Annals of Pharmacotherapy最新文献

Background: The optimal dosing of intravenous ganciclovir in patients receiving sustained low-efficiency dialysis (SLED) remains unclear.

Objective: The primary objective is to characterize the dosing of ganciclovir for treating and preventing cytomegalovirus (CMV) in Solid Organ Transplant Recipients receiving SLED. The secondary objective is to evaluate the safety and efficacy of the dosing practices described in this study.

Methods: Retrospective review of electronic medical records from solid organ transplant recipients (SOTRs) admitted to the Medical Surgical Intensive Care Unit at the Toronto General Hospital (TGH) between November 28, 2016, and September 1, 2021, was conducted. Patients concurrently receiving ganciclovir and SLED were included.

Results: Among the 27 encounters for CMV prevention, 18 patients underwent 8-hour SLED, 6 underwent 24-hour SLED, and 3 received other SLED durations. Most patients (80%) on 8-hour SLED began ganciclovir at 2.5 mg/kg/d, whereas 80% of those on 24-hour SLED started at 5 mg/kg/d. No breakthrough viremia occurred at 5 mg/kg/d, with 1 instance at 2.5 mg/kg/d. Cytopenia rates were higher at 5 mg/kg/d (33% vs 20%). For treatment (n = 20), 16 patients underwent 8-hour SLED, 2 underwent 24-hour SLED, and 2 underwent 12-hour SLED. Most (75%) on 8-hour SLED started at 2.5 mg/kg/d, whereas all on 24-hour SLED began at 5 mg/kg/d. Viral eradication rates were 75% and 60% at 2.5 and 5 mg/kg/d, respectively, with higher cytopenia rates at 5 mg/kg/d (37.5% vs 0%). Dose adjustments were primarily in response to refractory disease or cytopenia.

Conclusion and relevance: At our institution, ganciclovir dosing patterns suggest that for patients requiring 8-hour SLED, there is clinician comfort in using 2.5 mg/kg/d for prevention and 5 mg/kg/d for treatment. In 24-hour SLED, 5 mg/kg/d may be considered for prevention. Higher doses may be considered for CMV treatment; however, we found greater variability in the dosing practices for these patients. Further research with larger sample sizes and ganciclovir drug-level assessments is needed to optimize dosing strategies for CMV treatment.

Background: Patients admitted with acute myocardial infarction (AMI) are at high risk for morbidity and rehospitalizations. Pharmacists can play a vital role in secondary prevention by providing services such as medication reconciliation and patient education upon discharge. Objective: The purpose of this study was to evaluate the impact of a pharmacist-led transitions of care (TOC) service on readmissions in patients hospitalized with AMI. Methods: This single center, pre-post observational cohort study evaluated adults with AMI who received pharmacist TOC services compared with a historical cohort who did not. Patients were excluded if they underwent cardiac surgery during admission. The primary outcome was the difference in 90-day cardiovascular (CV)-related readmissions. Secondary outcomes included 30- and 90-day all-cause readmissions, 30-day CV-related readmissions, and patients discharged on defect-free guideline-directed medical therapy (GDMT) for AMI. Results: There were 252 patients in each cohort included. No difference was found in 90-day CV readmissions, with a rate of 10.7% in the pre-TOC group versus 9.9% in the post-TOC group (OR 0.937, 95% CI [0.493, 1.769]; P = 0.842). Patients discharged on defect-free GDMT significantly increased from 61.5% pre-TOC to 87.7% post-TOC (OR 5.424, 95% CI [3.204, 9.468]; P < 0.001). There were no significant differences found in other key secondary outcomes. Conclusion and relevance: This study did not find a significant difference in hospital readmissions after implementation of a pharmacist-led TOC service. However, the service was associated with a significant increase in patients discharged on defect-free GDMT. Further studies are needed to confirm the impact of increased GDMT on clinical outcomes.

Background: Sympathomimetic vasopressors may be administered through a peripheral catheter, but there are limited data available on the safety of peripheral use.

Objective: The purpose of this study was to analyze the safety of peripherally infused sympathomimetic vasopressors.

Methods: A multicenter, retrospective observational study was conducted to evaluate patients who received peripheral vasopressors. The study's primary outcome was to assess the incidence of extravasation during the administration of peripheral vasopressors. Secondary outcomes include avoidance of central venous catheter (CVC) placement and institution protocol deviations.

Results: There were 198 patients included in the study, of which 142 patients received norepinephrine, 48 patients received phenylephrine, and 8 patients received epinephrine peripherally. Extravasation events occurred in 11 (5.6%) patients. Seven patients required a pharmacologic antidote and 10 patients required a warm compress. No significant differences were seen in characteristics of patients who extravasated compared with those who did not. Protocol deviations identified during the study included 24 (12.1%) patients receiving doses above the protocol maximum, 19 (9.6%) with a body mass index above the protocol maximum, and 45 (22.7%) patients receiving peripheral vasopressor over 24 hours. The majority of patients were able to avoid CVC placement (59.1%).

Conclusion and relevance: Peripherally infused sympathomimetic vasopressors are safe to administer up to 24 hours with a low incidence of extravasation events while avoiding CVC placement in the majority of patients.

Objective: To review the pharmacology, efficacy, safety, dosing and administration, and relevance to patient care and clinical practice of B-cell maturation antigen (BCMA) directed immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAb), for the management of relapsed/refractory multiple myeloma (RRMM).

Data sources: A literature review of PubMed (1966 to July 2024) was conducted using the keywords idecabtagene vicleucel, ciltacabtagene autoleucel, teclistamab, elranatamab, and multiple myeloma. Data was also obtained from unpublished meeting abstracts and prescribing information.

