The direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, have favorable pharmacokinetic and pharmacodynamic properties and equal or superior efficacy and an improved safety profile compared with warfarin. Noted shortcomings with DOACs are shorter half‐lives requiring stricter adherence, lack of standardized laboratory monitoring, lack of anticoagulation reversal agents, and loss of routine coagulation monitoring leading to fewer patient–clinician interactions. This review addresses many of these limitations including monitoring of DOACs for efficacy and toxicity, an assessment of selected qualitative and quantitative tests, and development of monitoring strategies for special populations. Coagulation monitoring is generally recommended only in overdose situations, but once standardized assays are readily available, they could be helpful to ensure efficacy, assess bleeding, and aid in drug selection in a number of other patient scenarios. Coagulation tests that may provide qualitative assessment include activated partial thromboplastin time, prothrombin time, and thrombin time. Methods with potential utility for quantitative assessment of DOACs include plasma drug concentrations, ecarin clotting time, dilute thrombin time, and anti–factor Xa concentrations. Noncoagulation laboratory monitoring should include serum creatinine, liver function tests, and complete blood counts. Clinical monitoring of the DOAC‐treated patient should include routine assessment of adherence, bleeding risks, and drug interactions. Frequency of monitoring should be 1–3 months after initiation and then at least every 6 months, with more frequent follow‐up (i.e., 3 months) based on patient specific characteristics such as age, renal impairment, hepatic impairment, and concomitant drug therapy. The authors provide a practical tool to assist in DOAC monitoring and recommend that pharmacists collaborate with physicians in selecting appropriate patients and tailoring patient‐specific monitoring plans.
{"title":"Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know","authors":"S. Conway, Andrew Y. Hwang, C. Ponte, J. Gums","doi":"10.1002/phar.1884","DOIUrl":"https://doi.org/10.1002/phar.1884","url":null,"abstract":"The direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, have favorable pharmacokinetic and pharmacodynamic properties and equal or superior efficacy and an improved safety profile compared with warfarin. Noted shortcomings with DOACs are shorter half‐lives requiring stricter adherence, lack of standardized laboratory monitoring, lack of anticoagulation reversal agents, and loss of routine coagulation monitoring leading to fewer patient–clinician interactions. This review addresses many of these limitations including monitoring of DOACs for efficacy and toxicity, an assessment of selected qualitative and quantitative tests, and development of monitoring strategies for special populations. Coagulation monitoring is generally recommended only in overdose situations, but once standardized assays are readily available, they could be helpful to ensure efficacy, assess bleeding, and aid in drug selection in a number of other patient scenarios. Coagulation tests that may provide qualitative assessment include activated partial thromboplastin time, prothrombin time, and thrombin time. Methods with potential utility for quantitative assessment of DOACs include plasma drug concentrations, ecarin clotting time, dilute thrombin time, and anti–factor Xa concentrations. Noncoagulation laboratory monitoring should include serum creatinine, liver function tests, and complete blood counts. Clinical monitoring of the DOAC‐treated patient should include routine assessment of adherence, bleeding risks, and drug interactions. Frequency of monitoring should be 1–3 months after initiation and then at least every 6 months, with more frequent follow‐up (i.e., 3 months) based on patient specific characteristics such as age, renal impairment, hepatic impairment, and concomitant drug therapy. The authors provide a practical tool to assist in DOAC monitoring and recommend that pharmacists collaborate with physicians in selecting appropriate patients and tailoring patient‐specific monitoring plans.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88784053","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}
Nicole E. Cieri, Kristen Kusmierski, C. Lackie, August Van Opdorp, Amany K. Hassan
To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate postoperative period following major orthopedic surgery.
{"title":"Retrospective Evaluation of Postoperative Adverse Drug Events in Patients Receiving Rivaroxaban After Major Orthopedic Surgery Compared with Standard Therapy in a Community Hospital","authors":"Nicole E. Cieri, Kristen Kusmierski, C. Lackie, August Van Opdorp, Amany K. Hassan","doi":"10.1002/phar.1888","DOIUrl":"https://doi.org/10.1002/phar.1888","url":null,"abstract":"To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate postoperative period following major orthopedic surgery.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84576765","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}
C. Frei, Sylvie B. Rehani, Grace C. Lee, N. Boyd, Erene M. Attia, A. Pechal, Rachel S. Britt, E. Mortensen
To assess the impact of empiric Pseudomonas pharmacotherapy on 30‐day mortality in hospitalized patients with community‐onset pneumonia stratified according to their risk (low, medium, or high) of drug‐resistant pathogens.
