Pharmacotherapy最新文献

Antibiotics constitute the majority of prescriptions for women during pregnancy. Common bacterial infections, including urinary tract infections, skin and soft tissue infections, and upper and lower respiratory tract infections, are expected in pregnancy, similar to the general public. These infections carry additional risks to both the woman and fetus; thus, antibiotics are often prescribed. Antibiotics, like other drugs, are not benign and may carry additional risks to the fetus beyond commonly encountered adverse drug events seen across most patient populations. Since 2014, 19 new antibiotics have been approved by the United States Food and Drug Administration. Additionally, in 2018, the previously held pregnancy category rating expired, and all manufacturers' labeling was updated with new narrative language reflecting safety in pregnancy, lactation, and males and females of reproductive potential. This review provides a comprehensive summary of available data and an update to the 2015 publication regarding the safe use of antibiotics in pregnancy. The primary focus of this review is on newly approved antibiotics, along with any additional published evidence on previously reviewed antibiotics. Data on lactation or antiviral or antifungal use in pregnancy are not included. Clinicians should remain updated on current available evidence and vigilant to provide safe and effective antibiotic decision-making in pregnant women.

Study objective: The primary objective of this study was to determine if there was a significant change in potassium levels with sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy in people with type 2 diabetes (T2D). A co-primary objective was to evaluate which factors may predispose a patient to changes in potassium levels.

Design: Multicenter retrospective cohort chart review.

Data source: Study patients were identified through an electronic medical record-generated report if they had T2D and were prescribed an SGLT2 inhibitor from January 2013 to September 2019.

Patients: Patients were included if they had T2D, were receiving care at Advocate Medical Group, and were confirmed to have taken one of the four SGLT2 inhibitors available at the time of study approval, canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin, for at least 7 days. Patients were excluded if they did not have a basic metabolic panel or comprehensive metabolic panel recorded 1 year prior to or 6 months after SGLT2 inhibitor therapy initiation.

Results: Data extraction from the electronic medical record identified 6425 patients receiving an SGLT2 inhibitor, of which 1926 met inclusion criteria. The SGLT2 inhibitor most prescribed was canagliflozin (43.7%), followed by empagliflozin (36.9%) and dapagliflozin (19.4%). Concomitant baseline medications were thiazide diuretics (27.5%); angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors (72.1%); and/or mineralocorticoid receptor antagonists (27.2%). A statistically significant change in potassium levels was found with dapagliflozin (p = 0.018); albeit not clinically significant. No other statistically significant changes or patterns were identified. The overall mean change in serum potassium from baseline was 0.021 mmol/L within 3 months; 0.007 mmol/L from 3 to 5.9 months; -0.017 mmol/L within 6-12 months; and 0.004 mmol/L after more than 12 months.

Conclusions: No clinically significant increase or decrease in potassium levels was observed upon initiation of SGLT2 inhibitor therapy in patients with T2D. This was consistent across background medication use and patient-specific factors. Baseline potassium should not be a factor in initiating SGLT2 inhibitor therapy, if clinically indicated, in patients with T2D.

Introduction: The prevalence of exposure to supratherapeutic doses or contraindicated medications based on renal dosing criteria, also known as potentially inappropriately prescribed medications (PIPM), is currently unknown among patients on peritoneal dialysis (PD). The primary objective of this study was to evaluate the prevalence of PIPM in the first year of PD among Medicare patients in the United States.

Methods: This was a retrospective longitudinal cohort analysis of patients starting PD in 2018 in the United States Renal Data System database. Inclusion criteria were patients >65 years of age, continuously enrolled in Medicare Part D for 12 months, and prescribed ≥1 medication(s) at the start of dialysis. Prevalence of exposure to PIPM was determined at the start of dialysis and quarterly over 1 year. Logistic regression evaluated which patient characteristics (age, sex, race, Hispanic ethnicity, rurality, social deprivation index (SDI), United States region, polypharmacy, and diagnosis of diabetes and hypertension) were associated with exposure to ≥1 PIPM at the start of PD.

Results: There were 3760 patients included, and 28% were exposed to PIPM at the start of dialysis, and 21.8% were still exposed by the end of the first year. Patients with ≥4 versus <4 medications were at 2.8-14.1 times the odds of being exposed to PIPM (<0.001). Other key characteristics associated with exposure to PIPM were age ≥85 versus <75 years (adjusted odds ratio [aOR] 0.67, 95% confidence interval [CI] 0.48-0.95 p = 0.03), living in the South versus the Northeast (aOR 1.30 95% CI 1.02-1.66, p = 0.04), and diagnosis of diabetes (aOR 1.52, 95% CI 1.29-1.78, p < 0.001).

Conclusion: This study found that approximately 20%-30% of patients receiving PD were exposed to PIPM from 2018 to 2019. Results from this study support the need to create medication management programs to decrease exposure to PIPM.

