American Journal of Health-System Pharmacy最新文献

Purpose: Hemophilia B is a rare, hereditary bleeding disorder characterized by a deficiency in clotting factor IX (FIX). Traditional therapeutic strategies involve an economically and physically burdensome combination of prophylactic and episodic (ie, on-demand) administration of clotting factor concentrates (CFCs). The first gene therapy for hemophilia B, etranacogene dezaparvovec (Hemgenix), was approved by the Food and Drug Administration (FDA) in November 2022, with approval for fidanacogene elaparvovec (Beqvez) following in April 2024, produced by CSL Behring and Pfizer, respectively. This literature review aims to provide an overview of current therapeutic strategies for the treatment of hemophilia B, introducing and focusing on the efficacy and safety of the novel gene therapies etranacogene dezaparvovec and fidanacogene elaparvovec.

Summary: Both FDA-approved hemophilia B gene therapies, etranacogene dezaparvovec and fidanacogene elaparvovec, utilize adeno-associated virus (AAV) vectors for delivery of the gene encoding FIX. Each of these medications has a distinct AAV serotype, but they have the same treatment modality, with the goal of curing the disease and reducing or eliminating prophylactic CFC requirements. Despite their different AAV serotypes, both products deliver a functional copy of the gene encoding the Padua variant (variant R338L) of human FIX. Recent clinical trials have demonstrated efficacy in increasing FIX concentrations leading to reduced frequency of spontaneous bleeding episodes; however, safety and response durability remain concerns.

Conclusion: For the first time in history, individuals with hemophilia B have access to potentially curative therapies through gene therapy. Both etranacogene dezaparvovec and fidanacogene elaparvovec offer significant efficacy, reducing the number of bleeding episodes and raising FIX concentrations with a single lifetime administration. While concerns remain regarding long-term safety and durability, these therapies represent a major advancement in reducing treatment burden and improving quality of life for patients. The future of hemophilia B management now holds the promise of greater independence from frequent prophylactic treatments.

Purpose: Risks of occupational exposures to hazardous drugs (HDs) have been documented and identified as needing to be monitored. To decrease potential exposures in a community hospital, this project evaluated the impact of implementing a hazardous drug wipe sampling technology (BD HD Check system; BD, Franklin Lakes, NJ) and accompanying environmental procedures, risk level scoring assessment, and recordkeeping tools on identifying HD surface contamination.

Methods: The 16-week evaluation focused on HD wipe sampling of locations (25 sites) within a cleanroom suite and infusion areas at the largest hospital of a multihospital community health system. Sites were determined through a risk stratification assessment to which areas were given a high, medium, or low-risk category to determine frequency of testing. HD wipe samples were tested for methotrexate, doxorubicin, and cyclophosphamide. Standard operating procedures (SOPs) were developed to address testing, decontamination, and retesting procedures.

Results: A total of 238 samples were collected over 16 weeks across 25 sample sites. Fifteen of 25 sites resulted in at least 1 positive, totaling 37 initially positive results. Following initial positives, 92.5% of sites successfully tested negative following decontamination. Three sites that remained positive after decontamination underwent a corrective and preventative action (CAPA) analysis and were negative after a second round of decontamination.

Conclusion: Sampling led to reduction in contamination and more transparency in HD monitoring. The HD wipe sampling technology (BD HD Check system) and accompanying procedures were shown to be helpful in establishing and refining SOPs for HD preparation, cleaning/decontamination, and wipe sampling.

Purpose: This case series explores the use of thrombin time (TT) to transition 2 patients from dabigatran to unfractionated heparin (UFH) in the setting of acute kidney injury (AKI) and coagulopathy concerning for dabigatran accumulation.

Summary: Serial TT monitoring was employed until the value began to trend below 120 seconds, indicating ongoing drug clearance, at which point UFH was initiated. Patient 1 experienced rectal bleeding following initiation of UFH, while patient 2 experienced hemoglobin drops without an apparent bleeding source. No thrombotic events occurred during either hospitalization.

Conclusion: Individualized management remains paramount to balance bleeding and thrombotic risk based on patient-specific factors. Further research is warranted to validate the safety and efficacy of a TT-guided transition strategy and optimize protocols for hospitalized patients transitioning from dabigatran to UFH.

Purpose: Authorization of nirmatrelvir/ritonavir expanded outpatient treatment options for those with coronavirus disease 2019 (COVID-19), but prescribing of the medication is complex. The objective of this study was to evaluate the appropriateness of nirmatrelvir/ritonavir prescribing through a pharmacist-driven service as compared to usual care.

