Characterization of Medication Errors in a Medical Intensive Care Unit of a University Teaching Hospital in South Korea.

OBJECTIVES: The objective of this study was to characterize the current status of medication errors (MEs) throughout the medication therapy process from prescribing to use and monitoring in a medical intensive care unit (MICU) in Korea. METHODS: Four trained research pharmacists collected data through retrospectively reviewing electronic medical records for adults hospitalized in the MICU in 2017. The occurrence of MEs was determined through interprofessional team discussion led by an academic faculty pharmacist and a medical intensivist based on the medication administration records (MARs). The type of MEs and the consequent ME-related outcome severity were categorized according to the Pharmaceutical Care Network Europe and the National Coordinating Council for Medication Error Reporting and Prevention, respectively. RESULTS: Overall, electronic medical records for 293 patients with 78,761 MARs were reviewed in this study. At least one type of ME occurred in 271 patients (92.5%) in association with 16,203 MARs (21%), primarily caused by inappropriate dose (35.5%), drug (27.8%), and treatment duration (25.1%). Clinically significant harmful events occurred in 24 patients (8%), including life-threatening (n = 5) and death (n = 2) cases. The 2 patients died of enoxaparin-induced fatal hemorrhage and neutropenia associated with ganciclovir and cefepime. Antibiotics were the most common culprit medications leading to clinically significant harmful events. CONCLUSIONS: In conclusion, MEs are prevalent in the MICU in Korea, most commonly prescribing errors. Although mostly benign, harmful events including deaths may occur due to MEs, mainly associated with antibiotics. Systematic strategies to minimize these potentially fatal MEs are urgently needed.

Prevalence and Seriousness of Analgesic-Induced Adverse Events in Korea: A 10-Year Nationwide Surveillance.

OBJECTIVES: The objectives of this study were to describe the prevalence and seriousness of analgesic-induced adverse events (AEs) and to identify factors associated with serious analgesic-related AEs in Korea. METHODS: Voluntarily reported analgesic-induced AEs to the Korea Adverse Event Reporting System from 2007 to 2016 were retrospectively reviewed. Analgesic medications were classified into nonopioids and opioids based on the Anatomical Therapeutic Chemical classification system. All AEs were grouped using System Organ Classes according to the World Health Organization-Adverse Reaction Terminology. Logistic regression was performed to identify factors associated with serious AEs. RESULTS: Overall, 194,566 AEs (32.2% for nonopioids, 67.8% for opioids) were included in this analysis. The most common causative nonopioid and opioid analgesics was ketorolac (n = 10,789) and tramadol (n = 53,727), respectively. The most frequent AEs were skin and appendage disorders for nonopioids (31.8%) and gastrointestinal disorders (59.5%) for opioids. Serious AEs occurred in 6102 (9.7%) and 3326 (2.5%) cases of the nonopioid and opioid groups, respectively. The most common serious AEs were skin and appendage disorders (33.2%) for nonopioids and neurologic disorders (19.3%) for opioids. Serious AEs were significantly associated with male (odds ratio [OR] = 1.423), advanced age (OR = 1.570), certain causality (OR = 2.304), nonopioid analgesics (OR = 4.182), and polypharmacy (OR = 1.009; P <0.001 for all). CONCLUSIONS: In Korea, analgesic-induced AEs are prevalent with opioids more commonly implicated. Tramadol is the most common etiologic medication. Serious AEs are more frequently caused by nonopioids with skin and appendage disorders most common.

Population pharmacokinetics of vactosertib, a new TGF-ß receptor type Ι inhibitor, in patients with advanced solid tumors.

PURPOSE: Vactosertib, a novel inhibitor of transforming growth factor-ß type Ι receptor, is under development for the treatment of various cancers. The objective of this study was to characterize the population pharmacokinetics of vactosertib in patients with solid tumors. METHODS: Vactosertib population pharmacokinetics was assessed by nonlinear mixed-effects modelling of plasma concentration-time data obtained from a first-in-human phase 1 trial conducted in patients with advanced solid tumors. The final population pharmacokinetic model was constructed by assessing the effect of covariates on pharmacokinetic parameters including demographic characteristics, laboratory values, hepatic and renal function, and concomitant medications. The robustness of the final model was evaluated using a bootstrap method as well as visual predictive check based on Monte Carlo simulations and goodness-of-fit plots. RESULTS: A total of 559 concentrations from 29 patients were available for pharmacokinetic analysis. A two-compartment linear model with first-order absorption and absorption lag time adequately described the population pharmacokinetics of vactosertib. The estimates of apparent clearance (CL/F) and volume of central compartment (Vc/F) were 31.9 L/h (inter-individual variability, 0.481) and 82.9 L (inter-individual variability, 0.534), respectively. The mixture model accounts for both typical absorption profile in the majority of patients and distinct profile in some patients with uncommon gastrointestinal conditions. Body mass index was significantly associated with Vc/F. CONCLUSIONS: The model developed in this study adequately describes the population pharmacokinetics of vactosertib in patients with advanced solid tumors. The pharmacokinetic characteristics assessed using the model would provide useful quantitative information to assist the future clinical development of vactosertib.