Introduction: With recent clinical implementation of tirzepatide, patients with type 2 diabetes mellitus (T2DM) are transitioning from glucagon-like peptide 1 receptor agonists (GLP-1 RA) to a dual gastric inhibitory polypeptide (GIP)/GLP-1 RA-like tirzepatide. Limited literature is available for insulin dose adjustments for patients concurrently using insulin during this transition. In clinical trials, tirzepatide has shown greater glycated hemoglobin (A1c) reduction and glucose-lowering effects compared to GLP-1 RAs, such as semaglutide, suggesting a potential elevated risk of hypoglycemia without proactive insulin adjustments.

Objectives: The primary objective of this study was to assess the percent change in daily insulin requirements 6 months after transitioning patients from GLP-1 RAs to tirzepatide.

Methods: This retrospective cohort study includes patients with T2DM who transitioned from a GLP-1 RA to tirzepatide while concurrently using insulin therapy. Patient-reported doses of insulin and study medications were collected by chart review by investigators, along with baseline demographics and adverse effects as additional endpoints.

Results: Sixty-six patients were included. The median insulin dose reduced from 101 units at baseline to 71 units after 6 months, with a median decrease of 9.5 units (p < 0.001). The median percent change in insulin dose was -9.2%. Patients with a baseline A1c of 8.0% or lower required a larger decrease in insulin compared to patients with a higher baseline A1c (-22.6% vs. 0%, p = 0.018). The intensity of GLP-1 RA and tirzepatide, determined by agent and dose, did not show a difference in insulin requirements (p = 0.279 and p = 0.317, respectively). Hypoglycemia occurred in eight patients (12.1%).

Conclusion: Patients require a reduction in insulin when transitioning from GLP-1 RAs to tirzepatide, especially if baseline A1c is less than or equal to 8.0%. Larger, comparative studies need to be performed to provide specific recommendations for various doses and product types of incretin receptor agonists.

Osteoarthritis (OA) is the most common form of arthritis, affecting over 500 million people globally. Current treatments are primarily symptom-focused, with no approved therapies to halt disease progression. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in type 2 diabetes (T2D) and obesity, demonstrate significant weight loss and glucose-lowering effects and have been shown to possess anti-inflammatory properties. Given the central role of inflammation and metabolic dysfunction in OA, this review examines the potential utility of GLP-1 RAs in OA management, focusing on both indirect effects, such as weight reduction, and possible direct effects on inflammatory pathways and cartilage preservation. Clinical studies suggest that GLP-1 RAs may benefit people with OA by reducing weight, improving glycemic control, and modulating inflammatory markers relevant to OA progression. Notable findings include significant weight loss and pain reduction in people with knee OA (KOA) treated with semaglutide in the STEP-9 trial. In other studies, GLP-1 RAs have shown potential to lower oxidative stress and pro-inflammatory cytokines, such as tumor necrosis factor (TNF-α) and interleukin (IL)-6, with reductions in OA-related pain and functional impairment observed in some cohorts. However, results vary, with some studies showing limited effects, potentially linked to the degree of weight loss achieved. Although some studies report variability in pain relief, likely influenced by the degree of weight loss achieved, GLP-1 RAs have shown overall promise in reducing both OA symptoms and markers associated with disease progression. This emerging evidence supports the utility of GLP-1 RAs as a potential disease-modifying option for OA, offering a dual benefit in metabolic and joint health. Future research should focus on establishing the long-term efficacy and safety and elucidating the mechanism by which GLP-1 RAs influence OA pathology.

Introduction: Heart failure (HF) affects more than 6 million adults in the United States, contributing to substantial morbidity, mortality, and health care costs. Despite advances in medical care, many medications can exacerbate HF, yet their prevalence of use remains unknown. This study examined the national use of prescription medications that could exacerbate HF in adults with self-reported HF.

Methods: We analyzed data from US adults with self-reported HF in the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020. Medications known to exacerbate HF, identified from HF guidelines, were documented through pill bottle reviews. Weighted estimates were used to calculate prevalence overall and by sex, race and ethnicity, and level of evidence for avoidance. Multivariable logistic regression models calculated adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for the use of these high-risk medications by sex and race and ethnicity.

Results: A total of 687 participants, representing 5.2 million U.S. adults with HF after applying sampling weights, were included (mean age, 66.1 [95% CI 64.9, 67.4] years; 50.4% female [95% CI 45.9%, 55.0%]). Overall, 14.5% (95% CI 10.4%, 19.5%; n = 92) of adults with HF were prescribed at least one medication known to exacerbate HF, with the most common being diltiazem, meloxicam, and ibuprofen. Use of these medications was not significantly different by sex nor by race and ethnicity. Of these medications, 21.7% (95% CI 10.7%, 38.8%) had level A evidence warning against use, and 78.3% (95% CI 61.2%, 89.3%) had B level evidence.

Conclusion: Over one-seventh of U.S. adults with HF were likely to have been prescribed medications that could exacerbate the condition, underscoring the need to optimize care. Reducing high-risk medication use may mitigate HF exacerbations and improve outcomes in this vulnerable population.

