Adverse Drug Events Associated With Remdesivir in Real-World Hospitalized Patients With COVID-19, Including Vulnerable Populations: A Retrospective Multicenter Study

Background@#Remdesivir is a US Food and Drug Administration-approved drug for coronavirus disease 2019 (COVID-19). Clinical trials were conducted under strictly controlled situations for a selected population, and their reported adverse events may not fully represent conditions in real-world patients. We aimed to estimate the incidence of adverse drug events (ADEs) associated with remdesivir in hospitalized patients with COVID-19, including vulnerable subpopulations, such as those with impaired renal or hepatic function and pregnant women. @*Methods@#This retrospective observational study included hospitalized patients with confirmed COVID-19 treated with remdesivir between January and December 2021 at ten hospitals. ADEs and severe ADEs (Common Toxicity Criteria for Adverse Events grade ≥ 3) were operationally defined and analyzed through laboratory investigations. The incidence of ADEs was compared with that of each matched control in subpopulations with renal or hepatic impairment and pregnant women. @*Results@#Among 2,140 patients, 1,416 (66.2%) and 295 (13.8%) experienced at least one ADE and severe ADE, respectively. The most frequent ADE was 'hepatic injury' (42.9%), followed by anemia (27.6%). The most common severe ADEs were 'hypokalemia' (5.3%), 'hepatic injury' (2.9%), and 'anemia' (3.6%). There was no significant difference in the incidence of ADEs in patients relative to their respective matched-control groups, including those with renal impairment (80.0% vs. control 71.8%, P = 0.063), hepatic impairment (70.4% vs. control 75.0%, P = 0.623) and pregnant women (78.6% vs. control 63.7%, P = 0.067). However, severe ADE incidence was significantly higher in patients with renal impairment (40.8% vs. 16.0%, P < 0.001). The most common severe ADEs in those were 'anemia' (15.3%), 'hypokalemia' (10.5%), and 'thrombocytopenia' (8.9%). There was no statistically significant difference in the incidence of severe ADEs in patients with hepatic impairment or in pregnancy (P = 0.230; P = 0.085). @*Conclusion@#A significant proportion of patients with COVID-19 treated with remdesivir experienced ADEs and severe ADEs. Given the high incidence of severe ADEs, caution is required in patients with renal impairment. Further studies are needed to investigate ADEs in pregnant women and patients with hepatic impairment.

Evaluation of Nivolumab Use and Factors related to Treatment Outcomes in a Cancer Center of a Top Tier General Hospital

BACKGROUND: We strived to evaluate the status of nivolumab use and associated factors on the clinical efficacy of the drug. METHODS: The study was retrospectively conducted in patients who had been administered nivolumab at least once at the cancer center of Seoul National University Hospital from June 2015 to April 2017. Data were collected from electronic medical records. A medication-use evaluation was performed based on the American Society of Health-System Pharmacists mediation-use guidelines. RESULTS: Sixty-six of the 74 patients (89.2%) showed indications approved for nivolumab use by the Korean Ministry of Food and Drug Safety (MFDS; n=55) or the US Food and Drug Administration (FDA; n=11). Approximately 73.0% of the patients were administered the approved dose of 3 mg/kg but 25.7% were administered an unapproved fixed dose of 100 mg. The overall response rate was 21.7%, and the response rate of non-small cell lung cancer patients, who accounted for the largest number of indications, was 18.8%. Adverse reactions were found in 90.1% of the patients and were mostly mild (86%). The expression of programmed death-ligand 1 (PD-L1) was analyzed as a factor affecting treatment response (p=0.028, odds ratio [OR]=11.331). CONCLUSION: PD-L1 expression was found to affect treatment response. However, caution is required while using an unapproved dosage and in the absence of monitoring for effectiveness and safety. Therefore, an effective protocol or instruction manual for the proper use of nivolumab should be considered.

Evaluation of Perioperative Antithrombotic Management in Patients Undergoing Moderate to High Risk Surgery

OBJECTIVE: The perioperative management of antithrombotic therapy is often challenging and it requires a fine balance between the risk of hemorrhage and thrombosis. We aimed to evaluate the antithrombotic management for moderate to high risk patients in real world setting. METHODS: Among the patients who were consulted to the neurologist for the evaluation of perioperative risk from 2010 to 2012, patients undergoing moderate to high risk surgery and taking antithrombotics within 30 days were identified. We analyzed the timing of discontinuation and reinitiation of antithrombotic drugs before or after surgery as well as the status of bridging therapy. In addition, the conformity with the guideline suggested by American College of Chest Physicians was assessed. The rate of thromboembolic event and major hemorrhage were also investigated. RESULTS: A total of 329 patients were included. The concordance rate of warfarin stop and restart time with guideline was 23.4% and 10.3%, respectively. Continuing aspirin in patients undergoing coronary artery bypass surgery or non-cardiac surgery in patients with high risk for cardiovascular events were 59.2% and 2.6%, respectively. Bridging therapy was adopted in 92.9% and 81.2% in patients who had received anticoagulant before surgery and who were at high and low risk thromboembolism, respectively. In entire cohorts, 30-day incidence of major bleeding and thromboembolic event were 31.9% and 3.0%. Co-morbid renal disease were shown as independent predictor for major bleeding (adjusted OR 2.65. 95% CI 1.33-5.28). CONCLUSION: The concordance rate with guideline regarding perioperative antithrombotic use was low and bridging therapy was prevalent in patients undergoing moderate to high risk surgery.

