Pharmacotherapy [JOURNAL]
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200 papers
Assessment of the association between mixed-oil lipid injectable emulsion use and 30-day mortality or infection persistence from fungal catheter-related bloodstream infections in pediatric patients following receipt of parenteral nutrition: A retrospective cohort study.
Alvira-Arill GR, Yarbrough A, Tansmore J … +5 more , Sierra CM, Bashqoy F, Herrera OR, Peters BM, Stultz JS
Pharmacotherapy · 2025 Aug · PMID 40589409 · Full text
BACKGROUND: Compared to soybean-oil and fish-oil formulations, the use of mixed-oil lipid injectable emulsion is associated with reduced catheter-related bloodstream infection rates in pediatric patients receiving parent...
BACKGROUND: Compared to soybean-oil and fish-oil formulations, the use of mixed-oil lipid injectable emulsion is associated with reduced catheter-related bloodstream infection rates in pediatric patients receiving parenteral nutrition. The objective of this study was to compare clinical outcomes of fungal catheter-related bloodstream infections in pediatric patients following receipt of parenteral nutrition with mixed-oil (SMOFlipid) lipid injectable emulsion or other formulations (soybean-oil [Intralipid] or fish-oil [Omegaven]). METHODS: A retrospective cohort study of pediatric patients with fungal catheter-related bloodstream infections following administration of parenteral nutrition and injectable lipid emulsion from five pediatric hospitals in the United States during a 5-year period was conducted. Differences in a composite outcome of 30-day mortality from first positive blood culture and/or infection persistence based on type of lipid injectable emulsion received prior to infection were assessed through generalized linear mixed models with binomial distribution. RESULTS: One-hundred twelve fungal catheter-related bloodstream infections were assessed from 104 patients who received mixed-oil lipid injectable emulsion (n = 43) or other formulations (n = 69) prior to infection. Thirty-nine infections met the composite outcome (32 with persistent infection, three with 30-day mortality, and four with both). On multivariable analysis, receipt of mixed-oil lipid injectable emulsion demonstrated a non-statistically significant increase in the composite outcome (odds ratio [OR] [95% confidence interval {CI}]: 1.80 [0.75-4.34]; p = 0.19). Factors independently associated with the composite outcome include receipt of systemic antifungal prophylaxis (OR [95% CI]: 5.72 [1.33-24.7]; p = 0.019) and delay in central venous catheter removal (OR [95% CI]: 1.09 [1.01-1.19]; p = 0.03). Notable factors not associated with the composite outcome included continued receipt of lipid injectable emulsion, empiric antifungal choice, time to antifungal administration, and gastrointestinal surgery within 90 days prior to infection. CONCLUSION: Use of mixed-oil lipid injectable emulsion compared to other formulations (soybean-oil or fish-oil) demonstrated a non-statistically significant increase in 30-day mortality and/or infection persistence from fungal catheter-related bloodstream infections in pediatric patients receiving parenteral nutrition.
Response to comment on "Prevalence of potentially inappropriately prescribed medications among older adults receiving peritoneal dialysis".
Almodovar AS, Nahata MC
Pharmacotherapy · 2025 Aug · PMID 40583814 · Publisher ↗
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Cefepime-taniborbactam: Ushering in the era of metallo-β-lactamase inhibition.
Van Helden SR, Al Musawa M, Bleick CR … +2 more , Herbin SR, Rybak MJ
Pharmacotherapy · 2025 Jul · PMID 40542539 · Publisher ↗
Carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CR-PA) continue to pose a significant threat to human health. Furthermore, the prevalence of metallo-β-lactamase (MBL)-producing CRE and CR-PA is in...
Carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CR-PA) continue to pose a significant threat to human health. Furthermore, the prevalence of metallo-β-lactamase (MBL)-producing CRE and CR-PA is increasing, which are capable of hydrolyzing nearly all β-lactam antibiotics. Cefepime-taniborbactam (FTB) is a novel bicyclic boronate β-lactam-β-lactamase inhibitor combination with direct inhibitory activity against MBLs (Ambler Class B), in addition to Ambler Class A, C, and D serine-β-lactamases. FTB has demonstrated high in vitro activity against CRE and CR-PA, including isolates producing NDM, VIM, KPC, AmpC, OXA-48, and extended-spectrum β-lactamases (ESBLs). Furthermore, FTB has demonstrated in vitro activity against Stenotrophomonas maltophilia and Burkholderia cepacia complex. Resistance to FTB is observed in isolates producing IMP, as well as MBL variants NDM-9, NDM-30, and VIM-83. FTB remains susceptible to non-β-lactamase resistance mechanisms, including penicillin-binding protein 3 (PBP3) target mutations. The pharmacodynamic driver of taniborbactam efficacy is the ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC), and the study dose of FTB 2 g/0.5 g every 8 h infused over 2 h achieves sufficient serum and tissue exposures to maintain therapeutic efficacy. Both components are primarily renally eliminated as unchanged drug; therefore, dose adjustments for renal impairment are required. The clinical efficacy of FTB was demonstrated in the phase III Cefepime Rescue with Taniborbactam in Complicated Urinary Tract Infection (CERTAIN-1) trial, where it demonstrated both non-inferiority and superiority (prespecified analysis) to meropenem in the composite of clinical and microbiologic success at the test of cure for the treatment of complicated urinary tract infection. The safety of FTB was demonstrated throughout its clinical development. Thirteen percent of patients experienced a treatment-related adverse drug event in the phase III clinical trial, with 3% of patients requiring discontinuation of the study agent. Cefepime-taniborbactam appears to be a promising addition to the antibiotic arsenal, particularly as the prevalence of infections caused by MBL-producing organisms continues to rise.