Objective: Hyponatremia is a common electrolyte disorder among older adults that can cause serious adverse effects. The purpose of this study was to assess the risk of hyponatremia with the concurrent use of selective serotonin reuptake inhibitors (SSRIs) and thiazide diuretics in an older population.

Methods: Two retrospective nested case-control studies were conducted with exposure to an SSRI or a thiazide diuretic. Persons of interest were those enrolled in Medicare and who received parts A, B, and D benefits from 2017 to 2019 and who were receiving either an SSRI or thiazide diuretic. Cases were individuals with a diagnosis of hyponatremia. Controls had no documented history of hyponatremia. A logistic regression was conducted to determine the odds of hyponatremia.

Results: Of the 551,298 patients receiving a SSRIs, the mean age was 77.8 years (Standard Deviation (SD) ± 8.0 years), 69% were female, and 91.23% were classified as White. We identified 701,007 individuals receiving a thiazide diuretic, with a mean age of 77.1 years (SD ± 7.2 years), 60.2% female, and 82.72% White. The prevalence of hyponatremia was 10.4% in patients taking thiazides alone and 9.0% in those taking SSRIs alone. On the other hand, patients on both medications had a hyponatremia prevalence of approximately 13.0%. Among SSRI users, the adjusted odds ratio (OR) of hyponatremia with concomitant use of thiazide diuretics was 1.24 (95% Confidence Interval (CI): 1.22-1.26). For thiazide users, the adjusted OR of hyponatremia with exposure to SSRIs was 1.27 (95% CI:1.24-1.29).

Conclusion: The concurrent use of thiazide diuretics and SSRIs is associated with an increased risk of hyponatremia in older populations.

Introduction: The use of serum creatinine (SCr) for drug dosing has significant limitations and is influenced by many non-kidney factors. Cystatin C (cysC) is an alternative or additional marker of kidney function that is less affected by non-kidney factors. Although cysC may be useful in hospitalized patients, the use of cysC to calculate drug dosing in critically ill patients has been incompletely investigated.

Objective: The objective of this study was to determine the rate of discordance in estimated glomerular filtration rate (eGFR) between SCr-based calculations and SCr/cysC-based calculations that affect drug dosing in critically ill patients.

Methods: This was a single-center, retrospective, observational cohort study at an academic medical center including critically ill adult patients admitted in 2023 with SCr and cysC ordered. Data were collected via chart review. Demographic data were analyzed via descriptive statistics. Discordance, defined as the percentage of times at which there is at least one discrepancy in kidney dosing for a medication using Cockcroft-Gault (CG) creatinine clearance versus Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR creatinine-cystatin C (eGFRcr-cys) equations, was analyzed via Wilcoxon matched pair signed ranked sum. eGFR calculations were normalized for patients' body surface area for comparison.

Results: The study population included 232 patients (53.02% female; mean age 58.7 +/- 14.9 years; with 62.5% in medical, 23.28% in surgical, and 8.62% in neurological intensive care) with a median SCr of 0.94 mg/dL IQR [0.57-1.58] and median cysC of 1.92 mg/L IQR [1.27-2.77]. The median clearance rates were 68.5 mL/min (45.3-111.5) for CG and 53.9 mL/min (30.9-80.7) for CKD-EPI eGFRcr-cys; p < 0.001. The discordance rate across all study drugs was 32.3% (75/232). The four most common study drugs demonstrating discordance were cefepime 40.6% (52/128), vancomycin 38.3% (46/120), levetiracetam 35.1% (13/37), and piperacillin/tazobactam 11.6% (5/43).

Conclusion: Clinically significant discordance exists between SCr and SCr/cysC-based estimates of kidney function. This study established a discordance rate, as defined by drug dosing, of 32.3% in adult patients admitted to the ICU.

Introduction: Clozapine and risperidone are second-generation antipsychotics used in the treatment of schizophrenia. There are no guidelines on cross-titration of antipsychotics and, additionally, there is a paucity of published data to support the potential utility of using serum drug levels to guide dosing in these situations.

Case report: A 68-year-old female patient with a history of schizophrenia, taking risperidone and fluoxetine, and a recent diagnosis of Parkinson's disease was admitted to the hospital after a fall at home. During the patient's hospital stay, utilizing serum clozapine levels as guidance, the patient was cross-titrated from risperidone 12 mg daily to a final dose of clozapine 75 mg daily over the span of 17 days, in the setting of multiple possible drug-drug interactions.

Discussion: There is no evidence-based guidance on transitioning patients from one antipsychotic to another especially in the setting of drug-drug interactions. In this case, the patient was successfully transitioned from risperidone to clozapine using serum clozapine levels and clinical status to guide decision-making.

Conclusions: Utilizing serum clozapine levels may be helpful in guiding dose changes during antipsychotic cross-titration, especially when multiple drug interactions are involved.