Annals of Pharmacotherapy最新文献

Background: Intravenous (IV) ganciclovir is used in the management of herpesvirus infections, including cytomegalovirus (CMV). Ganciclovir is usually administered inpatient given the need for close monitoring of laboratory parameters.

Objective: This study describes our experience with administering IV ganciclovir via an outpatient parenteral antimicrobial therapy (OPAT) program.

Methods: This is a retrospective review of patients discharged on IV ganciclovir via OPAT at a tertiary medical center from August 2019 to August 2024. Demographics and treatment outcomes were collected.

Results: Ganciclovir was the preferred agent in all patients either due to concern for gastrointestinal absorption or provider preference. Eighteen patients with a median age of 59.5 (interquartile range [IQR]: 53-65) years met criteria. The most common underlying immunocompromising condition was receipt of a transplanted organ in 16 (88.9%) patients, most commonly heart (8 patients) and kidney transplants (7 patients). Median duration of therapy after hospital discharge was 22 (IQR: 20-27) days. Fifteen (83.3%) patients transitioned to valganciclovir on completion of parenteral therapy either as secondary prophylaxis or continuation of therapy. The most common adverse event was leukopenia in 6 (33.3%) patients. One patient developed acute kidney injury (AKI) requiring dose modification and eventual discontinuation.

Conclusion and relevance: Ganciclovir via OPAT is a viable option in patients requiring an extended duration of IV therapy. In our cohort of 18 patients, only one had early discontinuation of therapy due to ganciclovir-related AKI. Close monitoring of labs and an established OPAT protocol can allow for successful completion of therapy.

Objective: Aztreonam-avibactam (ATM-AVI) is used for difficult-to-treat gram-negative infections. The objective of this review is to analyze the pharmacology, safety, and clinical application of ATM-AVI.

Data sources: PubMed, Embase, and ClinicalTrials.gov were searched using the terms aztreonam avibactam, PF-06947387, Emblaveo, and ATM-AVI.

Study selection and data extraction: Articles written in English and published from January 1, 1985, to June 10, 2025, that related to pharmacology, safety, clinical trials, and clinical application of ATM-AVI were reviewed.

Data synthesis: The ATM-AVI has shown similar efficacy to comparator antibiotics in complicated intra-abdominal infection (cIAI) and hospital/ventilator-acquired pneumonia (HAP/VAP). The REVISIT trial showed cIAI clinical cure rates of 76.4% and 74% for the ATM-AVI and meropenem groups, respectively (treatment difference 2.4% [95% confidence interval, CI = -7.4 to 13.0]). For HAP/VAP, clinical cure rates were 45.9% and 41.7% for the ATM-AVI and meropenem groups, respectively (treatment difference 4.3% [95% CI = -15.1 to 23.1]). The ATM-AVI was generally well tolerated, with hepatic adverse effects being the most commonly reported.Relevance to patient care and clinical practice comparison to existing drugs:The ATM-AVI has demonstrated clinical efficacy for the treatment of cIAI. However, its role needs to be further studied for other infections such as HAP/VAP, urinary tract, and other serious infections. Pharmacoeconomic analysis may be needed to assess the cost-benefit impact in the United States.

Conclusion: The ATM-AVI may be an alternative option for the treatment of cIAI and other complicated gram-negative infections. Further studies are needed to delineate the role of ATM-AVI in clinical practice.

Background: Voriconazole is widely used for patients with fungal infections, but the correlations between the unbound concentration (C_free) of voriconazole in plasma and clinical outcomes remains unclear.

Objective: The aim of this study was to analyze the correlation between C_free and clinical outcomes.

Methods: A retrospective analysis was conducted at the Second Hospital of Hebei Medical University from February 2021 to March 2024 (Shijiazhuang, China). Patients who received voriconazole with at least one measured concentration in our center were enrolled. Based on determined the C_free of voriconazole, factors that might affect C_free were analyzed in conjunction with patient characteristics, and the correlations between voriconazole C_free and the clinical efficacy as well as AEs in patients were investigated.

Results: A total of 60 blood samples were collected from 56 patients. Voriconazole C_free was positive correlation with creatinine, while negative correlation with creatinine clearance. The C_free of patients in the clinical effective group was significantly higher than that in the clinical ineffective group, and the C_free of patients in the group with AEs was significantly higher than that in the group without AEs (P = 0.006, 0.025). Voriconazole C_free (odds ratio [OR] = 2.617, 95% confidence interval [CI]:1.142-6.000, P = 0.023) and albumin level (OR = 1.085, 95% CI: 1.000-1.177, P = 0.050) were independent influencing factors of clinical efficacy, the receiver operating characteristic (ROC) cut off for C_free and efficacy was 0.8 μg·mL^-1. Voriconazole C_free (OR = 1.979, 95% CI: 1.008-3.888, P = 0.048) was an independent risk factor for AEs, the ROC cut off for C_free and AEs was 1.2 μg·mL^-1.

