JournalTOCs

Annals of Pharmacotherapy
Journal Prestige (SJR): 1.096

Citation Impact (citeScore): 2
Number of Followers: 51

Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1060-0280 - ISSN (Online) 1542-6270
Published by Sage Publications

[1176 journals]

The Incidence of Torsades de Pointes With Perioperative Triple Antiemetic
Administration
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  Authors: Gregory A. Nuttall, Alyssa M. Reed, Khue D. Pham (Louis), Lance J. Oyen, Samuel P. Marsland, Michael J. Ackerman
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The safety of triple antiemetic therapy consisting of ondansetron, haloperidol, and a steroid, to surgical patients is unknown.Objective:To determine the incidence of torsade de pointes (TdP) or death following perioperative administration of triple antiemetic therapy.Methods:A retrospective cohort study identified 19,874 patients who received 22,202 doses of triple antiemetics during the 2.5-year time frame from March 4, 2020 to September 7, 2022 for surgical nausea prophylaxis or treatment of nausea. These patients above were cross-matched with an electrocardiogram and adverse outcome database; this identified 226 patients with documentation of a QTc> 450 ms, all ventricular tachycardias including TdP within 48 hours of receiving triple antiemetic therapy, or death within 7 days of receiving ondansetron.Results:There were 3 patients who had documented VT (n = 3), but there were no documented incidents of TdP (n = 0). There were 9 codes called on patients within 48 hours of medication administration, and none of them were due to ventricular arrythmias (n = 0). A total of 11 patients died within 7 days of triple antiemetic therapy. Ten of the 11 deaths were determined to not be from the triple antiemetic. One patient died at home within 24 hours of the procedure of an unknown cause (n = 1).Conclusions and Relevance:No episodes of TdP were identified in patients receiving triple antiemetic therapy perioperatively, though the cause of death in 1 patient could not be determined. This suggest that low-dose triple antiemetic therapy is low risk for the development of TdP.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-12-06T08:15:39Z
  DOI: 10.1177/10600280231215786
Efficacy of Fluvoxamine in Outpatients With COVID-19: Understanding
Conflicting Conclusions From 2 Recent Meta-Analyses of the Same Clinical
Trials
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  Authors: Marina Sánchez-Rico, Katayoun Rezaei, Eric J. Lenze, Frédéric Limosin, Nicolas Hoertel
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-28T12:50:45Z
  DOI: 10.1177/10600280231211304
Assessing the Clinical, Economic, and Health Resource Utilization Impacts
of Prefilled Syringes Versus Conventional Medication Administration
Methods: Results From a Systematic Literature Review
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  Authors: Dan Benhamou, Mia Weiss, Matthias Borms, Julia Lucaci, Haymen Girgis, Cecile Frolet, Wesley T. Baisley, Gio Shoushi, Kristen A. Cribbs, Manuel Wenk
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:The objective of this systematic review was to assess the clinical, economic, and health resource utilization outcomes associated with the use of prefilled syringes in medication administration compared with traditional preparation methods.Data Sources:We conducted a systematic literature review to evaluate outcomes such as medication errors, wastage, time savings, and contamination in prefilled syringes. Our search encompassed multiple databases, including PubMed and Embase, for studies published between January 1, 2017, and November 1, 2022.Study selection and data extraction:Peer-reviewed publications meeting our inclusion criteria underwent rigorous screening, including title, abstract, and full-text article assessments, performed by two reviewers.Data synthesis:Among reviewed articles, 24 met our eligibility criteria. Selected studies were primarily observational (46%) and conducted in Europe (46%). Our findings indicated that prefilled syringes consistently reduced medication errors (by 10%-73%), adverse events (from 1.1 to 0.275 per 100 administrations), wastage (by up to 80% of drug), and preparation time (from 4.0 to 338.0 seconds) (ranges varied by drug type, setting, and dosage). However, there was limited data on contamination. Economically, prefilled syringes reduced waste and error rates, which may translate into overall savings.Relevance to patient care and clinical practice:This review highlights the value of prefilled syringes, which can streamline medication delivery, save nursing time, and reduce preventable medication errors. Moreover, prefilled syringes have the potential to minimize medication wastage, optimizing resource utilization and efficiency in health care settings.Conclusion and relevance:Our findings provide new insights into clinical and economic benefits of prefilled syringe adoption. These benefits include improved medication delivery and safety, which can lead to time and cost reductions for health care departments, hospitals, and health systems. However, further real-world research on clinical and economic outcomes, especially in contamination, is needed to better understand the benefits of prefilled syringes.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-28T12:48:25Z
  DOI: 10.1177/10600280231212890
Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in
Heart Failure
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  Authors: Allissa Long, Marissa Salvo
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To describe the pharmacology, clinical efficacy, and safety evidence of sotagliflozin, the first approved dual inhibitor of sodium-glucose cotransporter (SGLT) 1 and SGLT2, in heart failure (HF) management.Data sources:A literature search of studies published between January 2012 and September 2023 were identified using PubMed, MEDLINE, and clinicaltrials.gov with search terms of “sotagliflozin,” “Inpefa,” or “LX4211.”Study selection and data extraction:All available studies in English were considered. Studies were included if they investigated drug pharmacology, efficacy, or safety information.Data synthesis:Two phase 3 trials of sotagliflozin, SOLOIST-WHF and SCORED, evaluated sotagliflozin compared with placebo in patients with type 2 diabetes mellitus (T2DM). SOLOIST-WHF reported a statistically decreased rate of cardiovascular and HF events with sotagliflozin (hazard ratio [HR] = 0.67, 95% CI = 0.52-0.85), while SCORED found a statistically significant decrease in incidence of cardiovascular events in patients with T2DM, chronic kidney disease (CKD), and risk factors for cardiovascular disease in patients in the sotagliflozin group (HR = 0.74, 95% CI = 0.63-0.88).Relevance to patient care and clinical practice in comparison to existing agents:While approval of sotagliflozin expands treatment options for patients with HF, the SGLT2 inhibitors, dapagliflozin and empagliflozin, have more data supporting their use in HF, additional risk reduction benefits in patients with CKD, and approval for use in T2DM. Landmark trials of sotagliflozin required a previous diagnosis of T2DM, despite the broader approved indication. Where sotagliflozin will be adopted into the treatment of HF is unclear due to the evidence and benefits of already established SGLT2 inhibitors and the need for comparison with SGLT2 inhibitors.Conclusion:Given the limitations of currently available evidence, including difficulty in fully interpreting the trial results due to changes in primary endpoints, not adjudicating the events, and not reaching the original power calculations, more investigation is warranted to determine the benefit of sotagliflozin compared with SGLT2 inhibitors.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-28T12:46:26Z
  DOI: 10.1177/10600280231211179
Analysis of Atypical Antipsychotics-Induced Adverse Events Related to
Diabetes Mellitus in Patients With Dementia Using the Japanese Adverse
Drug Event Report Database
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  Authors: Fuga Habuchi, Natsuko Ishida, Ryo Matsushita, Junko Ishizaki, Yukio Suga
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Patients with dementia are prescribed low-dose atypical antipsychotics (AAPs) to treat psycho-behavioral symptoms. Although AAPs are known to cause diabetes mellitus–related adverse events (DMAEs), information regarding AAPs-induced DMAEs experienced by patients with dementia is lacking.Objective:To use the Japan Adverse Drug Event Report (JADER) database to assess the onset tendencies and patterns of DMAEs attributable to AAPs prescribed to patients with dementia.Methods:We performed an analysis using dementia cases from the JADER database that were registered from April 2004 to December 2022. Data in the JADER database are completely anonymized; thus, we did not require institutional review board approval for using the JADER database in our study. The reporting odds ratio and proportional reporting ratio (PRR) were used to assess the onset tendencies of DMAEs with AAPs. In addition, Weibull shape parameters were used to assess the patterns of DMAEs that occur with the use of AAPs.Results:We identified AAPs associated with DMAEs. In particular, low doses of quetiapine showed the potential to induce DMAEs. An analysis of the onset of DMAEs showed the early failure patterns for AAPs (median onset = 38 days).Conclusion and Relevance:The AAPs may cause DMAEs in patients with dementia. Low doses of quetiapine may induce DMAEs. Health care workers should focus on the development of DMAEs during the early administration period of AAPs. These results may assist with the safe management of patients with dementia who use AAPs.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-24T10:30:29Z
  DOI: 10.1177/10600280231213507
A Complement to Traditional Treatments for Antibody-Mediated Rejection'
Use of Eculizumab in Lung Transplantation: A Review and Early Center
Experience
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  Authors: Hanna L. Kleiboeker, Alyson Prom, Krista Paplaczyk, Catherine N. Myers
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review the efficacy and safety of eculizumab for prevention and treatment of antibody-mediated rejection (AMR) in lung transplant recipients (LTRs).Data Sources:A literature search of PubMed and the Cochrane Controlled Trials Register (2007 to mid-October 2023) was performed using the following search terms: eculizumab, complement inhibitor, solid organ transplant, lung transplant, and AMR.Study Selection and Data Extraction:All relevant English-language studies were reviewed and considered.Data Synthesis:Eculizumab, a monoclonal antibody that binds complement protein C5 to inhibit its cleavage and subsequent generation of the membrane attack complex, is currently approved to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia and neuromyelitis optica spectrum disorder. Given the role of antibodies directed against donor antigens that are produced by allospecific B-cells and plasma cells in AMR, eculizumab is being investigated for use within this indication. Three case reports have described the successful use of eculizumab for the prevention and treatment of AMR in LTRs. Given this lack of robust data, evidence for the use of eculizumab in other solid organ transplant recipients is of increased value. Early experiences from a single center’s use of eculizumab in LTRs are also described.Relevance to Patient Care and Clinical Practice:Lung transplant is a recognized treatment for end-stage lung disease, though complications posttransplant can be associated with significant morbidity and mortality. While prevention and management of AMR remains a substantial challenge without comprehensive guidance from societal guidelines, recently published literature may be helpful to guide clinical practice using alternative treatment options. However, this remains an area of great clinical importance, given the impact of AMR on long-term allograft function.Conclusions:Optimizing use of current therapies, as well as identifying and advancing novel therapeutic modalities such as eculizumab, are vital for the improvement of AMR prevention and treatment in LTRs to extend long-term allograft function and survival.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-23T09:49:02Z
  DOI: 10.1177/10600280231213112
Direct Oral Anticoagulants: Probability of Recurrent Venous
Thromboembolism and Bleeding Risk in an Obese Population
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  Authors: Courtney S. Pilkerton, Megan Adelman, Emily Crocetti, Jun Xiang, Victoria Strick, Charles D. Ponte, Shaylee Peckens, Benjamin P. Jackson, Kylen Whipp, Amie M. Ashcraft
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Direct-acting oral anticoagulants (DOACs) have become the preferred drugs for managing venous thromboembolism (VTE). Despite their advantages over vitamin K antagonists such as warfarin, their use in obese patients remains controversial with many providers reluctant to switch patients managed on warfarin. Outcome research that opts to increase provider confidence when prescribing DOACs for patients with obesity will be invaluable.Objective:This investigation evaluated whether patients with a body mass index (BMI) 35 kg/m2 or greater who were prescribed a DOAC had a higher risk for a recurrent VTE or bleed event relative to warfarin.Methods:The study was conducted in West Virginia which has the highest rate of obesity in the United States.Results:Of the total study population (1633), 2.3% (37) had a recurrent thrombotic event, 5.5% (89) had a major bleed event, and 10.7% (174) had some type of bleeding event. No individual patient characteristic was associated with recurrent thrombosis—including BMI. Older age, antiplatelet use, and taking a medication with a theoretical risk of increasing the effect of DOACs were associated with any and major bleeding events. The use of warfarin was associated with major bleeding events more frequently versus a DOAC. Body mass index was not a predictor for recurrent VTE or any bleed or major bleed events.Conclusions:These findings support the conclusion that DOACs are an appropriate and effective drug class for the management of VTE in patients with obesity.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-23T09:36:37Z
  DOI: 10.1177/10600280231212186
Valoctocogene Roxaparvovec and Etranacogene Dezaparavovec: Novel Gene
Therapies for Hemophilia A and B
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  Authors: John A. Dougherty, Kristiann M. Dougherty
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review efficacy and safety data of valoctocogene roxaparvovec (Roctavian) and etranacogene dezaparavovec (Hemgenix), novel gene therapies for the treatment of the life-threatening bleeding disorders hemophilia A and B, respectively.Data Sources:A PubMed/Google Scholar search from inception through August 11, 2023 was conducted using the following keywords: gene therapy, hemophilia A, hemophilia B, etranacogene dezaparavovec, valoctocogene roxaparvovec, and bleeding.Study Selection and Data Extraction:Data, including phase 1 to 3 clinical trials (non-comparator), were obtained from primary literature and package inserts. These reports evaluated clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions.Data Synthesis:Valoctocogene phase 3 study in males (n = 134): 87% had factor VIII (FVIII) levels that at least met criteria for mild hemophilia. Etranacogene phase 3 study in males (n = 54): within 3 weeks of infusion, mean factor IX (FIX) levels had reached 26.8 IU/dL. Both therapies provided clinically and statistically significant decreases in bleeding events and prophylactic factor infusions. Most common adverse event was elevations in liver function tests that were treated with glucocorticoids.Relevance to Patient Care and Clinical Practice in Comparison with Existing Drugs:The endogenous production of clotting factors mimics physiological production while decreasing morbidity and mortality related to bleeding events similar to the effects of existing replacement strategies. Gene therapy was also shown to increase patient quality of life.Conclusion:Valoctocogene and etranacogene provide another treatment for selected patients with hemophilia. Treatment for the patient with hemophilia (gene therapy vs replacement strategy) must be personalized as new clinical data are published being cognizant of drug affordability.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-18T07:26:38Z
  DOI: 10.1177/10600280231202247
Combination of Rivaroxaban and Amiodarone Increases Bleeding in Patients
With Atrial Fibrillation
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  Authors: Zi Wang, Xiaoyu Li, Ye Zou, Xiaoye Li, Qianzhou Lv
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Rivaroxaban and amiodarone are commonly used for treating patients with atrial fibrillation. Drug-drug interactions between rivaroxaban and amiodarone may increase exposure to rivaroxaban. However, the clinical relevance of this drug-drug interaction is still not clear.Objective:The aim was to investigate the risk of bleeding in patients receiving a combination of rivaroxaban and amiodarone.Methods:This was a prospective observational study in which we included atrial fibrillation patients treated with rivaroxaban. The patients were divided into the rivaroxaban group and the combination of rivaroxaban and amiodarone group (the combination group). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust between-group differences. The primary endpoint was defined as the time to the first occurrence of a composite of major, clinically relevant nonmajor, and minor bleeding.Results:In total, 481 atrial fibrillation patients were included in the analysis. After PSM, 154 patients in the rivaroxaban group were matched with 154 patients in the combination group. The bleeding events mainly consisted of clinically relevant nonmajor and minor bleeding. Only one patient experienced major bleeding. The primary outcome was recorded in 26.0% of patients in the combination group and 10.4% of patients in the rivaroxaban group (hazard ratio = 2.76, 95% CI = 1.55-4.93, P < 0.001). The bleeding risk was significantly higher in the combination group compared with that in the rivaroxaban group in the IPTW and stabilized IPTW analyses (hazard ratio = 2.17, 95% CI = 1.32-3.56, P = 0.002).Conclusion and Relevance:The combination of rivaroxaban and amiodarone increased the risk of bleeding in patients with atrial fibrillation, especially clinically relevant nonmajor and minor bleeding. Physicians prescribing rivaroxaban and amiodarone together should be concerned about an increase in the risk of nonmajor bleeding.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-14T06:54:15Z
  DOI: 10.1177/10600280231211306
Effectiveness of Patiromer Versus Sodium Zirconium Cyclosilicate for the
Management of Acute Hyperkalemia
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  Authors: Alison Rydell, Corianne Thackrey, Maryam Molki, Brandon P. Mullins
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Patiromer and sodium zirconium cyclosilicate (SZC) are 2 oral potassium binders approved for chronic hyperkalemia. It is unknown if one is more effective at reducing serum potassium than the other in acute hyperkalemia.Objective:The objective of this study was to determine if there was a difference between patiromer and SZC in the reduction of serum potassium in patients with acute hyperkalemia.Methods:This was a single-center, retrospective, observational study. Patients with a nonhemolyzed serum potassium level of 5.5 mEq/L or greater and received at least one dose of patiromer or SZC were included. The primary outcome was to determine the difference in effectiveness between patiromer and SZC in lowering of serum potassium 6 to 24 hours after administration. Secondary outcomes included description of total dosage received in 24 hours and incidence of electrolyte changes.Results:A total of 200 patients were included in this study, with 100 patients in each group. Serum potassium was significantly reduced by both patiromer (−1.2 mEq/L, 95% confidence interval [CI]: −2.3 to −0.2) and SZC (−0.8 mEq/L, 95% CI: −1.0 to −0.7), but there was no difference between the 2 medications in the amount of potassium reduction (P = 0.464). No clinically significant differences in electrolyte changes were seen.Conclusions and Relevance:This study represents the first head-to-head comparison of patiromer and SZC in the setting of acute hyperkalemia. No difference in effectiveness between patiromer and SZC in reducing serum potassium was seen. Both agents can be considered in acute hyperkalemia management.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-13T05:42:49Z
  DOI: 10.1177/10600280231209968
Risk of Tendon Injury in Patients Treated With Fluoroquinolone (FQ) Versus
Non-Fluoroquinolone Antibiotics for Community-Acquired Pneumonia (CAP)
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  Authors: Virginia H. Fleming, Jianing Xu, Xianyan Chen, Daniel Hall, Robin L. Southwood
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Fluoroquinolones (FQs) are associated with increased risk of tendon injury but comparative risk versus other antibiotic options for the same indication has yet to be evaluated.Objective:Describe the incidence (relative risk) of any tendon injury in patients receiving FQ compared with other (non-FQs) antibiotics for treatment of community-acquired pneumonia (CAP).Methods:A retrospective propensity score weighted cohort study was performed to evaluate the association between FQ antibiotics and tendon injury risk at 2 time points (within 1 month and within 6 months of use) compared with non-FQ regimens for treatment of CAP. The evaluation was performed using the CCAE (MarketScan Commercial Claims and Encounters) and COB (Medicare Supplemental and Coordination of Benefits) databases from 2014 to 2020. Patients with ICD (International Classification of Diseases) 9/10 coding for outpatient pneumonia who were>18 years and without history of tendon injury were included. Patients with history of tendon injury, who received multiple antibiotic therapies for recurrent pneumonia, or who received both FQ and non-FQ regimens during the study period were excluded. Propensity score weighting was used to adjust for selection bias due to contributing risk factors, including demographics (age, sex), comorbidities (diabetes mellitus, chronic kidney disease), and concurrent medications (corticosteroids).Results:At 1 month, the odds of tendon injury were estimated to be significantly higher (41.9%) in patients receiving FQs compared with those receiving a non-FQ-based regimen (odds ratio [OR] = 1.419, 95% confidence interval [CI] = [1.188-1.698]). The odds of tendon injury were also estimated to be higher (OR = 1.067, 95% CI = [0.975-1.173]) in the FQ population within 180 days, but this effect was not statistically significant. The most frequent sites of tendon injuries were rotator cuff, shoulder, and patellar tendon.Conclusions and Relevance:Prescribers should recognize the risk of tendon injury within 1 month of FQ use when considering treatment regimens for CAP and use alternative options with lower risk whenever possible.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-10T05:43:38Z
  DOI: 10.1177/10600280231210275
Fanconi Syndrome in Patients With Human Immunodeficiency Virus Treated
With Tenofovir-Based Antiretroviral Therapy: A Systematic Literature
Review
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  Authors: Mrinmayee Joshi, Brendan Clark, Todd A. Lee
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:Several cases of Fanconi syndrome (FS), a severe form of nephrotoxicity, have been reported in patients with HIV on tenofovir-containing antiretroviral therapy. A systematic review of the published literature on tenofovir-related FS in patients with HIV was conducted.Data Sources:PubMed and Embase were queried to identify articles in English published between January 2005 and June 2023, reporting tenofovir-related FS in adults with HIV. Preclinical studies, conference/poster abstracts, commentaries and responses, and review papers were excluded.Study Selection and Data Extraction:Of the 256 articles screened, 57 met the inclusion criteria. These comprised 37 case reports, 11 case series, 1 cross-sectional study, 1 case-control study, 4 cohort studies, 1 single-arm open-label clinical trial, 1 sub-analysis of clinical trials, and 1 pooled analysis of clinical trials.Data Synthesis:Among 56 cases on which information was abstracted, median age at FS diagnosis was 50 years, 51.8% were men, and duration of tenofovir use ranged from 6 weeks to 11 years. Ritonavir was co-prescribed in almost half the cases. In observational and interventional studies, incidence of FS was low. Many studies reported resolution of FS symptoms after tenofovir discontinuation. All FS occurrences were identified in those on tenofovir disoproxil fumarate (TDF), except for one patient on tenofovir alafenamide (TAF).Relevance to Patient Care and Clinical Practice:Continuous monitoring of signs and symptoms of renal and bone toxicity is essential for patients with HIV on tenofovir-containing therapy.Conclusions:Occurrence of FS is low in patients with HIV treated with tenofovir-based regimens. Concomitant use of ritonavir may increase risk of FS. TAF may be a safer alternative than TDF in terms of nephrotoxicity.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-11-07T05:19:43Z
  DOI: 10.1177/10600280231206703
The Tolerability and Safety of Psilocybin in Psychiatric and
Substance-Dependence Conditions: A Systematic Review
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  Authors: Dana Kaminski, Justin P. Reinert
