Pub Date : 2024-10-01DOI: 10.1016/j.clinthera.2024.06.017
Ekwu B. Ochigbo RPhPhD, Molly T. Beinfeld MPH, James D. Chambers MPharmPhD
Purpose
Variations in US commercial health plan coverage policies affect how patients access medications. Plans may vary in treatment access criteria, line of therapy, and prescriber requirements. In this study, we examined coverage of esketamine hydrochloride (Spravato) for major depressive disorder (MDD) and treatment-resistant depression (TRD) to answer the following question: how do US commercial health plans cover esketamine, and how do they guide prompt patient access to the drug?
Methods
We used information from the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes coverage policies issued by 18 large commercial health plans in the United States. Esketamine coverage policies for MDD and TRD active in December 2022 were collated and analyzed. We compared coverage policies according to step therapy protocols, patient subgroup restrictions, and prescriber requirement criteria, evaluating patient access using the number of restrictions and proportion of plans including each criterion.
Findings
Plans more often imposed step therapy requirements for access to esketamine for TRD than for MDD, with line of treatment of ≤9 steps for MDD compared with 1 to 5 steps for TRD. Plans also varied with respect to the therapies they required patients to first try and experience treatment failure before granting access to esketamine for both indications. Clinical coverage requirements varied in thresholds and rating scales used to assess severity of depressive symptoms.
Implications
Plans vary in terms of line of therapy and clinical coverage requirements for access to esketamine. Variation in health plan coverage policies may result in inequitable access and added complexity for patients and clinicians navigating care, which may delay access to urgent treatment.
{"title":"Balancing Evidence and Need: Variation in US Commercial Payer Coverage of Esketamine","authors":"Ekwu B. Ochigbo RPhPhD, Molly T. Beinfeld MPH, James D. Chambers MPharmPhD","doi":"10.1016/j.clinthera.2024.06.017","DOIUrl":"10.1016/j.clinthera.2024.06.017","url":null,"abstract":"<div><h3>Purpose</h3><div>Variations in US commercial health plan coverage policies affect how patients access medications. Plans may vary in treatment access criteria, line of therapy, and prescriber requirements. In this study, we examined coverage of esketamine hydrochloride (Spravato) for major depressive disorder (MDD) and treatment-resistant depression (TRD) to answer the following question: how do US commercial health plans cover esketamine, and how do they guide prompt patient access to the drug?</div></div><div><h3>Methods</h3><div>We used information from the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes coverage policies issued by 18 large commercial health plans in the United States. Esketamine coverage policies for MDD and TRD active in December 2022 were collated and analyzed. We compared coverage policies according to step therapy protocols, patient subgroup restrictions, and prescriber requirement criteria, evaluating patient access using the number of restrictions and proportion of plans including each criterion.</div></div><div><h3>Findings</h3><div>Plans more often imposed step therapy requirements for access to esketamine for TRD than for MDD, with line of treatment of ≤9 steps for MDD compared with 1 to 5 steps for TRD. Plans also varied with respect to the therapies they required patients to first try and experience treatment failure before granting access to esketamine for both indications. Clinical coverage requirements varied in thresholds and rating scales used to assess severity of depressive symptoms.</div></div><div><h3>Implications</h3><div>Plans vary in terms of line of therapy and clinical coverage requirements for access to esketamine. Variation in health plan coverage policies may result in inequitable access and added complexity for patients and clinicians navigating care, which may delay access to urgent treatment.</div></div><div><h3>ClinicalTrials.gov identifiers</h3><div>Not applicable.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 10","pages":"Pages 808-811"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747611","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}
Pub Date : 2024-10-01DOI: 10.1016/j.clinthera.2024.07.012
Giacomo Ponta , Martina Ranzenigo , Alessandra Marzi , Chiara Oltolini , Chiara Tassan Din , Caterina Uberti-Foppa , Vincenzo Spagnuolo , Patrizio Mazzone , Paolo Della Bella , Paolo Scarpellini , Antonella Castagna , Marco Ripa
Purpose
Cardiac implantable electronic device (CIED) infections are increasingly common. Gram-positive bacteria such as coagulase negative staphylococci and Staphylococcus aureus are the most commonly involved pathogens. The aim of this study was to describe the characteristics and outcome of patients with CIED infections who underwent device removal and were empirically treated with high dose (8–12 mg/kg daily) daptomycin (DAP) in combination with ceftriaxone (CRO).