Study selection and data extraction: All relevant published articles, unpublished abstracts, and prescribing information on anti-BCMA immunotherapies for the treatment of RRMM were reviewed.

Data synthesis: Idecabtagene vicleucel and ciltacabtagene autoleucel are BCMA-directed CAR-T cell therapies that have been compared to standard of care (SOC) regimens for MM in early relapse in the phase III trials KarMMa-3 and CARTITUDE-4, respectively. Both studies demonstrated a significantly improved in response rates, depth of response, and progression-free survival compared to SOC. BsAbs teclistamab and elranatamab have been evaluated in the phase II trials MajesTEC-1 and MagnetisMM-3, respectively. Overall response rates of 63 and 61% were observed with teclistamab and elranatamab, respectively, in a population of patients with heavily pretreated RRMM.Relevance to Patient Care and Clinical Practice in Comparison with Existing Drugs:BCMA-directed immunotherapies have demonstrated efficacy in the treatment of RRMM. Safety issues with BCMA-directed immunotherapies include cytokine release syndrome, neurotoxicity, infections, and cytopenias. Operational challenges and issues with access to care exist with these therapies as they may be limited to institutions with the infrastructure to safely administer and monitor patients for toxicities.

Conclusion: BCMA-directed immunotherapies represent an important advancement in the management of RRMM and have significantly added to the available treatment options for this disease.

Objective: To review the therapeutic profile of elranatamab, a novel bispecific T-cell-redirecting therapy, in treating relapsed or refractory (R/R) multiple myeloma (MM).

Data sources: A PubMed search was conducted for English-language articles published from January 2000 through June 2024, using the search terms: PF-06863135, elranatamab, Elrexfio, and "Multiple Myeloma." Additional data were obtained from ClinicalTrials.gov and other pertinent publications and meeting abstracts.

Study selection and data extraction: Clinical trials, guidelines, and prescribing information pertaining to elranatamab were included.

Data synthesis: The phase II MagentisMM-3 trial demonstrated an overall response rate of 61.0% (95% confidence interval, 51.8-69.6) in patients naïve to B-cell maturation antigen targeting therapy (cohort A, n = 123), establishing elranatamab monotherapy as a viable treatment option for patients with R/R MM who have received at least 4 prior lines of therapy. The duration of response and progression-free survival at 12 months were 75.3% and 56.6%, respectively.Relevance to patient care and clinical practice in comparison with existing drugs:Despite the promising activity of elranatamab in R/R MM, the significant treatment-related adverse effects (AEs) associated with this therapy necessitate careful monitoring and expert management. Common AEs include cytokine release syndrome, neurotoxicity, hematologic toxicity, and infectious complications. The cost-effectiveness of elranatamab has yet to be evaluated.

Conclusions: Elranatamab is approved by the Food and Drug Administration as a treatment option for patients with heavily pretreated R/R MM. Further studies are warranted to identify the optimal treatment strategy for elranatamab and other bispecific antibodies in the management of R/R MM.

Background: A protocol was established for ventilator-associated tracheitis or pneumonia using inhaled tobramycin 300 mg every 12 hours in mechanically ventilated children via a vibrating mesh nebulizer, 30 cm from the endotracheal tube in the inspiratory loop of the mechanical ventilator.

Objectives: The primary objective was to determine the incidence of detectable tobramycin trough concentrations >0.5 µg/mL. Secondary objectives included a comparison of clinical characteristics between those with and without detectable concentrations and identification of patients with acute kidney injury (AKI) as defined by the Kidney Diseases Improving Global Outcomes (KDIGO) criteria.

Methods: This was a single-center retrospective study of critically ill children <18 years without cystic fibrosis receiving inhaled tobramycin between July 1, 2016, and August 31, 2021. Data collection included demographics, tobramycin regimen, and renal function. Analysis was performed using SAS 9.4, with a P-value <0.05, and a multivariable regression model was performed to identify factors for detectable concentrations and AKI.

Results: Forty-four patients (66 courses) were included, with an overall age of 0.83 years. Thirty (68%) patients had detectable concentrations and 9 (20.5%) developed AKI. No significant differences in demographics, diagnosis, mechanical ventilation settings, and number of nephrotoxins were noted between those with and without detectable concentrations or AKI. Multivariable regressions did not identify factors associated with detectable concentrations or AKI.

Conclusion and relevance: Detectable concentrations occurred with the majority of courses, with AKI associated with approximately one-fourth of courses. Clinicians should consider utilizing trough monitoring for all mechanically ventilated critically ill children receiving inhaled tobramycin.

The objective of this project was to develop a standardized list of renally eliminated and potentially nephrotoxic drugs that will help inform initiatives to improve medication safety. Several available lists of medications from the published literature including original research articles and reviews, and from regulatory agencies, tertiary references, and clinical decision support systems were compiled, consolidated, and compared. Only systemically administered medications were included. Medication combinations were included if at least 1 active ingredient was considered renally dosed or potentially nephrotoxic. The medication list was reviewed for completeness and clinical appropriateness by a multidisciplinary team of individuals with expertise in critical care, nephrology, and pharmacy. An initial list of renally dosed and nephrotoxic drugs was created. After reconciliation and consensus from clinical experts, a standardized list of 681 drugs is proposed. The proposed evidence-based standardized list of renally dosed and potentially nephrotoxic drugs will be useful to harmonize epidemiologic and medication quality improvement studies. In addition, the list can be used for clinical purposes with surveillance in nephrotoxin stewardship programs. We suggest an iterative re-evaluation of the list with emerging literature and new medications on an approximately annual basis.