Methods: This was a retrospective cohort study. Patients prescribed nirmatrelvir/ritonavir by a pharmacist between May 1 and December 31, 2022, were temporally matched to those who received nirmatrelvir/ritonavir through usual care. The primary outcome was the percentage of patients appropriately prescribed nirmatrelvir/ritonavir by meeting criteria related to authorization-specific requirements, assessment of hepatic and renal function, and management of drug interactions. Descriptive and inferential statistics were performed.

Results: There were 106 patients in each cohort (N = 212). Patients were mainly female (n = 135, 63.7%) and 65 years of age or older (n = 117, 55.2%). All study-defined criteria for appropriate nirmatrelvir/ritonavir prescribing were met in 88.7% of patients (n = 94) who received care through the pharmacist-driven service, as compared to 41.5% of patients (n = 44) managed through usual care (P < 0.0001). In both groups nirmatrelvir/ritonavir was consistently prescribed within 5 days of symptom onset (P > 0.999) and to patients with a qualifying comorbid condition (P = 0.498). However, hepatic (P = 0.030) and renal (P = 0.024) laboratory values were more likely to be current when the prescription arose from a pharmacist as opposed to the usual care process. Drug interactions also were more likely to be identified and mitigated by pharmacists (P < 0.0001).

Conclusion: Nirmatrelvir/ritonavir was appropriately prescribed by pharmacists in most cases, demonstrating that pharmacists can support safe and effective use of nirmatrelvir/ritonavir for patients with complex comorbidities and medication regimens.

Purpose: Data regarding the incidence, onset, and management of complex outpatient antimicrobial therapy-induced neutropenia (COIN) are limited, and pharmacist involvement in COIN management has not been reported. This report describes the incidence, onset, and management of COIN at a large academic medical center.

Methods: This multisite retrospective cohort study examined adult patients undergoing serum laboratory monitoring for antimicrobials over a 4-year period. Patients receiving chemotherapy or immunosuppressants were excluded. Data collected included the antimicrobial regimen, complete blood count, duration of antimicrobial therapy until outcome occurrence, infectious syndrome, type of intervention, outcome, and pharmacist involvement. Logistic regression was used to assess risk factors for COIN incidence. The primary outcome was the incidence of COIN by antimicrobial drug.

Results: From 4,261 treatment episodes, 161 cases of COIN were identified (3.8% COIN incidence). The most common antimicrobials associated with COIN were intravenous piperacillin/tazobactam, cefepime, and meropenem. The majority of COIN events were attributed to a combination of at least 2 antimicrobials. Piperacillin/tazobactam was significantly associated with higher odds of developing COIN (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.04-3.34; P = 0.038), whereas ertapenem was associated with significantly lower odds of COIN (OR, 0.43; 95% CI, 0.24-0.77; P = 0.005). The median time to neutropenia diagnosis was 22 days (interquartile range, 14-29 days) from the time of inpatient antimicrobial start. Intervention for COIN occurred in 66.5% of cases, with neutrophil count recovering in 96.9% of these patients. Clinical pharmacists initiated 74.8% of interventions.

Conclusion: COIN can be effectively identified and managed by a multidisciplinary team reviewing routine laboratory monitoring, enabling most patients to safely complete antimicrobial treatment.

Purpose: Expanding access to pharmacogenomics (PGx) testing to veterans has been an emphasis in the Veterans Health Administration (VHA); using population dashboard tools (PDTs) may identify additional patients who qualify for testing. Involving pharmacy residents in PGx can help prepare them for precision medicine practice and more efficiently provide PGx care to patients.

Methods: Veterans treated in the outpatient setting at the Lt. Col. Luke Weathers, Jr. Veterans Affairs (VA) Medical Center from March 2023 to June 2024 were included in this study. Upon creation of a virtual PGx clinic, a PGx PDT was used to identify patients newly prescribed medications on the VA PGx gene testing panel. The clinic was driven by a postgraduate year 2 pharmacy resident with a preceptor overseeing the practice, and patients were contacted for consent and testing. The number and type of PGx gene variants identified were assessed, with results discussed with patients and recommendations made to providers.

Results: A total of 130 patients were screened, of whom 104 had PGx testing, corresponding to an 80% consent rate. Overall, 247 PGx gene variants were identified, including 149 informational and 78 actionable drug-gene variants, 18 variants indicating inheritable conditions, and 17 variants corresponding to phenoconversion. A total of 90 recommendations were made to providers, and patients had an average of 2.3 PGx-impacted medications prescribed. Of the actionable drug-gene variants, the majority were related to use of clopidogrel, statins, sertraline, and proton pump inhibitors.

Conclusion: Novel use of a PDT was helpful in identifying patients qualifying for PGx testing. Creation of the resident-driven clinic resulted in PGx interventions for the majority of patients who underwent testing.