Managing attention-deficit/hyperactivity disorder in a breastfeeding mother: A case report.
Kim J, Nichols DA, Zhang T … +2 more , Faraone SV, Radonjić NV
Pharmacotherapy · 2025 Aug · PMID 40536085 · Publisher ↗
INTRODUCTION: Attention-deficit/Hyperactivity Disorder (ADHD) is increasingly recognized in adult women. However, clinical guidance on prescribing ADHD medications during breastfeeding remains limited. Despite the effect...
INTRODUCTION: Attention-deficit/Hyperactivity Disorder (ADHD) is increasingly recognized in adult women. However, clinical guidance on prescribing ADHD medications during breastfeeding remains limited. Despite the effectiveness of ADHD medications, concerns about drug transfer into breastmilk often lead to conservative prescribing or discontinuation of therapy during the perinatal period, compromising maternal well-being. CASE SUMMARIES: In this report, we present a case of a 25-year-old woman at 3 weeks postpartum and exclusively breastfeeding, who presented with ADHD combined type, with inadequate symptom control on extended-release bupropion 300 mg daily. Given poor tolerance at higher doses of bupropion, she was initiated on immediate-release methylphenidate and switched later to the extended-release formulation to minimize the risk of activation previously experienced with antidepressant use. DISCUSSION: Both mother and infant were monitored for 6 months after medication initiation, during which the mother reported improvements in hyperactive and impulsive symptoms as reflected by scoring of the Adult ADHD Self-Report Scale. She also reported improvements in concentration, mood, and functioning. There were no adverse effects on milk supply, and the infant demonstrated normal growth and development. CONCLUSIONS: This case underscores the feasibility of cautiously escalating stimulant therapy in a breastfeeding mother with ADHD, showing improved functioning in the mother without immediate effects on development in the infant. Significant gaps persist in guidance for postpartum ADHD care, underscoring the need for more research to inform safe and effective treatment.
Heterogeneous effects of sodium-glucose cotransporter-2 inhibitors compared to dipeptidyl peptidase-4 inhibitors on nephrolithiasis in older adults with type 2 diabetes.
Radwan RM, Huang W, Li Y … +9 more , Shao H, Guo Y, Zhang Y, Fonseca V, Shi L, Huang Y, Schatz D, Bian J, Guo J
Pharmacotherapy · 2025 Jul · PMID 40525798 · Full text
BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of nephrolithiasis. Emerging evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2i) may reduce this risk; however, data remain inc...
BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of nephrolithiasis. Emerging evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2i) may reduce this risk; however, data remain inconclusive. OBJECTIVE: To examine the risk of nephrolithiasis among users of SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP4i) in a real-world population of older adults with T2D. METHODS: A retrospective cohort study was conducted using claims data from a sample of national Medicare beneficiaries. Individuals with T2D who initiated SGLT2i or DPP4i therapy between January 1, 2016, and December 31, 2018, were identified. The index date was defined as the date of the first prescription for either SGLT2i or DPP4i, with no prior use of either drug in the preceding year. Patients were followed from the index date until the earliest occurrence of a medical encounter with a primary diagnosis of nephrolithiasis, death, or December 31, 2018. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates, including sociodemographic characteristics, comorbidities, and comedication use. Cox proportional hazards regression models were applied to compare the risk of nephrolithiasis between SGLT2i and DPP4i users. Additional analyses were conducted within subgroups defined by sex, race, and baseline nephrolithiasis status. RESULTS: Of 116,506 included Medicare beneficiaries with T2D (mean age 72 ± 10 years, 53% women), 0.96% developed nephrolithiasis over a median follow-up of 360 days (interquartile range [IQR] 200-467 days). The incidence rate of nephrolithiasis was 9.89 (95% confidence interval [CI] 8.49-11.52) and 11.02 (95% CI 10.34-11.73) events per 1000 person-years in the SGLT2i and DPP4i groups, respectively. After applying IPTW, baseline characteristics were well balanced between the two groups. SGLT2i use was associated with a significantly lower risk of nephrolithiasis compared to DPP4i use (hazard ratio [HR], 0.81; 95% CI 0.66-0.99; p = 0.04). In subgroup analyses, SGLT2i use compared to DPP4i was associated with a significantly lower risk of nephrolithiasis among males (HR 0.75; 95% CI 0.58-0.98; p = 0.04), non-Hispanic Black (NHB) individuals (HR 0.22; 95% CI 0.07-0.64; p < 0.01), and those without baseline nephrolithiasis (HR 0.68; 95% CI 0.53-0.88; p < 0.01). CONCLUSIONS: In older adults with T2D, SGLT2i use was associated with a lower risk of nephrolithiasis compared to DPP4i, particularly among men, NHB individuals, and those without baseline nephrolithiasis. Although causality cannot be established, these findings provide real-world evidence supporting a potential benefit of SGLT2is in reducing nephrolithiasis risk, offering valuable insights to guide the selection of glucose-lowering drugs in older adults with T2D.