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:The objective of this systematic review is to determine the tolerability and safety of psilocybin in a variety of psychiatric and substance-dependence conditions.Data sources:A systematic review was conducted using Embase, PubMed, Cochrane Central, and Web of Science through September 2023 using the following terminology: “psilocybin” AND “mental-disease” OR “substance-dependence” AND “disease-therapy,” in addition to other synonymous key words.Study selection and data extraction:Literature reporting acute effects and safety data following the use of psilocybin as the pharmacologic intervention in a clinical trial in adult patients with a psychiatric or substance-dependence condition were included. Following the application of inclusion and exclusion criteria, 16 studies were ultimately included in this review.Data synthesis:The most common treatment-emergent adverse effects reported were transient nausea and headache. Transient anxiety was reported as a frequent psychiatric effect, and 3 participants received a benzodiazepine for refractory anxiety during the psilocybin session. Psilocybin demonstrated modest increases in blood pressure and heart rate, and 1 participant received an antihypertensive for sustained hypertension during the psilocybin session. No cases of psilocybin-induced psychosis or Hallucinogen Persisting Perception Disorder were reported.Relevance to patient care and clinical practice:Treatment resistance remains a concern for psychiatric patients and novel therapies are needed to help alleviate the burden of morbidity and mortality. Psilocybin demonstrates promising acute and long-term safety that may allow for its use in psychiatric or substance-dependence conditions as an alternative to standards of care or in treatment-resistant patients.Conclusions:Psilocybin has demonstrated tolerability and safety in recent literature that has investigated its therapeutic potential in a variety of psychiatric or substance-dependence conditions.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-30T10:06:56Z
  DOI: 10.1177/10600280231205645
Real-World Experience With CMV inSIGHT T Cell Immunity Testing in
High-Risk Kidney and Pancreas Transplant Recipients
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  Authors: Jillian L. Descourouez, Jeannina A. Smith, Christopher M. Saddler, Didier A. Mandelbrot, Jon S. Odorico, Margaret R. Jorgenson
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Cytomegalovirus (CMV)-specific cell-mediated immunity is important for control of CMV after transplant. Assays exist to measure this, but their place in therapy is unclear, particularly in CMV high-risk recipients, without pretransplant exposure.Objective:The objective of this study was to evaluate predictive potential of a positive assay to determine freedom from DNAemia and describe subsequent 3-month CMV outcomes.Methods:Adult CMV high-risk kidney and/or pancreas transplant recipients were included if a CMV inSIGHT T Cell Immunity Panel (TCIP, Eurofins Viracor) was ordered and resulted between 1 August, 2019 and 30 July, 2022.Results:Seventy-six patients were included in our study; 49 tested during prophylaxis and 27 during treatment. Most TCIP assays obtained in the prophylaxis cohort were negative (n = 46, 93.9%). Rate of post-TCIP CMV infection was 10.2%. In those tested during treatment, 33.3% were positive and rate of post-TCIP CMV recurrence was 22.2%. The positive predictive value of the assay to successfully predict immunity was 66.7% during both prophylaxis and treatment. There were 4 cases of TCIP predictive failure with progressive CMV replication. At time of replication, 2 patients had concomitant clinical confounders thought to influence immune control of viral replication. All patients had intensification of immunosuppression prior to recurrent replication, but after TCIP was collected.Conclusion and Relevance:The data obtained from the TCIP are not static, immune control of CMV in latency can change and must be evaluated in clinical context. Timing of TCIP after transplant is significant, and patient-specific factors remain important to assess the likelihood of CMV in each unique patient-specific scenario. A CMV stewardship program can aid in application and interpretation of results.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-28T09:55:25Z
  DOI: 10.1177/10600280231207899
Zavegepant Intranasal Spray for Migraines
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  Authors: Amber Lanae Martirosov, Christopher Giuliano, Macy Shupp, Sarah Channey, Pramodini B. Kale-Pradhan
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:The objective is to review the pharmacology, efficacy, and safety of intranasal zavegepant in the acute treatment of migraine with or without aura.Data source:PubMed, Embase database, and ClinicalTrials.gov were searched using the following terms: Zavzpret, Zavegepant, BHV-3500, and migraine.Study selection and data extraction:Articles published in English from January 2013 to September 2023 related to pharmacology, safety, efficacy, and clinical trials were assessed.Data synthesis:In a phase 2/3 trial, zavegepant 10 and 20 mg were more effective than placebo on primary endpoints of freedom of pain (22.5%, 23.1%, and 15.5%, respectively), and freedom from most bothersome symptoms (MBSs) (41.9%, 47.9%, and 33.7%, respectively) 2 hours after treatment. The incidence of adverse effects for both doses was similar to placebo. In a phase 3 trial, zavegepant 10 mg was compared with placebo. Two hours after treatment, more patients in the zavegepant group achieved pain freedom (24% vs 15%) and relief from MBSs (40% vs 31%) compared with placebo. Common adverse events included dysgeusia (21% zavegepant vs 5% placebo) and nasal discomfort (5% zavegepant vs 1% placebo).Relevance to patient care and clinical practice in comparison with existing drugs:Zavegepant is indicated for acute treatment of migraine with or without aura in adults. Zavegepant method of administration and prompt relief of migraine symptoms may be an attractive alternative to triptans for those in need of relief.Conclusion:Zavegepant may be a convenient and useful acute treatment option for migraines with and without aura.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-28T09:37:17Z
  DOI: 10.1177/10600280231209439
Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer
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  Authors: Elizabeth Hageman, Mia E. Lussier
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:This article aims to discuss elacestrant, an oral selective estrogen receptor downregulator approved by the Food and Drug Administration (FDA) in January 2023 for the treatment of hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer.Data sources:PubMed, Embase, Medline, Clinicaltrials.gov, and the National Comprehensive Cancer Network (NCCN) were searched from inception to August 31, 2023.Study selection and data extraction:Clinical trials published in English were included and relevant information regarding methodology and results were extracted.Data synthesis:Phase 1 and 3 trials showed elacestrant was safe and improved progression-free survival in patients with endocrine receptor 1 (ESR1) mutations who failed cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) plus 1 prior endocrine therapy compared with standard of care (SOC) (fulvestrant, anastrozole, letrozole, or exemestane monotherapy).Relevance to patient care and clinical practice in comparison to existing drugs:Elacestrant maintains a comparable adverse event profile with other endocrine therapies and offers an alternative to typical sequential therapy which can delay the use of or be used after traditional chemotherapy. Elacestrant is currently being studied in CDK 4/6 inhibitor naïve patients and as a component of combination therapy for first-line use which could lead to future indications.Conclusions:Elacestrant gained FDA approval in January 2023 and can be considered in patients with HR+ HER2− advanced breast cancer and ESR1 mutations who have progressed despite therapy with either CDK 4/6i plus aromatase inhibitors (AI) or fulvestrant or chemotherapy.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-27T11:05:25Z
  DOI: 10.1177/10600280231206131
LCP-Tacrolimus Requires a Similar Empiric Dose Adjustment to
Immediate-Release Tacrolimus When Given Concomitantly With Letermovir for
Cytomegalovirus Primary Prophylaxis
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  Authors: Jillian L. Descourouez, Didier A. Mandelbrot, Jon Odorico, Margaret R. Jorgenson
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-27T09:58:19Z
  DOI: 10.1177/10600280231208430
Evaluation of Newly Integrated Bivalirudin Titration Protocol in Patients
With Mechanical Circulatory Support
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  Authors: Madeline Mitchell, Danine Sullinger, Duke Dyer, Gavin Hickey, David Kaczorowski, Joni Minor, Holt Murray, Raj Ramanan, Zachary Rhinehart, Mark Schmidhofer, Ryan M. Rivosecchi
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Patients with cardiogenic shock or end-stage heart failure can be maintained on mechanical circulatory support (MCS) devices. Once a patient undergoes placement of a device, obtaining and maintaining therapeutic anticoagulation is vital. Guidelines recommend the use of institutional protocols to assist in dosing and titration of anticoagulants.Objective:The purpose of this study was to characterize the use of bivalirudin before and after the implementation of a standardized titration protocol in patients with MCS.Methods:A retrospective review of patients who received bivalirudin for MCS (VA ECMO [veno-arterial extracorporeal membrane oxygenation], Impella, or LVAD [left ventricular assist device]) before and after the implementation of the titration protocol into the electronic health record (EHR) was conducted. The primary outcome was to compare the proportion of therapeutic activated partial thromboplastin time (aPTT). Secondary outcomes included number of subtherapeutic and supratherapeutic aPTTs, incidence of bleeding and clotting events, bivalirudin titrations per day, and percentage of patients with therapeutic aPTT level.Results:A total of 100 patients were included (precohort = 67; postcohort = 33). The proportion of therapeutic aPTTs was significantly higher in the postcohort than that in the precohort (62% vs 48%; P < 0.001). The postcohort had 0% of patients failing to achieve therapeutic aPTT levels. The number of titrations per day was significantly lower in the postcohort, with 1.20 titrations per day versus 1.93 in the precohort (P < 0.001).Conclusions:Implementation of the bivalirudin titration nomograms within the EHR significantly increased the number of therapeutic aPTTs, reduced the number of patients who never achieved a therapeutic aPTT, and reduced the required number of titrations per day.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-27T09:54:51Z
  DOI: 10.1177/10600280231206130
Risk of Pancreatitis With Incretin Therapies Versus Thiazolidinediones in
the Veterans Health Administration
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  Authors: Kristen Wilhite, Jennifer Meyer Reid, Matthew Lane
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Incretin therapies, comprised of the dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have been increasingly utilized for the treatment of type 2 diabetes (T2DM). Previous studies have conflicting results regarding risk of pancreatitis associated with these agents—some suggest an increased risk and others find no correlation. Adverse event reporting systems indicate that incretin therapies are some of the most common drugs associated with reports of pancreatitis.Objectives:This study aimed to compare the odds of developing pancreatitis in veterans with T2DM prescribed an incretin therapy versus thiazolidinediones (TZDs: pioglitazone and rosiglitazone) within the Veterans Health Administration (VHA).Methods:This was a retrospective cohort study analyzing veterans with T2DM first prescribed an incretin therapy or a TZD between January 1, 2011, and December 31, 2021. A diagnosis of pancreatitis within 365 days of being prescribed either therapy was counted as a positive case. Data was collected and analyzed utilizing VA’s Informatics and Computing Infrastructure (VINCI) and an adjusted odds ratio was calculated.Results:The TZD cohort consisted of 42 912 patients compared with the incretin cohort of 304 811 patients. The TZD cohort had a pancreatitis incidence rate of 1.94 cases per 1000 patients. The incretin cohort had a incidence rate of 2.06 cases per 1000 patients. An adjusted odds ratio found no statistical difference of pancreatitis cases between the TZD and incretin cohorts (adjusted odds ratio [AOR] = 0.94, 95% CI [0.75, 1.18]).Conclusion and Relevance:This retrospective cohort study of national VHA data found a relatively low incidence of pancreatitis in both cohorts, and an adjusted odds ratio found no statistical difference of pancreatitis in patients prescribed an incretin therapy compared with a control group. This data adds to growing evidence that incretin therapies do not seem to be associated with an increased risk of developing pancreatitis.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-26T08:39:42Z
  DOI: 10.1177/10600280231205490
Ertapenem Versus Meropenem for the Treatment of Extended Spectrum
Beta-Lactamase-Producing Enterobacterales Bacteremia in Critically Ill
Patients
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  Authors: Sydney VanDorf, Prakash Shah, Christine N. Yost
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The preferred carbapenem for treatment of infections caused by extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in critically ill patients is debated.Objective:The purpose of this study was to evaluate the difference in clinical failure between ertapenem and meropenem for treatment of ESBL-E bacteremia in critically ill patients. Of concern is ertapenem use in hypoalbuminemia given the potential for higher drug clearance.Methods:This retrospective, matched cohort study compared critically ill patients treated with ertapenem or meropenem for ESBL-E bacteremia between October 2016 and August 2022. Patients were matched on age, sex, lowest albumin, and in a 1:2 ratio of ertapenem to meropenem. The primary outcome, clinical failure, was a composite of 30-day mortality, antibiotic escalation, and microbiological failure. Secondary outcomes included all-cause readmission and development of superinfection.Results:Of 54 patients, 18 received ertapenem and 36 meropenem. Most had a urinary infection source (55.6% vs 41.7%, P = 0.393). There was no difference in clinical failure (50.0% vs 38.9%, P = 0.436). Ertapenem patients had antibiotic escalation more often (33.3% vs 2.8%, P = 0.002). There was no difference in 30-day mortality (11.1% vs 27.8%, P = 0.298), microbiological failure (27.8% vs 11.1%, P = 0.142), all-cause readmission (22.2% vs 13.9%, P = 0.461), or development of superinfection (11.1% vs 13.9%, P = 1.000).Conclusion and relevance:There was no difference in clinical failure in a small, retrospective cohort of critically ill patients receiving ertapenem or meropenem for ESBL-E bacteremia. Ertapenem may be appropriate in some critically ill and hypoalbuminemic patients, though additional data are needed.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-26T08:35:22Z
  DOI: 10.1177/10600280231205219
Naloxegol versus Methylnaltrexone for Opioid-Induced Constipation in
Critically Ill Patients
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  Authors: Daniel Tobben, Sheniece Carpenter, Rachel Kolar, Tyler Merritt, Tramaine Young, Paloma Hauser, Tia Collier
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Constipation impacts 58% to 83% of critically ill patients and is associated with increased time on mechanical ventilation, delirium, and increased length of stay (LOS) in the intensive care unit (ICU).Objective:The purpose of this study was to evaluate the efficacy of enteral naloxegol (NGL) versus subcutaneous methylnaltrexone (MNTX) for the management of opioid-induced constipation (OIC) in critically ill patients.Methods:A retrospective analysis was conducted on adult patients admitted to the ICU who received a parenteral opioid infusion for at least 4 hours and experienced no bowel movement (BM) within the 48-hour period preceding the administration of NGL or MNTX. The primary outcome was time to first BM from the start of NGL or MNTX therapy. Secondary outcomes included number of BMs 72 hours following NGL or MNTX administration, ICU LOS, and cost-effectiveness.Results:After exclusion criteria were applied, 110 and 51 patients were included in the NGL and MNTX groups, respectively. With a 10% noninferiority margin, NGL was noninferior to MNTX (Wald statistic = 1.67; P = 0.047). Median time to first BM was 23.7 hours for NGL and 18.3 hours for MNTX patients. Median LOS was 14 days (NGL) and 12 days (MNTX), and the average number of BMs in 72 hours was 3.9 for NGL and 3.8 for MNTX. Using wholesale acquisition cost (WAC), the cost per BM for NGL and MNTX was $21.74 and $170.00, respectively.Conclusion and relevance:This study determined that NGL and MNTX had similar time to BM. NGL appears to be a safe and effective alternative with cost-saving potential in treating OIC in critically ill patients.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-26T08:32:42Z
  DOI: 10.1177/10600280231205023
Hydroxychloroquine-Chloroquine, QT-Prolongation, and Major Adverse Cardiac
Events: A Meta-analysis and Scoping Review
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  Authors: Michael Cristian Garcia, Kai La Tsang, Simran Lohit, Jiawen Deng, Tyler Schneider, Jessyca Matos Silva, Lawrence Mbuagbaw, Anne Holbrook
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objectives:We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ).Data sources:We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians.Study selection and data extraction:Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies.Data synthesis:By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I2 = 0%).Relevance to patient care and clinical practice:These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications.Conclusions:Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-26T08:29:23Z
  DOI: 10.1177/10600280231204969
Zuranolone: The First FDA-Approved Oral Treatment Option for Postpartum
Depression
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  Authors: Kylie N. Barnes, Claire M. Vogl, Leigh Anne Nelson
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:The objective of this study was to review the characteristics, efficacy, and safety of zuranolone in the management of postpartum depression (PPD).Data sources:Literature was identified using PubMed (1966-August 2023) and EMBASE (1973-August 2023) and clinicaltrials.gov. Search terms included zuranolone, SAGE-217, and PPD with further limitation of those published in English.Study selection and data extraction:Articles selected for inclusion included trials evaluating zuranolone for the treatment of PPD.Data synthesis:Zuranolone was evaluated for the treatment of moderate to severe PPD in 2 phase III trials. Both studies resulted in statistically significant improvement in depressive symptoms at day 15 (P = 0.003 and P < 0.001). Sustained differences in remission rates favoring zuranolone were found in both studies at day 45 compared with placebo (P = 0.01 and P < 0.05). Zuranolone was well tolerated, with somnolence, dizziness, headache, and sedation reported as the most common side effects.Relevance to patient care and clinical practice in comparison to existing drugs:Zuranolone is only the second medication approved by the Food and Drug Administration (FDA) for PPD and offers an advantage over brexanolone in that it can administered orally in the outpatient setting. The rapid onset of effect of zuranolone is advantageous to traditional antidepressant therapy which can be weeks to months; however, limited information is available on safety during lactation.Conclusions:The recent FDA approval of oral zuranolone for PPD offers a second rapid-acting treatment for PPD, extending the opportunity for treatment to patients in the outpatient setting.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-25T04:52:23Z
  DOI: 10.1177/10600280231204953
Sulbactam-Durlobactam in the Treatment of Carbapenem-Resistant
Acinetobacter baumannii Infections
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  Authors: Benjamin August, Andrew Matlob, Pramodini B. Kale-Pradhan
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review the pharmacology, efficacy, and safety of intravenous sulbactam-durlobactam (SUL-DUR) in the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections.Data Sources:PubMed databases and ClinicalTrials.gov were searched using the following terms: Sulbactam Durlobactam, ETX2514, Xacduro, Sulbactam-ETX2514, ETX2514SUL.Study Selection and Data Extraction:Articles published in English between January 1985 and September 13, 2023, related to pharmacology, safety, efficacy, and clinical trials were reviewed.Data Synthesis:A phase II trial compared SUL-DUR with placebo with imipenem and cilastatin in both groups. Overall treatment success in the microbiological intention-to-treat analysis was reported in 76.6% of patients in the SUL-DUR group compared with 81% patients in the placebo group. A phase III trial compared SUL-DUR with colistin in adults with confirmed CRAB infections. Patients received either SUL-DUR or colistin and background therapy with imipenem-cilastatin. SUL-DUR was noninferior to colistin for 28-day all-cause mortality (19% vs 32.3%, treatment difference −13.2%; 95% CI [−30.0 to 3.5]).Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Clinicians have limited options to treat CRAB infections. SUL-DUR has demonstrated efficacy against CRAB in patients with pneumonia and may be considered a viable treatment option. Nonetheless, potential impact of concomitant imipenem-cilastatin as background therapy on clinical trial findings is unclear. Further studies are needed to elucidate the role of SUL-DUR alone or in combination with other active antimicrobials for the treatment of CRAB infections.Conclusions:SUL-DUR has shown to be predominantly noninferior to alternative antibiotics in the treatment of pneumonias caused by CRAB, making it a viable treatment option. Further postmarketing data is needed to ascertain its role in other infections.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-11T06:44:51Z
  DOI: 10.1177/10600280231204566
Incorporation of Innovative Strategies for Patient Education in
Pharmacist-Led Transition of Care Initiatives
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  Authors: Maria Miller Thurston, Lori H. Dupree, Angela Shogbon Nwaesei, Lydia C. Newsom
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  As patients transition between health care settings, they are at an increased risk of adverse events and medication errors as a result of medication changes and miscommunication. Pharmacists have traditionally provided transitions of care (TOC) services, including patient education, in a face-to-face manner with the goal of reducing medication errors and enhancing patient safety and understanding. However, changes in care delivery models, a burdened health care workforce, and diminishing resources necessitate innovative approaches for the provision of patient education within TOC. Pharmacists should consider novel approaches to expand scope, reduce barriers, and creatively use existing resources to optimize patient education in TOC.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-10-11T06:42:31Z
  DOI: 10.1177/10600280231204118
The Impact of Ketamine for Treatment of Post-Traumatic Stress Disorder: A
Systematic Review With Meta-Analyses
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  Authors: Dakota J. Sicignano, Ryan Kurschner, Nissen Weisman, Ava Sedensky, Adrian V. Hernandez, C. Michael White
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Ketamine has been used in anesthesia, pain management, and major depressive disorder. It has recently been studied in patients with post-traumatic stress disorder (PTSD).Objective:To determine the impact of ketamine on PTSD symptomatology and depression scores.Methods:We conducted a literature search of Medline 1960 to May 20, 2023, and found 6 randomized controlled trials that met our inclusion criteria. We extracted data on the Clinician-Administered PTSD (CAPS), PTSD Checklist (PCL), or Montgomery-Asberg Depression Rating (MADRS) scales.Results:The use of ketamine significantly reduced CAPS scores (n = 5, MD: −10.63 [95% CI −14.95 to −6.32]), PCL scores (n = 3, MD: −6.13 [95% CI −8.61 to −3.64]), and MADRS scores (n = 3, MD: −6.33 [95% CI −8.97 to −3.69]) at the maximal follow-up times versus control. Significant benefits were found at day 1 and weeks 1, 2, and 4 for CAPS and PCL scores as well as MADRS scores at day 1, week 1, and week 4 for ketamine versus control. The time to PTSD relapse was prolonged in the patients receiving ketamine versus control (n = 2, 15.74 days [95% CI 3.57 to 29.91 days]). More dry mouth (n = 2, OR 5.85 [95% CI 1.32 to 25.95]), dizziness (n = 2, OR 3.83 [95% CI 1.28 to 11.41]), and blurred vision (n = 2, OR 7.57 [1.00 to 57.10]) occurred with ketamine than control therapy.Conclusions and Relevance:Ketamine modestly reduced PTSD and depression scores as early as 1 day of therapy, but the longevity of effect needs to be determined. Given similar magnitude of benefit with SSRIs and venlafaxine, ketamine would not supplant these traditional options for chronic use.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-30T12:56:51Z
  DOI: 10.1177/10600280231199666
Pharmacokinetics of Levetiracetam Seizure Prophylaxis in Severe Traumatic
Brain Injury
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  Authors: Sarah Schuman Harlan, Carolyn D. Philpott, Shaun P. Keegan, Molly E. Droege, Aniruddha S. Karve, Brandon Foreman, Devin Wakefield, Eric W Mueller, Kiranpal Sangha, Laura B. Ngwenya, Joshua D. Courter, Pankaj Desai, Christopher Droege