Conclusions and relevance: Voriconazole C_free was positively correlated with clinical efficacy and the incidence of AEs in patients.

Celiac disease can significantly impair levothyroxine absorption, complicating hypothyroidism management despite appropriate dosing. While a gluten-free diet often improves absorption, some patients continue to require high doses. Switching to liquid or softgel formulations can enhance levothyroxine bioavailability and symptom control. Optimizing therapy requires individualized approaches, including dietary intervention, formulation changes, and close monitoring, to achieve and maintain a euthyroid state. Relevant studies were reviewed and incorporated into this commentary to support evidence-based recommendations and highlight clinical considerations.

Background: Poor colon preparation may negatively affect colonoscopy accuracy, result in cancelation, or need for repeat procedure. The glucagon-like peptide-1 receptor agonist (GLP-1RA) class of medications delay gastric emptying, although the clinical impact of this on the quality of colon preparation is not known.

Methods: This was a retrospective matched cohort study in a multi-center, outpatient setting. Colonoscopy reports for patients prescribed GLP-1RA at the time of procedure were compared to a cohort matched for diabetes and cirrhosis who were not prescribed GLP-1RA at the time of procedure. The primary endpoint was a composite of indicators for inadequate bowel preparation.

Objective: The current study's objective is to analyze the effects of GLP-1RA medications on the quality of colonoscopy preparation.

Results: There were 503 patients in each cohort and baseline characteristics were similar. Use of GLP-1RA at the time of colonoscopy was associated with a greater odds of the composite outcome (125 vs 56, odds ratio [OR] = 2.6; 95% CI, 1.9-3.7). There were also increased odds for individual outcome components including proceduralist documenting inadequate, suboptimal, or poor bowel preparation, narrative comments related to inadequate bowel preparation, and recommendation for extended bowel preparation with future colonoscopy. Repeat procedure was also more common in the GLP-1RA cohort (26 vs 9, OR = 3.0; 95% CI, 1.4-6.5).

Conclusion and relevance: This study assessed the impact of the GLP-1RA class of medication on the quality of bowel preparation for lower endoscopies. Glucagon-like peptide-1 receptor agonist use increased the odds of inadequate bowel preparation and repeat procedure.

Objective: The objective of this systematic review and meta-analysis was to compare the efficacy and safety of glucagon-like peptide-1 (GLP-1) receptor agonists for the management of antipsychotic-induced weight gain.

Data sources: A systematic review was conducted following PRISMA methodology through July 2025 that evaluated the efficacy and safety of GLP-1 agonists for the management of antipsychotic-induced weight gain.

Study selection and data extraction: Efficacy endpoints were change in body weight (kg), change in body mass index (BMI) (kg/m²), and change in HbA_1c (%). The safety endpoint was gastrointestinal (GI) adverse effects. A P-value of 0.05 was considered statistically significant, and heterogeneity was reported as I².

Data synthesis: Six studies were included in this systematic review, of which 4 trials were included in the meta-analysis. The difference found between GLP-1 agonists and placebo was a change in weight of -5.85 kg (P = 0.0622, 95% CI = -9.72 to -1.97), a change in BMI of -2.11 kg/m² (P = 0.7692, 95% CI = -5.51 to 1.29), and a change in HbA_1c of -1.58 (P = 0.6659, 95% CI = -4.75 to 1.58). The overall risk ratio for a patient to experience a GI-related adverse effect when taking a GLP-1 agonist compared to placebo was 1.83 (95% CI = 1.42 to 2.37).

Relevance to patient care and clinical practice: While the efficacy endpoints did not reach significance, this meta-analysis shows that select GLP-1 receptor agonists may be used to promote weight loss in patients taking antipsychotics. Controlling antipsychotic-induced weight gain helps patients remain adherent to therapeutic doses of their antipsychotic medications.

Conclusion: The use of certain GLP-1 agonists may be considered to help promote weight loss in patients experiencing antipsychotic-induced weight gain.

Objective: To critically evaluate the available evidence for low-dose oral ketamine for analgesia and provide summary recommendations for clinicians on its use in practice.

Data sources: A search of the primary literature was performed in PubMed from 2010 through 2025 using the following keywords: "Administration, oral," "Administration, sublingual," "ketamine," and "pain."

Study selection and data extraction: All studies and case reports involving the use of oral or sublingual ketamine for analgesia as the primary focus were included.

