Pharmacotherapy [JOURNAL]
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200 papers
Severe Persistent Urinary Retention Following Treatment With Intravenous Lecanemab.
Navarra AN, Wang LA, Al-Sahlani H … +2 more , Liu AJ, Doraiswamy PM
Pharmacotherapy · 2025 Oct · PMID 40910338 · Publisher ↗
Lecanemab is an amyloid-targeted antibody indicated for treating patients with amyloid-confirmed early Alzheimer's Disease in mild dementia or mild cognitive impairment stages. We report here a case of a subject with ear...
Lecanemab is an amyloid-targeted antibody indicated for treating patients with amyloid-confirmed early Alzheimer's Disease in mild dementia or mild cognitive impairment stages. We report here a case of a subject with early stage of Alzheimer's Disease dementia, amyloid positive, who developed severe acute urinary retention following his first dose of intravenous lecanemab. His urinary retention resolved after a week but recurred following the second intravenous dose 2 weeks later. Lecanemab was discontinued, but the urinary retention has persisted for 8 months indicating possible permanent adverse impact on the bladder. The Naranjo causality probability score was 6. The incidence of urinary retention with intravenous lecanemab is not known but given that elderly patients with dementia may have multiple risks for bladder dysfunction, clinicians should remain vigilant. It is hoped that newer formulations, such as subcutaneous lecanemab, may prove safer in such patients.
A Multicenter, Open-Label Study to Assess the Safety of Nebulized Tissue Plasminogen Activator for the Acute Treatment of Pediatric Plastic Bronchitis: The PLATyPuS Trial.
Stringer KA, Goldberg D, Chen S … +8 more , Thrush P, Graham EM, Lubert A, Myers J, McLellan L, Flott T, Nasr S, Schumacher KR
Pharmacotherapy · 2025 Oct · PMID 40910281 · Full text
INTRODUCTION: Pediatric plastic bronchitis (PB) is a rare complication of surgically palliated congenital heart disease (CHD). Fibrin casts obstruct airways and can cause respiratory distress. There are no therapeutics a...
INTRODUCTION: Pediatric plastic bronchitis (PB) is a rare complication of surgically palliated congenital heart disease (CHD). Fibrin casts obstruct airways and can cause respiratory distress. There are no therapeutics approved by the United States Food and Drug Administration to treat PB, but inhaled tissue plasminogen activator (tPA) has been anecdotally used to relieve symptoms. We conducted a phase II open-label clinical trial to test the safety of inhaled tPA in pediatric PB. METHODS: Patients with an acute exacerbation of PB requiring hospitalization were enrolled to test the safety of an inhaled tPA regimen (5 mg every 6 h). The primary end point was to assess the safety and tolerability of repeated doses of nebulized, inhaled tPA in pediatric patients with acute PB. Safety parameters consisted of clinical laboratories to assess bleeding, which were measured prior to, during, and after tPA treatment. To benchmark efficacy using spirometry and oxygen saturation, children with Fontan-palliated CHD without a history of PB, with and without protein losing enteropathy (PLE), and healthy children were enrolled in a control arm that did not receive tPA. RESULTS: Of the 10 patients with PB screened for enrollment, eight qualified for immediate treatment with inhaled tPA. A total of 29 non-PB participants (PLE, n = 8 [10-18 yo]; CHD, n = 9 [8-17 yo]; and healthy, n = 12 [7-16 yo]) were enrolled. There were no differences in pretreatment clinical blood laboratory values of hemostasis and those during and after treatment with the study drug (primary safety outcome). However, there were four episodes of self-limiting epistaxis related to the study drug. Inhaled tPA statistically improved oxygen saturation although this was moderate and likely not clinically significant; inhaled tPA did not alter spirometry values. CONCLUSION: In this small, phase II study, repeated doses of inhaled tPA in patients with an acute exacerbation of PB did not result in disrupted systemic coagulation or hematological homeostasis or serious bleeding. However, patients should be monitored for localized bleeding. Larger, randomized trials are needed to provide more comprehensive assessments of bleeding risk and to further assess efficacy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02315898.
Restarting Oral Anticoagulation in Patients With Atrial Fibrillation After Admission for a Gastrointestinal Bleeding Event: Effectiveness and Safety of Direct Oral Anticoagulants Compared to Warfarin.
Lawal OD, Aronow HD, Shobayo F … +6 more , Zhang Y, Hume AL, Taveira TH, Matson KL, Gold J, Wen X
Pharmacotherapy · 2025 Oct · PMID 40852894 · Full text
BACKGROUND: There are sparse data to guide resumption of direct oral anticoagulants (DOACs) versus warfarin in patients with atrial fibrillation (AF) who survive a major gastrointestinal bleeding (GIB) event. OBJECTIVE:...