{"title":"Application of a Risk Score to Identify Older Adults with Community‐Onset Pneumonia Most Likely to Benefit From Empiric Pseudomonas Therapy","authors":"C. Frei, Sylvie B. Rehani, Grace C. Lee, N. Boyd, Erene M. Attia, A. Pechal, Rachel S. Britt, E. Mortensen","doi":"10.1002/phar.1891","DOIUrl":"https://doi.org/10.1002/phar.1891","url":null,"abstract":"To assess the impact of empiric Pseudomonas pharmacotherapy on 30‐day mortality in hospitalized patients with community‐onset pneumonia stratified according to their risk (low, medium, or high) of drug‐resistant pathogens.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86276492","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}
To evaluate the odds of achieving viral suppression in human immunodeficiency virus (HIV) patients using antiretroviral therapy as a single‐tablet regimen (STR) or multiple‐tablet regimen (MTR).
{"title":"Odds of Viral Suppression by Single‐Tablet Regimens, Multiple‐Tablet Regimens, and Adherence Level in HIV/AIDS Patients Receiving Antiretroviral Therapy","authors":"S. Sutton, J. Magagnoli, J. Hardin","doi":"10.1002/phar.1889","DOIUrl":"https://doi.org/10.1002/phar.1889","url":null,"abstract":"To evaluate the odds of achieving viral suppression in human immunodeficiency virus (HIV) patients using antiretroviral therapy as a single‐tablet regimen (STR) or multiple‐tablet regimen (MTR).","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72995577","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}
Tyler K Liebenstein, Lucas T. Schulz, Chris Viesselmann, E. Bingen, Jackson S. Musuuza, N. Safdar, W. Rose
Because patients with abdominal solid organ transplants (SOTs) are at increased risk of polymicrobial intraabdominal infections (IAIs) following transplantation, the objective of this study was to compare the effectiveness and adverse event profile of tigecycline with those of other broad‐spectrum therapies for polymicrobial IAIs in this population.
{"title":"Effectiveness and Safety of Tigecycline Compared with Other Broad‐Spectrum Antimicrobials in Abdominal Solid Organ Transplant Recipients with Polymicrobial Intraabdominal Infections","authors":"Tyler K Liebenstein, Lucas T. Schulz, Chris Viesselmann, E. Bingen, Jackson S. Musuuza, N. Safdar, W. Rose","doi":"10.1002/phar.1883","DOIUrl":"https://doi.org/10.1002/phar.1883","url":null,"abstract":"Because patients with abdominal solid organ transplants (SOTs) are at increased risk of polymicrobial intraabdominal infections (IAIs) following transplantation, the objective of this study was to compare the effectiveness and adverse event profile of tigecycline with those of other broad‐spectrum therapies for polymicrobial IAIs in this population.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79197453","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}
D. Lasoff, Cynthia Koh, B. Corbett, Alicia B. Minns, F. Cantrell
With the increasing amount of information available on the Internet describing techniques for using loperamide either for self‐treatment of opioid withdrawal syndromes or for recreational use (so‐called legal highs), the objective was to describe a statewide poison control system's experience with loperamide misuse and abuse, with specific interest in cases of cardiotoxicity, and to determine if reported loperamide misuse or abuse cases have recently increased.
{"title":"Loperamide Trends in Abuse and Misuse Over 13 Years: 2002–2015","authors":"D. Lasoff, Cynthia Koh, B. Corbett, Alicia B. Minns, F. Cantrell","doi":"10.1002/phar.1885","DOIUrl":"https://doi.org/10.1002/phar.1885","url":null,"abstract":"With the increasing amount of information available on the Internet describing techniques for using loperamide either for self‐treatment of opioid withdrawal syndromes or for recreational use (so‐called legal highs), the objective was to describe a statewide poison control system's experience with loperamide misuse and abuse, with specific interest in cases of cardiotoxicity, and to determine if reported loperamide misuse or abuse cases have recently increased.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81493624","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}
K. Covert, C. Mardis, J. Fleming, N. Pilch, H. Meadows, B. A. Mardis, Prince Mohan, M. Posadas-Salas, T. Srinivas, D. Taber
Drug‐related problems (DRPs) are associated with increased rates of infection, rejection, and graft loss in kidney transplant recipients. This study aimed to develop a model to predict which patients are at highest risk of DRPs to streamline pharmacists’ workflow in a chronic kidney transplant clinic.
