAP. To the best of our knowledge, this is the first case report looking at the safety of long-term DAP doses up to 18 mg/kg.</p></div><div><h3>Case summary</h3><p>A 65-year-old male with a medical history significant for end-stage renal disease on intermittent HD was diagnosed as having prosthetic valve endocarditis secondary to vancomycin-resistant <em>Enterococcus faecium</em> (VRE)<em>.</em> He was deemed a poor surgical candidate and the decision was made for conservative management. DAP was continued for approximately 4 months at a dose of 12 mg/kg on 48-hour interdialytic days and 18 mg/kg on the 72-hour interdialytic day. Creatine phosphokinase (CPK) was monitored once or twice weekly. Average CPK during therapy was 92.3 U/L ± 38.9. Overall, DAP was well tolerated and the patient did not experience any signs or symptoms of myopathy or rhabdomyolysis based on daily review of systems.</p></div><div><h3>Practice implications</h3><p>Although more data are needed to assess the safety of this particular dosing strategy, our case findings suggest that prolonged DAP doses ≥ 12 mg/kg can be safely considered in those receiving intermittent HD, especially when aggressive treatment is needed for invasive VRE infection.</p></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"1 3","pages":"Article 100008"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949962324000044/pdfft?md5=80ed4a633d14b485f15364b5b943cdd8&pid=1-s2.0-S2949962324000044-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proportion of intensive care unit patients receiving sedation after rapid sequence intubation with rocuronium","authors":"Joanna Dukes,&nbsp;Preeyaporn Sarangarm,&nbsp;Nicole Murtagh,&nbsp;Kevin A. Kaucher","doi":"10.1016/j.japhar.2024.100007","DOIUrl":"10.1016/j.japhar.2024.100007","url":null,"abstract":"<div><h3>Background</h3><p>Rocuronium has a longer duration of action than the sedative effects of induction agents used during rapid sequence intubation (RSI), introducing a potential window for inadequate sedation. When rocuronium is used for paralysis in the emergency department, delays in sedation have been observed, but have not been described in intensive care units (ICUs).</p></div><div><h3>Objectives</h3><p>The primary objective is the proportion of patients in the ICU who received sedation within 15 minutes after intubation using rocuronium. Secondary objectives include (1) time to sedation (minutes), (2) time to sedation between ICUs (minutes), (3) time to sedation between provider specialties (minutes), (4) time to sedation by Glasgow coma scale (GCS), and (5) first-hour versus second-hour Sedation Intensity Score (SIS) after RSI.</p></div><div><h3>Methods</h3><p>This is a retrospective review at a single academic tertiary care center of patients intubated in an ICU between July 2019 and August 2020. Inclusion criteria were age 18 to 89 years, intubation using rocuronium, and intubation in an ICU. Exclusion criteria were sedative exposure before intubation, no charted induction agent or charting delays from paralytic, incomplete charting, intubation outside an ICU, intubation during cardiac arrest, pregnancy, or incarceration.</p></div><div><h3>Results</h3><p>A total of 192 intubations using rocuronium were included and 77 (40.1%) received sedation within 15 minutes of induction agent administration. There was no difference in proportion of patients receiving sedation by GCS ≤ 8 and GCS &gt; 8 before intubation (38.1% vs. 41.1%, <em>P</em> = 0.69). Using a SIS to describe amount of sedative administered, more sedation was administered in the second hour after intubation than the first hour (median score 5.5 [interquartile range {IQR} 0-20] vs. 4.5 [IQR 0-12.5], <em>P</em> &lt; 0.001).</p></div><div><h3>Conclusion</h3><p>In this single-center analysis, a large proportion of patients intubated in ICUs with rocuronium did not receive additional sedation within 15 minutes of induction, exposing them to risk of awareness while paralyzed.</p></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"1 3","pages":"Article 100007"},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949962324000032/pdfft?md5=52094e0f34a9dd0f3422885bcc7587bd&pid=1-s2.0-S2949962324000032-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140768501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of loperamide on heart rhythm: Randomized, double-blind, controlled study in healthy adults","authors":"Iolanda Cirillo,&nbsp;Jay Ariyawansa,&nbsp;Saberi Rana Ali,&nbsp;Evren Atillasoy","doi":"10.1016/j.japhar.2024.100006","DOIUrl":"https://doi.org/10.1016/j.japhar.2024.100006","url":null,"abstract":"<div><h3>Background</h3><p>Excessively high doses of loperamide (of up to 792 mg/day) have recently been associated with reports of cardiac events. However, no data currently demonstrate a direct effect of high doses of loperamide on the occurrence of cardiovascular abnormalities.</p></div><div><h3>Objectives</h3><p>This study aimed to assess the effects of loperamide on QT/corrected QT (QTc) intervals, electrocardiogram (ECG) morphology, and overall safety and tolerability at therapeutic and supratherapeutic exposures in healthy adults.</p></div><div><h3>Methods</h3><p>This randomized, double-blind, 4-way-crossover study enrolled 65 healthy adults to receive loperamide 8 mg (therapeutic dose), loperamide 48 mg (supratherapeutic dose), moxifloxacin 400 mg (positive control), and placebo. Least square (LS) mean difference in change from baseline in Fridericia-corrected QT (ΔQTcF) intervals between loperamide (8 mg and 48 mg) and placebo with the 2-sided 90% CI was calculated for each time point. A noninferiority criterion of mean difference in ΔQTcF of 10 ms evaluated whether loperamide was noninferior to placebo. Treatment safety was assessed throughout the study.</p></div><div><h3>Results</h3><p>Most participants were female (66.2%) and white (95.4%). The age was 36.4 years (SD 9.77). The highest upper limit of the 2-sided 90% CI for LS mean difference in ΔQTcF between loperamide and placebo was 3.39 ms for the therapeutic dose and 9.28 ms for the supratherapeutic dose of loperamide, which were below the 10 ms threshold, thereby demonstrating noninferiority of loperamide to placebo. There were no statistically significant morphologic ECG changes after loperamide administration. There were no deaths, serious adverse events, or severe treatment-emergent adverse events.</p></div><div><h3>Conclusion</h3><p>Single-dose loperamide at therapeutic (8 mg) and supratherapeutic (48 mg) doses do not show evidence of QTc prolongation of clinical concern in healthy participants. No new safety findings were identified.</p></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"1 3","pages":"Article 100006"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949962324000020/pdfft?md5=9cd0ee4479f64d543e4c8feaa9ec4bcd&pid=1-s2.0-S2949962324000020-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140633463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}