Comment on "Establishing discordance rate of estimated glomerular filtration rate between serum creatinine-based calculations and cystatin-C-based calculations in critically ill patients".
Khan RW, St Peter WL
Pharmacotherapy · 2025 Jul · PMID 40511814 · Publisher ↗
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Response to Comment on "Establishing discordance rate of estimated glomerular filtration rate between serum creatinine-based calculations and cystatin-C-based calculations in critically ill patients".
Williams VL, Gerlach AT
Pharmacotherapy · 2025 Jul · PMID 40511790 · Publisher ↗
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Transdermal rivastigmine as a therapeutic option in severe diphenhydramine-induced anticholinergic toxicity: A case report and literature review.
Gilbert BW, Santiago RD, Huffman JB … +2 more , Yoder NM, Hunninghake JC
Pharmacotherapy · 2025 Jul · PMID 40492363 · Publisher ↗
Diphenhydramine overdose is a common toxicological emergency characterized by anticholinergic symptoms such as delirium, hallucinations, and cardiovascular instability. Physostigmine, a centrally acting acetylcholinester...
Diphenhydramine overdose is a common toxicological emergency characterized by anticholinergic symptoms such as delirium, hallucinations, and cardiovascular instability. Physostigmine, a centrally acting acetylcholinesterase inhibitor, is the standard antidote but is currently unavailable within the United States due to supply limitations. We present the case of a 21-year-old female with confirmed diphenhydramine overdose (3600 mg) who demonstrated rapid clinical improvement after administration of a 9.5 mg/24-h rivastigmine transdermal patch. This case supports growing evidence suggesting that rivastigmine may serve as a safe and effective alternative when physostigmine is not accessible.
Chloride dipstick to rapidly estimate urine sodium during diuresis in acute heart failure.
Shah V, Cordwin D, Hummel SL … +1 more , Dorsch MP
Pharmacotherapy · 2025 Jun · PMID 40391751 · Full text
BACKGROUND: Rapid assessment of diuretic efficacy is necessary in the treatment of acute decompensated heart failure. European guidelines advocate for the use of spot urinary sodium measurements, but recent data suggest...
BACKGROUND: Rapid assessment of diuretic efficacy is necessary in the treatment of acute decompensated heart failure. European guidelines advocate for the use of spot urinary sodium measurements, but recent data suggest urinary chloride is the better marker. Laboratory turnaround, however, delays clinical decision-making. We tackle this by using a commercially available chloride urinary dipstick to estimate sodium and measure chloride. METHODS: This was a prospective pilot study involving patients hospitalized at the University of Michigan for acute decompensated heart failure (ADHF) with an indication for intravenous diuresis; patients were eligible for enrollment within 24 h of admission. Patients with end-stage kidney disease or receiving continuous loop diuretic infusions or thiazide-type diuretics were excluded. A spot urine sample was collected after the loop diuretic dose. A chloride dipstick was used, and results were compared against laboratory-obtained measurements of urinary chloride and sodium. RESULTS: In a total of 22 patients (mean age 62.2 ± 11.8 years, 50% female, and LVEF 31.8 ± 17.4%), dipstick chloride concentrations correlated highly with laboratory-measured urine chloride (r = 0.98, p < 0.001) with slight overestimation across the physiological range and with laboratory-measured urine sodium (r = 0.86, p < 0.001), although with greater variation. Dipstick interpretation preceded laboratory results by a median of 136 minutes (IQR 103-170, p < 0.001). CONCLUSIONS: The chloride dipstick rapidly and accurately assessed urine chloride almost 2 h faster than traditional laboratory output in patients undergoing diuresis for ADHF. It may be a new tool to evaluate loop diuretic treatment for ADHF. However, more studies are needed to assess its impacts on clinical outcomes.
Pharmacokinetic and pharmacodynamic evaluation of sulbactam-durlobactam in a critically ill patient on continuous venovenous hemofiltration infected with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex.