Methods
Retrospective, single center study including patients admitted at IRCCS San Raffaele Hospital (Milan, Italy), from June 2011 to June 2021, who underwent device removal for CIED infection and were empirically treated with DAP/CRO.
Findings
Overall, 147 patients were included in this study. Median duration of therapy was 16 days (IQR 14–26). Empirical treatment with DAP/CRO was confirmed as definitive treatment in 140 patients (95.2%). In 7 (4.8%) patients DAP/CRO were discontinued according to the definite microbiological isolates: Corynebacterium spp. (4), Pseudomonas aeruginosa (2), Enterobacter cloacae (1). Ten patients (6.8%) underwent treatment simplification to narrow-spectrum antibiotics. One patient (0.6%) interrupted DAP-CRO due to pancytopenia.
6-month follow-up was available for 123/147 patients (83.7%): 9 patients recurred with a CIED infection (7.3%), and 9 died (7.3%).
Implications
In our 10-year experience, high-dose DAP in combination with CRO represented a good option for empirical therapy of CIED infections. DAP-CRO combination was safe and effective, showing no significant drug-related adverse events and low rates of 6-month recurrence and mortality.
{"title":"Combination of High-Dose Daptomycin and Ceftriaxone for Cardiac Implantable Electronic Device Infections: A 10-Year Experience","authors":"Giacomo Ponta , Martina Ranzenigo , Alessandra Marzi , Chiara Oltolini , Chiara Tassan Din , Caterina Uberti-Foppa , Vincenzo Spagnuolo , Patrizio Mazzone , Paolo Della Bella , Paolo Scarpellini , Antonella Castagna , Marco Ripa","doi":"10.1016/j.clinthera.2024.07.012","DOIUrl":"10.1016/j.clinthera.2024.07.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Cardiac implantable electronic device (CIED) infections are increasingly common. Gram-positive bacteria such as coagulase negative staphylococci and <em>Staphylococcus aureus</em> are the most commonly involved pathogens. The aim of this study was to describe the characteristics and outcome of patients with CIED infections who underwent device removal and were empirically treated with high dose (8–12 mg/kg daily) daptomycin (DAP) in combination with ceftriaxone (CRO).</div></div><div><h3>Methods</h3><div>Retrospective, single center study including patients admitted at IRCCS San Raffaele Hospital (Milan, Italy), from June 2011 to June 2021, who underwent device removal for CIED infection and were empirically treated with DAP/CRO.</div></div><div><h3>Findings</h3><div>Overall, 147 patients were included in this study. Median duration of therapy was 16 days (IQR 14–26). Empirical treatment with DAP/CRO was confirmed as definitive treatment in 140 patients (95.2%). In 7 (4.8%) patients DAP/CRO were discontinued according to the definite microbiological isolates: Corynebacterium spp. (4), Pseudomonas aeruginosa (2), Enterobacter cloacae (1). Ten patients (6.8%) underwent treatment simplification to narrow-spectrum antibiotics. One patient (0.6%) interrupted DAP-CRO due to pancytopenia.</div><div>6-month follow-up was available for 123/147 patients (83.7%): 9 patients recurred with a CIED infection (7.3%), and 9 died (7.3%).</div></div><div><h3>Implications</h3><div>In our 10-year experience, high-dose DAP in combination with CRO represented a good option for empirical therapy of CIED infections. DAP-CRO combination was safe and effective, showing no significant drug-related adverse events and low rates of 6-month recurrence and mortality.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 10","pages":"Pages 819-821"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055162","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}
Pub Date : 2024-10-01DOI: 10.1016/j.clinthera.2024.08.002
Rui Wu MS , Gaochao Zhu BS , Yinghui Ju MS , Yue Zhu MS , Menglin Wang MS , Yangyu Zhao MS , Sheng Liu BS
Purpose
Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes.
