Journal of Pharmacy Technology最新文献

Retatrutide, a hormone receptor agonist targeting glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide, is being developed to treat obesity. A literature review from April 2019 to April 2024 included such terms as "retatrutide," "LY3437943," "overweight," and "obesity." Phase I proof-of-concept studies led to phase II trials showing up to 24% body weight reduction and nearly 20 cm waist circumference reduction. The most common adverse effects were gastrointestinal. Ongoing phase II and III studies aim to further evaluate the safety and efficacy of retatrutide as a novel triagonist for obesity treatment.

Objective: To evaluate the safety of utilizing multimodal analgesic regimens in critically ill, nonintubated patients. Data Sources: A systematic review was conducted using Embase, MEDLINE, Cochrane, SciELO, Web of Science, and the Korean Journal Index. Clinical trials of critically ill, nonintubated patients that contained complete safety outcomes date, including the incidence of specific adverse drug effects (ADE) associated with a multimodal analgesic medication or regimen, were included. Study Selection and Data Extraction: The primary outcome was the incidence of adverse drug effects associated with multimodal analgesics in comparison to standard-of-care analgesic strategies in our patient population. The secondary outcome was a subgroup analysis of adverse drug effect by type and by medication. Data Synthesis: 10 trials were included in this systematic review, of which 6 were randomized control trials that were evaluated in the meta-analysis. There was no statistically significant difference with respect to the primary outcome (mean difference = -0.11, P = 0.31, 95% CI = [-0.35, 0.13]). The subgroup analysis, which was conducted on randomized clinical control trials that documented a single adjunctive analgesic rather than a multimodal regimen, was stratified by the type of adverse effect encountered and the medication in question. There were no statistically significant findings regarding the incidence of specific ADE. Nonrandomized data included in this study support these findings. Conclusions: While concerns of the additive deleterious adverse effects commonly encountered in polypharmacy are valid, our findings support the use of multimodal analgesic regimens in the provision of analgesic in critically ill, nonintubated patients.

Background: Closed system transfer devices (CSTD) help to reduce the exposure of healthcare professionals to hazardous drugs. They may be used in stability studies conducted on anticancer drugs. During a stability study about polyolefin bags of gemcitabine, Tevadaptor® device was suspected of causing a bias in the evaluation of the concentrations of the first aliquots extracted from the bags.

Objective: The objectives are to determine whether the use of a CSTD to prepare a drug solution and to withdraw it from a bag can interfere on the measured concentration compared to the expected one and to suggest hypothesis to explain the phenomenon.

Method: In the first experiment, three polyolefin bags of gemcitabine (5.4 mg/mL) were prepared under aseptic conditions using the Tevadaptor Luer Lock Adaptor®. The day of preparation, five aliquots of 3.8 ml each were sequentially withdrawn from each polyolefin bag using the same device. After one day, a new aliquot was withdrawn from each bag. In the second experiment, three polyolefin bags of gemcitabine (5.4 mg/ml) were prepared under aseptic conditions using a needle. One aliquot was extracted using a needle after the preparation from each bag, and another aliquot was extracted after one day. The concentrations of all aliquots were measured by liquid chromatography coupled to a photodiode array detector during the same run.

Results and discussion: The concentrations of the first aliquots extracted on day zero from the polyolefin bags using the Tevadaptor Luer Lock Adaptor® exhibit an overestimation of 26% ([95%CI: 23%-29%] P<0.001) compared to the others. Overestimation is not found for subsequent aliquots, or while using a needle to bypass the Tevadaptor® device.

Conclusion: This case highlights the bias that may arise when using CSTDs in stability studies. They should be used with comprehensive understanding of their technical specifications.