BACKGROUND: There are sparse data to guide resumption of direct oral anticoagulants (DOACs) versus warfarin in patients with atrial fibrillation (AF) who survive a major gastrointestinal bleeding (GIB) event. OBJECTIVE: To compare the risk-benefit profile of restarting DOACs versus warfarin among patients with AF following hospitalization for major GIB. METHODS: Using claims submitted to a commercial health insurance database from January 2010 to December 2017, we identified adult patients with AF hospitalized for a major GIB while receiving oral anticoagulants. Eligible patients were required to have survived and restarted oral anticoagulation with DOACs or warfarin within 90 days following hospital discharge for major GIB. The outcomes of interest were subsequent hospitalization for major bleeding, hospitalization for ischemic stroke/systemic embolism (SE), all-cause mortality, and net adverse clinical effect (NACE), which was a composite of all-cause mortality, hospitalization for ischemic stroke/SE, and hospitalization for major bleeding. Stabilized inverse probability of treatment weighting was used to balance measured covariates. RESULTS: Overall, 4,389 patients resumed oral anticoagulation, with 3016 (68.7%) on warfarin and 1373 (31.3%) on DOACs, within 90 days of hospital discharge for major GIB. The median (interquartile range) time from hospital discharge for major GIB to resumption of oral anticoagulant was 24 (10, 47) days. The weighted hazards ratio (HR) among individuals that resumed DOACs versus warfarin after major GIB was 0.76 (95% confidence interval, CI: 0.60, 0.96) for subsequent hospitalization for major bleeding, 0.91 (95% CI: 0.53, 1.55) for subsequent hospitalization for ischemic stroke/SE, and 0.83 (95% CI: 0.72, 0.97) for NACE. CONCLUSIONS: Among patients with AF who survived and resumed oral anticoagulation within the first 90 days after hospitalization for a major GIB event, restarting oral anticoagulation treatment with DOACs was associated with a lower risk of subsequent hospitalization for major bleeding and the composite outcome of ischemic stroke, SE, all-cause mortality, and recurrent or incident major bleeding.
Correction to Chloride Dipstick to Rapidly Estimate Urine Sodium During Diuresis in Acute Heart Failure.
Pharmacotherapy · 2025 Dec · PMID 40808357 · Full text
V. Shah, D. Cordwin, S. L. Hummel, M. P. Dorsch, "Chloride Dipstick to Rapidly Estimate Urine Sodium During Diuresis in Acute Heart Failure." Pharmacotherapy. 45, (2025): 352-355. https://doi.org/10.1002/phar.70026. The...
V. Shah, D. Cordwin, S. L. Hummel, M. P. Dorsch, "Chloride Dipstick to Rapidly Estimate Urine Sodium During Diuresis in Acute Heart Failure." Pharmacotherapy. 45, (2025): 352-355. https://doi.org/10.1002/phar.70026. The author's name, V Shah, was corrected to Vacha Shah in the online version. We apologize for this error.
Drug-Drug Interactions and Combination Therapy Strategies of Amiodarone With Digoxin, Rivaroxaban, and Phenytoin Assessed by Physiologically Based Pharmacokinetic Modeling.
Chen Y, Liu Z, Li Y … +5 more , Wang W, Chen T, Li S, Wu Y, Xie H
Pharmacotherapy · 2025 Sep · PMID 40798896 · Publisher ↗
BACKGROUND: Amiodarone (AMI) is a potent inhibitor of Cytochrome P450 (CYP) 2C9 and P-glycoprotein (P-gp), as well as a weak inhibitor of CYP3A4. Concomitant administration of AMI with digoxin (DIG), rivaroxaban (RIV), o...
BACKGROUND: Amiodarone (AMI) is a potent inhibitor of Cytochrome P450 (CYP) 2C9 and P-glycoprotein (P-gp), as well as a weak inhibitor of CYP3A4. Concomitant administration of AMI with digoxin (DIG), rivaroxaban (RIV), or phenytoin (PHT) can significantly increase the exposure of the victim drugs. Elevated RIV exposure raises the risk of bleeding, whereas DIG and PHT have narrow therapeutic windows, potentially leading to severe toxicity when co-administered with AMI. PURPOSE: Physiologically based pharmacokinetic (PBPK) modeling was employed to simulate, validate, and predict the impact of drug-drug interactions (DDIs) between AMI and DIG, RIV, or PHT on the pharmacokinetics (PK) of victim drugs. The findings aim to provide evidence-based recommendations for optimizing combination therapy regimens. METHODS: PBPK models for AMI, RIV, and PHT were developed using PK-Sim, while the DIG model was adopted from previously published literature. DDI scenarios were simulated to assess exposure levels. Model performance was evaluated by comparing predicted plasma concentration-time (PCT) profiles and PK parameter values with clinical trial data from healthy subjects in previously published PK studies. Finally, dosing regimens for combination therapy were adjusted based on changes in exposure levels. RESULTS: According to model simulations, when the perpetrator drug AMI was co-administered with DIG, RIV, or PHT following label-recommended dosing regimens, the steady-state exposure of the victim drugs increased by 79%, 38%, and 59%, respectively. Compared to monotherapy, reducing the doses of DIG, RIV, and PHT by 40%, 25%, and 45%, respectively, achieved similar steady-state concentrations. CONCLUSIONS: We have successfully developed PBPK models for AMI, RIV, and PHT. These models effectively simulate the DDIs that occur when AMI is co-administered with DIG, RIV, or PHT, thereby providing guidance for dosing regimens in clinical combination therapies.