Methods
Simulated Y-site administration was conducted in vitro by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values.
Findings
GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours.
Implications
This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.
{"title":"Physical Compatibility of Reduced Glutathione for Injection With 44 Intravenous Drugs During Simulated Y-site Administration","authors":"Rui Wu MS , Gaochao Zhu BS , Yinghui Ju MS , Yue Zhu MS , Menglin Wang MS , Yangyu Zhao MS , Sheng Liu BS","doi":"10.1016/j.clinthera.2024.08.002","DOIUrl":"10.1016/j.clinthera.2024.08.002","url":null,"abstract":"<div><h3>Purpose</h3><div>Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes.</div></div><div><h3>Methods</h3><div>Simulated Y-site administration was conducted <em>in vitro</em> by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values.</div></div><div><h3>Findings</h3><div>GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours.</div></div><div><h3>Implications</h3><div>This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 10","pages":"Pages 785-790"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145351","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}
Pub Date : 2024-10-01DOI: 10.1016/j.clinthera.2024.08.004
Essy Mozaffari PharmD, MPH, MBA , Aastha Chandak PhD , Andrew Ustianowski MD, PhD , Christina G. Rivera PharmD, RPh , Neera Ahuja MD, FACP , Heng Jiang MPH , Mark Berry PhD , Jason F. Okulicz MD , Alpesh N. Amin MD
<div><h3>Purpose</h3><div>Clinicians consider polypharmacy, comorbidities, and other factors including the potential for drug-drug interactions (DDIs) when evaluating therapeutic options for specific clinical diagnoses. Contemporary treatment for coronavirus disease 2019 (COVID-19) includes direct-acting antivirals (DAAs). We sought to characterize patients’ characteristics, comorbidities, and medications received during their hospitalization for COVID-19 and quantify potential DDIs that clinicians consider in selecting appropriate DAAs.</div></div><div><h3>Methods</h3><div>Patients hospitalized with a primary diagnosis of COVID-19 between May 2020 and December 2022 from the PINC AI Healthcare Database were identified. Medications administered during the hospitalization with the potential to cause DDIs with nirmatrelvir/ritonavir, remdesivir, or molnupiravir (per the Emergency Use Authorization factsheet or package insert) were assessed. For DDIs with nirmatrelvir/ritonavir, medications are categorized as “Contraindicated,” “Avoid Concomitant Use,” or “Other DDIs” (includes recommendation for dose modification or clinical and laboratory monitoring). For remdesivir, coadministration with chloroquine phosphate and hydroxychloroquine sulfate was not recommended. For molnupiravir, no drugs are listed as having potential DDIs. In a subset of patients, a multivariable logistic regression model was used to examine the association between documented patient/hospital characteristics and the likelihood of being “Contraindicated” to receive nirmatrelvir/ritonavir.</div></div><div><h3>Findings</h3><div>Of the 788,238 patients hospitalized for COVID-19 in 920 hospitals, 53% were ≥ 65 years old, and 31% had Charlson Comorbidity Index (CCI) ≥ 3. During the study period, about half of the patients received medications categorized as “Contraindicated” (11%) and/or “Avoid Concomitant Use” (41%) with nirmatrelvir/ritonavir. The frequency of administered drugs was higher in those aged ≥ 65 years (68%), CCI ≥ 3 (78%), with high-risk underlying conditions (55%). About 1% of patients received medications that were not recommended to be coadmistered with remdesivir. Among a subset of patients hospitalized for COVID-19 in 2022, those who were older, had higher CCI, high-risk underlying conditions, severe hepatic impairment, Medicare insurance, and hospitalized in larger hospitals were significantly more likely to be categorized as “Contraindicated” when considering nirmatrelvir/ritonavir as a therapeutic option to manage COVID-19.</div></div><div><h3>Implications</h3><div>A significant proportion of patients hospitalized for COVID-19 receive medications for other conditions that have the potential to result in DDIs with DAAs; most predominantly with nirmatrelvir/ritonavir, a strong CYP3A enzyme inhibitor, fewer with remdesivir, and none with molnupiravir. Higher age and comorbidity burden were significantly associated with a higher likelihood of receiving medications tha