Kufel WD, Zeineddine N, Fouad A … +6 more , Roenfanz HF, Shields RK, Kline EG, Warner J, Hanrahan K, Kuti JL
Pharmacotherapy · 2025 Jul · PMID 40371868 · Full text
BACKGROUND: Drug databases currently do not provide dosing guidance for sulbactam-durlobactam in continuous renal replacement therapy. Herein, we present the first in vivo pharmacokinetic (PK) evaluation of sulbactam-dur...
BACKGROUND: Drug databases currently do not provide dosing guidance for sulbactam-durlobactam in continuous renal replacement therapy. Herein, we present the first in vivo pharmacokinetic (PK) evaluation of sulbactam-durlobactam during continuous venovenous hemofiltration (CVVH) in a patient with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) bacteremia and ventilator-associated bacterial pneumonia (VABP). METHODS: A 59-year-old critically ill patient (body mass index 60 kg/m) required CVVH and developed CRAB bacteremia secondary to VABP. Sulbactam-durlobactam 2 g every 4 h infused over 3 h was initiated based on previous ex vivo data and the effluent rate of 6 L/h. The sulbactam-durlobactam minimum inhibitory concentration (MIC) was determined by reference broth microdilution, and whole genome sequencing (WGS) was performed. Steady-state pre-filter blood, post-filter blood, and effluent samples were collected on three different dosing intervals to characterize plasma exposure and estimate the sieving coefficient (SC). RESULTS: The sulbactam-durlobactam MIC was 4/4 mcg/mL (susceptible). WGS revealed penicillin-binding protein (PBP)-1b and PBP-3 mutations. The selected dose exceeded sulbactam and durlobactam PK/pharmacodynamic (PD) targets with 100% free time above MIC (fT > MIC) and the ratio of area under the unbound concentration-time curve to MIC (fAUC/MIC) = 139, respectively. The SC for sulbactam and durlobactam was 0.68 and 0.67, respectively, and protein binding was 54% and 51%, respectively. Sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for CRAB bacteremia but recurred later in hospitalization 11 days after sulbactam-durlobactam treatment. The patient was ultimately transitioned to comfort care. CONCLUSION: Sulbactam-durlobactam monotherapy dosed at 2 g every 4 h (3-h infusion) in CVVH achieved PD targets for this CRAB isolate with a MIC of 4/4 mcg/ml. Although sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for the CRAB bacteremia, recurrence occurred, and the patient ultimately died.
Pharmacotherapy research landscape and knowledge gaps of opioids in maternal and pediatric populations.
Shendre A, Liu X, Chiang C … +18 more , Goodwin A, Oteng SR, Deypalubos JAF, Zhang S, Wang L, Liu J, Abbasi MY, Aruldhas BW, Zaidi SS, Kirkpatrick LM, Silva LD, Overholser BR, O'Kane AM, Kannankeril PJ, Patrick SW, Wiese AD, Quinney SK, Li L
Pharmacotherapy · 2025 Jun · PMID 40371673 · Full text
The use and misuse of opioids has surged in the past decade, with nearly half of the users being female. Although opioid use is lower among pregnant women, trends mirror the general population. While pediatric exposures...
The use and misuse of opioids has surged in the past decade, with nearly half of the users being female. Although opioid use is lower among pregnant women, trends mirror the general population. While pediatric exposures largely occur through prescriptions. This review presents a novel landscape analysis of pharmacology knowledge gaps in opioids in the maternal and pediatric populations. We queried PubMed for studies on 27 opioids, focusing on pharmacokinetics (PK), and pharmacoepidemiology (PE) or clinical trials (CT) in maternal and pediatric populations. English-language publications were included, and data were synthesized to identify gaps. Additionally, MarketScan claims data and United States Food and Drug Administration (FDA) drug labels were analyzed to compare scientific evidence, opioid prescriptions/orders, and FDA recommendations. Morphine, fentanyl, methadone, and buprenorphine are the most researched opioids in PK and PE/CT literature in both populations, but hydrocodone, oxycodone, and codeine are the most prescribed. Nine opioids lack FDA labels, and four of the 18 labeled drugs lack any human data. Hydrocodone, oxycodone, and codeine labels include lactation-focused PK information, with some pediatric clinical data for the latter two. Seven opioids lack PK and PE/CT studies in the maternal population, and PK research is absent for seven opioids, and PE/CT data is lacking for eight opioids in the pediatric population. PK studies often focus on labor, delivery, and lactation accompanied by neonatal data, whereas pregnancy research mainly occurs in PE studies. In pediatric populations, study types are evenly distributed among children, but PE studies focus more on adolescents. Drug concentration is the most reported parameter in PK studies, and neonatal opioid withdrawal syndrome (NOWS) is a key outcome in both PK and PE studies. NOWS is also researched more using real-world data, whereas neurodevelopmental outcomes are often captured in prospective observational studies. There is substantial disparity between the most commonly researched and prescribed opioids. In particular, the opioid pharmacology knowledge gaps are larger in pregnant women and for the highly prescribed opioids hydrocodone and oxycodone. The limited human data in FDA labels underscores the need for additional studies. Studies using real-world data can potentially help address these gaps.
