PharmacotherapyPub Date : 2024-12-01Epub Date: 2024-12-19DOI: 10.1002/phar.4628
Nicholas R Nelson, Nicholas J Quinn, Stephanie Bills, Alexander Dellabella, Sarah E Gregar, Alyssa Lear, Legacy Marsolek, Crystal Mounce, Morgan Tobin
{"title":"Scoping review of drug dosing recommendations in sustained low-efficiency dialysis.","authors":"Nicholas R Nelson, Nicholas J Quinn, Stephanie Bills, Alexander Dellabella, Sarah E Gregar, Alyssa Lear, Legacy Marsolek, Crystal Mounce, Morgan Tobin","doi":"10.1002/phar.4628","DOIUrl":"10.1002/phar.4628","url":null,"abstract":"<p><p>The objective of this scoping review was to answer the question, \"What has been published describing drug dosing in sustained low-efficiency dialysis (SLED)?\" PubMed, Embase, and Scopus were searched on November 18, 2022. Methodology followed the Arksey and O'Malley framework for scoping reviews and Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guidelines. Two investigators independently screened abstracts and full-texts of citations identified related to drug dosing and SLED. Exclusion criteria included case reports, conference abstracts, pediatrics, treatment dialysis, and non-human subjects. A standardized data extraction sheet was used to collate and summarize data. The quality of evidence was evaluated by two investigators using the Mixed Methods Appraisal Tool. A total of 230 citations were identified for screening. Of these, 29 studies met criteria for inclusion after full-text review. Four drug groups including beta-lactam antibiotics, non-beta-lactam antibiotics, antifungals, and levetiracetam were identified. Dialysate rates, dialysis durations, and medication doses used varied widely across studies. Outcomes and pharmacokinetic parameters that were assessed were also heterogenous. Drug dosing in SLED is challenging and there is minimal evidence available to guide appropriate dosing. Larger studies are needed to more accurately determine how to appropriately dose medications in SLED. Therapeutic drug monitoring should be used in all patients on SLED when available.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"948-955"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865046","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}
PharmacotherapyPub Date : 2024-12-01Epub Date: 2024-12-23DOI: 10.1002/phar.4630
Natalie R Rose, Julianna Bailey, Justin D Anderson, Ashritha R Chalamalla, Kevin J Ryan, Edward P Acosta, Jennifer S Guimbellot
{"title":"Pilot and feasibility study of dietary composition with elexacaftor-tezacaftor-ivacaftor concentrations in people with cystic fibrosis.","authors":"Natalie R Rose, Julianna Bailey, Justin D Anderson, Ashritha R Chalamalla, Kevin J Ryan, Edward P Acosta, Jennifer S Guimbellot","doi":"10.1002/phar.4630","DOIUrl":"10.1002/phar.4630","url":null,"abstract":"<p><strong>Background: </strong>Nutritional support for people with cystic fibrosis (PwCF) after the implementation of novel drug therapies is shifting from managing malnutrition through a high-fat, high-calorie diet to managing emerging incidences of obesity in this population. Additionally, dietary recommendations prescribed with elexacaftor/tezacaftor/ivacaftor (ETI) recommend taking this drug with a fat-containing meal, which is variably interpreted by patients. This pilot and feasibility study was conducted to assess dietary fat intake and body composition on ETI plasma concentrations.</p><p><strong>Methods: </strong>Ten participants were enrolled in a 1:1 crossover design by dietary recommendations. To mimic recommendations made during routine clinical care, participants were instructed to consume either a general healthful diet (no more than 30% calories from fat) or a high-fat diet (>40% calories from fat) for a week before crossing over to the alternative diet.</p><p><strong>Results: </strong>This pilot study was acceptable to and feasible for study participants. Most participants increased fat intake calories when following a high-fat diet. Body composition measurements showed a trending correlation between lean mass and fat-free mass with ETI plasma concentrations. ETI compounds were quantified in plasma at 0 h (prior to the ETI morning dose) and 6 h after ingestion, and consuming a high-fat diet did not significantly impact ETI concentrations.</p><p><strong>Conclusions: </strong>Consuming a higher-fat diet did not significantly impact ETI plasma concentrations, and all participants were in range for clinical effectiveness of ETI regardless of fat intake. This work provides vital pilot data to design larger studies to clarify dietary composition for optimal ETI exposure for PwCF on this therapy.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"920-926"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882581","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":"Response to comment on: \"The power and pitfalls of underpowered studies\".","authors":"Ryan M Carnahan, Grant D Brown","doi":"10.1002/phar.4625","DOIUrl":"https://doi.org/10.1002/phar.4625","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"44 12","pages":"957-958"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907519","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}