{"title":"Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients","authors":"Essy Mozaffari PharmD, MPH, MBA , Aastha Chandak PhD , Andrew Ustianowski MD, PhD , Christina G. Rivera PharmD, RPh , Neera Ahuja MD, FACP , Heng Jiang MPH , Mark Berry PhD , Jason F. Okulicz MD , Alpesh N. Amin MD","doi":"10.1016/j.clinthera.2024.08.004","DOIUrl":"10.1016/j.clinthera.2024.08.004","url":null,"abstract":"<div><h3>Purpose</h3><div>Clinicians consider polypharmacy, comorbidities, and other factors including the potential for drug-drug interactions (DDIs) when evaluating therapeutic options for specific clinical diagnoses. Contemporary treatment for coronavirus disease 2019 (COVID-19) includes direct-acting antivirals (DAAs). We sought to characterize patients’ characteristics, comorbidities, and medications received during their hospitalization for COVID-19 and quantify potential DDIs that clinicians consider in selecting appropriate DAAs.</div></div><div><h3>Methods</h3><div>Patients hospitalized with a primary diagnosis of COVID-19 between May 2020 and December 2022 from the PINC AI Healthcare Database were identified. Medications administered during the hospitalization with the potential to cause DDIs with nirmatrelvir/ritonavir, remdesivir, or molnupiravir (per the Emergency Use Authorization factsheet or package insert) were assessed. For DDIs with nirmatrelvir/ritonavir, medications are categorized as “Contraindicated,” “Avoid Concomitant Use,” or “Other DDIs” (includes recommendation for dose modification or clinical and laboratory monitoring). For remdesivir, coadministration with chloroquine phosphate and hydroxychloroquine sulfate was not recommended. For molnupiravir, no drugs are listed as having potential DDIs. In a subset of patients, a multivariable logistic regression model was used to examine the association between documented patient/hospital characteristics and the likelihood of being “Contraindicated” to receive nirmatrelvir/ritonavir.</div></div><div><h3>Findings</h3><div>Of the 788,238 patients hospitalized for COVID-19 in 920 hospitals, 53% were ≥ 65 years old, and 31% had Charlson Comorbidity Index (CCI) ≥ 3. During the study period, about half of the patients received medications categorized as “Contraindicated” (11%) and/or “Avoid Concomitant Use” (41%) with nirmatrelvir/ritonavir. The frequency of administered drugs was higher in those aged ≥ 65 years (68%), CCI ≥ 3 (78%), with high-risk underlying conditions (55%). About 1% of patients received medications that were not recommended to be coadmistered with remdesivir. Among a subset of patients hospitalized for COVID-19 in 2022, those who were older, had higher CCI, high-risk underlying conditions, severe hepatic impairment, Medicare insurance, and hospitalized in larger hospitals were significantly more likely to be categorized as “Contraindicated” when considering nirmatrelvir/ritonavir as a therapeutic option to manage COVID-19.</div></div><div><h3>Implications</h3><div>A significant proportion of patients hospitalized for COVID-19 receive medications for other conditions that have the potential to result in DDIs with DAAs; most predominantly with nirmatrelvir/ritonavir, a strong CYP3A enzyme inhibitor, fewer with remdesivir, and none with molnupiravir. Higher age and comorbidity burden were significantly associated with a higher likelihood of receiving medications tha","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 10","pages":"Pages 778-784"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145352","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}
Pub Date : 2024-10-01DOI: 10.1016/j.clinthera.2024.09.015
Paul Beninger MD, MBA
{"title":"The Hard Work of Developing New Therapies for Pediatric Populations","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2024.09.015","DOIUrl":"10.1016/j.clinthera.2024.09.015","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 10","pages":"Pages 727-729"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364681","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}
Pub Date : 2024-10-01DOI: 10.1016/j.clinthera.2024.08.001
Randolph E. Regal PharmD
Purpose
When one considers the significant role of the liver in medication absorption and metabolism, clinicians must appreciate the important ramifications for medication dosing and monitoring in patients with cirrhosis. For many medications, dose adjustments may be necessary to minimize toxicities or avoid adverse effects from drug accumulation. Clinicians could be well served if they can understand in some detail how pharmacokinetic properties are altered in cirrhosis.