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Drug pharmacokinetics (PK) are altered in neurocritically ill patients, and optimal levetiracetam dosing for seizure prophylaxis is unknown.Objective:This study evaluates levetiracetam PK in critically ill patients with severe traumatic brain injury (sTBI) receiving intravenous levetiracetam 1000 mg every 8 (LEV8) to 12 (LEV12) hours for seizure prophylaxis.Methods:This prospective, open-label study was conducted at a level 1 trauma, academic, quaternary care center. Patients with sTBI receiving seizure prophylaxis with LEV8 or LEV12 were eligible for enrollment. Five sequential, steady-state, postdose serum levetiracetam concentrations were obtained. Non-compartmental analysis (NCA) and compartmental approaches were employed for estimating pharmacokinetic parameters and projecting steady-state trough concentrations. Pharmacokinetic parameters were compared between LEV8 and LEV12 patients. Monte Carlo simulations (MCS) were performed to determine probability of target trough attainment (PTA) of 6 to 20 mg/L. A secondary analysis evaluated PTA for weight-tiered levetiracetam dosing.Results:Ten male patients (5 LEV8; 5 LEV12) were included. The NCA-based systemic clearance and elimination half-life were 5.3 ± 1.2 L/h and 4.8 ± 0.64 hours. A one-compartment model provided a higher steady-state trough concentration for the LEV8 group compared with the LEV12 group (13.7 ± 4.3 mg/L vs 6.3 ± 1.7 mg/L; P = 0.008). Monte Carlo simulations predicted regimens of 500 mg every 6 hours, 1000 mg every 8 hours, and 2000 mg every 12 hours achieved therapeutic target attainment. Weight-tiered dosing regimens achieved therapeutic target attainment using a 75 kg breakpoint.Conclusion and Relevance:Neurocritically ill patients exhibit rapid levetiracetam clearance resulting in a short elimination half-life. Findings of this study suggest regimens of levetiracetam 500 mg every 6 hours, 1000 mg every 8 hours, or 2000 mg every 12 hours may be required for optimal therapeutic target attainment. Patient weight of 75 kg may serve as a breakpoint for weight-guided dosing to optimize levetiracetam therapeutic target attainment for seizure prophylaxis.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-30T09:07:12Z
  DOI: 10.1177/10600280231202246
Trimethoprim/Sulfamethoxazole vs Minocycline for the Treatment of
Nonurinary Monomicrobial Stenotrophomonas maltophilia Infections in
Hospitalized Patients
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  Authors: Emma C. Hevia, Leslie Wooten, Amy L. Carr
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Stenotrophomonas maltophilia is an opportunistic, gram-negative bacillus with few therapeutic options due to a high level of intrinsic resistance. Trimethoprim/sulfamethoxazole (SXT) is recommended as the first-line treatment; however, minocycline (MIN) has been shown to have similar clinical outcomes in treating S. maltophilia and addresses concern for increasing resistance to SXT.Objective:The objective of this study is to evaluate the efficacy and safety outcomes of nonurinary, monomicrobial infections due to S. maltophilia in hospitalized patients treated with MIN or SXT.Methods:This was a retrospective study of hospitalized adult patients receiving MIN or SXT for nonurinary monomicrobial S. maltophilia infection from April 1, 2018 to March 31, 2020. The primary outcome was clinical disposition classified as rates of clinical failure, clinical improvement, or clinical success.Results:Eighty-two patients (88.2%) received MIN and 11 patients (11.8%) received SXT initially. Clinical failure occurred in 16 (19.5%) patients in the MIN group and in 4 (36.4%) patients in the SXT group (P = 0.242). Clinical improvement occurred in 11 (13.4%) patients in the MIN group and in 1 (9.1%) patient in the SXT group (P = 1.0). Clinical success occurred in 55 (67.1%) patients in the MIN group and in 6 (54.5%) patients in the SXT group (P = 0.503). Total duration of antimicrobial therapy (P = 0.3198), in-hospital mortality (P = 1.0), hospital length of stay (P = 0.9668), intensive care unit (ICU) length of stay (P = 0.1384), and 30-day readmission (P = 0.686) were similar between groups.Conclusions and Relevance:Rates of clinical failure, clinical improvement, or clinical success were similar between MIN and SXT for nonurinary monomicrobial S. maltophilia infections.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-30T09:02:55Z
  DOI: 10.1177/10600280231201850
Treatment Outcomes for Carbapenem-Resistant and Cephalosporin-Susceptible
Pseudomonas aeruginosa Pneumonia
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  Authors: Tsz Hin Ng, Jing J. Zhao, Ryan Gumbleton, Shannon Olson, Stephanie Smith, Marco R. Scipione
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Carbapenem-resistant (Car-R) Pseudomonas aeruginosa is an urgent threat. These isolates may remain susceptible to traditional noncarbapenem antipseudomonal β-lactams, but it is unclear if carbapenem resistance impacts the effectiveness of these agents.Objective:The purpose of this study was to compare clinical outcomes in Car-R and cephalosporin-susceptible (Ceph-S) P. aeruginosa pneumonia treated with cefepime versus other susceptible agents.Methods:This retrospective cohort study evaluated patients diagnosed with hospital-acquired or ventilator-associated pneumonia who had a respiratory isolate of Car-R Ceph-S P. aeruginosa. Patients were excluded if they had polymicrobial respiratory cultures, other concomitant infections, empyema, death within 3 days of index culture, or received less than 3 days of susceptible therapy. Patients treated with cefepime were compared to other susceptible therapies. The primary endpoint was 30-day in-hospital mortality.Results:Eighty-seven patients were included: cefepime, n = 61; other susceptible therapies, n = 26. There were no differences in 30-day in-hospital mortality between cefepime and other susceptible therapies (19.6% vs. 19.2%, p value = 0.719). In addition, there were no differences between clinical cure rates (cefepime 65.6% vs. other therapies 72 %, p value = 0.47). In multivariate logistic regression, treatment with cefepime (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.11-2.52) was not independently associated with 30-day in-hospital mortality.Conclusion and Relevance:For the treatment of Car-R Ceph-S P. aeruginosa pneumonia, cefepime showed similar rates of 30-day in-hospital mortality and clinical outcomes when compared to other susceptible therapies. Cefepime may be utilized to conserve novel β-lactam and β-lactamase inhibitors.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-27T06:19:41Z
  DOI: 10.1177/10600280231201953
Comparison of the Effectiveness and Safety of Clozapine Between Once-Daily
and Divided Dosing Regimen in Patients With Treatment-Resistant
Schizophrenia
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  Authors: Thanompong Sathienluckana, Thaksin Jansing, Supakan Srisuriyakamon, Aunchalee thonkhunthod, Parsiri Sangsuwanto, Pholphat Losatiankij, Suttha Supanya
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Clozapine is the most effective antipsychotic with respect to the incidence of discontinuation and is indicated for treatment-resistant schizophrenia. Although the recommendation for clozapine administration is divided dosing, once-daily dosing of clozapine is commonly prescribed in many countries. However, there is currently no clinical data comparing all-cause discontinuation between the 2 methods of administration of clozapine.Objectives:To compare the all-cause discontinuation and safety of clozapine administration between once-daily and divided dosing regimens.Methods:This was a retrospective cohort study. Participants were patients with treatment-resistant schizophrenia who had received 300 to 600 mg/day of clozapine for at least 3 months. Data were collected from outpatient medical records at Somdet Chaopraya Institute of Psychiatry. Eligible patients were classified into 2 groups: once-daily dosing and divided dosing. The primary outcome was the all-cause discontinuation rate between groups. The duration of the study was 2 years.Results:One hundred eighteen patients were included and analyzed in this study (once-daily dosing group: n = 58; divided dosing group: n = 60). There was no significant difference in all-cause discontinuation between the 2 groups (odds ratio 1.03; 95% confidence interval: [0.28, 3.79]: P = 1.00), or adverse events between groups.Conclusion and Relevance:In patients with treatment-resistant schizophrenia, there were no significant differences in effectiveness or safety between once-daily and divided dosing of clozapine. Further prospective studies with larger sample sizes are required to confirm these findings.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-25T06:13:16Z
  DOI: 10.1177/10600280231201708
Real-world Impact of 3 and 4.5 mg Doses of Dulaglutide on Weight and
Hemoglobin A1c in Patients With Type 2 Diabetes Mellitus
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  Authors: Amy Duong, Samantha Heacock, Sarah Amering, Lillian Brennan, Jineane Venci, Nicole M. Acquisto
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Limited real-world data on the benefits and risks associated with 3 and 4.5 mg doses of dulaglutide currently exists, making it difficult to determine the impact of dose titration for patients currently managed with dulaglutide 1.5 mg weekly.Objective:To determine the impact of dulaglutide 3 and 4.5 mg doses on weight and hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM), in clinical practice.Methods:Retrospective, observational study of adult T2DM patients receiving dulaglutide 3 or 4.5 mg weekly within a large, university-affiliated, primary care network. The primary outcome was change in weight and HbA1c from baseline to 24 weeks. Secondary outcomes included incremental changes in weight and HbA1c, and describing trends related to dose reductions.Results:Ninety-five patients were included, 62 in the dulaglutide 3 mg group and 33 in the dulaglutide 4.5 mg group. After 24 weeks, the mean changes in weight and HbA1c from baseline were −1.8 kg (P < 0.01) and −0.4% (P < 0.01) in the 3 mg group, and −4.2 kg (P < 0.01) and −0.4% (P = 0.119) in the 4.5 mg group. Incremental change in weight and HbA1c among patients who were titrated from dulaglutide 3 to 4.5 mg weekly were −2.6 kg (P < 0.01) and −0.2% (P = 0.04), respectively.Conclusion and Relevance:Titration from dulaglutide 1.5 to 3 mg resulted in significant reductions in weight and HbA1c after 24 weeks. Additional, statistically significant, reductions in weight and HbA1c were seen when patients were further titrated to dulaglutide 4.5 mg weekly.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-25T06:10:36Z
  DOI: 10.1177/10600280231199852
Keeping It “Current”: A Review of Treatment Options for the Management
of Supraventricular Tachycardia
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  Authors: Patrick Tednes, Samantha Marquardt, Shannon Kuhrau, Kristin Heagler, Megan Rech
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review treatment options and updates that exist for the management of paroxysmal supraventricular tachycardia (PSVT).Data Sources:A literature search of PubMed was performed including articles from 1974 to June 2023 using the terms: arrhythmias, adenosine, verapamil, diltiazem, esmolol, propranolol, metoprolol, beta-blockers, amiodarone, PSVT, synchronized cardioversion, methylxanthines, dipyridamole, pediatrics, heart transplant, and pregnancy. Primary literature and guidelines were reviewed.Study Selection and Data Extraction:Studies were considered if they were available in English and conducted in humans.Data Synthesis:PSVT is a subset of supraventricular tachycardia (SVT) that presents as a rapid, regular tachycardia with an abrupt onset and termination. Due to frequent emergency department (ED) visits annually with symptoms of PSVT, appropriate and efficient management of these patients is vital. This review provides an overview of the pathophysiology of PSVT, while also describing the literature behind nonpharmacologic and pharmacologic management of PSVT.Relevance to Patient Care and Clinical Practice:This review describes new literature regarding the improved success of the modified Valsalva maneuver as a nonpharmacologic therapy in PSVT. In addition, it describes a new technique in administration of adenosine that has improved outcomes, defines dose adjustments needed for drug interactions with adenosine, compares the utilization of nondihydropyridine calcium channel blockers with adenosine, and provides management recommendations for patients in special populations.Conclusions:With high annual rates of ED visits for SVT, providers should be aware of the data behind management and modifications of therapy based on patient-specific factors (ie, patient preference, pharmacokinetics/pharmacodynamics, drug interactions, and special populations).
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-25T06:06:55Z
  DOI: 10.1177/10600280231199136
Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation
and Associated Outcomes
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  Authors: Ashley M. Campbell, Elizabeth Pae, Eunice Lee, Timothy Jacisin, Alina Price, Jessica DeAngelo
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios.Objective:The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing.Methods:A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, “underdosed”) were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences.Results:Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) “underdosed.” The 147 “underdosed” patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05).Conclusion and Relevance:Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-15T11:26:17Z
  DOI: 10.1177/10600280231199137
Sparsentan: A First-in-Class Dual Endothelin and Angiotensin II Receptor
Antagonist
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  Authors: Ada W. Chiu, Nina Bredenkamp
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To provide an overview of the guidelines on the management of immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS), review the evidence for sparsentan, and discuss its place in therapy.Data Sources:A literature search was conducted using MEDLINE, EMBASE, and clinicaltrials.gov using the search terms “sparsentan” and “RE-021” up to the end of Jun 2023.Study Selection and Data Extraction:English studies were included if they evaluated the pharmacology, pharmacokinetics, efficacy, and safety of sparsentan in human subjects. Information from the Food and Drug Administration (FDA) and manufacturer’s monograph were also extracted.Data Synthesis:In comparison with irbesartan, sparsentan reduced urine protein-to-creatinine ratio (UPCR) in both IgAN (−49.8% vs −15.1% at interim 36 weeks) and FSGS (−44.8% vs −18.5% at 8 weeks). Hypotension and edema were the most common adverse events in the sparsentan groups. Hepatotoxicity appears to be comparable between sparsentan and irbesartan in short-term results.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Sparsentan provides a new option for patients with IgAN who are otherwise at high risk of progressive kidney disease. Continued FDA approval is dependent on long-term study results on renal function decline and safety.Conclusion:Sparsentan reduces proteinuria in IgAN and FSGS, and has expedited approval by the FDA for IgAN in patients at risk of rapid disease progression, generally at urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g. Interim results from PROTECT and results from DUET showed promise for improving proteinuria in IgAN and FSGS. Long-term renal function benefit and safety data are pending.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-14T08:53:44Z
  DOI: 10.1177/10600280231198925
CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and
Voriconazole in Chinese Kidney Transplant Patients
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  Authors: Yundi Zhang, Yue Du, Shuyu Ren, Yue Li, Xiaoming Zhang, Xiaohong Cao, Fengxi Liu, Huiying Zong, Yan Li
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The effect of drug-drug interaction (DDI) between tacrolimus and voriconazole on the pharmacokinetics of tacrolimus in different CYP3A5 genotypes has not been reported in previous studies.Objective:The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-voriconazole DDI in Chinese kidney transplant patients.Methods:All kidney transplant patients were divided into combination and non-combination groups based on whether tacrolimus was combined with or without voriconazole. Each group was subdivided into CYP3A5 expresser (CYP3A5*1/*1 or CYP3A5*1/*3) and CYP3A5 nonexpresser (CYP3A5*3/*3). A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C0) (C0/D) between combination and non-combination groups, respectively. Tacrolimus C0/D was also compared between CYP3A5 expresser and nonexpresser in both groups.Results:The C0/D values of tacrolimus were significantly different between CYP3A5 expresser and nonexpresser in combination group (378.20 [219.38, 633.48] ng/mL/[mg/kg/d] vs 720.00 [595.35, 1681.50] ng/mL/[mg/kg/d], P = 0.0010). Either in CYP3A5 expresser or nonexpresser, we found a statistically significant difference in tacrolimus C0/D between combination and non-combination group (P < 0.0001). The increase in CYP3A5 nonexpresser was 1.38 times higher than that in CYP3A5 expresser (320.93% vs 232.19%).Conclusion and Relevance:The median C0/D values were 90.38% higher in kidney transplant recipients with CYP3A5*3/*3 genotype than in those with CYP3A5*1/*1 or CYP3A5*1/*3 genotype when treated with both tacrolimus and voriconazole. A CYP3A5 genotype-dependent DDI was found between tacrolimus and voriconazole. Therefore, personalized therapy accounting for CYP3A5 genotype detection and therapeutic drug monitoring is necessary for kidney transplant patients when treating with tacrolimus and voriconazole.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-13T11:37:41Z
  DOI: 10.1177/10600280231197399
Targeted Therapies for Previously “Undruggable” KRAS-Mutated
Non–Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib
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  Authors: Natalie Mausey, Zachery Halford
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To evaluate the safety and efficacy of the novel KRAS-targeting agents, sotorasib and adagrasib, in treating KRAS G12C-mutated non–small cell lung cancer (NSCLC).Data Sources:A comprehensive English-based literature search of PubMed and Clinicaltrials.gov between January 2000 and July 2023 was conducted using the terms sotorasib, Lumakras, AMG 510, adagrasib, Krazati, and MRTX849.Study Selection and Data Extraction:Relevant prescribing information, clinical trials, and treatment guidelines were evaluated.Data Synthesis:Sotorasib and adagrasib received accelerated US Food and Drug Administration (FDA) approval following pivotal phase I/II clinical trials. Sotorasib, a first-in-class KRAS inhibitor, demonstrated an overall response rate (ORR) of 41% and a progression-free survival (PFS) of 6.3 months. In a phase III confirmatory trial, sotorasib showed significantly longer PFS compared with docetaxel (5.6 vs. 4.5 months; P = 0.0017). Adagrasib produced an ORR of 42.9% and a PFS of 6.5 months. Both drugs present unique safety profiles, with common toxicities, including diarrhea, musculoskeletal pain, fatigue, and hepatotoxicity.Relevance to Patient Care and Clinical Practice:With KRAS mutations being among the most common oncogenic alterations in NSCLC, sotorasib and adagrasib offer new therapeutic avenues for this previously “undruggable” target. Current treatment guidelines list sotorasib and adagrasib as second-line options in patients with confirmed KRAS G12C-mutated NSCLC. Additional studies are required to further differentiate the safety and efficacy profiles of these 2 agents and identify their optimal place in therapy.Conclusion:Sotorasib and adagrasib demonstrated promising outcomes in targeting the constitutively active KRAS G12C oncogenic driver, underscoring the need for further research to optimize their therapeutic application in this high-risk population.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-13T06:14:30Z
  DOI: 10.1177/10600280231197459
Evaluation of Basal Plus Versus Sliding Scale Insulin Therapy on Glucose
Variability in Critically Ill Patients Without Preexisting Diabetes
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  Authors: Rachel E. Webster, Julie J. Belfer, Kyle J. Schmidt
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:There is limited evidence evaluating the impact of insulin treatment strategies on glucose variability in critically ill patients without preexisting diabetes.Objective:Compare basal plus insulin (BPI) and sliding scale insulin (SSI) impact on glycemic control outcomes in critically ill patients without preexisting diabetes experiencing hyperglycemia.Methods:This multicenter, retrospective review analyzed critically ill patients with hyperglycemia who received either BPI or SSI. Patients with a hemoglobin A1C>6.5% during the admission of interest or in the previous 3 months, or a diagnosis of diabetes at the time of discharge were excluded. The primary outcome was glucose variability during the intensive care unit (ICU) admission. Secondary outcomes included hypoglycemia frequency, frequency of goal glucose levels, mortality, and length of stay.Results:The analysis included 228 patients (39 in BPI, 189 in SSI). Average glucose variability was higher in the BPI group compared with the SSI group (85.8 mg/dL ± 33.1 vs 70.2 mg/dL ± 30.7; P = 0.009), which remained when controlling for baseline confounding (−12.1 [5.6], 95% CI −23.2 to −0.99; P = 0.033). Hypoglycemia incidence was similar between groups. BPI patients had a lower incidence of glucose values within goal range than SSI patients (P = 0.046). There was no difference in length of stay or hospital mortality.Conclusions and Relevance:The use of SSI compared with a BPI regimen may result in reduced glycemic variability in critically ill patients without preexisting diabetes. Future prospective studies, with a larger sample size, are warranted to confirm our exploratory findings and characterize clinically significant benefits.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-13T06:09:02Z
  DOI: 10.1177/10600280231197255
Intranasal Theophylline: Potential Treatment for Long COVID Olfactory
Dysfunction'
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  Authors: Olga Hilas, Tina Caliendo
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-09-07T12:17:05Z
  DOI: 10.1177/10600280231194960
Invasive SCC and Tirbanibulin: Experience in Patient With
Epidermodysplasia Verruciformis
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  Authors: Andrea Agostini, Nicole Macagno, Rebecca Senetta, Pietro Quaglino, Paolo Broganelli
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-31T10:05:08Z
  DOI: 10.1177/10600280231195899
Oteseconazole for the Treatment of Recurrent Vulvovaginal Candidiasis: A
Drug Review
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  Authors: Cameron Lanier, Tyler C. Melton
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:The objective of the study is to describe and analyze the pharmacodynamics and pharmacokinetics of oteseconazole as well as the clinical evidence supporting the efficacy of oteseconazole in treating recurrent vulvovaginal candidiasis (RVVC).Data Sources:A literature search was conducted using MEDLINE and EMBASE databases (2015-June 2023). Search terms included “oteseconazole” OR “VT-1161” or “VIVJOA” AND “RVVC” or “recurrent vulvovaginal candidiasis” or “vulvovaginal candidiasis.” Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review.Study Selection and Data Extraction:Relevant studies in English and clinical trials conducted in humans were reviewed.Data Synthesis:Oteseconazole is approved for the treatment of RVVC. In 2 identical phase III studies, oteseconazole was superior to placebo through 48 weeks for preventing recurrence of RVVC (6.7% vs 42.8%, P < 0.001 and 3.9% vs 39.4%, P < 0.001). In the only phase III trial comparing oteseconazole against active drug, oteseconazole was well tolerated and exhibited noninferiority to fluconazole in acute treatment and superiority to placebo for prevention maintenance through 50 weeks (5.1% vs 42.2%, P < 0.001).Relevance to Patient Care and Clinical Practice in Comparison to Existing Agents:This review describes the use of oteseconazole for the treatment of RVVC as compared with fluconazole. Oteseconazole is an effective treatment option for common pathogens causing vulvovaginal candidiasis, including Candida and fluconazole-resistant Candida.Conclusions:Oteseconazole is an effective and safe treatment option for the management of RVVC though current research lacks comparison with established maintenance regimens. Additional research is needed to ascertain the placement of oteseconazole in the treatment of RVVC.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-31T10:00:44Z
  DOI: 10.1177/10600280231195649
Authors Reply to Comment on Rotshild et al’s “The Risk for Prostate
Cancer With Calcium Channel Blockers”
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  Authors: Victoria Rotshild, Ilan Matok
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-24T05:19:34Z
  DOI: 10.1177/10600280231185784
Comment on Rotshild et al’s “The Risk for Prostate Cancer With Calcium
Channel Blockers”
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  Authors: Kuan-Fu Liao, Bing-Fang Hwang, Chiu-Shong Liu, Shih-Wei Lai
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-24T05:19:15Z
  DOI: 10.1177/10600280231185781
The Role of Dexmedetomidine in Paroxysmal Sympathetic Hyperactivity: A
Systematic Review
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  Authors: Cole R. Jerousek, Justin P. Reinert