{"title":"Development of a Predictive Model for Drug‐Related Problems in Kidney Transplant Recipients","authors":"K. Covert, C. Mardis, J. Fleming, N. Pilch, H. Meadows, B. A. Mardis, Prince Mohan, M. Posadas-Salas, T. Srinivas, D. Taber","doi":"10.1002/phar.1886","DOIUrl":"https://doi.org/10.1002/phar.1886","url":null,"abstract":"Drug‐related problems (DRPs) are associated with increased rates of infection, rejection, and graft loss in kidney transplant recipients. This study aimed to develop a model to predict which patients are at highest risk of DRPs to streamline pharmacists’ workflow in a chronic kidney transplant clinic.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87026000","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}
Abdalla A. Ammar, S. Lam, A. Duggal, E. Neuner, S. Bass, J. Guzman, Xiao-Feng Wang, Xiaozhen Han, S. Bauer
To describe compliance with antibiotic recommendations based on a previously published procalcitonin (PCT)‐guided algorithm in clinical practice, to compare PCT algorithm compliance rates between PCT assays ordered in the antibiotic initiation setting (PCT concentration measured less than 24 hours after antibiotic initiation or before antibiotic initiation) with those in the antibiotic continuation setting (PCT concentration measured 24 hours or more after antibiotic initiation), and to evaluate patient‐ and PCT‐related factors independently associated with algorithm compliance in patients in the medical intensive care unit (MICU).
{"title":"Compliance with Procalcitonin Algorithm Antibiotic Recommendations for Patients in Medical Intensive Care Unit","authors":"Abdalla A. Ammar, S. Lam, A. Duggal, E. Neuner, S. Bass, J. Guzman, Xiao-Feng Wang, Xiaozhen Han, S. Bauer","doi":"10.1002/phar.1887","DOIUrl":"https://doi.org/10.1002/phar.1887","url":null,"abstract":"To describe compliance with antibiotic recommendations based on a previously published procalcitonin (PCT)‐guided algorithm in clinical practice, to compare PCT algorithm compliance rates between PCT assays ordered in the antibiotic initiation setting (PCT concentration measured less than 24 hours after antibiotic initiation or before antibiotic initiation) with those in the antibiotic continuation setting (PCT concentration measured 24 hours or more after antibiotic initiation), and to evaluate patient‐ and PCT‐related factors independently associated with algorithm compliance in patients in the medical intensive care unit (MICU).","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75470597","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}
Extracorporeal membrane oxygenation (ECMO) is a life‐support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965–July 2016), EMBASE (1965–July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward.
{"title":"Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation","authors":"Michael Ha, A. Sieg","doi":"10.1002/phar.1882","DOIUrl":"https://doi.org/10.1002/phar.1882","url":null,"abstract":"Extracorporeal membrane oxygenation (ECMO) is a life‐support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965–July 2016), EMBASE (1965–July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89033967","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}
Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some individuals. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight literature focused on pharmacotherapy for individuals with DS. We discuss reports of altered drug disposition or response in patients with DS and explore social factors that may impact medication adherence in the DS setting. Enhanced monitoring during drug therapy in individuals with DS is justified based on reports of altered drug disposition, drug response, and other characteristics present in this population.
{"title":"Pharmacotherapeutic Considerations for Individuals with Down Syndrome","authors":"E. Hefti, J. Blanco","doi":"10.1002/phar.1880","DOIUrl":"https://doi.org/10.1002/phar.1880","url":null,"abstract":"Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some individuals. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight literature focused on pharmacotherapy for individuals with DS. We discuss reports of altered drug disposition or response in patients with DS and explore social factors that may impact medication adherence in the DS setting. Enhanced monitoring during drug therapy in individuals with DS is justified based on reports of altered drug disposition, drug response, and other characteristics present in this population.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79138935","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}
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