Methods
A PubMed search of the English medical literature starting with 1980 using keywords cirrhosis, pain management, and analgesics was performed, and additional papers were found using references from the first round of papers.
Findings
Patients with cirrhosis often have significant reductions in first-pass metabolism, altered volumes of distribution, and marked reductions in both renal and hepatic elimination of drugs. These factors may contribute to much higher levels of drug exposure compared to the general population. In terms of drug dosing, FDA labeling is often ambiguous and even incongruous with observed pharmacokinetic changes.
Implications
This article may provide guidance for clinicians to optimize pain management in people living with cirrhosis.
Key Message
Current FDA labeling for dosing analgesic drugs in patients with cirrhosis is either vague or not consistent with findings from newer pharmacokinetic research. With this review, we hope to provide insight and guidance to clinicians on how to dose-adjust medications commonly utilized in pain management in these patients.
{"title":"Treatment of Pain in Cirrhosis: Advice to Caregivers of Those with Rock Livers","authors":"Randolph E. Regal PharmD","doi":"10.1016/j.clinthera.2024.08.001","DOIUrl":"10.1016/j.clinthera.2024.08.001","url":null,"abstract":"<div><h3>Purpose</h3><div>When one considers the significant role of the liver in medication absorption and metabolism, clinicians must appreciate the important ramifications for medication dosing and monitoring in patients with cirrhosis. For many medications, dose adjustments may be necessary to minimize toxicities or avoid adverse effects from drug accumulation. Clinicians could be well served if they can understand in some detail how pharmacokinetic properties are altered in cirrhosis.</div></div><div><h3>Methods</h3><div>A PubMed search of the English medical literature starting with 1980 using keywords cirrhosis, pain management, and analgesics was performed, and additional papers were found using references from the first round of papers.</div></div><div><h3>Findings</h3><div>Patients with cirrhosis often have significant reductions in first-pass metabolism, altered volumes of distribution, and marked reductions in both renal and hepatic elimination of drugs. These factors may contribute to much higher levels of drug exposure compared to the general population. In terms of drug dosing, FDA labeling is often ambiguous and even incongruous with observed pharmacokinetic changes.</div></div><div><h3>Implications</h3><div>This article may provide guidance for clinicians to optimize pain management in people living with cirrhosis.</div></div><div><h3>Key Message</h3><div>Current FDA labeling for dosing analgesic drugs in patients with cirrhosis is either vague or not consistent with findings from newer pharmacokinetic research. With this review, we hope to provide insight and guidance to clinicians on how to dose-adjust medications commonly utilized in pain management in these patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 10","pages":"Pages 812-818"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145354","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}
Pub Date : 2024-09-30DOI: 10.1016/j.clinthera.2024.09.014
Xiufang Wang, Gangying Cheng, Xiaofang Liang, Junhui Yang, Aiping Deng, Dan Chen, Chao Liu, Ying Gao, Juyi Li
Purpose: To determine the relationship between HLA-B gene mutations and levofloxacin-induced toxic epidermal necrolysis (TEN).
Methods: A 71-year-old Chinese woman developed TEN after oral administration of solifenacin (5 mg) and levofloxacin (0.5 g) for cystitis. HLA-B*5801 and HLA-B*1502 alleles were detected using real-time PCR.
Findings: After supportive therapy (antiallergic treatments, plasma exchange, etc) and withdrawal of the culprit medication levofloxacin, the patient was discharged with re-epithelialization of the exfoliated skin. The patient was HLA-B*1502 allele positive and HLA-B*5801 allele negative.
Implications: This is the first report of levofloxacin-induced TEN suspected to be caused by mutations in the HLA-B*1502 allele.