Effect of creatine monohydrate on motor function in children with facioscapulohumeral muscular dystrophy: A multicenter, randomized, double-blind placebo-controlled crossover trial.
Woodcock IR, de Valle K, Cairns A … +11 more , Davidson ZE, Kean M, Varma N, Grobler A, Metz D, Carroll K, Dilek N, Heatwole C, Ryan MM, Delatycki MB, Yiu EM
Pharmacotherapy · 2025 Jun · PMID 40366059 · Full text
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive muscle disease with no available disease-modifying therapy. Creatine monohydrate (CrM) has been shown to improve muscle strength in individ...
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive muscle disease with no available disease-modifying therapy. Creatine monohydrate (CrM) has been shown to improve muscle strength in individuals with muscular dystrophies but has not been tested in young people with FSHD. This study aimed to explore the efficacy of CrM on motor function in children with FSHD. METHODS: In a randomized placebo-controlled double-blind crossover trial, powdered CrM at a dose of 100 mg/kg/day (maximum 10 g daily) was compared with placebo in two 12-week treatment periods with a 6-week washout between crossover arms. The primary outcome measure was the Motor Function Measure for Neuromuscular Disease (MFM-32) with secondary outcomes assessing safety, endurance, strength, patient-reported outcome measures, and muscle morphology measurements as assessed by whole-body magnetic resonance imaging (MRI). RESULTS: Thirteen children were enrolled (mean (standard deviation, SD) 12.2 (2.67) years of age) and 11 patients completed both trial treatment periods. In an intention-to-treat analysis, no clinically meaningful difference was seen between treatment groups as measured by the mean difference in MFM-32 (0.19, 95% confidence interval (CI) -0.71 to 1.08). However, there was an improvement in 6-minute walk distance of 27.74 m (95% CI -1.41 to 56.88) and trends to improvement in the FSHD-Composite Outcome Measure for Pediatrics (FSHD-COM Peds), 10 meter walk/run, and in MRI measures. There were no serious adverse events. Serum creatinine increased by a mean 12.63 μmol/L (95% CI 1.14 to 24.12) post-CrM treatment, though this was presumed to reflect increased creatinine production. No participants discontinued CrM due to adverse events. CONCLUSION: CrM is safe and well tolerated in children with FSHD. Although CrM had no effect on motor function as measured by the MFM-32 compared with placebo, there were trends toward improvement in the 6-minute walk distance and other secondary outcome measures. This study confirms the feasibility of conducting clinical trials in children with FSHD. Further assessment of the efficacy of CrM in pediatric FSHD is warranted in a larger randomized controlled clinical trial. Future studies may benefit from stratifying population cohorts according to functional ability or by MRI fat infiltration measurements.
Predictive performance of population pharmacokinetic models in InsightRX® for model-informed precision dosing for Cefepime.
König C, Kuti JL, Fratoni AJ
Pharmacotherapy · 2025 Jul · PMID 40353524 · Publisher ↗
BACKGROUND: Model-informed precision dosing (MIPD) is a promising tool used to ensure therapeutic antimicrobial concentrations. Model selection and sampling strategy might lead to different pharmacokinetic (PK) parameter...
BACKGROUND: Model-informed precision dosing (MIPD) is a promising tool used to ensure therapeutic antimicrobial concentrations. Model selection and sampling strategy might lead to different pharmacokinetic (PK) parameter estimates. Herein, we assess the predictive performance for cefepime PK in two models implemented within the InsightRX software using differing sampling approaches. METHODS: Historic cefepime PK data and individual Bayesian estimates in predominantly critically ill patients, some of whom had extracorporeal support, served as the reference standard. Two population PK models (A; B) were evaluated using four sampling scenarios: (i) trough only, (ii) midpoint only, (iii) trough + midpoint, and (iv) peak + midpoint + trough. The median prediction error (MPE) and median absolute prediction error (MAPE) were calculated for clearance (CL) and volume of central compartment (V). Predicted categorical achievement of ≥70% time that the free drug concentration was greater than the minimum inhibitory concentration [fT>MIC] was compared. RESULTS: MAPE and MPE for CL and V resulted in variability that was dependent on model and sampling strategy. Both models' overall MPE and MAPE for CL were <±20 and <30% for all tested scenarios, respectively, with a low MPE of -2.4% to 4.4% on CL for sampling scenario 4. For V, MPE and MAPE were >±20 and >30% for the majority of test scenarios across both models, respectively. When excluding patients with extracorporeal support, MPE/MAPE for V decreased to 3.7-4.8/23.3%-34.5% and -7.9-2.5/25.2%-29.6% for model A and B, respectively. Using each model and sampling scheme, only four patients had discordant predicted achievement of ≥70% fT>MIC. CONCLUSIONS: These two population PK models and all sampling scenarios demonstrated acceptable prediction of cefepime PK parameters and pharmacodynamic exposures; therefore, they demonstrated suitability for utilizing MIPD for cefepime therapeutic drug monitoring.