Trends in Initiation of Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis Among Commercially Insured Adults in the United States, 2001-2021.
Lee LY, Sparks JA, Yalamanchili P … +4 more , Horton DB, Khan ZM, Barone J, Dave CV
Pharmacotherapy · 2025 Sep · PMID 40791194 · Publisher ↗
OBJECTIVE: To evaluate patterns in disease-modifying antirheumatic drugs (DMARDs) initiations between 2001 and 2021 among adults with Rheumatoid Arthritis (RA) in the United States METHODS: This retrospective cohort stud...
OBJECTIVE: To evaluate patterns in disease-modifying antirheumatic drugs (DMARDs) initiations between 2001 and 2021 among adults with Rheumatoid Arthritis (RA) in the United States METHODS: This retrospective cohort study used a US commercial claims database (2001-2021) to identify patients (≥ 18 years) with RA newly initiating a DMARD. We calculated the annual proportion of initiations for 22 DMARDs, categorized as conventional synthetic (csDMARDs), biologic (bDMARDs), and targeted synthetic (tsDMARDs). Secondary analyses examined trends in first-line non-csDMARD initiation and biosimilar uptake. RESULTS: We identified 407,728 DMARD initiation episodes among 229,365 unique patients with RA (median age: 50 years [IQR], 44-58 years; 79.4% female). There were shifts in DMARD initiations, with csDMARD initiation declining from 79.9% of initiations in 2001 to 54.7% by 2021 (p < 0.001 for trend). Meanwhile, bDMARDs and tsDMARDs initiations increased from 20.3% in 2001 to 33.1% in 2021 (p < 0.001) and from 0.1% in 2012 to 12.2% in 2021 (p = 0.171), respectively. Methotrexate remained the most initiated DMARD over the 21-year study period, albeit declining from 28.7% to 15.0% of initiations over the study period (p < 0.001). Adalimumab was the most frequently initiated bDMARD (13.3% in 2003 and 12.2% in 2021; p = 0.05). Among tsDMARDs, tofacitinib initiation peaked at 8.9% in 2019 and declined to 4.4% in 2021, while upadacitinib initiation increased from 1.2% to 7.6% during the same period (p < 0.001). For secondary analyses, adalimumab was the predominant first-line b/tsDMARD initiated (> 40%). Biosimilar uptake stayed below 1%. CONCLUSION: Expanded DMARD options over the last two decades have led to decreased csDMARD initiations and increased b/tsDMARD initiations, reflecting patient- and system-level factors.
Hereditary Pseudocholinesterase Deficiency and Succinylcholine: Historical Perspective, Therapeutic Implications, and Future Considerations.
Nguyen JQ, Paetznick C, Donnelly RS
Pharmacotherapy · 2025 Sep · PMID 40778538 · Publisher ↗
Succinylcholine, a commonly used neuromuscular blocker, is hydrolyzed by the pseudocholinesterase (also known as butyrylcholinesterase) enzyme in the plasma to inactive metabolites. Individuals who have inherited genetic...
Succinylcholine, a commonly used neuromuscular blocker, is hydrolyzed by the pseudocholinesterase (also known as butyrylcholinesterase) enzyme in the plasma to inactive metabolites. Individuals who have inherited genetic variants in the BCHE gene that result in decreased or no pseudocholinesterase enzyme activity are at increased risk of prolonged neuromuscular blockade with succinylcholine. Although succinylcholine/BCHE is one of the earliest identified pharmacogenomic drug/gene associations, clinical implementation remains the exception rather than the norm today. This review will explore the historical roots of pseudocholinesterase deficiency, its therapeutic implications for succinylcholine use, and future considerations for BCHE genetic testing to minimize the occurrence of prolonged neuromuscular blockade that can cause serious physical (i.e., apnea) and psychological (i.e., post-traumatic stress) consequences for patients. A summary and critical examination of the published literature that includes BCHE genetic testing in relation to succinylcholine response is also provided. Prolonged paralysis with succinylcholine may be prevented with preemptive BCHE genetic testing.
Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta-Analysis.
Gorski D, Lazo REL, de Souza DA … +3 more , Borba HHL, Pontarolo R, Tonin FS
Pharmacotherapy · 2025 Sep · PMID 40772520 · Full text
First-line therapeutic approaches for Crohn's disease include immunosuppressants, aminosalicylates, and corticosteroids. However, more than one-third of patients are resistant to these treatments and require second-line...