Pharmacotherapeutic Problems and Pharmacist Interventions in a Medical Intensive Care Unit / 대한중환자의학회지

BACKGROUND: Interest in pharmacist participation in the multidisciplinary intensive care team is increasing. However, studies examining pharmacist interventions in the medical intensive care unit (MICU) are limited in Korea. The aim of this study was to describe the current status of pharmacist interventions and to identify common pharmacologic problems requiring pharmacist intervention in the MICU. METHODS: Between September 2013 and August 2014, a retrospective, observational study was conducted in the 22-bed MICU at a university hospital. Data were obtained from two trained pharmacists who participated in MICU rounds three times a week. In addition to patient characteristics, data on the cause, type, related drug, and acceptance rate of interventions were collected. RESULTS: In 340 patients, a total of 1211 pharmacologic interventions were performed. The majority of pharmacologic interventions were suggested by pharmacists at multidisciplinary rounds in the MICU. The most common pharmacologic interventions were adjustment of dosage and administration (n = 328, 26.0%), followed by parenteral/enteral nutritional support (n = 228, 18.1%), the provision of drug information (n = 228, 18.1%), and advice regarding pharmacokinetics (n = 118, 9.3%). Antimicrobial agents (n = 516, 42.6%) were the most frequent type of drug associated with pharmacist interventions. The acceptance rate of interventions was 84.1% with most accepted by physicians within 24 hours (n = 602, 92.8%). CONCLUSIONS: Medication and nutritional problems are frequently encountered pharmacotherapeutic problems in the MICU. Pharmacist interventions play an important role in the management of these problems.

Pharmacotherapeutic Problems and Pharmacist Interventions in a Medical Intensive Care Unit / 대한구급학회지

BACKGROUND: Interest in pharmacist participation in the multidisciplinary intensive care team is increasing. However, studies examining pharmacist interventions in the medical intensive care unit (MICU) are limited in Korea. The aim of this study was to describe the current status of pharmacist interventions and to identify common pharmacologic problems requiring pharmacist intervention in the MICU. METHODS: Between September 2013 and August 2014, a retrospective, observational study was conducted in the 22-bed MICU at a university hospital. Data were obtained from two trained pharmacists who participated in MICU rounds three times a week. In addition to patient characteristics, data on the cause, type, related drug, and acceptance rate of interventions were collected. RESULTS: In 340 patients, a total of 1211 pharmacologic interventions were performed. The majority of pharmacologic interventions were suggested by pharmacists at multidisciplinary rounds in the MICU. The most common pharmacologic interventions were adjustment of dosage and administration (n = 328, 26.0%), followed by parenteral/enteral nutritional support (n = 228, 18.1%), the provision of drug information (n = 228, 18.1%), and advice regarding pharmacokinetics (n = 118, 9.3%). Antimicrobial agents (n = 516, 42.6%) were the most frequent type of drug associated with pharmacist interventions. The acceptance rate of interventions was 84.1% with most accepted by physicians within 24 hours (n = 602, 92.8%). CONCLUSIONS: Medication and nutritional problems are frequently encountered pharmacotherapeutic problems in the MICU. Pharmacist interventions play an important role in the management of these problems.

Effect of Clinical Pharmacist Interventions on Prevention of Adverse Drug Events in Surgical Intensive Care Unit / 대한구급학회지

BACKGROUND: A pharmacist's participation in medical rounds in intensive care unit (ICU) is becoming popular nowadays. In this study, we investigated the effect of pharmacologic intervention by a pharmacist's participation in medical round in ICU on prevention of adverse drug events (ADEs). METHODS: From March 2011 to July 2011, the intervention data were obtained by participating in medical round two or three times a week, and by reviewing electronic medical records of patients admitted to surgical ICU. The incidence, cause, and type of ADEs were noted, respectively. Expected cost avoidance was calculated from interventions, which were considered to be preventive of ADEs. The acceptance rate of pharmacologic interventions was noted. RESULTS: Among 2781 patients, a total of 159 intervention data were collected in 90 patients. Recommendation for drug dosage adjustment or monitoring in patients with potential overdose and sub-therapeutic dose made up 82% of the total interventions. In 8% of interventions, initiation of drug therapy was recommended. 83% of the interventions were accepted and the acceptance rate of interventions within 24 hrs was 58%. The rate of the interventions, which were considered to be preventive of ADEs was 62%. Expected cost reduction obtained by preventing ADEs was 25,867,083 Won during a 5-month period. CONCLUSIONS: A pharmacist's participation in physician rounds in ICU was associated with prevention of ADEs and subsequent reduction of the cost in drug therapy.