Proton pump inhibitor concomitant use to prevent oxaliplatin-induced peripheral neuropathy: Clinical retrospective cohort study.
Mine K, Kawashiri T, Mori K … +12 more , Mori Y, Ishida H, Kudamatsu H, Fujita S, Uchida M, Yamada T, Egashira N, Ieiri I, Koyanagi S, Ohdo S, Shimazoe T, Kobayashi D
Pharmacotherapy · 2025 Jul · PMID 40347077 · Full text
BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is a major clinical challenge because it leads to discontinuation of chemotherapy. Omeprazole, a proton pump inhibitor (PPI), has been shown to prevent OIPN in...
BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is a major clinical challenge because it leads to discontinuation of chemotherapy. Omeprazole, a proton pump inhibitor (PPI), has been shown to prevent OIPN in a rat model. Therefore, we aimed to test whether the concomitant use of a PPI reduces oxaliplatin discontinuation due to OIPN. METHODS: This retrospective study used data from 1015 patients who started treatment with oxaliplatin and evaluated two cohorts (PPI vs. non-PPI). The primary outcome measure was oxaliplatin discontinuation due to OIPN. A Kaplan-Meier curve was generated for cumulative doses and evaluated using the log-rank test and Cox proportional hazards analysis. RESULTS: The log-rank test showed that the number of patients who discontinued oxaliplatin due to OIPN was significantly lower in the PPI group (p = 0.0264). Cox proportional hazards analysis incorporated and analyzed factors previously reported as potentially affecting neuropathy (sex, age, use of PPIs, calcium channel antagonists, opioids and adjuvant analgesics, and the CAPOX [capecitabine + oxaliplatin] regimen). The analysis suggested that the concomitant use of PPIs was a factor in reducing oxaliplatin discontinuation (adjusted hazard ratio [HR] = 0.568, 95% confidence interval [CI], 0.344-0.937, p = 0.0269). Since there were significant differences in some patient demographics between the two groups, propensity score matching was performed to align the patient demographics and then reanalyzed. After propensity score matching, the same analysis as above showed that oxaliplatin discontinuation due to OIPN was significantly less common in the PPI group (p = 0.0081); cox proportional hazards analysis showed that PPI use was a factor that significantly reduced oxaliplatin discontinuation due to OIPN (adjusted HR = 0.478, 95% CI, 0.273-0.836, p = 0.0096). CONCLUSIONS: These results suggest that concomitant PPI use may reduce oxaliplatin discontinuation due to OIPN in patients receiving oxaliplatin.
Retrospective cohort study of oral switch versus intravenous antibiotics for carbapenem-resistant enterobacterales and Pseudomonas aeruginosa infections on hospital discharge.
Arena CJ, Abed A, Kenney RM … +4 more , Suleyman G, Shallal A, Davis SL, Veve MP
Pharmacotherapy · 2025 May · PMID 40345979 · Publisher ↗
OBJECTIVES: To compare outcomes of oral switch versus intravenous antibiotics for the treatment of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) infections at hospital discharge. METHODS:...
OBJECTIVES: To compare outcomes of oral switch versus intravenous antibiotics for the treatment of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) infections at hospital discharge. METHODS: Institutional review board approved, retrospective cohort of adults infected with CRE or CRPA who received oral switch or intravenous antibiotics at hospital discharge from January 1, 2017, to April 30, 2024. Patients were included if they were eligible for oral switch and infected with an isolate susceptible to one or more oral antibiotics; non-bacteremic urinary tract infections were excluded. The primary outcome was 30-day clinical success at end of therapy, defined as lack of infection-related hospitalization, infection-related recurrence, or change/escalation of therapy. Secondary outcomes included hospital length of stay (LOS) and 30-day all-cause mortality from end of therapy. RESULTS: Fifty-five patients were included; 51% received oral switch antibiotics and 49% received intravenous antibiotics. Thirty-three percent of patients had CRE, 67% had CRPA, and 38% of cultures were polymicrobial. The most common infection types were pneumonia (33%), intra-abdominal (26%), and bone/joint (22%). The median (interquartile range [IQR]) duration of outpatient therapy was 12 (6-25) days versus 20 (4-34) days for the oral switch and intravenous antibiotic groups, respectively (p = 0.341). 30-day clinical success was 61% in the oral switch and 48% in the intravenous antibiotic groups (p = 0.349); the median (IQR) hospital LOS for the oral switch and intravenous antibiotic groups was 14 (9-25) days and 16 (9-49) days, respectively (p = 0.165); 30-day mortality was 4% in the oral switch group and 15% in the intravenous antibiotic group (p = 0.193). CONCLUSION: A limited sample of patients who received oral switch antibiotics had similar outcomes to intravenous outpatient treatment of carbapenem-resistant organisms, with a shorter hospital LOS.