PharmacotherapyPub Date : 2024-12-01Epub Date: 2024-11-27DOI: 10.1002/phar.4627
Brandy N Hernandez, Patrick M Wieruszewski, Jason N Barreto, Kristin C Cole, Shivam Damani, Sandra L Kane-Gill, Kianoush B Kashani, Ellen Kelly, Andrew D Rule, Hilary R Teaford, Jaleh Zand, Erin F Barreto
{"title":"Challenges in renally eliminated medication use: Evaluating cystatin C and serum creatinine eGFR discordance.","authors":"Brandy N Hernandez, Patrick M Wieruszewski, Jason N Barreto, Kristin C Cole, Shivam Damani, Sandra L Kane-Gill, Kianoush B Kashani, Ellen Kelly, Andrew D Rule, Hilary R Teaford, Jaleh Zand, Erin F Barreto","doi":"10.1002/phar.4627","DOIUrl":"10.1002/phar.4627","url":null,"abstract":"<p><strong>Background: </strong>Accurately estimating glomerular filtration rate (GFR) is crucial for dosing medications in hospitalized patients. Due to limitations of serum creatinine for GFR estimation, serum cystatin C (CysC) has been explored as an alternative functional kidney biomarker. This study assessed discordance between eGFR<sub>Cr</sub> and eGFR<sub>CysC</sub> in a large sample of hospitalized patients and examined the frequency of renally eliminated medications affected by eGFR discordance.</p><p><strong>Methods: </strong>This multisite historical study included adults hospitalized between 2011 and 2023 with CysC and serum creatinine reported within 24 h of each other. The first concurrent biomarker pair for each patient was analyzed. eGFR discordance and use of renally eliminated medications were described.</p><p><strong>Results: </strong>17,718 hospitalized patients with concurrent creatinine and CysC assessments were included. The median eGFR<sub>Cr</sub> was 65 mL/min, and the eGFR<sub>CysC</sub> was 46 mL/min. The median absolute difference of eGFR<sub>Cr</sub>-eGFR<sub>CysC</sub> was 15 mL/min, and 7972 patients (45%) had a > 30% absolute difference. There was a significantly greater percentage of patients with an eGFR <30 mL/min based on eGFR<sub>CysC</sub> (26%) compared to eGFR<sub>Cr</sub> (15%) (p < 0.001). Patients were prescribed an average of 20 medications in the 24 h surrounding the concurrent biomarker assessment. Renally eliminated medications accounted for 39% ± 13% of medication orders, and 80% of patients with eGFR discordance were prescribed five or more renally eliminated medications.</p><p><strong>Conclusion: </strong>Substantial eGFR discordance between eGFR<sub>CysC</sub> and eGFR<sub>Cr</sub> was observed in hospitalized patients, which directly affects the dosing of renally eliminated medications. Further research is needed to optimize the pharmacotherapy of renally eliminated medications with discordant GFR assessments to improve medication safety and effectiveness.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"898-906"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731827","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":"External evaluation of neonatal vancomycin population pharmacokinetic models: Moving from first-order equations to Bayesian-guided therapeutic monitoring.","authors":"Mathieu Blouin, Marie-Élaine Métras, Camille Gaudreault, Marie-Hélène Dubé, Marie-Christine Boulanger, Karine Cloutier, Mehdi El Hassani, Aysenur Yaliniz, Isabelle Viel-Thériault, Amélie Marsot","doi":"10.1002/phar.4623","DOIUrl":"10.1002/phar.4623","url":null,"abstract":"<p><strong>Introduction: </strong>Guidelines for vancomycin therapeutic monitoring recommend using a Bayesian approach with a population pharmacokinetic model to estimate the 24 h area under the concentration-time curve over first-order equations. Thus, we performed an external evaluation of population pharmacokinetic models of vancomycin in neonates and compared Bayesian results with those observed in clinical practice via pharmacokinetic equations to improve therapeutic monitoring by proposing optimized initial dosing nomograms and assessing the feasibility of reduced blood sampling strategies using the most predictive models.