항히스타민제 이상반응

강혜련,안경민,김현지 대한약물역학위해관리학회 2023 약물역학위해관리학회지 Vol.15 No.1

Histamine is one of the most essential biochemical molecules involved in various responses, including inflammation, neurotransmission, and cell proliferation, in diverse organs. Clinical manifestations of allergic diseases are often triggered or initiated by histamine. In order to prevent histamine reactions in allergic disease, clinicians have attempted to develop antagonist of histamine receptors. Due to its effectiveness, antihistamine has been widely used in the treatment of allergic diseases, such as allergic rhinitis and urticaria by inhibiting histamine actions. Although antihistamines are generally safe, there are patients who experience unexpected side effects, such as sedation, cardiotoxicity, hepatotoxicity, nephrotoxicity, and change of appetite. Due to their ability to penetrate through blood-brain barrier, first-generation antihistamines potentially impair alertness, cognition, and memory. The safety profiles of the second-generation antihistamines are relatively superior to the first-generation antihistamines; the second-generation antihistamines cause relatively less central nervous system adverse reactions. However, serious cardiotoxicity of early second-generation antihistamines, such as terfenadine and astemizole, was reported. Moreover, widely-used second-generation antihistamine, cetirizine and loratadine, can present hepatotoxicity. In addition, body weight gain caused by both first- and second-generation antihistamines had been reported. In recent decades, pharmacologic mechanisms that are involved in these sides effect of antihistamine have been elucidated. Understanding detailed mechanisms and consequences of commonly observed side effects may help clinicians prescribe antihistamines safely. Herein, we summarize the mechanisms of histamine action, roles of antihistamines, and their common side effects in order to provide better understanding of antihistamines in clinical practice

계획되지 않은 재입원 예측인자 고찰

이수현,이인화,김우연,이주연 대한약물역학위해관리학회 2023 약물역학위해관리학회지 Vol.15 No.1

Unplanned hospital readmission could have negative consequences, including financial burdens. Identifying factors that affect readmission risk can help predict those at high risk. This review aimed to identify risk factors for hospital readmission after discharge in adult general population. A systematic search of PubMed, EMBASE and Cochrane Review databases was conducted for review articles on predictive models or risk factors for unplanned readmission up to January 18 2023. Of 965 articles identified, 11 review articles met inclusion criteria. The identified risk factors associated with readmission included demographic and social-determinants of health, healthcare utilization prior to index admission, overall health and function score, illness severity, index admission and discharge diagnosis, co-morbid disease, comorbidity index, medications, and polypharmacy. The identified risk factors for unplanned readmission are useful for developing prediction models or targeting hospitalized patients for preventive interventions to reduce unplanned readmission.

미국, 유럽, 한국의 실사용데이터/실사용근거를 활용한 연구설계 및 데이터분석의 최신 가이드라인 비교 및 향후 발전방향 고찰

전민정,하민영,성희진,이혜성,송재환,신주영 대한약물역학위해관리학회 2023 약물역학위해관리학회지 Vol.15 No.1

After enacting the 21st Century Cures Act of 2016, real-world data (RWD) and realworld evidence (RWE) have been increasingly used to support drug development and approval worldwide. The importance of RWD/RWE is growing for decisionmaking, while the reliability of RWD/RWE is still a concern regarding the quality of data, reproducibility, and transparency. Regulatory agencies have published diverse guidelines to encourage the appropriate use of RWD/RWE, but there are differences in practical information detailing methodological and analytic approaches among countries. We compared guidelines focusing on study design and data analysis for RWD/RWE in the United States, Europe, South Korea from 2017 to 2022. We summarized RWD/RWE guidelines according to the timeline and conducted a GAP analysis from the following perspectives: (1) the roadmap for the use of RWD/RWE; (2) the current guideline for study design and data analysis; (3) features of guideline. Based on our findings, we suggest a future direction for developing governance in terms of study design and data analysis to enhance the utilization of RWD/RWE in South Korea.

단일클론항체 항암제의 과민반응

최보윤,장하영,강혜련,오정미 대한약물역학위해관리학회 2023 약물역학위해관리학회지 Vol.15 No.1

Therapeutic monoclonal antibodies (TmAbs) are new treatment options for cancer. While their use is more common, hypersensitivity reactions (HSRs) to these drugs have been increased, preventing the use of first-line therapies. The aim of this review is to update and discuss the HSRs to TmAbs in their clinical features and management. Type 1 hypersensitivity is the most common type of the HSRs to TmAbs, followed by cytokine release reactions (CRRs) and type 4 hypersensitivity. Mixed reactions of various types might also occur. TmAbs can have different immunogenicity depending on their non-human epitope contents, target proteins, and solubilizing additives. It may be also affected by the patient’s baseline condition and the number of administrations. When HSRs occur, it is recommended to classify the mechanism into type 1/type 4 hypersensitivity and CRRs. A skin test and desensitization are generally the most useful management for type 1 hypersensitivity but there is no standardized protocol for TmAbs yet. Readministration is contraindicated in type 4 hypersensitivity reactions and supportive care is effective in CCRs. Understanding the characteristics and measures for each HSRs may be helpful to ensure the safe use of anticancer monoclonal antibodies. (PeRM 2023;15:1-10)