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:The objective was to evaluate the efficacy and safety of dexmedetomidine in the treatment and prophylaxis of paroxysmal sympathetic hyperactivity (PSH).Data Sources:A review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and queried Embase, MEDLINE (PubMed), Cochrane CENTRAL, Web of Science, SciELO, Korean Journal Index (Clarivate), Global Index Medicus, and CINAHL Plus for results through June 2023.Study Selection and Data Extraction:Studies providing efficacy or safety data associated with dexmedetomidine with a reported diagnosis of PSH were included. Exclusion of studies in pediatric populations, without quantitative and qualitative outcome data, and not readily translatable to English was adhered to.Data Synthesis:Thirteen observational studies of 178 patients were included in the qualitative analysis. Reductions in PSH frequency or symptom severity were reported in 44 of 48 patients who received dexmedetomidine for acute treatment. Prophylactic use of dexmedetomidine was associated with reductions in PSH-Assessment Measure (PSH-AM) scores in postsurgical patients with traumatic brain injuries (TBIs). Adverse events associated with dexmedetomidine were either absent or reported as none.Relevance to Patient Care and Clinical Practice:This review supports the safe and effective use of dexmedetomidine in the treatment and prophylaxis of PSH. Further investigation is required to determine optimal dosing strategies and the extent to which PSH etiology correlated to the efficacy of dexmedetomidine.Conclusions:The use of dexmedetomidine appears to be both efficacious and safe for the treatment and prevention of PSH in patients experiencing a TBI. Additional research is needed to elucidate dosing strategies, titration parameters, and duration of therapy.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-23T04:18:07Z
  DOI: 10.1177/10600280231194708
A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed
Management of Severe Alcohol Withdrawal
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  Authors: Kendall H. Brickel, Emily K. Hodge, Daria Zavgorodnyaya, John M. Schroeder, Lawrence H. Brown, Mitchell J. Daley
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies.Objectives:The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS).Methods:Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment.Results:A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01).Conclusion and Relevance:DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-22T12:36:37Z
  DOI: 10.1177/10600280231194790
E-Cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI)
Continues: An Opportunity for Pharmacist Intervention
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  Authors: Miranda R. Andrus
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Electronic cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) was first identified and reported in 2019, but media coverage and reporting of cases drastically decreased when the COVID-19 pandemic started in early 2020. The syndrome has continued to occur since that time and it is critical that pharmacists are aware of how EVALI presents, and when it should be considered as a potential diagnosis. Inpatient and outpatient pharmacists play a vital role in the treatment of EVALI, and should be knowledgeable of the utility of corticosteroids, even though data are extremely limited. Pharmacists should understand the importance of collecting detailed and accurate information about vaping from patient interviews. Pharmacists also play a leading role in cessation counseling and treatment, selecting medications that can be used to treat nicotine addiction from vaping, and assisting with transitions of care and follow-up.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-22T05:21:34Z
  DOI: 10.1177/10600280231193770
Bacterial Vaginosis Treatment Patterns, Associated Complications, and
Health Care Economic Burden of Women With Medicaid Coverage in the United
States
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  Authors: Eren Watkins, Clifton M. Chow, Melissa Lingohr-Smith, Jay Lin, Candice Yong, Krishna Tangirala, Kevin Collins, James Li, Roy Brooks, Jennifer Amico
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  BackgroundBacterial vaginosis (BV) is a highly prevalent vaginal infection.ObjectivesPrimary objectives of this study were to examine treatment patterns among female patients with Medicaid coverage who were diagnosed with incident BV, the frequency of BV-associated complications, and health care resource utilization (HCRU) and associated costs of incident BV and its recurrence. Secondary objectives were to identify predictors of total all-cause health care costs and number of treatment courses.MethodsFemale patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication were selected from the Merative MarketScan Medicaid database (2017-2020). Additional treatment courses were evaluated during a ≥12-month follow-up period, in which new cases of BV-associated complications and HCRU and the associated costs were also measured. Generalized linear models were used to identify baseline predictors of total all-cause health care costs and number of treatment courses.ResultsAn incident vaginitis diagnosis and ≥1 BV medication claim were present in 114 313 patients (mean age: 28.4 years; 48.6% black). During the follow-up, 56.6% had 1 treatment course, 24.9% had 2, 10.2% had 3, and 8.3% had ≥4; 43.4% had BV recurrence. Oral metronidazole (88.5%) was the most frequently prescribed medication. Nearly 1 in 5 had a new occurrence of a BV-associated complication; most (76.6%) were sexually transmitted infections (STIs). Total all-cause and BV-related costs averaged $5794 and $300, respectively, per patient; both increased among those with more treatment courses. Older age, pregnancy, comorbidity, any STIs, postprocedural gynecological infection (PGI), and infertility were predictive of higher total all-cause health care costs, while race/ethnicity other than white was predictive of lower costs. Older age, black race, any STIs, pelvic inflammatory disease, and PGI were predictive of>1 treatment courses.Conclusion and RelevanceThe high recurrence of BV represents an unmet need in women’s health care and better treatments are necessary.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-17T11:37:48Z
  DOI: 10.1177/10600280231190701
A Narrative Review on the Administration of Inhaled Prostaglandins in
Critically Ill Adult Patients With Acute Respiratory Distress Syndrome
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  Authors: Lydia R. Ware, Christine S. Kim, Paul M. Szumita, Jeremy R. DeGrado
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To describe the effect of inhaled prostaglandins on both oxygenation and mortality in critically ill patients with acute respiratory distress syndrome (ARDS), with a focus on safety and efficacy in coronavirus disease 2019 (COVID-19)-associated ARDS and non-COVID-19 ARDS.Data Sources:A literature search of MEDLINE was performed using the following search terms: inhaled prostaglandins, inhaled epoprostenol, inhaled nitric oxide, ARDS, critically ill. All abstracts were reviewed.Study Selection and Data Extraction:Relevant English-language reports and studies conducted in humans between 1980 and June 2023 were considered.Data Synthesis:Data regarding inhaled prostaglandins and their effect on oxygenation are limited but show a benefit in patients who respond to therapy, and data pertaining to their effect on mortality is scarce. Concerns exist regarding the formulation of inhaled epoprostenol (iEPO) utilized in addition to modes of medication delivery; however, the limited data surrounding their use have shown a reasonable safety profile. Other avenues and beneficial effects may exist with inhaled prostaglandins, such as use in COVID-19-associated ARDS or non-COVID-19 ARDS patients undergoing noninvasive mechanical ventilation or during patient transport.Relevance to Patient Care and Clinical Practice:The use of inhaled prostaglandins can be considered in critically ill patients with COVID-19-associated ARDS or non-COVID-19 ARDS who are experiencing difficulties with oxygenation refractory to nonpharmacologic strategies.Conclusions:The use of iEPO and other inhaled prostaglandins requires further investigation to fully elucidate their effects on clinical outcomes, but it appears these medications may have a potential benefit in COVID-19-associated ARDS and non-COVID-19 ARDS patients with refractory hypoxemia but with little effect on mortality.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-17T08:38:59Z
  DOI: 10.1177/10600280231194539
Baclofen and Tizanidine Adverse Effects Observed Among Community-Dwelling
Adults Above the Age of 50 Years: A Systematic Review
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  Authors: Lisa Killam-Worrall, Romana Brand, Janine R. Castro, Dipa S. Patel, Katherine Huynh, Bryn Lindley, Brittany Palasik Torres
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:This review highlights adverse effects of baclofen and tizanidine in older community-dwelling adults.Data Sources:A literature search was conducted, including search terms of “adverse effect,” “baclofen,” “elderly,” “falls,” “fractures,” and “tizanidine.” Studies were included if they described community-dwelling adults aged 50 years and older who received oral baclofen or tizanidine. The Federal Drug Administration Adverse Event Reporting System (FAERS) data were compiled for adverse effect incidence.Study Selection and Data Extraction:The literature search was completed in July 2019 and updated in June 2023. Reviews performed by 2 independent reviewers yielded 15 records. FAERS identified 486 (baclofen) and 305 (tizanidine) adverse effects of interest.Data Synthesis:Two retrospective cohort studies evaluating baclofen use in older adults showed increased hospitalizations for encephalopathy in chronic kidney disease (7.2% vs 0.1%) and end-stage renal disease (daily dose 20 mg or more; relative risk [RR] 19.8, 95% CI = [14.0-28.0]). Other articles were case reports; 10 articles reported dyskinesias, encephalopathy or disorientation, and drowsiness associated with baclofen, and 5 articles reported bradycardia and/or hypotension with tizanidine. The FAERS Public Dashboard revealed 12.1% and 28.7% overall incidence of adverse effects of interest, with a 27.8% and 29.2% incidence of falls for baclofen and tizanidine, respectively. Baclofen and tizanidine are associated with concerning adverse effects in older adults. Alternative agents should be considered, but, if necessary, providers should start at lower doses and increase slowly.Conclusions:This review highlights the importance of using baclofen and tizanidine with caution in older adults.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-17T08:36:40Z
  DOI: 10.1177/10600280231193080
A Review of the Safety and Efficacy of Bexagliflozin for the Management of
Type 2 Diabetes
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  Authors: Kevin Cowart, Scott Coon, Nicholas W. Carris
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review the pharmacology of bexagliflozin in addition to its safety and efficacy from available clinical trials used for its approval, as well as available clinical evidence to date.Data Sources:A search of the National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov) and PubMed database was performed from inception through June 1, 2023.Study Selection and Data Extraction Quantification:The following study designs were included: meta-analyses, systematic review, clinical trial, or observational study design. Abstracts and drug monographs were also reviewed. Narrative or scoping reviews were excluded. Only articles in the English language and those evaluating the pharmacology, pharmacokinetics, safety, or efficacy of bexaglifozin in humans were included.Data Synthesis:Bexagliflozin reduces hemoglobin A1c ~0.5% with similar reductions in systolic blood pressure and body weight to other SGLT2 inhibitors. No cardiovascular outcomes trial is published, nor ongoing at this time. Adverse effects are similar to other SGLT2 inhibitors (genital mycotic and urinary tract infections, increased urination) including a warning for lower extremity amputation similar to canagliflozin.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Although no cost-effectiveness data are available, statements from the manufacturer suggest a competitive price point. Given limited trial data, lower cost, if chosen, may create a temporary niche for bexagliflozin pending generic availability of other SGLT2 inhibitors. However, given lack of cardiovascular and renal outcome data, empagliflozin, dapagliflozin, or canagliflozin may be preferred.Conclusion:Bexagliflozin appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2D.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-12T04:32:46Z
  DOI: 10.1177/10600280231190443
Angiotensin Receptor Blocker–Related Sprue-like Enteropathy: Review of
Food and Drug Administration Adverse Event Reporting System
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  Authors: Ryan Meader, Sam Papasotiriou, Hardeep Ahdi, Hoang Dang, Eli D. Ehrenpreis
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Sprue-like enteropathy (SE) related to olmesartan use was first reported in 2012. In 2017, the manufacturer of Benicar paid $300 million for 2300 claims for olmesartan-related SE.Objective:A study in 2019 suggested that SE was related to olmesartan and with the possibility of angiotensin receptor blocker (ARB) class effect. To further characterize this condition, our group examined reports of ARB-related SE to Food and Drug Administration Adverse Event Reporting System (FAERS).Methods:All reports of ARB-related SE from January 2017 to December 2021 were downloaded from the FAERS database. Gastrointestinal adverse events including SE were reviewed. Reporter categories included physicians, pharmacists, other health care professionals, consumers, and attorneys.Results:A total of 106 590 reports of ARB-related adverse effects were analyzed. Sprue-like enteropathy was identified in 4337 cases (4.1% of total reports). Of these, 4240 cases (98.0%) of ARB-related SE were reported in patients using products with olmesartan, and 97 cases of SE were reported for all other ARBs (eprosartan, losartan, telmisartan, irbesartan, valsartan, and candesartan). Reports of olmesartan-related SE increased rapidly in 2017, continued at a high rate in 2018 and 2019, and essentially stopped in 2020 and 2021.Conclusions and Relevance:Reports to FAERS for ARB-related SE are mostly related to olmesartan. There was a steep decline in reports of olmesartan-related SE following the lawsuit with potential of lawyer interference. There are reports of SE related to ARBs other than olmesartan, with increased physician awareness and the potential to discover a class effect with future studies.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-10T04:51:03Z
  DOI: 10.1177/10600280231191834
Artificial Neural Network Analysis of Determinants of Tacrolimus
Pharmacokinetics in Liver Transplant Recipients
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  Authors: Yue Du, Yundi Zhang, Zhiyan Yang, Yue Li, Xinyu Wang, Ziqiang Li, Lei Ren, Yan Li
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  BackgroundThe efficacy and toxicity of tacrolimus are closely related to its trough blood concentrations. Identifying the influencing factors of pharmacokinetics of tacrolimus in the early postoperative period is conducive to the optimization of the individualized tacrolimus administration protocol and to help liver transplant (LT) recipients achieve the target blood concentrations.ObjectiveThis study aimed to develop an artificial neural network (ANN) for predicting the blood concentration of tacrolimus soon after liver transplantation and for identifying determinants of the concentration based on Shapley additive explanation (SHAP).MethodsIn this retrospective study, we enrolled 31 recipients who were first treated with liver transplantation from the Department of Liver Transplantation and Hepatic Surgery, the First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) from November 2020 to May 2021. The basic information, biochemical indexes, use of concomitant drugs, and genetic factors of organ donors and recipients were used for the ANN model inputs, and the output was the steady-state trough concentration (C0) of tacrolimus after oral administration in LT recipients. The ANN model was established to predict C0 of tacrolimus, SHAP was applied to the trained model, and the SHAP value of each input was calculated to analyze quantitatively the influencing factors for the output C0.ResultsA back-propagation ANN model with 3 hidden layers was established using deep learning. The mean prediction error was 0.27 ± 0.75 ng/mL; mean absolute error, 0.60 ± 0.52 ng/mL; correlation coefficient between predicted and actual C0 values, 0.9677; and absolute prediction error of all blood concentrations obtained by the ANN model, ≤3.0 ng/mL. The results indicated that the following factors had the most significant effect on C0: age, daily drug dose, genotype at CYP3A5 polymorphism rs776746 in both recipient and donor, and concomitant use of caspofungin. The predicted C0 value of tacrolimus in LT recipients increased in a dose-dependent manner when the daily dose exceeded 3 mg, whereas it decreased with age when LT recipients were older than 48 years. The predicted C0 was higher when recipients and donors had the genotype CYP3A5*3*3 than when they had the genotype CYP3A5*1. The predicted C0 value also increased with the use of caspofungin or Wuzhi capsule.Conclusion and relevanceThe established ANN model can be used to predict the C0 value of tacrolimus in LT recipients with high accuracy and good predictive ability, serving as a reference for personalized treatment in the early stage after liver transplantation.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-10T04:47:44Z
  DOI: 10.1177/10600280231190943
Comparison of Early Versus Late Adjunctive Vasopressin and Corticosteroids
in Patients With Septic Shock
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  Authors: Abdulmajeed M. Alshehri, Mary P. Kovacevic, Kevin M. Dube, Kenneth E. Lupi, Jeremy R. DeGrado
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  BackgroundVasopressin (VP) and hydrocortisone (HC) have been shown to improve outcomes in patients with septic shock. However, there is very little literature addressing the impact of the timing of the combination.ObjectiveThis study was conducted to evaluate the impact of early versus late initiation of both VP and HC on time to shock reversal in septic shock patients.MethodsThis was a retrospective study conducted at a tertiary academic medical center. Data were collected from system-generated reports, which were used to identify patients with septic shock who were admitted to an intensive care unit (ICU) and received both VP and HC. The primary endpoint was time to shock reversal. Patients were divided into the “early” group if both VP and HC were initiated within 12 hours of vasopressor initiation or into the “late” group if either VP or HC (or both agents) were initiated after 12 hours of vasopressor initiation.ResultsA total of 122 patients were included in the analysis. Early initiation was associated with a shorter time to shock reversal (34 hours vs 65 hours; P = 0.012) compared to late initiation. There were no differences in ICU length of stay, mortality, the number patients requiring renal replacement therapy, or the duration of mechanical ventilation in either group.Conclusion and relevanceOur study addressed a major gap in the literature and suggests that adding the combination of VP and HC within 12 hours of septic shock may be associated with improved patient outcomes.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-05T10:49:51Z
  DOI: 10.1177/10600280231191131
Agreement Between Two-Concentration and One-Concentration Area Under the
Curve (AUC) Estimates When Using Bayesian Modeling to Dose Vancomycin in
Patients With Obesity
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  Authors: Elizabeth W. Covington, Addison M. Watkins
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Vancomycin Bayesian modeling provides 24-hour area under the curve (AUC24) estimations. However, the agreement between two-concentration and one-concentration Bayesian estimates in patients with obesity is unknown.Objective:The purpose of this study was to determine the agreement between two-concentration and one-concentration Bayesian AUC24 estimates in patients with obesity receiving vancomycin.Methods:This retrospective within-subjects cohort study included patients with obesity and two vancomycin concentrations. The first concentration was hidden from dosing software to record the one-concentration AUC24. AUC24 estimates were categorized into 1 of 3 groups: 600 mg*h/L. Patients were excluded for vancomycin duration less than 48 hours or renal dysfunction. The primary outcome was AUC24 agreement with two versus one concentration. Secondary outcomes included the AUC24 category, matching of AUC24 categorization, and correlation between two-concentration versus one-concentration AUC24. AUC24 estimate agreement was assessed by Bland Altman plot and bias via linear regression. Statistical analyses were performed using SPSS (version 20.0).Results:A total of 31 patients were included. The mean difference in AUC24 between two versus one concentration was 11.4 mg*h/L (95% limits of agreement = −72 to 95 mg*h/L). Linear regression indicated the presence of proportional bias at higher AUC24 values (β = 0.16; P = 0.015). Matching of AUC24 categorization with two versus one concentration was 87% (27/31 patients).Conclusion and Relevance:This study demonstrated overall agreement between AUC24 estimates when using two versus one vancomycin concentration in patients with obesity, though proportional bias was detected at higher AUC24. Future studies with larger sample sizes are needed to confirm these results.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-05T10:47:47Z
  DOI: 10.1177/10600280231190910
Daptomycin Plus Oxacillin for Persistent Methicillin-Susceptible
Staphylococcus aureus Bacteremia
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  Authors: Wesley D. Kufel, Zoey Zagoria, Bruce E. Blaine, Jeffrey M. Steele, Rahul Mahapatra, Kristopher M. Paolino, Stephen J. Thomas
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection.Objective:We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB.Methods:This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation.Results:Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively.Conclusions and Relevance:D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-05T10:26:31Z
  DOI: 10.1177/10600280231189888
The Impact of SGLT2 Inhibitors on Cardiovascular Outcomes in Patients With
Heart Failure With Preserved Ejection Fraction
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  Authors: Jessica A. Starr, Nathan A. Pinner
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  ObjectiveTo evaluate the role of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with preserved ejection fraction (HFpEF).Data sourcesA literature search of PubMed, the Cochrane Library, and Google Scholar databases (January 2015 to June 20, 2023) was performed with keywords: sodium-glucose co-transporter 2 inhibitors OR SGLT2 inhibitors OR bexagliflozin OR canagliflozin OR dapagliflozin OR empagliflozin OR ertugliflozin OR sotagliflozin AND heart failure OR heart failure with preserved ejection fraction, and terms related to CV outcomes including cardiovascular death, hospitalization, hospitalization for heart failure, mortality, death, and major adverse cardiovascular event (MACE).Study selection and data extractionThe reference list from retrieved articles as well as relevant review articles was considered. Pivotal randomized controlled trials and meta-analyses with a primary or secondary end point of CV death or heart failure hospitalization were included. Studies conducted solely in a diabetic patient population were excluded.Data synthesisDapagliflozin and empagliflozin, in a broad population of heart failure patients including, HFrEF, HFmrEF, HFpEF, and without diabetes, have shown consistent improvement in the combined outcome of CV death and hospitalization for heart failure (HR 0.80, 95% CI 0.73-0.87) and in the reduction of heart failure hospitalizations (HR 0.74, 95% CI 0.67-0.83). In patients with HFpEF, cardiovascular mortality was not demonstrated (HR 0.88, 95% CI 0.77-1.00). Rates of adverse events were low.Relevance to patient care and clinical practicePatients with HFpEF and NYHA class II-III with frequent symptoms or hospitalizations for heart failure derive the most benefit from SGLT2 inhibitors with an overall goal of a reduction in heart failure hospitalizations.ConclusionsThe treatment of HFpEF has made progress, but there is still work to be done. Now, SGLT2 inhibitor therapy can be used to further help with symptom control and reduce overall hospitalizations for heart failure.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-08-05T10:24:11Z
  DOI: 10.1177/10600280231189508
Dosing and Administration Strategies of Tocilizumab in Patients With
COVID-19: A Retrospective Cohort Analysis
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  Authors: Taylor D. Steuber, Thomas Rosandich, Tiffany Cadwallader, Lauren Steil, Madeline Belk, Usha Yendrapalli, Ali Hassoun, Jonathan Edwards