</p><p><strong>Methods: </strong>Models were identified from the literature and evaluated via an external neonatal population. A priori predictive performance was first assessed by prediction-based diagnostics, then by simulation-based diagnostics and a posteriori analyses only if deemed satisfactory; model-informed vancomycin exposure was also compared with reference first-order pharmacokinetic equations. The best-performing models were ultimately subjected to Monte Carlo simulations to develop new initial dosing nomograms offering the highest probability of achieving therapeutic target.</p><p><strong>Results: </strong>A total of 28 population pharmacokinetic models were evaluated in the external dataset, which includes 72 neonates and 380 vancomycin concentrations. Eleven models had an adequate predictive performance with bias ≤ ± 15% and imprecision <math><mo>≤</mo></math> 30%, while the Bayesian approach yielded over 75% agreement with reference exposure values in most cases. Nonetheless, Capparelli et al. and Mehrotra et al. models performed the best overall, showing the lowest imprecisions of 16.8% and 16.9%, respectively; both models recommended higher dosage regimens than the theoretical nomogram currently applied to favor therapeutic target attainment.</p><p><strong>Discussion: </strong>We externally evaluated numerous neonatal population pharmacokinetic models of vancomycin and used the most predictive ones to advocate new initial dosing nomograms. Clinical implementation of the Bayesian approach could reduce the time needed to reach therapeutic target and limit the number of blood samples in newborns compared with traditional pharmacokinetic equations.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"907-919"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625954","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":"DPYD and fluoropyrimidines: Using the data as our guide.","authors":"Christine M Walko","doi":"10.1002/phar.4634","DOIUrl":"https://doi.org/10.1002/phar.4634","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"44 12","pages":"896-897"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907518","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}
PharmacotherapyPub Date : 2024-11-01Epub Date: 2024-11-16DOI: 10.1002/phar.4621
Mohammed Aldhaeefi, Dhakrit Rungkitwattanakul, Ilyas Saltani, Antoinette Muirhead, Alexander J Ruehman, W Anthony Hawkins, Monika N Daftary
{"title":"Update and narrative review of avian influenza (H5N1) infection in adult patients.","authors":"Mohammed Aldhaeefi, Dhakrit Rungkitwattanakul, Ilyas Saltani, Antoinette Muirhead, Alexander J Ruehman, W Anthony Hawkins, Monika N Daftary","doi":"10.1002/phar.4621","DOIUrl":"10.1002/phar.4621","url":null,"abstract":"<p><p>The avian influenza is a serious infection caused by influenza virus that is native to birds. Avian influenza remains a global challenge due to high transmission and mortality rates. The highly pathogenic strain of H5N1 resulted in significant outbreaks and deaths globally since the late 1800s. The most recent outbreaks in wild birds, domestic birds, and cows with some genetic variations and mutations among H5N1 strains has raised major concerns about potential transmission and public health risks. Symptoms range from asymptomatic to mild flu-like illness to severe illness that requires hospitalization. There are multiple vaccines in development for humans to protect against avian influenza, specifically the H5N1 virus. This includes a cell-based vaccine approved by the FDA for people aged 6 months and older who are at higher risk of exposure to the H5N1 virus called Audenz. Chemoprophylaxis against avian influenza following a suspected exposure should be started as soon as possible or no later than 48 h, and it is recommended to be continued for 7 days. The majority of avian influenza viruses are susceptible to neuraminidase inhibitors and cap-dependent endonuclease inhibitor. Neuraminidase inhibitors are the mainstay of the avian influenza treatment and includes oseltamivir, peramivir, and zanamivir. Baloxavir marboxil is a cap-dependent endonuclease inhibitor. This clinical review aims to highlight the background, epidemiology, clinical presentation, complications and current treatment and prevention strategies for avian influenza H5N1.