Response to comment on "Association of atrial fibrillation with lamotrigine: An observational cohort study".
Kim S, Welch L, Santos BL … +3 more , Radwański PB, Munger MA, Kim K
Pharmacotherapy · 2025 May · PMID 40341685 · Publisher ↗
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Belzutifan's role in the treatment landscape of clear cell renal cell carcinoma.
Chen AH, Grana AK
Pharmacotherapy · 2025 Jun · PMID 40331637 · Publisher ↗
The treatment of metastatic clear cell renal cell carcinoma (RCC) has changed significantly in the last 20 years with the advent of targeted therapies and immune checkpoint inhibitors. Belzutifan, a hypoxia-inducible fac...
The treatment of metastatic clear cell renal cell carcinoma (RCC) has changed significantly in the last 20 years with the advent of targeted therapies and immune checkpoint inhibitors. Belzutifan, a hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, has a novel mechanism of action and was approved by the United States Food and Drug Administration (FDA) in 2023 for patients with advanced RCC. In the phase III LITESPARK-005 trial, patients receiving belzutifan had significant improvement in progression-free survival (PFS) compared with everolimus (PFS rate at 12 months: 33.4% vs. 17.1%; PFS rate at 18 months: 24.0% vs. 8.3%, respectively), as well as in objective response rate compared with everolimus (22.7% vs. 3.5%, respectively). There was no significant difference in median overall survival, with 21.4 months for belzutifan and 18.1 months for everolimus (hazard ratio [HR] 0.88; p = 0.20). In clinical practice, patients on belzutifan most often require intervention for anemia and hypoxia. This article describes the current preferred treatment options in clear cell RCC, the pharmacology of belzutifan, clinical trial data for belzutifan in clear cell RCC, our clinical experience with belzutifan and managing associated anemia and hypoxia, and future directions of belzutifan in RCC treatment.
Relationship of the revised anticholinergic drug scale with cultured cell-based serum anticholinergic activity and cognitive measures in older adults with mild cognitive impairment or remitted depression.
Carnahan RM, Chandramouleeshwaran S, Ahsan N … +12 more , Raymond R, Nobrega JN, Wang W, Fischer CE, Flint AJ, Herrmann N, Kumar S, Lanctôt KL, Mah L, Mulsant BH, Pollock BG, Rajji TK
Pharmacotherapy · 2025 Jun · PMID 40326412 · Full text
OBJECTIVE: The Anticholinergic Drug Scale (ADS) is a commonly used measure of anticholinergic exposure. This study describes an expanded and revised version of the ADS (rADS) and its relationship with cultured cell-based...
OBJECTIVE: The Anticholinergic Drug Scale (ADS) is a commonly used measure of anticholinergic exposure. This study describes an expanded and revised version of the ADS (rADS) and its relationship with cultured cell-based serum anticholinergic activity (cSAA) and cognitive measures. STUDY PARTICIPANTS: Adults aged 60 years and older with mild cognitive impairment (MCI), remitted major depressive disorder (rMDD), or both, participate in the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study. STUDY DESIGN: Cross-sectional investigation of data from the PACt-MD study. MEASURES: The rADS includes ratings for 1047 distinct products, about twice as many as the originally published scale; previously published ratings were revised for 40 drugs. Total rADS scores were calculated as sums of ratings of all drugs taken by participants; cSAA was measured in the participants' sera; cognitive performance included measures of executive function, language, processing speed, verbal memory, visuospatial memory, working memory, and an overall composite score. STATISTICAL ANALYSIS: The relationship between rADS total scores and cSAA was examined using a Spearman rank correlation coefficient. Relationships between rADS total scores and cognitive performance measures were explored in multivariable linear regression models. RESULTS: The sample included 310 participants (mean [standard deviation] age: 72 (6) years; 61.6% were women, and 81.6% had MCI [with or without rMDD]). Total rADS scores were positively correlated with cSAA (Spearman's correlation coefficient: 0.178, p = 0.0016). Total rADS scores were not significantly associated with cognitive performance. CONCLUSIONS: The revised scale is recommended as a replacement for the original ADS since it includes ratings for more drugs and was significantly, albeit weakly, associated with cSAA, similar to previous findings using the original ADS.
Fluoroquinolones and the risk of aortic aneurysm or dissection: A population-based propensity score-matched German cohort study.
Wicherski J, Peltner J, Becker C … +6 more , Schüssel K, Brückner G, Schlotmann A, Schröder H, Kern WV, Haenisch B
Pharmacotherapy · 2025 Jun · PMID 40285433 · Full text
OBJECTIVE: To investigate the risk of aortic aneurysm or dissection associated with fluoroquinolone (FQ) prescription compared to macrolides in German routine health care data in order to replicate the recent study (Phar...