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Tocilizumab may reduce the risk of death, length of stay, and time of mechanical ventilation in patients hospitalized with COVID-19. Limited data are available evaluating low-dose subcutaneous administration of tocilizumab in this setting.Objective:To compare outcomes of 2 tocilizumab dosing and administration strategies in patients hospitalized with COVID-19.Methods:A retrospective, observational cohort study was conducted to compare clinical outcomes in patients hospitalized with COVID-19 receiving tocilizumab 400 mg intravenously (400 mg IV) or 162 mg subcutaneously (162 mg SC). Hospitalized patients receiving a single dose of tocilizumab were eligible for inclusion and grouped by dosing and administration strategy. The primary endpoint was ventilator-free days at day 28. Secondary endpoints included length of stay (LOS), intensive care unit (ICU) LOS, mechanical ventilation required after dose, 28-day readmission, 28-day mortality, and change in inflammatory markers.Results:A total of 303 patients were included, with 147 who received tocilizumab 400 mg IV and 156 who received 162 mg SC. There was no significant difference in average ventilator-free days at day 28 in patients receiving 400 mg IV compared with 162 mg SC (26.4 ± 5.3 vs 25.6 ± 6.8 days, respectively; P = 0.812). There was also no difference in LOS (10.4 ± 12.6 vs 10.5 ± 14.0 days; P = 0.637), ICU LOS (3.9 ± 9.0 vs 3.5 ± 8.3 days; P = 0.679), mechanical ventilation after dose (15.6% vs 19.2%; P = 0.412), 28-day readmission (6.1% vs 9.6%; P = 0.268), or 28-day mortality (23.1% vs 25.6%; P = 0.611). Finally, there was no difference regarding change in inflammatory markers at 48 hours (P> 0.05 for all interactions).Conclusion and Relevance:In this retrospective study involving hospitalized patients with COVID-19, there was no difference between tocilizumab 162 mg SC and 400 mg IV in terms of efficacy. The 162 mg SC dose may be a reasonable alternative to traditional doses.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-31T12:19:50Z
  DOI: 10.1177/10600280231190401
Incretin Analogs for Weight Management in Adults Without Diabetes
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  Authors: Alison Lobkovich, Pramodini Kale-Pradhan, Melissa Lipari
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:This is a narrative review of incretin analogs and their effect on weight management in adult without diabetes.Data Sources:Randomized controlled trials were identified by English language. PubMed/MEDLINE, Scopus, and Embase databases were searched from inception through June 2023 to identify all pertinent trials reporting outcomes on efficacy and safety search using the terms: tirzepatide, semaglutide, liraglutide, and obesity.Study Selection and Data Extraction:Selected studies were included if the study population was composed of adults without diabetes being treated by glucagon-like peptide 1 (GLP-1) receptor agonists or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists for weight management, and weight loss was assessed as a primary outcome.Data Synthesis:Fifteen studies involving 3 pharmacotherapies (liraglutide, semaglutide, and tirzepatide) were identified. Efficacy data supporting the use of these agents for weight management were promising when compared to placebo and/or other behavioral therapies. Percent weight loss ranged from 5.7% to 11.8%, 14.9% to 17.4%, and 15% to 20.9% for liraglutide, semaglutide, and tirzepatide, respectively. Safety data were relatively similar across all trials and identified gastrointestinal adverse effects as most common.Relevance to Patient Care and Clinical Practice:Glucagon-like peptide 1 agonists are preferred for overweight or obese patients by the American Gastroenterological Association. Future guidelines may address tirzepatides’ place in therapy as new evidence comes forth. Providers should consider patient-specific factors such as cost, adverse effects, drug interactions, and comorbidities when prescribing these agents and provide education regarding the need for concurrent diet and exercise modifications.Conclusions:All incretin analogs in this review are superior to placebo when used for weight management in adults without diabetes.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-31T11:22:55Z
  DOI: 10.1177/10600280231190089
A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic
Anemia in the FDA Adverse Event Reporting System
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  Authors: Linlin Tang, Chuanhua Ding, Hongying Li, Xueheng Zhou, Guoqiang Yin
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance.Objective:This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods:We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term “anaemias haemolytic immune” according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR).Results:There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children.Conclusions:Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-31T11:20:33Z
  DOI: 10.1177/10600280231189897
Risk Stratification for Supratherapeutic Peak Anti-Xa Levels in Adult
Patients on Therapeutic Enoxaparin
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  Authors: Shane A. Sheredy, Andrew C. Stone, Ahmad M. Mostafavifar, Lisa G. Mostafavifar, Rachel M. Smith, Bruce A. Doepker
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The American Society of Hematology Guidelines for the management of venous thromboembolism recommend against the use of anti-Xa monitoring for assessing enoxaparin dosing based on a low level of evidence associating supratherapeutic levels with an increased risk of bleeding. However, institutions still utilize anti-Xa levels in select patient populations with altered volume of distribution and/or excretion to monitor and adjust therapy.Objective:The primary objective of this study was to identify risk factors associated with supratherapeutic peak anti-Xa levels (≥1.10 IU/mL) for patients receiving therapeutic enoxaparin.Methods:This was a retrospective single-center study performed at an academic tertiary care hospital. Patients who received enoxaparin at 1 mg/kg twice daily and peak anti-Xa monitoring were separated into supratherapeutic and therapeutic/subtherapeutic cohorts.Results:A total of 436 patients were screened, and 215 were included, with a mean age of 62 years. There were 108 in the therapeutic/subtherapeutic cohort and 107 in the supratherapeutic cohort. Acute kidney injury (AKI), body mass index (BMI), weight, female sex, intensive care unit (ICU) service, Sequential Organ Failure Assessment (SOFA) score ≥4, and creatinine clearance at the time of peak anti-Xa level collection were associated with supratherapeutic anti-Xa levels in univariate models. Adjusted logistic regression models were created and identified BMI in the 30 to 34.9 kg/m2 (odds ratio [OR] 4.35; 95% confidence interval [CI] 1.70-11.13, P < 0.005) and ≥35 kg/m2 (OR 6.75; 95% CI 3.05-14.94, P < 0.005) and AKI (OR 2.62; 95% CI 1.04-6.62, P = 0.042) as significant risk factors for supratherapeutic anti-Xa levels.Conclusion and Relevance:Our study identified BMI ≥ 30 kg/m2, AKI, female sex, ICU service, SOFA score ≥4, and creatinine clearance as risk factors for supratherapeutic anti-Xa levels in patients receiving 1 mg/kg twice daily dosing of enoxaparin. Further research should be done to provide evidence for the association between anti-Xa levels and bleeding risk.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-29T11:56:47Z
  DOI: 10.1177/10600280231189488
Efficacy and Safety of Immune Checkpoint Inhibitors Combined With
Chemotherapy as First-line Treatment for Recurrent or Metastatic
Nasopharyngeal Carcinoma: A Network Meta-analysis of Randomized Controlled
Trials
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  Authors: Hong Sun, Fengjiao Bu, Ling Li, Xiuwen Zhang, Xiu Xin, Jingchao Yan, Taomin Huang
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  BackgroundDifferent clinical trials for recurrent or metastatic nasopharyngeal carcinoma have studied different combinations of immuno-oncology in first-line treatment, but the optimal choice has not been determined.ObjectiveTo systematically examine and compare the efficacy and safety of different immune checkpoint inhibitors (ICIs) combined with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma.MethodsSeveral electronic databases were systematically searched up to February 2023. Articles meeting the inclusion criteria were included.ResultsThree RCTs were eligible in the study. Compared with placebo plus gemcitabine-cisplatin (GP), toripalimab plus GP (HR = 0.59, 95% CI: 0.37-0.95) was significantly associated with a better OS. Tislelizumab plus GP generated best progression-free survival (PFS) benefit (HR = 0.50, 95% CI: 0.37-0.67), greatest improvement in 1-year PFS rate (RR = 3.00, 95% CI: 1.84-5.22), and objective response rate (ORR) (RR = 1.26, 95% CI: 1.04-1.53) over the placebo plus GP. Furthermore, tislelizumab plus GP appeared to be safer than toripalimab plus GP and camrelizumab plus GP in terms of adverse events (AEs)-grade ≥3, treatment-related AEs (TRAEs)-grade ≥3, serious AEs (SAEs), treatment-related SAEs (TRSAEs), and AEs leading to discontinuation of treatment.Conclusion and RelevanceIn recurrent or metastatic nasopharyngeal carcinoma, programmed death 1 (PD-1) inhibitors plus GP as first-line treatment have better survival outcomes than placebo plus GP with comparable toxicity. Toripalimab plus GP shows the best OS benefit over placebo plus GP, while tislelizumab plus GP generates the best PFS, 1-year PFS rate, ORR, and safety. Tislelizumab plus GP could be the best choice among the ICIs combined with chemotherapy regimens as first-line treatment in recurrent or metastatic nasopharyngeal carcinoma.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-25T05:31:00Z
  DOI: 10.1177/10600280231188171
Pharmacist Prescribing Models for HIV Pre-exposure and Post-exposure
Prophylaxis
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  Authors: Alex J. Adams, Michael E. Klepser
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  State strategies for pharmacist prescribing exist on a continuum from most restrictive to least restrictive. Using human immunodeficiency virus (HIV) pre-exposure prophylaxis and post-exposure prophylaxis as a case study, there are 3 viable pharmacist prescribing models: (1) population-based collaborative practice agreements; (2) government protocols; and (3) standard of care prescribing. The advantages and disadvantages of these 3 models are reviewed.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-22T06:17:16Z
  DOI: 10.1177/10600280231187171
Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part
Sarcoma
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  Authors: Emilie J. Bergsma, Mariam Elgawly, David Mancuso, Roger Orr, Theresa Vuskovich, Nathan D. Seligson
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  ObjectiveThe objective was to review the pharmacology, efficacy, and safety of atezolizumab (Tecentriq) for the treatment of adult and pediatric patients aged 2 years and older with unresectable or metastatic alveolar soft part sarcoma (ASPS).Data SourcesA literature search was conducted using PubMed and MEDLINE databases, published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and May 31, 2023. Keywords included atezolizumab, Tecentriq, MPDL3280, immunotherapy, PD-L1, PD-1, pediatrics, sarcoma, and ASPS.Study selection and data extractionAll English-language studies involving atezolizumab for ASPS were included and discussed.Data synthesisAtezolizumab is an anti-programmed death-ligand 1 (PD-L1) monoclonal antibody designed to block the interaction between PD-L1 and the programmed cell death protein 1 (PD-1) receptor. Atezolizumab was granted approval by the FDA specifically for ASPS based on a phase II clinical trial in adult and pediatric patients (n = 49), which reported an overall response rate of 24% and a durable response rate at 6 and 12 months of 67% and 42%, respectively. Common grade 3/4 adverse reactions include musculoskeletal pain (8%), followed by hypertension (6%), weight gain (6%), headache (4%), and dizziness (4%).Relevance to patient care and clinical practice in comparison with existing drugsAdvanced ASPS is a high-risk disease with limited treatment options. Atezolizumab appears to be a viable treatment option in ASPS demonstrating clinical efficacy and a manageable toxicity profile.ConclusionsWith no other treatments that are FDA approved specifically for ASPS, and few demonstrating efficacy in the advanced setting, the approval of atezolizumab, including the first approval for pediatric patients, represents a landmark improvement to the therapeutic arsenal against this rare disease.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-19T10:30:50Z
  DOI: 10.1177/10600280231187421
Hydroxyurea-Associated Relapsing Polychondritis in a Patient With
Myeloproliferative Neoplasm
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  Authors: İrfan Yavaşoğlu, Atakan Turgutkaya, Ali Zahit Bolaman
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-07T05:12:12Z
  DOI: 10.1177/10600280231180197
Association of Argatroban Dose With Coagulation Laboratory Test in
Patients on Extracorporeal Membrane Oxygenation: Activated Clotting Time
vs Activated Partial Thromboplastin Time
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  Authors: Hyun-Young Ahn, Yuju Jung, Tae Wan Kim, Yang Hyun Cho, Jeong Hoon Yang, Chi Ryang Chung, Myung-Sook Min, Ryoung-Eun Ko
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Only some studies have directly compared and analyzed the roles of activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in coagulation monitoring during argatroban administration.Objectives:This study aims to assess the correlation of argatroban dose with ACT and aPTT values and to identify the optimal coagulation test for argatroban dose adjustment.Methods:We evaluated 55 patients on extracorporeal membrane oxygenation (ECMO) who received argatroban for more than 72 hours. The correlation between argatroban dose and aPTT and ACT values was evaluated. To compare argatroban dose and bleeding events according to liver dysfunction, the patients were divided into 2 groups based on alanine aminotransferase and total bilirubin.Results:Among the 55 patients, a total of 459 doses and coagulation tests were evaluated. The aPTT and ACT values showed a weak correlation with argatroban dose, with the Pearson correlation coefficients of 0.261 (P < 0.001) and 0.194 (P = 0.001), respectively. The agreement between the target 150 to 180 seconds for ACT and 55 to 75 seconds for aPTT was observed in 140 patients (46.1%). Twenty-four patients (43.6%) had liver dysfunction when they started argatroban. The median argatroban dose was lower in the liver dysfunction group than in the control group (0.094 mcg/kg/min vs 0.169 mcg/kg/min, P = 0.020). Difference was not observed between the 2 groups in the amount of red blood cell (0.47 vs 0.43 pack, P = 0.909) and platelet (0.60 vs 0.08 pack, P = 0.079) transfusion per day.Conclusion and Relevance:A weak correlation was observed between argatroban dose and the aPTT and ACT values. However, the agreement between aPTT and ACT was only 46.1% regarding the scope of target range. Further research is necessary to determine how to assess the optimal argatroban dose for patients administered argatroban while undergoing ECMO at the intensive care unit.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-07-04T05:32:00Z
  DOI: 10.1177/10600280231183510
A Review of Topical Sirolimus for the Treatment of Facial Angiofibromas in
Tuberous Sclerosis Complex
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  Authors: Diem-Phuong D. Dao, Jessica N. Pixley, Zeynep M. Akkurt, Steven R. Feldman
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:This article assesses the efficacy, safety, pharmacology, and clinical applications of topical sirolimus 0.2% gel for the treatment of tuberous sclerosis complex (TSC)–associated facial angiofibromas.Data sources:A review of the literature was conducted using the Medline (PubMed) and EMBASE databases using the keywords topical sirolimus, rapamycin, Hyftor, and tuberous sclerosis.Study selection and data extraction:Articles written in English and relevant to the topic were included.Data synthesis:In the phase 2 trial, the mean improvement factor, a composite measure of improved tumor size and redness, was achieved in all patient groups (P < 0.001) with significant responses among the adult and pediatric subgroups at week 12. There were no serious adverse events recorded. In the phase 3 trial, 60% of participants responded to treatment in the sirolimus group compared with 0% in the placebo group with different response rates between the adult and pediatric subgroups at week 12. Sirolimus gel had no serious adverse events, and dry skin was the most common adverse reaction. Patients who had completed the 12-week trials were then enrolled in a long-term trial; angiofibromas had response rates of 78.2% to 0.2% sirolimus gel.Relevance to patient care and clinical practice in comparison to existing drugs:Topical sirolimus 0.2% is a first-in-class, newly Food and Drug Administration (FDA)–approved, mammalian target of rapamycin (mTOR) inhibitor that is a promising and safe, noninvasive alternative to surgical procedures for TSC-associated angiofibromas.Conclusions:Topical sirolimus 0.2% gel is a moderately effective treatment for TSC-associated facial angiofibromas with an adequate safety profile.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-30T06:26:58Z
  DOI: 10.1177/10600280231182421
Pembrolizumab-Induced Axial Spondyloarthritis
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  Authors: Prashant Kaushik, Stephen Bastible, Mark Bannon, C. Drew Williams
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-27T05:12:03Z
  DOI: 10.1177/10600280231181400
Latency Antibiotics in Preterm Prelabor Rupture of Membranes: A Comparison
of Azithromycin Regimens
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  Authors: Kimberly N. Day, Julie A. Vircks, Christine E. Henricks, Kaci M. Reaves, Ashley K. Holmes, Karen L. Florio
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Treatment with antibiotics at the time of preterm prelabor rupture of membranes (PPROM) has been shown to prolong pregnancy. Due to the recurrent shortage of erythromycin, azithromycin has been substituted in the traditional regimen; however, there are little data on optimal dosing.Objective:The objective of this study was to determine whether there is a difference in latency from onset of PPROM to delivery in patients who received a single dose of azithromycin compared with a 5-day course.Methods:This was a single-center, multisite, retrospective, IRB approved analysis of patients admitted with a diagnosis of PPROM. Patients were included if rupture occurred between 22 0/7 and 33 6/7 weeks of gestation and received either a single dose or a 5-day course of azithromycin along with a beta lactam.Results:A total of 376 patients were reviewed with 296 patients included in the final analysis. There was no statistical difference in the primary outcome of latency days in patients who received the 5-day versus the single-dose course (4 vs 5 days, P = 0.641). There was a significantly higher rate of histologic chorioamnionitis in the single-dose course of azithromycin (46.4% vs 62.6%, P = 0.006).Conclusions and Relevance:There was no difference in latency for patients who received a 5-day course of azithromycin versus a single dose for the treatment of PPROM. A higher rate of histologic chorioamnionitis was observed in those who received the single-day course. Prospective follow-up studies are needed to confirm these findings.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-26T07:06:10Z
  DOI: 10.1177/10600280231181135
Safety and Effectiveness of a Standardized Intravenous Insulin Infusion
Order Set for Managing Uncontrolled Hyperglycemia Outside the Intensive
Care Unit
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  Authors: Francisco Ibarra
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Few studies have evaluated the administration of intravenous (IV) insulin infusions for uncontrolled hyperglycemia in non-intensive care unit (ICU) patients, and there is inadequate data to guide how to appropriately administer IV insulin infusions to this patient population.Objective:Determine the effectiveness and safety of our institution’s non-critical care IV insulin infusion order set.Methods:This retrospective study was conducted at 2 institutions within a health care system. The primary outcome was the number of individuals who achieved a glucose level ≤180 mg/dL. For those meeting this endpoint, the time to achieving this outcome and the percentage of glucose checks within the goal range were determined. The primary safety endpoint was the number of individuals who experienced hypoglycemia (glucose level
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-26T07:03:13Z
  DOI: 10.1177/10600280231178876
Choosing Systemic Agents for Psoriasis
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  Authors: Christina Kontzias, Rithi Chandy, Steven R. Feldman
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Treatment options for moderate-to-severe psoriasis depend on drug efficacy and safety, patient preferences, comorbidities, and cost—no drug dominates across all dimensions. Interleukin (IL)-17 inhibitors may be preferred for fast-acting treatment, while the 3-month schedule of risankizumab, ustekinumab, or tildrakizumab may be attractive for patients who prioritize fewer injections. Phototherapy is suitable for patients who wish to avoid systemic agents or when cost is a concern. For patients with poor adherence, infliximab or tildrakizumab may be well suited as they require in-office administration. Dermatologists can educate patients on available therapies to find a regimen best suited to their needs.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-21T10:49:51Z
  DOI: 10.1177/10600280231170031
Deucravacitinib: The First FDA-Approved Oral TYK2 Inhibitor for Moderate
to Severe Plaque Psoriasis
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  Authors: Thu Minh Truong, Gaurav N. Pathak, Amit Singal, Viktoriia Taranto, Babar K. Rao
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  ObjectiveThe objective of this study was to review the safety and efficacy of deucravacitinib, a tyrosine kinase 2 (TYK2) inhibitor for moderate to severe plaque psoriasis.Data SourcesLiterature was reviewed from MEDLINE and Clinicaltrials.gov up to December 2022 using the terms “deucravacitinib” and “BMS-986165.”Study SelectionRelevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of deucravacitinib were included. A total of 6 trial results were included.Study Selection and Data ExtractionDeucravacitinib showed clinical efficacy across all the phase II and III clinical trials. Excluding the long-term extension study, there were 2248 subjects across all studies, with 63.2% of patients receiving deucravacitinib 6 mg daily. Of these subjects, the average proportion achieving a PASI 75 (a reduction of greater than 75% in the Psoriasis Area and Severity Index) at week 16 was 65.1%. Patients receiving deucravacitinib 6 mg once daily had a higher rate of achieving both PASI 75 response and a Static Physician’s Global Assessment (sPGA) score of 0 or 1, compared with oral apremilast 30 mg twice daily. The safety profile of deucravacitinib includes mild adverse events (AEs), most commonly nasopharyngitis, with serious AEs reported ranging from 1.35% to 9.5%.Relevance to Patient Care and Clinical Practice in Comparison With Existing MedicationsWhile many available therapies for moderate to severe plaque psoriasis rely on an injectable dosage form or extensive monitoring, deucravacitinib can potentially reduce patient medication-related burden. This review summarizes the efficacy and safety of oral deucravacitinib for the treatment of severe plaque psoriasis.ConclusionDeucravacitinib shows a consistent efficacy and safety profile as the first oral TYK2 inhibitor approved for adult patients with moderate to severe plaque psoriasis who are eligible for systemic therapy or phototherapy treatment.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-21T10:49:45Z
  DOI: 10.1177/10600280231153863
Physical and Chemical Compatibility of Medications Commonly Used in
Critically Ill Patients With Balanced Crystalloids: A Systematic Review
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  Authors: Christopher T. Buckley, Julie E. Farrar, Mary Schleicher, Joanna L. Stollings, Abhijit Duggal, Seth R. Bauer
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:Evaluate available evidence of physical and/or chemical compatibility of commonly used medications in critically ill patients with balanced crystalloids.Data sources:Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were queried from inception to September 2022.Study selection and data extraction:This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language studies reporting physical and/or chemical compatibility data between 50 selected medications and balanced crystalloids were included. A previously designed tool to assess risk of bias was adapted for use.Data synthesis:Twenty-nine studies encompassing 39 (78%) medications and 188 unique combinations with balanced crystalloids were included. Combinations included 35 (70%) medications with lactated Ringer’s, 26 (52%) medications with Plasma-Lyte, 10 (20%) medications with Normosol, and one (2%) medication with Isolyte. Studies commonly evaluated physical and chemical compatibility (55.2%). More medications were evaluated via Y-site than admixture. Incompatibilities were identified in 18% of combinations comprising 13 individual drugs.Relevance to patient care and clinical practice:This systematic review evaluates the compatibility of select critical care medications with balanced crystalloid solutions. Results may be used as a tool to guide clinicians on balanced crystalloid compatibility, potentially increasing ubiquitous use and reducing patient exposure to normal saline.Conclusion and relevance:Data are limited regarding chemical/physical compatibility of commonly used medications in critically ill patients with balanced crystalloids. Additional compatibility studies are warranted, particularly methodologically rigorous studies assessing Plasma-Lyte, Normosol, and Isolyte. Of the evaluated medications, there was a low frequency of incompatibilities with balanced crystalloids.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-21T09:19:09Z
  DOI: 10.1177/10600280231179999
Influence of Weight and Body Size on the Pharmacokinetics of Heart Failure
Pharmacotherapy: A Systematic Review
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  Authors: Jessica Hindi, Myriam Fréchette-Le Bel, Jean Lucien Rouleau, Simon de Denus