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"870-879"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644384","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":"Sex differences in LDL-C reduction response to evolocumab: A propensity score matching analysis.","authors":"Ye-Qian He, Yu-Qing Wei, Guang-Ming Huang, Guo-Ping Liu, Zhong-Qiu Lin, Tao-Tao Liu, Xia Jiang, Jie-Jiu Lu","doi":"10.1002/phar.4619","DOIUrl":"10.1002/phar.4619","url":null,"abstract":"<p><strong>Background: </strong>Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been shown to improve cardiovascular outcomes by reducing low-density lipoprotein cholesterol (LDL-C). However, sex differences in the efficacy of evolocumab remain unclear. This study aimed to investigate sex differences in the efficacy of evolocumab using real-world data.</p><p><strong>Method: </strong>Data were collected from the First Affiliated Hospital of Guangxi Medical University. A total of 416 eligible patients were selected from 1463 patients treated with evolocumab for secondary prevention. Clinical data, including individual characteristics and lipids profiles, were recorded. Propensity score matching (PSM) was used to control for potential confounders, with covariates including age, body mass index, smoking status, and diabetes. All eligible participants were propensity-matched 1:1 for female versus male with a match tolerance of 0.02. The efficacy of evolocumab in females and males was compared by PSM-adjusted analysis.</p><p><strong>Results: </strong>In the PSM analysis, a significant difference was found in the relative percentage reduction of LDL-C between females and males (-42.7% vs. -54.4%, p < 0.001). In addition, the absolute LDL-C reduction was lower in females compared to males (interquartile range: -1.5 [-2.2, -0.8] mmol/L vs. -1.9 [-2.5, -1.0] mmol/L, p = 0.018). The rate of target LDL-C attainment was lower in females than in males after treatment with evolocumab (21.6% vs. 39.8%, p = 0.009).</p><p><strong>Conclusion: </strong>These results suggest that males have a better response to evolocumab in term of LDL-C reduction compared to females.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"861-869"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505803","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}
PharmacotherapyPub Date : 2024-11-01Epub Date: 2024-11-05DOI: 10.1002/phar.4622
Paul M Boylan, Melissa Santibañez, Jennifer Thomas, Erin Weeda, Zachary R Noel, Joshua Caballero
{"title":"Cannabinoids for obstructive sleep apnea: A systematic review.","authors":"Paul M Boylan, Melissa Santibañez, Jennifer Thomas, Erin Weeda, Zachary R Noel, Joshua Caballero","doi":"10.1002/phar.4622","DOIUrl":"10.1002/phar.4622","url":null,"abstract":"<p><p>Cannabinoids have emerged as a potential treatment for obstructive sleep apnea (OSA). This systematic review aimed to summarize the efficacy and safety of cannabinoids to treat OSA. Databases including Ovid MEDLINE, EMBASE, Scopus, PsycINFO, and International Pharmaceutical Abstracts were searched; experimental and observational studies were eligible for inclusion. One-hundred seventy unique records were screened, and nine studies included: five full-text studies and four published abstracts. The five full-text studies were judged for quality appraisal: two studies deemed at low risk for bias, one study deemed to have some concerns for bias, and two studies deemed to have high risk for bias. Seven of nine total studies were experimental designs and evaluated dronabinol, and the other two studies were observational designs evaluating cannabis. The range of cannabinoid therapy duration spanned from 1 to 6 weeks, and the median duration was 3 weeks. Eight of nine total studies reported statistically significant, positive OSA outcomes due to cannabinoid therapy including reductions in the apnea hypopnea index and improvements in patient-reported daytime sleepiness scales. Between 70% and 80% of study participants reported neuropsychiatric and gastrointestinal adverse events attributable to cannabinoids. The American Academy of Sleep Medicine does not recommend using cannabinoids to treat OSA due to a lack of long-term safety and efficacy data. This systematic review found similar limitations, with the median cannabinoid treatment duration being only 3 weeks. Adequately powered experimental trials over longer time frames are necessary to more completely assess the long-term efficacy and safety of cannabinoids in the treatment of OSA and its effects on common comorbid conditions, such as obesity and cardiovascular disease.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"880-891"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576475","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}