공통데이터 모델과 임상 데이터 웨어하우스를 이용한 Fimasartan과 Losartan의 약물 유발 간 손상의 발생 비교: 단일 의료기관 후향적 코호트 연구

강혜련,윤진,김현지,고예희,이시연,안경민,정지웅,이지향,김광수 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

: Fimasartan, an angiotensin II receptor blocker (ARB) with superior potency and longer-lasting effects than losartan, demonstrates a good safety profile. However, recent case reports have emerged, linking fimasartan to hepatotoxicity. The aim of the study is to compare the occurrence of liver injury induced by fimasartan. Methods: Patients prescribed with fimasartan and losartan from 2011 to 2021 were identified from electronic health recordbased Common Data Model (CDM) of Seoul National University Hospital. Using clinical data warehouse, clinical information was collected and employed to cross-reference the results retrieved from the CDM. To assess causality and compare the incidence of drug-induced liver injury (DILI), 100 randomly selected patients with liver function abnormalities were evaluated. Results: The CDM analysis included 3,063 patients on fimasartan and 9,688 patients on losartan, among which 302 patients (2.37%) exhibited liver function abnormalities within the first year of ARB therapy. Specifically, 107 (3.49%) patients on fimasartan showed elevated serum alanine aminotransferase or aspartate aminotransferase, compared to 195 (2.01%) patients on losartan. However, when causality was assessed, patients with causality graded as probable or certain did not show any significant difference between the two medications. Conclusion: Although patients taking fimasartan exhibited a slightly higher incidence of mild liver enzyme elevations, this study did not find a significant difference in the occurrence of DILI. Consequently, fimasartan is less safe than losartan in terms of hepatotoxicity cannot be asserted. However, similar to other ARBs, fimasartan poses a risk of DILI, underscoring the importance of monitoring liver function tests to promote safer use of the medication. (PeRM 2024;16:79-89)

페니실린 알레르기 꼬리표 떼기

이지향,강혜련,송수정 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

Penicillin allergy labels are associated with significant challenges, including antimicrobial resistance, restricted prescribing options, and negative outcomes for both patients and health care systems. However, only 10% of individuals labeled as penicillin allergic are found to be truly allergic after formal assessment. The evaluation process for a penicillin allergy encompasses a detailed allergy history, often followed by skin testing, and drug challenge. Researchers have suggested assessment tools and clinical decision rules for risk stratification for efficient and precise removal of incorrect penicillin allergy labels. In particular, patients categorized as low risk based on the assessment may undergo direct challenge test with penicillin, a practice supported by accumulating evidence. This comprehensive approach, emphasizing history taking and risk stratification, highlights the important role of healthcare providers in reducing the burden related to penicillin allergy labels. This review aims to understand the process of penicillin allergy evaluation and potential benefits of delabeling. (PeRM 2024;16:18-28)

소아 급성림프구성백혈병 환자에서 Sulfamethoxazole/ Trimethoprim에 의한 간독성 및 관련인자

이주연,박유빈,홍석민,장혜진,김성환,조은정,조윤숙,강형진 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

: This study aimed to examine the causality of hepatotoxicity related to sulfamethoxazole/trimethoprim (SMX/TMP) in pediatric patients with acute lymphoblastic leukemia (ALL). Methods: We retrospectively analyzed medical records of pediatric ALL patients, who were transitioned from SMX/TMP to aerosolized pentamidine (AP) for Pneumocystis jirovecii pneumonia prevention due to suspected hepatotoxicity between 2010 and 2023. The Roussel Uclaf causality assessment method (RUCAM) was used to assess hepatotoxicity due to SMX/ TMP, emphasizing cases considered “high probability” (RUCAM ≥ 6). Results: Of the 176 pediatric ALL patients who switched from SMX/TMP to AP, 112 did so due to elevated liver enzyme levels, and 38 of these (33.9%) were classified as “high probability” for hepatotoxicity according to RUCAM. Hepatotoxicity induced by SMX/TMP is characterised by an average ALT level of 430.6 IU/L, a total bilirubin level of 1.2 mg/dL at onset, typically manifesting after 223.1 days and resolving within 110.7 days. Multivariable analysis identified significant factors such as age (1–5 years), obesity, onset time (≤ 20 days), recovery time (≤ 20 days), and treatments with L-asparaginase and 6-mercaptopurine as associated with an increased risk of hepatotoxicity. Conclusion: This study found that 21.6% of pediatric ALL patients who discontinued SMX/TMP for prophylaxis had hepatotoxicity with a ‘probable or higher’ causality due to SMX/TMP. Identifying factors associated with ‘probable or higher’ causality for SMX/TMP-induced hepatotoxicity in these patients may be valuable for future research in this domain. (PeRM 2024;16:49-56)

스타틴 관련 근육이상반응 보고와 관련된 요인 식별을 위한 머신러닝 기반 클러스터링 분석

정선영,김정연,박세원,이민택,유승훈,이주원,남달리 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