First-line therapeutic approaches for Crohn's disease include immunosuppressants, aminosalicylates, and corticosteroids. However, more than one-third of patients are resistant to these treatments and require second-line therapies. Our goal was to synthesize the evidence on the efficacy and safety of biologics and small molecules for inducing remission in patients with moderate-to-severe Crohn's disease. A systematic review was conducted by searching for randomized controlled trials on the target population in PubMed, Scopus, and Web of Science (March 2025). Data synthesis for the outcomes of remission, health-related quality of life (HRQoL), and safety was performed using network meta-analyses and surface under the cumulative rating curve (SUCRA) analyses. The results were presented as risk ratios with 95% credible intervals. We included 55 trials (n = 16,113 patients) evaluating 26 biological drugs across 83 doses and six small molecules across 15 doses. Similar results were obtained in the sensitivity analyses conducted across different measurement time points. Alongside infliximab 5 mg/kg (SUCRA 98.6%), 10 mg/kg (92%), and 20 mg/kg intravenous (91.8%), the recently approved drugs guselkumab 1200 mg (83.2%), 600 mg (89.2%), and 200 mg intravenous (90.1%), as well as mirikizumab 600 mg (91.5%) and 1000 mg intravenous (82.4%) presented higher probabilities of disease remission and were associated with increased HRQoL. Drugs such as certolizumab, andecaliximab, fontolizumab, abatacept, and etanercept ranked low for remission (SUCRA < 40%) and presented high probabilities of serious adverse events (over 60%). Small molecules presented an intermediate profile. Inhibitors of interleukin-23 appear to be promising alternatives for the treatment of moderate-to-severe Crohn's disease. Given their safety profile, some anti-TNF drugs should be avoided in practice. Trial Registration: PROSPERO: CRD42024519150.
Comment on "Proton Pump Inhibitor Concomitant Use to Prevent Oxaliplatin-Induced Peripheral Neuropathy: Clinical Retrospective Cohort Study".
Khalilizad M, Hejazian E, Barary M … +2 more , Zohrevand A, Ebrahimpour S
Pharmacotherapy · 2025 Sep · PMID 40772516 · Publisher ↗
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Response to Comment on "Proton Pump Inhibitor Concomitant Use to Prevent Oxaliplatin-Induced Peripheral Neuropathy: Clinical Retrospective Cohort Study".
Mine K, Kawashiri T, Mori Y … +9 more , Fujita S, Uchida M, Yamada T, Egashira N, Ieiri I, Koyanagi S, Ohdo S, Shimazoe T, Kobayashi D
Pharmacotherapy · 2025 Sep · PMID 40772502 · Publisher ↗
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Precision Daptomycin Dosing: Comparison of 3-, 2-, 1-, and 0-Concentration Sample Strategies.
Giuliano S, Pai MP, Angelini J … +4 more , Flammini S, Martini L, Baraldo M, Tascini C
Pharmacotherapy · 2025 Sep · PMID 40772492 · Full text
BACKGROUND: Daptomycin is a once-daily lipopeptide antibiotic with a narrow therapeutic window. As higher doses (8-12 mg/kg) are increasingly used to treat resistant gram-positive infections, achieving therapeutic exposu...
BACKGROUND: Daptomycin is a once-daily lipopeptide antibiotic with a narrow therapeutic window. As higher doses (8-12 mg/kg) are increasingly used to treat resistant gram-positive infections, achieving therapeutic exposure while minimizing toxicity has become critical. Understanding daptomycin therapeutic drug monitoring (TDM) and what sampling strategy may be most precise and feasible are key to guiding appropriate dosing. The primary objective of this study was to ascertain the precision and bias of a mid-point sample area under the curve over 24-h (AUC) determination compared to a peak and trough sample AUC determination using both simple calculation-based methods and a Bayesian model versus no TDM. METHODS: Adult patients receiving daptomycin with at least three steady-state concentrations (peak, mid-point, trough) were included in this analysis. A previously published one-compartment population pharmacokinetic model was applied using Bayesian estimation (Monolix Suite 2024R1). AUC values were estimated using all three concentrations (AUC), and then re-estimated using individual samples (peak, mid-point, or trough) or paired samples (peak + trough). Performance of each strategy was evaluated using regression analysis with the coefficient of determination for precision (R) and mean bias. RESULTS: The cohort included 210 patients (60% male) with a mean (range) age of 66 (18-91) years, body weight 78 (41-140) kg, and BMI 27 (14-51) kg/m. A total of 880 daptomycin concentrations were analyzed in patients receiving a mean (range) daptomycin dose of 9 (5-17) mg/kg. The mean (range) AUC was 869 (385-1692) mg·h/L; only 45.7% of patients achieved the target range of 666 to 939 mg·h/L. A single mid-point sample had similar correlation to AUC (R = 0.57) as trough-only (R = 0.55), and greater precision than peak-only (R = 0.44). Bayesian estimation with two samples (peak + trough) provided the highest accuracy (R = 0.87) and lowest bias. CONCLUSIONS: A mid-interval sampling strategy offers a practical alternative to traditional TDM for daptomycin, enabling more consistent AUC estimation when full sampling is not feasible. A two-sample Bayesian approach remains the most accurate, supporting broader implementation of individualized daptomycin dosing.