Data synthesis: Oral ketamine was well tolerated in dose ranges from 25 to 300 mg/day, which were associated with reduced pain scores, improved quality of life, and decreased opioid requirements in line with low-dose infusions for pain management. Weight-based doses above 6 mg/kg corresponded with an increase in adverse effects. Optimal parenteral-to-oral dose conversions are not known; however, dose reductions by 75% from the daily infusion dose maintained analgesia in a small number of cases. Treatment durations ranged from single doses up to 12 years but were predominantly studied in less than 2 years of use.

Relevance to patient care and clinical practice: There remains a dearth of safe and effective pharmacologic pain management options which serve as alternatives to opioids. Low-dose ketamine is an oft-overlooked analgesic with evidence dating back over 50 years, but clinical uptake is poor. Oral ketamine presents a pragmatic formulation, and this review uses the current evidence to address pertinent clinical queries raised by clinicians in practice.

Conclusions: Subanesthetic oral ketamine is an analgesic with continually growing evidence investigating use in a variety of acute and chronic pain syndromes. Based on the current evidence, ketamine may be helpful for refractory pain, as a component of multimodal analgesia, or in patients with high opioid requirements. Adverse effects are typically mild, but the risks of long-term use ultimately remain unclear.

Background: Teicoplanin is widely used to treat Gram-positive infections in adult cancer patients, but early attainment of recommended trough concentrations and clinical determinants of those concentrations are not well characterized in patients receiving standardized, high-dose loading regimens.

Objective: This study aimed to characterize day 4 teicoplanin trough concentrations and to identify clinical predictors of under- and over-target levels in adult cancer patients receiving a standardized high-dose loading regimen.

Methods: This retrospective study included adult cancer patients who received a standardized high-dose teicoplanin loading regimen (600 mg intravenously twice daily on days 1-2 and once on day 3) and had a post-loading trough measurement on day 4. Patients were classified as under (< 20 mg/L), within (20-30 mg/L), or over target (> 30 mg/L). Clinical variables were compared across groups, and multivariable Firth-penalized logistic regression analysis was used to identify factors associated with under- and over-target trough concentrations vs within-target ones.

Results: The study included 211 patients: 71 (33.6%) in the under-, 112 (53.1%) in the within-, and 28 (13.3%) in the over-target group. Higher body weight and febrile neutropenia were associated with higher odds of under-target trough concentrations, whereas higher serum albumin was associated with lower odds; febrile neutropenia was associated with lower odds of over-target concentrations.

Conclusion and relevance: The fixed high-dose loading regimen of teicoplanin evaluated in this study achieves a day 4 trough concentration of 20 to 30 mg/L in about half of adult cancer patients. Higher body weight, febrile neutropenia, and lower serum albumin may help identify patients who require intensified loading and early therapeutic drug monitoring.

Background: It is challenging for patients with heart failure to obtain all core classes of guideline-directed medical therapy (GDMT), especially because sacubitril-valsartan and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are cost-prohibitive for many. Pharmacy technicians in an outpatient heart failure clinic can provide support for medication access.

Objective: The objective of this study was to determine the impact of a pharmacy technician on access to high-cost GDMT for patients with heart failure.

Methods: This retrospective, pre-post cohort study evaluated adults with heart failure who were eligible for treatment with both sacubitril-valsartan and SGLT2i and had a heart failure clinic visit prior to the addition of a pharmacy technician (September 1, 2022, through February 28, 2023) or after the addition (September 1, 2023, through February 29, 2024). Excluded patients were pregnant, incarcerated, Veterans Affairs patients, had an estimated glomerular filtration rate <20 mL/min/1.73 m², or received a heart transplant. The primary composite outcome was a binary variable identifying if patients were prescribed and filled sacubitril-valsartan and/or SGLT2i, evaluated using logistic regression controlling for patient prescription drug coverage. Secondary outcomes included affordable access to ivabradine and vericiguat and 30-day hospitalization rate. Pharmacy technician time spent was evaluated in the post-cohort.

Results: There were 192 patients included; 96 in each cohort. Access to sacubitril-valsartan and/or SGLT2i increased from 71.9% pre-cohort to 86.5% post-cohort (OR = 2.46, 95% CI = [1.18, 5.34]; P = 0.02). No differences were observed in secondary outcomes. The pharmacy technician spent an average of 66.4 minutes per patient assisted (n = 21/96).

Conclusion and relevance: This study demonstrated a significant increase in access to sacubitril-valsartan and/or SGLT2i after the implementation of a pharmacy technician. Larger, prospective studies are needed to evaluate the impact of a pharmacy technician on clinical outcomes in this population.