Background: The ever-increasing complexity and demand for antineoplastic therapy necessitates innovative solutions to improve the accuracy and safety of drug preparation. Objective: To evaluate the utilization of an advanced robotic chemotherapy drug compounding system (APOTECAchemo) at a Community Cancer Center (CCC), examining accuracy, efficiency, and staff perceptions. Methods: This single-center, retrospective study evaluated the preparation of 7 intravenous (IV) antineoplastics at a CCC over a 1-year period. We compared manual methods with the APOTECAchemo system. The primary measure of accuracy was the absolute drug error percentage, with a comparison of pass and fail rates. Secondary endpoints included the overall use of APOTECAchemo for all IV antineoplastic preparations and average preparation times. An end-user satisfaction survey gathered feedback from pharmacists and pharmacy technicians. Results: A total of 8210 doses were prepared at the CCC, with 52.1% compounded by APOTECAchemo and 47.9% manually. Of these, the CCC prepared 5526 doses of the 7 routinely compounded antineoplastics. APOTECAchemo prepared 3851 (69.7%) doses, while manual compounding accounted for 1675 (30.3%) doses. The average absolute drug error was 1.44% (95% CI, 1.35-1.53) with robot compounding versus 1.17% (95% CI, 1.03-1.32) with manual (P < 0.001). The overall failure rate was 0.72%. There were 25 failed doses (0.45%), with 8 (0.2%) failures attributed to APOTECAchemo and 17 (1%) to manual compounding (P < 0.001). The average dose preparation time was longer with APOTECAchemo compared with manual methods. The end-user satisfaction survey indicated a positive reception toward APOTECAchemo. Conclusions: Our study demonstrates the successful implementation, extensive utilization, and high accuracy of both APOTECAchemo and manual compounding methods in the preparation of routinely administered antineoplastics at a CCC.

Objective: This review evaluated the impact of a digitized computerized prescriber order entry (CPOE) system and described barriers and facilitators for introducing a digitized system.

Data sources: A systematic literature search was conducted in PubMed, Medline, and CINAHL using keywords. Articles in English during the last 10 years were included.

Study selection and data extraction: Study selection was presented using a PRISMA flow diagram. Forty-eight studies were included. Data from the articles were presented to address each of the three objectives.

Data synthesis: CPOE systems improved the quality of care provided but also introduced new types of errors. Facilitating factors for implementation included leadership, stakeholder engagement, training, and user-centered design. Inadequate training, software design, changes in workload, and workflow disruptions were identified as barriers. Recommendations for implementation included dedicated training of users, user-centered design, a backup for system downtimes, and stakeholder engagement.

Conclusion: Application of knowledge of the facilitators and barriers for the introduction of a CPOE system supports this change-management process within the specific context and augurs for more successful implementation.

Background: Sickle cell disease (SCD) is a prevalent autosomal recessive hemoglobinopathy affecting millions worldwide, particularly individuals of African ancestry. Sickle cell disease is a lifelong condition associated with a negative impact on quality of life and mortality, causing complications such as painful vaso-occlusive episodes, acute chest syndrome, stroke, long-term anemia, and end-organ damage. Currently, there are 4 U.S. Food and Drug Administration (FDA)-approved drugs, including hydroxyurea, l-glutamine, voxelotor, and crizanlizumab, which work to alleviate symptoms and prevent complications associated with SCD, albeit without addressing the underlying cause of SCD. Allogeneic hematopoietic stem cell transplant (HSCT) has shown promise as a curative approach to SCD but is limited by donor availability and associated complications. This paper aims to review the efficacy and safety of exagamglogene autotemcel and lovotibeglogene autotemcel for managing patients with SCD, including their place in therapy, cost, and accessibility in clinical care. Data Sources: The authors searched PubMed and Medline from 2017 to 2024, for primary literature on both exagamglogene autotemcel and lovotibeglogene autotemcel. Results: The authors identified relevant studies and summarized the data on the two gene therapies. Conclusion: Exagamglogene autotemcel and lovotibeglogene autotemcel are two management strategies that address the underlying cause of SCD and provide curative potential for patients with SCD.

Objective: To evaluate the safety, efficacy, and tolerability of gepirone (Exxua) in the treatment of adult patients with major depressive disorder. Data Sources: A literature search was performed through PubMed, Embase, and PsycINFO using the following terms: Exxua, gepirone, depression, major depressive disorder, anxiety, and anxiety disorders. Study Selection and Data Extraction: Articles that were selected included English-language dominant studies, or studies that could be translated into English by the authors, with terms associated with the safety, efficacy, and/or tolerability of gepirone. Data Synthesis: Gepirone exhibits its antidepressant activity through agonism of 5HT_1A serotonin receptors. Phase 3 clinical trials showed that gepirone at a dose of 20 to 80 mg was proven to be effective in the treatment of major depressive disorder in adult patients. Common adverse effects reported in clinical trials included dizziness, nausea, headache, fatigue, and insomnia. Conclusion: This review evaluates the pharmacokinetic, pharmacologic, efficacy, and safety profile of gepirone and includes a discussion on its place in therapy for the treatment of major depressive disorder. Most clinical guidelines recommend second-generation antidepressants consisting of selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors as first-line therapy options. Gepirone is expected to receive greater clinical relevance and recommendations when compared to other azapirone medications (buspirone) within practice guidelines. Gepirone could be considered as either an alternative option for patients failing first-line therapies or for initial use to avoid unwanted side effects of other therapy options in the treatment of adult patients with major depressive disorder.