Genome-wide associations with metabolic syndrome among UK Biobank participants reporting use of second-generation antipsychotics.
Rouby NE, Owusu-Obeng A, Preuss M … +9 more , Lee S, Shi M, Lape M, Martin LJ, Namjou-Khales B, Kottyan LC, Van Driest SL, Mosley JD, DelBello MP
Pharmacotherapy · 2025 Aug · PMID 40762455 · Full text
OBJECTIVES: Second-generation antipsychotic (SGA) medications are frequently prescribed for mental health conditions; however, they are associated with an increased risk of metabolic syndrome (MetS). We aimed to identify...
OBJECTIVES: Second-generation antipsychotic (SGA) medications are frequently prescribed for mental health conditions; however, they are associated with an increased risk of metabolic syndrome (MetS). We aimed to identify genetic associations of SGA-associated MetS (SGA-MetS) using genome-wide approaches within the UK Biobank. We also set out to evaluate if genetically predicted obesity is associated with an increased risk of SGA-MetS. METHODS: We defined SGA-MetS based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria using cross-sectional data from 1318 UK Biobank participants who reported being on an SGA medication. An SGA-MetS case was defined as meeting three or more of the five NCEP-ATP III criteria. We performed a genome-wide association study (GWAS) and gene-based analysis to identify significant variants and gene associations. We computed the polygenic risk score (PGS) for body mass index (BMI) using 2,100,302 variants validated for obesity and metabolic traits from imputed single-nucleotide polymorphism (SNP) data. We tested the association of PGS-BMI with SGA-MetS using logistic regression. RESULTS: GWAS identified suggestive associations (p < 1 × 10) on chromosome 15. The variant rs12914956 in CHD2 was associated with increased risk of SGA (odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.4-2.4, p = 3.6 × 10). The gene-based analysis identified significant gene associations with RBFOX1 (p = 4.85 × 10), PTPRD (p = 7.6 × 10), CSMD1 (p = 2.2 × 10), and CHD2 (p = 1.3 × 10). The PGS-BMI (β = 0.23, p = 6.8 × 10), was associated with increased MetS in a model adjusted for age, sex, physical activity, alcohol consumption, antidepressant medications, schizophrenia diagnosis, and principal components of ancestry. CONCLUSION: Using a gene-based analysis, we identified significant gene associations with SGA-MetS that have been previously associated with obesity and metabolic traits. The PGS-BMI was associated with MetS, suggesting that a genetic predisposition to a higher BMI may increase the risk of SGA-MetS. Future research should replicate the findings in a larger dataset with more diverse populations.
A Large Cohort Study to Identify Risk Factors of Acute Kidney Injury in Pediatric Patients Undergoing Intravenous Vancomycin Therapy.
Goyal RK, Moffett BS, Parbuoni KA … +2 more , Heil EL, Gobburu JVS
Pharmacotherapy · 2025 Aug · PMID 40715988 · Full text
BACKGROUND AND OBJECTIVES: The relative contribution of vancomycin exposure versus clinical factors to acute kidney injury (AKI) development in pediatric patients remains unclear. This study examined risk factors for AKI...
BACKGROUND AND OBJECTIVES: The relative contribution of vancomycin exposure versus clinical factors to acute kidney injury (AKI) development in pediatric patients remains unclear. This study examined risk factors for AKI in pediatric patients receiving intravenous vancomycin therapy, with particular focus on elucidating the role of vancomycin concentrations and evaluating the safety implications of recent dosing guideline changes published in 2020. METHODS: For this retrospective cohort study, Texas Children's Hospital database was queried between 2011 and 2019 for demographics, concomitant medications, vancomycin dosing and levels, serum creatinine, and mortality. AKI was defined using modified KDIGO criteria. Empirical Bayesian forecasting with a published population pharmacokinetic (PK) model generated rich PK profiles from sparse sampling data. Multivariate logistic regression was used to identify risk factors, and simulations were performed to evaluate 2020 guideline recommendations. RESULTS: The final analysis dataset included 2318 vancomycin courses in 1714 unique patients. The typical dosing regimen in our dataset was 45 mg/kg/day every 8 h. AKI occurred in 18.9% of patients. Independent risk factors included lower age, ICU residence, vasopressor administration, concurrent piperacillin/tazobactam, and amphotericin B use. While vancomycin 24-h area under the curve (AUC) showed statistically significant association with AKI, the relationship was modest with minimal improvement in model performance compared to clinical factors alone. Simulations of 2020 guideline recommendations (60-80 mg/kg/day) predicted modest increases in AKI incidence from 19% to 21% when AUC was capped at 600 mg·h/L. However, given low mortality rate (1.9%) in our dataset despite only 43% of patients achieving the recommended AUC target of 400 mg·h/L, the clinical necessity for increased dosing remains questionable. CONCLUSIONS: Clinical factors are substantially more predictive of AKI than vancomycin exposure in pediatric patients. Given the questionable clinical necessity for increased dosing based on low mortality rates, prospective studies incorporating clinical efficacy endpoints are needed to establish optimal dosing strategies that balance therapeutic benefit with nephrotoxicity risk.