{"title":"Toxic Epidermal Necrolysis Observed in a Patient With the HLA-B*1502 Treated With Levofloxacin.","authors":"Xiufang Wang, Gangying Cheng, Xiaofang Liang, Junhui Yang, Aiping Deng, Dan Chen, Chao Liu, Ying Gao, Juyi Li","doi":"10.1016/j.clinthera.2024.09.014","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.014","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the relationship between HLA-B gene mutations and levofloxacin-induced toxic epidermal necrolysis (TEN).</p><p><strong>Methods: </strong>A 71-year-old Chinese woman developed TEN after oral administration of solifenacin (5 mg) and levofloxacin (0.5 g) for cystitis. HLA-B*5801 and HLA-B*1502 alleles were detected using real-time PCR.</p><p><strong>Findings: </strong>After supportive therapy (antiallergic treatments, plasma exchange, etc) and withdrawal of the culprit medication levofloxacin, the patient was discharged with re-epithelialization of the exfoliated skin. The patient was HLA-B*1502 allele positive and HLA-B*5801 allele negative.</p><p><strong>Implications: </strong>This is the first report of levofloxacin-induced TEN suspected to be caused by mutations in the HLA-B*1502 allele.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364682","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}
Pub Date : 2024-09-30DOI: 10.1016/j.clinthera.2024.09.016
Mohamed Ismail Hassan, Nabila Ibrahim Laz, Yasmin M Madney, Mohamed E A Abdelrahim, Hadeer S Harb
Purpose: Suboptimal peak inspiratory flow rate (PIFR) is highly prevalent in patients with chronic obstructive pulmonary disease (COPD) owing to the mismatch of their PIFR with the corresponding inhaler-device resistance. This study aimed to investigate the impact of a preliminary dose of pressurized metered dose inhalers (pMDIs) on patients with COPD with suboptimal PIFR using Diskus dry powder inhalers (DPIs).
Methods: A prospective, randomized, case-control study included 24 patients with COPD. PIFR was measured using the In-Check Dial G16 with low-to-medium resistance. Spirodoc was used to measure baseline spirometric data and compare it before and 30 minutes after the administration of Diskus DPI. On a different day, the study dose was given to each suboptimal patient by the same aerosol generator with preceded 2 puffs of salbutamol pMDI and re-evaluated for spirometric parameters 30 minutes after the study dose.
Findings: There was a significant difference between the optimal and suboptimal groups in peak expiratory flow (2.38 ± 1.20 vs 1.49 ± 1.06 L/s, P = 0.050). PIFR showed a statistically significant difference between the optimal and suboptimal groups (71.66 ± 6.15 vs 41.25 ± 9.79 L/min, P < 0.0001). There was a significant difference in forced vital capacity (ΔFVC) between optimal and suboptimal groups without a preliminary dose (0.42 ± 0.21 vs 0.16 ± 0.11 L, P = 0.002), forced expiratory volume in 6 seconds (ΔFEV6) (0.53 ± 0.49 vs 0.17 ± 0.11 L, P = 0.022), forced expiratory volume in 3 seconds (ΔFEV3) (0.41 ± 0.38 vs 0.1 ± 0.16 L, P = 0.013), forced expiratory volume in 1 second (ΔFEV1)/FVC (-2.38 ± 8.41 vs 2.96% ± 2.95%, P = 0.033), and ΔFEV1/FEV6 (-4.32 ± 11.23 vs 2.91% ± 4.35%, P = 0.015). There was a significant difference in ΔFVC between optimal and suboptimal groups with a preliminary dose (0.42 ± 0.21 vs 0.23 ± 0.18 L, P = 0.046), ΔFEV1/FVC (-2.38 ± 8.41 vs 5.67% ± 6.53%, P = 0.009), ΔFEV1/FEV6 (-4.32 ± 11.23 vs 5.16% ± 4.99%, P = 0.008), and forced expiratory time (ΔFET) (0.28 ± 0.45 vs -0.31 ± 0.70 seconds, P = 0.022). The only parameter that showed a significant difference between suboptimal groups without and with a preliminary dose is Δ peak expiratory flow (0.24 ± 0.59 vs 0.65 ± 0.68 L/s, P = 0.004).
Implications: Administering a preliminary dose of pMDI can minimally enhance the effectiveness of DPIs in patients with COPD with suboptimal PIFR and health outcomes.