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To conduct a review of studies evaluating the influence of body size and weight (WT) on the pharmacokinetics (PK) of drugs recommended for heart failure (HF) treatment.Data Sources:A systematic search of the MEDLINE (1946 to April 2023) and EMBASE (1974 to April 2023) databases was conducted for articles that focused on the impact of WT or body size on the PK of drugs of interest used in HF patients.Study Selection and Data Extraction:Articles written in English or French related to the aim of our study were retained for analysis.Data Synthesis:Of 6493 articles, 20 were retained for analysis. Weight was associated with the clearance of digoxin, carvedilol, enalapril, and candesartan as well as the volume of distribution of eplerenone and bisoprolol. There was no documented direct impact of WT on the PK of furosemide, valsartan, and metoprolol, although these studies were limited or confounded by the small sample size, adjustment of PK factors by WT, or the use of the Cockroff-Gault equation for the evaluation of creatinine clearance, which includes WT.Relevance to Patient Care and Clinical Practice:This review highlights and summarizes the available data on the importance of WT on the PK of HF treatment.Conclusion:Considering the significant impact of WT on most HF drugs in this review, it may be important to further investigate it in the context of personalized therapy, particularly in patients presenting extreme WTs.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-20T12:53:31Z
  DOI: 10.1177/10600280231179484
Cardiac Myosin Inhibitors: Expanding the Horizon for Hypertrophic
Cardiomyopathy Management
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  Authors: Alyssa Sykuta, Connie H. Yoon, Sarah Baldwin, Natalie I. Rine, Michael Young, Adam Smith
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review the current literature on the efficacy and safety of cardiac myosin inhibitors (CMIs) for the treatment of hypertrophic cardiomyopathy (HCM).Data Sources:A literature search was conducted on PubMed from origin to April 2023, using the search terms “MYK-461,” “mavacamten,” “CK-3773274,” and “aficamten.” Studies were limited to English-based literature, human subjects, and clinical trials resulting in the inclusion of 13 articles. ClinicalTrials.gov was also used with the same search terms for ongoing and completed trials.Study Selection and Data Extraction:Only phase II and III studies were included in this review except for pharmacokinetic studies that were used to describe drug properties.Data Synthesis:CMIs enable cardiac muscle relaxation by decreasing the number of myosin heads that can bind to actin and form cross-bridges. Mavacamten, the first Food and Drug Administration (FDA)-approved drug in this class, has been shown to improve hemodynamic, functional, and quality of life measures in HCM with obstruction. In addition, aficamten is likely to become the next FDA-approved CMI with promising phase II data and an ongoing phase III trial expected to release results in the next year.Relevance to Patient Care and Clinical Practice in Comparison with Existing Drugs:CMIs provide a novel option for obstructive hypertrophic cardiomyopathy, particularly in those not suitable for septal reduction therapy. Utilization of these agents requires knowledge of drug interactions, dose titration schemes, and monitoring parameters for safety and efficacy.Conclusions:CMIs represent a new class of disease-specific drugs for treatment of HCM. Cost-effectiveness studies are needed to delineate the role of these agents in patient therapy.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-17T05:00:09Z
  DOI: 10.1177/10600280231180000
Use of Cardioprotective Antidiabetic Medications in Adults With and
Without Cardiovascular Disease, 2015 to March 2020
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  Authors: Christina H. Sherrill, Andrew Y. Hwang
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Certain glucagon-like peptide-1 receptor (GLP-1) agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2-inhibitors) can reduce cardiovascular risk in individuals with type 2 diabetes and cardiovascular disease (CVD). However, these medications can be expensive, potentially limiting their use. Objectives: The primary objective was to characterize the use of cardioprotective GLP-1 agonists and SGLT2-inhibitors among adults with diabetes with and without CVD. The secondary objective was to investigate the association of socioeconomic factors and health care utilization with the use of these medications.Methods:Adults aged ≥20 years old with self-reported diabetes, A1c ≥6.5%, or fasting glucose ≥126 mg/dL were identified using the 2015 to March 2020 National Health and Nutrition Examination Survey. The primary outcome was the use of cardioprotective GLP-1 agonists or SGLT2-inhibitors compared in individuals with and without CVD. Secondary analyses included identification of socioeconomic factors and health care utilization associated with the use of cardioprotective antidiabetic medications, stratified by CVD status. Weighted analyses were conducted to account for the complex survey design.Results:Use of cardioprotective antidiabetic medications was higher in adults with CVD compared to those without CVD (7.8% vs. 4.6%, P = 0.02), which was driven by the use of cardioprotective SGLT2-inhibitors (4.6% versus 1.9%, P = 0.002). Lower income level and less frequent health care visits within the past year were associated with lower likelihood of using these medications.Conclusion and Relevance:Despite preferential use in individuals with diabetes and CVD, the prevalence of cardioprotective antidiabetic medication use remains relatively low. Disparities in use appear to exist based on income level and health care utilization.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-16T05:58:50Z
  DOI: 10.1177/10600280231178886
Comparison of the Efficacy and Safety of Rivaroxaban and Low Molecular
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  Authors: Shuyi Wu, Chengfu Guan, Sijie Chang, Chunhua Wang, Jinhua Zhang
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:There are few studies on using rivaroxaban and low molecular heparin (LMWH) to prevent venous thromboembolism (VTE) in hospitalized cancer patients.Objective:We conducted a retrospective study to evaluate the efficacy and safety of rivaroxaban versus LMWH for the primary prevention of VTE in inpatient cancer patients.Methods:Information on patients was collected through 6-month follow-up and medical record inquiries. Clinical outcomes included VTE, total bleeding, thrombosis, major bleeding, minor bleeding, all-cause death, and a composite endpoint of bleeding, thrombosis, and death.Results:A total of 602 hospitalized cancer patients were included in this study. During 6 months of follow-up, there were 26 VTE events (8.6%), 42 total bleeding events (7.0%), 62 all-cause deaths (10.3%), and 140 composite endpoints (23.3%). After adjusting for various confounding factors, there were no significant differences between the rivaroxaban and LMWH for VTE events (OR = 0.851, 95% CI [0.387-1.872], P=0.688), total bleeding (OR = 1.690, 95% CI [0.768-3.719], P = 0.192], thrombosis events (OR = 0.919, 95% CI [0.520-1.624], P = 0.772], major bleeding (OR = 0.276, 95% CI [0.037-2.059], P = 0.209), all-cause death (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), and composite endpoints (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), while minor bleeding (OR = 3.661 95% CI [1.000-7.083], P = 0.050) was significantly higher in the rivaroxaban than in the LMWH.Conclusions and Relevance:In thromboprophylaxis in inpatient cancer patients, rivaroxaban has a similar rate of VTE and bleeding events as LMWH. Our results may provide a reference for the clinical use of rivaroxaban to prevent VTE in hospitalized cancer patients.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-14T06:22:05Z
  DOI: 10.1177/10600280231178335
Comparison of the Effect of Intracarpal Injection of Ketorolac With
Triamcinolone in Carpal Tunnel Syndrome: A Randomized Controlled Trial
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  Authors: Afshin Karimzadeh, Hadi Esmaily, Seyed Ahmad Raeissadat, Maryam Esmaelzade, Seyed Hossein Aghamiri, Najmeh Sadat Bolandnazar
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The most prevalent entrapment neuropathy is carpal tunnel syndrome (CTS). Although nonsteroidal antiinflammatory drugs (NSAIDs) are frequently prescribed for musculoskeletal disorders, oral NSAIDs do not provide any additional benefits for CTS. Nevertheless, the use of NSAID phonophoresis has shown significant improvement, possibly due to increased concentration in the target tissue. The effects of intracarpal injection of NSAIDs on CTS have not been studied.Objective:We conducted a controlled trial to compare the efficacy of ketorolac and triamcinolone in treating CTS.Methods:Mild to moderate CTS patients were randomly assigned to receive either a local injection of 30 mg ketorolac or 40 mg triamcinolone. Patients were evaluated using visual analog scale (VAS) for pain, severity, function, electrodiagnostic findings, patient satisfaction, and any complications at the injection site, at baseline and 12 weeks after the procedures.Results:Fifty patients participated, and 43 completed the study. Both groups showed significant improvement in the VAS, severity, function, and electrodiagnostic scores at 3 months compared with the baseline. A comparison of the groups showed significant differences in VAS, severity, and function, with the improvement being significantly higher in the triamcinolone group.Conclusion and Relevance:The present study showed that injection of triamcinolone or ketorolac into the carpal tunnel relieved pain, increased function, and improved electrodiagnostic findings in patients with mild to moderate CTS. It also showed that triamcinolone was superior to ketorolac in terms of analgesic effect and resulted in greater improvement in symptom severity and function.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-06T05:38:00Z
  DOI: 10.1177/10600280231175146
Cidofovir for Viral Infections in Immunocompromised Children: Guidance on
Dosing, Safety, Efficacy, and a Review of the Literature
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  Authors: Daniel L. Riggsbee, Muayad Alali, Michelle L. Kussin
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To describe the use of cidofovir (CDV) for viral infections in immunocompromised children (IC) and provide guidance on dosing and supportive care.Data Sources:A PubMed search was conducted for literature published between 1997 and January 2022 using the following terms: cidofovir, plus children or pediatrics.Study Selection and Data Extraction:Limits were set to include human subjects less than 24 years of age receiving intravenous (IV) or intrabladder CDV for treatment of infections due to adenovirus, polyomavirus-BK (BKV), herpesviruses, or cytomegalovirus.Data Synthesis:Data were heterogeneous, with largely uncontrolled studies. Conventional dosing (CDV 5 mg/kg/dose weekly) was commonly used in 60% (31/52) of studies and modified dosing (CDV 1 mg/kg/dose 3 times/week) was used in 17% (9/52) of studies, despite being off-label. Nephrotoxicity reported across studies totaled 16% (65/403 patients), which was higher for conventional dosing 29 of 196 patients (15%) than modified dosing 1 of 27 patients (4%). Saline hyperhydration and concomitant probenecid remain the cornerstones of supportive care, while some regimens omitting probenecid are emerging to target BKV.Relevance to Patient Care and Clinical Practice:To our knowledge, this is the first comprehensive review of CDV use (indications, dosing, supportive care, response, and nephrotoxicity) in pediatric IC.Conclusions:Effective utilization of CDV in IC remains challenging. Further prospective studies are needed to determine the optimal CDV dosing; however, less aggressive dosing regimens such as modified thrice weekly dosing or low dosing once weekly omitting probenecid to enhance urinary penetration may be reasonable alternatives to conventional dosing in some IC.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-05T10:29:10Z
  DOI: 10.1177/10600280231176135
Candidemia in Adult Patients in the ICU: A Reappraisal of Susceptibility
Testing and Antifungal Therapy
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  Authors: Daniel B. Chastain, Bryan P. White, Patrick J. Tu, Sophea Chan, Brittany T. Jackson, Kara A. Kubbs, Aiman Bandali, Steven McDougal, Andrés F. Henao-Martínez, David B. Cluck
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To provide updates on the epidemiology and recommendations for management of candidemia in patients with critical illness.Data Sources:A literature search using the PubMed database (inception to March 2023) was conducted using the search terms “invasive candidiasis,” “candidemia,” “critically ill,” “azoles,” “echinocandin,” “antifungal agents,” “rapid diagnostics,” “antifungal susceptibility testing,” “therapeutic drug monitoring,” “antifungal dosing,” “persistent candidemia,” and “Candida biofilm.”Study Selection/Data Extraction:Clinical data were limited to those published in the English language. Ongoing trials were identified through ClinicalTrials.gov.Data Synthesis:A total of 109 articles were reviewed including 25 pharmacokinetic/pharmacodynamic studies and 30 studies including patient data, 13 of which were randomized controlled clinical trials. The remaining 54 articles included fungal surveillance data, in vitro studies, review articles, and survey data. The current 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Management of Candidiasis provides recommendations for selecting empiric and definitive antifungal therapies for candidemia, but data are limited regarding optimized dosing strategies in critically ill patients with dynamic pharmacokinetic changes or persistent candidemia complicated.Relevance to Patient Care and Clinical Practice:Outcomes due to candidemia remain poor despite improved diagnostic platforms, antifungal susceptibility testing, and antifungal therapy selection for candidemia in critically ill patients. Earlier detection and identification of the species causing candidemia combined with recognition of patient-specific factors leading to dosing discrepancies are crucial to improving outcomes in critically ill patients with candidemia.Conclusions:Treatment of candidemia in critically ill patients must account for the incidence of non-albicans Candida species and trends in antifungal resistance as well as overcome the complex pathophysiologic changes to avoid suboptimal antifungal exposure.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-05T10:25:10Z
  DOI: 10.1177/10600280231175201
Hepatorenal Syndrome With Acute Kidney Injury: Diagnosis and Medical
Management
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  Authors: Brian L. Erstad
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objectives:To review the current definitions and diagnostic criteria for acute kidney injury (AKI) and type 1 hepatorenal syndrome (HRS) now termed HRS-AKI and discuss the challenges in deciding the most appropriate medication regimens to treat patients with HRS-AKI.Data sources:PubMed (inception to April 2023) with bibliographies of retrieved articles searched for additional articles; organizational websites for clinical practice guidelines (CPGs).Study selection and data extraction:Randomized controlled trials (RCTs) evaluating albumin and vasoconstrictors for HRS-AKI.Data synthesis:A major change in the most recent revision of definitions and diagnostic criteria for HRS-AKI is the elimination of the set cutoff serum creatinine values for AKI. This change should be considered when comparing studies of HRS-AKI over time. Albumin has been administered to both vasoconstrictor treatment and placebo groups in all recent RCTs; however, there has never been a large RCT evaluating a no-albumin group. Most prospective trials comparing a midodrine/octreotide combination or norepinephrine to placebo or terlipressin have enrolled less than 100 patients limiting any conclusions regarding clinically important outcomes. Terlipressin with albumin has shown mixed results for complete HRS-AKI reversal with no reductions in crude mortality but adverse effect concerns involving ischemic and pulmonary events.Relevance to patient care and clinical practice:Type 1 hepatorenal syndrome with acute kidney injury is a potentially life-threatening syndrome with diagnostic and treatment challenges. Albumin plus a vasoconstrictor has become the routine HRS-AKI treatment even though there has not been a large RCT evaluating a no-albumin group. Terlipressin is the vasoconstrictor of choice for HRS-AKI in current CPGs, but it has adverse effect concerns and, until recently, was not available in the United States.Conclusions:In conjunction with changes in the definitions and diagnostic criteria for HRS-AKI, debate continues regarding the optimal therapy for HRS-AKI, particularly considering recent trials demonstrating ischemic and pulmonary adverse events with terlipressin used in combination with albumin.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-05T04:55:07Z
  DOI: 10.1177/10600280231177698
Sodium Phenylbutyrate and Taurursodiol: A New Therapeutic Option for the
Treatment of Amyotrophic Lateral Sclerosis
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  Authors: Ali Alqallaf, Drew W. Cates, Kandon P. Render, Katie A. Patel
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review the safety and efficacy of sodium phenylbutyrate and taurursodiol (SP + T) in slowing progression of amyotrophic lateral sclerosis (ALS) compared with pre-existing therapies.Data Sources:A PubMed (from January 1, 2009, to April 13, 2023) and ClinicalTrials.gov search conducted using sodium phenylbutyrate, taurursodiol, AMX0035, riluzole, and edaravone. Additional articles were identified by hand from references.Data Selection and Data Extraction:This included English-language articles evaluating SP + T efficacy or safety in humans for decreasing neuronal death and slowing the progression of ALS.Data Synthesis:In one phase II clinical trial that encompassed an open-label extension phase, disease severity, assessed by the rate of decline in overall score on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised with higher scores indicating more functional ability, was –1.24 points per month with active drug and –1.66 points per month with placebo (difference, 0.42 points per month; 95% CI, 0.03-0.81; P = 0.03). Post hoc analysis found survival benefit of median 4.8 months with active medication compared with placebo.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:SP + T is a new US Food and Drug Administration–approved oral suspension for the treatment of ALS. Patients who received active medication through the phase II trial showed decreased rates of disease progression. Overall, SP + T could be considered a potential agent for the treatment of ALS which has a high unmet need.Conclusion:SP + T is an option for the treatment of ALS; however, additional data regarding efficacy in phase III trials with long-term safety profile considerations, as well as trials to compare current therapy with SP + T, are needed.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-06-03T10:46:22Z
  DOI: 10.1177/10600280231172802
The Impact of Midodrine Tapering Versus Nontapering Regimens on the
Clinical Outcomes of Critically Ill Patients: A Retrospective Cohort Study
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  Authors: Jawaher Gramish, Ahmed Hattan, Ohoud Aljuhani, P. J. Parameaswari, Shaden Alshehri, Ghazwa B. Korayem, Hadeel Alkofide, Mai Alalawi, Ramesh Vishwakarma, Yazed Saleh Alsowaida, Rahaf Alqahtani, Luluh Binorayir, Mohammed Abutaleb, Alanoud Alotaibi, Majidah Aljohani, Sarah Aljohani, Sana Samreen, Suad Jawhari, Raghad Alanazi, Khalid A. Al Sulaiman
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine.Objectives:To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients.Methods:A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation.Results:The incidence of inotropes or vasopressors’ re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay.Conclusion and Relevance:These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-30T05:09:41Z
  DOI: 10.1177/10600280231173290
Reply: Drugs That Interact With Colchicine Via Inhibition of Cytochrome
P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database
of Spontaneously Reported Adverse Events (FAERS)
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  Authors: Daniel C. Malone, Ainhoa Gómez-Lumbreras, Richard D. Boyce, Lorenzo Villa-Zapata, Malinda S. Tan, Philip D. Hansten, John Horn
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-27T09:46:50Z
  DOI: 10.1177/10600280231168860
Comment: Evaluation of Response to High—Dose Intravenous Vitamin K
Administration
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  Authors: Brian W. Gilbert
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-26T10:06:29Z
  DOI: 10.1177/10600280231174896
Reply: Evaluation of Response to High-Dose Intravenous Vitamin K
Administration
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  Authors: April R. Chapman, Jason R. Yerke, Michael A. Rudoni, Mollie Lumpkin, Michael Militello, Lu Wang, Stephanie N. Bass
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-26T10:03:29Z
  DOI: 10.1177/10600280231174893
Comment on: Drugs That Interact With Colchicine via Inhibition of
Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using
a Database of Spontaneously Reported Adverse Events (FAERS)
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  Authors: Yoshihiro Noguchi, Miao Yan, Tomoaki Yoshimura
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-26T09:59:59Z
  DOI: 10.1177/10600280231168858
Evaluation of Goal Phenytoin Levels After an Initial Intravenous Loading
Dose at an Academic Medical Center
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  Authors: Christine S. Kim, Lena K. Tran, Melanie Z. Goodberlet, Paul M. Szumita, Kaylee K. Marino
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Phenytoin intravenous loading doses are administered in status epilepticus to rapidly achieve therapeutic levels. Accurately assessing phenytoin levels after the initial load can be challenging because of its complex pharmacokinetic profile and nonstandardized weight-based loading doses.Objectives:The objectives of this analysis were to determine the incidence of patients achieving goal phenytoin levels after the initial loading dose and characterize factors that contribute to achieving the goal level.Methods:This single-center, retrospective cohort analysis was approved by our institutional review board and included adult patients who received a phenytoin load from May 2016 to March 2021. Patients were excluded if no total phenytoin level was drawn within 24 hours of the load, if the maintenance dose was given before the first level was drawn, or if the patient was on phenytoin before the load. The major endpoint was the percentage of patients achieving a corrected goal phenytoin level of ≥10 mcg/mL after the initial load. Multivariate regression was used to determine predictors of achieving the goal phenytoin level.Results:Of the 152 patients included, 139 patients (91.4%) achieved a corrected goal level after the first load. Patients at goal received a significantly higher median weight-based loading dose (19.1 mg/kg [15.0-20.0] vs 12.6 mg/kg [10.1-15.0], P < 0.01). The multivariate analysis identified weight-based dosing as a statistically significant predictor of achieving the corrected goal level (odds ratio, 1.30; 95% CI, 1.12-1.53; P < 0.01).Conclusion and Relevance:Most patients achieved a corrected goal phenytoin level after the initial load. A higher median weight-based loading dose was shown to be a predictor of achieving the goal level and should be encouraged for rapid seizure termination. Future studies are warranted to confirm patient-specific factors that affect rapid achievement of the goal phenytoin level.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-26T05:27:49Z
  DOI: 10.1177/10600280231174570
Risk of Acute Kidney Injury Based on Vancomycin Target Trough Attainment
Strategy: Area-Under-the-Curve-Guided Bayesian Software, Nomogram, or
Trough-Guided Dosing
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  Authors: Joshua M. Knight, Tomona Iso, Katherine K. Perez, Joshua T. Swan, Charles E. Janak, Judy O. Ikwuagwu, William L. Musick
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Guidelines support area-under-the-curve (AUC) monitoring for vancomycin dosing which may lower overall doses and reduce acute kidney injury (AKI).Objective:The aim of this study was to compare incidence of AKI across 3 vancomycin dosing modalities: AUC-targeted Bayesian pharmacokinetic software, AUC-targeted empiric dosing nomogram, and trough-guided dosing using clinical pharmacists’ judgment.Methods:This retrospective study included adult patients with a pharmacy dosing consult who received ≥1 dose of vancomycin and ≥1 serum vancomycin level documented between January 1, 2018, and December 31, 2019. Patients with baseline serum creatinine ≥2 mg/dL, weight ≥100 kg, receiving renal replacement therapy, AKI prior to vancomycin therapy, or vancomycin ordered only for surgical prophylaxis were excluded. The primary analysis was incidence of AKI adjusted for baseline serum creatinine, age, and intensive care unit admission. A secondary outcome was adjusted incidence of an abnormal trough value (20 μg/mL).Results:The study included 3459 encounters. Incidence of AKI was 21% for Bayesian software (n = 659), 22% for the nomogram (n = 303), and 32% for trough-guided dosing (n = 2497). Compared with trough-guided dosing, incidence of AKI was lower in the Bayesian (adjusted odds ratio [OR] = 0.72, 95% confidence interval [CI]: 0.58-0.89) and the nomogram (adjusted OR = 0.71, 95% CI: 0.53-0.95) groups. Compared with trough-guided dosing, abnormal trough values were less common in the Bayesian group (adjusted OR = 0.83, 95% CI: 0.69-0.98).Conclusion and Relevance:Study results suggest that use of AUC-guided Bayesian software reduces the incidence of AKI and abnormal trough values compared with trough-guided dosing.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-05T11:34:18Z