Effect of P2Y12 Inhibitors on Major Adverse Cardiovascular Events After Coronary Artery Bypass Graft Surgery: A Population-Based Cohort Study.
Barry AR, Helisaz H, Safari A … +1 more , Loewen PS
Pharmacotherapy · 2025 Sep · PMID 40719229 · Full text
BACKGROUND: Patients who undergo coronary artery bypass graft (CABG) surgery remain at high risk for major adverse cardiovascular events (MACE) despite contemporary preventive pharmacotherapy. Although commonly used in p...
BACKGROUND: Patients who undergo coronary artery bypass graft (CABG) surgery remain at high risk for major adverse cardiovascular events (MACE) despite contemporary preventive pharmacotherapy. Although commonly used in practice, it is uncertain whether P2Y12 inhibitors reduce MACE in patients post-CABG surgery. METHODS: This retrospective, population-based cohort study evaluated the effect of exposure to P2Y12 inhibitors, versus no exposure, on MACE using linked administrative databases that included all cardiac revascularization procedures, hospitalizations, and prescriptions for the population of British Columbia, Canada. All adults who underwent CABG surgery from 2002 to 2020 were eligible. The primary outcome was time to MACE, defined as a composite of all-cause death, nonfatal myocardial infarction, and nonfatal ischemic stroke using Cox proportional hazards models with inverse probability treatment weighting. RESULTS: Included were 15,439 patients. Mean age was 66 years, and 83% were male. Fifty-seven percent had a previous myocardial infarction. Sixteen percent were prescribed a P2Y12 inhibitor (of which, 83% were prescribed clopidogrel) within 30 days of CABG surgery. Median exposure time was 23 months. After probability-weighting and adjustment for relevant covariates, exposure to P2Y12 inhibitors reduced the 1- and 5-year hazard of MACE (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.27-0.55 and HR 0.65, 95% CI 0.54-0.79, respectively). Exposure to P2Y12 inhibitors was also associated with a lower hazard of all-cause death, cardiovascular death, and an extended MACE outcome that included unstable angina and percutaneous coronary intervention. Adherence to P2Y12 inhibitor therapy, based on the proportion of days covered, did not affect these outcomes. CONCLUSIONS: In this population-based cohort study, use of P2Y12 inhibitors reduced the hazard of MACE in patients post-CABG surgery at 1 and 5 years of follow-up. These results support the use of P2Y12 inhibitors (primarily clopidogrel), in addition to other standard cardiovascular preventive therapy, in patients who undergo CABG surgery.
Intraperitoneal Granisetron for Post-Laparoscopic Cholecystectomy Pain Management: A Double-Blinded, Randomized Controlled Trial.
Bayoumi HM, Abdelaziz DH, Boraii S … +2 more , Bendas ER, El Said NO
Pharmacotherapy · 2025 Sep · PMID 40698525 · Publisher ↗
BACKGROUND: Laparoscopic cholecystectomy (LC) may cause significant pain, increasing morbidity. Granisetron, an antiemetic selective serotonin (5HT3)-antagonist, demonstrates analgesic properties through sodium channel b...
BACKGROUND: Laparoscopic cholecystectomy (LC) may cause significant pain, increasing morbidity. Granisetron, an antiemetic selective serotonin (5HT3)-antagonist, demonstrates analgesic properties through sodium channel blockade. The current study aims to assess the efficacy of adjuvant intraperitoneal granisetron in post-LC pain. RESEARCH DESIGN AND METHODS: In this prospective randomized controlled trial, 48 patients undergoing LC were randomized into placebo (intraperitoneal saline) and intervention (intraperitoneal granisetron) groups. Pain intensity was measured via visual analog scale (VAS) at 2-, 4-, 8-, 12-, and 24-h post-surgery, with comparative analysis of the area under the curve (AUC) of the 24-h VAS scores. Additional outcomes included sedation levels, persistent pain incidence, quality of life improvement, postoperative nausea and vomiting (PONV), time to first rescue analgesic request, total analgesic consumption, and independent mobilization. RESULTS: The treatment group showed significantly lower VAS at 8, 12, and 24 h (p = 0.039, 0.004, 0.030) and lower VAS score AUC (542.7 ± 260.5 vs. 767.1 ± 317.8, p = 0.011) compared to controls, respectively. No significant differences were observed in (2-4 h) pain scores, persistent pain incidence, quality of life, sedation levels, PONV, analgesic requirements, or mobilization time (p < 0.05). CONCLUSIONS: Granisetron could improve multimodal pain control after LC, offering better outcomes while maintaining its established safety profile. TRIAL REGISTRATION: NCT06281418.