{"title":"Impact of Preliminary Bronchodilator Dose in Chronic Obstructive Pulmonary Disease Patients With Suboptimal Peak Inspiratory Flow.","authors":"Mohamed Ismail Hassan, Nabila Ibrahim Laz, Yasmin M Madney, Mohamed E A Abdelrahim, Hadeer S Harb","doi":"10.1016/j.clinthera.2024.09.016","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.016","url":null,"abstract":"<p><strong>Purpose: </strong>Suboptimal peak inspiratory flow rate (PIFR) is highly prevalent in patients with chronic obstructive pulmonary disease (COPD) owing to the mismatch of their PIFR with the corresponding inhaler-device resistance. This study aimed to investigate the impact of a preliminary dose of pressurized metered dose inhalers (pMDIs) on patients with COPD with suboptimal PIFR using Diskus dry powder inhalers (DPIs).</p><p><strong>Methods: </strong>A prospective, randomized, case-control study included 24 patients with COPD. PIFR was measured using the In-Check Dial G16 with low-to-medium resistance. Spirodoc was used to measure baseline spirometric data and compare it before and 30 minutes after the administration of Diskus DPI. On a different day, the study dose was given to each suboptimal patient by the same aerosol generator with preceded 2 puffs of salbutamol pMDI and re-evaluated for spirometric parameters 30 minutes after the study dose.</p><p><strong>Findings: </strong>There was a significant difference between the optimal and suboptimal groups in peak expiratory flow (2.38 ± 1.20 vs 1.49 ± 1.06 L/s, P = 0.050). PIFR showed a statistically significant difference between the optimal and suboptimal groups (71.66 ± 6.15 vs 41.25 ± 9.79 L/min, P < 0.0001). There was a significant difference in forced vital capacity (ΔFVC) between optimal and suboptimal groups without a preliminary dose (0.42 ± 0.21 vs 0.16 ± 0.11 L, P = 0.002), forced expiratory volume in 6 seconds (ΔFEV<sub>6</sub>) (0.53 ± 0.49 vs 0.17 ± 0.11 L, P = 0.022), forced expiratory volume in 3 seconds (ΔFEV<sub>3</sub>) (0.41 ± 0.38 vs 0.1 ± 0.16 L, P = 0.013), forced expiratory volume in 1 second (ΔFEV<sub>1</sub>)/FVC (-2.38 ± 8.41 vs 2.96% ± 2.95%, P = 0.033), and ΔFEV<sub>1</sub>/FEV<sub>6</sub> (-4.32 ± 11.23 vs 2.91% ± 4.35%, P = 0.015). There was a significant difference in ΔFVC between optimal and suboptimal groups with a preliminary dose (0.42 ± 0.21 vs 0.23 ± 0.18 L, P = 0.046), ΔFEV<sub>1</sub>/FVC (-2.38 ± 8.41 vs 5.67% ± 6.53%, P = 0.009), ΔFEV<sub>1</sub>/FEV<sub>6</sub> (-4.32 ± 11.23 vs 5.16% ± 4.99%, P = 0.008), and forced expiratory time (ΔFET) (0.28 ± 0.45 vs -0.31 ± 0.70 seconds, P = 0.022). The only parameter that showed a significant difference between suboptimal groups without and with a preliminary dose is Δ peak expiratory flow (0.24 ± 0.59 vs 0.65 ± 0.68 L/s, P = 0.004).</p><p><strong>Implications: </strong>Administering a preliminary dose of pMDI can minimally enhance the effectiveness of DPIs in patients with COPD with suboptimal PIFR and health outcomes.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364679","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}
Pub Date : 2024-09-28DOI: 10.1016/j.clinthera.2024.09.002
Adili Tuersun, Munire Mohetaer, Munire Tuerhong, Guanxin Hou, Gang Cheng
{"title":"Response to Letter Regarding Article, \"Pancreatitis and Pancreatic Cancer Risk Among Patients with Type 2 Diabetes Receiving Dipeptidyl Peptidase 4 Inhibitors: An Updated Meta-Analysis of Randomized Controlled Trials\".","authors":"Adili Tuersun, Munire Mohetaer, Munire Tuerhong, Guanxin Hou, Gang Cheng","doi":"10.1016/j.clinthera.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.002","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343083","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}
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