  DOI: 10.1177/10600280231171373
Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the
FAERS Database
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  Authors: Viraaj Pannu, Ndausung Udongwo, Steven Imburgio, Anmol Johal, Anton Mararenko, Helen Pozdniakova, Tasnuva Amin, Swapnil Patel, Mohammad Hossain, Arman Mushtaq, Edward Liu, Jose M. Fune, Joseph Heaton
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo.Objective:Our study’s aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19.Method:We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with “Covid-19” excluded.Results:A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively.Conclusions and Relevance:This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-05T11:30:40Z
  DOI: 10.1177/10600280231169256
Lenacapavir: A Novel Long-Acting Capsid Inhibitor for HIV
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  Authors: Marylee W. Tailor, Elias B. Chahine, David Koren, Elizabeth M. Sherman
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review the efficacy, safety, and role of lenacapavir (LEN) in the treatment of HIV-1 infection.Data Sources:A literature search was performed using PubMed and Google Scholar (through March 2023) with the search term LEN and GS-6207. Other resources included abstracts presented at recent conferences, the manufacturer’s Web site, and prescribing information.Study Selection and Data Extraction:All relevant articles, trial updates, and conference abstracts in the English language were included.Data Synthesis:Lenacapavir represents a new class of antiretrovirals (ARVs) with a novel mechanism of action as a capsid inhibitor and a unique twice-a-year subcutaneous administration schedule. Lenacapavir when combined with other ARVs has proven to benefit heavily treatment-experienced (HTE) patients with HIV-1 infection in achieving viral suppression and immune restoration.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Lenacapavir is a new treatment option that patients who are HTE can consider adding as part of an ARV regimen.Conclusions:Lenacapavir is an effective and well-tolerated option for HTE patients which is a valuable addition to the arsenal of ARVs.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-04T05:29:01Z
  DOI: 10.1177/10600280231171375
Evaluation of an Association Between Enoxaparin Dose per Estimated Blood
Volume and Clinically Relevant Bleeding in Low-Weight Trauma Patients
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  Authors: Chris Carter, Kailey Denny, Thomas W. Carver, Benjamin Jung, Lisa Rein, William J. Peppard
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The optimal dosing for enoxaparin venous thromboembolism (VTE) prophylaxis in low-weight trauma patients is unknown. Estimated blood volume (EBV) has shown promise as a dose modifier.Objective:To characterize the association of enoxaparin dose per EBV with the prevalence of VTE and bleeding in low-weight trauma patients.Methods:This was a retrospective study of trauma patients admitted over a 4-year period. Included patients were adults weighing
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-04T05:26:41Z
  DOI: 10.1177/10600280231169523
Bictegravir/Emtricitabine/Tenofovir Alafenamide in a Multicentre Cohort:
Real-Life Experience From Spain
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  Authors: Miguel Torralba, Gema Rodríguez, Francisco Javier González Gasca, Fernando Cuadra, José Barberá, Paloma Geijo, Andrea Silva, María Isabel García, Marcos Alexander Ostaiza, Ana María García Pérez, Esther Arroyo, Juan Ramón Larrubia, Almudena Gutiérrez, María Lourdes Porras, Henar Calvo Sánchez, Julia Peña-Asensio, Julio Gabriel Arias, Inés Mendoza
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce.Objective:To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort.MethodsThis observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022. Treatment effectiveness (based on intention-to-treat [ITT], modified ITT [mITT], and on-treatment [OT]), tolerability, and safety were evaluated in all patients who started BIC/FTC/TAF antiretroviral therapy.Results:We included a total of 505 PLWH of whom 79 (16.6%) were TN and 426 (83.4%) were TE. Patients were followed up for a median (interquartile range [IQR]) of 19.6 (9.6-27.3) months, and 76% and 56% of PLWH reached month 6 and month 12 of treatment, respectively. Rates of TN PLWH with HIV-RNA
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-03T05:05:17Z
  DOI: 10.1177/10600280231168852
Prevention of Skeletal-Related Events With Extended-Interval Denosumab: A
Review of the Literature
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  Authors: Sidney Veach Keisner
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review published clinical trial data related to efficacy and safety of administering denosumab at extended dosing intervals for prevention of skeletal-related events (SREs) in cancer patients.Data Sources:A literature search of PubMed was performed (January 2006 to February 2023) using the following search terms: denosumab, bone metastasis, bone lesions, and lytic lesions. Abstracts from conferences, article bibliographies, and product monographs were also reviewed.Study Selection and Data Extraction:Relevant English-language studies were considered.Data Synthesis:Early phase II denosumab trials included treatment arms that utilized extended-interval denosumab, and various retrospective reviews, meta-analyses, and prospective trials have included extended-interval regimens. Most recently, the ongoing randomized REDUSE trial is comparing the efficacy and safety of extended-interval denosumab to standard dosing. At this time, the best available data are restricted to small, randomized trials not designed to compare efficacy and safety of extended-interval denosumab to conventional dosing and did not use consistent endpoints. Furthermore, primary endpoints of available trials largely consisted of surrogate markers of efficacy that may not be reflective of clinical outcomes.Relevance to Patient Care and Clinical Practice:Historically, denosumab has been dosed at 4-week intervals for prevention of SREs. If efficacy is maintained, extending the dosing interval could potentially reduce toxicity, drug cost, and clinic visits compared to every 4-week dosing.Conclusions:At this time, data demonstrating efficacy and safety of extended-interval denosumab remain limited, and the results of the REDUSE trial are eagerly anticipated to help answer remaining questions.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-05-03T05:02:57Z
  DOI: 10.1177/10600280231168456
Dexmedetomidine Sublingual Film: A New Treatment to Reduce Agitation in
Schizophrenia and Bipolar Disorders
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  Authors: Danielle M. Karlin, Leigh Anne Nelson, Austin R. Campbell
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:The objective of this study was to review the available literature for dexmedetomidine sublingual film use in the treatment of acute agitation associated with schizophrenia and bipolar disorders.Data Sources:A literature search of PubMed (January 2017-March 2023) and EMBASE (January 2017-March 2023) was performed using the terms: Igalmi, dexmedetomidine, schizophrenia, bipolar disorder, and agitation. Additional information sources include ClinicalTrials.gov, scientific posters, and articles identified through review of references from clinical trials publications.Study Selection and Data Extraction:Relevant English-language articles conducted in humans were considered, with a preference for phase 3 clinical trials. Trial analyses and articles discussing pharmacology, pharmacokinetics, efficacy, and safety were also evaluated.Data Synthesis:Dexmedetomidine sublingual film was evaluated for use in schizophrenia in the SERENITY 1 pivotal trial and for bipolar disorders in the SERENITY 2 pivotal trial. Both studies found treatment of mild to moderate agitation with dexmedetomidine sublingual film 180 and 120 μg to be superior to placebo in reducing the severity of agitation. Treatment effect was seen as early as 20 minutes. Somnolence was the most common adverse effect in both studies. Cardiovascular adverse effects were mild and transient in most cases.Relevance to Patient Care and Clinical Practice:Dexmedetomidine sublingual film is a new and novel treatment for agitation and gives clinicians an alternative to antipsychotic and benzodiazepine use. It has advantageous properties including its noninvasive route of administration, fast absorption, and rapid onset of effect. Cost may limit its use.Conclusion:Dexmedetomidine sublingual film provides an alternative approach to treatment of acute agitation in adults with schizophrenia and bipolar disorders based on both mechanism of action and route of administration.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-29T01:22:57Z
  DOI: 10.1177/10600280231171179
Fixed Versus Body-Sized-Based Dosing of Monoclonal Antibodies
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  Authors: Brian L. Erstad, Lisa E. Davis
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Monoclonal antibody products are an increasing portion of novel drug approvals. The labeling of initial drug approvals frequently involves body-size-based rather than fixed-dose administration regimens for adults without clear rationale for doing so. This presents challenges when prescribing these products for patients with extremes of body habitus who constitute a small portion of enrollment in pre-approval investigations. Fixed-dose regimens allow for standardized preparation with the potential to reduce the risk of calculation errors, drug waste, and make home administration more practical. Fixed-dose rather than body-size-based monoclonal antibody regimens should serve as the initial approach in early phase 1 clinical trials.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-27T12:00:32Z
  DOI: 10.1177/10600280231170650
SAMe-TT2R2 to Predict Clinical Outcomes and Time in Therapeutic Range in
Patients on Vitamin K Antagonists: A Systematic Review and Meta-Analysis
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  Authors: Supatcha Incomenoy, Surasak Saokaew, Natnicha Poonchuay
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The SAMe-TT2R2 score identifies patients on vitamin K antagonists (VKAs) who are more likely to have poor time in therapeutic range (TTR); however, the association between SAMe-TT2R2 and clinical outcomes remains controversial.Objectives:The objective is to assess the association of SAMe-TT2R2 score with clinical outcomes and poor TTR in patients on VKAs.Methods:We searched using the term “SAMe-TT2R2.” Original articles reporting clinical outcomes and SAMe-TT2R2 scores before October 2021 were included. Odds ratios (ORs) of clinical outcomes, diagnostic accuracy parameters of poor TTR (
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-26T12:01:10Z
  DOI: 10.1177/10600280231166643
Comparison of Doxycycline or Minocycline to Sulfamethoxazole-Trimethoprim
for Treatment of Stenotrophomonas maltophilia Pneumonia
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  Authors: Taha Alhayani, Carolyn D. Philpott, Siyun Liao, Anthony J. Gentene, Eric W. Mueller
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Stenotrophomonas maltophilia is a multidrug-resistant organism with limited antibiotic treatment options. Minocycline and doxycycline may be appropriate, but clinical data are limited.Objective:To compare tetracyclines (minocycline and doxycycline [TCN]) with standard of care, sulfamethoxazole-trimethoprim (TMP-SMZ), in S. maltophilia pneumonia treatment.Methods:This retrospective, 2-center study evaluated patients treated for S. maltophilia pneumonia with TCN or TMP-SMZ for clinical success, defined as resolution of leukocytosis, fever, and tachypnea. Patients were classified as treatment with TCN or TMP-SMZ based on definitive agent used for ≥50% of the treatment course and ≥4 days. Inclusion criteria were age ≥18 years, S. maltophilia confirmed on respiratory culture from January 2013 to November 2020, and appropriate definitive antibiotic dosing. Pregnancy, incarceration, S. maltophilia–resistant or intermediate to definitive therapy, and combination therapy for treatment of S. maltophilia pneumonia were exclusion criteria. Secondary outcomes were microbiologic success and recurrence or reinfection within 30 days requiring treatment.Results:A total of 80 patients were included (21 TCN [15 minocycline, 6 doxycycline], 59 TMP-SMZ). There was no difference in clinical success (28.6% vs 25.4%; P = 0.994), microbiologic success (n = 28, 55.6% vs 66.4%; P = 0.677), or recurrence or reinfection (n = 24, 66.7% vs 26.7%; P = 0.092) between TCN and TMP-SMZ, respectively.Conclusion and Relevance:Clinical and microbiologic success rates were similar in patients treated with TCN compared with TMP-SMZ for S. maltophilia pneumonia. These data suggest minocycline and doxycycline may be options to treat S. maltophilia pneumonia, but conclusive clinical data continue to be lacking.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-26T11:56:50Z
  DOI: 10.1177/10600280231166413
A Systematic Approach to Understanding Acid-Base Disorders in the
Critically Ill
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  Authors: Jeffrey F. Barletta, Justin Muir, Judah Brown, Amy Dzierba
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:The objective of this review is to discuss acid-base physiology, describe the essential steps for interpreting an arterial blood gas and relevant laboratory tests, and review the 4 distinct types of acid-base disorders.Data Sources:A comprehensive literature search and resultant bibliography review of PubMed from inception through March 7, 2023.Study Selection and Data Extraction:Relevant English-language articles were extracted and evaluated.Data Synthesis:Critically ill patients are prone to significant acid-base disorders that can adversely affect clinical outcomes. Assessing these acid-base abnormalities can be complex because of dynamic aberrations in plasma proteins, electrolytes, extracellular volume, concomitant therapies, and use of mechanical ventilation. This article provides a systematic approach to acid-base abnormalities which is necessary to facilitate prompt identification of acid-base disturbances and prevent untoward morbidity and mortality.Relevance to Patient Care and Clinical Practice:Many acid-base disorders result from medication therapy or are treated with medications. Pharmacists are uniquely poised as the medication experts on the multidisciplinary team to assist with acid-base assessments in the context of pharmacotherapy.Conclusion:The use of a systematic approach to address acid-base disorders can be performed by all pharmacists to improve pharmacotherapy and optimize patient outcomes.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-26T11:51:24Z
  DOI: 10.1177/10600280231165787
Comparison of the Correlation Between Coagulation Indices and Rivaroxaban
Concentrations
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  Authors: Tingting Wu, Shuyi Wu, Meijuan Li, Jinhua Zhang
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Rivaroxaban has predictable pharmacokinetics and pharmacodynamics. However, monitoring rivaroxaban concentrations should be provided for special patients with hepatic insufficiency, high bleeding risk, and high thrombotic risk.Objective:This study aimed to correlate chromogenic anti-Xa assay, prothrombin time (PT), activated partial thromboplastin time (APTT), thromboelastogram reaction time (TEG R-time), and rivaroxaban concentration measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) (MS-Riva).Methods:Peripheral venous blood was collected from recruited patients 30 minutes before and 2 to 4 hours after drug administration. High-performance liquid chromatography-tandem mass spectrometry and chromogenic anti-Xa assay measured rivaroxaban concentration. Different assays were compared by Pearson correlation coefficient and Bland-Altman analysis.Results:A total of 104 patients with 191 plasma were included in the study. Overall analysis shows that chromogenic anti-Xa assay, PT, APTT, and TEG R-time strongly correlated with MS-Riva (r = 0.986; r = 0.884; r = 0.741; r = 0.739; P < 0.001). Rivaroxaban peak concentration detected by HPLC-MS/MS (MS-peak) showed a very strong correlation with the chromogenic anti-Xa assay (r = 0.977, P < 0.001) and moderate correlation with PT, APTT, and TEG R-time (r = 0.670; r = 0.571; r = 0.481, P < 0.001). Rivaroxaban trough concentration detected by HPLC-MS/MS (MS-trough) correlated strongly with the chromogenic anti-Xa assay (r = 0.884, P < 0.001), weakly with APTT (r = 0.313; P = 0.043), and not significantly with PT and TEG R-time (P = 0.140; P = 0.341).Conclusion and Relevance:High-performance liquid chromatography-tandem mass spectrometry/MS is the preferred choice for monitoring peak and tough concentrations, followed by anti-Xa, while PT is only suitable for peak concentrations. This study can help the clinicians to better adjust the medication regimen and reduce the risk of recurrence of thrombosis as well as the risk of bleeding.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-26T11:49:05Z
  DOI: 10.1177/10600280231158929
Considerations for Treating Nonobstetric Diseases in Pregnant Patients in
the Emergency Department Setting
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  Authors: Lea S. Eiland, John Brock Harris, Amy P. Holmes
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To provide nonobstetric practitioners with an overview of key concepts for the pregnant patient and review treatment of 3 common acute nonobstetric diseases encountered in the emergency department setting.Data Sources:A literature search of PubMed was performed (1997-February 2023) using key search terms related to pregnancy, pain, urinary tract infection (UTI), venous thromboembolism (VTE), and anticoagulants.Study Selection and Data Extraction:Relevant articles in English and humans were considered.Data Synthesis:When caring for a pregnant patient, it is important to utilize appropriate assessments, understand terms used in this population, and recognize how the physiological and pharmacokinetic changes that occur in pregnancy can influence medication use. Pain, UTIs, and VTE are common in this population. Acetaminophen is the most widely used medication for the management of pain during pregnancy and the drug of choice for mild pain in pregnancy not responsive to nonpharmacologic treatment. Pyelonephritis is the most common nonobstetric cause of hospitalization for pregnant patients. Antimicrobial treatment should consider maternal-fetal safety and local resistance patterns. Pregnant and postpartum patients have a 4- to 5-fold increased risk of developing a VTE compared with nonpregnant patients. Low-molecular-weight heparin is the preferred treatment.Relevance to Patient Care and Clinical Practice:Pregnant patients often seek acute care in the emergency department setting for nonobstetric needs. Pharmacists in this setting should understand appropriate assessment questions and terms used within this population, the basics of physiological and pharmacokinetic changes in pregnancy that can impact treatment, and which resources are best to utilize for drug information of the pregnant patient.Conclusion:Practitioners in the acute care setting commonly encounter pregnant patients seeking care for nonobstetric concerns. This article covers key pregnancy-related information for the nonobstetric practitioner and focuses on the management of acute pain, UTI, and VTE during pregnancy.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-20T04:58:51Z
  DOI: 10.1177/10600280231167775
A Review of Topical Tapinarof for the Treatment of Plaque Psoriasis
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  Authors: Meghan C. Grossmann, Jessica N. Pixley, Steven R. Feldman
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:This article reviews the efficacy and safety of 1% tapinarof cream for plaque psoriasis.Data sources:A literature search was conducted from August 2022 to February 2023. The terms tapinarof, VTAMA, benvitimod, GSK2894512, DMVT-505, and WBI-1001 were queried in PubMed. ClinicalTrials.gov was searched to identify ongoing or unpublished studies.Study selection and data extraction:All clinical trials written in English and relevant to pharmacology, efficacy, and safety were included.Data synthesis:In two 12-week phase III clinical trials, disease severity assessed by a Physician’s Global Assessment (PGA) score of clear or almost clear and a 2-point PGA improvement was 35.4% and 40.2% at week 12 in the 2 trials, respectively. In the 40-week, open-label extension trial, the efficacy and safety results were similar: 40.9% of patients achieved a PGA of 0 at least once during the trial, and 58.2% of patients with PGA ≥ 2 achieved PGA 0/1 at least once.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Tapinarof is a topical aryl hydrocarbon receptor agonist and a first-in-class, potentially promising treatment for plaque psoriasis recently approved by the U.S. Food and Drug Administration.Conclusion:Compared with placebo, tapinarof may be an effective and safe topical treatment for mild to severe plaque psoriasis. Head-to-head trials to compare the efficacy and adverse effect profile of tapinarof to other topical treatments are still needed, as are investigation in patients with recent or current use of phototherapy or biologic or nonbiologic systemics. Cost and adherence to treatment may be barriers for treatment efficacy.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-20T04:57:12Z
  DOI: 10.1177/10600280231164775
Comment: Does Early Vasopressin in Septic Shock Improve Outcomes' An
Important Piece to This Emerging Puzzle Has Arrived
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  Authors: Michele M. McCloskey, Gabrielle A. Gibson, Hannah E. Pope, Bria D. Giacomino, Nicholas Hampton, Scott T. Micek, Marin H. Kollef, Kevin D. Betthauser
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-14T05:26:43Z
  DOI: 10.1177/10600280221096886
Does Early Vasopressin in Septic Shock Improve Outcomes' An Important
Piece to This Emerging Puzzle Has Arrived
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  Authors: C. Michael White
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  In this month’s Annals of Pharmacotherapy, the largest observational study assessing the early versus later use of vasopressin has been published. When this new study is combined with the other available observational studies, there are 2 important outcomes to focus on. When all the observational studies are pooled together, no reduction in new onset arrhythmias is seen (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.41-1.95) with early versus late vasopressin use while the reduction in renal replacement therapy just missed statistical significance (OR = 0.56, 95% CI = 0.32-1.00). Early vasopressin likely does not reduce new onset arrhythmias versus later use but might reduce the need for renal replacement therapy.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-14T05:25:44Z
  DOI: 10.1177/10600280221096881
Effect of Early Administration of Vasopressin on New-Onset Arrhythmia
Development in Patients With Septic Shock: A Retrospective, Observational
Cohort Study
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  Authors: Michele M. McCloskey, Gabrielle A. Gibson, Hannah E. Pope, Bria D. Giacomino, Nicholas Hampton, Scott T. Micek, Marin H. Kollef, Kevin D. Betthauser
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Adjunctive vasopressin use in septic shock reduces catecholamine requirements and is associated with a lower incidence of new-onset arrhythmias (NOAs). The association of vasopressin timing on NOA development is ill-described.Objective:To determine whether early administration of vasopressin was associated with a lower incidence of NOA in septic shock patients.Methods:A retrospective analysis of intensive care unit (ICU) patients at a large, academic medical center. Septic shock patients who required vasopressin and norepinephrine were eligible for inclusion. Patients were excluded for receipt of other vasoactive agents, history of cardiac arrhythmias, or outside hospital admission. Early vasopressin was defined as receipt within 6 hours of septic shock onset. The primary outcome was incidence of NOA.Results:In total, 436 patients, 220 (50.4%) in the early and 216 (49.6%) in the late vasopressin group, were included. Early vasopressin was not associated with a lower incidence of NOA compared with late vasopressin (9% vs 7%, median absolute difference [95% confidence interval, CI]: −2.1 [−7.2, 3.0], P = 0.41). Early vasopressin patients were observed to have shorter shock duration (2 vs 4 days, median absolute difference [95% CI]: 2 [1, 2], P < 0.001), and ICU length of stay (6 vs 7 days, median absolute difference [95% CI]: 1 [0, 2], P = 0.02).Conclusions and Relevance:Early vasopressin use was not associated with a lower incidence of NOA. Additional studies are needed to elucidate the effect of vasopressin timing on NOA and other clinical outcomes.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-14T05:24:19Z
  DOI: 10.1177/10600280221095543
Pregabalin Does Not Increase Risk of Heart Failure Exacerbation in
Patients With Pre-existing Heart Failure
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  Authors: Emma Wynn, Joseph Biskupiak, Kibum Kim, Mark A. Munger