Association of Pneumonia, Fracture, Metabolic, and Renal Events With Long-Term Proton Pump Inhibitor Use in Patients With Chronic Kidney Disease.
Chien YF, Chen YY, Wu CK
Pharmacotherapy · 2025 Aug · PMID 40678972 · Publisher ↗
BACKGROUND: Proton pump inhibitors (PPIs) have been commonly used for gastroesophageal reflux disease (GERD) and peptic ulcers (PU), which are even more prevalent in patients with chronic kidney disease (CKD). Although P...
BACKGROUND: Proton pump inhibitors (PPIs) have been commonly used for gastroesophageal reflux disease (GERD) and peptic ulcers (PU), which are even more prevalent in patients with chronic kidney disease (CKD). Although PPI-related adverse outcomes are well documented in the general population, evidence in patients with CKD remains limited. This study investigated the associations of PPI use and adverse outcomes in patients with CKD who had GERD or PU. METHODS: In this nationwide, retrospective cohort study, patients with CKD and also PU or GERD from 2006 to 2015 were enrolled and sorted into no-, short-term, and long-term PPI groups. Incidence and risks of outcome events between these three groups were analyzed with the Cochran-Armitage test and Cox proportional hazard analyses. Events-free probability was estimated with the Kaplan-Meier method during follow-up. RESULTS: In the study, 384,411 patients with CKD with PU or GERD were enrolled. The numbers of no-, short-term, and long-term PPI treatments were 147,976, 14,153, and 3459, respectively. Relative to the no-PPI group, the adjusted hazard ratios (aHRs) of admission for pneumonia and fracture, new diagnosis of type 2 diabetes mellitus (DM), and progression to end-stage kidney disease (ESKD) in the short-term (1.089, 1.083, 1.175, 1.22) and long-term PPI groups (1.882, 2.601, 1.951, 1.714) remained statistically significant, respectively, even after adjustment for significant baseline variables; the aHR of dialysis was significant only in the long-term PPI group. Kaplan-Meier analysis revealed significant outcome events in the long-term PPI group during follow-up. CONCLUSION: PPI use is associated with an increased risk of pneumonia, fracture, incidence of type 2 DM, and progression to ESKD in patients with CKD, and the risk increases substantially with increased duration of PPI use.
Pharmacokinetics of Sulbactam/Durlobactam in a Patient With Acute Renal Failure, Severe Obesity, and Carbapenem-Resistant Acinetobacter baumannii Bacteremia: A Case Report.
Ilges D, Fu Y, Dickinson DT … +3 more , Robinson JC, Speiser L, Nicolau DP
Pharmacotherapy · 2025 Aug · PMID 40678932 · Publisher ↗
Carbapenem-resistant Acinetobacter baumannii (CRAB) are difficult-to-treat pathogens that primarily cause health care-associated infections. Sulbactam/durlobactam (SUL/DUR) is a novel antibiotic combination that is uniqu...
Carbapenem-resistant Acinetobacter baumannii (CRAB) are difficult-to-treat pathogens that primarily cause health care-associated infections. Sulbactam/durlobactam (SUL/DUR) is a novel antibiotic combination that is uniquely formulated to target CRAB isolates. However, investigations of SUL/DUR's pharmacokinetics in obese patients are limited. Here, we report on the successful treatment of CRAB bacteremia in a patient with acute renal failure and severe obesity (weight 273 kg, body mass index 103 kg/m) with SUL/DUR and meropenem combination therapy. The patient had a calculated creatinine clearance of 25 mL/min and received therapy with intravenous SUL/DUR 1 g/1 g every 8 h over 3 h in combination with intravenous meropenem 500 mg every 8 h to complete 14 days of therapy. Pharmacokinetic analysis revealed target attainment with prolonged half-life (T) and volume of distribution (Vd) of 35.3 h and 81.3 L for sulbactam and 30.5 h and 169.1 L for durlobactam, respectively. Susceptibility testing using the broth disk elution test did not show synergy between SUL/DUR and meropenem. No adverse effects were observed, and the patient achieved clinical cure without recurrence of A. baumannii infection.
Adverse events with co-prescription of angiotensin receptor blockers and clarithromycin compared to azithromycin: A population-based retrospective cohort study.
Tonial NC, Bota SE, Kang Y … +3 more , Muanda FT, Urquhart BL, Weir MA
Pharmacotherapy · 2025 Jul · PMID 40671487 · Full text
BACKGROUND: Clinically relevant drug-drug interactions (DDIs) are a common cause of adverse drug reactions (ADRs). Hepatic organic anion transporting polypeptides (OATPs) have recently been studied for their role in DDIs...