OBJECTIVE: To investigate the risk of aortic aneurysm or dissection associated with fluoroquinolone (FQ) prescription compared to macrolides in German routine health care data in order to replicate the recent study (Pharmacotherapy 2023;43:883) extending the results by contributing evidence for six additional broad-spectrum antibiotic classes as active comparators. DESIGN: Cohort study in active comparator new user design comparing FQ with macrolides, tetracyclines, penicillins with extended spectrum, penicillins and beta-lactamase inhibitor combinations, second- and third-generation cephalosporins, sulfonamide and trimethoprim combinations, and lincosamides. SETTING: German statutory health insurance, the "Allgemeine Ortskrankenkasse" (AOK), January 2013 to December 2019. PARTICIPANTS: Adults with at least one new prescription fill for FQ or active comparator antibiotics. New users were defined as individuals without antibiotic prescription fills, aortic aneurysm or dissection diagnoses, and hospitalization within 365 days prior to the cohort entry date. Users of FQ and active comparators were matched by nearest neighbor 1:1 propensity score matching. MAIN OUTCOME MEASURES: Incident inpatient aortic aneurysm or dissection was observed within a 60-day risk window. In sensitivity analyses, an extended risk window of 90 days was applied, and specific FQ agents, dosages, and diagnoses were stratified. RESULTS: FQ episodes were associated with an increased risk for aortic aneurysm or dissection compared to macrolides (aHR = 1.52 [1.33; 1.74]), which replicates the risk estimate of Garg et al. (aHR = 1.34 [1.17; 1.54]). This association was robust in a 90-day risk window and for ciprofloxacin, levofloxacin, and moxifloxacin. Moxifloxacin comprised the greatest risk of aortic aneurysm or dissection compared to macrolides (aHR = 2.13 [1.64; 2.77]). Moreover, we observed similar associations when comparing FQ to tetracyclines, penicillins with extended spectrum, cephalosporins, and lincosamides (aHR = 1.86 [1.54; 2.24], aHR = 1.45 [1.28; 1.65], aHR = 1.23 [1.10; 1.37], and aHR = 1.73 [1.43; 2.11]), respectively. CONCLUSION: In a German cohort study, FQ use was associated with a 52% increased risk for aortic aneurysm or dissection within 60 days compared with macrolide use. The risk of FQ-associated aortic aneurysm or dissection compared to macrolides can be replicated in German routine health care data. Extending the analysis, we provided new insights that the effect size may depend on the chosen AC.
Correction of posaconazole concentrations for hypoalbuminemia.
Nix DE, Sime F, Roberts JA
Pharmacotherapy · 2025 Jun · PMID 40251837 · Publisher ↗
BACKGROUND: Posaconazole is an example of a highly protein-bound drug (>98%) in which therapeutic drug monitoring (TDM) is commonplace. Total drug concentration is typically measured, and in the setting of hypoalbuminemi...
BACKGROUND: Posaconazole is an example of a highly protein-bound drug (>98%) in which therapeutic drug monitoring (TDM) is commonplace. Total drug concentration is typically measured, and in the setting of hypoalbuminemia, total concentrations are lower despite no anticipated change in unbound concentration. Data support that unbound posaconazole concentration is responsible for antifungal activity and, in theory, is responsible for adverse effects that are dose-related. However, the therapeutic range of posaconazole is expressed as total concentration. The objective of this study was to investigate the use of an equation to correct posaconazole concentrations for albumin concentration as a surrogate for measurement of unbound concentration. METHODS: Data on unbound and total posaconazole concentration were acquired retrospectively from a study of posaconazole pharmacokinetics in critically ill patients. The relationship between total and unbound concentration was explored with and without albumin as a covariate using linear regression. Correction equations were used to normalize total concentration to an albumin concentration of 4.4 g/dL. RESULTS: A total of 78 pairs of total and unbound concentrations were available. Total and unbound posaconazole concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The median fraction unbound was 0.00645 (interquartile range of 0.00331-0.00794). Albumin concentration plays a highly significant role in the interpretation of TDM results. In a patient with hypoalbuminemia, a corrected concentration (C) = C/(0.01 + 0.99·Alb/4.4), where C is the total concentration and Alb is the albumin concentration in units of g/dL, is suggested. This equation can be further simplified to C = C·4.4/Alb, where C is a close approximation of C. CONCLUSIONS: Hypoalbuminemia is associated with lower total concentrations of posaconazole; however, the "active" unbound concentration is not expected to systematically change. As a result, total posaconazole concentrations in the therapeutic range for patients with hypoalbuminemia are more likely to be associated with toxicity, especially when doses are increased to achieve "therapeutic" concentrations.
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