Background: The International Society for Heart and Lung Transplantation recommends patients receive warfarin and aspirin following left ventricular assist device (LVAD) placement. Optimal warfarin management in this population has not been well established. Objectives: The objectives of this study were to evaluate warfarin practices in patients immediately post-LVAD implantation. Methods: This single-center, retrospective cohort study included patients 18 years and older following LVAD placement from August 1, 2012 to April 1, 2020. The primary outcome was to assess patient-specific risk factors affecting time to therapeutic range. Secondary outcomes included bleeding events, thrombotic events, and warfarin dosing patterns. Results: Of 104 included patients, 91% reached the therapeutic range at a median of 8 days. A higher proportion of patients started on 3.5 mg or higher reached therapeutic international normalized ratio (INR) and faster (96% vs 90%; 8 vs 5 days) compared to lower doses. Univariate analysis of associations with reaching therapeutic INR range included initial warfarin dose, cumulative warfarin, and warfarin dosing changes, whereas HAS-BLED and CHA₂DS₂VAC were associated with slower time to therapeutic INR. Overall, 44% of patients met Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) bleeding criteria. There were a total of 12 thrombotic events and no pump thrombotic events. Total weekly warfarin dosing was significantly lower post-LVAD (24.3 mg vs 35 mg, P = 0.0009). In addition, warfarin requirements were statistically higher after the first week of therapy (4.0 mg vs 2.89 mg, P < 0.0001). Conclusion: Based on the results, consider warfarin starting dose between 2.5 and 4 mg for patients on LVAD therapy, while balancing patient-specific risks for bleeding.

Background: Current guidelines and literature suggest apixaban may be used in patients with severe kidney disease and atrial fibrillation (AF) for stroke and systemic embolism risk reduction (SSE) or patients with acute venous thromboembolism (VTE). Limited data is available for long-term safety and efficacy outcomes in this patient population. Objective: Evaluate the use of apixaban for AF or VTE in patients with advanced kidney disease. Methods: This single-center, retrospective, Investigational Review Board approved study evaluated patients ≥18 years of age with severe kidney disease on apixaban therapy for VTE or AF from March 1, 2018, to December 31, 2020. The primary outcome was major bleeding from apixaban initiation/continuation until 12 months after discharge. The secondary outcomes included a composite bleed (major bleeding, clinically relevant non-major bleeding, and minor bleeding), the occurrence of VTE or SSE, and death during hospitalization from any cause other than bleeding. Results: Overall, 156 patients met inclusion criteria. Six patients experienced major bleeding (3.8%). Composite bleeding occurred in 16 patients (10.3%); no patients had SSE or VTE, and 4 patients died from causes other than bleeding (2.6%). Limitations included the small sample size and retrospective nature of the study. Conclusion: This study demonstrated that patients with advanced chronic kidney disease on apixaban for AF or VTE had low major bleeding and similar overall bleeding rates compared with previously published literature. When considering the use of apixaban in this population, risks and benefits should be weighed in addition to the consideration of FDA-label dosing guidance.

Objective: To determine the most appropriate phenobarbital dosing regimen by evaluating the safety and efficacy of the drug when specifically used in alcohol withdrawal syndrome (AWS). Data sources: A comprehensive literary search was conducted using PubMed and bibliographic mining in October 2023. Study selection and data extraction: An established monotherapy phenobarbital regimen needed to be established within the article to be included in analysis. Location of implementation was not a deterrent to evaluation, nor was the route of phenobarbital administration. Data synthesis: Six publications were evaluated in this review, and two main phenobarbital dosing regimens emerged. While fix-based dosing strategies and weight-based dosing strategies resulted, the dosing within the regimens resulted in the same or relatively similar doses employed, respectively. Each of the studies had a statistically significant decrease in their primary outcome being studied, and the use of phenobarbital as monotherapy was proven to improve AWS symptoms, significantly decrease intensive care unit and hospital length of stay, decrease the use of adjunctive medications, decrease the use of a ventilator, and prevent seizures. Conclusions: Despite benzodiazepines having been the clinical first-line therapy for AWS, research shows that the pharmacokinetic stability and clinical benefits of phenobarbital are in support creation of phenobarbital protocols, as monotherapy, in hospitals or institutions for patients with AWS.