: We aimed to identify factors associated with adverse event (AE) reports in statin-associated muscle symptoms (SAMS) using hierarchical clustering of patients in the Korea Institute of Drug Safety and Risk Management - Korea Adverse Event Reporting System database (KIDS-KAERS DB) (2105A0027). Methods: To explore the characteristics and risk factors of SAMS reports, we analysed the KIDSKAERS DB from 2016 to 2020. We included reports with a causality category level of “possible” or higher. Hierarchical clustering analysis was used to identify distinctive patterns within the dataset, with a particular focus on variables such as sex, age, statin type, contraindicated drugs and concomitant drugs. The reporting characteristics were described according to the cluster. Results: Four clusters of AE reports were distinguished by hierarchical clustering: atorvastatin- and rosuvastatinassociated AE (cluster 1), pitavastatin- and simvastatin-associated AE (cluster 2), rosuvastatin-associated AE (cluster 3), and atorvastatin-associated AE (cluster 4). Cluster 1 had a relatively higher proportion of men (57 cases, 50.9%) and a higher mean age (64.8 years) than the other clusters. Concomitant drug use was more common in cluster 1 (56 cases, 50.0%) than in other clusters (33.5%–46.2%), and all serious AEs were observed in cluster 1. Conclusion: Using hierarchical clustering, we found four distinct clusters based on SAMS report characteristics. Our findings further emphasize that patients prescribed statins, especially elderly male patients taking rosuvastatin and atorvastatin concomitantly with other medications, should be closely monitored for the development of rhabdomyolysis. (PeRM 2024;16:29-39)

노인의 퇴원 시 당뇨병 약제 강화 현황 및 단기 임상결과에 미치는 영향 분석

이주연,한주희,정애희,김민정,정선회 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

This study aimed to assess diabetes medication intensification at discharge in older adults hospitalized for non-glycemic reasons, examining its shortterm benefits and risks. Methods: A retrospective review of electronic medical records from Boramae Medical Center (September 1, 2020, to August 31, 2022) was conducted. Medication intensification was defined as either increasing the dosage of existing diabetes medications, adding insulin or initiating new medications. We compared glycated hemoglobin (HbA1c) levels 90 days post-discharge and the incidence of blood glucose-related emergency department visits or diabetesrelated unplanned readmission within 90 days post-discharge between patients with and without medication intensification. Results: Out of 1,278 patients, 480 (37.6%) underwent medication intensification at discharge. Factors associated with intensification included longer hospital stays, consultations with endocrinologist, higher HbA1c at admission, frequent hyperglycemic events, and changes in steroid or immunosuppressant use. The intensification group showed a significant reduction (8.6% to 7.0%) in HbA1c 90 days post-discharge compared to the non-intensification group (6.9% to 6.9%, p < 0.001). However, there was no significant impact on postdischarge emergency visits or unplanned readmissions related to blood glucose (aOR 0.34; 95% CI 0.07–1.53). Conclusion: A third of older adults admitted for nonglycemic issues was discharged with intensified diabetes medications, leading to improved short-term glycemic control but did not significantly affect diabetesrelated unplanned readmissions or emergency visits. (PeRM 2024;16:40-48)

접종 차수에 따른 코로나19 백신의 국내 실사용 효과: 체계적 문헌 고찰 및 메타분석

전나경,윤금비,이한길,정세원 대한약물역학위해관리학회 2025 약물역학위해관리학회지 Vol.17 No.1

The real-world effectiveness of Coronavirus disease 2019 (COVID-19) vaccines varies depending on dose, population, and outcome (infection, severe infection, and death). This study conducted a systematic review and meta-analysis of observational studies in Korea to assess vaccine effectiveness by dose. A systematic literature search was conducted in PubMed, Embase, and Research information sharing service (RISS) from January 1, 2020, to August 6, 2024. Studies evaluating COVID-19 vaccine effectiveness (VE) based on vaccination dose and reporting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severe infection, or death as outcomes were included. VE was either directly extracted from studies or calculated as VE = (1 − Odds ratio [OR]) × 100. The risk of bias was assessed using the Risk of bias in non-randomized studies - of interventions (ROBINS-I) tool, and meta-analysis was performed using Review Manager 5.4. A total of 12 studies were included in the systematic review and meta-analysis. The meta-analysis showed that vaccination reduced the risk of SARS-CoV-2 infection by 76% (OR: 0.24, 95% CI: 0.07–0.83). The effectiveness in preventing severe infection and death was 79% (OR: 0.21, 95% CI: 0.15–0.30) and 79% (OR: 0.21, 95% CI: 0.15–0.28), respectively. Protection increased with additional doses, with third-dose recipients showing over 90% effectiveness in preventing both severe infection and death. COVID-19 vaccination plays a crucial role in reducing the risk of SARS-CoV-2 infection, severe infection, and death. This study underscores the importance of regular vaccination across all age groups as a key strategy for the ongoing management of SARS-CoV-2 and the response to emerging variants