BACKGROUND: Clinically relevant drug-drug interactions (DDIs) are a common cause of adverse drug reactions (ADRs). Hepatic organic anion transporting polypeptides (OATPs) have recently been studied for their role in DDIs. The commonly prescribed antihypertensive angiotensin receptor blockers (ARBs) are known to be eliminated by hepatic OATPs. ARBs are commonly prescribed to patients with reduced kidney function, and kidney disease can result in profound changes to nonrenal drug elimination through reduced hepatic drug transport-mediated excretion. The antibiotic clarithromycin inhibits OATP activity whereas azithromycin does not, making them useful comparators to study DDIs with OATP substrate drugs. OBJECTIVE: To investigate whether co-prescription of ARBs and clarithromycin results in increased adverse events compared to azithromycin and whether kidney function modifies this risk. METHODS: We conducted a retrospective population-based cohort study in Ontario, Canada (2010-2021) using linked health care data for 106,322 older individuals (≥66 years) receiving an OATP substrate ARB (candesartan, olmesartan, telmisartan, valsartan) and newly co-prescribed clarithromycin (n = 32,693) or azithromycin (n = 73,629). Primary outcomes were hospital admissions or emergency department visits for hyperkalemia or acute kidney injury (AKI) within 14 days of antibiotic prescription. Adjusted risk ratios (aRR) were obtained using modified Poisson regression after controlling for eight potential confounders. Pre-specified effect measure modification analysis evaluated whether kidney function influenced these outcomes. RESULTS: Compared to those co-prescribed azithromycin, patients receiving clarithromycin had a significantly higher risk of hyperkalemia (aRR 2.05, 95% confidence interval (CI) 1.32-3.18) and AKI (aRR 1.75, 95% CI 1.41-2.17). The risk of hyperkalemia increased as kidney function declined (multiplicative interaction; p = 0.01). CONCLUSIONS: This population-based retrospective cohort study provides evidence of OATP-mediated drug interactions between ARBs and clarithromycin that warrants further investigation to guide clinical practice, especially for patients with reduced kidney function.
Comment on "Prevalence of potentially inappropriately prescribed medications among older adults receiving peritoneal dialysis".
Li R, Yang X
Pharmacotherapy · 2025 Aug · PMID 40650446 · Publisher ↗
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Comparative safety and efficacy of bisphosphonates, denosumab, and parathyroid hormone analogs for osteoporosis following lung transplantation.
January SE, Fester KA, Escamilla JE … +1 more , Cano M
Pharmacotherapy · 2025 Aug · PMID 40605738 · Publisher ↗
BACKGROUND: Parathyroid hormone (PTH) analogs, denosumab, and bisphosphonates are used to treat osteoporosis but have been associated with infections in the general population. Osteoporosis is a common comorbidity follow...
BACKGROUND: Parathyroid hormone (PTH) analogs, denosumab, and bisphosphonates are used to treat osteoporosis but have been associated with infections in the general population. Osteoporosis is a common comorbidity following lung transplantation. However, infections increase the risk of developing chronic lung allograft dysfunction, which reduces survival. Evidence for safe and effective use of PTH analogs, denosumab, or bisphosphonates in lung transplant recipients is lacking. METHODS: This single-center retrospective study evaluated lung transplant patients treated with the PTH analogs teriparatide or abaloparatide, RANKL inhibitor denosumab, or bisphosphonates. The primary outcome of interest was the incidence of infection while on the osteoporosis medication, and a multivariable logistic regression was employed to control for infection confounders. Secondary endpoints were treated allograft rejection episodes, the incidence of new donor-specific antibodies, the incidence of fracture while on medication, and the change in bone mineral density (BMD) from the start to the end of osteoporosis medication use. RESULTS: Forty-four PTH analog courses and 48 denosumab courses were compared with 92 bisphosphonate courses. Infection incidence was significantly lower in the PTH analog group than the denosumab or bisphosphonate group, but this did not retain significance on multivariable modeling. Treated allograft rejection episodes were higher in those with bisphosphonate use, significantly so when compared to PTH analog patients, but patients treated with bisphosphonates were also started on therapy earlier after their transplant when rejection risk is higher. All agents were effective at increasing BMD of the lumbar spine, none improved BMD of the femoral neck, and only PTH analogs significantly improved hip BMD. CONCLUSION: In this retrospective study of lung transplant patients treated for osteoporosis post-transplant, there was no difference in risk of infections in patients treated with PTH analogs, denosumab, or bisphosphonate therapies when examined with multivariable modeling. PTH analogs were the most effective since they significantly improved BMD at both the hip and lumbar spine, whereas denosumab and bisphosphonates only improved lumbar spine BMD. This study supports that PTH analogs and denosumab, despite their association with infection in the general population, may be safely utilized compared to bisphosphonates in the post-lung transplant population for the treatment of osteoporosis, but larger studies are needed to confirm these findings.
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