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Through actions of calcium channel trafficking inhibition and sodium/water retention, pregabalin may increase the risk of acute heart failure (AHF).Objective:The objective of this study was to determine the prevalence of heart failure (HF) acute exacerbations, measured by a composite of emergency department (ED) visits, per-patient per-year (PPPY) hospitalizations, time-to first ED admission, and time-to hospitalizations in pre-existing HF patients taking pregabalin compared with those who were pregabalin-naive.Methods:A retrospective cohort study of pregabalin users with HF were propensity score–matched to pregabalin-naïve patients with HF to evaluate the composite of ED admissions or PPPY hospitalizations, time-to first ED admission, and time-to hospitalizations during the 365 days post-index. Doubly robust generalized linear regression and Cox-proportional hazard regression modeling were undertaken for analysis of differences between groups.Results:The matched cohort of 385 pregabalin users and 3460 pregabalin nonusers were principally middle-aged, equally gender distributed, and primary Caucasian. Most patients were on guideline-directed HF medical therapy. The estimated cumulative incidence of the primary outcome was a hazard ratio of 1.099 (95% CI: 0.789-1.530; P = 0.58).Conclusion and Relevance:This large, single-center, cohort study shows pregabalin is not associated with an increased risk of AHF events in patients with pre-existing HF.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-12T09:27:38Z
  DOI: 10.1177/10600280231165259
Determining the Risk of Elevated Digoxin Concentrations Following Loading
Dose in Patients With Acute and Chronic Kidney Disease
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  Authors: Mikaela R. Young, Stephen H. Rappaport, Sarah Belz, David C. Kaufman, Curtis E. Haas
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:The optimal loading dose of digoxin in patients with reduced kidney function is unknown. Tertiary references recommend reduced loading doses; however, these recommendations are based on immunoassays that are falsely elevated by the presence of digoxin-like immunoreactive substances, a problem that is minimized in modern assays.Objective:To determine whether chronic kidney disease (CKD) or acute kidney injury (AKI) is associated with supratherapeutic digoxin concentrations after a digoxin loading dose.Methods:A retrospective analysis on patients who received an intravenous loading dose of digoxin with a digoxin concentration collected 6 to 24 hours after the end of the dose. Patients were stratified into 3 groups: AKI, CKD, and non-AKI/CKD (NKI) based on glomerular filtration rate and serum creatinine. The primary outcome was frequency of supratherapeutic digoxin concentrations (>2 ng/mL) and secondary outcomes included frequency of adverse events.Results:A total of 146 digoxin concentrations were included (AKI = 59, CKD = 16, NKI = 71). Frequencies of supratherapeutic concentrations were similar between groups (AKI: 10.2%, CKD: 18.8%, NKI: 11.3%; P = 0.61). Pre-planned logistic regression demonstrated no significant relationship between kidney function group and the development of a supratherapeutic concentration (AKI: odds ratio [OR]: 1.3, 95% confidence interval [CI]: 0.4-4.5; CKD: OR 4.3, 95% CI: 0.7-23).Conclusion and Relevance:This is the first study in routine clinical practice evaluating the relationship between kidney function and digoxin peak concentrations that differentiates AKI from CKD. We did not find a relationship between kidney function and peak concentrations; however, the group with CKD was underpowered.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-12T09:21:39Z
  DOI: 10.1177/10600280231163256
Prevention of Cardiovascular Events in Patients With Chronic Kidney
Disease
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  Authors: Chris M. Terpening
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To examine the evidence base for lifestyle and pharmacologic interventions to reduce the risk of cardiovascular events in patients with chronic kidney disease, with an emphasis on reporting available data in distinct subtypes.Data Sources:A PubMed search (origin to February 2023) was conducted and references for selected studies were reviewed to identify additional articles. Search terms included chronic kidney disease, major adverse cardiovascular events, and heart failure hospitalization.Study Selection and Data Analysis:English language studies reporting cardiovascular outcomes data in patients with chronic kidney disease were included.Data Synthesis:Much of the data on interventions to prevent cardiovascular events in patients with chronic kidney disease are derived from observational studies or subgroup analyses of trials of broader populations. Some common recommendations, such as weight loss, may be harmful in certain patients. Others may only offer benefits in subgroups, such as those with albuminuria. Newer agents, such as SGLT2 inhibitors and finerenone, have clearer evidence of cardiovascular benefit, but these may also apply only to specific subgroups.Relevance to Patient Care and Clinical Practice:Given the prevalence of chronic kidney disease and its attendant cardiovascular risk, it is important to understand which interventions offer the greatest benefit.Conclusions:Patients diagnosed with chronic kidney disease have markedly increased risk of cardiovascular events, including myocardial infarction, stroke, heart failure, and cardiovascular death. However, until recently, there were few cardiovascular outcome studies that targeted enrollment specifically to those patients. Certain drugs now have shown benefits to cardiovascular end points in this population.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-08T06:45:46Z
  DOI: 10.1177/10600280231165774
Sacituzumab Govitecan as a Second-Line Treatment in Relapsed/Refractory
Metastatic Triple-Negative Breast Cancer Patients: A Systematic Review and
Meta-analysis
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  Authors: Meghavi Kathpalia, Anurag Sharma, Navkiran Kaur
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Chemotherapy, the only treatment option for metastatic triple-negative breast cancer (mTNBC), showed decreased survival rates. Trophoblast cell surface antigen-2 (Trop-2) could be a possible target for antibody-drug conjugates (ADCs).Objective:Sacituzumab govitecan (SG), an anti-Trop-2 ADC for pretreating relapsed/refractory mTNBC patients, was studied to know the efficacy and safety profile of the drug in mTNBC.Methods:The present review searched MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until December 25, 2022. The studies searched comprised randomized trials and observational studies (retrospective [case-control, cross-sectional] and prospective [cohort designs]). Efficacy assessment was performed in terms of complete response (CR), partial response (PR), objective response rate (ORR), stable disease (SD), progressive disease (PD), and clinical benefit rate (CBR), and safety in terms of adverse events.Results:The overall random-effects pooled prevalence of CR was 4.9 (95% CI: 3.2-7.1), PR was 35.6 (95% CI: 31.5-39.9), ORR was 6.8 (95% CI: 5.9-7.8), SD was 8.0 (95% CI: 6.7-9.4), PD was 5.1 (95% CI: 4.1-6.3), and CBR was 13.4 (95% CI: 11.8-15.1). Adverse events associated with the drug were neutropenia, fatigue, anemia, nausea, and others.Conclusion and Relevance:This is the first meta-analysis conducted in relapsed/refractory mTNBC patients and found that SG is efficacious but associated with some adverse effects that are related to exposure to the drug. The application of these results will allow clinicians to use SG in the management of patients with mTNBC.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-07T06:26:20Z
  DOI: 10.1177/10600280231164110
Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as
Adjunctive Therapy in Septic Shock: A Retrospective Cohort Study
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  Authors: Ashley E. Lock, G. Christina Gutierrez, Elizabeth O. Hand, Colleen A. Barthol, Rebecca L. Attridge
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Trials evaluating hydrocortisone (HC) for septic shock are conflicting with all finding decreased time to shock reversal but few with mortality difference. Those with improved mortality included fludrocortisone (FC), but it is unknown if FC affected the outcome or is coincidental as there are no comparative data.Objective:The objective of this study was to determine the effectiveness and safety of FC + HC versus HC alone as adjunctive therapy in septic shock.Methods:A single-center, retrospective cohort study was conducted of medical intensive care unit (ICU) patients with septic shock refractory to fluids and vasopressors. Patients receiving FC + HC were compared with those receiving HC. Primary outcome was time to shock reversal. Secondary outcomes included in-hospital, 28-, and 90-day mortality; ICU and hospital length of stay (LOS); and safety.Results:There were 251 patients included (FC + HC, n = 114 vs HC, n = 137). There was no difference in time to shock reversal (65.2 vs 71 hours; P = 0.24). Cox proportional hazards model showed time to first corticosteroid dose, full-dose HC duration, and use of FC + HC were associated with shorter shock duration, while time to vasopressor therapy was not. However, in 2 multivariable models controlling for covariates, use of FC + HC was not an independent predictor of shock reversal at greater than 72 hours and in-hospital mortality. No differences were seen in hospital LOS or mortality. Hyperglycemia occurred more frequently with FC + HC (62.3% vs 45.6%; P = 0.01).Conclusion and Relevance:FC + HC was not associated with shock reversal at greater than 72 hours or decreased in-hospital mortality. These data may be useful for determining corticosteroid regimen in patients with septic shock refractory to fluids and vasopressors. Future prospective, randomized studies are needed to further evaluate the role of FC in this patient population.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-07T06:25:01Z
  DOI: 10.1177/10600280231164210
Comparison of COVID-19 Vaccination and Infection Rates in Adult Patients
With Autoimmune Inflammatory Disease on b/tsDMARD Therapy
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  Authors: Viktoriya Avlasevich, Katharine McCarthy
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-06T06:37:26Z
  DOI: 10.1177/10600280231164109
Extended-Release Viloxazine for the Treatment of Attention-Deficit
Hyperactivity Disorder in School-Age Children and Adolescents
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  Authors: Haley Raible, Manoranjan S. D’Souza
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To describe the efficacy and safety of extended-release viloxazine (viloxazine ER; Qelbree) for the treatment of attention-deficit hyperactivity disorder (ADHD) in school-age children and adolescents (6-17 years).Data Sources:A literature search was conducted with PubMed using the following terms: viloxazine and ADHD (August 1, 2017 to February 1, 2023).Study Selection and Data Extraction:All relevant English-language articles examining the efficacy and safety of viloxazine ER were considered for inclusion.Data Synthesis:Phase III studies reported significant improvement in ADHD symptoms after viloxazine ER treatment in both school-age children (100 mg/d, P = 0.0004 and 200 mg/d, P < 0.0001; NCT03247530) and adolescents (200 mg/d, P = 0.0232; 400 mg/d, P = 0.0091; NCT03247517) compared with placebo. Common adverse effects associated with viloxazine ER included somnolence, fatigue, irritability, decreased appetite, and headache. Together, the studies demonstrated the efficacy and safety of viloxazine ER in patients with ADHD.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Viloxazine ER is a serotonin-norepinephrine modulator, which is administered once daily orally. It is classified as a nonstimulant medication, which can be used in patients with ADHD who do not respond to or cannot tolerate stimulant medications. Even though atomoxetine and viloxazine ER have not been directly compared, clinical studies have suggested that viloxazine ER has a faster onset of action (~1-2 weeks) compared with atomoxetine (~4 weeks). Like atomoxetine, viloxazine ER carries a boxed warning for suicidal ideation and/or behavior.Conclusion:Viloxazine ER is a useful addition to other nonstimulant medications available to treat patients with ADHD.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-06T06:36:26Z
  DOI: 10.1177/10600280231163252
Impact on Diabetic Ketoacidosis Resolution After Implementation of a 2-Bag
Fluid Order Set
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  Authors: Hannah E. Gilchrist, Colman J. Hatton, Matthew A. Roginski, Alyson M. Esteves
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Diabetic ketoacidosis (DKA) is a serious acute complication of both type 1 and type 2 diabetes that requires prompt management. Limited data exist supporting the use of a 2-bag DKA protocol in adult patients across all levels of care.Objective:To evaluate the efficacy and safety of a 2-bag DKA protocol in comparison with a traditional DKA management strategy.Methods:Retrospective review of patients admitted with DKA between January 1, 2021, and February 28, 2022, at a single center. Patients were separated into 2 cohorts, traditional or 2-bag. The primary outcome was time to anion gap closure and/or beta-hydroxybutyrate normalization. Secondary outcomes include length of hospitalization, insulin infusion time, and hypoglycemic events.Results:One hundred forty-three patients had a DKA order set initiated during their admission, 59 in the traditional cohort and 84 in the 2-bag cohort. Mean time to anion gap closure was shorter in the 2-bag cohort (12.7 vs 16.9 hours; P = 0.005) and beta-hydroxybutyrate normalization (15.6 vs 25.6 hours; P = 0.026). No difference in hospital length of stay (4 vs 6 days; P = 0.113), duration of insulin infusion (41.6 vs 40.6 hours; P = 0.455), or rates of hypoglycemia (6 vs 4; P = 0.872) was seen.Conclusion and Relevance:Implementation of a 2-bag DKA protocol in the inpatient setting was associated with a shorter time to anion gap closure and beta-hydroxybutyrate normalization. These findings support the option of expansion of a 2-bag DKA protocol to adult patients across all levels of care irrespective of the admission diagnosis.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-06T06:35:06Z
  DOI: 10.1177/10600280231163838
Antidepressants and Risk of Liver Cancer: A Systematic Review and
Meta-Analysis
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  Authors: Xiaofeng Chen, Yifan Wang, Tiange Lu, Yutian Ao, Wei Wei, Wenzhe Duan, Hongjun Li, Rongjuan Guo
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Previous results regarding the association between the antidepressants use and risk of liver cancer are controversial.Objective:This study aimed to assess whether antidepressants use increases liver cancer risk.Methods:We systematically searched several English and Chinese databases, including the Cochrane Library, MEDLINE, Embase, PsycINFO, Web of Science, CNKI, CQVIP database, Wanfang database, and SinoMed, and 3 clinical trial registration platforms through May 2022. Observational studies evaluating liver cancer risk in patients on antidepressants use were included, and the quality of studies was assessed using the Newcastle-Ottawa scale. A random-effects model was used to calculate the pooled effect estimates and 95% confidence intervals (CIs).Results:We included 11 studies with a total of 132 396 liver cancer cases. The meta-relative risk (RR) for liver cancer associated with antidepressants use was 0.72 (95% CI 0.59-0.86). In subgroup analyses, only selective serotonin reuptake inhibitors were negatively correlated with risk of liver cancer (RR 0.64, 95% CI 0.51-0.79); both dose subgroups ≤365cDDD (RR 0.77, 95% CI 0.69-0.85) and>365cDDD (RR 0.57, 95% CI 0.40-0.81) were associated with lower liver cancer risk; only in patients with chronic viral hepatitis, the use of antidepressants reduced liver cancer risk (RR 0.70, 95% CI 0.54-0.90).Conclusions and Relevance:The result of the current meta-analysis shows antidepressants use is not associated with increased risk of liver cancer and appears to be correlated with decreased risk. However, the observed association needs to be verified by more powerful evidence from prospective, methodologically rigorous studies.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-05T04:59:58Z
  DOI: 10.1177/10600280221143512
Efficacy and Safety of Fluvoxamine as Outpatient Treatment for Patients
With Covid-19: A Systematic Review and Meta-analysis of Clinical Trials
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  Authors: Akhil Deepak Vatvani, Andree Kurniawan, Timotius Ivan Hariyanto
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Fluvoxamine may be beneficial for the management of coronavirus disease 2019 (Covid-19) because of its effect on the sigma-1 receptor. Available evidence from randomized clinical trials (RCTs) has shown conflicting results.Objective:This study sought to analyze the efficacy and safety of fluvoxamine as an outpatient treatment for Covid-19.Methods:Using specific keywords, we comprehensively go through the potential articles on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until February 1, 2023. We collected all published clinical trials on fluvoxamine and Covid-19. We were using Review Manager 5.4 to conduct statistical analysis.Results:We include a total of 6 trials. Our pooled analysis revealed that fluvoxamine did not offer any significant benefit when compared with placebo in reducing the risk of clinical deterioration (risk ratio [RR] = 0.83; 95% CI: 0.65-1.06, P = 0.14, I2 = 29%), and hospitalization (RR = 0.80; 95% CI: 0.62-1.04, P = 0.09, I2 = 0%) of Covid-19 outpatients. The serious adverse events did not differ significantly between the 2 groups.Conclusions and Relevance:This study indicates that although safe, fluvoxamine was not effective for outpatient treatment of Covid-19. Until more evidence can be obtained from larger RCTs, our study did not encourage the use of fluvoxamine as routine management for patients with Covid-19.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-04-01T05:17:20Z
  DOI: 10.1177/10600280231162243
Trajectories of Oral Anticoagulation Adherence and Associated Clinical
Outcomes During Long-Term Anticoagulation Among Medicare Beneficiaries
With Venous Thromboembolism
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  Authors: Haesuk Park, Bobby L. Jones, Pei-Lin Huang, Hye-Rim Kang, Eric A. Dietrich, Christina E. DeRemer, Wei-Hsuan Lo-Ciganic
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Little is known about anticoagulation medication nonadherence patterns impacting effectiveness and safety outcomes in clinical practice.Objective:We identified adherence trajectories of extended therapy with direct-acting oral anticoagulants (DOACs) and warfarin after 6 months initial anticoagulant therapy among Medicare beneficiaries with venous thromboembolism (VTE). We further assessed the associated recurrent VTE and major bleeding risks.Methods:Using group-based trajectory models, this retrospective cohort study identified distinct beneficiary subgroups with similar adherence patterns of extended-phase anticoagulant treatment (DOACs or warfarin) for patients with VTE who completed 6 months of initial anticoagulant treatment. We examined associations between adherence trajectories and risks of recurrent VTE and major bleeding using inverse probability treatment weighted Cox proportional hazards models.Results:Compared with no extended treatment, consistently high DOAC adherence was associated with decreased recurrent VTE risk (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.21-0.51) without increased major bleeding risk, and consistently high warfarin adherence was associated with decreased recurrent VTE risk (HR = 0.62, 95% CI = 0.40-0.95) and increased major bleeding risk (HR = 1.64, 95% CI = 1.12-2.41). Gradually declining adherence to DOACs (HR = 1.80, 95% CI = 1.07-3.03) or warfarin (HR = 2.34, 95% CI = 1.57-3.47) was associated with increased bleeding risk with no change in recurrent VTE risk.Conclusion and relevance:This real-world evidence suggests persistently adhering to extended DOAC therapy is associated with lower recurrent VTE risk without increasing major bleeding among Medicare beneficiaries with VTE. Persistently adhering to extended warfarin therapy was associated with lower recurrent VTE risk but higher major bleeding risk.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-03-31T09:31:26Z
  DOI: 10.1177/10600280231155489
Comparison of Droperidol and Midazolam Versus Haloperidol and Lorazepam
for Acute Agitation Management in the Emergency Department
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  Authors: Patrick J. Allen, Kendra E. Johanson, Kelly R. Reveles, Luke A. Neff, Ashley E. Lock
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Acute agitation accounts for up to 2.6% of visits to the emergency department (ED). To date, a standard of care for the management of acute agitation has not been established. Few studies have evaluated antipsychotic and benzodiazepine combinations.Objective:The purpose of this study was to evaluate effectiveness and safety of combination therapy for acute agitation with intramuscular (IM) droperidol and midazolam (D+M) compared with IM haloperidol and lorazepam (H+L) in patients in the ED.Methods:This was a single-center, retrospective medical record review of patients presenting to a large, academic ED with acute agitation from July 2020 through October 2021. The primary outcome was percentage of patients requiring additional agitation medication within 60 minutes of combination administration. Secondary outcomes included average time to repeat dose administration and average number of repeat doses required before ED discharge.Results:A total of 306 patients were included for analysis: 102 in the D+M group and 204 in the H+L group. Repeat dose within 60 minutes occurred in 7 (6.9%) and 28 (13.8%) patients in the D+M and H+L groups, respectively (P = 0.065). A total of 28.4% of D+M patients and 30.9% of H+L patients required any repeat dose during their ED visit. Time to repeat dose was 12 and 24 minutes in the D+M and H+L, respectively (P = 0.22). The adverse event rate was 2.9% in each group.Conclusion and Relevance:IM D+M resulted in a lower rate of repeat doses of acute agitation medication compared with IM H+L, though this was not statistically significant. Both therapies were safe, and the adverse event rate was low.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-03-31T09:25:28Z
  DOI: 10.1177/10600280231163192
Correlation of Calculated Vancomycin Trough Concentrations and Exposure: A
Monte Carlo Simulation
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  Authors: Hans Haag, Anthony Lau
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Background:Current recommendations are to dose vancomycin to target 24-hour area under the curve (AUC) of 400-600 mg·h/L to optimize efficacy and safety. Limited data support AUC monitoring, and some centers continue to use trough concentrations. A target of 10-20 mg/L has been proposed to reduce nephrotoxicity risk.Objective:To use previously published pharmacokinetic equations in a Monte Carlo simulation relating AUC exposure to trough concentrations when targeting an AUC between 400 and 600 mg·h/L.Methods:Previously published pharmacokinetic data were used as input parameters for a Monte Carlo simulation using previously published formulae to correlate AUC to simulated trough concentrations. Pharmacokinetic parameters were assumed to occur in a normal distribution pattern. We excluded irrelevant simulated cases. Maintenance doses of 15 mg/kg were rounded to the nearest 250 mg. Calculated trough concentrations for AUCs of both 400 and 600 mg·h/L were evaluated in each simulation.Results:A total of 10 000 Monte Carlo simulations were performed. Targeting an AUC of 400 mg·h/L resulted in a mean trough concentration of 10.3 ± 0.8 mg/L. Targeting an AUC of 600 mg·h/L resulted in a mean trough concentration of 15.4 ± 1.2 mg/L.Conclusion and Relevance:We demonstrate that a lower trough concentration range may be supported by an AUC of 400-600 mg·h/L, which may reduce risk and rates of nephrotoxicity without compromising previously established efficacious target trough concentrations.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-03-31T09:18:50Z
  DOI: 10.1177/10600280231160571
Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody
(ANCA)-Associated Vasculitis
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  Authors: Christopher Alihosseini, Hannah Kopelman, Mallory Zaino, Steven R. Feldman
  Abstract: Annals of Pharmacotherapy, Ahead of Print.
  Objective:To review the safety and efficacy of avacopan for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.Data Sources:A systematic review of the literature was performed using the terms avacopan OR tavneos OR CCX168 OR ANCA-associated vasculitis in PubMed and Google Scholar. Articles between January 2016 and January 2023 were considered for inclusion. Bibliographies and ClinicalTrials.gov were also searched for completion.Study Selection and Data Extraction:Relative English language and human studies related to pharmacology, clinical trials, and safety were included.Data Synthesis:The 52-week ADVOCATE and 12-week CLEAR clinical trials evaluated the safety and efficacy of avacopan. The remission rate was 65.7% and 54.9% in the avacopan and placebo group, respectively, in the ADVOCATE trial. The Birmingham Vasculitis Activity Score improved by ≥50% in 86.4% of avacopan treated patients and 70% of prednisone treated patients in the CLEAR trial.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Glucocorticoids in combination with cyclophosphamide, azathioprine, and/or rituximab have been a mainstay of ANCA-associated vasculitis treatment. However, short- and long-term medication-related adverse effects risk negative outcomes for patients. Avacopan may provide equivalent to better treatment with fewer side effects due to a reduction, if not elimination, of glucocorticoids.Conclusions:Avacopan used in isolation or combination is safe and effective for ANCA-associated vasculitis.
  Citation: Annals of Pharmacotherapy
  PubDate: 2023-03-28T12:39:26Z
  DOI: 10.1177/10600280231161592